bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in spinal distribution and neurochemical phenotype of colonic afferents in mouse and rat
Authors: Christianson Julie A. , Traub Richard J. , Davis Brian M.
Published: November 2005

Visceral pain is a prevalent clinical problem and one of the most common ailments for which patients seek medical attention. Recent studies have described many of the physiological properties of visceral afferents, but not much is known regarding their anatomical characteristics. To determine the spinal distribution and neurochemical phenotype of colonic afferents in rodents, Alexa Fluor‐conjugated cholera toxin‐β (CTB) was injected subserosally into the proximal and distal portions of the descending colon in Sprague Dawley rats and C57Bl/6 mice. Dorsal root ganglia (T10–S2) were processed for fluorescent immunohistochemistry and visualized by confocal microscopy. In the mouse, CTB‐positive neurons were most numerous in the lumbosacral region (LS; L6–S1), with a smaller contribution in the thoracolumbar ganglia (TL; T13–L1). In contrast, CTB‐positive neurons in the rat were most numerous in the TL ganglia, with a smaller contribution in the LS ganglia. The vast majority of CTB‐positive neurons in both mouse and rat were positive for TRPV1 and CGRP and most likely unmyelinated, in that most colonic afferents were not positive for neurofilament heavy chain. In the mouse, the TL ganglia had a significantly higher percentage of TRPV1‐ and CGRP‐positive neurons than did the LS ganglia, whereas no differences were observed in the rat. The high incidence of TRPV1‐positive colonic afferents in rodents suggests that hypersensitivity from the viscera may be partially a TRPV1‐mediated event, thereby providing a suitable target for the treatment of visceral pain. J. Comp. Neurol. 494:246–259, 2006. © 2005 Wiley‐Liss, Inc.
From Pentalene to Dicyclopenta[b,g]naphthalene, or the Change towards Delocalized Structures
Authors: García Cuesta Inmaculada , Coriani Sonia , Lazzeretti Paolo , Sánchez de Merás Alfredo M. J.
Published: November 2005

Using triples‐corrected coupled‐cluster methods as well as other high‐level theoretical approximations, the optimized parameters and isomerization barriers of the family of compounds cyclopentadiene–(benzene)x–cyclopentadiene (x=0, 1, 2) are computed. In contrast to previous studies, s‐indacene presents a localized C2h geometry. Also, the localized structure of pentalene is found to be the most stable, but when two benzene rings are intercalated between the five‐member rings of pentalene, the resulting molecule preferably adopts a delocalized D2h conformation.
Flexible Synthetic Approach to a (S)‐Norcamphor‐Based Hydroperoxide: An Efficient Oxidant for Asymmetric Sulfoxidations
Authors: Lattanzi Alessandra , Piccirillo Sandro , Scettri Arrigo
Published: November 2005

The renewable tertiary (S)‐norcamphor‐based hydroperoxide 3 has been efficiently obtained by a simple 4‐step route. Remarkably, complete diastereocontrol was observed in the hydroperoxidation step. This oxidant, when used in the Ti‐catalyzed asymmetric sulfoxidation, showed to be as reactive as previously reported hydroperoxide 2, but more importantly, high chemoselectivity and improved asymmetric induction were achieved. The synthetic approach used offers the opportunity for designing a variety of functionalized and potentially more efficient norcamphor‐based hydroperoxides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Relay Propagation of Crowding: The Trifluoromethyl Group as Both an Emitter and Transmitter of Steric Pressure
Authors: Schlosser Manfred , Cottet Fabrice , Heiss Christophe , Lefebvre Olivier , Marull Marc , Masson Eric , Scopelliti Rosario
Published: November 2005

Whereas lithium 2,2,6,6‐tetramethylpiperidide (LITMP) abstracts a proton exclusively from the 4‐position of 3‐bromobenzotrifluoride, the same base attacks selectively the 2‐position when employed in the presence of N,N,N′,N′′,N′′‐pentamethyldiethylenetriamine and potassium tert‐butoxide (“Faigl mix”). 1‐Bromo‐3,5‐bis(trifluoromethyl)benzene also undergoes metalation at the 2‐position but [2‐bromo‐4‐(trifluoromethyl)phenyl]silane does not react at all, evidently locked up by a C–SiR3/C–Br buttressing effect. 2‐Bromo‐4‐(trifluoromethyl)pyridine, aza‐analogous to the parent model arene 3‐bromobenzotrifluoride, and both the benzo‐aza‐analogous 2‐bromo‐4‐(trifluoromethyl)quinoline and its regioinverted isomer 4‐bromo‐2‐(trifluoromethyl)quinoline are again readily deprotonated at the Br‐ and CF3‐flanked positions. However, the buttressing caused by the introduction of a methoxy group at the peri‐(5‐)position impedes the deprotonation of either bromo(trifluoromethyl)quinoline. Compared with methoxy, a peri‐methyl substituent (to be assimilated to an ortho‐tert‐butyl substituent) exerts a smaller buttressing effect. Although 4‐bromo‐5,7‐dimethoxy‐4‐(trifluoromethyl)quinoline proves to be again totally inert towards bases, 4‐bromo‐5,7‐dimethyl‐4‐(trifluoromethyl)quinoline can be lithiated at the 3‐position. Obviously, methoxy is more powerful as an emitter of steric pressure than methyl is and bromine is superior to trifluoromethyl as a transmitter of steric pressure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Adjustment procedures to account for non‐ignorable missing data in environmental surveys
Authors: Munoz Breda , Lesser Virginia M.
Published: November 2005

