bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of Triazinium‐Imidothioate Zwitterions and Their Role as Key Intermediates for Novel SN(ANRORC) Reaction Pathways
Authors: Wermann Kurt , Walther Martin , Günther Wolfgang , Görls Helmar , Anders Ernst
Published: March 2003

The formation of highly reactive zwitterionic triaziniumimidothioate intermediates 10 from bis(1,3,4‐thiadiazolo)‐1,3,5‐triazinium halides is reported. These intermediates are the first structures to be isolated from the reaction pathway between bis(1,3,4‐thiadiazolo)‐1,3,5‐triazinium halides 1 and benzylamines 2. The reaction between 1 and 2 has a very complicated hypersurface and can yield unusual bis(1,2,4‐triazolo)‐1,3,5‐triazinium halides 6, [1,2,4]triazolo[1,3,4]thiadiazolo[1,3,5]triazinium halides 7 or highly substituted guanidines 5. The formation of 6 and 7 can be understood in terms of an SN(ANRORC) process. As could be demonstrated for the tricyclic cations 6, these compounds, together with 7, could be interesting in further synthetic applications. The salts 6 react with KOH/tBuOK to give novel aminals 16 in good to excellent yields. Most of the important steps in the course of the transformation of 1 into 5, 6 and 7 are supported by B3LYP/6−311++G(d,p) calculations and the X‐ray structures of 6a, 7b, 14b and 16c. From an electronic point of view, the more important reaction steps are governed by the conformation‐controlling effect of negative hyperconjugation, accompanied by intramolecular proton‐transfer reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Asymmetric Radical Synthesis of 2,5‐Diaryl‐2,3‐dihydrofurans − Application to the Preparation of (+)‐Phyltetralin
Authors: Garzino Frédéric , Méou Alain , Brun Pierre
Published: March 2003

The diastereoselective MnIII‐promoted radical addition of β‐oxo ester1ontoN‐cinnamoyloxazolidinone2affords, after removal of the chiral auxiliary, the enantiopure 2,5‐diaryl‐2,3‐dihydrofuran (−)‐4. Its SnCl4‐induced rearrangement leads to a 4‐aryltetralone immediate precursor of the aryltetralin lignan (+)‐phyltetralin (9). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Domino [3+2] Cycloaddition/Annulation Reactions of β‐(2‐Aminophenyl)‐α,β‐ynones with Nitrile Oxides: Synthesis of Isoxazolo[4,5‐c]quinolines
Authors: Abbiati Giorgio , Arcadi Antonio , Marinelli Fabio , Rossi Elisabetta
Published: March 2003

β‐(2‐Aminophenyl)‐α,β‐ynones react with nitrile oxides by domino [3+2] cycloaddition/annulation reactions giving rise to isoxazolo[4,5‐c]quinolines in satisfactory yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Ectyoceramide, the First Natural Hexofuranosylceramide from the Marine Sponge Ectyoplasia ferox
Authors: Costantino Valeria , Fattorusso Ernesto , Imperatore Concetta , Mangoni Alfonso
Published: March 2003

Ectyoceramide (1a), a unique monoglycosylceramide with a galactose in the furanose form, was isolated from Ectyoplasia ferox, and its structure was determined by NMR spectroscopy, multiple tandem mass spectrometry, and chemical degradation. Ectyoceramide is the first example of a monohexofuranosylceramide and, more generally, the first natural glycosphingolipid with its first sugar in the furanose form. (Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The Direct Metalation and Subsequent Functionalization of Trifluoromethyl‐Substituted Pyridines and Quinolines
Authors: Schlosser Manfred , Marull Marc
Published: March 2003

Depending on the choice of the reagent, 2‐(trifluoromethyl)pyridine can be selectively metalated and subsequently carboxylated or otherwise functionalized either at the 3‐ or at the 6‐position. “Optional site selectivity” can also be achieved with 4‐(trifluoromethyl)pyridine, which may be deprotonated either at the 2‐ or at the 3‐position. In contrast, 3‐(trifluoromethyl)pyridine undergoes nucleophilic addition and ensuing decomposition whatever the base. Depending on the reaction conditions, 2‐(trifluoromethyl)quinoline displays reactivity toward lithium reagents at its 3‐, 4‐, or 8‐positions, 3‐(trifluoromethyl)quinolines at the 2‐ or 4‐positions, and 4‐(trifluoromethyl)quinoline at the 2‐ or 3‐positions. It was therefore possible to prepare four trifluoromethyl‐substituted pyridinecarboxylic acids (1, 4, 9, and 10) and six trifluoromethyl‐substituted quinolinecarboxylic acids (11, 13, 14, 15, 17, and 18) regioisomerically uncontaminated and in a most straightforward way. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Thermal kinetics of color degradation of mulberry fruit extract
Authors: Suh Hyung Joo , Noh Dong Ouk , Kang Chang Soo , Kim Jin Man , Lee Seog Won
Published: March 2003

The effects of temperature and pH on color degradation kinetics of the mulberry fruit extract were investigated. The absorbance at 510 nm was decreased with increase of heating time, but that at 420 nm was increased with the increase of heating time at 100°C. The change of the browning index (A510/A420) was increased with increase of pH and was lower at pH 2.0 than that at pH 5.0. The browning index variation was adequately described by both the first‐order and the zero‐order kinetic. However, the zero‐order kinetic model was proposed because of the better fit. According to the Arrhenius model, the activation energies for the browning index in the range of 80–100°C for the four different pH values were 30.68 kJ/mol for pH 2.0, 35.87 kJ/mol for pH 3.0, 42.67 kJ/mol for pH 4.0, and 43.49 kJ/mol for pH 5.0.
Modelling trends in central England temperatures
Authors: Harvey David I. , Mills Terence C.
Published: March 2003

