bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Image Microscope Array for the Compilation of Multimodality Whole Organ Image Databases
Authors: Namati Eman , de Ryk Jessica , Thiesse Jacqueline , Towfic Zaid , Hoffman Eric , Mclennan Geoffrey
Published: September 2007

Three‐dimensional, structural and functional digital image databases have many applications in education, research, and clinical medicine. However, to date, apart from cryosectioning, there have been no reliable means to obtain whole‐organ, spatially conserving histology. Our aim was to generate a system capable of acquiring high‐resolution images, featuring microscopic detail that could still be spatially correlated to the whole organ. To fulfill these objectives required the construction of a system physically capable of creating very fine whole‐organ sections and collecting high‐magnification and resolution digital images. We therefore designed a large image microscope array (LIMA) to serially section and image entire unembedded organs while maintaining the structural integrity of the tissue. The LIMA consists of several integrated components: a novel large‐blade vibrating microtome, a 1.3 megapixel peltier cooled charge‐coupled device camera, a high‐magnification microscope, and a three axis gantry above the microtome. A custom control program was developed to automate the entire sectioning and automated raster‐scan imaging sequence. The system is capable of sectioning unembedded soft tissue down to a thickness of 40 μm at specimen dimensions of 200 × 300 mm to a total depth of 350 mm. The LIMA system has been tested on fixed lung from sheep and mice, resulting in large high‐quality image data sets, with minimal distinguishable disturbance in the delicate alveolar structures. Anat Rec 290:1377‐1387, 2007. © 2007 Wiley‐Liss, Inc.
Synthesis and In‐Vitro Activity of Novel 1β‐Methylcarbapenems Having Spiro[2,4]heptane Moieties
Authors: Park Hyeong Beom , Jo Nam Hyun , Hong Joon Hee , Chei Jung Hoon , Cho Jung‐Hyuck , Yoo Kyung Ho , Oh Chang‐Hyun
Published: September 2007

The synthesis of a new series of 1β‐methylcarbapenems having spiro[2,4]heptane moieties is described. Their in‐vitro antibacterial activities against both gram‐positive and gram‐negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. Most compounds were shown to be more active than the compared meropenem and imipenem against Escherichia coli. One particular compound, IIIb, having hydroxy a moiety showed the most potent antibacterial activity.
SDX‐308 and SDX‐101, Non‐Steroidal Anti‐Inflammatory Drugs, as Therapeutic Candidates for Treating Hematologic Malignancies Including Myeloma
Authors: Lentzsch Suzanne , Elliott Gary , Roodman G. David
Published: September 2007

Non‐steroidal anti‐inflammatory drugs have been shown to inhibit carcinogenesis in colon cancer, and to induce apoptosis in a variety of tumor cell lines. Some anti‐tumor effects are thought to be related to their cyclooxygenase‐2‐inhibitory activity, but recent studies have shown that non‐steroidal anti‐inflammatory drugs exert their anti‐tumor effect via cyclooxygenase‐2‐independent mechanism. SDX‐308 (CEP‐18082) is a non‐cyclooxygenase‐2‐inhibiting indole‐pyran analog and is structurally related to SDX‐101, an R‐enantiomer of etodolac. SDX‐308 has a potent anti‐myeloma effect and shows synergism in combination with other drugs for the treatment of chronic lymphocytic leukemia. In addition SDX‐308 inhibits osteoclast formation and activity and thereby might be an attractive drug for the treatment of diseases with increased osteoclast activity such as osteolytic lesions in multiple myeloma and metastatic carcinomas, as well as osteoporosis. This review covers future application of SDX‐308 as an anti‐myeloma drug regulating increased osteoclast activity.
Nickel‐Catalyzed Mizoroki–Heck‐ versus Michael‐Type Addition of Organoboronic Acids to α,β‐Unsaturated Alkenes through Fine‐Tuning of Ligands
Authors: Lin Pao‐Shun , Jeganmohan Masilamani , Cheng Chien‐Hong
Published: September 2007

Various arylboronic acids reacted with activated alkenes in the presence of [Ni(dppe)Br2], ZnCl2, and H2O in CH3CN at 80 °C to give the corresponding Mizoroki–Heck‐type addition products in good to excellent yields. Furthermore, 1 equivalent of the hydrogenation product of the activated alkene was also produced. By tuning the ligands of the nickel complexes and the reaction conditions, Michael‐type addition was achieved in a very selective manner. Thus, various p‐ and o‐substituted arylboronic acids or alkenylboronic acid reacted smoothly with activated alkenes in CH3CN at 80 °C for 12 h catalyzed by Ni(acac)2, P(o‐anisyl)3, and K2CO3 to give the corresponding Michael‐type addition products in excellent yields. However, for m‐substituted arylboronic acids, the yields of Michael‐type addition products are very low. The cause of this unusual meta‐substitution effect is not clear. By altering the solvent or phosphine ligand, the product yields for m‐substituted arylboronic acids were greatly improved. In contrast to previous results in the literature, the present catalytic reactions required water for Mizoroki–Heck‐type products and dry reaction conditions for Michael‐type addition products. Possible mechanistic pathways for both addition reactions are proposed.
Simultaneous versus sequential pharmacokinetic‐pharmacodynamic population analysis using an Iterative Two‐Stage Bayesian technique
Authors: Proost Johannes H. , Schiere Sjouke , Eleveld Douglas J. , Wierda J. Mark K. H.
Published: September 2007

A method for simultaneous pharmacokinetic‐pharmacodynamic (PK‐PD) population analysis using an Iterative Two‐Stage Bayesian (ITSB) algorithm was developed. The method was evaluated using clinical data and Monte Carlo simulations.

