bluuebunny/crossref_metadata_2025 huggingface dataset:
Size Selective Synthesis of Surface-modified EuS Nanocrystals Using Pyridine and Their Physical Properties
Authors: Thongchant Supitcha , Hasegawa Yasuchika , Wada Yuji , Yanagida Shozo
Published: July 2003

The particle size of EuS nanocrystals was gradually increased by addition of pyridine to the reaction mixture of europium metal and hydrogen sulfide in liquid ammonia. The size effect of EuS nanocrystals was found in the absorption spectra for the first time. The size effect on the magnetic properties of the nanocrystals was also observed.
EuO Nanocrystal Formation under ArF Laser Irradiation
Authors: Hasegawa Yasuchika , Thongchant Supitcha , Kataoka Tomoharu , Wada Yuji , Yatsuhashi Tomoyuki , Nakashima Nobuaki , Yanagida Shozo
Published: July 2003

EuO (Europium(II) oxide) nanocrystals are prepared under irradiation by means of an ArF excimer laser. The formation of EuO nanocrystals with the clear lattice fringes was confirmed by TEM image. The crystal growth was monitored by the emission spectra.
Intercalation and Photochemical Behavior of Azobenzene Derivatives with Layered Polymer Crystals as the Organic Host
Authors: Oshita Shinya , Matsumoto Akikazu
Published: July 2003

A photofunctional organic solid was fabricated by the intercalation of azobenzene derivatives containing an amino group into poly(muconic acid) as the layered polymer crystals. The organic intercalation and photoisomerization behaviors depended on the structure of the spacer between the azobenzene and amino groups of the guest.
Acridine-bearing PNA for Efficient Protection of Designated Site of DNA from Nuclease S1
Authors: Ren Binzhi , Ye Sheng , Liang Xingguo , Komiyama Makoto
Published: July 2003

By using peptide nucleic acid (PNA) bearing an acridine at its N-terminus, a predetermined portion of DNA substrate was efficiently protected from nuclease S1. Promotion of the protecting activity by the acridine is remarkable enough to provide the target DNA fragment in high selectivity and yield.
Conversion of Vegetable Oil to Biodiesel Using Ultrasonic Irradiation
Authors: Stavarache Carmen , Vinatoru Mircea , Nishimura Rokuro , Maeda Yasuaki
Published: July 2003

The influence of low frequency ultrasounds (28 and 40 kHz) versus mechanical stirring on the transesterification reaction of neat vegetable oil with methanol under base-catalysis was studied and the results are presented. It was found that the optimized variables of 6:1 methanol/oil (mol/mol), 0.5% NaOH (wt/wt), and 40 kHz ultrasonic irradiation at 25 °C for 20 min gave a maximum isolated ester yield of 98%.
Radiation-induced Degradation of Nitrobenzene in Aqueous Solutions
Authors: Feng Shao-Hong , Zhang Shu-Juan , Yu Han-Qing , Li Qian-Rong
Published: July 2003

Both the efficiency and pathways of nitrobenzene degradation induced by γ-ray irradiation were significantly influenced by the addition of reactive species scavengers. Experimental results showed that the degradation of nitrobenzene was more favorable under oxidative conditions than under reductive conditions. Based on the product analysis by GC–MS, possible degradation mechanisms of nitrobenzene under both oxidative and reductive conditions were proposed.
Regioselective Radical Cyclization by Electrochemical Reduction Using an Arene Mediator. Environmentally Benign Method
Authors: Kurono Nobuhito , Honda Eiichi , Komatsu Fumikazu , Orito Kazuhiko , Tokuda Masao
Published: July 2003

Electrochemical reduction of 2-(but-3-enyl)-1-haloarenes in the presence of phenanthrene as a mediator generated the corresponding aryl radicals and gave cyclized products in good yields. Higher regio- and stereoselectivities than those of usual radical cyclization using AIBN-TBTH were achieved.
Nitrate Ion-sieve Properties of Layered Double Hydroxides
Authors: Tezuka Satoko , Chitrakar Ramesh , Sonoda Akinari , Ooi Kenta , Tomida Tahei
Published: July 2003

Layered double hydroxides (LDHs) with different kinds of metals in the brucite layer were prepared and their anion exchange properties were studied batchwise. A nitrate ion-sieve property was observed for LDHs depending on the basal spacing of the brucite layer. The distribution coefficient of nitrate ion was a maximum on the Ni–Fe type LDHs having a basal spacing of 0.81 nm.
Enantiomerically Convergent Synthesis of Phosphatidyl-d-myo-inositol 3,5-Bisphosphate from Both l- and d-1,2-O-Cyclohexylidene-myo-inositol
Authors: Han Fushe , Hayashi Minoru , Watanabe Yutaka
Published: July 2003

The synthesis of phosphatidyl-d-myo-inositol 3,5-bisphosphate [PtdIns(3,5)P2] has been conveniently accomplished via convergent routes starting from both enantiomers, 1,2-O-cyclohexylidene-myo-inositol. The synthetic strategy involves completely regioselective phosphorylation of 3,4-diol and 2,3,6-triol of the suitably protected inositols with the corresponding phosphite in the presence of pyridinium tribromide and 2,6-lutidine, resulting in the formation of 3-O-phosphorylated products, respectively.
Naphthoquinone and Iridoid with NGF-potentiating Activity from Verbena littoralis
Authors: Li Yushan , Satake Masayuki , Oshima Yasukatsu , Ohizumi Yasushi
Published: July 2003

