bluuebunny/crossref_metadata_2025_split huggingface dataset:
R&D and Absorptive Capacity: Theory and Empirical Evidence*
Authors: Griffith Rachel , Redding Stephen , Van Reenen John 
Published: November 2004

AbstractThis paper presents a single unified framework that integrates the theoretical literature on Schumpeterian endogenous growth and major strands of the empirical literature on R&D, productivity growth and productivity convergence. Starting from a structural model of endogenous growth following Aghion and Howitt (1992, 1998), we provide microeconomic foundations for the reduced‐form equations for total factor productivity (TFP) growth frequently estimated empirically using industry‐level data. R&D affects both innovation and the assimilation of others’ discoveries (“absorptive capacity”). Long‐run cross‐country differences in productivity emerge endogenously, and the analysis implies that many existing studies underestimate R&D's social rate of return by neglecting absorptive capacity.
The Managers versus the Consultants*
Authors: Grifell‐Tatjé Emili , Knox Lovell C. A. 
Published: November 2004

AbstractSince engineering information is rarely available, standard practice is to benchmark managerial performance against best observed practice. We exploit a rare opportunity to benchmark managerial performance against engineering standards. Our managerial performance describes the activities of Spanish electricity distributors, and our engineering standards are obtained from an engineering grid created by an international consultancy. We find the consultancy's network to be much less costly to operate. When we decompose the cost differential, we find that the superior network design, combined with lower input prices, accounts for more than all of the predicted cost savings. However we also find that the managers are more cost efficient than the consultancy, presumably because they exploit their incentive to be cost efficient under a revenue cap regulatory regime.
Horwitz’s Rule, Transforming Both Sides and the Design of Experiments for Mechanistic Models
Authors: Atkinson Anthony C. 
Published: November 2004

SummaryThe paper develops methods for the design of experiments for mechanistic models when the response must be transformed to achieve symmetry and constant variance. The power transformation that is used is partially justified by a rule in analytical chemistry. Because of the nature of the relationship between the response and the mechanistic model, it is necessary to transform both sides of the model. Expressions are given for the parameter sensitivities in the transformed model and examples are given of optimum designs, not only for single-response models, but also for experiments in which multivariate responses are measured and for experiments in which the model is defined by a set of differential equations which cannot be solved analytically. The extension to designs for checking models is discussed.
A Bounded Influence Regression Estimator Based on the Statistics of the Hat Matrix
Authors: Chave Alan D. , Thomson David J. 
Published: November 2004

SummaryMany geophysical regression problems require the analysis of large (more than 104 values) data sets, and, because the data may represent mixtures of concurrent natural processes with widely varying statistical properties, contamination of both response and predictor variables is common. Existing bounded influence or high breakdown point estimators frequently lack the ability to eliminate extremely influential data and/or the computational efficiency to handle large data sets. A new bounded influence estimator is proposed that combines high asymptotic efficiency for normal data, high breakdown point behaviour with contaminated data and computational simplicity for large data sets. The algorithm combines a standard M-estimator to downweight data corresponding to extreme regression residuals and removal of overly influential predictor values (leverage points) on the basis of the statistics of the hat matrix diagonal elements. For this, the exact distribution of the hat matrix diagonal elements pii for complex multivariate Gaussian predictor data is shown to be β(pii, m, N−m), where N is the number of data and m is the number of parameters. Real geophysical data from an auroral zone magnetotelluric study which exhibit severe outlier and leverage point contamination are used to illustrate the estimator’s performance. The examples also demonstrate the utility of looking at both the residual and the hat matrix distributions through quantile–quantile plots to diagnose robust regression problems.
An Extreme Value Analysis for the Investigation into the Sinking of the M. V. Derbyshire
Authors: Heffernan Janet E. , Tawn Jonathan A. 
Published: November 2004

Summary
The paper describes our involvement in the high court reopened formal investigation into the sinking of the bulk carrier M. V. Derbyshire. The statistical problem that we addressed concerned the estimation of the probability that the ship had sunk from a particular form of structural failure, resulting from large wave impacts on the ship, for each of a range of possible sea-state and vessel conditions. We considered several statistical models for the wave impacts on the ship with the generalized Pareto distribution, motivated by extreme value theory, providing an excellent description and aiding the investigation to draw clear conclusions about the cause of the sinking.
Randomization Tests for Small Samples: An Application for Genetic Expression Data
Authors: Gadbury Gary L. , Page Grier P. , Heo Moonseong , Mountz John D. , Allison David B. 
Published: November 2004