Methods for non‐response are well‐known techniques used in survey practice for handling missing data. In this approach, sampling units (respondents and non‐respondents) are classified in non‐response classes, and the sampling weight for each respondent unit is weighted by the inverse of an estimate of its response probability (also known as propensity score). Optimal weighting classes are selected using variables associated with the response but uncorrelated with the response indicator. We explore the assumptions needed to construct optimal adjustment classes in the case of non‐ignorable missing data in environmental surveys. We propose a modified Horvitz–Thompson non‐response estimator for the population total of the spatial random process of interest, and study some of its properties. By using the weighting class adjustment, we will account for the non‐ignorable missing data. Copyright © 2005 John Wiley & Sons, Ltd.
Uterine leiomyomata with deletions of Ip represent a distinct cytogenetic subgroup associated with unusual histologic features
Authors: Christacos Nicole C. , Quade Bradley J. , Cin Paola Dal , Morton Cynthia C.
Published: November 2005

Cytogenetic analysis of uterine leiomyomata (UL) shows that about 40% of these benign tumors have simple, clonal chromosomal rearrangements. In contrast, their presumed malignant counterpart, leiomyosarcomas (LMSs), typically has complex numerical and structural abnormalities. Several variants of benign uterine smooth‐muscle tumors are defined by histologic phenotypes intermediate between typical UL and LMS, and currently, little is known about their cytogenetic and molecular genetic features. From a subset of more than 800 karyotyped ULs, we identified a group of nine cases exhibiting near‐diploid karyotypes with loss of almost the entire short (p) arm of chromosome 1 [i.e., del(1)(p11p36)]. Loss of 1p was often associated with other aberrations, particularly loss of chromosomes 19 and/or 22. Of eight UL for which the histologic diagnosis was known, four were diagnosed as cellular UL; one displayed both hypercellularity and nuclear atypia. Loss of heterozygosity (LOH) analysis for chromosomal regions 1p36.23 and 1p21.1 demonstrated allelic loss for either a portion or the majority of 1p in 5 of 10 additional archival UL diagnosed with either cellular or atypical histology. RNA from two UL with loss of 1p was profiled using Affymetrix GeneChips, and those profiles were compared to our previously reported smooth‐muscle tumor expression profile. The transcriptional profiles of tumors with 1p deletion were more similar to those of leiomyosarcoma than to profiles of myometrium and UL, as determined by hierarchical cluster analysis. Comparison of the transcriptional profiles for UL with and without 1p− revealed 53 genes with differential regulation. Loss of 1p appears to define a subgroup of UL distinct from those previously recognized. Furthermore, 1p− appears to be associated with a specific histologic phenotype. The similarity between the transcriptional profiles of LMS and UL with 1p− suggests the possibility of a common pathogenetic mechanism. © 2005 Wiley‐Liss, Inc.
Array CGH analysis of pediatric medulloblastomas
Authors: Rossi Michael R. , Conroy Jeffrey , McQuaid Devin , Nowak Norma J. , Rutka James T. , Cowell John K.
Published: November 2005

Brain tumors are the second most common childhood cancer. We used high‐resolution array comparative genomic hybridization (aCGH) to analyze losses and gains of genetic material from 24 medulloblastomas. The bacterial artificial chromosome clones were ordered on the array, allowing for an average resolution of approximately 420 kilobases. The advantage of this high resolution is that the breakpoints associated with subregional chromosome copy number aberrations can be accurately defined, which in turn allows candidate genes within these regions to be readily defined. In this analysis, we confirmed the frequent involvement of loss of 17p and gain of 17q, although we have now established the position of the breakpoint that consistently lies in the chr17:18318880–19046234 region of the chromosome. Other frequent losses were seen on 8p, 10q, 16q, and 20p, and frequent gains were seen on 2p, 4p, 7, and 19. In addition, the fine‐resolution mapping provided by aCGH made it possible to define small chromosome deletions in 1q23.3–q24.2, 2q13.12–q13.2, 6q25–qter, 8p23.1, 10q25.1, and 12q13.12–q13.2. Overall, amplification events were rare, the most common involving MYC (16%), on 8q, although isolated events were seen in 10p11 and 3q. © 2005 Wiley‐Liss, Inc.
D324N single‐nucleotide polymorphism in the FLT3 gene is associated with higher risk of myeloid leukemias
Authors: Schnittger Susanne , Kohl Tobias M. , Leopold Nina , Schoch Claudia , Wichmann H.‐Erich , Kern Wolfgang , Lohse Peter , Hiddemann Wolfgang , Haferlach Torsten , Spiekermann Karsten
Published: November 2005