One new naphthoquinone, (4R)-4,9-dihydroxy-8-methoxy-α-lapachone (1), and two new iridoids, 7a-hydroxygelsemiol (2) and 6-methoxysemperoside (3) were isolated from Verbena littoralis H. B. K. 1 (3-30 μM) and 2 (3 μM) showed a markedly enhancing activity of nerve growth factor (NGF)-mediated neurite outgrowth from PC12D cells.
An Effective System to Synthesize Arylacetones. Substrate-ionic Liquid-ultrasonic Irradiation
Authors: Yinghuai Zhu , Bahnmueller Stefan , Hosmane Narayan S , Maguire John A
Published: July 2003

Manganese(III) acetate-promoted aromatic acetonylation has been accomplished with ultrasonic irradiation in ionic liquids, [N-n-pentyl-4-picolinium] [closo-CB11H12] (1), [OMIM] [BF4] and [BMIM] [PF6] in 62-93% yields, with excellent chemical selectivity.
Microwave-polythiol Method. A New Route to Preparation of Tellurium with Various Morphologies
Authors: Zhu Ying-Jie , Hu Xian-Luo
Published: July 2003

A new microwave-polythiol method has been developed for preparation of tellurium (Te) with various morphologies. 1,2-Ethanedithiol (EDT) was used as both a reducing reagent and a solvent. Reduction of TeO2 by EDT was achieved by microwave-heating at ≤140 °C for 30 min. The morphology of Te could be controlled by changing experimental parameters.
Electrocardiographic and Cardiovascular Effects of the 5-Hydroxytryptamine3 Receptor Antagonists
Authors: Navari Rudolph M , Koeller Jim M
Published: July 2003

OBJECTIVE:

To review the electrocardiographic (ECG) and cardiovascular effects of 5-hydroxytryptamine3 (5-HT3) receptor antagonists preclinically, in healthy volunteers, and in patients undergoing chemotherapy or surgery.

DATA SOURCES:

A MEDLINE search was performed of clinical trials and preclinical data published between 1963 and December 2002 assessing the ECG and cardiovascular effects of 5-HT3 receptor antagonists, supplemented with reviews and secondary sources.

STUDY SELECTION AND DATA EXTRACTION:

All of the articles identified were evaluated and all information deemed relevant was included in this review.

DATA SYNTHESIS:

There are no clinically relevant differences in efficacy and safety among the available 5-HT3 receptor antagonists for prevention and treatment of chemotherapy-induced and postoperative nausea and vomiting. As a class, they have well-defined electrophysiologic activity. Changes in ECG parameters (PR, QRS, QT, QTc, JT intervals) are small, reversible, clinically insignificant, and independent of the patient population studied, and patients are asymptomatic during these changes. ECG changes are most prominent 1–2 hours after a dose of dolasetron, ondansetron, and granisetron and return to baseline within 24 hours. Clinically important adverse cardiovascular events associated with these changes are rare. No serious cardiac events (including torsade de pointes) arising from ECG interval changes have been attributed to 5-HT3 receptor antagonist use.

CONCLUSIONS:

Clinical data demonstrate that ECG interval changes are a class effect of the 5-HT3 receptor antagonists. Theoretical concern regarding cardiovascular adverse events with these agents is not supported by clinical experience. The significant benefits of these agents outweigh the theoretical small risk of meaningful cardiovascular events.
Conditional Inference Following Group Sequential Testing
Authors: Ohman Strickland Pamela A. , Casella George
Published: July 2003

The work ofFisher(1959) andBuehler(1959) discuss the importance of conditioning on recognizable subsets of the sample space. The stopping time yields an easily identifiable partition of the sample space when considering group sequential testing. We first present confidence intervals that are correct when conditioning on the subset of data for which a trial stopped at a particular analysis. These intervals have very desirable properties for observations that are highly unusual (given any value of the mean). In addition, they provide insight into how information about the mean is distributed between the two sufficient statistics. We then use conditional coverage probabilities to compare the sample mean, stagewise, and repeated confidence intervals. We find that none of these intervals outperforms the others when conditioning on stopping time, and no interval is a uniformly acceptable performer.
Estimation of Heritability in Heteroscedastic One‐Way Unbalanced Random Model
Authors: Singh B.
Published: July 2003

A modified estimator of heritability is proposed under heteroscedastic one way unbalanced random model. The distribution, moments and probability of permissible values (PPV) for conventional and modified estimators are derived. The behaviour of two estimators has been investigated, numerically, to devise a suitable estimator of heritability under variance heterogeneity. The numerical results reveal that under balanced case the heteroscedasticity affects the bias, MSE and PPV of conventional estimator, marginally. In case of unbalanced situations, the conventional estimator underestimates the parameter when more variable group has more observations and overestimates when more variable group has less observations, MSE of the conventional estimator decreases when more variable group has more observations and increases when more variable group has less observations and PPV is marginally decreased. The MSE and PPV are comparable for two estimators while the bias of modified estimator is less than the conventional estimator particularly for small and medium values of the parameter. These results suggest the use of modified estimator with equal or more observations for more variable group in presence of variance heterogeneity.
Hadamard randomization: a valid restriction of random permuted blocks
Authors: Bailey R.A. , Nelson P.R.
Published: July 2003

Random permuted blocks can result in treatment imbalance if entry to the trial stops in mid‐block. This paper presents a restriction of this method of randomization. The restriction avoids severe treatment imbalance but gives unbiased estimators of the treatment difference and its variance.
Inference for the Break Point in Segmented Regression with Application to Longitudinal Data
Authors: Piepho H.P. , Ogutu J.O.
Published: July 2003

This paper considers inference for the break point in the segmented regression or piece‐wise regression model. Standard likelihood theory does not apply because the break point is absent under the null hypothesis. We use results by Davies for this type of non‐standard set‐up [Biometrika 64 (1977), 247–254 and 74 (1987), 33–43] to obtain a test for the null hypothesis of no break point. A confidence interval can be constructed provided replicate data are available. The methods are exemplified using two longitudinal datasets, the one from ecology, the other from pharmacology.
Quantile Inference with Multivariate Failure Time Data
Authors: Yin Guosheng , Cai Jianwen , Kim Jinheum
Published: July 2003

