bluuebunny/crossref_metadata_2025 huggingface dataset:
Down-regulation of candidate tumor suppressor genes within chromosome band 13q14.3 is independent of the DNA methylation pattern in B-cell chronic lymphocytic leukemia
Authors: Mertens Daniel , Wolf Stephan , Schroeter Petra , Schaffner Claudia , Döhner Hartmut , Stilgenbauer Stephan , Lichter Peter
Published: October 2002

Loss of genomic material from chromosomal band 13q14.3 is the most common genetic imbalance in B-cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma, pointing to the involvement of this region in a tumor suppressor mechanism. From the minimally deleted region, 3 candidate genes have been isolated, RFP2, BCMS, and BCMSUN. DNA sequence analyses have failed to detect small mutations in any of these genes, suggesting a different pathomechanism, most likely haploinsufficiency. We, therefore, tested B-CLL patients for epigenetic aberrations by measuring expression of genes from 13q14.3 and methylation of their promotor region.RB1, CLLD7, KPNA3, CLLD6, andRFP2 were down-regulated in B-CLL patients as compared with B cells of healthy donors, with RFP2 showing the most pronounced loss of expression. To test whether this loss of gene expression is associated with methylation of CpG islands in the respective promotor regions, we performed methylation-sensitive quantitative polymerase chain reaction analyses and bisulfite sequencing on DNA from B-CLL patients. No difference in the methylation patterns could be detected in any CpG island of the minimally deleted region. Down-regulation of genes within chromosomal band 13q14.3 in B-CLL is in line with the concept of haploinsufficiency, but this tumor-specific phenomenon is not associated with DNA methylation.
Arp2/3 complex is required for actin polymerization during platelet shape change
Authors: Li Zhi , Kim Eric S. , Bearer Elaine L.
Published: October 2002

Platelets undergo a series of actin-dependent morphologic changes when activated by thrombin receptor activating peptide (TRAP) or when spreading on glass. Polymerization of actin results in the sequential formation of filopodia, lamellipodia, and stress fibers, but the molecular mechanisms regulating this polymerization are unknown. The Arp2/3 complex nucleates actin polymerization in vitro and could perform this function inside cells as well. To test whether Arp2/3 regulated platelet actin polymerization, we used recombinant Arp2 protein (rArp2) to generate Arp2-specific antibodies (αArp2). Intact and Fab fragments of αArp2 inhibited TRAP-stimulated actin-polymerizing activity in platelet extracts as measured by the pyrene assay. Inhibition was reversed by the addition of rArp2 protein. To test the effect of Arp2/3 inhibition on the formation of specific actin structures, we designed a new method to permeabilize resting platelets while preserving their ability to adhere and to form filopodia and lamellipodia on exposure to glass. Inhibition of Arp2/3 froze platelets at the rounded, early stage of activation, before the formation of filopodia and lamellipodia. By morphometric analysis, the proportion of platelets in the rounded stage rose from 2.85% in untreated to 63% after treatment with αArp2. This effect was also seen with Fab fragments and was reversed by the addition of rArp2 protein. By immunofluorescence of platelets at various stages of spreading, the Arp2/3 complex was found in filopodia and lamellipodia. These results suggest that activation of the Arp2/3 complex at the cortex by TRAP stimulation initiates an explosive polymerization of actin filaments that is required for all subsequent actin-dependent events.
Endothelial von Willebrand factor recruits platelets to atherosclerosis-prone sites in response to hypercholesterolemia
Authors: Theilmeier Gregor , Michiels Carine , Spaepen Erik , Vreys Ingrid , Collen Désiré , Vermylen Jos , Hoylaerts Marc F.
Published: October 2002

Platelets are thought to play a causal role during atherogenesis. Platelet-endothelial interactions in vivo and their molecular mechanisms under shear are, however, incompletely characterized. Here, an in vivo platelet homing assay was used in hypercholesterolemic rabbits to track platelet adhesion to plaque predilection sites. The role of platelet versus aortic endothelial cell (EC) activation was studied in an ex vivo flow chamber. Pathways of human platelet immobilization were detailed during in vitro perfusion studies. In rabbits, a 0.125% cholesterol diet induced no lesions within 3 months, but fatty streaks were found after 12 months. ECs at segmental arteries of 3- month rabbits expressed more von Willebrand factor (VWF) and recruited 5-fold more platelets than controls (P < .05, n = 5 and 4, respectively). The 3-month ostia had an increased likelihood to recruit platelets compared to control ostia (56% versus 18%, P < .0001, n = 89 and 63, respectively). Ex vivo, the adhesion of 3-month platelets to 3-month aortas was 8.4-fold increased compared to control studies (P < .01, n = 7 and 5, respectively). In vitro, endothelial VWF–platelet glycoprotein (GP) Ib and platelet P-selectin– endothelial P-selectin glycoprotein ligand 1 interactions accounted in combination for 83% of translocation and 90% of adhesion (P < .01, n = 4) of activated human platelets to activated human ECs. Platelet tethering was mainly mediated by platelet GPIbα, whereas platelet GPIIb/IIIa contributed 20% to arrest (P < .05). In conclusion, hypercholesterolemia primes platelets for recruitment via VWF, GPIbα, and P-selectin to lesion-prone sites, before lesions are detectable.
Human acute stem cell leukemia with multilineage differentiation potential via cascade activation of growth factor receptors
Authors: Testa Ugo , Torelli Giovanni F. , Riccioni Roberta , Muta Andrea Onetti , Militi Stefania , Annino Luciana , Mariani Gualtiero , Guarini Anna , Chiaretti Sabina , Ritz Jerome , Mandelli Franco , Peschle Cesare , Foa Robin
Published: October 2002

