bluuebunny/crossref_metadata_2025 huggingface dataset:
A model for predicting non-sentinel lymph node metastatic disease when the sentinel lymph node is positive
Authors: Pal A , Provenzano E , Duffy S W , Pinder S E , Purushotham A D
Published: September 2007

Background

Women with axillary sentinel lymph node (SLN)-positive breast cancer usually undergo completion axillary lymph node dissection (ALND). However, not all patients with positive SLNs have further axillary nodal disease. Therefore, in the patients with low risk of further disease, completion ALND could be avoided. The Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram to estimate the risk of non-SLN disease. This study critically appraised the nomogram and refined the model to improve predictive accuracy.

Methods

The MSKCC nomogram was applied to 118 patients with a positive axillary SLN biopsy who subsequently had completion ALND. Predictive accuracy was assessed by calculating the area under the receiver–operator characteristic (ROC) curve. A further predictive model was developed using more detailed pathological information. Backward stepwise multiple logistic regression was used to develop the predictive model for further axillary lymph node disease. This was then converted to a probability score. After k-fold cross-validation within the data, an inverse variance weighted mean ROC curve and area below the ROC curve was calculated.

Results

The MSKCC nomogram had an area under the ROC curve of 68 per cent. The revised predictive model showed the weighted mean area under the ROC curve to be 84 per cent.

Conclusion

The modified predictive model, which incorporated size of SLN metastasis, improved predictive accuracy, although further testing on an independent data set is desirable.
Protective effects of melatonin and N‐acetylserotonin on aflatoxin B1‐induced lipid peroxidation in rats
Authors: Gesing Adam , Karbownik‐Lewinska Malgorzata
Published: September 2007

Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin. Reactive oxygen species are considered to participate in the main mechanism of aflatoxin toxicity. Melatonin (Mel) is a hormone which has antioxidative activities. N‐acetylserotonin (NAc‐5HT) is an immediate precursor of Mel. Melatonin is documented to be completely safe in humans and animals. The aim of our study was to examine the potential protective effects of Mel or NAc‐5HT against lipid peroxidation (LPO), caused by AFB1 in male Wistar rats. Mel and NAc‐5HT were intraperitoneally (i.p.) injected for 3 weeks in late afternoon (16:00–18:00) injections (20 mg kg−1 BW/daily). AFB1 (50 µg kg−1 BW/daily) was administered i.p. 6 h prior to indoleamine injections. Concentrations of malondialdehyde + 4‐hydroxyalkenals (MDA + 4‐HDA), as an index of LPO, were measured in liver, brain, lung, testis and kidney homogenates. The level of LPO in tissue homogenates was expressed as the amount of MDA + 4‐HDA (nmol) per milligram of protein. AFB1 increased LPO in the liver, lung, brain and testis, but not the kidney. The increase of LPO caused by AFB1 injections was completely prevented by either Mel or NAc‐5HT in all the tissues examined. Melatonin can be considered as a protective pharmacological agent in intoxication with AFB1 and the protective effect of NAc‐5HT against aflatoxin‐induced LPO broadens the knowledge about its antioxidative properties. Copyright © 2007 John Wiley & Sons, Ltd.
The Role Played by the α‐Helix in the Unfolding Pathway and Stability of Azurin: Switching Between Hierarchic and Nonhierarchic Folding
Authors: Manetto Gaetano D. , Grasso Domenico M. , Milardi Danilo , Pappalardo Matteo , Guzzi Rita , Sportelli Luigi , Verbeet Martin P. , Canters Gerard W. , La Rosa Carmelo
Published: September 2007

The role played by the α‐helix in determining the structure, the stability and the unfolding mechanism of azurin was addressed by studying a helix‐depleted azurin variant produced by sitedirected mutagenesis. The protein structure was investigated by CD, 1D 1H NMR, fluorescence spectroscopy measurements and MD simulations, whilst EPR, UV‐visible and cyclic voltammetry experiments were carried out to investigate the geometry and the properties of the CuII site. The effects of the α‐helix depletion on the thermal stability and the unfolding pathway of the protein were determined by DSC, UV/visible and fluorescence measurements at increasing temperature. The results show that, in the absence of the α‐helix segment, the overall protein structure is maintained, and that only the Cu site is slightly modified. In contrast, the protein stability is diminished by about 60 % with respect to the wild‐type azurin. Moreover, the unfolding pathway of the mutant azurin involves the presence of detectable intermediates. In comparison with previous studies concerning other small β‐sheet cupredoxins, the results as a whole support the hypothesis that the presence of the α‐helix can switch the folding of azurin from a hierarchic to a nonhierarchic mechanism in which the highly conserved β‐sheet core provides a scaffold for cooperative folding of the wild‐type protein.
Biochemical Studies of the Thermal Effects on DNA Modifications by the Antitumor Cisplatin and Their Repair
Authors: Halamikova Anna , Vrana Oldrich , Kasparkova Jana , Brabec Viktor
Published: September 2007

Using biochemical methods, we have examined the effect of two factors that might play a role in the mechanism of the biological activity of cisplatin at elevated temperatures (>37°C). We show that increased temperatures result in distinct alterations in the modification of the target DNA by cisplatin, and in the repair of these modifications. Our in vitro results support the view that the enhanced DNA‐cross‐linking efficiency of cisplatin and the lower efficiency of native DNA repair mechanisms at higher temperature play at least a partial role in the potentiation of the antitumor effects of cisplatin under conditions of mild hyperthermia.
Synthesis and Characterization of the First Fluorescent Nonpeptide NPY Y1 Receptor Antagonist
Authors: Schneider Erich , Keller Max , Brennauer Albert , Hoefelschweiger Bianca K. , Gross Dietmar , Wolfbeis Otto S. , Bernhardt Günther , Buschauer Armin
Published: September 2007