SummaryAn advantage of randomization tests for small samples is that an exact P-value can be computed under an additive model. A disadvantage with very small sample sizes is that the resulting discrete distribution for P-values can make it mathematically impossible for a P-value to attain a particular degree of significance. We investigate a distribution of P-values that arises when several thousand randomization tests are conducted simultaneously using small samples, a situation that arises with microarray gene expression data. We show that the distribution yields valuable information regarding groups of genes that are differentially expressed between two groups: a treatment group and a control group. This distribution helps to categorize genes with varying degrees of overlap of genetic expression values between the two groups, and it helps to quantify the degree of overlap by using the P-value from a randomization test. Moreover, a statistical test is available that compares the actual distribution of P-values with an expected distribution if there are no genes that are differentially expressed. We demonstrate the method and illustrate the results by using a microarray data set involving a cell line for rheumatoid arthritis. A small simulation study evaluates the effect that correlated gene expression levels could have on results from the analysis.
Women at Sea: An Other Category
Authors: Stanley Jo 
Published: November 2004

Books reviewed in this article:David Cordingly, Women Sailors and Sailors’ Women: An Untold Maritime HistoryJoan Druett, She Captains: Heroines and Hellions of the SeaLizabeth Paravisini–Gebert and Ivette Romero–Cesareo (eds), Women at Sea: Travel Writing and the Margins of Caribbean DiscourseSena Jeter Naslund, Ahab's Wife or The Star–GazerNancy Pagh, At Home Afloat: Women on the waters of the Pacific North–WestDee Pigneguy, Saltwater in Her Hair: Stories of women in the New Zealand maritime industry
An Applied Econometricians' View of Empirical Corporate Governance Studies
Authors: Börsch-Supan Axel , Köke Jens 
Published: November 2004

Abstract
The economic analysis of corporate governance is in vogue. In addition to a host of theoretical papers, an increasing number of empirical studies analyze how ownership structure, capital structure, board structure, and the market for corporate control influence firm performance. This is not an easy task, and indeed, for reasons explained in this survey, empirical studies on corporate governance have more than the usual share of econometric problems. This paper is a critical survey of the recent empirical literature on corporate governance - to show which methodological lessons can be learned for future empirical research in the field of corporate governance, paying particular attention to German institutions and data availability.
The Dialectics of Redemption. Autonomous Language, Heresy and Divine Truth in Francisco de Quevedo's Dream of Hell
Authors: Kluge Sofie 
Published: November 2004

The present article proposes a reading of ‘El sueño del infierno’ that may clarify the connection between at least some of the diverse elements of Quevedo's strange world, concentrating on the relation between his ubiquitous awareness of the arbitrarity of human language — separated from divine truth after the Fall, and hence autonomous — and his quest for authoritative metaphysical meaning.Man is the shadow of a dream. (Pindar,Pythian Odes, 8.135)
Adjuvant guided polarization of the immune humoral response against a protective multicomponent antigenic protein (Q) from Leishmania infantum. A CpG + Q mix protects Balb/c mice from infection
Authors: Parody N. , Soto M. , Requena J. M. , Alonso C. 
Published: November 2004

SUMMARY It has been shown that vaccination with three doses of the Leishmania infantum poly‐protein Q containing five genetically fused antigenic determinants from the Lip2a, Lip2b, H2A and P0 proteins, mixed with BCG induces clearance of parasites in 9 out of 10 Leishmania infantum‐infected Beagle dogs, in addition to clinical protection. In the present paper we analysed the immunogenic potential of the poly‐protein Q and the specificity and polarization of the response against the antigenic determinants of Q when mixed with various adjuvants. The data showed that the Q protein had high intrinsic immunogenic potential and that it was able to induce a long‐lasting IgG response. The IgM immunogenic potential of the poly‐protein was mainly due to the LiP2a and LiP2b determinants, whereas the IgG immunogenic potential was mainly due to the LiP2a component. It was observed that the protein itself elicited a mixed IgG2a/IgG1 response and that the determinants of Q were endowed with different IgG2a/IgG1 potential. It was also observed that the adjuvants did not influence the intensity or specificity of the IgM response but that they modulated the intensity, the specificity and the polarization of the IgG response against the determinants of Q. CpG‐ODN motifs or double‐stranded DNA plasmids containing CpG motifs when mixed with Q induced a predominant IgG2a response mainly observed at early stages post‐immunization. The data showed that a CpG + Q mix induced significant protection against L. infantum infection in Balb/c mice.
Modulation of Cytokine Release by Differentiated CACO‐2 Cells in a Compartmentalized Coculture Model with Mononuclear Leucocytes and Nonpathogenic Bacteria
Authors: Parlesak A. , Haller D. , Brinz S. , Baeuerlein A. , Bode C. 
Published: November 2004