The morphologic, immunophenotypic, genotypic, genomic, and functional features of an undifferentiated acute leukemia with stem cell features are reported. At light and electron microscopy, the leukemic population was represented by primitive progenitor cells with no evidence of differentiation. The blasts were CD34+, AC133+, CD71−, HLA-DR−, CD38−/dim+, CD90+, CD117dim+, flt3+; did not express B, T, or myeloid-associated antigens; and showed a germline configuration of the immunoglobulin and T-cell receptor. Genomic profiling documented the expression of early stem cell and myeloid-associated genes. Receptors for early-acting hemopoietic growth factors (HGFs) were detected, while receptors for unilineage HGF were not expressed. Incubation with the flt3 or Kit ligand induced the expression of unilineage HGF receptors, allowing these cells to respond to their respective ligands. Growth without differentiation was sustained only in the presence of early-acting HGF, namely flt3 ligand, while early and unilineage HGF gave rise to all types of hemopoietic colonies.
Processing of the lipocalin α1-microglobulin by hemoglobin induces heme-binding and heme-degradation properties
Authors: Allhorn Maria , Berggård Tord , Nordberg Jonas , Olsson Martin L. , Åkerström Bo
Published: October 2002

α1-Microglobulin is a 26-kd protein, widespread in plasma and tissues and well-conserved among vertebrates. α1-Microglobulin belongs to the lipocalins, a protein superfamily with highly conserved 3-dimensional structures, forming an internal ligand binding pocket. The protein, isolated from urine, has a heterogeneous yellow-brown chromophore bound covalently to amino acid side groups around the entrance of the lipocalin pocket. α1-Microglobulin is found in blood both in free form and complex-bound to immunoglobulin A (IgA) via a half-cystine residue at position 34. It is shown here that an α1-microglobulin species, which we name t–α1-microglobulin (t = truncated), with a free Cys34 thiol group, lacking its C-terminal tetrapeptide, LIPR, and with a more polar environment around the entrance of the lipocalin pocket, is released from IgA–α1-microglobulin as well as from free α1-microglobulin when exposed to the cytosolic side of erythrocyte membranes or to purified oxyhemoglobin. The processed t–α1-microglobulin binds heme and the α1-microglobulin–heme complex shows a time-dependent spectral rearrangement, suggestive of degradation of heme concomitantly with formation of a heterogeneous chromophore associated with the protein. The processed t–α1-microglobulin is found in normal and pathologic human urine, indicating that the cleavage process occurs in vivo. The results suggest that α1-microglobulin is involved in extracellular heme catabolism.
Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia
Authors: Dworzak Michael N. , Fröschl Gertraud , Printz Dieter , Mann Georg , Pötschger Ulrike , Mühlegger Nora , Fritsch Gerhard , Gadner Helmut
Published: October 2002

Detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) predicts outcome. Previous studies were invariably based on relative quantification and did not investigate sample-inherent parameters that influence test accuracy, which makes comparisons and clinical conclusions cumbersome. Hence, we conducted a prospective, population-based MRD study in 108 sequentially recruited children with ALL uniformly treated with the ALL-Berlin-Frankfurt-Münster (ALL-BFM) 95 protocol in Austria (median follow-up of 40 months). Using sensitive, limited antibody panel flow cytometry applicable to 97% of patients, we investigated 329 bone marrow samples from 4 treatment time points. MRD was quantified by blast percentages among nucleated cells (NCs) and by absolute counts (per microliter). Covariables such as NC count, normal B cells, and an estimate of the test sensitivity were also recorded. Presence and distinct levels of MRD correlated with a high probability of early relapse at each of the time points studied. Sequential monitoring at day 33 and week 12 was most useful for predicting outcome independently from clinical risk groups: patients with persistent disease (≥ 1 blast/μL) had a 100% probability of relapse, compared to 6% in all others. Absolute MRD quantification was more appropriate than relative, due to considerable variations in total NC counts between samples. Regeneration of normal immature B cells after periods of rest from treatment limited the test sensitivity. In conclusion, MRD detection by flow cytometry is a strong and independent outcome indicator in childhood ALL. Standardization regarding absolute quantification on the basis of NCs and assessment during periods of continuous treatment promise to increase the accuracy, simplicity, and cost efficiency of the approach.
Infant hypervitaminosis A causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition
Authors: Perrotta Silverio , Nobili Bruno , Rossi Francesca , Criscuolo Maria , Iolascon Achille , Di Pinto Daniela , Passaro Irene , Cennamo Lucia , Oliva Adriana , Della Ragione Fulvio
Published: October 2002