Cyanine‐5‐labelled neuropeptide Y (NPY) was demonstrated to be an ideal universal fluorescent ligand for the combined investigation of NPY Y1, Y2 and Y5 receptors. With respect to improved stability, detection of receptor subtypes in cells and tissues, and prevention of receptor internalization, small nonpeptidic fluorescent antagonists should be superior. Here we present a set of four fluorescent nonpeptide NPY Y1 receptor (Y1R) antagonists. The highest affinity was obtained by labelling an NG‐(6‐aminohexanoyl)argininamide derived from the Y1R antagonist BIBP 3226, with Py‐1, a small pyrylium dye. The fluorescent pyridinium‐type Y1R antagonist, compound 4 had Ki values of 29 nM and 2.7 nM, which were determined by radioligand binding and flow cytometry under equilibrium conditions, respectively; 4 had a Kb value of 0.6 nM (Ca2+ assay). The large Stoke's shift (541 vs. 615 nm) in buffer (PBS, pH 7.4) in the presence of 1 % BSA and the red emission (quantum yield 56 %) are advantageous with respect to the signal‐to‐noise ratio. The new probe was successfully used in fluorescence‐based binding experiments evaluated by flow cytometry and confocal microscopy; this demonstrates the potential of pyrylium dyes for the preparation of fluorescent ligands that are applicable for the study of G protein‐coupled receptors on living cells.
On the Characterization of Dynamic Supramolecular Systems: A General Mathematical Association Model for Linear Supramolecular Copolymers and Application on a Complex Two‐Component Hydrogen‐Bonding System
Authors: Odille Fabrice G. J. , Jónsson Stefán , Stjernqvist Susann , Rydén Tobias , Wärnmark Kenneth
Published: September 2007

A general mathematical model for the characterization of the dynamic (kinetically labile) association of supramolecular assemblies in solution is presented. It is an extension of the equal K (EK) model by the stringent use of linear algebra to allow for the simultaneous presence of an unlimited number of different units in the resulting assemblies. It allows for the analysis of highly complex dynamic equilibrium systems in solution, including both supramolecular homo‐ and copolymers without the recourse to extensive approximations, in a field in which other analytical methods are difficult. The derived mathematical methodology makes it possible to analyze dynamic systems such as supramolecular copolymers regarding for instance the degree of polymerization, the distribution of a given monomer in different copolymers as well as its position in an aggregate. It is to date the only general means to characterize weak supramolecular systems. The model was fitted to NMR dilution titration data by using the program Matlab®, and a detailed algorithm for the optimization of the different parameters has been developed. The methodology is applied to a case study, a hydrogen‐bonded supramolecular system, salen 4+porphyrin 5. The system is formally a two‐component system but in reality a three‐component system. This results in a complex dynamic system in which all monomers are associated to each other by hydrogen bonding with different association constants, resulting in homo‐ and copolymers 4n5m as well as cyclic structures 6 and 7, in addition to free 4 and 5. The system was analyzed by extensive NMR dilution titrations at variable temperatures. All chemical shifts observed at different temperatures were used in the fitting to obtain the ΔH° and ΔS° values producing the best global fit. From the derived general mathematical expressions, system 4+5 could be characterized with respect to above‐mentioned parameters.
Synthesis of Highly Modified DNA by a Combination of PCR with Alkyne‐Bearing Triphosphates and Click Chemistry
Authors: Gierlich Johannes , Gutsmiedl Katrin , Gramlich Philipp M. E. , Schmidt Alexandra , Burley Glenn A. , Carell Thomas
Published: September 2007

We report the combination of “click chemistry” with PCR by using alkyne‐modified triphosphates for efficient and homogeneous labeling of DNA. A series of modified PCR products of different lengths (300, 900, and 2000 base pairs) were prepared by using a variety of alkyne‐ and azide‐containing triphosphates and different polymerases. After intensive screening of real‐time PCR methods, protocols were developed that allow the amplification of genes by using these modified triphosphates with similar efficiency to that of standard PCR. The click reaction on the highly modified PCR fragments provided conversion rates above 90 % and resulted in the functionalization of hundreds of alkynes on large DNA fragments with superb selectivity and efficiency.
Configurational Stability of Oxymethyllithiums as Intermediates in Intramolecular Rearrangements
Authors: Kapeller Dagmar C. , Brecker Lothar , Hammerschmidt Friedrich
Published: September 2007

Several homochiral oxymethyllithiums, chiral by virtue of the hydrogen isotopes protium and deuterium, were prepared. They were tested for their microscopic configurational stability in intramolecular isomerizations, such as the silyl‐ and germyl‐[1,2]‐retro‐Brook and the sigmatropic[2,3]‐Wittig rearrangement. The influence of temperature, solvent, and migrating group on the stability of the intermediate carbanions was studied. Furthermore, the stereochemical course of these rearrangements was elucidated, resulting in highly enantioenriched alcohols (90–97 % ee; ee=enantiomeric excess) up to temperatures of 0 °C.
Investigation of the Adsorption and Self Assembly of Isocyanide Derivatives on Au(111) Surface
Authors: Zhou Jun‐Hong , Shi Liang‐Wei , Zhang Tao , Chen Min‐Bo
Published: September 2007

