bluuebunny/crossref_metadata_2025 huggingface dataset:
A familial balanced inverted insertion ins(15)(q15q13q11.2) producing Prader–Willi syndrome, Angelman syndrome and duplication of 15q11.2‐q13 in a single family: Importance of differentiation from a paracentric inversion
Authors: Collinson Morag N. , Roberts Siân E. , Crolla John A. , Dennis Nicholas R.
Published: March 2004

We reascertained a family in which first cousins were affected by Angelman syndrome and Prader–Willi syndrome. A paracentric inversion of 15q11‐q15 had previously been reported in this family but we show, using fluorescence in situ hybridization (FISH), that the rearrangement segregating in this family is not a paracentric inversion but an inverted intrachromosomal insertion, inv ins(15)(q15q13q11.2). We also describe a further recombinant resulting in a maternal duplication of the Prader–Willi/Angelman critical region. This family illustrates the importance of distinguishing paracentric inversions from intrachromosomal insertions. © 2004 Wiley‐Liss, Inc.
A Factorized High Dimensional Model Representation on the Partitioned Random Discrete Data
Authors: Alper Tunga M. , Demiralp Metin
Published: March 2004

The main purpose of this work is to obtain the general structure of a product type of multivariate function when the values of the function are given randomly at the nodes of a hyperprism. When the dimensionality of multivariate interpolation and the number of the data sets increase unboundedly, many problems can be encountered in the standard numerical methods. Factorized High Dimensional Model Representation (FHDMR) is used to obtain the general structure of this given multivariate function. The components of FHDMR are determined by using the components of the Generalized High Dimensional Model Representation (GHDMR).The given random discrete data is partitioned by GHDMR method. This partitioned data produces a structure for the multivariate function by using single variable Lagrange interpolation formula including only the constant term and the univariate terms of the GHDMR components. Finally, a general structure is obtained via FHMDR by using these components. By this way, the multidimensionality of a multivariate interpolation is approximated by lower dimensional interpolations like univariate ones. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Parametric Sensitivity Analysis for the Solution of Extrema Evaluation Problems via a Dimensionality Reducing Approximation Method
Authors: Kaman Tülin , Demiralp Metin
Published: March 2004

This work aims to apply High Dimensional Model Representation (HDMR) to the sensitivity coefficient determination of the solutions of a multivariate extrema problem. The derivations are made for general functional structure and the illustrative applications are related to structures where the resulting extrema equations are matrix eigenvalue problems. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Diastereoselective C‐arylation of prochiral enolates by the SRN1 reaction
Authors: Baumgartner María T. , Lotz Guillermo A. , Palacios Sara M.
Published: March 2004

Chiral phenyl acetamide enolate ions were diastereoselectively arylated using aromatic substrates by means of the SRN1 reaction. The substitution took place with a diastereomeric excess that varied from 31–98%, depending on the enolate counterion, the reaction temperature, the solvent, and the aromatic substrate. The absolute configuration of the new stereogenic center of the products (4R,5S)‐1,5‐dimethyl‐4‐phenyl‐3‐[2′‐phenyl‐2′‐arylacetyl]‐imidazolidin‐2‐one (Aryl = 3‐quinolyl, 1‐naphthyl, 4‐anisyl, 4‐benzonitryl, 4‐tolyl, 9‐phenanthryl) was determined by 1H NMR spectroscopy and theoretical calculations. Chirality 16:212–219, 2004. © 2004 Wiley‐Liss, Inc.
Calculations of protein circular dichroism from first principles
Authors: Rogers David M. , Hirst Jonathan D.
Published: March 2004

Understanding the relationship between the amino acid sequence of a protein and its unique, compact 3D structure is one of the grand challenges in molecular biophysics. One particularly exciting approach is time‐resolved electronic circular dichroism (CD) spectroscopy, which offers resolution on a nanosecond (or faster) time scale, although it does not provide the spatial resolution of techniques like X‐ray crystallography or NMR. The thrust of our work is to underpin fast time scale spectroscopic studies of protein folding with a stronger theoretical foundation. Ultimately, we seek to use molecular dynamics simulations to study the influence of conformational dynamics and conformational transitions on the electronic CD spectra of proteins. We discuss how improved quantum chemical models of individual chromophores, including aromatic sidechains, can be incorporated into calculations of the electronic structure of proteins and their CD. Chirality 16:234–243, 2004. © 2004 Wiley‐Liss, Inc.
Study of the characterization and crystallization of 4‐hydroxy‐2‐pyrrolidone
Authors: Wang Xiu Juan , Wiehler Harald , Ching Chi Bun
Published: March 2004

A systematic study of the characterization for racemic species of 4‐hydroxy‐2‐pyrrolidone was undertaken. The melting point phase diagram of (R)‐ and (S)‐4‐hydroxy‐2‐pyrrolidone was determined by differential scanning calorimetry. The ternary phase diagram of (R)‐ and (S)‐4‐hydroxy‐2‐pyrrolidone with isopropanol was constructed at 15, 20, 25, and 35°C. The crystalline nature of 4‐hydroxy‐2‐pyrrolidone racemate was also characterized by means of comparison of solid‐state FTIR spectra and powder X‐ray diffraction patterns of the racemic mixture with those of one of the enantiomers. It is shown that (±)‐4‐hydroxy‐2‐pyrrolidone is a racemic conglomerate. The enthalpies of fusion of (R)‐4‐hydroxy‐2‐pyrrolidone and (±)‐4‐hydroxy‐2‐pyrrolidone and entropy of mixing of (R)‐ and (S)‐4‐hydroxy‐2‐pyrrolidone were calculated using the thermodynamic data. The solubility and supersolubility diagrams of (R)‐ and (S)‐4‐hydroxy‐2‐pyrrolidone in isopropanol were determined over a temperature range of 4–35°C. The optical resolution of (±)‐4‐hydroxy‐2‐pyrrolidone was successfully achieved by preferential crystallization. Chirality 16:220–227, 2004. © 2004 Wiley‐Liss, Inc.
Transfer of chirality by dithiophosphate ligands and chiral discrimination in the stereoselective formation of square‐planar Ni(II) complexes
Authors: Biscarini Paolo , Benedetti Michele , Ferranti Francesco , Kuroda Reiko , Foresti Elisabetta , Sabatino Piera
Published: March 2004