Vitamin A is a pivotal biochemical factor required for normal proliferation and differentiation as well as for specialized functions, such as vision. The dietary intake of 1500 IU/day is recommended in the first year of life. Here, we report the case of an infant who had been given 62 000 IU/day for 80 days. The infant showed several clinical signs of retinol intoxication, including severe anemia and thrombocytopenia. Bone marrow showed a remarkably reduced number of erythroid and megakaryocytic cells. The interruption of vitamin A treatment was immediately followed by clinical and biochemical recovery. To clarify whether the effects of retinol are due to a direct action on bone marrow cell proliferation, we investigated the activity of retinol (both the drug and the pure molecule) on the growth of K-562, a multipotent hematopoietic cell line, and on bone marrow mesenchymal stem cells. We observed that vitamin A strongly inhibited the proliferation of the cells at concentrations similar to those reached in vivo. Subsequent biochemical analyses of the cell cycle suggested that the effect was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21Cip1 and p27Kip1. These are the first findings to demonstrate that infant hypervitaminosis A causes a severe anemia and thrombocytopenia and that this is probably due to the direct effect of the molecule on the growth of all bone marrow cellular components. Our data also suggest potential bone marrow functional alterations after excessive vitamin A intake because of emerging social habits.
Expression of C/EBPβ from the C/ebpα gene locus is sufficient for normal hematopoiesis in vivo
Authors: Jones Letetia C. , Lin Meng-Liang , Chen Shih-Shun , Krug Utz , Hofmann Wolf-K. , Lee Stephen , Lee Ying-Hue , Koeffler H. Phillip
Published: October 2002

CCAAT/enhancer-binding proteins (C/EBPs) are critical transcriptional regulators of differentiation of hematopoietic cells. Previous studies have shown that targeted disruption of theC/ebpα gene results in a lack of granulocytic differentiation with an arrest at the stage of immature myeloblasts. By using a gene replacement strategy in which C/EBPβ was expressed from the C/ebpα gene locus of C/EBPα-null mice, we have evaluated the ability of C/EBPβ to function for C/EBPα in directing differentiation along the granulocytic pathway. We show that the morphology and the differential cell counts of the bone marrow and peripheral blood cells from C/EBPβ knockin mice are indistinguishable from those of their wild-type littermates, indicating that hematopoiesis occurs normally in these animals. Additionally, we analyzed expression of 21 myeloid-specific genes, including markers for distinct stages of granulocytic differentiation, and found no significant differences in their levels of expression in the bone marrow of C/EBPβ knockin and wild-type mice. These results imply that C/EBPβ can substitute for C/EBPα during hematopoiesis when expressed from the C/ebpα gene locus.
Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow–derived and circulating human CD34+ hematopoietic stem cells
Authors: Steidl Ulrich , Kronenwett Ralf , Rohr Ulrich-Peter , Fenk Roland , Kliszewski Slawomir , Maercker Christian , Neubert Peter , Aivado Manuel , Koch Judith , Modlich Olga , Bojar Hans , Gattermann Norbert , Haas Rainer
Published: October 2002

CD34+ hematopoietic stem cells are used clinically to support cytotoxic therapy, and recent studies raised hope that they could even serve as a cellular source for nonhematopoietic tissue engineering. Here, we examined in 18 volunteers the gene expressions of 1185 genes in highly enriched bone marrow CD34+(BM-CD34+) or granulocyte–colony-stimulating factor–mobilized peripheral blood CD34+(PB-CD34+) cells by means of cDNA array technology to identify molecular causes underlying the functional differences between circulating and sedentary hematopoietic stem and progenitor cells. In total, 65 genes were significantly differentially expressed. Greater cell cycle and DNA synthesis activity of BM-CD34+ than PB-CD34+ cells were reflected by the 2- to 5-fold higher expression of 9 genes involved in cell cycle progression, 11 genes regulating DNA synthesis, and cell cycle–initiating transcription factor E2F-1. Conversely, 9 other transcription factors, including the differentiation blocking GATA2 and N-myc, were expressed 2 to 3 times higher in PB-CD34+ cells than in BM-CD34+cells. Expression of 5 apoptosis driving genes was also 2 to 3 times greater in PB-CD34+ cells, reflecting a higher apoptotic activity. In summary, our study provides a gene expression profile of primary human CD34+ hematopoietic cells of the blood and marrow. Our data molecularly confirm and explain the finding that CD34+ cells residing in the bone marrow cycle more rapidly, whereas circulating CD34+ cells consist of a higher number of quiescent stem and progenitor cells. Moreover, our data provide novel molecular insight into stem cell physiology.
Migration velocity analysis from locally coherent events in 2‐D laterally heterogeneous media, Part I: Theoretical aspects
Authors: Chauris Hervé , Noble Mark S. , Lambaré Gilles , Podvin Pascal
Published: October 2002

We present a new method based on migration velocity analysis (MVA) to estimate 2‐D velocity models from seismic reflection data with no assumption on reflector geometry or the background velocity field. Classical approaches using picking on common image gathers (CIGs) must consider continuous events over the whole panel. This interpretive step may be difficult—particularly for applications on real data sets. We propose to overcome the limiting factor by considering locally coherent events. A locally coherent event can be defined whenever the imaged reflectivity locally shows lateral coherency at some location in the image cube.