The adsorption and self‐assembly of isocyanide derivatives on Au(111) surface were investigated by density functional theory (DFT) and molecular dynamics simulation. The calculation for phenyl isocyanide by DFT was based on cluster and slab models. The self‐assembled monolayers of 2‐isocyanoazulene and 1,3‐diethoxycarbonyl‐ 2‐isocyanoazulene on Au(111) were simulated using Au‐C force field parameters developed by us. It was found that the top site was the most preferred position, and the isocyanoazulene and its derivatives could form the ordered face to edge self‐assembled monolayer on gold surface indeed, and the molecules stood on the gold surface vertically.
Adsorption Behavior of Potassium Ion on Planting Materials
Authors: Paunpassanan Dechprasitthichokea , Sunanta Wangkarna , Sakdiphon Thiansemb , Ponlayuth Sooksamitic , Orn‐anong Arquero
Published: September 2007

Characterization of planting materials used as adsorbent has been studied in order to compare potassium ion adsorption on two types of planting materials, which are a fired planting material (FPM) made from a mixture of 4 kinds of wastes (bottom ash, flue gas desulfurization (FGD) gypsum, paddy soil and sawdust) formed and fired at 850 °C and the commercial planting material called "hydroball" (HDB) bought from Jatujak market, Bangkok. The physical characteristics of both types of planting materials indicate that the FPM has a larger specific surface area than the HDB. The factors affecting potassium adsorption on both the planting materials such as an equilibration time and some solid/solution ratios were investigated. The suitable equilibration time for the adsorption to reach an equilibrium on the FPM and HDB is one and two hours, respectively. The highest amounts of potassium ion adsorbed on both the planting materials were obtained when the solid/solution ratio was 1:15. The adsorption behavior on both the planting materials tends to correspond with the Freundlich isotherm.
Study on the Interaction of Colloidal Gold with Taq DNA Polymerase
Authors: Zhu Hong‐Ping , Mi Li‐Juan , Chen Shi‐Mou , Wang Wen‐Feng , Yao Si‐Dea
Published: September 2007

The interaction of colloidal gold with Taq DNA polymerase (Taq) was investigated in this study. Taq‐gold conjugate was formed by adding the enzyme to the colloidal gold solution, as evidenced by UV‐Vis spectroscopy, X‐ray photoelectron spectroscopy, and photon cross correlation spectroscopy measurements. The conjugate was further characterized by transmission electron microscopy. It was found that the Taq‐gold conjugate particles were still spherical and well‐dispersed. The influence of gold nanoparticles on the bioactivity of Taq was studied by analyzing the yield of the polymerase chain reaction amplification. Results indicated that the enzymatic activity of Taq decreased after interaction with the colloidal gold.
Photovoltaic Characteristics of a Naphthylamine Derivative
Authors: Fu Hui‐Ying , Song Qun‐Liang , Sun Xiao‐Yu , Hou Xiao‐Yuan , Xiao Fei , Shao Bing‐Xian
Published: September 2007

Organic photovoltaic (OPV) cells were fabricated via vacuum vapor deposition with {4‐[2‐(3‐dicyanomethylidene‐5,5‐dimethylcyclohexenyl)vinyl]phenyl}di(1‐naphthyl)amine (DNP‐2CN) as the electron donor, and fullerene (C60) as the electron acceptor. A thin film (10 nm) of tris(8‐quinolinolato)aluminum (Alq3) was adopted as the buffer layer. A device based on this DNP‐2CN exhibited an open circuit voltage (Voc) of 370 mV, a short‐circuit current density (Jsc) of 0.61 mA·cm−2, and a white‐light power conversion efficiency (() of 0.09% (AM1.5, 75 mW·cm−2).
Comparative Study of Hypophosphite H2PO−2Adsorption on Ni(111) and Ag(111) Surfaces by DFT
Authors: Zeng Yue , Ou Li‐Hui , Li Ze‐Lin , Xiao Xiao‐Ming , Xia Shao‐Xi
Published: September 2007

Surface structures and electronic properties of hypophosphiteon Ni(111) and Ag(111) surfaces were investigated by means of density functional theory at B3LYP/6‐31++G(d,p) level. The most stable structure was that in which theadsorbs with its two P–O bonds faced to the substrate surface. The results of the Mulliken population analysis showed that because of the subtle difference of electron configuration, the adsorption energy was larger on the Ni surface than on the Ag surface, and the amounts of both donation and back donation were larger on the Ni(111) surface than on the Ag(111) surface. There were more negative Mulliken charge transfer from H2PO−2to substrate clusters on Ni surface than on Ag surface and more positive Mulliken charges on P atom in Ni4H2PO−2than in Ag4H2PO−2, which means that P atom in Ni4H2PO−2is easily attacked by a nucleophile such as OH−. Thus, H2PO−2is more easily oxidated on Ni(111) surface than on Ag(111) suface. These results indicated that the silver surface is inactive for the oxidation reaction of the hypophosphite anion.
Spectrofluorimetric Study on the Weak Interaction between ATP and Nα‐4‐Tosyl‐L‐arginine Methyl Ester Hydrochloride
Authors: Ma Yan‐Qing , LÜ Gong‐Xuan , Li Ying , Liu Shu‐Hua , Xian Liang
Published: September 2007

In this paper, some new results on the selective weak interaction between Nα‐4‐tosyl‐L‐arginine methyl ester hydrochloride (TAME) and adenosine‐5′‐triphosphate (ATP) have been reported. Fluorescence spectrophotometry and Fourier transform infrared (FT‐IR) spectroscopy were used to investigate this kind of weak interaction. In fluorescence experiments, obvious fluorescence quenching phenomena were observed when TAME was added, which indicated the weak interactions between TAME and ATP. It has been identified by fluorescence titration experiments that TAME exhibited high selectivity to ATP over ADP and AMP. FT‐IR spectral results showed that an ATP‐TAME adduct was formed. The experimental results indicated that the interaction sites were the guanidinium group of TAME main‐chain and the γ‐phosphate group of ATP, and the interaction took place through hydrogen bonding and electrostatic force. In addition, the effects of metal ions on the weak interaction between ATP and TAME, or between ATP and analogues of L‐arginine were studied.
Ionic Conduction in Ba0.95Ce0.8Ho0.2O3−α
Authors: Wang Mao‐Yuan , Qiu Li‐Gan , Ma Gui‐Lin
Published: September 2007