Trends are extracted from the central England temperature (CET) data available from 1723, using both annual and seasonal averages. Attention is focused on fitting non‐parametric trends and it is found that, while there is no compelling evidence of a trend increase in the CET, there have been three periods of cooling, stability, and warming, roughly associated with the beginning and the end of the Industrial Revolution. There does appear to have been an upward shift in trend spring temperatures, but forecasting of current trends is hazardous because of the statistical uncertainty surrounding them. Copyright © 2003 John Wiley & Sons, Ltd.
A novel cryptic translocation t(12;17)(p13;p12–p13) in a secondary acute myeloid leukemia results in a fusion of the ETV6 gene and the antisense strand of the PER1 gene
Authors: Penas Eva Maria Murga , Cools Jan , Algenstaedt Petra , Hinz Kristina , Seeger Doris , Schafhausen Philippe , Schilling Georgia , Marynen Peter , Hossfeld Dieter K. , Dierlamm Judith
Published: March 2003

The ETV6 gene is a member of the ETS family of transcription factors and the main target of chromosomal rearrangements affecting chromosome band 12p13. To date, more than 15 fusion partners of ETV6 have been characterized at the molecular level. Most of these fusions encode chimeric proteins with oncogenic properties. However, some of the translocations do not produce a functional fusion protein, but may induce ectopic expression of oncogenes located close to the breakpoint. We herein report the characterization and cloning of a novel cryptic translocation, t(12;17)(p13;p12–p13), occurring in a patient with an acute myeloid leukemia evolving from a chronic myelomonocytic leukemia. Cytogenetic analysis suggested the presence of a deletion of the short arm of chromosome 12, del(12)(p13), in three of the five metaphase cells analyzed. However, fluorescence in situ hybridization (FISH) with the ETV6‐specific cosmid clones 179A6, 50F4, 163E7, and 148B6 as well as probes hybridizing to the TP53 gene on 17p13 and the subtelomeric region of 17p revealed the presence of a translocation between 12p and 17p. By FISH, the breakpoints could be localized in intron 1 of ETV6 and centromeric to TP53. By 3′ rapid amplification of cDNA ends–polymerase chain reaction (3′ RACE‐PCR), a fusion transcript between exon 1 of ETV6 and the antisense strand of PER1 (period homolog 1, Drosophila), a circadian clock gene, could be identified. This ETV6‐PER1 (antisense PER1 strand) fusion transcript does not produce a fusion protein, and no other fusion transcripts could be detected. We hypothesize that in the absence of a fusion protein, the inactivation of PER1 or deregulation of a gene in the neighborhood of PER1 may contribute to the pathogenesis of leukemias with a t(12;17)(p13;p12–p13). © 2003 Wiley‐Liss, Inc.
Fusion of ALK to the Ran‐binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor
Authors: Ma Zhigui , Hill D. Ashley , Collins Margaret H. , Morris Stephan W. , Sumegi Janos , Zhou Ming , Zuppan Craig , Bridge Julia A.
Published: March 2003

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal proliferation of transformed myofibroblasts, with a prominent inflammatory cell component, that can mimic other spindle cell processes such as nodular fasciitis, desmoid tumor, and gastrointestinal stromal tumor. Genetic analyses have recently demonstrated rearrangements of anaplastic lymphoma kinase (ALK), located at 2p23, in a subset of IMTs. Molecular characterizations have identified ALK fusions involving tropomyosin‐3 and ‐4 (TPM‐3 and ‐4), the clathrin heavy chain (CLTC), and the cysteinyl‐tRNA synthetase (CARS) genes as fusion partners. Here we describe two IMTs with a novel ALK fusion that involves the Ran‐binding protein 2 (RANBP2) gene at 2q13, which normally encodes a large (358‐kDa) nucleopore protein localized at the cytoplasmic side of the nuclear pore complex. The N‐terminal 867 residues of RANBP2 are fused to the cytoplasmic segment of ALK in the 1,430–amino acid RANBP2‐ALK chimeric protein. Myofibroblasts that express RANBP2‐ALK exhibit nuclear membrane‐associated ALK staining that is unique compared to the subcellular localization observed with other ALK fusions in IMT, presumably attributable to heteroassociation of the fusion with normal RANBP2 at the nuclear pore. These findings expand the spectrum of ALK abnormalities observed in IMT and further confirm the clonal, neoplastic nature of these lesions. © 2003 Wiley‐Liss, Inc.
Mutations of CEBPA in acute myeloid leukemia FAB types M1 and M2
Authors: Snaddon Jennifer , Smith Matthew L. , Neat Michael , Cambal‐Parrales Maxine , Dixon‐McIver Amanda , Arch Rachael , Amess John A. , Rohatiner Ama Z. , Lister T. Andrew , Fitzgibbon Jude
Published: March 2003