In the prestack depth‐migrated volume obtained for an a priori velocity model, locally coherent events are picked automatically, without interpretation, and are characterized by their positions and slopes (tangent to the event). Even a single locally coherent event has information on the unknown velocity model, carried by the value of the slope measured in the CIG. The velocity is estimated by minimizing these slopes.

We first introduce the cost function and explain its physical meaning. The theoretical developments lead to two equivalent expressions of the cost function: one formulated in the depth‐migrated domain on locally coherent events in CIGs and the other in the time domain. We thus establish direct links between different methods devoted to velocity estimation: migration velocity analysis using locally coherent events and slope tomography.

We finally explain how to compute the gradient of the cost function using paraxial ray tracing to update the velocity model. Our method provides smooth, inverted velocity models consistent with Kirchhoff‐type migration schemes and requires neither the introduction of interfaces nor the interpretation of continuous events. As for most automatic velocity analysis methods, careful preprocessing must be applied to remove coherent noise such as multiples.
Predrill pore‐pressure prediction using seismic data
Authors: Sayers C. M. , Johnson G. M. , Denyer G.
Published: October 2002

1A predrill estimate of pore pressure can be obtained from seismic velocities using a velocity‐to–pore‐pressure transform, but the seismic velocities need to be derived using methods having sufficient resolution for well planning purposes. For a deepwater Gulf of Mexico example, significant differences are found between the velocity field obtained using reflection tomography and that obtained using a conventional method based on the Dix equation. These lead to significant differences in the predicted pore pressure. Parameters in the velocity‐to–pore‐pressure transform are estimated using seismic interval velocities and pressure data from nearby calibration wells. The uncertainty in the pore pressure prediction is analyzed by examining the spread in the predicted pore pressure obtained using parameter combinations which sample the region of parameter space consistent with the available well data. If calibration wells are not available, the ideas proposed in this paper can be used with measurements made while drilling to predict pore pressure ahead of the bit based on seismic velocities.
Molecular Detection of Cytokeratin-19–Positive Cells in the Peripheral Blood of Patients With Operable Breast Cancer: Evaluation of Their Prognostic Significance
Authors: Stathopoulou A. , Vlachonikolis I. , Mavroudis D. , Perraki M. , Kouroussis Ch. , Apostolaki S. , Malamos N. , Kakolyris S. , Kotsakis A. , Xenidis N. , Reppa D. , Georgoulias V.
Published: October 2002

PURPOSE: To evaluate the prognostic significance of molecular detection of cytokeratin 19 (CK-19) mRNA-positive cells by nested reverse transcriptase polymerase chain reaction (RT-PCR) in the peripheral blood of women with stages I and II breast cancer before adjuvant chemotherapy.

PATIENTS AND METHODS: The sensitivity and specificity of CK-19 mRNA detection by nested RT-PCR were investigated using MCF-7 and ARH-77 cells and blood from healthy women and patients with hematologic malignancies, metastatic colorectal cancer, and early and metastatic breast cancer. Peripheral blood from 148 patients with operable breast cancer, obtained before initiation of any adjuvant therapy, was tested for the presence of CK-19 mRNA-positive cells.

RESULTS: The nested RT-PCR assay for CK-19 mRNA detected one MCF-7 tumor cell in 106 normal peripheral blood mononuclear cells in four of five experiments; no signal was detected with the CK-19–negative ARH-77 cells. CK-19 mRNA was detected in the peripheral blood of 3.7% of healthy blood donors, 14.3% of patients with hematologic malignancies, and 3.2% of patients with metastatic colorectal cancer. Detection rates for CK-19 mRNA-positive cells in the bone marrow/blood of patients with early or metastatic breast cancer were 63%/30% and 74%/52%, respectively. For stages I and II breast cancer, detection of CK-19–positive cells in the peripheral blood before adjuvant therapy was associated with reduced disease-free interval (P = .0007) and overall survival (P = .01). In multivariate analysis, detection of peripheral-blood CK-19–positive cells was an independent prognostic factor for disease relapse and death.

CONCLUSION: Molecular detection of CK-19 mRNA-positive cells by RT-PCR in the peripheral blood of patients with stages I and II breast cancer before initiation of adjuvant therapy has independent prognostic value as a marker of poor clinical outcome.
Prognostic Significance of Partial Tandem Duplications of the MLL Gene in Adult Patients 16 to 60 Years Old With Acute Myeloid Leukemia and Normal Cytogenetics: A Study of the Acute Myeloid Leukemia Study Group Ulm
Authors: Döhner Konstanze , Tobis Karen , Ulrich Regina , Fröhling Stefan , Benner Axel , Schlenk Richard F. , Döhner Hartmut
Published: October 2002

PURPOSE: To evaluate the incidence and clinical significance of partial tandem duplications (PTDs) of the mixed lineage leukemia (MLL) gene in a large series of newly diagnosed adult patients (16 to 60 years old) with acute myeloid leukemia (AML) intensively treated within the multicenter treatment trials AML-HD93 and AML-HD98A.

PATIENTS AND METHODS: Identification of MLL PTD was performed centrally using Southern blot analysis in pretreatment samples from 525 of 683 assessable patients. PTD was confirmed by polymerase chain reaction (PCR) and sequencing of the PCR products.

