bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene therapy for tissue regeneration
Authors: Cutroneo Kenneth R. 
Published: January 2003

AbstractTissue repair and regeneration are the normal biological responses of many different tissues in the body to injury. During the healing process, profound changes occur in cell composition and extracellular matrix (ECM) formation. Fibroblasts and equivalent reparative cells migrate to the wounded area and subsequently proliferate. These cells and reparative cells from the surrounding tissue are responsible for the rapid repair which results in tissue regeneration. Growth factors, one of which is transforming growth factor‐β (TGF‐β), stimulate fibroblasts and smooth muscle cells to proliferate and synthesize ECM proteins. This process of early repair provides a rapid way to restore new tissue and mechanical integrity. This early tissue repair process is normally followed by involution, which requires the production and activation of proteases, tissue maturation and remodeling, reorganization and finally regeneration. Alternately, failure to replace the critical components of the ECM, including elastin and basement membrane, results in abnormal regeneration of the epithelial cell layer. Although remodeling should occur during healing, provisional repair may be followed by excessive synthesis and deposition of collagen, which results in irreversible fibrosis and scarring. This excessive fibrosis which occurs in aberrant healing is at least in part mediated by persistent TGF‐β. Because of the central role of collagen in the wound healing process, the pharmacological control of collagen synthesis has been of paramount importance as a possible way to abrogate aberrant healing and prevent irreversible fibrosis. Fibrosis is an abnormal response to tissue injury. J. Cell. Biochem. 88: 418–425, 2003. © 2002 Wiley‐Liss, Inc.
HGF/SF‐met signaling in the control of branching morphogenesis and invasion
Authors: Zhang Yu‐Wen , Vande Woude George F. 
Published: January 2003

AbstractHepatocyte growth factor/Scatter factor (HGF/SF) is a multifunctional growth factor which can induce diverse biological events. In vitro, these include scattering, invasion, proliferation and branching morphogenesis. In vivo, HGF/SF is responsible for many processes during embryonic development and a variety of activities in adults, and many of these normal activities have been implicated in its role in tumorgenesis and metastasis. The c‐Met receptor tyrosine kinase is the only known receptor for HGF/SF and mediates all HGF/SF induced biological activities. Upon HGF/SF stimulation, the c‐Met receptor is tyrosine‐phosphorylated which is followed by the recruitment of a group of signaling molecules and/or adaptor proteins to its cytoplasmic domain and its multiple docking sites. This action leads to the activation of several different signaling cascades that form a complete network of intra and extracellular responses. Different combinations of signaling pathways and signaling molecules and/or differences in magnitude of responses contribute to these diverse series of HGF/SF‐Met induced activities and most certainly are influenced by cell type as well as different cellular environments. In this review, we focus on HGF/SF‐induced branching morphogenesis and invasion, and bring together recent new findings which provide insight into how HGF/SF, via c‐Met induces this response. J. Cell. Biochem. 88: 408–417, 2003. © 2002 Wiley‐Liss, Inc.
Intestinal calcium absorption: Molecular vitamin D mediated mechanisms
Authors: Bouillon R. , Van Cromphaut S. , Carmeliet G. 
Published: January 2003

AbstractRickets and hyperparathyroidism caused by a defective Vitamin D receptor (VDR) can be prevented in humans and animals by high calcium intake, suggesting that intestinal calcium absorption is critical for 1,25(OH)2 vitamin D [1,25‐(OH)2D3] action on calcium homeostasis. We assessed the rate of serum 45Ca accumulation within 10 min after oral gavage in two strains of VDR‐knock out (KO) mice (Leuven and Tokyo KO) and observed a threefold lower area under the curve in both KO‐strains. Moreover, we evaluated the expression of intestinal candidate genes, belonging to a new class of calcium channels (TRPV), involved in transcellular calcium transport. The calcium transport protein ECaC2 was more abundantly expressed at mRNA level than ECaC1 in duodenum, but both were considerably reduced (ECaC2 > 90%, ECaC1 > 60%) in the two VDR‐KO strains on a normal calcium diet. Calbindin‐D9K expression was only significantly decreased in the Tokyo KO, whereas PMCA1b expression was normal in both VDR‐KOs. In Leuven wild type mice, a high calcium diet inhibited (> 90%), and 1,25(OH)2D3 or low calcium diet induced (sixfold) duodenal ECaC2 expression and, to a lesser degree, ECaC1 and calbindin‐D9K expression. In Leuven KO mice, however, high or low calcium intake decreased calbindin‐D9K and PMCA1b expression, whereas both ECaC mRNA expressions remained consistently low on any diet. These results suggest that the expression of the novel duodenal epithelial calcium channels (in particular ECaC2 or TRPV6) is strongly vitamin D dependent and that calcium influx, probably interacting with calbindin‐D9K, should be considered as a rate‐limiting step in the process of vitamin D dependent active calcium absorption. J. Cell. Biochem. 88: 332–339, 2003. © 2002 Wiley‐Liss, Inc.
Functional‐adaptive anatomy of the axial skeleton of some extant marsupials and the paleobiology of the paleocene marsupials mayulestes ferox and pucadelphys andinus
Authors: Argot Christine 
Published: January 2003