Quantiles, especially the medians, of survival times are often used as summary statistics to compare the survival experiences between different groups. Quantiles are robust against outliers and preferred over the mean. Multivariate failure time data often arise in biomedical research. For example, in clinical trials, each patient in the study may experience multiple events which may be of the same type or distinct types, while in family studies of genetic diseases or litter matched mice studies, failure times for subjects in the same cluster may be correlated. In this article, we propose nonparametric procedures for the estimation of quantiles with multivariate failure time data. We show that the proposed estimators asymptotically follow a multivariate normal distribution. The asymptotic variance‐covariance matrix of the estimated quantiles is estimated based on the kernel smoothing and bootstrap techniques. Simulation results show that the proposed estimators perform well in finite samples. The methods are illustrated with the burn‐wound infection data and the Diabetic Retinopathy Study (DRS) data.
More Powerful Likelihood Ratio Tests for Isotonic Binomial Proportions
Authors: Tebbs Joshua M. , Swallow William H.
Published: July 2003

Binomial group testing involves pooling individuals into groups and observing a binary response on each group. Results from the group tests can then be used to draw inference about population proportions. Its use as an experimental design has received much attention in recent years, especially in public‐health screening experiments and vector‐transfer designs in plant pathology. We investigate the benefits of group testing in situations wherein one desires to test whether or not probabilities are increasingly ordered across the levels of an observed qualitative covariate, i.e., across strata of a population or among treatment levels. We use a known likelihood ratio test for individual testing, but extend its use to group‐testing situations to show the increases in power conferred by using group testing when operating in this constrained parameter space. We apply our methods to data from an HIV study involving male subjects classified as intraveneous drug users.
Comparison of Diagnostic Accuracy of Biomarkers With Pooled Assessments
Authors: Liu Aiyi , Schisterman Enrique F.
Published: July 2003

New biomarkers are frequently being developed in laboratory settings for the early diagnosis of diseases. However, the assay can be so expensive to assess in some cases that the evaluation of a large number of assays becomes unfeasible. Under this setting pooling biospecimens becomes an appealing alternative. In this paper, we present the methodology to allow for general pooling strategies and different data structures, which include balanced and unbalanced pooling cases. An estimate of the area under the ROC curve of a single biomarker with its asymptotic mean and variance is provided. Furthermore, we develop a test statistic for comparing the areas under the ROC curves of two biomarkers. The methods are illustrated with data from a study evaluating biomarkers for coronary heart disease.
Reducing ethnic prejudice: an evaluation of seven recommended principles for incorporation in public campaigns
Authors: Vrij Aldert , Akehurst Lucy , Smith Beverley
Published: July 2003

The present study investigated the effects of seven principles drawn from cognitive models of ethnic prejudice, general information processing models and persuasion models, on levels of ethnic prejudice. It was hypothesized that exposure to cue cards incorporating these principles would result in lower levels of prejudice than cue cards which did not incorporate the principles. A total of 400 caucasian participants were randomly assigned to experimental conditions (where participants were exposed to a cue card incorporating or omitting each of the seven principles), or the control condition (with no cue card exposure), and completed a questionnaire measuring ethnic prejudice. Results revealed that the absence of the principles in the cards led in several cases to unwanted negative effects (higher levels of prejudice than the control group). Reasons for these findings and implications for launching poster campaigns to reduce ethnic prejudice are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
O2 Evolution in the Fenton Reaction
Authors: Buda Francesco , Ensing Bernd , Gribnau Michiel C. M. , Baerends Evert Jan
Published: July 2003

We investigated the mechanism involved in the oxygen production in the Fenton chemistry by means of density functional theory calculations. This study extends previous work in which we proposed that the FeIVO2+ complex is the key active intermediate in the Fenton reaction. Here we provide a consistent picture of the entire reaction cycle by analyzing how the active species, FeIVO2+, can react with hydrogen peroxide to produce O2 and regenerate the Fe2+ catalyst. These results are also relevant in view of the analogies with important enzyme‐catalyzed oxidation reactions.
Control of Calcium Carbonate Polymorphism and Morphology through Biomimetic Mineralization by means of Nanotechnology
Authors: Ichikawa Kazuhiko , Shimomura Noriyuki , Yamada Masanori , Ohkubo Naoki
Published: July 2003

In vitro biomimetic mineralization by means of nanotechnology allows the formation of calcium carbonate polymorphs at low temperatures (<25 °C) under a CO2 atmosphere of 500–1500 ppm . A two‐dimensional zinc‐ion ordered array (zinc array), which acts as an active‐site mimic of carbonic anhydrase, has been prepared by immersing the self‐organized monolayer of 3‐(2‐imidazolin‐1‐y)propyltriethosilane on mica (ImSi substrate) into aqueous zinc solution. The zinc array mounted on the ImSi substrate catalyzed the conversion from CO2 to HCO3−, and accelerated the formation of calcium carbonate. In situ X‐ray diffraction data of the formed calcium carbonate on the poly(L‐aspartate)‐coated chitin substrate (pAsp substrate), with calcium ion‐recognition sites, demonstrated that the interaction between the zinc array and pAsp substrates formed both vaterite and calcite at low temperature (15 °C) and mainly vaterite at 25 °C; this interaction also controlled the morphology of calcium carbonate formed on pAsp substrate.
Polynuclear Palladium Complexes with 3,5‐Dimethylpyrazolate Exhibiting Three Different Coordination Modes
Authors: Forniés Juan , Martín Antonio , Sicilia Violeta , Martín L. Francisco
Published: July 2003