Data from a clinical study with rocuronium in nine anesthetized patients and data generated by Monte Carlo simulation using a similar study design were analysed by sequential PK‐PD analysis, PD analysis with nonparametric PK data and simultaneous PK‐PD analysis. Both PK and PD data sets were ‘rich’ with respect to the number of measurements per individual. The accuracy and precision of the estimated population parameters were evaluated by comparing their mean error (ME) and root mean squared error (RMSE), respectively. The influence of PD model misspecification on the results was also investigated.

The simultaneous PK‐PD analysis resulted in slightly more precise population parameter estimates than the sequential PK‐PD analysis and the nonparametric PK method. In the presence of PD model misspecification, however, simultaneous analysis resulted in poor PK parameter estimates, while sequential PK‐PD analysis performed well.

In conclusion, ITSB is a valuable technique for PK‐PD population analysis of rich data sets. The sequential PK‐PD method is better suited for the analysis of rich data than the simultaneous analysis. Copyright © 2007 John Wiley & Sons, Ltd.
Nutrient intakes in women and risks of anophthalmia and microphthalmia in their offspring
Authors: Shaw Gary M. , Carmichael Suzan L. , Laurent Cecile , Louik Carol , Finnell Richard H. , Lammer Edward J.
Published: September 2007

BACKGROUND There is a paucity of information about risk factors for the human eye anomalies anophthalmia and microphthalmia. In this population‐based case‐control study we investigated whether periconceptional intakes of supplemental folic acid, dietary folate, vitamin A, and several other nutrients were associated with these eye defects. METHODS This study included data on deliveries that had estimated due dates from 1997–2002 and were part of the National Birth Defects Prevention Study (the National Birth Defects Prevention Study is a population‐based case‐control study of a wide spectrum of birth defects, incorporating data from 10 birth defects surveillance systems in the United States [Arkansas, California, Georgia/Centers for Disease Control and Prevention, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah]). Cases were those infants or fetuses born with either anophthalmia or microphthalmia. Liveborn infants without major malformations were eligible as controls. Maternal interviews were conducted, primarily by telephone, in English or Spanish. Participation in the interview was 71% among case mothers and 68% among control mothers. Interviews were completed with 89 case mothers and 4,143 control mothers. A shortened version of the food frequency questionnaire from the Nurse's Health Study was used to assess frequency of intake of 58 food items during the year before pregnancy. RESULTS Our results did not indicate reduced risks for these eye malformations associated with maternal intake of vitamin supplements containing folic acid. The data did not show an association between malformation risk and higher or lower intakes of vitamin A. We also did not observe strong evidence that an abundance or a lack of dietary intake of any other nutrient was associated with increased risk of the studied eye malformations. CONCLUSIONS Our observations contribute to a limited body of findings on these rare eye defects. © 2007 Wiley‐Liss, Inc.
Experimental induction of palate shelf elevation in glutamate decarboxylase 67‐deficient mice with cleft palate due to vertically oriented palatal shelf
Authors: Iseki Sachiko , Ishii‐Suzuki Masako , Tsunekawa Naoko , Yamada Yoko , Eto Kazuhiro , Obata Kunihiko
Published: September 2007

BACKGROUND:

Gamma‐aminobutyric acid is an inhibitory neurotransmitter, synthesized by two isoforms of glutamate decarboxylase (GAD), GAD65 and ‐67. Unexpectedly, inactivation of GAD67 induces cleft palate in mice. Reduction of spontaneous tongue movement resulting from decreased motor nerve activity has been related to the development of cleft palate in GAD67−/− fetuses. In the present study, development of cleft palate was examined histologically and manipulated with culture of the maxilla and partial resection of fetal tongue.

METHODS:

GAD67−/− mice and their littermates were used. Histological examination and immunohistochemistry were performed conventionally. Organ culture of the maxilla was carried out as reported previously. Fetuses were maintained alive under anesthesia and tips of their tongues were resected.

RESULTS:

Elevation of palatal shelves, the second step of palate formation, was not observed in GAD67−/− mice. In wild‐type mice, GAD67 and gamma‐aminobutyric acid were not expressed in the palatal shelves, except in the medial edge epithelium. During 2 days of culture of maxillae dissected from E13.5–E14.0 GAD67−/− fetuses, elevation and fusion of the palatal shelves were induced. When E13.5–15.5 mutant fetuses underwent partial tongue resection, the palatal shelves became elevated within 30 min.