CEBPA encodes the transcription factor C/EBPα and is specifically up‐regulated during granulocytic differentiation. The gene is mutated in approximately 20% of patients with acute myeloid leukemia (AML) FAB type M2 and occurs in the absence of the t(8;21). In much the same way as specific translocations are associated with a particular AML FAB type, the identification of non‐random associations of gene mutation with karyotype or FAB type may be helpful in elucidating the molecular basis of certain forms of leukemia. To confirm these initial findings, 99 patients with AML FAB type M1 or M2 were screened for CEBPA mutations by use of a PCR–single‐strand conformational polymorphism and sequencing approach. Nine CEBPA mutations were identified in eight patients. The mutations were clustered toward the COOH terminal of the protein and occurred exclusively in the intermediate cytogenetic risk group (8/64, 12.5%). Two patients with biallelic mutation, one homozygous for 1137Ins (57 bp) and another with two CEBPA mutations, 1096Ins (27 bp) and 363Ins (GGCC), were observed. There was no evidence for deletion of this region in the other six mutated samples analyzed by fluorescence in situ hybridization with a BAC clone spanning the CEBPA locus. CEBPA mutation status was not demonstrated to be of prognostic importance in this patient group, although this may reflect the selection and size of the AML population studied. In conclusion, mutation of CEBPA is a recurrent finding in AML and appears specific to the intermediate cytogenetic risk group patients. © 2003 Wiley‐Liss, Inc.
High expression of B‐cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma
Authors: van den Berg Anke , Kroesen Bart‐Jan , Kooistra Klaas , de Jong Debora , Briggs Jane , Blokzijl Tjasso , Jacobs Susan , Kluiver Joost , Diepstra Arjan , Maggio Ewerton , Poppema Sibrand
Published: March 2003

In a search for genes specifically expressed in Reed–Sternberg (RS) cells of Hodgkin lymphoma (HL), we applied the serial analysis of gene expression (SAGE) technique on the HL‐derived cell line DEV. Genes highly expressed in DEV were subjected to an RT‐PCR analysis to confirm the SAGE results. For one of the genes, a high expression was observed in DEV and other HL‐derived cell lines but not in non‐Hodgkin lymphoma (NHL)–derived cell lines and normal controls, suggesting an HL‐specific expression. This gene corresponds to the human BIC gene, a member of the noncoding mRNA‐like molecules. RNA in situ hybridization (ISH) indicated an exclusive nucleolar localization of BIC transcripts in all RS cells in 91% of HL cases, including nodular lymphocyte predominance (NLP) HL and classical HL. Analyses of normal human tissues revealed BIC transcripts in only a small number of CD20‐positive B‐cells in lymph node and tonsil tissue, albeit at a much lower level compared to that of RS cells. BIC RT‐PCR in the Burkitt lymphoma–derived cell line Ramos demonstrated a significant up‐regulation upon cross‐linking of the B‐cell receptor (BcR). IκBα‐mediated blocking of NF‐κB translocation in Ramos did not effect the up‐regulation of BIC expression upon BcR triggering, suggesting that activation of NF‐κB is not involved in regulation of BIC expression. In summary, our data show that expression of BIC is specific for RS cells of HL. In normal tissue, BIC is expressed weakly in a minority of germinal center B cells. Expression of BIC can be modified/influenced by BcR triggering, indicating that BIC might play a role in the selection of B cells. © 2003 Wiley‐Liss, Inc.
CDKN2A, CDKN2B, and MTAP gene dosage permits precise characterization of mono‐ and bi‐allelic 9p21 deletions in childhood acute lymphoblastic leukemia
Authors: Bertin Raphaëlle , Acquaviva Cécile , Mirebeau Delphine , Guidal‐Giroux Christine , Vilmer Etienne , Cavé Hélène
Published: March 2003

Deletion of the 9p21 chromosomal region is frequently found in childhood acute lymphoblastic leukemia (ALL). The target of these deletions is CDKN2A, a gene encoding both p16INK4a and p14ARF. However, contiguous genes such as CDKN2B, encoding p15INK4b, or MTAP, encoding methylthioadenosine phosphorylase, can be included in the deletions. Gene dosage by use of real‐time PCR has recently been proposed as a promising technical option for the diagnosis of deletions. However, its reliability and its capacity to detect mono‐allelic deletions in tumor samples are controversial. To evaluate the frequency and extent of deletions in 284 children with ALL, we devised a real‐time PCR assay for CDKN2A, CDKN2B exons 1β and 3, and MTAP gene dosage and validated it by comparison with loss‐of‐heterozygosity analysis. We show that, if several controls and adjustments are performed, real‐time PCR can provide a reliable test for mono‐ and bi‐allelic deletions in ALL. We propose a strategy that overcomes the major caveats of such a dosage in tumor samples: aneuploidy and contamination by normal cells. By use of this assay, we found bi‐allelic deletions in 58 and 17% of T‐ and B‐lineage ALL, respectively. Mono‐allelic deletion was observed in about 15% of cases, stressing the importance of their detection in ALL. CDKN2B and/or MTAP co‐deletions were highly variable in both T‐ and B‐lineage ALL, making ALL with 9p21 a rather heterogeneous group. Because proteins encoded by these genes might influence the response to treatment, the prognosis of 9p21‐deleted ALL could vary according to the extent of the deletion. © 2003 Wiley‐Liss, Inc.
Role of short telomeres in inducing preferential chromosomal aberrations in human ovarian surface epithelial cells: A combined telomere quantitative fluorescence in situ hybridization and whole‐chromosome painting study
Authors: Deng Wen , Tsao Sai Wah , Guan Xin‐Yuan , Lucas Joe N. , Cheung Annie L. M.
Published: March 2003