Ba0.95Ce0.8Ho0.2O3−α was prepared by high temperature solid‐state reaction. X‐ray diffraction (XRD) pattern showed that the material was of a single perovskite‐type orthorhombic phase. Using the material as solid electrolyte and porous platinum as electrodes, the measurements of ionic transport number and conductivity of Ba0.95Ce0.8Ho0.2O3−α were performed by gas concentration cell and ac impedance spectroscopy methods in the temperature range of 600–1000 °C in wet hydrogen, dry and wet air respectively. Ionic conduction of the material was investigated and compared with that of BaCe0.8Ho0.2O3−α. The results indicated that Ba0.95Ce0.8Ho0.2O3−α was a pure protonic conductor with the protonic transport number of 1 during 600–700 °C in wet hydrogen, a mixed conductor of protons and electrons with the protonic transport number of 0.97–0.93 in 800–1000 °C. But BaCe0.8Ho0.2O3−α was almost a pure protonic conductor with the protonic transport number of 1 in 600–900 °C and 0.99 at 1000 °C in wet hydrogen. In dry air and in the temperature range of 600–1000 °C, they were both mixed conductors of oxide ions and electronic holes, and the oxide‐ionic transport numbers were 0.24–0.33 and 0.17–0.30 respectively. In wet air and in the temperature range of 600–1000 °C, they were both mixed conductors of protons, oxide ions and electronic holes, the protonic transport numbers were 0.11–0.00 and 0.09–0.01 respectively, and the oxide‐ionic transport numbers were 0.41–0.33 and 0.27–0.30 respectively. Protonic conductivity of Ba0.95Ce0.8Ho0.2O3−α in both wet hydrogen and wet air was higher than that of BaCe0.8Ho0.2O3−α in 600–800 °C, but lower in 900–1000 °C. Oxide‐ionic conductivity of the material was higher than that of BaCe0.8Ho0.2O3−α in both dry air and wet air in 600–1000 °C.
Determination of Tetracyclines in Honey Using Liquid Chromatography with Ultraviolet Absorbance Detection and Residue Confirmation by Mass Spectrometry
Authors: Liu Yan , Xu Jin‐Zhong , Ding Tao , Li Gong‐Hai
Published: September 2007

A determination method has been optimized and validated for the simultaneous analysis of tetracycline (TC), oxytetracycline (OTC), chlortetracycline (CTC) and doxycycline (DC) in honey. Tetracyclines (TCs) were removed from honey samples by chelation with metal ions bound to small Chelating Sepharose Fast Flow columns and eluted with Na2EDTA‐Mcllvaine pH 4.0 buffers. Extracts were further cleaned up by Oasis HLB solid‐phase extraction (SPE), while other solid‐phase extraction cartridges were compared. Chromatographic separation was achieved using a polar end‐capped C18 column with an isocratic mobile phase consisting of oxalic acid, acetonitrile, and methanol. LC with ultraviolet absorbance at 355 nm resulted in the quantitation of all four tetracycline residues from honey samples fortified at 15, 50, and 100 ng/g, with liner ranges for tetracyclines of 0.05 to 2 µg/mL. Mean recoveries for tetracyclines were greater than 50% with R.S.D. values less than 10% (n=18). Detection limits of 5, 5, 10, 10 ng/g for oxytetracycline, tetracycline, chlortetracycline and doxycycline, respectively and quantitation limits of 15 ng/g for all the four tetracyclines were determined. Direct confirmation of the four residues in honey(2–50 ng/g) was realized by liquid chromatography‐tandem mass spectrometry (LC/MS/MS). The linear ranges of tetracyclines determined by LC/MS/MS were between 5 to 300 ng/mL, with the linear correlation coefficient r>0.995. The limits of detection of 1 to 2 ng/g were obtained for the analysis of the TCs in honey.
Synthesis of a 1,2,7,8‐Tetraoxa‐spiro[5.5]undecane
Authors: Zhang Qi , Li Yun , Wu Yi‐Kang
Published: September 2007

Synthesis of a new spiro organic peroxide is described. The peroxy bonds were incorporated into the substrate framework via an acid‐catalyzed ketal exchange reaction using hydrogen peroxide as the source of peroxy linkage. The hydroperoxyl groups were then bonded at the OH ends via Hg(II)‐induced electrophilic additions to the C‐C double bonds, giving a novel sprio structure with one peroxy bond in each of the two six‐membered rings. The ester functionalities in the side chains also make it possible to conduct further structural modifications.
Three‐Component Barbier Allylation‐Friedel‐Crafts Alkylation Promoted by BuPyCl/SnCl2·2H2O: Application to the Synthesis of 4‐(Substituted phenyl)chromans
Authors: Zhao Xian‐Liang , Liu Li , Chen Yong‐Jun , Wang Dong
Published: September 2007

Barbier allylation and Friedel‐Crafts alkylation of (un)substituted benzaldehydes, allylbromide and phenols can be combined in a one‐pot process in ionic liquid (BuPyCl/SnCl2·2H2O) to directly synthesize 4‐(2‐hydroxyphenyl)‐ 4‐[(un)substituted phenyl]but‐1‐ene compounds, which were applied to the synthesis of 4‐(substituted phenyl)chromans through intramolecular cyclization reactions.
Inhibition of Homo‐coupling of Arylboronic Acids in Ligand Free Pd(II)‐Catalyzed Suzuki Reaction
Authors: Tao Xiao‐Chun , Zhang Yue‐Ping , He Tian‐Xiong , Shen Dong
Published: September 2007