The characterisation of dinuclear pyrazolato‐bridged PdII complexes, [{Pd(μ‐dmpz)Cl(Hdmpz)}2] (1) and [{Pd(μ‐dmpz)(dmpz)(Hdmpz)}2] (2) (Hdmpz=dimethylpyrazole), has been carried out. An X‐ray study of compound 2 reveals the existence of intramolecular NH⋅⋅⋅N hydrogen bonds between neighbouring dmpz groups. Compound 2 has been deprotonated and both acidic hydrogen atoms substituted by two metal atoms of CuI, AgI or AuI to give the tetranuclear compounds [Pd2M2(μ2‐dmpz‐κN,N′)6] (M=Cu, Ag, Au). The structure of these compounds resembles a box with a small cavity inside. There are also three π‐electron‐rich clefts between each of the three pairs of azolato rings, capable of further complexation. The reactions of [Pd2M2(μ2‐dmpz‐κN,N′)6] (M=Cu, Ag, Au) with AgClO4 render compounds of the type [{Pd2M2(μ2‐dmpz‐κN,N′)2(μ3‐dmpz‐κN,N′,C4)4Ag2(μ2‐O2ClO2)}2] (M=Cu, Ag, Au). The X‐ray structures of crystals obtained from a solution of compounds [{Pd2M2(μ2‐dmpz‐κN,N′)2(μ3‐dmpz‐κN,N′,C4)4Ag2(μ2‐O2ClO2)}2] (M=Ag, Au) in acetone reveals a [{Pd2M2(μ2‐dmpz‐κN,N′)2(μ3‐dmpz‐κN,N′,C4)4Ag(OCMe2)(OClO3)Ag(μ2‐O2ClO2)}2] stoichiometry, indicating that only two of the three π‐electron‐rich clefts have been used to accommodate Ag+ ions. Each of the silver atoms are located in between two 3,5‐dmpz rings and are η1‐bonded to the C4 atom of each group.
Absolute Potassium Cation Affinities (PCAs) in the Gas Phase
Authors: Lau Justin Kai‐Chi , Wong Carrie Hoi Shan , Ng Po Shan , Siu Fung Ming , Ma Ngai Ling , Tsang Chun Wai
Published: July 2003

The potassium cation affinities (PCAs) of 136 ligands (20 classes) in the gas phase were established by hybrid density functional theory calculations (B3‐LYP with the 6‐311+G(3df,2p) basis set). For these 136 ligands, 70 experimental values are available for comparison. Except for five specific PCA values—those of phenylalanine, cytosine, guanine, adenine (kinetic‐method measurement), and Me2SO (by high‐pressure mass spectrometric equilibrium measurement)—our theoretical estimates and the experimental affinities are in excellent agreement (mean absolute deviation (MAD) of 4.5 kJ mol−1). Comparisons with previously reported theoretical PCAs are also made. The effect of substituents on the modes of binding and the PCAs of unsubstituted parent ligands are discussed. Linear relations between Li+/Na+ and K+ affinities suggest that for the wide range of ligands studied here, the nature of binding between the cations and a given ligand is similar, and this allows the estimation of PCAs from known Li+ and/or Na+ affinities. Furthermore, empirical equations relating the PCAs of ligands with their dipole moments, polarizabilities (or molecular weights), and the number of binding sites were established. Such equations offer a simple method for estimating the PCAs of ligands not included in the present study.
Coordinated and Clathrated Guests in the ${_{\infty }^{3}}$[Hg6As4]4+ Bicompartmental Framework: Synthesis, Crystal and Electronic Structure, and Properties of the Novel Supramolecular Complexes [Hg6As4](CrBr6)Br and [Hg6As4](FeBr6)Hg0.6
Authors: Olenev Andrei V. , Oleneva Olga S. , Lindsjö Martin , Kloo Lars A. , Shevelkov Andrei V.
Published: July 2003

Two new supramolecular complexes [Hg6As4](CrBr6)Br (1) and [Hg6As4](FeBr6)Hg0.6 (2) have been prepared by the standard ampoule technique and their crystal structures determined. Both crystallize in the cubic space group Pa$\bar 3$ with the unit cell parameter a=12.275(1) (1) and 12.332(1) Å (2), and Z=4. Their structures consist of bicompartmental, three‐dimensional [Hg6As4]4+ frameworks with cavities of two different sizes occupied by guest anions of different type. The bigger cavities are filled with the octahedral MBr6n− ions (M=Cr or Fe; n=3 or 4), whereas the smaller cavities trap either Br− ions (1) or Hg0 (2). The analysis of the host–guest contacts has allowed a classification of the octahedral guests as coordinated and the monatomic guests as clathrated. Magnetic measurements and ESR spectroscopy data have given information about the interaction between the host and guests. Band structure calculations (HF and hybrid DFT level) indicate that both 1 and 2 are non‐metallic, with a band gap of approximately 1.5 eV (B3LYP), and that the interaction between the host and guests is of predominantly electrostatic character. It is shown that though the electrostatic host–guest interaction is weak it plays an important role in assembling the perfectly ordered supramolecular architectures.
Synthesis, Structure, and Reactivity of sp Carbon Chains with Bis(phosphine) Pentafluorophenylplatinum Endgroups: Butadiynediyl (C4) through Hexadecaoctaynediyl (C16) Bridges, and Beyond
Authors: Mohr Wolfgang , Stahl Jürgen , Hampel Frank , Gladysz J. A.
Published: July 2003