It is well established that specific cancers and immortalized cells have nonrandom chromosome aberrations. However, little is understood about the underlying mechanism that initiates these aberrations in human cells. To examine whether human chromosomes with the shortest telomeres initiate the preferential chromosomal aberrations before cellular immortalization, we simultaneously applied telomere quantitative fluorescence in situ hybridization and specific whole‐chromosome painting on chromosomes 1, 5, 8, 17, 19, and 20 in human ovarian surface epithelial (HOSE 6‐3) cells expressing human papilloma viral oncogenes (HPV16 E6E7). The HPV16 E6E7–expressing cells, with extended in vitro life span and telomerase‐negative status, were previously identified as having nonrandom chromosomal imbalances and high frequencies of dicentrics. Our analyses showed that among six pairs of targeted chromosomes, chromosomes 8 and 20 showed critically short telomeres with an undetectable telomere signal in more than 50% of cells analyzed. These chromosomes with the critically short telomeres were preferentially involved in various types of chromosomal aberrations including dicentrics, translocations, breaks, insertions, and losses or gains of chromosomal elements. Our findings suggest that nonrandom chromosome aberrations in HOSE cells occurring before cellular immortalization could be caused by the telomere length heterogeneity. © 2003 Wiley‐Liss, Inc.
Activation of HOX11L2 by juxtaposition with 3′‐BCL11B in an acute lymphoblastic leukemia cell line (HPB‐ALL) with t(5;14)(q35;q32.2)
Authors: MacLeod Roderick A.F. , Nagel Stefan , Kaufmann Maren , Janssen Johannes W.G. , Drexler Hans G.
Published: March 2003

Cytogenetic analysis of a pediatric T‐cell acute lymphoblastic leukemia (ALL) cell line (HPB‐ALL) revealed the cryptic t(5;14)(q35;q32.2), recently found in 15–20% pediatric T‐ALL patients, with 5q35 and 14q32.2 breakpoints at 5′‐HOX11L2 and 3′‐BCL11B, respectively. Expression of both BCL11B, which is hematologically restricted to T cells, and HOX11L2 was detected, whereas adjacent genes at 5q35 (RANBP17) and 14q32 (VRK1, HSU88895) were not dysregulated. Apparently, t(5;14)(q35;q32.2) serves to activate HOX11L2 by juxtaposition with elements downstream of BCL11B, implying a novel dysregulatory mechanism comparable to TCRA/D or IGH juxtaposition. As well as providing molecular cytogenetic documentation of t(5;14) ALL, this report validates HPB‐ALL cells for investigating this important new disease entity in vitro. © 2003 Wiley‐Liss, Inc.
Identification of microsatellite instability and mismatch repair gene mutations in breast cancer cell lines
Authors: Seitz Susanne , Waβmuth Peter , Plaschke Jens , Schackert Hans K. , Karsten Uwe , Santibanez‐Koref Mauro‐F. , Schlag Peter M. , Scherneck Siegfried
Published: March 2003

At present, there is conflicting evidence whether microsatellite instability (MSI) plays a role in the pathogenesis of breast cancer. Here we describe for the first time an MSI+ phenotype in two breast cancer cell lines, CAL51 and MT‐3, resembling that observed in colorectal cancers. These cell lines are characterized by near‐diploid and hyperdiploid karyotypes, respectively. We detected MSI in these cell lines within two non‐coding (BAT‐25 and BAT‐26) and within coding repeat sequences of genes known to be mutated in MSI+ cancer (TGFBR2, IGF2R, BAX). We provide evidence that the inactivation of MMR genes is responsible for MSI in these cell lines. © 2003 Wiley‐Liss, Inc.
Prenatal origin of TEL‐AML1–positive acute lymphoblastic leukemia in children born in California
Authors: McHale Cliona M. , Wiemels Joseph L. , Zhang Luoping , Ma Xiaomei , Buffler Patricia A. , Guo Weihong , Loh Mignon L. , Smith Martyn T.
Published: March 2003

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. The peak incidence of ALL between ages 2 and 5 is accounted for by one subtype, referred to as common acute lymphoblastic leukemia (cALL). About 25% of cALL patients have the TEL‐AML1 gene fusion derived from the t(12;21) chromosomal translocation. Recent evidence from retrospective analysis of neonatal blood spots (Guthrie cards) in Europe has demonstrated that this chromosome translocation may arise prenatally. The aim of our study was to determine whether TEL‐AML1 fusions arise prenatally in a U.S. population of cALL patients. TEL‐AML1–positive cALL cases (n = 14) were identified by fluorescence in situ hybridization, and the genomic breakpoints were identified by a streamlined long‐distance PCR approach and sequenced. Clonotypic primers were designed for each patient breakpoint, and a nested PCR assay was used to determine the presence of the TEL‐AML1 fusion sequence in neonatal Guthrie cards. Seven of 14 cases demonstrated clonotypic sequences on the archival Guthrie cards. The oldest patient that was positive was 6.7 years old at the time of diagnosis of leukemia. These results confirm previously published findings of a prenatal origin of TEL‐AML1 in Europe by demonstrating its occurrence in a California‐born population. Secondary changes were also similar to those described previously, with deletion of the second TEL allele being the most common. Other secondary changes included duplication of the fusion gene, trisomy 21, and monosomy X. © 2003 Wiley‐Liss, Inc.
Genetics of dermatofibrosarcoma protuberans family of tumors: From ring chromosomes to tyrosine kinase inhibitor treatment
Authors: Sirvent Nicolas , Maire Georges , Pedeutour Florence
Published: March 2003