AbstractIn this study, the axial skeletons of two Early Paleocene marsupials, Mayulestes ferox and Pucadelphys andinus, were analyzed functionally and compared to that of six South American and three Australian species of extant marsupials. In the case of the South American opossums, myological data of the epaxial musculature were collected and analyzed and osteological‐myological associations were related to locomotor behavior. Various features of the vertebral column that relate to diet or to locomotor or postural patterns were pointed out. These features include: the craniocaudal development of the neural process of the axis; the position of the anticlinal vertebra; the morphology of the neural processes of the thoracolumbar vertebrae (orientation, length, and craniocaudal width); the length, orientation, and curvature of the transverse processes of the lumbar vertebrae; and the length and robustness of the caudal vertebrae. In both fossil forms the vertebral column is mobile and allows a great range of flexion and extension of the spine, more so than in most of the living didelphids. It is emphasized here that the analysis of the axial skeleton complements and improves the conclusions provided by the forelimb and hindlimb analyses. It is proposed that Mayulestes and Pucadelphys represent an ancestral morphotype suggesting that the generalized type of locomotion of Paleocene marsupials was partly terrestrial with some climbing ability. J. Morphol. 255:279–300, 2003. © 2003 Wiley‐Liss, Inc.
Anatomy and histology of the brain and sense organs of the antarctic plunderfish dolloidraco longedorsalis (perciformes: notothenioidei: artedidraconidae), with comments on the brain morphology of other artedidraconids and closely related harpagiferids
Authors: Eastman Joseph T. , Lannoo Michael J. 
Published: January 2003

AbstractIn the high‐latitude shelf waters of Antarctica, fishes in the perciform suborder Notothenioidei dominate the fish fauna and constitute an adaptive radiation and a species flock. The 25 species of notothenioid plunderfishes, comprising four genera of the family Artedidraconidae, contribute substantially to fish species diversity on the high Antarctic shelf. A mental barbel is an autapomorphy for the family. Dolloidraco longedorsalis is the most abundant artedidraconid at depths over 400 m in these waters. In this article we present the anatomy and histology of the brain and special sense organs of Dolloidraco and compare it to the brains of other artedidraconids, closely related harpagiferids, and more generally to other notothenioids. We provide a detailed drawing of the brain and cranial nerves. The brain of Dolloidraco is simple, without external hypertrophy of sensory or motor regions, but contains several unusual features associated with the ventricular system and CSF, including well‐developed circumventricular organs, subependymal expansions, and subarachnoid cisterns; and a ventricle in the corpus cerebellum. The brain of Dolloidraco also contains a lobed chief sensory nucleus of the trigeminal nerve that is correlated across species with barbel length. The eyes are large and contain a small choroid rete, a structure previously thought to be absent from members of this family. We document the histology of the duplex retina, olfactory apparatus, cutaneous taste buds, and barbel musculature and innervation. We discuss the role of pedomorphy in producing simplified brain morphologies. We consider the possibility that Dolloidraco is a somatosensory specialist—an unusual feature among vertebrates—and decide that this is unlikely. J. Morphol. 255:358–377, 2003. © 2003 Wiley‐Liss, Inc.
Kuramoto–sivashinsky model for a dusty medium
Authors: Doronin G. G. , Larkin N. A. 
Published: January 2003

AbstractThe initial and initial‐boundary value problems for the Kuramoto–Sivashinsky model of “fluid‐solid particles” media are considered. Existence, uniqueness and asymptotic behaviour of strong solutions are proved. Copyright © 2003 John Wiley & Sons, Ltd.
Exact unconditional tests for testing non‐inferiority in matched‐pairs design
Authors: Sidik Kurex 
Published: January 2003