The reaction of trans‐[(C6F5)(p‐tol3P)2PtCl] (PtCl) and butadiyne (cat. CuI, HNEt2) gives trans‐[(C6F5)(p‐tol3P)2Pt(CC)2H] (PtC4H, 81 %), which reacts with excess HCCSiEt3 under Hay coupling conditions (O2, cat. CuCl/TMEDA, acetone) to yield PtC6Si (53 %). A solution of PtC6Si in acetone is treated with wet nBu4NF to generate PtC6H. The addition of ClSiMe3 (F− scavenger) and then excess HCCSiEt3 under Hay conditions gives PtC8Si (39 %). Hay homocouplings of PtC4H, PtC6H, and PtC8H (generated in situ analogously to PtC6H) yield PtC8Pt, PtC12Pt, and PtC16Pt (97–92 %). Reactions of PtC4H and PtC6H with PtCl (cat. CuCl, HNEt2) give PtC4Pt and PtC6Pt (69 %, 34 %). The attempted conversion of PtC8H to PtC10Si affords mainly PtC16Pt, with traces of PtC20Pt and PtC24Pt. The complexes PtCxPt are exceedingly stable (dec pts 234 to 288 °C), and Et3P displaces p‐tol3P to give the corresponding compounds Pt′C8Pt′ and Pt′C12Pt′ (94–90 %). The effect of carbon chain lengths upon IR νCC patterns (progressively more bands), UV/Vis spectra (progressively red‐shifted and more intense bands with ε>600 000 M−1 cm−1), redox properties (progressively more difficult and less reversible oxidations), and NMR values are studied, and analyzed with respect to the polymeric sp carbon allotrope “carbyne”. The crystal structure of PtC12Pt shows a dramatic, unprecedented degree of chain bending, whereas the chains in PtC8Pt, Pt′C12Pt′, and PtC16Pt are nearly linear.
Useful Dual Diels–Alder Behavior of 2‐Azetidinone‐Tethered Aryl Imines as Azadienophiles or Azadienes: A β‐Lactam‐Based Stereocontrolled Access to Optically Pure Highly Functionalized Indolizidine Systems
Authors: Alcaide Benito , Almendros Pedro , Alonso Jose M. , Aly Moustafa F.
Published: July 2003

Imines derived from 4‐oxoazetidine‐2‐carbaldehydes have been found to be versatile Diels–Alder reagents in that they exhibit two reactivity patterns. 2‐Azetidinone‐tethered imines undergo diastereoselective reaction with Danishefsky's diene in the presence of different Lewis acids. The effect of the amount of catalyst on the conversion rate as well as on the product ratio has been studied. Under standard reaction conditions, indium(III) chloride and zinc(II) iodide provided the best yields, and indium(III) triflate the highest diastereoselectivity in the Lewis acid promoted aza‐Diels–Alder cycloaddition. Treatment of the aforementioned imines with cyclopentadiene, 2,3‐dimethyl‐1,3‐butadiene or 3,4‐dihydro‐2 H‐pyran led to cycloadducts arising from inverse electron‐demand condensation involving the β‐lactam‐tethered aryl imine as the heterodiene component. In addition, the first methodology for preparing indolizidines from β‐lactams has been developed. This process involves amide bond cleavage of the β‐lactam ring in the aza‐Diels–Alder cycloadducts with concomitant cyclization. Full chirality transfer occurs when the reaction is performed with an enantiomerically pure substrate.
CCα Insertion: Insertion of an Alkyne into the CC Single Bond between the Carbene‐Carbon Atom and the α‐Carbon Atom of a Fischer Carbene Complex by an Unprecedented Metalla(di‐π‐methane) Skeletal Rearrangement
Authors: Ünaldi Seda , Aumann Rudolf , Fröhlich Roland
Published: July 2003

The first examples of insertion of a CC bond of an alkyne into a CcarbeneCα single bond of a carbene complex (CCα insertion) are reported. (prim‐Alkyl)carbene complexes [(OC)5MC(OEt)CH2R] (1 a–f; M=Cr, W; R=nPr, C7H7, Ph) undergo CCα insertion of electron‐deficient alkynes [PhCCC(XEt)NMe2]BF4 (5 a,b; X=O, S) to give zwitterionic carbiminium carbonylmetalates 3 a–g, which are thermally transformed into (CO)4M chelate carbene complexes 4 a–g by elimination of CO. The overall reaction is highly regio‐ and stereoselective. It involves an unprecedented metalla(di‐π‐methane) rearrangement as the key step.
Through‐Space Delocalized Water‐Soluble Paracyclophane Bichromophores: New Fluorescent Optical Reporters
Authors: Hong Janice W. , Benmansour Hadjar , Bazan Guillermo C.
Published: July 2003

Conjugated polymers and oligomers can serve as highly responsive fluorescent reporters for biosensor applications. However, their optical properties in aqueous media are highly dependent upon environmental conditions. The structure of the paracyclophane framework provides a platform for designing optical reporters that show little sensitivity to surfactants, and thus is well‐suited for fluorescent assays. The permanent intramolecular delocalization through the paracyclophane core dominates intermolecular perturbations in spontaneously formed aggregates.
Template Effect Where 1‐3 Molecules Drive Formation of a Trimer Carceplex
Authors: Makeiff Darren A. , Sherman John C.
Published: July 2003

The template effect in the formation of a trimer carceplex using 1‐3 molecules as templates is explored. Thirteen different templates were studied and template ratios were measured for templates of like and unlike molecularity. Five transition‐state models were studied for their binding abilities to see if these mirror the template ratios. The chemical shifts of the guests and the thermodynamic and kinetic values for templation suggest that binding is key, often tight, and that the guest determining step is formation of the last covalent bond. The molecular dynamics of guests as well as the conformational dynamics of both hosts and guests further addresses nature of the recognition between host and guest. Finally, we were surprised to discover that water can bind reversibly to the trimer carceplexes, which will have ramifications to any inner phase reactions conducted inside the cage.
Optimization of Hydrolase Efficiency in Organic Solvents
Authors: Secundo Francesco , Carrea Giacomo
Published: July 2003