RESULTS: MLL PTD was identified in none of the 129 patients with t(8;21), inv(16), and t(15;17); in 19 (7.7%) of 247 patients with normal karyotype; and in 10 (8.5%) of 119 patients with all other abnormalities, with 30 cases of t(11q23) excluded. In the group of patients with a normal karyotype, there was no difference in the presenting clinical features between the PTD-positive and the PTD-negative cases. Sixteen (89%) of the 18 assessable PTD-positive patients and 158 (78%) of the 203 PTD-negative patients achieved a complete remission. After a median follow-up time of 19 months, 11 of the 16 PTD-positive patients relapsed compared with 54 of the 158 PTD-negative patients; the median remission durations of the PTD-positive and the PTD-negative groups were 7.75 months and 19 months, respectively (P < .001). Multivariate analysis identified the MLL PTD status as the single prognostic factor for remission duration.

CONCLUSION: Within the subgroup of young adult AML patients with normal karyotype, MLL PTD is associated with short remission duration.
Receptor-Mediated Adenylyl Cyclase Activation Through XLαs, the Extra-Large Variant of the Stimulatory G Protein α-Subunit
Authors: Bastepe Murat , Gunes Yasemin , Perez-Villamil Beatriz , Hunzelman Joy , Weinstein Lee S. , Jüppner Harald
Published: October 2002

XLαs, the large variant of the stimulatory G protein α subunit (Gsα), is derived from GNAS1 through the use of an alternative first exon and promoter. Gsα and XLαs have distinct amino-terminal domains, but are identical over the carboxyl-terminal portion encoded by exons 2–13. XLαs can mimic some functions of Gsα, including βγ interaction and adenylyl cyclase stimulation. However, previous attempts to demonstrate coupling of XLαs to typically Gs-coupled receptors have not been successful. We now report the generation of murine cell lines that carry homozygous disruption of Gnas exon 2, and are therefore null for endogenous XLαs and Gsα (GnasE2−/E2−). GnasE2−/E2− cells transfected with plasmids encoding XLαs and different heptahelical receptors, including the β2-adrenergic receptor and receptors for PTH, TSH, and CRF, showed agonist-mediated cAMP accumulation that was indistinguishable from that observed with cells transiently coexpressing Gsα and these receptors. Our findings thus indicate that XLαs is capable of functionally coupling to receptors that normally act via Gsα.
A New Strategy for Construction of Covalently Linked Giant Porphyrin Arrays with One, Two, and Three Dimensionally Arranged Architectures
Authors: Aratani Naoki , Osuka Atsuhiro
Published: October 2002

Synthesis, structural characteristics, and optical and electrochemical properties of various meso–meso-linked porphyrin arrays were described. The AgI-salt-promoted meso–meso coupling reaction of 5,15-diaryl and 5,10,15-triaryl ZnII-porphyrins is advantageous in light of its high regioselectivity as well as its easy extension to large porphyrin arrays. A similar coupling reaction is also possible by electrochemical oxidations for ZnII- and MgII-porphyrins, while the electrochemical oxidation of NiII-, PdII, and CuII-porphyrins led to formation of meso-β linked biporphyrins with high regio-selectivity. As an extension of the above AgI-promoted coupling reaction, 1,4-phenylene-bridged linear porphyrin arrays were coupled to give orthogonally arranged windmill-like porphyrin arrays, which in turn were further coupled to afford grid-like porphyrin arrays of giant size. In all the ZnII-metallated windmill arrays, the intramolecular singlet–singlet excitation energy transfer proceeds efficiently from the peripheral porphyrins to the central biporphyrin core. The doubling reaction was repeated up to the synthesis of 128-mer. During these attempts, many meso–meso-linked porphyrin arrays were isolated in a discrete form by repetitive gel-permeation chromatography (GPC)–HPLC, all exhibiting high solubility in common organic solvents in spite of their giant molecular sizes. Finally, the oxidation with strong oxidant tris(4-bromophenyl)aminium hexachloroantimonate allowed the coupling of 5,10,15-triaryl NiII- and PdII-porphyrins to meso-β doubly-linked fused biporphyrins and the smooth conversion of meso–meso-linked CuII-biporphyrin to meso–meso  β–β  β–β triply-linked biporphyrin. These fused biporphyrins exhibit full π-conjugation over the arrays.
Intramolecular Pauson-Khand Reaction of Various 2-Aryl-1,6-Enynes: Synthesis of Bicyclic Compounds Bearing Quaternary Carbon Center
Authors: Ishizaki Miyuki , Satoh Hiroshi , Hoshino Osamu
Published: October 2002

Intramolecular Pauson-Khand reaction of various 2-aryl-1-hepten-6-ynes and its aza-derivative (acyclic exo-methylene compounds) efficiently produced 1-aryl-bicyclo[3.3.0] octenones and azaoctenone bearing quaternary carbon center in good yields. The reaction of 1,7-enynes was also investigated.
A comparison of two schemes for the convective transport of chemical species in a Lagrangian global chemistry model
Authors: Collins W. J. , Derwent R. G. , Johnson C. E. , Stevenson D. S.
Published: October 2002

We have developed a detailed parametrization scheme to represent the effects of subgrid‐scale convective transport in a three‐dimensional chemistry‐transport model (CTM). The CTM utilizes the meteorological fields generated by a general‐circulation model (GCM) to redistribute over 70 chemical species. The convective transport is implemented using the convective mass fluxes, entrainment rates and detrainment rates from the GCM.