In the formation reaction of Ni2+ with the chiral racemic ligand, (R)(R)bdtp−/(S)(S)bdtp−, bdtp− = [SSPOCH)CH3)CH(CH3)O]−, cyclo‐ O,O′‐[1,2‐dimethylethylene] dithiophosphato ion, the meso‐complex Ni[(R)(R)(λ)bdtp][(S)(S)(δ)‐bdtp] is stereoselectively produced. The meso‐complex was compared with the enantiopure crystals of (+)589Ni[(R)(R)(λ)bdtp]2 or (−)589Ni[(S)(S)(δ)bdtp]2, as well as racemic crystals, rac‐(±)Ni[bdtp]2, which were prepared from the solution containing the two enantiomers in a 1:1 ratio. Dissociation constants in solutions indicate different stability of the meso and enantiopure complexes depending on the solvent, whereas a more efficient crystal packing, weak H‐bonding, and nonbonding interactions contribute to stabilization of the meso‐species over the racemic one. Molecular structures show that the outer five‐membered ligand ring adopts the half‐chair conformation C2 with either the λ or the δ chirality and the methyl groups are in equatorial (e) positions. Enantiopure ligands of (+)589Ni[(R)(R)(λ)bdtp]2 and (−)589Ni[(S)(S)(δ)bdtp]2 induce chirality into the symmetric SSNiSS chromophore with slightly helical distortion. Thus, their CD spectra exhibit weak negative or positive Cotton effects at 662 nm. CD spectra in L(+)‐ and D(−)diethyltartrate of the meso‐complex and racemic crystal, rac‐(±)Ni[bdtp]2, exhibit different weak Cotton effects of opposite sign. Complexes dissociate in methanol; rac‐(±)Ni[bdtp]2 in methanol undergoes a crystallization‐induced second‐order asymmetric transformation which finally yields crystals of the meso‐Ni[(R)(R)(λ)bdtp][(S)(S)(δ)bdtp] complex. Chirality 16:251–262, 2004. © 2004 Wiley‐Liss, Inc.
Utilizing hydrolases of opposite enantiopreference for the preparation of both enantiomers of (1R,7aR)‐(−)‐ and (1S,7aS)‐(+)‐3,6,7,7a‐tetrahydro‐1‐hydroxy‐7a‐methyl‐1H‐inden‐5(2H)‐one
Authors: Lo Lee‐Chiang , Chou Tzyy‐Chao , Shie Jung‐Jing
Published: March 2004

Four racemic esters of (1R*,7aR*)‐3,6,7,7a‐tetrahydro‐1‐hydroxy‐7a‐methyl‐1H‐inden‐5(2H)‐one were prepared and subjected to hydrolysis with two types of hydrolases, including alcalase and three lipases. Alcalase and lipase showed opposite enantiopreference on these esters. Based on this result, we developed a gram‐scale procedure using butanoate as the substrate, which was treated consecutively with alcalase and lipase from Candida rugosa (CRL), to give both enantiomers of the title compound in high yields and high enantiomeric excess. Chirality 16:267–271, 2004. © 2004 Wiley‐Liss, Inc.
Enantioseparation of hydrochloride salts using carbon dioxide‐based mobile phases with on‐line polarimetric detection
Authors: Geiser Fiona , Shah Rekha
Published: March 2004

Most HPLC enantioseparations of amine analytes are performed using normal‐phase systems containing mobile phases of heptane with ethanol (or 2‐propanol) and an amine additive. Since salt‐forms of amine analytes are usually insoluble in normal‐phase eluents, free‐base forms are synthesized for preparative chromatography. It would be highly desirable to directly chromatograph salt forms of amine analytes using mobile phases of carbon dioxide (CO2) and methanol (MeOH). Such separations would be readily suitable for preparative chromatography, since most amine salts are highly soluble in MeOH. In this article, advantages are shown for the use of supercritical fluid chromatography (SFC) instrumentation with tandem UV and polarimetric detection for confirming enantioseparation as well as for determining optimum preparative column injections. Examples are shown for racemic mixtures of propranolol HCl (I), thioridazine HCl (II), tramadol HCl (III), and flurbiprofen (IV), all of which resolved on Chiralpak AD‐H chiral stationary phase using mobile‐phase systems of CO2 and MeOH without the use of basic or acidic additives. Chirality 16:263–266, 2004. © 2004 Wiley‐Liss, Inc.
An autonomous decentralized model with nonlocal interaction: Roles of an extracellular matrix in organization of a multicellular system
Authors: Ogawa Ken‐ichiro , Miyake Yoshihiro
Published: March 2004

The reaction‐diffusion model is one of the theoretical approaches used to realize autonomous decentralized systems. The model conventionally assumes that all components of a system locally interact with each other under ideal conditions, ignoring any effect from the environment. However, it has recently become clear that nonlocal interactions mediated by the environment play an important role in the ontogenesis of multicellular organisms, a typical autonomous decentralized system. In this paper, we discuss the “redifferentiation” phenomenon of cancer cells in which such a nonlocal interaction is considered to play an essential role. Further, we propose a model to reproduce this phenomenon and mathematically analyze our model to construct autonomous decentralized systems with nonlocal interactions mediated by the environment in the future. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(7): 55–65, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ ecjc.10101
Fast acquisition methods with code‐orthogonalizing filters in DS/CDMA
Authors: Takahashi Hirokazu , Hamamura Masanori , Tachikawa Shin'ichi
Published: March 2004