Mutations within the FLT3 gene are of growing importance for classification, risk assessment, and therapeutic targeting of acute myeloid leukemia (AML). We analyzed 656 AML patients for a recently described single‐nucleotide polymorphism (SNP) in the third immunoglobulin‐like domain of the extracellular region of FLT3. The FLT3 D324N variant was present in 42 cases (6.4%), but it was not associated with a specific AML subtype and did not show an elevated leukocyte count, as do other FLT3 mutations. In remission samples, a 50% ratio of the normal to the D324N variant was detectable. Stably expressed in IL‐3 dependent Ba/F3 cells, the D324N variant did not confer receptor autophosphorylation, factor independent growth, or increased resistance to apoptotic cell death in response to varying doses of FLT3 ligand. In 400 healthy donors, the FLT3 D324N variant was detected in 6 cases (1.5%) and segregated in a family. Thus, it was shown to be a polymorphism with a lower frequency in healthy controls than in patients with AML (P < 0.001). In addition, 21 of 234 CML (9.0%) and 7 of 155 ALL (4.5%) cases carried the FLT3 D324N. Our data suggest that the FLT3 D324N variant might be associated with a predisposition to different subtypes of leukemia. © 2005 Wiley‐Liss, Inc.
Monitoring of the principal carbonyl compounds involved in malolactic fermentation of wine by solid‐phase microextraction and positive ion chemical ionization GC/MS analysis
Authors: Flamini Riccardo , Vedova Antonio Dalla , Panighel Annarita , Perchiazzi Nicola , Ongarato Stefano
Published: November 2005

A new method has been developed to determine acetaldehyde, 2,3‐butanedione (diacetyl) and 3‐hydroxy‐2‐butanone (acetoin) in wine by solid‐phase microextraction (SPME) and positive ion chemical ionization GC/MS analysis of O‐(2,3,4,5,6‐pentafluorobenzyl)‐hydroxylamine (PFBOA) derivatives. For SPME, a 65‐µm PEG/DVB fibre was used; chemical ionization was performed with methane as reagent gas. The best analysis‐time/sensitivity compromise was to perform the PFBOA reaction at 50 °C for 20 min, followed by 5‐min SPME at the same temperature. Quantitative analysis was performed in SCAN mode using o‐chlorobenzaldehyde as internal standard (IS), on the signal of the [M + H]+ ion at m/z 240 for acetaldehyde, 266 for acetoin (corresponding to the [M + H − 18]+ ion), 282 for diacetyl (protonated mono‐derivatized compound), and 336 for IS. The accuracy and repeatability of the method were suitable for the study aims, and linearity was good in the range of concentration studied, with correlation coefficients of calibration curves 0.997, 0.998 and 0.988 for acetaldehyde, diacetyl and acetoin respectively. Due to the higher polarity of acetoin with respect to other two compounds, lower sensitivity in the detection of this compound was observed. By following the variation of the three carbonyl compounds, malolactic fermentations (MLF) were monitored in Merlot wines and this was carried out in the laboratory by two different bacteria strains. Copyright © 2005 John Wiley & Sons, Ltd.
Activity of anchored human matrix metalloproteinase‐1 catalytic domain on Au (111) surfaces monitored by ESI‐MS
Authors: Grasso Giuseppe , D'Agata Roberta , Rizzarelli Enrico , Spoto Giuseppe , D'Andrea Luca , Pedone Carlo , Picardi Andrea , Romanelli Alessandra , Fragai Marco , Yeo Kwon Joo
Published: November 2005

Matrix metalloproteinases (MMPs) are a family of Zn‐dependent endo‐peptidases known for their ability to cleave several components of the extracellular matrix, but which can also cleave many non‐matrix proteins. There are many evidences that MMPs are involved in physiological and pathological processes, and a huge effort has been put in the development of possible inhibitors that could reduce the activity of MMPs, as it is clear that the ability to monitor and control such activity plays a pivotal role in the search for potential drugs aimed at finding a cure for several diseases such as pulmonary emphysema, rheumatoid arthritis, fibrotic disorders and cancer.

A powerful method currently available to study enzyme–inhibitor interactions is based on the use of the surface plasmon resonance (SPR) technique. When MMP interactions are studied, a procedure by which inhibitors are normally anchored on sensor chips and SPR technique is used in order to study their interaction with MMPs molecules is usually followed. This is because it is currently believed that MMPs cannot be anchored on the sensor‐chip surface without losing their activity. However, this approach gives rise to problems, as the anchoring of low‐molecular‐weight inhibitors on gold surfaces easily affects their ability to interact with MMPs. For this reason, the anchoring of MMPs is highly desirable.

A new experimental protocol that couples the Fourier transform‐SPR (FT‐SPR) technique with electrospray ionization‐mass spectroscopy (ESI‐MS) is described here for the evaluation of the activity of MMP‐1 catalytic domain (cdMMP‐1) anchored on gold surfaces. The cdMMP‐1 surface coverage is calculated by using FT‐SPR and the enzyme activity is estimated by ESI‐MS. The proposed method is label‐free. Copyright © 2005 John Wiley & Sons, Ltd.
MALDI‐TOF mass spectrometry of a combinatorial peptide library: effect of matrix composition on signal suppression
Authors: Schlosser Gitta , Pocsfalvi Gabriella , Huszár Emőke , Malorni Antonio , Hudecz Ferenc
Published: November 2005