A series of solvents were examined for the ligand free Pd(II)‐catalyzed Suzuki reaction of 4‐bromotoluene with phenylboronic acid. It was found that the PdCl2/i‐PrOH system could efficiently inhibit the homo‐coupling of phenylboronic acid and give a cross‐coupling product in high yields. The substrates with a wide variety of functional groups were tolerated in the system. A possible mechanism for this system was proposed.
Synthesis and Luminescence Property of 4,4′‐Bis(2,2‐di(4‐fluorophenyl)vinyl)biphenyl for Organic Blue‐Light‐Emitting Diodes
Authors: Chai Sheng‐Yong , Bie Guo‐Jun , Li Tian‐Le , Li Wen‐Lian , Chen Zhi‐Qun , Liu Bo
Published: September 2007

The novel fluorinated distyrylarylene, 4,4′‐bis(2,2‐di(4‐fluorophenyl)vinyl)biphenyl (DFPVBi), was synthesized and fully characterized. The structure was confirmed with IR, 1H NMR, 13C NMR, 19F NMR and MS analyses. Its electronic and photoluminescence properties were investigated by UV‐Vis absorption, cyclic voltammetry and fluorescence spectroscopy. The energy levels of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) are −5.77 and −2.75 eV, respectively. The electroluminescence properties of the organic light‐emitting diode fabricated by DFPVBi were also studied. The device exhibits a pure blue emission peaked at 454 nm, which indicates a maximum luminance of 5872 cd/m2 at 14.2 V and a maximum current efficiency of 2.82 cd/A at 10V, respectively.
Measurement and Correlation of the Ionic Conductivity of Ionic Liquid‐Molecular Solvent Solutions
Authors: Li Wen‐Jing , Han Bu‐Xing , Tao Ran‐Ting , Zhang Zhao‐Fu , Zhang Jian‐Ling
Published: September 2007

The ionic conductivity of the solutions formed from 1‐n‐butyl‐3‐methylimidazolium tetrafluoroborate ([Bmim][BF4]) or 1‐n‐butyl‐3‐methylimidazolium hexafluorophosphate ([Bmim][PF6]) and different molecular solvents (MSs) were measured at 298.15 K. The molar conductivity of the ionic liquids (ILs) increased dramatically with increasing concentration of the MSs. It was found that the molar conductivity of the IL in the solutions studied in this work could be well correlated by the molar conductivity of the neat ILs and the dielectric constant and molar volume of the MSs.
Asymmetric Synthesis of the C(17)–C(28) Subunit of Didemnaketal B
Authors: Li Xue‐Qiang , He Qin , Tu Yong‐Qiang , Zhang Fu‐Min , Zhang Shu‐Yu
Published: September 2007

The stereocontrolled synthesis of the C(17)–C(28) fragment 3 of didemnaketal B was accomplished in 21 steps from the natural (R)‐(+)‐pulegone and (S)‐(−)‐citronellal. The key steps involved diastereoselective construction of two chiral carbon centers through the intramolecular chiral induction and uncommon Julia olefination of ketone forming the E‐trisubstituted C(22)–C(23) double bound.
Single Crystalline SnO Nanosheets as Anode Material for Lithium Secondary Battery
Authors: Pei Yan , Wang Shuai , Zhou Qin , Xie Song‐Hai , Qiao Ming‐Hua , Jiang Zhi‐Yu , Fan Kang‐Nian
Published: September 2007

Single crystalline SnO nanosheets with high aspect ratios have been synthesized by a simple solution‐based chemical route aided with sonication. The dimension and thickness of the SnO nanosheets are controllable by adjusting the amount of cetyltrimethyl ammonium bromide (CTAB) added. The as‐prepared SnO nanosheets have loosely packed {001} surfaces and expanded lattice, thus rendering a high reversible capacity approaching the theoretical value of SnO as anode material in Li secondary battery.
Designed Amyloid β Peptide Fibril—A Tool for High‐Throughput Screening of Fibril Inhibitors
Authors: Dolphin Gunnar T. , Ouberai Myriam , Dumy Pascal , Garcia Julian
Published: September 2007

Amyloid β peptide (Aβ) fibril formation is widely believed to be the causative event of Alzheimer’s disease pathogenesis. Therapeutic approaches are therefore in development that target various sites in the production and aggregation of Aβ. Herein we present a high‐throughput screening tool to generate novel hit compounds that block Aβ fibril formation. This tool is an application for our fibril model (Aβ16–37Y20K22K24)4, which is a covalent assembly of four Aβ fragments. With this tool, screening studies are complete within one hour, as opposed to days with native Aβ1–40. A Z′ factor of 0.84±0.03 was determined for fibril formation and inhibition, followed by the reporter molecule thioflavin T. Herein we also describe the analysis of a broad range of reported inhibitors and non‐inhibitors of Aβ fibril formation to test the validity of the system.
Virtual Screening for Selective Allosteric mGluR1 Antagonists and Structure–Activity Relationship Investigations for Coumarine Derivatives
Authors: Noeske Tobias , Jirgensons Aigars , Starchenkovs Igors , Renner Steffen , Jaunzeme Ieva , Trifanova Dina , Hechenberger Mirko , Bauer Tanja , Kauss Valerjans , Parsons Christopher G. , Schneider Gisbert , Weil Tanja
Published: September 2007