This paper presents a new acquisition method achieving reduction of acquisition time by improving the conventional acquisition method using the code‐orthogonalizing filter. In the acquisition method using the code‐orthogonalization filter, most of the acquisition time is spent on the orthogonalization process. Hence, in the proposed method, estimation of synchronous point candidates is performed several times so that the estimation accuracy is improved and the acquisition time is reduced by decreasing the number of orthogonalizations. After the scheme is explained, a performance evaluation of the proposed method is carried out by computer simulation. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(7): 36–44, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10148
A study of image segmentation based on a robust data clustering method
Authors: Ryu Heeburm , Miyanaga Yoshikazu
Published: March 2004

This paper considers intelligent image clustering and proposes a clustering method based on the self‐organizing mechanism, which is an adaptive and autonomous algorithm. The proposed method solves the problem of initial value setting, which has been a difficulty in the conventional clustering method, and has the feature that the effective clusters are always self‐organized. A method is realized which is robust and does not require empirical setting of the initial value. Thus, the effective initial cluster can always be selected for various kinds of data sets, and an excellent clustering is obtained. A method is proposed in which these features are utilized in image segmentation. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(7): 27–35, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10154
Iterative inverse filter relaxation algorithm for adaptation to acoustic fluctuation in sound reproduction system
Authors: Nagata Yu , Tatekura Yosuke , Saruwatari Hiroshi , Shikano Kiyohiro
Published: March 2004

This paper proposes a relaxation algorithm for an inverse filter that is adaptive to environmental change in a multichannel sound reproduction system. For a conventional multichannel sound reproduction system, a design method has been proposed for an inverse filter by means of the Moore–Penrose‐type generalized inverse matrix. However, in the inverse filter in the conventional method, background noise and line noise may be enhanced when the room transfer characteristics vary. In order to resolve this problem, an adaptive relaxation method based on the truncated singular value decomposition (TSVD) has been introduced. In the present paper, a microphone for monitoring the noise is placed at a location far from both ears of the listener. Relaxation of the inverse filter is carried out by using the reproduced sound observed by this microphone. From the results of computer simulation, it is found that the proposed method prevents amplification of the noise. Also, as a result of a subjective evaluation experiment on sound reproduction in a real acoustic environment, the sound quality was found to be improved significantly without damaging the sound localization of position. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(7): 15–26, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10159
Role of inherited defects of MYH in the development of sporadic colorectal cancer
Authors: Kambara Takeshi , Whitehall Vicki L. J. , Spring Kevin J. , Barker Melissa A. , Arnold Sven , Wynter Coral V. A. , Matsubara Nagahide , Tanaka Noriaki , Young Joanne P. , Leggett Barbara A. , Jass Jeremy R.
Published: March 2004

Biallelic germ‐line variants of the 8‐hydroxyguanine repair gene MYH have been associated with multiple colorectal adenomas that display somatic G:C→T:A transversions in APC. However, the effect of single germ‐line variants has not been widely studied. To examine the relationship between monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC), 92 cases of sporadic CRC, 19 cases of familial CRC not meeting the Bethesda guidelines, 17 cases with multiple adenomas, and 53 normal blood donors were screened for 8 potentially pathogenic germ‐line MYH variants. Loss of heterozygosity (LOH) at 1p adjacent to the MYH locus, microsatellite instability (MSI) status, and somatic mutations in KRAS2 and APC were analyzed in sporadic cancers. Neither homozygote nor compound heterozygote MYH variants were observed in the germ‐line of any subjects with sporadic CRC. There was no difference in the incidence of monoallelic variants between this group (20 of 92, 22%) and cancer‐free controls (14 of 53, 26%). However, the presence of monoallelic germ‐line MYH variants was negatively associated with an MSI‐high (MSI‐H) tumor phenotype, with an incidence of only 1 of 23 (4%) MSI‐H CRCs as contrasted with 19 of 69 (28%) non‐MSI‐H (P = 0.02). Further, 4 of 5 tumors with 1p LOH contained monoallelic MYH variants compared with 15 of 53 without 1p LOH (P = 0.04) and the normal population (P = 0.03). The presence of G:C→T:A transversions in KRAS2 or APC was significantly more common in single MYH variant tumors (9 of 12) than in MYH wild‐type tumors (11 of 33; P = 0.02). These results suggest that single germ‐line variants of MYH may influence genetic pathways in CRC. © 2004 Wiley‐Liss, Inc.
Method for manufacturing whole‐genome microarrays by rolling circle amplification
Authors: Smirnov Denis A. , Burdick Josh T. , Morley Michael , Cheung Vivian G.
Published: March 2004

Comparative genomic hybridization (CGH) to metaphase chromosomes is a method for genome‐wide detection of chromosomal aberrations in DNA samples. Recent advances in microarray technology have improved CGH by replacing metaphase chromosomes with a collection of mapped genomic clones placed on glass slides. However, it is quite expensive and labor‐intensive to prepare DNA from the genomic clones for use in constructing genomic microarrays. Here we used strand‐displacement rolling circle amplification (RCA) to manufacture whole‐genome microarrays by using a collection of about 4,500 mapped RPCI‐11 BAC clones that cover the human genome at approximately a 1‐Mb resolution. These genomic microarrays detected all major chromosomal aberrations in cancer cells lines and in cell lines with aneuploidy. In this article, we discuss the advantages of using RCA for the manufacturing of large genomic microarrays. © 2004 Wiley‐Liss, Inc.
Computational BAC clone contig assembly for comprehensive genome analysis
Authors: Lapuk Anna , Volik Stanislav , Vincent Robert , Chin Koei , Kuo Wen‐Lin , de Jong Pieter , Collins Colin , Gray Joe W.
Published: March 2004