The effect of matrix composition on signal suppression caused by a dominant compound under MALDI ionization was studied using the combinatorial TQTXT pentapeptide library as a model system. The peptide library is composed of 19 components with all proteinogenic amino acids except cysteine in position X. From these compounds, only the Arg peptide (TQTRT) was detected with sufficient intensity in the MALDI‐TOF mass spectrum under typical MALDI conditions (CCA matrix). The analysis of a set of compounds utilized as different matrix components, additives and a cationizing agent revealed that the composition of the matrix is a critical point in signal suppression. Highly improved ion yields were achieved by using a CCA/DHB mixture as a matrix. The addition of K+ as a cationizing agent to the CCA matrix resulted in MALDI‐TOF mass spectra with relative ion intensities very similar to those obtained by electrospray ionization. Copyright © 2005 John Wiley & Sons, Ltd.
Surface‐activated chemical ionization ion trap mass spectrometry in the analysis of drugs in dilute urine samples. Part II: analysis of morphine and other street drugs
Authors: Cristoni Simone , Cantu Marco , Bernardi Luigi Rossi , Gerthoux Piermario , Mocarelli Paolo , Brambilla Maura , Gonella Elisabetta , Guidugli Federico
Published: November 2005

The new ionization method, called surface‐activated chemical ionization (SACI), was employed for the analysis of fives drugs (morphine, codeine, 6‐monoacetylmorphine (6‐MAM), benzoylecgonine and cocaine) by ion trap mass spectrometry. The results so obtained have been compared with those achieved by using atmospheric pressure chemical ionization (APCI), no‐discharge‐APCI and electrospray ionization (ESI) clearly showing that SACI is the most sensible one mainly due to the high ionization efficiency and the lower chemical noise. The performance of SACI in terms of sensitivity and linearity was compared with the sensitivity and linearity obtained using APCI, no‐discharge‐APCI and ESI, showing that the new SACI approach gives rise to the best results. Then, SACI was used to analyze morphine, codeine, 6‐MAM, benzoylecgonine and cocaine in urine samples. After the optimization of the instrumental parameters for a mixture of the standard compounds, eight urine samples were analyzed. They were strongly diluted (1 : 20 and 1 : 100) in order to prevent the chromatographic column damage due to the matrix composition. Furthermore, the diluted urine samples were directly analyzed, without pretreatment, through LC‐MS and LC‐MS/MS, and the obtained results are reported. Copyright © 2005 John Wiley & Sons, Ltd.
Rate constant for the reaction of CH3C(O)CH2 radical with HBr and its thermochemical implication
Authors: Farkas Edit , Kovács Gergely , Szilágyi István , Dóbé Sándor , Bérces Tibor , Márta Ferenc
Published: November 2005

The fast flow method with laser induced fluorescence detection of CH3C(O)CH2 was employed to obtain the rate constant of k1 (298 K) = (1.83 ± 0.12 (1σ)) × 1010 cm3 mol−1 s−1 for the reaction CH3C(O)CH2 + HBr ↔ CH3C(O)CH3 + Br (1, −1). The observed reduced reactivity compared with n‐alkyl or alkoxyl radicals can be attributed to the partial resonance stabilization of the acetonyl radical. An application of k1 in a third law estimation provides ΔfH(CH3C(O)CH2) values of −24 kJ mol−1 and −28 kJ mol−1 depending on the rate constants available for reaction (‐1) from the literature. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 38: 32–37, 2006
Master equation modeling of wide range temperature and pressure dependence of CO + OH → products
Authors: Joshi Ameya V. , Wang Hai
Published: November 2005

The rate coefficient of CO + OH → products is analyzed with RRKM/master equation analyses and Monte Carlo simulations. The analyses are based on the recent CCSD(T)/cc‐pvTZ potential energy surface of Yu et al. Chem Phys Lett 2001, 349, 547–554). It is shown that the experimental data over the temperature range of 80–2500 K and pressure from 1 Torr to 800 bar can be satisfactorily reproduced by lowering the CCSD(T)/cc‐pvTZ energy barrier for the CO2 + H exit channel by 1 kcal/mol and more importantly, by considering an equilibrium factor in the thermal rate constant formulation. This factor accounts for the populations of rovibrationally excited trans‐ and cis‐HOCO, which are then allowed to dissociate only through specific paths that are open to them. By modeling the isothermal but pressure‐dependent rate data of Fulle et al. (J Chem Phys 1996, 105, 983–1000) over the temperature range from 98 to 819 K, we obtained an 〈Edown〉 value equal to 150 cm−1 for M = He. The 〈Edown〉 values for M = N2, Ar, CF4, and SF6 were also obtained by fitting the OH and OD data at 298 K. Based on the theoretical analyses, we recommended that the following rate expression be used for CO + OH → CO2 + H in the temperature range from 120 to 2500 K and pressure lower than P(bar) = 9 × 10−17T 5.9 exp(520/T): k1b,0(cm3 molecule−1s−1) =1.17 × 10−19 T2.053exp(139/T) + 9.56 × 10−12 T−0.664 exp(−167/T). Fall‐off parameterization is also proposed for the rate coefficient of CO + OH → CO2 + H under extremely high pressures and for CO + OH → HOCO over the temperature range from 120 to 2500 K. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 38:57–73, 2006
Polyphenolic apple juice extracts and their major constituents reduce oxidative damage in human colon cell lines
Authors: Schaefer Sandra , Baum Matthias , Eisenbrand Gerhard , Dietrich Helmut , Will Frank , Janzowski Christine
Published: November 2005