The application of hydrolases in organic solvents for synthetic purposes is a procedure routinely adopted in organic chemistry, especially for the preparation of chiral building blocks. Numerous studies have shed light on several aspects of the mechanism of hydrolase action in low‐water environments. Procedures suitable to improve the catalytic efficiency of enzymes and productivity of the synthetic processes have been reported. These fundamental and applied investigations have made hydrolase‐catalyzed reactions in organic solvents of industrial interest. In this article we describe and discuss various approaches adopted to optimize the performance of hydrolases in organic media, with special emphasis on the formulation of the biocatalysts which, under proper conditions, can display an activity equal to that displayed in aqueous buffers.
Development of the Traceless Phenylhydrazide Linker for Solid‐Phase Synthesis
Authors: Stieber Frank , Grether Uwe , Waldmann Herbert
Published: July 2003

The hydrazide group is a new oxidatively cleavable traceless linker for solid‐phase chemistry. It can be readily introduced by hydrazide formation between a carboxy‐functionalized resin and different substituted hydrazines. In order to achieve high yields in this step, new carboxylic acid resins were developed that are not prone to undesired imide formation upon activation of the carboxylic acid. The polymer‐bound acyl hydrazides were successfully employed in various transformations, namely Heck, Suzuki, Sonogashira, and Stille couplings, as well as Wittig and Grignard reactions. Traceless release of the coupling products from the solid support is achieved selectively under mild conditions and in high purity by oxidation of the aryl hydrazides to acyl diazenes with CuII salts or N‐bromosuccinimide (NBS) and subsequent nucleophilic attack of the acyl diazene intermediates. Traceless cleavage by oxidation with NBS can be carried out as a two‐step process in which stable acyl diazenes are first generated by treatment with NBS in the absence of a nucleophile. After removal of the reagents by simple resin washing, the traceless release is effected by the addition of methanol, which leads to products of high purity without any additional separation steps.
Multistep Solid‐Phase Synthesis of an Antibiotic and Receptor Tyrosine Kinase Inhibitors Using the Traceless Phenylhydrazide Linker
Authors: Stieber Frank , Grether Uwe , Mazitschek Ralph , Soric Natascha , Giannis Athanassios , Waldmann Herbert
Published: July 2003

The hydrazide group is an oxidatively cleavable traceless linker for solid‐phase chemistry. This linker technology was used to develop a multistep solid‐phase synthesis of an antibiotic that is active against Mycobacterium tuberculosis. Furthermore, we describe an efficient method for the traceless synthesis of 2‐aminothiazoles that display dual inhibitory activity against the receptor tyrosine kinases VEGFR‐2 and Tie‐2. The synthesis method proceeds through 9 steps on the solid phase and should give access to a much larger library of 2‐aminothiazoles, from which a new class of anti‐angiogenesis drugs may be developed.
The Solution Structure of (Me3Si)3CSiBr—An Ab Initio/NMR Study
Authors: Flock Michaela , Dransfeld Alk
Published: July 2003

The first halosilylene stable in solution was investigated by ab initio/NMR calculations (IGLO SOS‐DFPT PW91/B2//B3LYP/6‐31+G(d)). The δ 29Sicalc of (Me3Si)3CSiBr (446 ppm) does not agree with the measured NMR signal at 106 ppm assigned to the free halosilylene. From the possible silylene complexes in the reaction solution, two structures agree with the observed NMR signal: the (Me3Si)3CSiBr2 anion (δ 29Sicalc=124 ppm) and the unsolvated and solvated complex of the anion with two Li+ (δ 29Sicalc=117 and estimated 134 ppm). Additionally the δ 29Sicalc of alkylsilylenes, R‐Si‐X, ranging from 200 to 900 ppm are presented to guide NMR identification in future silylene synthesis.
Routes to Metallodendrimers: Synthesis of Isomeric Neutral Metallomacromolecules Based on Bis(2,2′:6′,2″‐terpyridine)ruthenium(II) Connectivity
Authors: Newkome George R. , Yoo Kyung Soo , Kim Hyung Jin , Moorefield Charles N.
Published: July 2003

Routes for the syntheses of isomeric, zwitterionic, bisterpyridine–RuII‐based macromolecules are described. Access to these novel architectures is facilitated by the construction of terpyridine‐modified, 1→3 C‐branched, ester‐terminated building blocks. Constitutional isomers result from the interchangable placement of methyl and tert‐butyl ester groups on both the branched framework near the RuII centers and the termini of the branched construct. Water solubility is imparted to each isomer through selective transformation of the tert‐butyl esters to their corresponding carboxylates. Along with the standard characterization techniques, electrochemical and spectroscopic data also support the structural formation.
The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons
Authors: Buijs Ruud M. , la Fleur Susanne E. , Wortel Joke , van Heyningen Caroline , Zuiddam Laura , Mettenleiter Thomas C. , Kalsbeek Andries , Nagai Katsuya , Niijima Akira
Published: July 2003

Opposing parasympathetic and sympathetic signals determine the autonomic output of the brain to the body and the change in balance over the sleep‐wake cycle. The suprachiasmatic nucleus (SCN) organizes the activity/inactivity cycle and the behaviors that go along with it, but it is unclear how the hypothalamus, in particular the SCN, with its high daytime electrical activity, influences this differentiated autonomic balance. In a first series of experiments, we visualized hypothalamic pre‐sympathetic neurons by injecting the retrograde tracer Fluoro‐Gold into the thoracic sympathetic nuclei of the spinal cord. Pre‐parasympathetic neurons were revealed by injection of the retrograde trans‐synaptic tracer pseudorabies virus (PRV) into the liver and by sympathetic liver denervation, forcing the virus to infect via the vagus nerve only. This approach revealed separate pre‐sympathetic and pre‐parasympathetic neurons in the brainstem and hypothalamus. Next, selective retrograde tracing with two unique reporter PRV strains, one injected into the adrenal and the other into the sympathetic denervated liver, demonstrated that there are two separate populations of pre‐sympathetic and pre‐parasympathetic neurons within the paraventricular nucleus of the hypothalamus. Interestingly, this segregation persists into the SCN, where, as a result, the day‐night balance in autonomic function of the organs is affected by specialized pre‐sympathetic or pre‐parasympathetic SCN neurons. These separate preautonomic SCN neurons provide the anatomical basis for the circadian‐driven regulation of the parasympathetic and sympathetic autonomic output. J. Comp. Neurol. 464:36–48, 2003. © 2003 Wiley‐Liss, Inc.
Ontogeny of γ‐aminobutyric acid–immunoreactive neurons in the rhombencephalon and spinal cord of the sea lamprey
Authors: Meléndez‐Ferro Miguel , Pérez‐Costas Emma , Villar‐Cheda Begoña , Rodríguez‐Muñoz Rolando , Anadón Ramón , Rodicio María Celina
Published: July 2003