Comparative genomic hybridization (CGH) has proved to be a powerful tool for the detection of genome copy number changes in human cancers and in other diseases caused by segmental aneusomies. Array versions of CGH allow the definition of these aberrations, with resolution determined by the size and distribution of the array elements. Resolution approaching 100 kb can be achieved by use of arrays comprising bacterial artificial chromosomes (BACs) distributed contiguously across regions of interest. We describe here a computer program that automatically assembles contigs of minimally overlapping BAC clones, using information about BAC end‐sequences and the normal genome DNA sequence. We demonstrate the characteristics of contigs assembled and annotated by use of this approach for regions of recurrent abnormality in human ovarian and breast cancers at chromosome bands 3q25–q27 and 8q24 and chromosome arm 20q. We also show illustrative analyses of regions of amplification in these regions in breast and ovarian tumor cell lines by use of array CGH with arrays comprising contiguous BACs. © 2004 Wiley‐Liss, Inc.
Gene copy mapping of the ERBB2/TOP2A region in breast cancer
Authors: Jacobson Kris K. , Morrison Larry E. , Henderson Benita T. , Blondin Beth A. , Wilber Kimberly A. , Legator Mona S. , O'Hare Anna , Van Stedum Susan C. , Proffitt John H. , Seelig Steve A. , Coon John S.
Published: March 2004

ERBB2 is one of the most important oncogenes in breast cancer, and its disordered expression is commonly associated with gene amplification. Amplification of at least one gene near ERBB2, topoisomerase IIα (TOP2A), has been shown to be clinically significant, but the prevailing patterns of gene amplification in this region of chromosome arm 17q have not been studied systematically in clinical cases of breast cancer. For characterizing this region, a commercial ERBB2‐containing contig probe and 7 probes prepared from single overlapping BAC and P1 clones lying telomeric to ERBB2 and including TOP2A were hybridized to 77 ERBB2‐amplified archival breast tumor specimens from 75 patients. The 7 single‐clone probes covered a region of approximately 650 kb starting 114 kb telomeric to ERBB2. Amplification of the ERBB2 contig target alone was found in 32% of the tumors, whereas all 8 probe targets were amplified in 12% of the tumors, based on an amplification criterion of there being more than or equal to 2 targets per chromosome 17 centromere. When one of the 7 overlapping probes encompassing TOP2A indicated amplification within a specimen, all probes telomeric to that probe usually showed amplification. Only 5 specimens had regions of normal or deleted targets separating 2 amplified targets. Also, tumors that showed deletion of TOP2A usually showed deletion of one or more contiguous targets. The observed patterns of amplification and deletion are consistent with the break–fusion–bridge model for gene amplification. TOP2A was amplified in 25% of all tumor specimens and was deleted in 24%, based on a deletion criterion of there being fewer than or equal to 0.75 targets per chromosome 17 centromere. Considering the relevance of the TOP2A gene product to anthracycline therapy and the wealth of other cancer‐associated genes within the ERBB2/TOP2A region, the pattern of amplification and deletion near ERBB2 and TOP2A may have a dramatic effect on the malignant potential of breast carcinomas and their response to therapy. © 2004 Wiley‐Liss, Inc.
Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome
Authors: Grand Effie K. , Grand Francis H. , Chase Andrew J. , Ross Fiona M. , Corcoran Martin M , Oscier David G. , Cross Nicholas C. P.
Published: March 2004

The 8p11 myeloproliferative syndrome (EMS) is an aggressive hematological malignancy caused by the fusion of diverse partner genes to fibroblast growth factor receptor 1 (FGFR1). The partner proteins promote dimerization and ligand‐independent activation of FGFR1‐encoded tyrosine kinase, deregulating hemopoiesis in a manner analogous to BCR‐ABL in chronic myeloid leukemia. Here, we describe the identification of a new FGFR1 fusion gene in a patient who presented with T‐cell lymphoblastic lymphoma in conjunction with an acquired ins(12;8)(p11;p11p22). Initial FISH analysis and Southern blotting confirmed that FGFR1 was disrupted. Using 5′‐RACE PCR, we identified part of a novel gene, FGFR1OP, at chromosome band 12p11 that was fused to exon 9 of FGFR1.FGFR1OP2 is predicted to be translated into an evolutionarily conserved protein containing coiled‐coil domains but no other recognizable motifs. The presence of the chimeric gene was confirmed by RT‐PCR, genomic DNA PCR, and FISH. These data further support the central role of deregulated FGFR1 in the pathogenesis of EMS. © 2004 Wiley‐Liss, Inc.
Cellular injury induces activation of MAPK via P2Y receptors
Authors: Yang LingLing , Cranson D. , Trinkaus‐Randall V.
Published: March 2004