Apple juice containing high amounts of antioxidative polyphenols might protect the intestine against oxidative cell damage. We investigated the preventive effectiveness of polyphenolic juice extracts of different origins (cider and table apples) in comparison to their major constituents in human colon cell lines (Caco‐2, HT29). Parameters studied were (oxidative) DNA damage (Comet assay), glutathione level (photometric kinetic assay), cellular redox status (dichlorofluorescein assay) and antioxidant capacity. The extracts (50–250 μg/mL) modulated DNA damage and redox status in a concentration‐dependent manner at 24‐h incubation. The pomace extraction technology, applied for juice preparation, and the preferential selection of cider apple varieties influenced the polyphenolic pattern and increased the biological effectiveness of the extracts. The preventive potential of major juice constituents (1–100 μM, 24 h) strongly differed: rutin, epicatechin and caffeic acid clearly reduced (oxidative) DNA damage (Caco‐2), chlorogenic acid efficiently decreased cellular reactive oxygen species level (HT29, Caco‐2). The aglyca quercetin and phloretin exhibited the highest preventive/antioxidant capacity in all assays. The stability of the compounds inversely correlated with their preventive effectiveness and might contribute to the observed cell specific sensitivities. In conclusion, apple juice extracts distinctly reduce oxidative cell damage in human colon cell lines, an effect, which in part can be accounted for by their major constituents.
The extracellular proteome of Bacillus licheniformis grown in different media and under different nutrient starvation conditions
Authors: Voigt Birgit , Schweder Thomas , Sibbald Mark J. J. B. , Albrecht Dirk , Ehrenreich Armin , Bernhardt Jörg , Feesche Jörg , Maurer Karl‐Heinz , Gottschalk Gerhard , van Dijl Jan Maarten , Hecker Michael
Published: November 2005

The now finished genome sequence of Bacillus licheniformis DSM 13 allows the prediction of the genes involved in protein secretion into the extracellular environment as well as the prediction of the proteins which are translocated. From the sequence 296 proteins were predicted to contain an N‐terminal signal peptide directing most of them to the Sec system, the main transport system in Gram‐positive bacteria. Using 2‐DE the extracellular proteome of B. licheniformis grown in different media was studied. From the approximately 200 spots visible on the gels, 89 were identified that either contain an N‐terminal signal sequence or are known to be secreted by other mechanisms than the Sec pathway. The extracellular proteome of B. licheniformis includes proteins from different functional classes, like enzymes for the degradation of various macromolecules, proteins involved in cell wall turnover, flagellum‐ and phage‐related proteins and some proteins of yet unknown function. Protein secretion is highest during stationary growth phase. Furthermore, cells grown in complex medium secrete considerably higher protein amounts than cells grown in minimal medium. Limitation of phosphate, carbon and nitrogen sources results in the secretion of specific proteins that may be involved in counteracting the starvation.
Multi‐modality of pI distribution in whole proteome
Authors: Wu Songfeng , Wan Ping , Li Jianqi , Li Dong , Zhu Yunping , He Fuchu
Published: November 2005

Multi‐modality of pI distribution is a common feature in different whole proteomes. Some researchers considered it relate to the proteins with different subcellular locations, indicating the result of natural selection. We explored the pI distribution of predicted proteomes (including animals, plants, bacterium, archaeans) and random proteome [random protein sequences constructed according to the special amino acid composition and molecular weight (MW) distribution of human predicted proteome]. Our results suggest that the multi‐modality is the result of discrete pKR values for different amino acids. Amino acid composition and MW distribution of a proteome also contributes to the specific pI distribution. Although protein subcellular location was related to pI value, our analyses revealed that comparing with the random proteome, neither the multi‐modality phenomenon nor the distribution bias of pI values is caused by subcellular location. It seems that the multi‐modality distribution is just a mathematical fun. The blank region near the neutral pI was caused by the absence of amino acids with neutral pKR, and suggests that the selection of amino acids with ionizable side chain might be restricted by the requirement for a special pH environment during the origin of life. From this point of view, the special distribution was the result of natural selection.
Protein interaction networks of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster: Large‐scale organization and robustness
Authors: Li Dong , Li Jianqi , Ouyang Shuguang , Wang Jian , Wu Songfeng , Wan Ping , Zhu Yunping , Xu Xiaojie , He Fuchu
Published: November 2005

High‐throughput screens have begun to reveal protein interaction networks in several organisms. To understand the general properties of these protein interaction networks, a systematic analysis of topological structure and robustness was performed on the protein interaction networks of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. It shows that the three protein interaction networks have a scale‐free and high‐degree clustering nature as the consequence of their hierarchical organization. It also shows that they have the small‐world property with similar diameter at 4–5. Evaluation of the consequences of random removal of both proteins and interactions from the protein interaction networks suggests their high degree of robustness. Simulation of a protein's removal shows that the protein interaction network's error tolerance is accompanied by attack vulnerability. These fundamental analyses of the networks might serve as a starting point for further exploring complex biological networks and the coming research of “systems biology”.
Proteome analysis of human liver carcinoma Huh7 cells harboring hepatitis C virus subgenomic replicon
Authors: Fang Caiyun , Yi Zhigang , Liu Feng , Lan Shuiyun , Wang Jiadong , Lu Haojie , Yang Pengyuan , Yuan Zhenghong
Published: November 2005