CONCLUSIONS:

These results suggest that the potential for palate formation is maintained in the palatal shelves of GAD67−/− fetuses, but it is obstructed by other, probably neural, factors, resulting in cleft palate. Birth Defects Research (Part A) 2007. © 2007 Wiley‐Liss, Inc.
The Log Multinomial Regression Model for Nominal Outcomes with More than Two Attributes
Authors: Blizzard L. , Hosmer D. W.
Published: September 2007

An estimate of the risk or prevalence ratio, adjusted for confounders, can be obtained from a log binomial model (binomial errors, log link) fitted to binary outcome data. We propose a modification of the log binomial model to obtain relative risk estimates for nominal outcomes with more than two attributes (the “log multinomial model”). Extensive data simulations were undertaken to compare the performance of the log multinomial model with that of an expanded data multinomial logistic regression method based on the approach proposed by Schouten et al. (1993) for binary data, and with that of separate fits of a Poisson regression model based on the approach proposed by Zou (2004) and Carter, Lipsitz and Tilley (2005) for binary data. Log multinomial regression resulted in “inadmissable” solutions (out‐of‐bounds probabilities) exceeding 50% in some data settings. Coefficient estimates by the alternative methods produced out‐of‐bounds probabilities for the log multinomial model in up to 27% of samples to which a log multinomial model had been successfully fitted. The log multinomial coefficient estimates generally had lesser relative bias and mean squared error than the alternative methods. The practical utility of the log multinomial regression model was demonstrated with a real data example. The log multinomial model offers a practical solution to the problem of obtaining adjusted estimates of the risk ratio in the multinomial setting, but must be used with some care and attention to detail. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Inference Methods for the Conditional Logistic Regression Model with Longitudinal Data
Authors: Craiu Radu V. , Duchesne Thierry , Fortin Daniel
Published: September 2007

This paper considers inference methods for case‐control logistic regression in longitudinal setups. The motivation is provided by an analysis of plains bison spatial location as a function of habitat heterogeneity. The sampling is done according to a longitudinal matched case‐control design in which, at certain time points, exactly one case, the actual location of an animal, is matched to a number of controls, the alternative locations that could have been reached. We develop inference methods for the conditional logistic regression model in this setup, which can be formulated within a generalized estimating equation (GEE) framework. This permits the use of statistical techniques developed for GEE‐based inference, such as robust variance estimators and model selection criteria adapted for non‐independent data. The performance of the methods is investigated in a simulation study and illustrated with the bison data analysis. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Solid‐phase synthesis of 4,8‐disubstituted‐8,9‐dihydropyrazino[2,3‐g]quinazolin‐7(6H)‐ones
Authors: Zhang Yandong , Yao Chao , Houghten Richard A. , Yu Yongping
Published: September 2007

An approach for the solid‐phase synthesis of 4,8‐disubstituted‐8,9‐dihydropyrazino[2,3‐g]quinazolin‐7(6H)‐ones from 4‐chloro‐7‐fluoro‐6‐nitroquinazoline scaffold is described. A chemoselective reaction of resin‐bound arylamines (3) with 4‐chloro‐7‐fluoro‐6‐nitroquinazoline (8) yielded resin‐bound 4‐arylamino‐7‐fluoro‐6‐nitroquinazolines (4), which were reacted with amino acid methyl esters to afford the corresponding resin‐bound compound (5). Following the reduction of nitro group and intramolecular cyclization of 5, resin‐bound 4,8‐disubstituted‐8,9‐dihydropyrazino[2,3‐g]quinazolin‐7(6H)‐one (6) was yielded. The desired products (7) were obtained in good yields and purities after cleavage from the resin. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 439–443, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Inhibition of autophosphorylation of epidermal growth factor receptor by a small peptide not employing an ATP‐competitive mechanism
Authors: Abe Mineo , Kuroda Yoshihiro , Hirose Munetaka , Kato Masaki , Murakami Masahiro , Watanabe Yoshihiko , Nakano Minoru , Handa Tetsurou
Published: September 2007

Previously we found that short peptides surrounding major autophosphorylation sites of EGFR (VPEY1068INQ, DY1148QQD, and ENAEY1173LR) suppress phosphorylation of purified EGFR to 30–50% at 4000 μM. In an attempt to improve potencies of the peptides, we modified the sequences by substituting various amino acids for tyrosine or by substituting Gln and Asn for Glu and Asp, respectively. Among the modified peptides, Asp/Asn‐ and Glu/Gln‐substitution in DYQQD (NYQQN) and ENAEYLR (QNAQYLR), respectively, improved inhibitory potencies. The inhibitory potency of NYQQN was not affected by the concentration of ATP, while that of QNAQYLR was affected. Docking simulations showed different mechanisms of inhibition for the peptides: inhibition by binding to the ATP‐binding site (QNAQYLR) and inhibition by binding to a region surrounded by αC, the activation loop, and the catalytic loop and interfering with the catalytic reaction (NYQQN). The inhibitory potency of NYQQN for insulin receptor drastically decreased, whereas QNAQYLR inhibited autophosphorylation of insulin receptor as well as EGFR. In conclusion, NYQQN is not an ATP‐competitive inhibitor and the binding site of this peptide appears to be novel as a tyrosine kinase inhibitor. NYQQN could be a promising seed for the development of anti‐cancer drugs having specificity for EGFR. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 40–51, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Nitric oxide synthase in critically ischaemic muscle and alterations in isoform expression during revascularization surgery
Authors: Tsui J C S , Baker D M , Shaw S G , Shi-Wen X , Dashwood M R
Published: September 2007

Background

Dysfunction of the nitric oxide pathway is implicated in peripheral arterial disease. Nitric oxide synthase (NOS) isoforms and NOS activity were studied in muscle from patients with critical leg ischaemia (CLI). Alterations in NOS during revascularization surgery were also assessed.

Methods

Muscle biopsies were taken from patients with CLI undergoing amputation and also from patients undergoing femorodistal bypass at the start of surgery, after arterial clamping and following reperfusion. The presence of NOS within muscle sections was confirmed using reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. NOS isoform distribution was studied by immunohistochemistry. NOS mRNA and protein levels were measured using real-time reverse transcriptase–polymerase chain reaction and western blotting. NOS activity was assessed with the citrulline assay.