We compare the modelled distributions of 222Rn with observations. This shows that the vertical profile of this species is affected by the choice of convective‐transpo rt parametrization. The new parametrization is found to improve significantly the simulation of 222Rn over the summertime continents. © Crown copyright, 2002. Royal Meteorological Society.
The 7.7‐year North Atlantic Oscillation
Authors: Costa E. D. Da , Verdiere A. Colin De
Published: October 2002

We present a statistical method, the extended canonical correlation analysis, to extract intermittent propagative coupled oscillations. We have applied this technique to a 136‐year‐long North Atlantic sea‐level‐pressure and sea‐surface‐temperature dataset. Nine ocean–atmosphere coupled oscillations with periods between 2.3 and 18 years were found. The 7.7 y period oscillation is presented in some detail and its links with the North Atlantic Oscillation are discussed. Copyright © 2002 Royal Meteorological Society.
An Experimental Test of an Optimal Growth Model
Authors: Lei Vivian , Noussair Charles N
Published: October 2002

This paper describes the design and behavior of an experimental economy with the structure of the Ramsey-Cass-Koopmans model of optimal growth. The experiment includes three different implementations of the model: a decentralized implementation with multiple agents and a market for capital, a treatment where individual subjects are placed in the role of social planners, and a treatment where the social planner consists of five agents making a joint decision. The findings highlight the role of market institutions in facilitating convergence to the optimal steady state.
What Explains the Industrial Revolution in East Asia? Evidence From the Factor Markets
Authors: Hsieh Chang-Tai
Published: October 2002

This paper presents dual estimates of total factor productivity growth (TFPG) for East Asian countries. While the dual estimates of TFPG for Korea and Hong Kong are similar to the primal estimates, they exceed the primal estimates by 1 percent a year for Taiwan and by more than 2 percent for Singapore. The reason for the large discrepancy for Singapore is because the return to capital has remained constant, despite the high rate of capital accumulation indicated by Singapore's national accounts. This discrepancy is not explained by financial market controls, capital income taxes, risk premium changes, and public investment subsidies.
Endogenous Federal Grants and Crowd-out of State Government Spending: Theory and Evidence from the Federal Highway Aid Program
Authors: Knight Brian
Published: October 2002

Contrary to simple theoretical predictions, existing evidence suggests that federal grants do not crowd out state government spending. A legislative bargaining model with endogenous grants documents a positive correlation between grant receipts and preferences for public goods; this correlation has likely biased existing work against measuring crowd-out. To correct for such endogeneity, the model motivates instruments based on the political power of state congressional delegations. Exploiting this exogenous variation in grants, the instrumental variables estimator reports crowd-out that is statistically and economically significant. This endogeneity may explain the flypaper effect, a nonequivalence between grant receipts and private income.
Recommendations for Further Reading
Authors: Saffran Bernard
Published: October 2002

This section will list readings that may be especially useful to teachers of undergraduate economics, as well as other articles that are of broader cultural interest. In general, the articles chosen will be expository or integrative and not focus on original research. They may include survey articles, discussion of related subjects in which economists might have an interest or analyses of economics from other perspectives. If you write or read an appropriate article, please send a copy of the article (and possibly a few sentences describing it) to Bernard Saffran, c/o Journal of Economic Perspectives, Department of Economics, Swarthmore College, Swarthmore, PA 19081.
Evolutionary Theorizing in Economics
Authors: Nelson Richard R , Winter Sidney G
Published: October 2002

This paper reviews the case for an evolutionary approach to problems of economic analysis, ranging from the details of individual firm behavior in the short run through industrial dynamics to the historical evolution of institutions and technologies. We draw upon a substantial body of recent research contributions. We characterize micro behavior as governed by skills and routines that are shaped by learning and selection. We then consider major areas of application of evolutionary thinking, including the analysis of competitive processes in technologically dynamic industries and the evolution of institutions and technologies.
A New Model for Heavy Metal Removal in a Biosorption Column
Authors: Yan Guangyu , Viraraghavan T. , Chen Min
Published: October 2002

Column kinetics for metal removal could be described more adequately by a modified dose–response model than by the Thomas model or Bohart–Adams model conventionally used. The new empirical model can be used either in a linearized form or a non-linearized form. Use of the model minimizes the error resulting from use of the Thomas model, especially at lower or higher time periods of the breakthrough curve.
Bond Strength of Reinforcement in High-Strength Concrete
Authors: Mendis P. , French C.
Published: October 2002

The use of high-strength concrete is becoming popular around the world. The american code, ACI 318–95 is used in many countries to calculate the development length of deformed bars in tension. However, current design provisions of ACI 318–95 are based on empirical relationships developed from tests on normal strength concrete. The results of a series of tests on high-strength concrete, reported in the literature, from six research studies are used to review the existing recommendations in ACI 318–95 for design of splices and anchorage of reinforcement. It is shown that ACI 318–95 equations may be unconservative for some cases beyond 62 MPa (9 ksi).
Influence of Concrete Compaction on the Behavior of Concrete Filled Steel Tubes with Rectangular Sections
Authors: Han Lin-Hai , Yang You-Fu
Published: October 2002