A virtual screening study towards novel noncompetitive antagonists of the metabotropic glutamate receptor 1 (mGluR1) is described. Alignment‐free topological pharmacophore descriptors (CATS) were used to encode the screening compounds. All virtual hits were characterized with respect to their allosteric antagonistic effect on mGluR1 in both functional and binding assays. Exceptionally high hit rates of up to 26 % were achieved, confirming the applicability of this virtual screening concept. Most of the compounds were found to be moderately active, however, one potent and subtype selective mGluR1 antagonist, 13 (IC50: 0.362 μM, SEM ±0.031; Ki: 0.753 μM, SEM ±0.048), based on a coumarine scaffold was discovered. In a following activity optimization program a series of coumarine derivatives was synthesized. This led to the discovery of potent (60, IC50: 0.058 μM, SEM ±0.008; Ki: 0.293 μM, SEM ±0.022) and subtype selective (rmGluR5 IC50: 28.6 μM) mGluR1 antagonists. From our homology model of mGluR1 we derived a potential binding mode within the allosteric transmembrane region. Potential interacting patterns are proposed considering the difference of the binding pockets between rat and human receptors. The study demonstrates the applicability of ligand‐based virtual screening for noncompetitive antagonists of a G‐protein coupled receptor, resulting in novel, potent, and selective agents.
Racial disparities in breast cancer outcome
Authors: Demicheli Romano , Retsky Michael W. , Hrushesky William J. M. , Baum Michael , Gukas Isaac D. , Jatoi Ismail
Published: September 2007

Since the 1970s, overall age‐adjusted breast cancer mortality rates in the U.S. have been higher among African American (AA) women than among Caucasian American (CA) women. The racial disparity is not fully explainable based on socioeconomic factors. Suspected biologic factors underlying this trend may be interpreted by both epidemiologic and clinical perspectives. Descriptive epidemiologic studies suggest that breast cancer may be a mixture of at least 2 main diseases and/or causal pathways. The first breast cancer is early‐onset, with peak incidence near age 50 years and generally more aggressive outcome. The second breast cancer is late‐onset, with peak incidence near age 70 years and more indolent course. The early‐onset type of breast cancer is overrepresented among AA women compared with CA women. Clinical studies suggest that the course of breast cancer may be characterized by a common pathway through sequential dormant and active states eventually resulting in clustered appearance of clinical metastases. A balance between tumor and host traits influences the pace of the common pathway. Therefore, the recurrence risk profile of a single patient is seemingly determined by a specific mix of hierarchical prognostic factors, resulting from the unique genetic, environmental, or behavioral traits of that individual, which may be affected by race‐related factors. We suggest that the components of the AA versus CA disparity not attributable to socioeconomic factors are a particular case of the more general issue of host‐tumor interaction and that epidemiologic and clinical views are complementary; each is observing biologic parameters, which are not completely captured by the other. A ‘unifying hypothesis’ incorporating findings from genetics, epidemiology, and clinical studies should be aggressively pursued. Cancer 2007. © 2007 American Cancer Society.
Race, biochemical disease recurrence, and prostate–specific antigen doubling time after radical prostatectomy
Authors: Hamilton Robert J. , Aronson William J. , Presti Joseph C. , Terris Martha K. , Kane Christopher J. , Amling Christopher L. , Freedland Stephen J.
Published: September 2007

BACKGROUND.

Whether black men are at increased risk for biochemical disease recurrence after radical prostatectomy (RP) is debatable. Once black men have developed disease recurrence, it is unknown whether they have more aggressive disease than white men. To address this issue, the authors examined racial differences in pathologic features, time to disease recurrence, and prostate–specific antigen (PSA) doubling time (PSADT) among a cohort of patients treated with RP.

METHODS.

The authors analyzed 953 white and 659 black men who were treated at 5 medical centers comprising the Shared Equal Access Regional Cancer Hospital (SEARCH) Database between 1988 and 2006. The association between race, adverse pathologic features, and biochemical disease recurrence was examined. Among those patients who developed disease recurrence, time to recurrence and PSADT were compared between the races.

RESULTS.

Black men were on average 2.1 years younger (P < .001) and had higher median preoperative PSA levels (7.6 ng/mL vs 7.0 ng/mL; P < .001), yet presented with a lower clinical stage of disease (T1: 62% vs 44%; P < .001) and similar biopsy Gleason scores (P = .59). After adjusting for multiple clinical characteristics, black men were found to be as likely as white men to have adverse pathologic features (Gleason score ≥7, positive surgical margins, and seminal vesicle invasion) in the RP specimen and were less likely to have extracapsular extension (P = .03). Black men were more likely to have a biochemical disease recurrence (hazards ratio [HR] of 1.28; 95% confidence interval [95% CI, 1.07–1.54 [P = .006]). This increased risk was reduced slightly after adjustment for multiple clinical and pathologic features, and no longer achieved statistical significance (HR of 1.19; 95% CI, 0.97–1.45 [P = .09]). Among men who developed disease recurrence, the median PSADT was found to be similar among black men (17.0 months) and white men (14.6 months) (P = .26).

CONCLUSIONS.

Despite presenting with earlier clinical stage and similar pathologic features at RP, black men were found to be at a slightly increased risk for biochemical disease recurrence. However, these recurrences appear to be no more aggressive than those found in white men. Cancer 2007;110:2202–9. © 2007 American Cancer Society.
Dipeptide Structure Determination by Vibrational Circular Dichroism Combined with Quantum Chemistry Calculations
Authors: Lee Kyung‐Koo , Oh Kwang‐Im , Lee Hochan , Joo Cheonik , Han Hogyu , Cho Minhaeng
Published: September 2007