Results

All three NOS isoforms were found in muscle, associated with muscle fibres and microvessels. NOS I and III protein expression was increased in CLI (P = 0·041). During revascularization, further ischaemia and reperfusion led to a rise in NOS III protein levels (P = 0·008). NOS activity was unchanged.

Conclusion

Alterations in NOS I and III occurred in muscle from patients with CLI and further changes occurred during bypass surgery.
Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy
Authors: Birgisson H , Påhlman L , Gunnarsson U , Glimelius B
Published: September 2007

Background

The aim of the study was to analyse late gastrointestinal disorders necessitating hospital admission following rectal cancer surgery and to determine their relationship to preoperative radiation therapy.

Methods

Curatively treated patients participating in the Swedish Rectal Cancer Trial during 1987–1990, randomized to preoperative irradiation (454 patients) or surgery alone (454), were matched against the Swedish Hospital Discharge Registry. Hospital records for patients admitted with gastrointestinal diagnoses were reviewed.

Results

Irradiated patients had an increased relative risk (RR) of late small bowel obstruction (RR 2·49 (95 per cent confidence interval (c.i.) 1·48 to 4·19)) and abdominal pain (RR 2·09 (95 per cent c.i. 1·03 to 4·24)) compared with patients treated by surgery alone. The risk of late small bowel obstruction requiring surgery was greatly increased (RR 7·42 (95 per cent c.i. 2·23 to 24·66)). Irradiated patients with postoperative anastomotic leakage were at increased risk for late small bowel obstruction (RR 2·99 (95 per cent c.i. 1·07 to 8·31)). The risk of small bowel obstruction was also related to the radiation technique and energy used.

Conclusion

Small bowel obstruction is more common in patients with rectal cancer treated with preoperative radiation therapy.
Acoustic chemometrics of complex natural systems: flume test rig feasibility studies for monitoring river bed‐load sediment transportation processes
Authors: Esbensen Kim H. , Ade Premus K. , Zuta John F. , Bogen Jim , Møen Knut
Published: September 2007

A feasibility study has been carried out on a meso‐scale experimental flume rig with the objective of developing a robust acoustic chemometrics facility of bed‐load mass flux quantification for deployment in rivers and hydroelectric power plant inlet canal systems. The test rig is equipped with an acoustic sensor attached to a steel plate flush with the flume bottom, reproducing natural sedimentary river bed‐load transportation characteristics. Sensor signals were preprocessed by the Fast Fourier Transform (FFT) and subjected to multivariate calibration (PLS1 regression), enabling prediction of sediment bed‐load transport interacting with varying sedimentary characteristics. Based on a comprehensive experimental design on two major factors (F1: mass flux; F2: grain‐size distribution), it is concluded that reliable, test set validated PLS‐prediction models can be established for bed‐load mass fluxes with effective compensation for widely varying sediment size. The main models developed display average relative prediction errors (RMSEP) spanning 4.8–13.2%; the highest errors reflect scenarios modelling for seven non‐overlapping size fraction ranges simultaneously. All real‐world river implementations will experience significantly less varied sediment variability than this worst case scenario, thus realistic models will be characterised by relative RMSEP of some 10% or lower, highly satisfactory for such complex natural systems. All results, interpretations and conclusions reached in the present study are based on the most stringent test set validation protocol. The specific acoustic impact on the sensor plate by sediments characterised by different grain‐size distributions must be expected to lead to significant interaction with the mass flux signals. The experimental design was therefore deployed as a full two‐factor design (7 and 8 levels, respectively), totaling 2 × 56 runs (calibration and test set). Because of a very high sensitivity to the specific time‐varying transportation regimen over the river bottom (successfully duplicated on the flume rig bottom), conventional cross‐validation of a single training set model predicting sediment mass flux runs a high risk of being over‐optimistic, unable to produce a realistic prediction performance assessment. Only true test set validation—an independent second set of all runs in the design covering the same experimental space as the training data—can substantiate a realiable, scientifically acceptable prediction performance validation. This setup allows practical evaluation of the relative merits of cross‐validation versus test set validation in situations in which there is a significant complement of sampling, analysis and measurement errors in both [X,Y] data. Copyright © 2007 John Wiley & Sons, Ltd.
Unusual Coexistence of Magnetic and Nonmagnetic Mo6 Octahedral Clusters in a Chalcohalide Solid Solution: Synthesis, X‐ray Diffraction, EPR, and DFT Investigations of Cs3Mo6Ii6Ii2−xSeixIa6
Authors: Kirakci Kaplan , Cordier Stéphane , Shames Alex , Fontaine Bruno , Hernandez Olivier , Furet Eric , Halet Jean‐François , Gautier Régis , Perrin Christiane
Published: September 2007