Dermatofibrosarcoma protuberans (DP) is a rare, slow‐growing, infiltrating dermal neoplasm of intermediate malignancy, made up of spindle‐shaped tumor cells often positive for CD34. The preferred treatment is wide surgical excision with pathologically negative margins. At the cytogenetic level, DP cells are characterized by either supernumerary ring chromosomes, which have been shown by using fluorescence in situ hybridization techniques to be derived from chromosome 22 and to contain low‐level amplified sequences from 17q22‐qter and 22q10–q13.1, or t(17;22), that are most often unbalanced. Both the rings and linear der(22) contain a specific fusion of COL1A1 with PDGFB. Similar to other tumors, the COL1A1‐PDGFB fusion is occasionally cryptic, associated with complex chromosomal rearrangements. Although rings have been mainly observed in adults, translocations have been reported in all pediatric cases. DP is therefore a unique example of a tumor in which (i) the same molecular event occurs either on rings or linear translocation derivatives, (ii) the chromosomal abnormalities display an age‐related pattern, and (iii) the presence of the specific fusion gene is associated with the gain of chromosomal segments, probably taking advantage of gene dosage effects. In all DP cases that underwent molecular investigations, the breakpoint localization in PDGFB was found to be remarkably constant, placing exon 2 under the control of the COL1A1 promoter. In contrast, the COL1A1 breakpoint was found to be variably located within the exons of the α‐helical coding region (exons 6–49). No preferential COL1A1 breakpoint and no correlation between the breakpoint location and the age of the patient or any clinical or histological particularity have been described. The COL1A1‐PDGFB fusion is detectable by multiplex RT‐PCR with a combination of forward primers designed from a variety of COL1A1 exons and one reverse primer from PDGFB exon 2. Recent studies have determined the molecular identity of “classical” DP, giant cell fibroblastoma, Bednar tumor, adult superficial fibrosarcoma, and the granular cell variant of DP. In approximately 8% of DP cases, the COL1A1‐PDGFB fusion is not found, suggesting that genes other than COL1A1 or PDGFB might be involved in a subset of cases. It has been proposed that PDGFB acts as a mitogen in DP cells by autocrine stimulation of the PDGF receptor. It is encouraging that inhibitory effects of the PDGF receptor tyrosine kinase antagonist imatinib mesylate have been demonstrated in vivo; such targeted therapies might be warranted in the near future for treatment of the few DP cases not manageable by surgery. © 2003 Wiley‐Liss, Inc.
Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21)
Authors: Charest Alain , Lane Keara , McMahon Kevin , Park Julie , Preisinger Elizabeth , Conroy Helen , Housman David
Published: March 2003

The transmembrane proto‐oncogene receptor tyrosine kinase (RTK) ROS is an orphan receptor that is aberrantly expressed in neoplasms of the central nervous system. Here, we report the fusion of its carboxy‐terminal kinase domain to the amino‐terminal portion of a protein called FIG (Fused in Glioblastoma) in a human glioblastoma multiforme (GBM). By characterizing both FIG and ROS genes in normal and in U118MG GBM cells, we determined that an intra‐chromosomal homozygous deletion of 240 kilobases on 6q21 is responsible for the formation of the FIG‐ROS locus. The FIG‐ROS transcript is encoded by 7 FIG exons and 9 ROS‐derived exons. We also demonstrate that the FIG‐ROS locus encodes for an in‐frame fusion protein with a constitutively active kinase activity, suggesting that FIG‐ROS may act as an oncogene. This is the first example of a fusion RTK protein that results from an intra‐chromosomal deletion, and it represents the first fusion RTK protein isolated from a human astrocytoma. © 2003 Wiley‐Liss, Inc.
Use of aiding and feedback in improving visual search performance for an inspection task
Authors: Chabukswar Samir , Gramopadhye Anand K. , Melloy Brian J. , Grimes Laurence W.
Published: March 2003

The objective of this research is to evaluate the effect of providing online feedback, process, and process plus performance on visual search performance for a printed circuit board inspection task. A training aid was developed that provided process and process plus performance feedback and enabled a comparison between the two feedback strategies. Two search strategies—search by area and search by component—were adopted to complete the task, and their sensitivity to the type of feedback and search performance was evaluated. Providing process plus performance feedback helped in improving speed and accuracy, whereas area search strategy proved beneficial in improving search speed for both feedback strategies. Graphical feedback on the component location helped in locating more component defects than area defects. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 115–136, 2003.
Evaluation of best system performance: Human, automated, and hybrid inspection systems
Authors: Jiang Xiaochun , Gramopadhye Anand K. , Melloy Brian J. , Grimes Laurence W.
Published: March 2003

Recently, 100% inspection with automated systems has seen more frequent application than traditional sampling inspection with human inspectors. Nevertheless, humans still outperform machines in most attribute inspection tasks. Because neither humans nor automation can achieve superior inspection system performance, hybrid inspection systems where humans work cooperatively with machines merit study. In response to this situation, this research was conducted to evaluate three of the following different inspection systems: (1) a human inspection system, (2) a computer search/human decision‐making inspection system, and (3) a human/computer share search/decision‐making inspection system. Results from this study showed that the human/computer share search/decision‐making system achieve the best system performance, suggesting that both should be used in the inspection tasks rather than either alone. Furthermore, this study looked at the interaction between human inspectors and computers, specifically the effect of system response bias on inspection quality performance. These results revealed that the risky system was the best in terms of accuracy measures. Although this study demonstrated how recent advances in computer technology have modified previously prescribed notions about function allocation alternatives in a hybrid inspection environment, the adaptability of humans was again demonstrated, indicating that they will continue to play a vital role in future hybrid systems. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 137–152, 2003.
Awareness support for asynchronous engineering collaboration
Authors: Xie Yunlong , Salvendy Gavriel
Published: March 2003