Wound healing is a complex process that involves cell communication, migration, proliferation, and changes in gene expression. One of the first events after injury is the rapid release of Ca2+ that propagates as a wave to neighboring cells (Klepeis et al. [2001]: J. Cell. Sci. 114:4185–4195). Our goal was to examine the signaling events induced by cellular injury and identify extracellular molecules that induce the activation of extracellular signal responsive kinase (ERK) (p42/44). In this study we demonstrated that injury induced ERK1/2 activation occurred within 2 min and was negligible by 15 min. Treatment of unwounded cells with wound media caused activation of ERK that could be inhibited by apyrase III. Stimulation with epidermal growth factor (EGF) did not mimic the injury response and it was not detected in the wound media. To identify the active component, size fractionation was performed and factor(s) less than 3 kDa that induced the release of Ca2+ and activation of ERK1/2 were identified. Activity was not altered by heat denaturation, incubation with proteinase K but it was lost by treatment with apyrase. Adenosine triphosphate (ATP), uridine triphosphate (UTP), adenosine diphosphate (ADP), and uridine diphosphate (UDP) promoted activation by 2 min with similar profiles as that generated by injury. Preincubation with phospholipase C inhibitor, U73122, inhibited activation that was induced by injury and/or nucleotides. Lack of activation by alpha‐beta‐methylATP (α, β‐MeATP) and beta‐gamma‐methylATP (β, γ‐MeATP) to purinergic (P)2X receptors further indicated that activation occurs via P2Y and not P2X purinergic receptors. These results indicate that injury‐induced activation of ERK1/2 is mediated by a P2Y signaling pathway. © 2004 Wiley‐Liss, Inc.
BRCA1 interacts with dominant negative SWI/SNF enzymes without affecting homologous recombination or radiation‐induced gene activation of p21 or Mdm2
Authors: Hill David A. , de la Serna Ivana L. , Veal Timothy M. , Imbalzano Anthony N.
Published: March 2004

BRCA1 is a tumor suppressor gene linked to familial breast and ovarian cancer. The BRCA1 protein has been implicated in a diverse set of cellular functions, including activation of gene expression by the p53 tumor suppressor and control of homologous recombination (HR) during DNA repair. Prior reports have demonstrated that BRCA1 can exist in cells in a complex with the BRG1‐based SWI/SNF ATP‐dependent chromatin remodeling enzymes and that SWI/SNF components contribute to p53‐mediated gene activation. To investigate the link between SWI/SNF function and BRCA1 mediated effects on p53‐mediated gene activation and on mechanisms of homologous recombination, we have utilized mammalian cells that inducibly express an ATPase‐deficient, dominant negative SWI/SNF enzymes. Mutant SWI/SNF ATPases retain the ability to interact with BRCA1 in cells. We report that expression of dominant negative SWI/SNF enzymes does not affect p53‐mediated induction of the p21 cyclin dependent kinase inhibitor or the Mdm2 E3 ubiquitin ligase that regulates p53 in cells exposed to UV or gamma irradiation. Similarly, integration of a reporter that monitors homologous recombination by gene conversion into these cells demonstrated no change in the recombination rate in the absence of functional SWI/SNF enzyme. We conclude that the SWI/SNF chromatin remodeling enzymes may contribute to but are not required for these processes. © 2004 Wiley‐Liss, Inc.
Mechanism of taxol‐induced apoptosis in human SKOV3 ovarian carcinoma cells
Authors: Ahn Hak Jun , Kim Yeong Shik , Kim Joung‐Uk , Han Sung Min , Shin Jin Woo , Yang Hyun Ok
Published: March 2004

Taxol is extensively used clinically for chemotherapy of patients with ovarian, breast, and lung cancer. Although taxol induces apoptosis of cancer cells, its exact mechanism of action is not yet known. To determine the mechanism of action of taxol in ovarian cancer, we tested the effects of the drug, on the human ovarian carcinoma cell line, SKOV3. We observed that taxol‐induced apoptosis of these cells by phosphatidylserine (PS) externalization and DNA fragmentation. While treatment of cells with taxol resulted in bcl‐2 phosphorylation and mitochondrial depolarization, cytochrome c was not released and pro‐caspase‐3 was not activated. Treatment of SKOV3 cells with taxol, however, resulted in the translocation of AIF from the mitochondria to the nucleus via the cytosol. Taken together, these findings suggest that in SKOV3 cells, taxol induces caspase‐independent AIF‐dependent apoptosis. © 2004 Wiley‐Liss, Inc.
SPARC regulates TGF‐beta1‐dependent signaling in primary glomerular mesangial cells
Authors: Francki Aleksandar , McClure Timothy D. , Brekken Rolf A. , Motamed Kouros , Murri Carrie , Wang Tongwen , Sage E. Helene
Published: March 2004

Secreted protein acidic and rich in cysteine (SPARC), a member of the family of matricellular proteins, regulates the interaction of cells with pleiotropic factors and proteins of the extracellular matrix (ECM). Although it has been appreciated that transforming growth factor beta 1 (TGF‐β1) induces SPARC and collagen type I, we have recently shown that SPARC regulates the expression of TGF‐β1 and collagen type I in renal mesangial cells via a TGF‐β1‐dependent pathway, and have proposed a reciprocal, autocrine regulatory feedback loop between SPARC and TGF‐β1. Herein, we sought to determine how SPARC regulates TGF‐β1‐dependent signal transduction. Our data indicate that SPARC modulates the TGF‐β1‐dependent phosphorylation of Smad‐2 in primary mesangial cells derived from wild‐type and SPARC‐null mice. We also show that SPARC regulates the levels and activation of the stress‐activated c‐jun‐N‐terminal kinase (JNK) in mesangial cells by augmentation of the stimulatory effects of TGF‐β1. Furthermore, we found that SPARC increases the levels and the activity of the transcription factor c‐jun. These effects of SPARC on the TGF‐β1 signaling pathway appear to be mediated through an interaction with the TGF‐β1‐receptor complex, but only in the presence of TGF‐β1 bound to its cognate type II receptor. That SPARC is directly involved in the regulation of the TGF‐β1 signaling cascade is consistent with the paradigm that matricellular proteins modulate interactions among cells, growth factors, and their respective receptors. © 2004 Wiley‐Liss, Inc.
Functional role of centrosomes in spindle assembly and organization
Authors: Varmark Hanne
Published: March 2004