Chronic infection by hepatitis C virus (HCV) is closely correlated with serious liver diseases. Although considerable progress has been made during recent years, the mechanism of replication and pathogenesis of HCV infection are still elusive. We have applied proteomic techniques in this work to globally analyze the protein expression profiles of a human liver cell lines Huh7 in absence and presence of HCV replication, aiming at elucidating the components of HCV replication and the cellular responses to HCV replication. The protein mixtures of three subcellular fractions from Huh7 and Huh7‐HCV were separated by 2‐DE under various pH gradients. Differentially expressed spots were identified by MALDI‐TOF MS, followed by database searching. A total of 179 comparative proteins were identified unambiguously, including proteins associated with host cytoskeleton, intracellular traffic, oxidative and ER stress, proteasome degradation, translation, apoptosis, proliferation, etc. Host proteins known to interact with HCV proteins, such as HSP27, α‐actinin, nucleolin and eukaryotic initiation factor 4A‐I, were elevated in Huh7‐HCV cells. Our study provides the global information of proteomic alteration of Huh7 cells in the presence of HCV replication and the clues for further understanding of the mechanism of HCV replication and pathogenesis.
Syntheses of conductive adhesives based on epoxy resin and polyanilines by using N‐tert‐butyl‐5‐methylisoxazolium perchlorate as a thermally latent curing reagent
Authors: Hino Tetsuo , Taniguchi Shunsuke , Kuramoto Noriyuki
Published: November 2005

Conductive composites consisted of epoxy resin and polyanilines (PANIs) doped with dodecylbenzenesulfonic acid (1), dodecylsulfonic acid (2), di(2‐ethylhexyl)sulfosuccinic acid (3), and HCl were synthesized by use of N‐tert‐butyl‐5‐methylisoxazolium perchlorate (5) under various reaction conditions. It was found that the composites with PANI doped with acid 2 (PANI‐2) prepared by curing with 10 mol % of reagent 5 at 80 °C for 12 h showed high electroconductivity along with the low conducting percolation threshold (3 wt % of PANI‐2). Furthermore, the composite with even ˜10 wt % of PANI‐2 exhibited ˜10−1 S/cm of electroconductivity. The UV–vis and IR measurements indicated that the conductive emeraldine salt form of PANI‐2 in the composite was maintained after the curing reaction. The thermal stability was studied by TGA and DSC measurements, and then, the Td10 and Tg of the composite with 5 and 10 wt % of PANI‐2 were found to be similar to those with the cured epoxy resin itself. In addition, the similar investigation with an oxetane resin instead of the epoxy resin was also carried out. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 718–726, 2006
Rheological properties of ferrite nanocomposites based on nylon‐66
Authors: Chae Dong Wook , Lee Ki Hyun , Kim Byoung Chul
Published: November 2005

Effects of ferrite nanoparticles (0.1–20 wt %) on the rheological and other physical properties of nylon‐66 were investigated. The presence of ferrite nanoparticles less than 1 wt % increased the crystallization temperature (Tc) by 4.2 °C with ferrite content, but further addition decreased Tc. The onset temperature of degradation was increased by 7.3 °C at only 0.1 wt % loading of ferrite, after which the thermal stability of nylon‐66 was decreased with ferrite content. The incorporation of ferrite nanoparticles more than 5 wt % increased the dynamic viscosity (η′) with the loading level. Further, it produced notably shear thickening behavior in the low frequency, after which high degree of shear thinning was followed with ferrite content. In the Cole–Cole plot, the nanocomposites with ferrite lower than 5 wt % presented a single master curve, while further addition gave rise to a deviation from the curve. The relaxation time (λ) was increased with ferrite content and the difference of λ between nylon‐66 and its nanocomposite was greater at lower frequency. The tensile strength was a little increased up to 1 wt % loading, after which it was decreased with increasing the loading level. In addition, the introduction of the nanoparticles increased tensile modulus and decreased the ductility with ferrite content. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 371–377, 2006
Instream flows for recreation are closely correlated with mean discharge for rivers of western North America
Authors: Rood Stewart B. , George Chris , George Bobbi , Tymensen Wilco
Published: November 2005

Effective river regulation requires consideration for environmental and economic aspects and also for social aspects including recreation. Our study investigated relationships between river hydrology and recreational flows (RF) for canoes, kayaks, rafts and other non‐motorized boats, for 27 river reaches in the Red Deer and Bow river basins of southern Alberta, Canada. A subjective RF method involved regression analyses of data from River Trip Report Cards, volunteer postcard‐style surveys rating flow sufficiency. A total of 958 trip reports were submitted for the rivers between 1983 and 1997 and about 30 reports permitted confident regression analysis for a river reach. Values from these analyses were very consistent with values from the ‘depth discharge method’, a hydraulic modelling approach that used stage–discharge ratings to determine flows that would produce typical depths of 60 and 75 cm for minimal and preferred flows, respectively. Values were also consistent with expert opinions from river guidebooks and maps and aggregate values were calculated from the combined RF methods. These were very closely correlated with mean discharge (Qm) across the rivers (r2 = 0.94 for minimal and 0.96 for preferred flows). The relationship best fitted a power function (straight plot on log versus log scales) with a consistent slope but vertical offset for minimal versus preferred flows. Close relationships between guidebook estimates of RF and Qm were also observed for rivers in the American Rocky Mountain states of Idaho (r2 = 0.55 and 0.74), Montana (r2 = 0.34 and 0.80) and Colorado (r2 = 0.43 and 0.51), but the association was weaker for the Pacific Northwest state of Oregon (r2 = 0.35 and 0.26). These analyses indicate that RF can be confidently determined through a combination of subjective and hydraulic methods and reveal that RF values represent a systematic function of discharge for a broad range of alluvial and constrained river reaches. From these analyses we provide the ‘Alberta equation’: minimal recreational flow = 3 × Qm0.59 (Qm in m3/s), and preferred flows would typically be 1.5 times higher. For other river regions the exponent ‘0.59’ may be relatively constant but adjustments to the coefficient ‘3’ could be applicable. Copyright © 2005 John Wiley & Sons, Ltd.
Nitrogen processing by biofilms along a lowland river continuum
Authors: Baldwin D. S. , Mitchell A. M. , Rees G. N. , Watson G. O. , Williams J. L.
Published: November 2005