AbstractTo further investigate the interaction between human mononuclear leucocytes [peripheral blood mononuclear cells (PBMC)] and enterocytes, the effect of a confluent layer of differentiated CACO‐2 cells on cytokine kinetics during challenge with bacteria in a compartmentalized coculture model was investigated. Nonpathogenic Escherichia coli were added either to the apical or the basolateral compartment of this transwell cell culture system, the latter of which contained human leucocytes. The synthesis of tumour necrosis factor (TNF‐α) and interleukin (IL)‐12 was significantly suppressed by CACO‐2 cells when leucocytes were stimulated directly with bacteria. This suppression was not paralleled by changes in the production of IL‐10, IL‐6 and transforming growth factor (TGF)‐β. When the bacteria were applied apically to the CACO‐2 cell layer, the production of TNF‐α, IL‐12, IL‐1β, IL‐8, IL‐6, IL‐10, TGF‐β and interferon‐γ was pronouncedly lower as compared to the bacterial stimulation of leucocytes beneath the CACO‐2 cells. In the latter experiments, IL‐6, IL‐8 and TNF‐α were the cytokines being mostly induced by apical addition of E. coli. Quantitative mRNA expression analysis revealed that IL‐8 gene expression was equally induced in both CACO‐2 and PBMC after apical stimulation with bacteria. Of note, bacteria‐stimulated CACO‐2 cells produced little or no cytokines in the absence of leucocytes, supporting the concept of leucocyte–epithelial cell cross‐talk in modulating cytokine responses in the gut mucosa.
Differential Expression of the C5a Receptor and Complement Receptors 1 and 3 after LPS Stimulation of Neutrophils and Monocytes
Authors: Furebring M. , Håkansson L. , Venge P. , Sjölin J. 
Published: November 2004

AbstractAnimal experiments recently suggested that administration of anti‐C5a, anti‐C5a receptor or soluble complement receptor type‐1 may be of value in the treatment of septic shock. Because results regarding C5a receptor expression (C5a‐R, CD‐88) have been found to differ between septic animals and patients, the aim of this study was to investigate the neutrophil and monocyte receptor expression of CD‐88 and complement receptor‐1 (CR‐1, CD‐35) after stimulation with lipopolysaccharide (LPS) ex vivo.Whole blood or isolated neutrophils and monocytes from healthy people were incubated with LPS in a dose range of 0.1–1000 ng/ml. The expressions of CD‐88 and CD‐35 were analysed by means of flow cytometry. For comparison, the expressions of complement receptor‐3 (CR‐3, CD‐11b/CD‐18), Fc‐γ receptor type‐I (CD‐64) and CEACAM‐8 (CD‐66b) were also investigated.In whole blood, CD‐88 expression on neutrophils was reduced (P < 0.05). The expressions of CD‐35 and CD‐11b were increased both on neutrophils (P < 0.001; P < 0.05) and on monocytes (P < 0.001; P < 0.001). No effect was observed on isolated cells.In agreement with the findings in septic patients, LPS reduced the neutrophil C5a‐R expression, whereas the expressions of CR‐1 and CR‐3 were increased. The effects of LPS were indirect and were mediated via factors in the blood. The clinical significance of this is not known, but may be associated with decreased chemotaxis.
Modulation of CD28 and CD86 Expression in Patients with Paracoccidioidomycosis in Different Periods of Treatment
Authors: Bozzi A. , Reis B. S. , Prado F. L. S. , Pedroso E. P. , Leite M. F. , Goes A. M. 
Published: November 2004