The centrosome is the main MT organizing center in animal cells, and has traditionally been regarded as essential for organization of the bipolar spindle that facilitates chromosome segregation during mitosis. Centrosomes are associated with the poles of the mitotic spindle, and several cell types require these organelles for spindle formation. However, most plant cells and some female meiotic systems get along without this organelle, and centrosome‐independent spindle assembly has now been identified within some centrosome containing cells. How can such observations, which point to mutually incompatible conclusions regarding the requirement of centrosomes in spindle formation, be interpreted? With emphasis on the functional role of centrosomes, this article summarizes the current models of spindle formation, and outlines how observations obtained from spindle assembly assays in vitro may reconcile conflicting opinions about the mechanism of spindle assembly. It is further described how Drosophila mutants are used to address the functional interrelationships between individual centrosomal proteins and spindle formation in vivo. © 2004 Wiley‐Liss, Inc.
Superinduction of IL‐6 by cycloheximide is associated with mRNA stabilization and sustained activation of p38 map kinase and NF‐κB in cultured caco‐2 cells
Authors: Hershko Dan D. , Robb Bruce W. , Wray Curtis J. , Luo Guan‐ju , Hasselgren Per‐Olof
Published: March 2004

Protein synthesis inhibitors paradoxically increase the expression of early‐gene products, including various cytokines, through a process known as superinduction. Superinduction is cell‐specific and the mechanisms involved are not fully understood but are usually attributed to decreased mRNA degradation. There is, however, increasing evidence that activation of signaling cascades and increased transcriptional activation may be involved as well. Recent studies suggest that IL‐6 production in the intestinal mucosa is particularly important due to its anti‐inflammatory and protective effects. The effect of protein synthesis inhibitors on IL‐6 production in enterocytes, however, is unknown. Treatment of Caco‐2 cells with cycloheximide (10 μg/ml) increased IL‐6 mRNA and protein levels in IL‐1β‐treated cells and this was associated with increased mRNA stabilization. In addition, cycloheximide suppressed IκBα resynthesis and prolonged p38MAP kinase activation and these changes were associated with sustained activation of the transcription factor NF‐κB. NF‐κB activation, in turn, was prevented by the specific p38MAP kinase inhibitor SB208350. Our results suggest that superinduction of IL‐6 by cycloheximide in enterocytes results from both increased mRNA stabilization and upregulated transcriptional activity mediated by prolonged activation of the p38 MAP kinase and NF‐κB. © 2004 Wiley‐Liss, Inc.
Cell cycle regulatory protein p27KIP1 is a substrate and interacts with the protein kinase CK2
Authors: Tapia Julio C. , Bolanos‐Garcia Victor M. , Sayed Muhammed , Allende Catherine C. , Allende Jorge E.
Published: March 2004

The protein kinase CK2 is constituted by two catalytic (α and/or α′) and two regulatory (β) subunits. CK2 phosphorylates more than 300 proteins with important functions in the cell cycle. This study has looked at the relation between CK2 and p27KIP1, which is a regulator of the cell cycle and a known inhibitor of cyclin‐dependent kinases (Cdk). We demonstrated that in vitro recombinant Xenopus laevis CK2 can phosphorylate recombinant human p27KIP1, but this phosphorylation occurs only in the presence of the regulatory β subunit. The principal site of phosphorylation is serine‐83. Analysis using pull down and surface plasmon resonance (SPR) techniques showed that p27KIP1 interacts with the β subunit through two domains present in the amino and carboxyl ends, while CD spectra showed that p27KIP1 phosphorylation by CK2 affects its secondary structure. Altogether, these results suggest that p27KIP1 phosphorylation by CK2 probably involves a docking event mediated by the CK2β subunit. The phosphorylation of p27KIP1 by CK2 may affect its biological activity. © 2004 Wiley‐Liss, Inc.
Tau isoforms which contain the domain encoded by exon 6 and their role in neurite elongation
Authors: Luo Min‐hua , Leski Michael L. , Andreadis Athena
Published: March 2004

The regulation of tau protein expression during different stages of cellular differentiation and development as well as its functional role in morphogenesis, neurofibrillary tangle formation, and neurodegeneration have been topics of extensive study but have not been completely clarified yet. Tau undergoes complex regulated splicing in the mammalian nervous system. Our previous study with tau exon 6 demonstrated that it shows a splicing regulation profile which is distinct from that of the other tau exons as well as a unique expression pattern which is spatially and temporally regulated. In this study, we investigated the expression, localization, and effects of tau isoforms which contain exon 6 in neuroblastoma cells which stably overexpress them. We found that expression of one particular combination of tau exons (the longest adult isoform plus the domain of exon 6) significantly inhibits neurite elongation. © 2004 Wiley‐Liss, Inc.
On graphs with strongly independent color‐classes
Authors: Gyárfás A. , Jensen T. , Stiebitz M.
Published: March 2004

We prove that for every k there is a k‐chromatic graph with a k‐coloring where the neighbors of each color‐class form an independent set. This answers a question raised by N. J. A. Harvey and U. S. R. Murty [4]. In fact we find the smallest graph Gk with the required property for every k. The graph Gk exhibits remarkable similarity to Kneser graphs. The proof that Gk is k‐chromatic relies on Lovász's theorem about the chromatic number of graphs with highly connected neighborhood complexes. © 2004 Wiley Periodicals, Inc. J Graph Theory 46: 1–14, 2004
A Steiner triple system which colors all cubic graphs
Authors: Grannell Mike , Griggs Terry , Knor Martin , Škoviera Martin
Published: March 2004