The solution structure and the local solvation environments of alanine dipeptide (AD, 1 a) and its isotopomer (AD*, 1 b, 13C on the acetyl end CO) are studied by using infrared (IR) spectroscopy and vibrational circular dichroism (VCD). From the amide I IR spectra of AD* in various protic solvents, it is found that each of the two carbonyl groups is fully H‐bonded to two water molecules. However, the number of alcohol molecules H‐bonded to each CO varies from one to two, and the local solvation environments are asymmetric around the two peptides of AD* in alcohol solutions. The amide I VCD spectra of AD and AD* in D2O are also measured, and a series of density functional theory (DFT, B3LYP/6‐311++G**) calculations are performed to obtain the amide I normal‐mode rotational strengths of AD and the intrinsic rotational strengths of its two peptide fragments. By combining the VCD‐measurement and DFT‐calculation results and employing a coupled oscillator theory, we show that the aqueous‐solution structure of the dipeptide can be determined. We believe that the present method will be of use in building up a library of dipeptide solution structures in water.
Spectral analysis and design approach for high force‐to‐volume extrusion damper‐based structural energy dissipation
Authors: Rodgers Geoffrey W. , Mander John B. , Chase J. Geoffrey , Dhakal Rajesh P. , Leach Nicholas C. , Denmead Caleb S.
Published: September 2007

High force‐to‐volume extrusion damping devices can offer significant energy dissipation directly in structural connections and significantly reduce seismic response. Realistic force levels up to 400 kN have been obtained experimentally validating this overall concept. This paper develops spectral‐based design equations for their application. Response spectra analysis for multiple, probabilistically scaled earthquake suites are used to delineate the response reductions due to added extrusion damping. Representative statistics and damping reduction factors are utilized to characterize the modified response in a form suitable for current performance‐based design methods. Multiple equation regression analysis is used to characterize reduction factors in the constant acceleration, constant velocity, and constant displacement regions of the response spectra.

With peak device forces of 10% of structural weight, peak damping reduction factors in the constant displacement region of the spectra are approximately 6.5 ×, 4.0 ×, and 2.8 × for the low, medium, and high suites, respectively. At T = 1 s, these values are approximately 3.6 ×, 1.8 ×, and 1.4 ×, respectively. The maximum systematic bias introduced by using empirical equations to approximate damping reduction factors in design analyses is within the range of +10 to −20%. The seismic demand spectrum approach is shown to be conservative across a majority of the spectrum, except for large added damping between T = 0.8 and 3.5 s, where it slightly underestimates the demand up to a maximum of approximately 10%. Overall, the analysis shows that these devices have significant potential to reduce seismic response and damage at validated prototype device force levels. Copyright © 2007 John Wiley & Sons, Ltd.
Seismic isolation by rubber–soil mixtures for developing countries
Authors: Tsang Hing‐Ho
Published: September 2007

This paper proposes a promising seismic isolation method particularly suitable for developing countries, which makes use of rubber–soil mixtures. Apart from reducing the level of shaking in the horizontal direction, the distinctive advantage of the proposed method is that it can also significantly reduce the shaking level of vertical ground motion, to which an increasing attention has been paid in the earthquake engineering community. On the other hand, the use of scrap tires as the rubber material can provide an alternative way to consume the huge stockpile of scrap tires all over the world. Moreover, the low cost of this proposed seismic protection scheme can greatly benefit those developing countries where resources and technology are not adequate for earthquake mitigation with well‐developed, yet expensive, techniques. The proposed method has been demonstrated through a series of numerical simulations and a parametric study has also been carried out. Lastly, five important issues regarding the concept and feasibility have been discussed. Copyright © 2007 John Wiley & Sons, Ltd.
The effect of temperature and ventilation condition on the toxic product yields from burning polymers
Authors: Stec A. A. , Hull T. R. , Lebek K. , Purser J. A. , Purser D. A.
Published: September 2007

A major cause of death or permanent injury in fires is inhalation of toxic gases. Moreover, every fire is unique, and the range of products, highly dependant on fire conditions, produces a wide variety of toxic and irritant species responsible for the most fire fatalities. Therefore, to fully understand each contribution to the toxicity it is necessary to quantify the decomposition products of the material under the test.

Fires can be divided into a number of stages from smouldering combustion to early well‐ventilated flaming through to fully developed under‐ventilated flaming. These stages can be replicated by certain bench‐scale physical fire models using different fuel‐to‐oxygen ratios, controlled by the primary air flow, and expressed in terms of the equivalence ratio (the actual fuel/air ratio divided by the stoichiometric fuel/air ratio).

This work presents combustion product yields generated using a small‐scale fire model. The Purser Furnace apparatus (BS7990 and ISO TS 19700) enables different fire stages to be created. Identification and quantification of combustion gases and particularly their toxic components from different fire scenarios were undertaken by continuous Fourier transform infrared spectroscopy. The relationship between type of the fire particularly the temperature and ventilation conditions and the toxic product yields for four bulk polymers, low‐density polyethylene, polystyrene (PS), Nylon 6.6 and polyvinyl chloride (PVC) is reported.

For all the polymers tested, except PVC, there is a dramatic increase in the yield of products of incomplete combustion (CO and hydrocarbons) with increase in equivalence ratio, as might be expected. For PVC there is a consistently high level of products of incomplete combustion arising both from flame inhibition by HCl and oxygen depletion. There is a low sensitivity to furnace temperature over the range 650–850°C, except that at 650°C PS shows an unexpectedly high yield of CO under well‐ventilated conditions and PVC shows a slightly higher hydrocarbon yield. This demonstrates the dependence of toxic product yields on the equivalence ratio, and the lack of dependence on furnace temperature, within this range. Copyright © 2007 John Wiley & Sons, Ltd.
Role of Kir4.1 channels in growth control of glia
Authors: Higashimori Haruki , Sontheimer Harald
Published: September 2007