Tests on sixteen concrete filled steel tubes to investigate the influence of concrete compaction methods on the section capacities of concrete filled steel tubes with rectangular sections are reported. The main objectives of these tests were twofold: firstly, to report a series of tests on composite stub columns under different concrete compaction methods; and secondly, to investigate the influence of concrete compaction on the section capacities and the modulus of elastic of concrete filled steel tubes with rectangular sections. It was found that better compaction of concrete resulted in higher section capacities and higher elastic moduli in concrete filled steel tubes. The tests showed the importance of good concrete compaction for concrete filled steel tubes with rectangular sections.
Parametric Study of Base-Isolated Structures
Authors: Jangid R.S.
Published: October 2002

A parametric study of base-isolated structure with different isolation systems is conducted for understanding their dynamic behaviour. The superstructure is idealized as a one-storey structure isolated by different isolation systems. The various isolation systems considered are: the elastomeric bearings (with and without lead core) and the sliding systems (with and without restoring force). The governing equations of motion of the isolated structural system are derived and solved in the time domain. Three time histories of simulated earthquake ground motion are applied to the isolated system and the peak average superstructure acceleration and bearing displacement of the system are plotted under different system parameters in order to study the comparative performance of different isolation systems. The important parameters considered in the study include (i) the time period and damping of the superstructure, (ii) the ratio of the base to superstructure mass, (iii) the isolation period, damping and yield strength of the elastomeric bearings and (iv) the isolation period, damping and coefficient of friction of the sliding systems. It was found that the above isolation system parameters significantly influence the earthquake response of structure. However, the damping and the period of the superstructure do not have noticeable effects on the peak response of base-isolated structure. In addition, the effects of viscous damping are found to be insignificant when the additional damping in the isolation system in the form of such as hysteretic (due to yielding of lead-core) or friction is present.
Social capital, value, and measure: Antonio Negri's challenge to capitalism
Authors: Day Ronald E.
Published: October 2002

This article engages one of the most important concepts in Knowledge Management, namely, the concept of “social capital,” focusing upon the problem of measure and value in capitalism, specifically within the period and conditions of post‐Fordist production. The article engages work that has emerged from out of the Italian Workerist and Autonomist Marxist movements (as well as French post‐structuralist theory) since the 1960s, and it particularly focuses upon the work of the contemporary Italian philosopher and political activist, Antonio Negri.1 In doing so, it presents a more politically “Left” development of the concept of social capital than is often possible within the largely Management‐defined discourses common to Knowledge Management. At the same time, however, the article points to the importance of Knowledge Management as a symptom of a turn in political economy, even though Knowledge Management, because of its provenance, has been unable to fully explore social capital as a shift in capitalist notions of value.
Dynamic and evolutionary updates of classificatory schemes in scientific journal structures
Authors: Leydesdorff Loet
Published: October 2002

Can the inclusion of new journals in the Science Citation Index be used for the indication of structural change in the database, and how can this change be compared with reorganizations of relations among previously included journals? Change in the number of journals (n) is distinguished from change in the number of journal categories (m). Although the number of journals can be considered as a given at each moment in time, the number of journal categories is based on a reconstruction that is time‐stamped ex post. The reflexive reconstruction is in need of an update when new information becomes available in a next year. Implications of this shift towards an evolutionary perspective are specified.
Thermodynamic and structural factors in the removal of bulky DNA adducts by the nucleotide excision repair machinery
Authors: Geacintov Nicholas E. , Broyde Suse , Buterin Tonko , Naegeli Hanspeter , Wu Min , Yan Shixiang , Patel Dinshaw J.
Published: October 2002

The function of the human nucleotide excision repair (NER) apparatus is to remove bulky adducts from damaged DNA. In an effort to gain insights into the molecular mechanisms involved in the recognition and excision of bulky lesions, we investigated a series of site specifically modified oligonucleotides containing single, well‐defined polycyclic aromatic hydrocarbon (PAH) diol epoxide‐adenine adducts. Covalent adducts derived from the bay region PAH, benzo[a]pyrene, are removed by human NER enzymes in vitro. In contrast, the stereochemically analogous N6‐dA adducts derived from the topologically different fjord region PAH, benzo[c]phenanthrene, are resistant to repair. The evasion of DNA repair may play a role in the observed higher tumorigenicity of the fjord region PAH diol epoxides. We are elucidating the structural and thermodynamic features of these adducts that may underlie their marked distinction in biologic function, employing high‐resolution nuclear magnetic resonance studies, measurements of thermal stabilities of the PAH diol epoxide‐modified oligonucleotide duplexes, and molecular dynamics simulations with free energy calculations. Our combined findings suggest that differences in the thermodynamic properties and thermal stabilities are associated with differences in distortions to the DNA induced by the lesions. These structural effects correlate with the differential NER susceptibilities and stem from the intrinsically distinct shapes of the fjord and bay region PAH diol epoxide‐N6‐adenine adducts. © 2002 Wiley Periodicals, Inc. Biopolymers (Nucleic Acid Sci) 65: 202–210, 2002
Factors that influence surgical choices in women with breast carcinoma
Authors: Staradub Valerie L. , Hsieh Yi‐Ching , Clauson Jennifer , Langerman Alexander , Rademaker Alfred W. , Morrow Monica
Published: October 2002

BACKGROUND

In the absence of medical contraindications, survival after undergoing breast‐conserving therapy (BCT), mastectomy (M), and mastectomy with immediate reconstruction (MIR) is equal. The authors studied demographic factors to identify the variables that differed significantly among women making different surgical choices.