This study addresses collaboration awareness for asynchronous distributed engineering collaboration with computer‐aided design (CAD) browsers. An analysis of the characteristics of asynchronous collaboration identified the information that needs to be presented. Two features for a CAD browser system, team member information enhancement and task information enhancement, were designed to improve collaborator and task awareness. An experiment was conducted to test the effectiveness of the new proposed features. The results of the experiment indicated the following. First, the enhancement of team member information and task information improved collaboration efficiency by 8.1 and 20.2%, respectively. Second, for asynchronous collaboration, the availability and workload of team members need to be presented rather than capturing and presenting dynamic information about team members. Third, the information about the status of each task, such as the progress, time passed, and dependability, needs to be enhanced for efficient collaboration. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 97–113, 2003.
Limiting design criteria framework for manual electronics assembly
Authors: Quintana Rolando , Hernandez‐Masser Vanesa
Published: March 2003

The electronics assembly industry is mainly characterized by high‐mix, low‐batch production of components that are becoming more miniaturized. The concomitant formidable physical and mental demands placed on operators goes well beyond the traditional scope of manual assembly. This research provides a framework for the design of manual electronics assembly by identifying the limiting design criteria from a human factors perspective that affect productivity. Collecting and analyzing in vivo biomechanical and throughput data, which provided the basis for quantifying ergonomic risks and productivity ratios, validated the design criteria. An increase of 53 PC boards per shift was obtained, thereby minimizing biomechanical risk factors associated with manual electronics assembly. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 165–179, 2003.
Measurement of physical work capacity during arm and shoulder lifting at various shoulder flexion and ad/abduction angles
Authors: Kim Jung‐Yong , Chung Min‐Keun , Park Ji‐Soo
Published: March 2003

The purpose of this study was to provide information on physical work capacity during arm and shoulder lifting at various shoulder flexion and ad/abduction angles. We measured the maximum voluntary contractions (MVCs) in 20 male participants during controlled one‐arm lifting. The lifting involved upward motion of the scapula at various shoulder angles. Simultaneously, the electromyographic (EMG) activity of 3 shoulder muscles and psychophysical workload were also recorded. The various measurements were compared to provide a multidimensional assessment of the physical work capacity of the shoulder at various working angles. In particular, 90 and 120 degrees of flexion, 30 degrees of adduction, and 90 degrees of abduction were found to be the most vulnerable angles based on the measured MVCs. The average root mean square value of the EMG increased most significantly at 90 to 150 degrees of flexion and at 30 and 60 degrees of abduction. Slightly different measurements were compared to validate the results. In addition, a 3‐D static biomechanical model was used to show whether the estimated shoulder workload matched the measured physical capacity of the shoulder. In conclusion, these results may help ergonomists to identify shoulder angles associated with a relatively high risk of injury, and to match the workload with the physical capacity of the shoulder. Task‐specific information on shoulder work capacity is needed in the manufacturing and shipbuilding industries to protect workers from acute injuries and cumulative trauma disorders of the shoulder. Experimental results provide various data on shoulder work capacity during realistic multijoint arm and shoulder lifting, and should help lead to improvements in workplace ergonomic design. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 153–163, 2003.
A Novel Dimeric Podophyllotoxin‐Type Lignan and a New Withanolide from Withania coagulans
Authors: Nur‐e‐Alam M. , Yousaf Muhummed , Qureshi Samina , Baig Irfan , Nasim Shama , Atta‐ur‐Rahman  , Choudhary M. Iqbal
Published: March 2003

A novel dimeric lignan, bispicropodophyllin glucoside (1) and a highly oxygenated new withanolide, coagulin S (2) were isolated from the ethanolic extract of Withania coagulans. The structures were established on the basis of the spectroscopic data and have been identified as (5S*,5aR*,8aR*,9S*,15S*,15aS*,18aS*,19S*)‐9,19‐di‐β‐D‐glucopyranosyl‐5,8a,9,15,15a,18,18a,19‐octahydro‐5,15‐bis(3,4,5‐trimethoxyphenyl)bis([1,3]dioxolo[4′,5′:6,7]naphtho)[2,3‐c:2,3‐h][1,6]dioxecin‐6,16(5aH,8H)‐dione (1) and (20S*,22R*)‐5α,6β,14α,15α,17β,20,27‐heptahydroxy‐1‐oxowith‐24‐enolide (2), respectively.
Stereoselective Access to γ‐Nitro Carboxylates, Precursors for Highly Functionalized γ‐Lactams
Authors: Meisterhans Christian , Linden Anthony , Hesse Manfred
Published: March 2003

A straightforward synthesis of the enantiomerically pure nitro derivatives 31 and epi‐32, which are particularly useful intermediates for the synthesis of highly functionalized γ‐lactams, is presented. (+)‐(R)‐3‐Hydroxy‐3‐phenylpropanoic acid (20) and its ethyl ester 25 were prepared from (+)‐L‐mandelic acid (21). Condensation of 20 with pivalaldehyde furnished the novel enantiomerically pure 1,3‐dioxan‐4‐one 17, the absolute configuration of which was established by X‐ray crystal‐structure analysis. Treating the lithium enolate of 17 with the nitro alkene 18 led, in a Michael‐type addition, to a 1 : 1 mixture of two diastereoisomeric products. The stereocontrol of the addition was limited to the novel stereogenic center next to the lactone function. When the lithium enolate of 25 was treated with 18, the same selectivity was observed but with a lower chemical yield. Very facile separation of the isomers was achieved later in the synthetic sequence, when one isomer cyclized selectively to the nitro lactone 31, while the other one was isolated as hydroxy ester epi‐32. The relative configuration of racemic epi‐32 could be established by X‐ray crystal‐structure analysis.
Total Synthesis of (−)‐Lithospermoside
Authors: Josien‐Lefebvre Delphine , Le Drian Claude
Published: March 2003