Abstract Paracoccidioides brasiliensis, a thermo‐dimorphic fungus, is the ethiologic agent of paracoccidioidomycosis (PCM). The recidive is the greatest obstacle of this disease, because the yeast usually returns after the long treatment period. In the present work, we have investigated the cellular immune response of cells from peripheral blood drawn from patients with different duration of PCM. The classification of patients ranged from nontreated to those with long‐standing disease over 5 years. Unstimulated as well as cells stimulated with phytohemaglutinin or two different antigen preparations, secreted (MEXO) or somatic (PbAg) of P. brasiliensis, were characterized. We found that cells from patients with disease proliferate considerably upon stimulation with the antigen preparations and that cells from patients with disease of long duration does not proliferate that vigorously as from patients with more recent diagnosis. Both interferon (IFN)‐γ and interleukin (IL)‐4 appear to be increased in patients, but IFN‐γ tended to increase upon treatment while IL‐4‐secretion decreased. With respect to CD28 and CD86, we found that the subset of CD28 positive CD8 cells are decreased in all stages of the disease as compared to control individuals. A subset of CD86 positive CD19 cells appeared to be considerably increased compared to the controls. Indeed, our results demonstrated that the treatment of PCM patients promoted a regulation of IFN‐γ, IL‐4 levels and CD28, CD86 expression bringing new insight to the cellular immune response in PCM.
Differential Adherence of Osteoarthritis and Rheumatoid Arthritis Synovial Fibroblasts to Cartilage and Bone Matrix Proteins and its Implication for Osteoarthritis Pathogenesis
Authors: Schedel J. , Wenglén C. , Distler O. , Müller‐Ladner U. , Schölmerich J. , Heinegård D. , Krenn V. 
Published: November 2004

AbstractIn osteoarthritis (OA), cartilage and bone fragments have been described within the synovial tissue which are surrounded by synovial cells (i.e. detritus synovitis). These cells appear to attach actively to the cartilage and bone fragments. In rheumatoid arthritis (RA), on the other hand, synovial fibroblasts (SF) have also been shown to be localized at sites of invasion into cartilage and bone and to degrade extracellular matrix (ECM) by secreting proteolytic enzymes. One prerequisite for exerting their aggressive properties is the attachment to cartilage and bone ECM. This attachment appears to be mediated by the expression of different adhesion molecules for which corresponding binding sites on ECM components are known. As it has not been addressed to which ECM proteins SF adhere and with which affinity this process takes place, we investigated the adherence of SF from patients with OA and RA to different cartilage and bone matrix proteins. Synovial tissue samples were obtained during synovectomy or arthroplastic surgery and used for isolating and culturing SF. Synovial cells attaching to cartilage/bone fragments were characterized using immunohistochemistry. The adherence of SF to ECM proteins was examined using an adhesion assay with the following proteins coated on 96‐well plates: aggrecan (AGG), bone sialoprotein (BSP), cartilage oligomeric matrix protein (COMP), collagen type I, II and VI, proline arginine‐rich, end leucine‐rich repeat protein (PRELP), osteopontin (OPN) and recombinant chondroadherin (CHAD). Bovine serum albumin was used as negative control. In addition, adhering fibroblasts were photographed using a phase‐contrast microscope. As compared with RA‐SF, significantly higher numbers of OA‐SF adhering to collagen type II, OPN and CHAD could be detected (P < 0.05). In contrast, RA‐SF showed increased attachment to collagen type II, OPN and BSP. Adhesion to AGG, COMP and PRELP appeared not to be significantly increased and differed widely among the SF samples, and, apart from one exception (BSP), OA‐SF adhered in higher numbers to the matrix proteins than did RA‐SF. Using immunohistochemistry, synovial cells attached to cartilage/bone fragments could be shown to predominantly express CD68 (≥50%). The CD68‐negative population was of the fibroblast phenotype (AS02 positive). The study demonstrates that the binding pattern of OA‐SF and RA‐SF to ECM proteins differs considerably and therefore provides novel insights into the difficult pathophysiology of OA and RA. In general, it appeared that SF adhere primarily to ECM proteins that contain known binding sites for adhesion molecules (e.g. integrins: collagen/integrin α2β1) and that higher numbers of OA‐SF adhered to the cartilage and bone matrix proteins than did RA‐SF.
High‐Polarity Mycobacterium avium‐Derived Lipids Interact with Murine Macrophage Lipid Rafts
Authors: Maldonado‐García G. , Chico‐Ortiz M. , Lopez‐Marin L. M. , Sánchez‐García F. J. 
Published: November 2004