The Cs3Mo6Ii6Ii2−xSeixIa6 series has been obtained by a solid‐state route. There is evidence for a solid solution between the compositions Cs3Mo6Ii6Ii0.8Sei1.2Ia6 and Cs3Mo6Ii6Ii0.4Sei1.6Ia6 (space group: R$\bar 3$c, Z=6; a=16.7065(4), c=20.5523(4) Å, V=4967.8(2) Å3 and a=16.6354(3), c=20.5444(4) Å, V=4923.7(2) Å3, respectively). The structure of this new series is based on magnetic [Mo6Ii6Sei2Ia6]3− and diamagnetic [Mo6Ii7SeiIa6]3− units with 23 and 24 valence electrons per Mo6 cluster, respectively. For a particular x, the structure of Cs3Mo6Ii6Ii2−xSexIa6 is based on a mixture of (x−1) [Mo6Ii6Sei2Ia6]3− with (2−x) [Mo6Ii7SeiIa6]3−. This leads to an average [Mo6Ii6Ii2−xSexIa6]3− ionic unit deduced from single‐crystal X‐ray diffraction investigations. The two inner positions of the average face‐capped [Mo6Ii8−xSeixIa6]3− ionic units (located on the threefold axis of the unit) are randomly occupied by iodine and selenium, whereas the other ligand positions are fully occupied by iodine. Low‐temperature electron paramagnetic resonance (EPR) studies reveal a signal split into two components with g∥>g⊥. The reciprocal double integration intensity of the EPR signal versus T graph reveals a typical Curie law behavior. A density functional theory (DFT) study indicates that occupation of the inner position on the threefold axis by selenium atoms is preferred energetically among the three possible distributions of selenium atoms. The comparison of experimental and theoretical g values confirms the crystallographic analysis and agrees with the axial elongation of the Mo6 cluster within the crystal structure.
Bis[bis‐(4‐alkoxyphenyl)amino] Derivatives of Dithienylethene, Bithiophene, Dithienothiophene and Dithienopyrrole: Palladium‐Catalysed Synthesis and Highly Delocalised Radical Cations
Authors: Odom Susan A. , Lancaster Kelly , Beverina Luca , Lefler Kelly M. , Thompson Natalie J. , Coropceanu Veaceslav , Brédas Jean‐Luc , Marder Seth R. , Barlow Stephen
Published: September 2007

Five diamines with thiophene‐based bridges—(E)‐1,2‐bis{5‐[bis(4‐butoxyphenyl)amino]‐2‐thienyl}ethylene (1), 5,5′‐bis[bis(4‐methoxyphenyl)amino]‐2,2′‐bithiophene (2), 2,6‐bis[bis(4‐butoxyphenyl)amino]dithieno[3,2‐b:2′,3′‐d]thiophene (3), N‐(4‐tert‐butylphenyl)‐2,6‐bis[bis(4‐methoxyphenyl)amino]dithieno[3,2‐b:2′,3′‐d]pyrrole (4 a) and N‐tert‐butyl‐2,6‐bis[bis(4‐methoxyphenyl)amino]dithieno[3,2‐b:2′,3′‐d]pyrrole (4 b)—have been synthesised. The syntheses make use of the palladium(0)‐catalysed coupling of brominated thiophene species with diarylamines, in some cases accelerated by microwave irradiation. The molecules all undergo facile oxidation, 4 b being the most readily oxidised at about −0.4 V versus ferrocenium/ferrocene, and solutions of the corresponding radical cations were generated by addition of tris(4‐bromophenyl)aminium hexachloroantimonate to the neutral species. The near‐IR spectra of the radical cations show absorptions characteristic of symmetrical delocalised species (that is, class III mixed‐valence species); analysis of these absorptions in the framework of Hush theory indicates strong coupling between the two amine redox centres, stronger than that observed in species with phenylene‐based bridging groups of comparable length. The strong coupling can be attributed to high‐lying orbitals of the thiophene‐based bridging units. ESR spectroscopy indicates that the coupling constant to the amino nitrogen atoms is somewhat reduced relative to that in a stilbene‐bridged analogue. The neutral species and the corresponding radical cations have been studied with the aid of density functional theory and time‐dependent density functional theory. The DFT‐calculated ESR parameters are in good agreement with experiment, while calculated spin densities suggest increased bridge character to the oxidation in these species relative to that in comparable species with phenylene‐based bridges.
Vesicles of a New Salt‐Free Cat‐anionic Fluoro/Hydrocarbon Surfactant System
Authors: Li Xin , Dong Shuli , Jia Xiangfeng , Song Aixin , Hao Jingcheng
Published: September 2007

Weakly basic tetradecyldimethylaminoxide (C14DMAO) molecules can be protonated to form a cationic surfactant, C14DMAOH+, by an acidic fluorocarbon surfactant, an 8‐2‐fluorotelomer unsaturated acid (C7F15CFCHCOOH), to form a salt‐free cationic and anionic (cat‐anionic) fluoro/hydrocarbon surfactant system in aqueous solution. The high Krafft point of C7F15CFCHCOOH was largely reduced as a result of being mixed with a C14DMAO micelle solution. A study of the phase behavior of the new salt‐free cat‐anionic fluoro/hydrocarbon surfactant system clearly indicates the existence of a birefringent Lα‐phase region at (25.0±0.1) °C. The birefringent Lα phase consists of vesicles, which include uni‐ and multilamellar vesicles with one to dozens of shells, and oligovesicular vesicles, as demonstrated by freeze‐fracture and cryo‐transmission electron microscopy (FF‐ and cryo‐TEM) images. The size distribution and structural transitions in the salt‐free cat‐anionic fluoro/hydrocarbon surfactant system were studied by dynamic light scattering (DLS) and 1H and 19F NMR spectroscopy. The formation of a salt‐free cat‐anionic vesicle phase could be induced by the strong electrostatic interaction between the cationic hydrocarbon C14DMAOH+ and the anionic fluorocarbon C7F15CFCHCOO−, which provided evidence that the electrostatic interaction between the cationic and anionic surfactants is larger than the nonsynergistic interaction between the stiff fluorocarbon and the soft hydrocarbon chains of the surfactants.
A Convergent Pd‐Catalyzed Asymmetric Allylic Alkylation of dl‐ and meso‐Divinylethylene Carbonate: Enantioselective Synthesis of (+)‐Australine Hydrochloride and Formal Synthesis of Isoaltholactone
Authors: Trost Barry M. , Aponick Aaron , Stanzl Benjamin N.
Published: September 2007