The total synthesis of the naturally occurring noncyanogenic cyanoglucoside (−)‐lithospermoside (1) was achieved starting from optically pure oxatrinorbornenone (+)‐2 in 12 steps and 10% overall yield. The key step of the synthesis, the glycosidation, turned out to be very sensitive to steric hindrance, and we had, therefore, to optimize the choice of the protection used for the two other OH functions of the aglycone. Finally, the desired β‐D‐glucoside 15 was obtained in a very good yield (72%) under Koenigs–Knorr‐glycosidation conditions, closely related to those used for the total synthesis of (−)‐bauhinin.
Two New Cyclopeptides from Arenaria oreophila (Caryophyllaceae)
Authors: Jia Ai‐qun , Tan Ning‐hua , Zhao You‐xing , Li Ning , Zhou Jun
Published: March 2003

Two new cyclopeptides, named arenariphilin A (1) and arenariphilin B (2), were isolated from the whole plants of Arenaria oreophila. Their structures were determined as cyclo‐(Thr‐Gly) (1) and cyclo‐(Ser1‐Gly ‐Ser2‐Ile ‐Phe1‐Phe2) (2) on the basis of spectral data, especially by 2D‐NMR.
Effect of Through‐Bond Interaction on Conformation and Structure in Rod‐Shaped Donor–Acceptor Systems. Part 1
Authors: De Ridder Dirk J. A. , Goubitz Kees , Schenk Henk , Krijnen Bert , Verhoeven Jan W.
Published: March 2003

The crystal structures of five N‐arylpiperidin‐4‐one derivatives 2P2, 3P2, 5P2, 1P3, and 2P3 are presented (Fig. 2 and Tables 1–5) and discussed together with the derivatives 1P2 and 4P2 published previously. In all but one structure, 1P2, the aryl group is in an equatorial position. The piperidine ring adopts a normal chair conformation. In 1P2, the piperidine ring central CC bonds are significantly elongated, which is consistent with the idea that through‐bond interaction is more pronounced in the axial conformation. Through‐bond interaction also influences the pyramidalization at the piperidine C(4)‐atom in such a way that a strong interaction is directing the ethylene C‐atom C(9) into the axial direction.
Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a review
Authors: Bourin Michel
Published: March 2003

Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive– compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post‐traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. There is wide interindividual variation in the pharmacokinetics of paroxetine in adults as well as in the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment, however, serious adverse events are extremely rare even in overdose. A Pub Med search was used to collect information on the efficacy and tolerability in elderly patients. There are few studies of depression in the elderly and only one study in the old–old. In anxiety disorders including general anxiety disorder, panic disorder, obsessive–compulsive disorder and social anxiety, there are no studies at all in the elderly. However, the safety of the drug allows its prescription in the elderly. In summary, paroxetine is well tolerated in the treatment of depression in those between the ages of 65 and 75, although few studies have examined its use in those of 75 and older. Copyright © 2002 John Wiley & Sons, Ltd.
Migration, embedded networks and social capital: towards theorising North American ethnic geography
Authors: Hardwick Susan W.
Published: March 2003

This paper critically evaluates the impacts of networks of ethnicity and social capital on the migration paths and settlement decision‐making of refugees now living on the Pacific Coast of the US. Of particular significance are the social networks of two complex groups who relocated in large numbers to communities in central California and the Pacific Northwest over the past decade. Postmodern sensitivities to race, space and place in recent years have revalidated humanistic approaches suggested by human geographers more than two decades ago. Today, however, this earlier humanistic approach is being reshaped to centre on unravelling and analysing social and place‐based relationships. Rather than viewing migration in a narrow perspective (as a process happening in a particular place at a particular fixed moment in time), human geographers have begun to use ethnographic methods to record migration processes. I build on the ideas and approaches of both the ‘old’ and the ‘new’ in this article, paying particular attention to the social relationships and networks that emerge at intersections of fluidity, fusion, motion and negotiation, to appraise their role in constantly shaping and reshaping migration processes. Copyright
© 2003 John Wiley & Sons, Ltd.
Situating Fijian transmigrants: towards racialised transnational social spaces of the undocumented
Authors: Scott Gwen Gustafson
Published: March 2003

As global interconnections have increased in our current era, many social scientists are placing added emphasis on immigration studies and rethinking migration processes. This paper offers a preliminary response to the call for more empirical, but theoretically grounded, work on ‘transnationalism’ and ‘transmigration’. It considers the case of indigenous Fijians, a growing but small population of largely undocumented immigrants to the United States. I situate and define Fijians as transmigrants by underscoring the important meso‐level links, including migration networks and social capital, which serve to build and maintain relationships between immigrants, their fellow immigrants, and their kin left behind in Fiji. Additionally, while I contend that Fijian transmigrants are contributing to the formation of transnational bridges and constructing multiple, but connected, localities in both Fiji and the US, I argue that because immigrant Fijians have yet to form staunch social and symbolic ties within the US, they have not emerged into transnational communities. The Fijian case, along with other groups of undocumented transmigrants, also raises questions about the nature and definition of transnational social spaces, since there has been little discussion that identifies or legitimises racialised transnational social spaces specifically organised and occupied by undocumented transmigrants. Copyright © 2003 John Wiley & Sons, Ltd.
A legacy of forced migration: the removal of the Miami Tribe in 1846
Authors: Berry Kate A. , Rinehart Melissa A.
Published: March 2003