While numerous studies have examined N dynamics along a river continuum, few have specifically examined the role of biofilms. Nitrogen dynamics and microbial community structure were determined on biofilms at six sites along a 120 km stretch of the lowland Ovens River, South Eastern Australia using artificial substrates. Terminal restriction fragment length polymorphism (T‐RFLP), chlorophyllaand protein analyses were used to assess biofilm microbial community composition. N dynamics was determined on the biofilms using the acetylene (C2H2) block technique and assessing changes in NH, NOxand N2O. Unlike microbial community structure, N dynamics were spatially heterogeneous. Nitrification, determined from the difference in accumulation of NHbefore and after addition of C2H2, occurred mostly in the upper sites with rates up to 1.4 × 10−5 mol m−2 h−1. The highest rates of denitrification occurred in the mid‐reaches of the river (with rates up to 1 × 10−5 mol m−2 h−1) but denitrification was not detected in the lower reaches. At the very most, only 50% of the observed uptake of NOxby the biofilms following addition of C2H2could be accounted for by denitrification. Copyright © 2005 John Wiley & Sons, Ltd.
Analysis of interval‐censored longitudinal data with application to onco‐haematology
Authors: De Lorenzo Paola , Henderson Robin , Valsecchi Maria Grazia
Published: November 2005

The analysis of repeated measurements on a biomarker, either alone or jointly with the analysis of time to the event of interest, is an area of active research. Nevertheless, we are not yet able to deal in complete generality with these complex data, which frequently consist of error‐prone, sparse and intermittent values. In many cancer studies, they arise in the framework of clinical trials and thus their relationship with prognosis is a primary focus. In such a setting, the Cox model is regarded as the standard technique for analysis. The aim of this work is to illustrate an alternative approach to the analysis of studies in which the biomarker values are complicated by interval censoring and an event occurs when the biomarker itself passes a certain threshold. We propose a linear mixed model with a Gaussian stochastic process that allows for interval‐censored data and can be used both to track the biomarker trajectory and to estimate the probability of event occurrence. It is developed within the classic approach to longitudinal data analysis that was previously adapted for left‐censored data, only. We apply this method to a study on the minimal residual disease (MRD) in childhood leukaemia. MRD is an interval‐censored measurement of residual leukaemic cells that was scheduled at 9 time‐points during treatment. The aim is to investigate the relationship between MRD and the disease process. Relapse, the event of interest, may conveniently be represented as MRD over a pre‐defined threshold. Our focus is on modelling the probability of relapse conditional on MRD observed prior to it. Results show that the approach is promising as it allows proper description of the data, while maintaining flexibility of modelling, feasibility of computations and interpretability of results. Copyright © 2005 John Wiley & Sons, Ltd.
Testing and estimation in flexible group sequential designs with adaptive treatment selection
Authors: Posch Martin , Koenig Franz , Branson Michael , Brannath Werner , Dunger‐Baldauf Cornelia , Bauer Peter
Published: November 2005

Integrating selection and confirmation phases into a single trial can expedite the development of new treatments and allows to use all accumulated data in the decision process. In this paper we review adaptive treatment selection based on combination tests and propose overall adjusted p‐values and simultaneous confidence intervals. Also point estimation in adaptive trials is considered. The methodology is illustrated in a detailed example based on an actual planned study. Copyright © 2005 John Wiley & Sons, Ltd.
Minimization—reducing predictability for multi‐centre trials whilst retaining balance within centre
Authors: Brown Sarah , Thorpe Helen , Hawkins Kim , Brown Julia
Published: November 2005

Minimization is often used to assign patients to treatment groups to ensure good balance in patient numbers within centre and other prognostic factors. Balance within centre is preferable since large imbalances between treatment arms may have logistical implications for centres, such as cost and resource implications. However, recent concern over high predictability of treatment allocation by centres when using minimization has caused this method to be questioned. We used data from current clinical trials to assess predictability and summarize subsequent within‐centre imbalances with the aim of finding the most effective minimization method for reducing predictability whilst still retaining sufficient balance within centre, when randomization is to one of two treatments. We compared prediction rates and imbalances for deterministic minimization, and minimization incorporating various random elements, p (p=0.95,0.90,0.80,0.75,0.70). We also compared prediction rates and imbalance when centre was and was not included as a stratification factor. Incorporating a random element proved successful in reducing prediction rates whilst minimizing the inevitable increase in within‐centre imbalance, whereas excluding centre as a stratification factor incurred major within‐centre imbalance. We therefore suggest that minimization can still be used, and that centre can be included as a stratification factor, but a random element has to be incorporated into the minimization algorithm. Minimization incorporating a random element of 0.80 is the most efficient method to use based upon the simulations undertaken in this study of real clinical trial data using different probabilities of allocation. Copyright © 2005 John Wiley & Sons, Ltd.
Bayesian implementation of a genetic model‐free approach to the meta‐analysis of genetic association studies
Authors: Minelli Cosetta , Thompson John R. , Abrams Keith R. , Lambert Paul C.
Published: November 2005