The use of a mixture of dl‐ and meso‐divinylethylene carbonate as an electrophile in palladium‐catalyzed asymmetric allylic alkylation reactions is reported. From the diastereomeric mixture of meso and chiral racemic starting materials, a single product is obtained in high optical purity employing either oxygen or nitrogen nucleophiles. The resulting dienes have proven to be versatile synthetic intermediates as each carbon is functionalized for further transformation and differentiated by virtue of the reaction. A mechanism for this intriguing transformation is proposed and a concise enantioselective total synthesis of (+)‐australine hydrochloride is reported as well as a formal synthesis of isoaltholactone.
Electronic Structures of Five‐Coordinate Complexes of Iron Containing Zero, One, or Two π‐Radical Ligands: A Broken‐Symmetry Density Functional Theoretical Study
Authors: Chłopek Krzysztof , Muresan Nicoleta , Neese Frank , Wieghardt Karl
Published: September 2007

The electronic structures of a series of five‐coordinate complexes of iron containing zero, one, or two bidentate, organic π‐radical ligands and a monodentate ligand (pyridine, iodide) have been studied by broken‐symmetry (BS) density functional theoretical (DFT) methods. By analyzing the set of corresponding orbitals5 (CO) a convenient division of the spin‐up and spin‐down orbitals into 1) essentially doubly‐occupied molecular orbitals (MO), 2) exactly singly‐occupied MOs, 3) spin‐coupled pairs, and 4) virtual orbitals can be achieved and a clear picture of the spin coupling between the ligands (non‐innocence vs. innocence) and the central metal ion (dN configuration) can be generated. We have identified three classes of complexes which all contain a ferric ion (d5) with an intrinsic intermediate spin (SFe= 3/2) that yield 1) an St=3/2 ground spin state if the two bidentate ligands are closed‐shell species (innocent ligands); 2) if one π‐radical ligand is present, an St=1 ground state is obtained through intramolecular antiferromagnetic coupling; 3) if two such radicals are present, an St=1/2 ground state is obtained. We show unambiguously for the first time that the pentane‐2,4‐dione‐bis(S‐alkylisothiosemicarbazonato) ligand can bind as π‐radical dianion (L.TSC)2− in [FeIII(L.TSC)I] (St=1) (6); the description as [FeIV(LTSC3−)I] is incorrect. Similarly, the diamagnetic monoanion in 14 must be described as [FeIII(CN)2(L.TSC)]− (St=0) with a low‐spin ferric ion (d5, SFe=1/2) coupled antiferromagnetically to a π‐radical ligand; [FeII(CN)2(LTSC−)]− is an incorrect description.
Intermediates in the Destruction of Chlorinated C1 Hydrocarbons on La‐Based Materials: Mechanistic Implications
Authors: van der Heijden Alwies W. A. M. , Garcia Ramos Maria , Weckhuysen Bert M.
Published: September 2007

Activity experiments using GC analysis of reactor effluent have been combined with in situ IR spectroscopy to elucidate the reaction steps in the destructive adsorption of CHCl3, CH2Cl2, and CH3Cl over LaOCl. The IR results show that during reaction, LaOCl is covered with carbonate, formate, and methoxy groups. The relative amount of each of these surface intermediates depends on the Cl/H ratio of the reactant. The decomposition of the surface species leads to formation of the reaction products, and is influenced by the temperature and the relative amount of Cl present on the surface. The GC results show that the activity for the destructive adsorption of H‐containing chlorinated C1 compounds decreases with increasing hydrogen content of the reactant. The acquired insight into the mechanism of destructive adsorption is crucial to the design of new catalyst materials for the efficient conversion of chlorinated hydrocarbons into nonhazardous products or reusable chemicals.
Contrasting pKa of Protonated Bis(3‐aminopropyl)‐Terminated Polyethylene Glycol “Jeffamine” and the Associated Thermodynamic Parameters in Solution and Covalently Attached to Graphite Surfaces
Authors: Abiman Poobalasingam , Wildgoose Gregory G. , Crossley Alison , Jones John H. , Compton Richard G.
Published: September 2007

The pKa value of protonated Jeffamine (bis(3‐aminopropyl) terminated polyethylene glycol) in solution and attached as a monolayer to graphite surfaces has been determined using potentiometric titration. The protonated Jeffamine was found to have a pKa value of 9.7 in solution at 25 °C, whereas this value decreases to 7.1 when it is attached to a graphite surface. Potentiometric titrations from 25 to 40 °C allowed us to determine the surface pKa of the protonated Jeffamine at each temperature studied and hence to determine the enthalpy, entropy and Gibbs energy changes associated with the deprotonation of the amino‐terminated surface bound Jeffamine groups. It was found that the enthalpic contribution is negligibly small and the evaluation of these thermodynamic parameters controlling the shift in surface pKa value indicates that this process is controlled by entropic contribution arising from the ordering/disordering of solvent molecules at the carbon–water interface. This suggests that the long chain Jeffamine molecules are oriented on the carbon surface rather than existing in the bulk solution.
Copper‐Catalyzed Asymmetric Conjugate Addition of Trialkylaluminium Reagents to Trisubstituted Enones: Construction of Chiral Quaternary Centers
Authors: Vuagnoux‐d'Augustin Magali , Alexakis Alexandre
Published: September 2007