The development of neurons expressing γ‐aminobutyric acid (GABA) in the rhombencephalon and spinal cord of the sea lamprey (Petromyzon marinus) was studied for the first time with an anti‐GABA antibody. The earliest GABA‐immunoreactive (GABAir) neurons appear in late embryos in the basal plate of the isthmus, caudal rhombencephalon, and rostral spinal cord. In prolarvae, the GABAir neurons of the rhombencephalon appear to be distributed in spatially restricted cellular domains that, at the end of the prolarval period, form four longitudinal GABAir bands (alar dorsal, alar ventral, dorsal basal, and ventral basal). In the spinal cord, we observed only three GABAir longitudinal bands (dorsal, intermediate, and ventral). The larval pattern of GABAir neuronal populations was established by the 30‐mm stage, and the same populations were observed in premetamorphic and adult lampreys. The ontogeny of GABAergic populations in the lamprey rhombencephalon and spinal cord is, in general, similar to that previously described in mouse and Xenopus. J. Comp. Neurol. 464:17–35, 2003. © 2003 Wiley‐Liss, Inc.
Cytoarchitecture and efferent projections of the nucleus incertus of the rat
Authors: Olucha‐Bordonau Francisco E. , Teruel Vicent , Barcia‐González Jorge , Ruiz‐Torner Amparo , Valverde‐Navarro Alfonso A. , Martínez‐Soriano Francisco
Published: July 2003

The nucleus incertus is located caudal to the dorsal raphe and medial to the dorsal tegmentum. It is composed of a pars compacta and a pars dissipata and contains acetylcholinesterase, glutamic acid decarboxylase, and cholecystokinin‐positive somata. In the present study, anterograde tracer injections in the nucleus incertus resulted in terminal‐like labeling in the perirhinal cortex and the dorsal endopyriform nucleus, the hippocampus, the medial septum diagonal band complex, lateral and triangular septum medial amygdala, the intralaminar thalamic nuclei, and the lateral habenula. The hypothalamus contained dense plexuses of fibers in the medial forebrain bundle that spread in nearly all nuclei. Labeling in the suprachiasmatic nucleus filled specifically the ventral half. In the midbrain, labeled fibers were observed in the interpeduncular nuclei, ventral tegmental area, periaqueductal gray, superior colliculus, pericentral inferior colliculus, pretectal area, the raphe nuclei, and the nucleus reticularis pontis oralis. Retrograde tracer injections were made in areas reached by anterogradely labeled fibers including the medial prefrontal cortex, hippocampus, amygdala, habenula, nucleus reuniens, superior colliculus, periaqueductal gray, and interpeduncular nuclei. All these injections gave rise to retrograde labeling in the nucleus incertus but not in the dorsal tegmental nucleus. These data led us to conclude that there is a system of ascending projections arising from the nucleus incertus to the median raphe, mammillary complex, hypothalamus, lateral habenula, nucleus reuniens, amygdala, entorhinal cortex, medial septum, and hippocampus. Many of the targets of the nucleus incertus were involved in arousal mechanisms including the synchronization and desynchronization of the theta rhythm. J. Comp. Neurol. 464:62–97, 2003. © 2003 Wiley‐Liss, Inc.
Identification of a cone bipolar cell in cat retina which has input from both rod and cone photoreceptors
Authors: Fyk‐Kolodziej Bozena , Qin Pu , Pourcho Roberta G.
Published: July 2003

It has been generally accepted that rod photoreceptor cells in the mammalian retina make synaptic contact with only a single population of rod bipolar cells, whereas cone photoreceptors contact a variety of cone bipolar cells. This assumption has been challenged in rodents by reports of a type of cone bipolar cell which receives input from both rods and cones. Questions remained as to whether similar pathways are present in other mammals. We have used an antiserum against the glutamate transporter GLT1‐B to visualize a population of cone bipolar cells in the cat retina which make flat contacts with axon terminals of both rod and cone photoreceptor cells. These cells are identified as OFF‐cone bipolar cells and correspond morphologically to type cb1 (CBa2) cone bipolar cells which are a major source of input to OFF‐beta ganglion cells in the cat retina. The GLT1‐B transporter was also localized to processes making flat contacts with photoreceptor terminals in rat and rabbit retinas. Examination of tissue processed for the GluR1 glutamate receptor subunit showed that cb1 cone bipolar cells, like their rodent counterparts, express this α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐selective receptor at their contacts with rod spherules. Thus, a direct excitatory pathway from rod photoreceptors to OFF‐cone bipolar cells appears to be a common feature of mammalian retinas. J. Comp. Neurol. 464:104–113, 2003. © 2003 Wiley‐Liss, Inc.
Notch‐associated gene expression in embryonic and adult taste papillae and taste buds suggests a role in taste cell lineage decisions
Authors: Seta Yuji , Seta Chihiro , Barlow Linda A.
Published: July 2003