AbstractCholesterol‐ and sphingolipid‐rich membrane microdomains (lipid rafts) are widely recognized as portals for pathogenic micro‐organisms. A growing body of evidence demonstrates mobilization of host plasma cell membrane lipid rafts towards the site of contact with several pathogens as well as a strict dependence on cholesterol for appropriate internalization. The fate of lipid rafts once the pathogen has been internalized and the nature of the pathogen components that interact with them is however less understood. To address both these issues, infection of the J774 murine cell line with Mycobacterium avium was used as a model. After demonstrating that M. avium induces lipid raft mobilization and that M. avium infects J774 by a cholesterol‐dependent mechanism, it is shown here that mycobacterial phagosomes harbour lipid rafts, which are, at least in part, of plasma cell membrane origin. On the other hand, by using latex microbeads coated with any of the three fractions of M. avium‐derived lipids of different polarity, we provide evidence that high‐polarity, in contrast to low‐polarity and intermediate‐polarity, mycobacterial lipids or uncoated latex beads have a strong capacity to induce lipid raft mobilization. These results suggest that high‐polarity mycobacterial lipid(s) interact with host cell cholesterol‐enriched microdomains which may in turn influence the course of infection.
Distribution of Entamoeba histolytica Gal/GalNAc Lectin‐Specific Antibody Response in an Endemic Area
Authors: Kaur U. , Sharma A. K. , Sharma M. , Vohra H. 
Published: November 2004

AbstractTo demonstrate the dynamics of specific antibody isotypes against Entamoeba histolytica Gal/GalNAc adhesin and its correlation, if any, with the development of immunity, we evaluated subjects suffering from a spectrum of amoebic infections ranging from amoebic liver abscess (ALA) to asymptomatic cyst passers. The quantitative analysis of antibody levels was done in the sera by enzyme‐linked immunosorbent assay. Gal/GalNAc adhesin‐specific immunoglobulin G (IgG) was higher in ALA (and their follow‐ups) and intestinal amoebiasis cases as compared with asymptomatic cyst passers (P < 0.05). Among the isotypes of IgG, high levels of IgG1 (60% of the total IgG concentration), suggestive of T‐helper 2‐type response, was associated with ALA cases. Intestinal amoebiasis cases and cyst passers had high percentage of IgG1 and IgG4 antibodies as compared with per cent IgG2 and IgG3 (of the total IgG), whereas follow‐up cases of ALA had predominantly IgG2 and IgG3 isotypes of antibodies. Gal/GalNAc lectin‐specific IgM antibodies were maximum in cases of intestinal amoebiasis. ALA cases and their follow‐ups had significantly lower levels of Gal/GalNAc‐specific IgM levels as compared with cyst passers (P < 0.05). Gal/GalNAc adhesin‐specific IgA antibodies were raised maximally in intestinal amoebic infection cases. ALA cases and their 3‐month follow‐ups had significantly higher concentrations of lectin‐specific IgA (P < 0.05) as compared with the healthy subjects.
Inflammatory pseudotumor of the spleen with EBV positivity: report of a case
Authors: Oz Puyan F. , Bilgi S. , Unlu E. , Yalcin O. , Altaner S. , Demir M. , Cakir B. 
Published: November 2004

Abstract:Inflammatory pseudotumor (IPT) of the spleen is a rare benign tumor with unknown etiology. It causes problems in the diagnosis because of mimicking some hematopoetic malignancies. Here we report the case of a 36‐yr‐old woman complaining of nausea and insomnia. Laboratory investigations were limited to increase of leukocyte and thrombocyte count. Ultrasonography and magnetic resonance (MR) imaging showed circumscribed solid lobulated mass, measuring about 6.5 cm in diameter, located in the dorsal region of the spleen. Splenectomy was performed with the differential diagnosis including hamartoma and lymphoma of the spleen. Histological examination of the sharply demarcated splenic mass consisted of myofibroblasts and admixture of inflammatory cells. Immunohistochemistry and in situ hybridization were performed. IPT of the spleen was diagnosed. Epstein–Barr virus (EBV) was detected in the tumor by in situ hybridization. This rare entity is presented because of its clinical, radiological and pathological difficulties in the differential diagnosis.