Me3Al, Et3Al, and vinylalane species undergo enantioselective conjugate addition to a wide range of 2‐ or 3‐substituted enones (cyclopent‐2‐enones, cyclohex‐2‐enones, 3‐methyl cyclohept‐2‐enone) in the presence of catalytic amount of copper salt (copper thiophene carboxylate, [Cu(CH3CN)4]BF4 or [CuOTf]2⋅C6H6) and tropos‐phosphoramidite‐based ligand. Thus, chiral quaternary centers can be built, with up to 98 % ee after rigorous optimization of experimental conditions. It was shown that the main important parameter was the order of the introduction of the reagents. Then, the generated enantioenriched aluminium enolates and the chiral conjugate adducts were functionalized and used for subsequent reactions.
Halogen—Magnesium Exchange on Unprotected Aromatic and Heteroaromatic Carboxylic Acids.
Authors: Kopp Felix , Wunderlich Stefan , Knochel Paul
Published: September 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Total Synthesis of Dolastatin 10 Through Ruthenium‐Catalyzed Asymmetric Hydrogenations.
Authors: Mordant Celine , Reymond Sebastien , Tone Hitoshi , Lavergne Damien , Touati Ridha , Ben Hassine Bechir , Ratovelomanana‐Vidal Virginie , Genet Jean‐Pierre
Published: September 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A New α‐Pyrone Derivative, 6‐[(E)‐Hept‐1‐enyl]‐α‐pyrone, with Tyrosinase Inhibitor Activity from a Marine Isolate of the Fungus Botrytis.
Authors: Zhang Dahai , Li Xianguo , Kang Jung Sook , Choi Hong Dae , Son Byeng Wha
Published: September 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Comparison of Topological, Shape, and Docking Methods in Virtual Screening.
Authors: McGaughey Georgia B. , Sheridan Robert P. , Bayly Christopher I. , Culberson J. Chris , Kreatsoulas Constantine , Lindsley Stacey , Maiorov Vladimir , Truchon Jean‐Francois , Cornell Wendy D.
Published: September 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Dendrimer‐Encapsulated Bimetallic Nanoparticles — Synthesis, Characterization, and Applications to Homogeneous and Heterogeneous Catalysis
Authors: Chandler Bert D. , Gilbertson John D.
Published: September 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Dystonin/Bpag1—A link to what?
Authors: Young Kevin G. , Kothary Rashmi
Published: September 2007

The dystonin/Bpag1 cytoskeletal interacting proteins play important roles in maintaining cytoarchitecture integrity in skin and in the neuromuscular system. The most profound phenotype observed in the dystonin mutant dystonia musculorum (dt) mice is a severe movement disorder, attributed in large part to sensory neuron degeneration. The molecular basis for this phenotype is currently not clear, despite several studies indicating possible causes for the pathology in dt mice. Complicating the picture of what essential dystonin functions are lost in dt mice is the fact that our understanding of the very nature of what dystonin is has evolved greatly over the past decade. Elucidating the roles of dystonin most relevant to neuronal function and survival should help to shed light on some of the common mechanisms underlying neurodegeneration. Cell Motil. Cytoskeleton 2007. © 2007 Wiley‐Liss, Inc.
Loss of programmed cell death 4 expression marks adenoma‐carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer
Authors: Mudduluru Giridhar , Medved Fabian , Grobholz Rainer , Jost Camela , Gruber Anette , Leupold Joerg H. , Post Stefan , Jansen Aaron , Colburn Nancy H. , Allgayer Heike
Published: September 2007

BACKGROUND.

Programmed cell death 4 (Pdcd4) inhibits malignant transformation, and initial studies of Pdcd4 suggested the regulation of Pdcd4 localization by protein kinase B (Akt). However, supporting patient tissue data are missing, and the diagnostic/prognostic potential of Pdcd4 rarely has been studied. The objectives of the current were 1) to determine Pdcd4 as a diagnostic marker in the adenoma‐carcinoma sequence, 2) to support phosphorylated Akt (pAkt)‐mediated Pdcd4 regulation in vivo, and 3) to obtain the first prognostic evidence of Pdcd4 in colorectal cancer.

METHODS.

Tumor samples and normal tissues from 71 patients with colorectal cancer who were followed prospectively (median follow‐up, 36 months) and 42 adenomas were analyzed for Pdcd4, Akt, and pAkt in immunohistochemical and Western blot analyses.

RESULTS.

A significant reduction in Pdcd4 was observed between normal mucosa and adenomas and between adenomas and tumor samples (P < .01 and P < .01, respectively). Normal mucosa demonstrated strong nuclear Pdcd4, which was reduced significantly in adenomas (P < .01) and almost was lost in tumors (P < .01). pAkt was correlated inversely with Pdcd4 and with the transition of Pdcd4 from nucleus to cytoplasm (P < .01). Kaplan‐Meier analysis (using the Mantel‐Cox log‐rank test) indicated a significant correlation between the loss of total and nuclear Pdcd4 in tumors and overall survival (P < .05 and P < .02, respectively) and disease‐specific survival (P < .01 and P < .01, respectively). In multivariate analysis, loss of total or nuclear Pdcd4 was an independent predictor of disease‐specific or overall survival.