The Notch signaling pathway is involved in cell fate decisions during development. To explore the role of this signaling cascade in the taste system, we investigated the expression patterns of Notch signaling genes in fetal and adult mouse tongues using in situ hybridization. Three of the four murine Notch receptors, their ligands, Delta‐like 1 (Dll‐1), Jagged1, and Jagged2, as well as three transcription factors, Hes1, Hes6, and Mash1, are expressed in the embryonic taste epithelium. Expression is first detected in the circumvallate papilla at embryonic day E14.5, when Notch1, Jagged1, and Jagged2 are expressed broadly in the papilla and general lingual epithelium. In contrast, Mash1 and Hes6 are restricted to only a few epithelial cells in the apical region of the developing papilla. By E18.5, many of the genes now exhibit a bimodal expression pattern in the papillary epithelium: apically and dorsally they are expressed in sparse clusters of cells, while more ventrally expression typically occurs throughout the lower regions of the trenches. The extent of papilla innervation was compared with Mash1 and Hes6 expression. At E14.5, when Hes6 and Mash1 are already expressed in small numbers of epithelial cells, PGP9.5 immunoreactive fibers have not yet invaded the epithelium, consistent with the specification of taste bud primordia prior to nerve contact. All of the genes examined (except Notch2) are also expressed in subsets of cells within circumvallate taste buds in adult mice, although Notch1 is restricted to basal cells adjacent to taste buds. The onset of embryonic Notch associated gene expression after the morphological differentiation of the circumvallate papilla argues that this signaling cascade may specify taste receptor cell lineages within an already specified taste papilla. Similarly, Notch gene expression in adult taste buds suggests continued roles in cell lineage determination and cell turnover. J. Comp. Neurol. 464:49–61, 2003. © 2003 Wiley‐Liss, Inc.
Centrosomal abnormality is common in and a potential biomarker for bladder cancer
Authors: Jiang Feng , Caraway Nancy P. , Sabichi Anita L. , Zhang Hua Z. , Ruitrok Arnout , Grossman H. Barton , Gu Jun , Lerner Seth P. , Lippman Scott , Katz Ruth L.
Published: July 2003

Centrosomal abnormalities have been implicated in chromosomal segregation aberrations that result from the formation of multipolar mitotic spindles and lead to aneuploidy. Aneuploidy is a characteristic of neoplasia and underlies the development and progression of bladder cancer. Therefore, centrosomal abnormality may play a key role in urothelial tumor transformation. The purpose of our investigation was to determine whether centrosomal abnormalities are present in malignant urothelial cells, define the relationship between centrosomal abnormalities and aneuploidy and determine whether the presence of centrosomal abnormalities might be a potential diagnostic marker for bladder cancer. Bladder wash specimens obtained from patients with and without a history of urothelial carcinoma were analyzed for centrosomal abnormalities using an immunoassay with a γ‐tubulin antibody. FISH with centromeric probes for chromosomes 4 and 9 and DNA ploidy image analysis were performed to detect aneuploidy. Defective centrosomes were found in 40 of 45 bladder wash specimens from patients with bladder cancer but in none of the 10 samples from patients without it. A large percentage (69%) of grade 1 tumors were positive for centrosomal abnormalities, and these abnormalities were increasing in numbers and size in grade 2 (93%) and grade 3 (100%) specimens. Centrosomal abnormalities and numerical chromosomal aberrations frequently appeared concomitantly in the same malignant cells. All of the specimens showing aneuploidy also exhibited centrosomal abnormalities: centrosomal defects and aneuploidy occurred together in 80% of malignant bladder tumors, with an especially high percentage in higher‐grade tumors. The overall positivity of centrosomal abnormalities was higher than that of aneuploidy (88% vs. 80%), especially in grade 1 tumors (69% vs. 46%), whereas aneuploidy was strongly associated with grade 2 and grade 3 tumors. Centrosomal abnormalities are common in bladder cancer, even in low‐grade tumors, and strongly associated with cancer grade and aneuploidy, especially in high‐grade neoplasms. Centrosomal abnormalities appear to be intrinsic to aneuploidy and tumorigenesis and may be potential markers for early detection of bladder cancer. © 2003 Wiley‐Liss, Inc.
Additive effects of tamoxifen and the farnesyl transferase inhibitor FTI‐277 on inhibition of MCF‐7 breast cancer cell‐cycle progression
Authors: Doisneau‐Sixou Sophie F. , Cestac Philippe , Faye Jean‐Charles , Favre Gilles , Sutherland Robert L.
Published: July 2003

The efficacy of tamoxifen in the hormonal therapy of breast cancer is well established, but therapeutic resistance is inevitable. FTIs are a new class of anticancer drugs that are in phase III clinical evaluation. Since the mechanisms of action of these 2 classes of drugs are different, we tested the combination of tamoxifen and FTI‐277 on inhibiting proliferation of hormone‐dependent MCF‐7 human breast cancer cells. An additive effect on cell proliferation was demonstrated, accompanied by an additive G0/G1 arrest. The major effect of the combination of the 2 drugs was to maintain p21waf/cip1 at an intermediate level, higher than that observed in the presence of tamoxifen alone. This was associated with an additive effect on inactivation of cyclin E–Cdk2 complexes and decreased phosphorylation of pRb and p130 pocket proteins. These effects were accompanied by increased association of 2 CDIs, p27kip1 and p21waf/cip1, with cyclin E–Cdk2 complexes. These data demonstrate that the additive effect is likely predominantly due to the recruitment of p27kip1 and, to a lesser extent, p21waf/cip1 into the cyclin E–Cdk2 complexes. Together, these results suggest that the combination of FTI and tamoxifen may increase the antitumor effect of either drug alone in breast cancer. © 2003 Wiley‐Liss, Inc.