We prove that there is a Steiner triple system 𝒯 such that every simple cubic graph can have its edges colored by points of 𝒯 in such a way that for each vertex the colors of the three incident edges form a triple in 𝒯. This result complements the result of Holroyd and Škoviera that every bridgeless cubic graph admits a similar coloring by any Steiner triple system of order greater than 3. The Steiner triple system employed in our proof has order 381 and is probably not the smallest possible. © 2004 Wiley Periodicals, Inc. J Graph Theory 46: 15–24, 2004
Planar graph colorings without short monochromatic cycles
Authors: Kaiser Tomáš , Škrekovski Riste
Published: March 2004

It is well known that every planar graph G is 2‐colorable in such a way that no 3‐cycle of G is monochromatic. In this paper, we prove that G has a 2‐coloring such that no cycle of length 3 or 4 is monochromatic. The complete graph K5 does not admit such a coloring. On the other hand, we extend the result to K5‐minor‐free graphs. There are planar graphs with the property that each of their 2‐colorings has a monochromatic cycle of length 3, 4, or 5. In this sense, our result is best possible. © 2004 Wiley Periodicals, Inc. J Graph Theory 46: 25–38, 2004
Monotone drawings of planar graphs
Authors: Pach János , Tóth Géza
Published: March 2004

Let G be a graph drawn in the plane so that its edges are represented by x‐monotone curves, any pair of which cross an even number of times. We show that G can be redrawn in such a way that the x‐coordinates of the vertices remain unchanged and the edges become non‐crossing straight‐line segments. © 2004 Wiley Periodicals, Inc. J Graph Theory 46: 39–47, 2004
On the number of quasi‐kernels in digraphs
Authors: Gutin Gregory , Koh Khee Meng , Tay Eng Guan , Yeo Anders
Published: March 2004

A vertex set X of a digraph D = (V, A) is a kernel if X is independent (i.e., all pairs of distinct vertices of X are non‐adjacent) and for every v ∈ V‐X there exists x ∈ X such that vx ∈ A. A vertex set X of a digraph D = (V, A), is a quasi‐kernel if X is independent and for every v ∈ V‐X there exist w ∈ V‐X, x ∈ X such that either vx ∈ A or vw, wx ∈ A. In 1974, Chvátal and Lovász proved that every digraph has a quasi‐kernel. In 1996, Jacob and Meyniel proved that if a digraph D has no kernel, then D contains at least three quasi‐kernels. We characterize digraphs with exactly one and two quasi‐kernels, and, thus, provide necessary and sufficient conditions for a digraph to have at least three quasi‐kernels. In particular, we prove that every strong digraph of order at least three, which is not a 4‐cycle, has at least three quasi‐kernels. © 2004 Wiley Periodicals, Inc.
Density of the circular chromatic numbers of series‐parallel graphs
Authors: Pan Zhishi , Zhu Xuding
Published: March 2004

Suppose G is a series‐parallel graph. It was proved in 3 that either χc(G) = 3 or χc(G) ≤ 8/3. So none of the rationals in the interval (8/3, 3) is the circular chromatic number of a series‐parallel graph. This paper proves that for every rational r ∈ [2, 8/3] ∪ {3} there exists a series‐parallel graph G with χc(G) = r. © 2004 Wiley Periodicals, Inc. J Graph Theory 46:57–68, 2004
The relaxed game chromatic number of outerplanar graphs
Authors: Dunn Charles , Kierstead Hal A.
Published: March 2004

The (r,d)‐relaxed coloring game is played by two players, Alice and Bob, on a graph G with a set of r colors. The players take turns coloring uncolored vertices with legal colors. A color α is legal for an uncolored vertex u if u is adjacent to at most d vertices that have already been colored with α, and every neighbor of u that has already been colored with α is adjacent to at most d – 1 vertices that have already been colored with α. Alice wins the game if eventually all the vertices are legally colored; otherwise, Bob wins the game when there comes a time when there is no legal move left. We show that if G is outerplanar then Alice can win the (2,8)‐relaxed coloring game on G. It is known that there exists an outerplanar graph G such that Bob can win the (2,4)‐relaxed coloring game on G. © 2004 Wiley Periodicals, Inc. J Graph Theory 46:69–78, 2004
The temporal and spatial patterns of thermal conditions in the area of the southwestern coast of the Gulf of Gdańsk (Poland) from 1951 to 1998
Authors: Miȩtus Mirosław , Filipiak Janusz
Published: March 2004

The variability of the thermal conditions in the environs of the southwestern coast of the Gulf of Gdańsk in the years 1951–98 has been analysed. The analyses were based on air temperature series from four stations characteristic of different locations. During the years analysed, the increase in minimum temperature was stronger than that of the maximum temperature; thus, a negative trend in the daily temperature range is observed. In the city, the statistically significant decrease in the daily temperature range is estimated as 0.015°C per annum. Mean values of both extreme temperatures indicate the thermally privileged areas, where stronger influences of local anthropogenic factors occur. The variability of heat and cold waves shows a positive trend in the number of heat waves and a negative trend for cold waves. The duration of heat waves is increasing. The duration of cold waves is characterized by a negative trend. Canonical correlation analysis was used to study the relationship between regional atmospheric circulation and local thermal conditions. The first two pairs of canonical maps explain 84% of the variance of the local daily temperature range and confirm the role of local factors in a differentiation of the thermal conditions. Copyright © 2004 Royal Meteorological Society
The upwelling regime off the West Portuguese Coast, 1941–2000
Authors: Lemos Ricardo T. , Pires Henrique O.
Published: March 2004