CONCLUSIONS.

To the authors' knowledge, this is the first study to demonstrate an independent prognostic impact of Pdcd4 and its expression pattern in colorectal cancer. Data from this study support the regulation of Pdcd4 localization by pAkt in vivo. Pdcd4 immunohistochemistry may be useful as a supportive diagnostic tool for the transition between normal, adenoma, and tumor tissues. Cancer 2007. Published 2007 by the American Cancer Society.
Descriptive nomograms of adjuvant radiotherapy use and patterns of care analysis for stage I and II endometrial adenocarcinoma: A surveillance, epidemiology, and end results population study
Authors: Lee Christopher M. , Szabo Aniko , Shrieve Dennis C. , Macdonald O. Kenneth , Tward Jonathan D. , Skidmore Thomas B. , Gaffney David K.
Published: September 2007

BACKGROUND.

Although endometrial cancer remains the most common gynecologic malignancy in the United States, differing approaches to adjuvant radiotherapy treatment for early disease exist within the medical community because of the lack of a national consensus.

METHODS.

The authors studied patterns of adjuvant care for stage I and II endometrial adenocarcinoma using a large United States population database. A retrospective analysis was conducted from the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute from 1988 to 2002, and 26,923 women with American Joint Committee on Cancer stage I and II endometrial adenocarcinoma were selected. The following prognostic factors were analyzed: age, race, stage, grade, year of diagnosis, SEER registry location, and use and type of postoperative radiotherapy (RT). Adjuvant RT was coded as none, external‐beam RT (EBRT), brachytherapy (BR), or a combination of the 2 (EBRT + BR).

RESULTS.

Higher tumor grade and stage led to greater use of RT. The odds ratio (OR) for adjuvant RT was 3.4 for stage IB versus stage IA and 51.8 for stage IC/II versus stage IA. The effect of grade depended on stage: for stages IA and IB, the OR was 2.9 for grade 2 versus grade 1 and 11.7 for grade 3/4 versus grade 1; whereas, for stage IC/II, the OR was 1.5 for grade 2 versus grade 1 and 2.0 for grade 3/4 versus grade 1. Within stage I, increasing substage and grade increased the odds of EBRT with or without BR compared with BR alone. Race did not effect the choice of therapy (all P > .1). Geographic location had a significant effect on overall RT use and therapy choice.

CONCLUSIONS.

To the authors' knowledge, this was the largest patterns of care analysis to date of adjuvant RT in patients with stage I and II endometrial adenocarcinoma. The current study revealed that there is significant diversity in the use of adjuvant RT across the United States, and the results reflected the absence of a national consensus on adjuvant treatment for early‐stage disease. Cancer 2007. © 2007 American Cancer Society.
Interleukin‐6 and its receptor in cancer
Authors: Hong David S. , Angelo Laura S. , Kurzrock Razelle
Published: September 2007

Interleukin‐6 (IL‐6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL‐6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL‐6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL‐6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL‐6 are observed in almost every type of tumor studied and predict a poor outcome. Furthermore, elevated IL‐6 levels are associated strongly with several of the striking phenotypic features of cancer. Several molecules have been developed recently that target the biologic function of IL‐6. Early results in the clinic suggest that this strategy may have a significant salutary impact on diverse tumors. The field of cytokine research has yielded a deep understanding of the fundamental role of IL‐6 and its receptor in health and disease. Therapeutic targeting of IL‐6 and its receptor in cancer has strong biologic rationale, and there is preliminary evidence suggesting that targeting of the IL‐6 system may be beneficial in the treatment of cancer. Cancer 2007. © 2007 American Cancer Society.
Surviving colorectal cancer
Authors: Schneider Eric C. , Malin Jennifer L. , Kahn Katherine L. , Ko Clifford Y. , Adams John , Epstein Arnold M.
Published: September 2007

BACKGROUND.

The number of long‐term survivors after a cancer diagnosis is increasing, yet relatively few studies have addressed survivors' reported symptoms beyond the initial year after diagnosis.

METHODS.

The symptom reports of 474 survivors of colon and rectal cancer from 5 US metropolitan areas were collected during 2002‐2003 as part a larger study of the quality of care for patients with cancer diagnosed in 1998. The relation between the prevalence of reported symptoms and prior treatments received was analyzed, adjusting statistically for other patient characteristics.

RESULTS.

Sixty‐nine percent of the survivors had colon cancer and 31% had rectal cancer. The most commonly reported symptoms were “fatigue” (23%), “negative feelings about body appearance” (14%), “diarrhea” (13%), and “constipation” (7%). Higher percentages of respondents attributed health effects to cancer or its treatment including “worry about health” (24%), “physical discomfort” (19%), and “activity limitations” (15%). In general, prior treatment was not associated with symptom prevalence. However, radiation therapy recipients and patients that received a diverting ostomy were more likely than others to report some of the symptoms we studied. Attribution of health effects to disease or treatment did not vary by prior treatment except that recipients of radiation therapy were more likely than others to report limitations in their activities (30% vs 10%; P = .003).

CONCLUSIONS.

Among colorectal cancer survivors the prevalence of symptoms at 4 years was low and relatively comparable to published estimates for the general population, but some survivors continue to attribute health effects to cancer or its treatment. Cancer 2007. © 2007 American Cancer Society.