A genetic model‐free method for the meta‐analysis of genetic association studies is described that estimates the mode of inheritance from the data rather than assuming that it is known. For a bi‐allelic polymorphism, with G as risk allele and g as wild‐type, the genetic model depends on the ratio of the two log odds ratios, λ = log ORGg/log ORGG, where ORGGcompares GG with gg and ORGgcompares Gg with gg. Modelling log ORGGas a random effect creates a hierarchical model that can be implemented within a Bayesian framework.

In Bayesian modelling, vague prior distributions have to be specified for all unknown parameters when no external information is available. When the data are sparse even supposedly vague prior distributions may have an influence on the posterior estimates. We investigate the impact of different vague prior distributions for the between‐study standard deviation of log ORGGand for λ, by considering three published meta‐analyses and associated simulations. Our results show that depending on the characteristics of the meta‐analysis the results may indeed be sensitive to the choice of vague prior distribution for either parameter.

Genetic association studies usually use a case‐control design that should be analysed by the corresponding retrospective likelihood. However, under some circumstances the prospective likelihood has been shown to produce identical results and it is usually preferred for its simplicity. In our meta‐analyses the two likelihoods give very similar results. Copyright © 2005 John Wiley & Sons, Ltd.
Permutation based methods for comparing quality of life between observed treatments
Authors: Moerkerke Beatrijs , Goetghebeur Els , Van Steen Kristel , Van Belle Simon , Cocquyt Veronique
Published: November 2005

Quality of life is becoming an important outcome for the comparison of aggressive therapies. To measure quality of life (QOL), questionnaires have been designed that ask patients about symptoms and functionality in several aspects of daily life. Primary analyses of such questionnaires typically focus on a summary statistic, such as a sum score or a single global question. This avoids inflated type I errors or loss of power due to multiple testing of individual items. In return, specific questions and answers that initially mattered to the patient may unfortunately get buried. To avoid reduced specificity and interpretability for both patients and physicians, we propose to also analyse all original questions. In this paper, we seek to detect items of the QOL questionnaire that differ significantly over observed treatments even in the face of multiple testing. We sequentially build a model that combines features which additionally discriminate between treatments. To achieve this, we draw on insights gained in the field of statistical genetics where one is often confronted with a vast amount of predictors, e.g. of a genotypic nature. Specifically, we adopt a permutation based approach to evaluate the null distribution of the maximum of many correlated test statistics and use it to build a regression model that explains QOL differences between treatment arms. We apply the new methodology to analyse QOL data in an observational study of four different treatments of breast cancer. We discover that a single question captures most of the observed treatment differences in this population. Copyright © 2005 John Wiley & Sons, Ltd.
Bayesian proportional hazards model with time‐varying regression coefficients: a penalized Poisson regression approach
Authors: Lambert Philippe , Eilers Paul H. C.
Published: November 2005

One can fruitfully approach survival problems without covariates in an actuarial way. In narrow time bins, the number of people at risk is counted together with the number of events. The relationship between time and probability of an event can then be estimated with a parametric or semi‐parametric model. The number of events observed in each bin is described using a Poisson distribution with the log mean specified using a flexible penalized B‐splines model with a large number of equidistant knots. Regression on pertinent covariates can easily be performed using the same log‐linear model, leading to the classical proportional hazard model. We propose to extend that model by allowing the regression coefficients to vary in a smooth way with time. Penalized B‐splines models will be proposed for each of these coefficients. We show how the regression parameters and the penalty weights can be estimated efficiently using Bayesian inference tools based on the Metropolis‐adjusted Langevin algorithm. Copyright © 2005 John Wiley & Sons, Ltd.
Concordance correlation coefficient applied to discrete data
Authors: Carrasco Josep L. , Jover Lluis
Published: November 2005

In any field in which decisions are subject to measurements, interchangeability between the methods used to obtain these measurements is essential. To consider methods as interchangeable, a certain degree of agreement is needed between the measurements they provide. The concordance correlation coefficient is an index that assesses the strength of agreement and it has been widely applied in situations in which measurements are made on a continuous scale. Recently the concordance correlation coefficient has been defined as a specific intraclass correlation coefficient estimated by the variance components of a Normal–Normal mixed linear model. Although this coefficient was defined for the continuous scale case, it may also be used with a discrete scale. In this case the data are often transformed and normalized, and the concordance correlation is applied. This study discusses the expression of the concordance correlation coefficient for discrete Poisson data by means of the Poisson–Normal generalized linear mixed model. The behaviour of the concordance correlation coefficient estimate is assessed by means of a simulation study, in which the estimates were compared using four models: three Normal–Normal mixed models with raw data, log‐transformed data and square‐root transformed data, and the Poisson–Normal generalized linear mixed model. An example is provided in which two different methods are used to measure CD34+cells. Copyright © 2005 John Wiley & Sons, Ltd.