The evolution of the upwelling regime off west Portugal between 1941 and 2000 was investigated. Monthly averages of the longshore (meridional) wind component at four coastal stations of the Institute for Meteorology were computed and subject to linear regression analysis. Several comparisons were made among stations until a final regression model was reached. The resulting residuals were checked for the presence of red noise, and pairwise correlation coefficients were estimated for residuals of different stations. To complement this study, monthly sea‐surface temperature averages were computed for six regions off west Portugal and subject to a similar procedure. In both analyses, it was concluded that the Portuguese upwelling regime has weakened since the 1940s. The waning of the northerly, upwelling‐favourable winds was significant throughout the traditional upwelling season (April–September). Sea‐surface temperature showed a steady year‐round increase from 1941 onwards, in both offshore (+0.002°C/year) and coastal (+0.010°C/year) regions. Copyright © 2004 Royal Meteorological Society
Winter precipitation on the US Pacific coast and El Niño–southern oscillation events
Authors: Castello Amy F. , Shelton M. L.
Published: March 2004

Winter precipitation increases as much as seven times from south to north along the US Pacific coast. For 1948–95, nine coastal grid points are used to identify spatial and temporal winter precipitation variations and to assess atmospheric circulation influences on precipitation variability. A strong negative correlation to the northwest of each precipitation grid point is revealed by one‐point correlation maps of precipitation at a given coastal grid point and 700 hPa geopotential heights at 288 grid points. The strength of the correlation decreases from north to south, and the northernmost precipitation grid point displays a correlation pattern nearly opposite that of the southernmost precipitation grid point. El Niño events are related to greater than average precipitation south of 43°N along the US Pacific coast. The largest negative height anomalies during an El Niño year are centred over the North Pacific Ocean west of Oregon. La Niña events display an asymmetric pattern relative to El Niño, with below‐normal rainfall along the California coast south of 41°N and above‐normal precipitation along coastal Oregon and Washington. La Niña years have negative 700 hPa geopotential height anomalies over the Gulf of Alaska. These characteristics delimit the region between 41 and 43°N as the transition zone defining El Niño–southern oscillation influences along the US Pacific coast. Copyright © 2004 Royal Meteorological Society
Rainfall and the length of the growing season in Nigeria
Authors: Odekunle T. O.
Published: March 2004

This study examines the length of the growing season in Nigeria using the daily rainfall data of Ikeja, Ondo, Ilorin, Kaduna and Kano. The data were collected from the archives of the Nigerian Meteorological Services, Oshodi, Lagos. The length of the growing season was determined using the cumulative percentage mean rainfall and daily rainfall probability methods.

Although rainfall in Ikeja, Ondo, Ilorin, Kaduna, and Kano appears to commence around the end of the second dekad of March, middle of the third dekad of March, mid April, end of the first dekad of May, and early June respectively, its distribution characteristics at the respective stations remain inadequate for crop germination, establishment, and development till the end of the second dekad of May, early third dekad of May, mid third dekad of May, end of May, and end of the first dekad of July respectively. Also, rainfall at the various stations appears to retreat starting from the early third dekad of October, early third dekad of October, end of the first dekad of October, end of September, and early second dekad of September respectively, but its distribution characteristics only remain adequate for crop development at the respective stations till around the end of the second dekad of October, end of the second dekad of October, middle of the first dekad of October, early October, and middle of the first dekad of September respectively. Thus, the active lengths of the growing season are approximately 5 months, 5 months, 4 months, 4 months, and 2 months respectively. Plants that are short‐dry‐spell tolerant may thrive early in the rainy season, i.e. from the end of the second dekad of March to the end of the second dekad of May (in Ikeja), middle of the third dekad of March to the early third dekad of May (in Ondo), mid April to the middle of the third dekad of May (in Ilorin), end of the first dekad of May to end of May (in Kaduna), and early June to the end of the first dekad in July (in Kano), but other less tolerant plants should be planted starting from the end of the second dekad of May, early third dekad of May, mid third dekad of May, end of May, and end of the first dekad of July respectively. The daily rainfall probability method is recommended as more efficient in the assessment of the nature and length of the growing season. Copyright © 2004 Royal Meteorological Society
Decadal and longer term changes in El Niño–southern oscillation characteristics
Authors: Mokhov I. I. , Khvorostyanov D. V. , Eliseev A. V.
Published: March 2004

The time variations of El Niño–southern oscillation (ENSO) amplitude A, period P, and their relationship were studied using observed Niño‐3 sea‐surface temperature (SST) (GISST 2.2, GISST 2.3) and the southern oscillation index (SOI). Different tendencies in the A–P relationship were found in the decadal and longer term variations.

On the decadal time scale, the SOI shows a statistically significant positive correlation between ENSO period and amplitude. This result was confirmed by analysing the observed Niño‐3 SST data as well.

A negative relationship between longer variations in A and P was then found for certain subintervals of the observed SST time series available, e.g. for 1921–80 and 1903–94, and the dataset representing the latter period is the GISST 2.2 dataset. These longer variations can be interdecadal, and/or secular trends in the A (positive) and P (negative). In contrast, the SOI showed no trends in P and A; consequently, there were no significant P–A correlations found in the SOI data on these time scales.

The ECHAM4/OPYC3 model was then tested in order to determine whether it could reproduce the tendencies found in the observed data. The ECHAM4/OPYC3 SST showed a negative A–P relationship in the simulation with increasing greenhouse‐gas concentration. This tendency did not manifest itself in the control run. The model SOI agrees with observation results, showing a positive correlation between ENSO period and amplitude on decadal time scales. Copyright © 2004 Royal Meteorological Society