The inwardly rectifying potassium channel Kir4.1 is widely expressed by astrocytes throughout the brain. Kir4.1 channels are absent in immature, proliferating glial cells. The progressive expression of Kir4.1 correlates with astrocyte differentiation and is characterized by the establishment of a negative membrane potential (> −70 mV) and an exit from the cell cycle. Despite some correlative evidence, a mechanistic interdependence between Kir4.1 expression, membrane hyperpolarization, and control of cell proliferation has not been demonstrated. To address this question, we used astrocyte‐derived tumors (glioma) that lack functional Kir4.1 channels, and generated two glioma cell lines that stably express either AcGFP‐tagged Kir4.1 channels or AcGFP vectors only. Kir4.1 expression confers the same K+ conductance to glioma membranes and a similar responsiveness to changes in [K+]o that characterizes differentiated astrocytes. Kir4.1 expression was sufficient to move the resting potential of gliomas from −50 to −80 mV. Importantly, Kir4.1 expression impaired cell growth by shifting a significant number of cells from the G2/M phase into the quiescent G0/G1 stage of the cell cycle. Furthermore, these effects could be nullified entirely if Kir4.1 channels were either pharmacologically inhibited by 100 μM BaCl2 or if cells were chronically depolarized by 20 mM KCl to the membrane voltage of growth competent glioma cells. These studies therefore demonstrate directly that Kir4.1 causes a membrane hyperpolarization that is sufficient to account for the growth attenuation, which in turn induces cell maturation characterized by a shift of the cells from G2/M into G0/G1. © 2007 Wiley‐Liss, Inc.
Modafinil and nicotine interactions in abstinent smokers
Authors: Sofuoglu Mehmet , Waters Andrew J. , Mooney Marc
Published: September 2007

In this study, we examined the effects of a wakefulness‐promoting medication, modafinil, alone and with the nicotine lozenge, on subjective, physiological and cognitive measures as well as on nicotine withdrawal in overnight abstinent cigarette smokers. Nineteen smokers, 13 male and 6 female, participated in a double‐blind, placebo‐controlled, crossover study. In each of three experimental sessions, subjects were treated orally with a single 200 mg or 400 mg dose of modafinil or placebo. Two hours and 10 min following the medication treatment, subjects received a single 2 mg nicotine lozenge. Both doses of modafinil alone increased the rating of elated‐depressed on the Profile of Mood States (POMS) subscale in the direction of depressed and increased ratings of negative affect on the Positive and Negative Affect Schedule (PANAS). In contrast, the 200 mg modafinil dose combined with a 2 mg nicotine lozenge, increased the rating of energetic‐tired in the direction of energetic on the POMS subscale. Modafinil attenuated self‐reported rating of ‘drug strength’ in response to the nicotine lozenge. Modafinil, alone or in combination with the nicotine lozenge, did not affect tobacco withdrawal symptoms. There was an increase in baseline heart rate and systolic blood pressure under modafinil treatment. In addition, modafinil speeded reaction times on a modified Stroop task. The clinical utility of modafinil for smoking cessation needs to be determined in future studies. Copyright © 2007 John Wiley & Sons, Ltd.
Loudness dependence of evoked dipole source activity during acute serotonin challenge in females
Authors: Norra Christine , Becker Stefanie , Bröcheler Anno , Kawohl Wolfram , Kunert Hanns Jürgen , Buchner Helmut
Published: September 2007

Objectives

Direct challenge of cortical serotonergic (5‐hydroxytryptamine, 5‐HT) availability by tryptophan depletion test (TDT) was used to assess the hypothesized inverse relationship between central 5‐HT function and loudness dependence of auditory evoked potentials (LDAEPs). Gender must be taken into particular account here, since there are gender differences in 5‐HT brain synthesis, with women reacting more strongly to TDT.

Methods

In a double‐blind, controlled cross‐over study, 16 healthy females were ingested two highly concentrated amino acid mixtures with (+TRP) or without TRP (−TRP). While monitoring TRP levels and mood states, the AEP of different loudness stimuli were recorded, followed by dipole source analysis.

Results

Under the −TRP condition, free plasma TRP levels decreased by 81.10% (±5.14). Most of the loudness change rates of the relevant N1/P2 tangential dipole activities were significantly increased under −TRP, but calculated LDAEP did not differ significantly between treatments. LDAEP and states of mood were not correlated.

Conclusions

Despite strong TRP depletion, the results did not reach sufficient evidence that LDAEP is a valid biological marker of central 5‐HT activity in females when using TDT. This agrees with the literature and supports the view that LDAEP indicates predominantly biological vulnerability in predisposed individuals. Copyright © 2007 John Wiley & Sons, Ltd.
Caffeine, sleep and wakefulness: implications of new understanding about withdrawal reversal
Authors: James Jack E. , Keane Michael A.
Published: September 2007

The broad aim of this review is to critically examine the implications of new understanding concerning caffeine withdrawal and withdrawal reversal in the context of research concerned with the effects of caffeine on sleep and wakefulness. A comprehensive search was conducted for relevant experimental studies in the PubMED and PsycINFO databases. Studies were assessed with particular reference to methodological adequacy for controlling against confounding due to caffeine withdrawal and withdrawal reversal. This assessment was used to clarify evidence of effects, highlight areas of ambiguity and derive recommendations for future research. It was found that researchers have generally failed to take account of the fact that habitual use of caffeine, even at moderate levels, leads to physical dependence evidenced by physiological, behavioural and subjective withdrawal effects during periods of abstinence. Consequently, there has been near‐complete absence of adequate methodological controls against confounding due to reversal of withdrawal effects when caffeine is experimentally administered. The findings of what has been a substantial research effort to elucidate the effects of caffeine on sleep and wakefulness, undertaken over a period spanning decades, are ambiguous. Current shortcomings can be redressed by incorporating suitable controls in new experimental designs. Copyright © 2007 John Wiley & Sons, Ltd.