METHODS

Women with ductal carcinoma in situ or clinical Stage I or II breast carcinoma with no contraindications for BCT or MIR who were treated between 1995 and 1998 were identified from a prospectively collected data base. Demographic and tumor factors were compared using the Fisher exact test.

RESULTS

There were 578 women with 586 tumors who did not have contraindications for BCT or MIR. Among this group, 85.2% of women chose BCT, 9.2% of women chose M, and 5.6% of women chose MIR. Women undergoing M alone were older and were more likely to have Stage II carcinoma compared with women undergoing BCT. Patients undergoing M or MIR were more likely to have had a prior breast biopsy compared with patients who chose BCT. Marital status and employment approached significance (P = 0.06); however, a family history of breast carcinoma was not a predictor of treatment choice.

CONCLUSIONS

The current findings suggest a need for patient education strategies that emphasize the lack of influence of age and prior breast biopsy on the use of BCT. Differences in demographic variables may reflect true variations in patient preference among groups, emphasizing the need to address the spectrum of treatment options with patients. Cancer 2002;95:1185–90. © 2002 American Cancer Society.

DOI 10.1002/cncr.10824
Medial forebrain bundle axotomy during development induces apoptosis in dopamine neurons of the substantia nigra and activation of caspases in their degenerating axons
Authors: El‐Khodor Bassem F. , Burke Robert E.
Published: October 2002

There is growing evidence that programmed cell death may play a role in degenerative neurologic disease. The caspases are a family of cell death proteins that mediate proteolytic cascades in the death process. Although there is clear evidence that caspases play a role in the destruction of the components of the neuronal soma, it has been controversial whether they play a role in the degeneration of axons that accompanies the death of the cell body. It is important to define the molecular mechanisms of axonal degeneration, because terminal degeneration may occur early in neurodegenerative disease. We have therefore investigated whether caspases play a role in axonal degeneration in the dopaminergic nigrostriatal system following axotomy of the median forebrain bundle during development. We find that this lesion induces apoptosis in midbrain dopaminergic neurons at the level of the cell soma. Concomitantly with this induction of apoptosis, degeneration of dopaminergic axons occurs and is characterized by the formation of axonal swellings and spheroids. Immunohistochemical analysis reveals that the activated form of caspase‐3 and a caspase cleavage product of β‐actin are abundantly expressed in these degenerating fibers. We conclude that caspases are activated in degenerating dopaminergic axons as the somata undergo programmed cell death in this model. These results raise the possibility that caspase activation may occur in other programmed cell death contexts for these neurons, and, if this is so, then their inhibition may be a useful therapeutic target. J. Comp. Neurol. 452:65–79, 2002. © 2002 Wiley‐Liss, Inc.
Mesh adaptation for Dirichlet flow control via Nitsche's method
Authors: Becker R.
Published: October 2002

The purpose of this paper is twofold: First, a Nitsche‐type method for the treatment of inhomogeneous Dirichlet boundary conditions for the Navier–Stokes equations is proposed. This formulation is then used for discretization of Dirichlet control problems using adaptive finite elements. The mesh adaptation is driven by an a posteriori error estimator for the whole optimization problem. Copyright © 2002 John Wiley & Sons, Ltd.
Are cognitively intact seniors with subjective memory loss more likely to develop dementia?
Authors: St John Philip , Montgomery Patrick
Published: October 2002

Background

Subjective memory loss (SML) is common in elderly persons. It is not clear if SML predicts the development of dementia.

Objectives

(1) to determine if SML in those with normal cognition predicts dementia or cognitive impairment without dementia (CIND); (2) to determine if an association is independent of the effect of age, gender and depressive symptoms.

Methods

Secondary analysis of the Manitoba Study of Health and Aging (MSHA), a population‐based prospective study. Data were collected in 1991, and follow‐up was done 5 years later. Community‐dwelling seniors sampled randomly from a population‐based registry in the Canadian province of Manitoba, stratified on age and region. Only those scoring in the normal range of the Modified mini‐mental state examination (3MS) were included. Predictor variables were self‐reported memory loss, 3MS, Center for epidemiological studies—depression scale (CES‐D), age, gender, and education. Outcomes were mortality and cognitive impairment five years later.

Results

In bivariate analyses, SML was associated with both death and dementia. In multivariate models, SML did not predict mortality. After adjusting for age, gender, and depressive symptoms, SML predicted dementia. However, after adjusting for baseline 3MS score, SML did not predict dementia.

Conclusions

Memory complaints predict the development of dementia over five years, and clinicians should monitor these persons closely. However, the proportion of persons developing dementia was small, and SML alone is unlikely to be a useful clinical predictor of dementia. Copyright © 2002 John Wiley & Sons, Ltd.