In the first half of the nineteenth century, dozens of Indian tribes and tens of thousands of tribal members were forced to move and resettle hundreds of miles away from their traditional homes in the eastern and mid‐western US. This process – which has come to be known as tribal or Indian removal – was initiated as white settlers encroached upon tribal resources, and was facilitated by the political and military actions of state and federal governments. After years of resistance, the Miami Tribe was brought into the removal programme and the Tribe was split between Indiana and Kansas. Removal also operated on an ideological level, infecting the political identity of the Miami Tribe and its members. This paper provides a detailed study of forced removal in order to provide insights into the complexity of colonialism within which the Miami Tribe, the State, and settlers were operating, as well as to provide an understanding of how political identity was – and continues to be – entangled with the processes, events and places associated with tribal removal. Copyright © 2003 John Wiley & Sons, Ltd.
Local dynamics in multi‐local, transnational spaces of rural Mexico: Oaxacan experiences
Authors: Conway Dennis , Cohen Jeffrey H.
Published: March 2003

Mexico's proximity to the United States, the two economies' increased integration, and the demand for low‐cost labour in el norte, has fuelled a transnational circulation of people that is most probably self‐perpetuating and is certainly firmly embedded. This investigation of local dynamics in the multi‐local transnational spaces of Oaxacan households draws upon a comprehensive set of sample surveys conducted in 12 municipios in the central valleys of Oaxaca over a six‐year period. We frame our Oaxaca empirical findings within two constructs developed by the authors. One is a typology of circulation behaviours differentiated by scale of interactive systems of mobility and by behavioural intentions; the other is a household migration and remittance framework that highlights the wide variations in the patterns of investment of remittances by recipient households. Extending these frameworks, we use village‐ and family‐level evidence to demonstrate the crucial significance of local contexts for determining household strategies of migration and remittance investment. What is most apparent from our Oaxacan biographies is, firstly, the wide range of experiences that are present both within and between the various communities; secondly, the strategic use of local circuit moves in concert with national and international (or transnational) sojourns; and thirdly, the various positive and negative impacts of migration and remittance investment that range from self‐aggrandisement to community investment. Our analysis concludes that local space is an essential contextual anchor, and the evolving nature of household migration decision‐making is in large part determined, or at least significantly influenced, by the spatial nature of the social linkages between people, their households/families, and their local, regional, national and transnational contexts. Copyright © 2003 John Wiley & Sons, Ltd.
The repopulation of the Americas in historical perspective
Authors: McNeill William H.
Published: March 2003

Migration is as old as humankind, a phenomenon that lies at the root of human dispersal across both ecological and cultural frontiers. It seems safe to assume that population growth and conflicts within and between adjacent bands were instrumental in the initial human dispersal. Then came a second wave of migration, leading to permanent settlements at places where food resources were either abundant, or could easily be concentrated. Eventually, agriculture emerged in those settlements and population increased, thus producing a new pattern of migration, as pioneers left overcrowded landscapes and sought out fertile soils. This constant process of settlement, population growth, conflicts, and migration was confined to the vast ecological and cultural frontiers of Africa and Eurasia. However, after 1492, the phenomenon of human dispersal that first started in the east African Savanna, where our ancestors evolved, eventually reached the New World where American immigration has been playing out in many forms and has left many different marks, including the destruction of Native Amerindians by European settlers as well as the many infectious diseases that they transmitted, the massive enslavements of Africans, and indentured labor, and where how cultural and other differences will be accommodated and modified remains a capital question for the 21st century. Copyright © 2003 John Wiley & Sons, Ltd.
Black migration at the margin of freedom
Authors: Shrestha Nanda R. , Smith Wilbur I. , Evans Charles L.
Published: March 2003

The history of Black migration is a story of continuity and change, a paradoxical story of hopes and despairs. Situating migration as a labour process within the general framework of labour–capital relations, this study examines the role of south‐to‐north migration in Black Americans' upward mobility and human capital accumulation for the period 1910–1970. The conceptual argument advanced is that labour market distortions, based on the historical legacy of colour as a marker of one's ability, affect the way capitalist forces use (underutilise) Black migrants, leading to the underdevelopment of their human capital. An analysis of IPUMS data samples showed: (1) Black migrants were far more likely to experience unemployment in the labour markets of the Midwest than their White counterparts; (2) the unemployment rate of more‐educated Black migrants was higher than that for less‐educated Black migrants; (3) race was revealed by regression analysis to be an important variable in explaining why Blacks were far more likely to be found in low‐wage, least upwardly mobile occupations than their White counterparts, whose proportionate employment share of the high‐end occupations was much greater than that of Blacks; and (4) geographically, the early advantage that Black migrants enjoyed from locating in the central city lost much of its value over time. This may reflect how, while Blacks remained trapped in central cities because of residential segregation, jobs – especially those in the private sector – have increasingly moved out of the city, thus creating a mismatch between their residence and the location(s) of jobs. Overall, the data analysis suggests that race still matters, as the colour of labour remains a source of discrimination in terms of both the extent to which Black labour was used (unemployment rate) and how it was used (occupation). The result was that capitalist forces in the American labour market systematically undervalued or suppressed Black migrants' pre‐existing human capital, thus denying them an opportunity fully to harness their potential and enhance their human capital accumulation. Copyright­© 2003 John Wiley & Sons, Ltd.