AbstractThe problem of testing non‐inferiority in a 2 × 2 matched‐pairs sample is considered. Two exact unconditional tests based on the standard and the confidence interval p‐values are proposed. Although tests of non‐inferiority have two nuisance parameters under the null hypothesis, the exact tests are defined by reducing the dimension of nuisance parameter space from two to one using the monotonicity of the distribution. The exact sizes and powers of these tests and the existing asymptotic test are considered. The exact tests are found to be accurate in view of their size property. In addition, the exact test based on the confidence interval p‐value is more powerful than the other exact test. It is shown that the asymptotic test is inaccurate, that is, its size exceeds the claimed nominal level α. Therefore, it recommends a cautious approach in use of the asymptotic test for the problem of testing non‐inferiority, particularly when sample sizes are small or moderately large. Copyright © 2003 John Wiley & Sons, Ltd.
TACT method for non‐inferiority testing in active controlled trials
Authors: Wang Sue‐Jane , James Hung H. M. 
Published: January 2003

Abstract In active controlled trials without a placebo arm, non‐inferiority testing is often considered but has different objectives. For the objective of demonstrating the efficacy of an experimental treatment or retention of a fraction of the control effect by the treatment, there are two types of statistical methods for testing – the synthesis method and the confidence interval method. According to the study of Wang, Hung and Tsong, the former is efficient under the so‐called constancy condition but may have the alpha error rate inflate rapidly if the condition does not hold. In contrast, the latter method with careful selection of the non‐inferiority margin tends to be conservative if the condition holds and may still have a valid alpha error otherwise unless the effect of the active control is less to a large extent in the active controlled trial than in the historical trials. We developed the TACT method, Two‐stage Active Control Testing, as a viable compromise between the two methods. Through the TACT method, the uninterpretable non‐inferiority testing may be avoided prior to the end of the trial. The TACT method carefully constructed can have a valid alpha error rate and the power close to the synthesis method if the constancy condition holds. In addition, the TACT method is more powerful than the confidence interval method for testing for the efficacy of the new treatment relative to the putative placebo and for showing that the new treatment is not inferior to the active control comparator. Copyright © 2003 John Wiley & Sons, Ltd.
Application of models for multivariate mixed outcomes to medical device trials: coronary artery stenting
Authors: O'Malley A. James , Normand Sharon‐lise T. , Kuntz Richard E. 
Published: January 2003

AbstractThe approval process for some medical devices involves a single‐arm trial in which the outcomes associated with the new device are compared to the expected outcomes associated with approved devices, the latter denoted the objective performance criterion (OPC). In this paper, models for multivariate mixed outcomes are applied to derive the OPC for a medical device to be used in clinical evaluations of the same type of device. We illustrate the techniques by determining the OPC for coronary artery stents, metal cages used to widen blocked coronary arteries in patients with coronary artery disease, using data from seven randomized trials of stents approved for use in the U.S.A. involving 5806 patients. The OPC is based on two 9‐month endpoints: target lesion revascularization, a binary outcome, and proportion diameter stenosis, a continuous outcome. To account for the correlation between mixed outcomes we consider factorization of the likelihood into marginal and conditional components, or adoption of a latent variable model. Because the models have different structural forms, standard methods for model comparison (such as the AIC and BIC) cannot be used. We discuss how model identifiability and valid inference are achieved, and then adapt the deviance information criterion (DIC) and the pseudo‐Bayes factor (PSBF) to select the best model. Nine months post‐stenting, we find that the average posterior probability (standard deviation) of target lesion revascularization ranges from 0.086 (0.008) for non‐diabetics with one diseased vessel to 0.163 (0.022) for diabetics with three diseased vessels. When considering proportion diameter stenosis, the corresponding posterior means are 0.375 (0.020) and 0.427 (0.030). The correlation coefficient of the components of the OPC lies in the range 0.042 to 0.116. Copyright © 2003 John Wiley & Sons, Ltd.
Design and analysis of non‐inferiority mortality trials in oncology
Authors: Rothmann Mark , Li Ning , Chen Gang , Chi George Y. H. , Temple Robert , Tsou Hsiao‐Hui 
Published: January 2003

AbstractThe recent revision of the Declaration of Helsinki and the existence of many new therapies that affect survival or serious morbidity, and that therefore cannot be denied patients, have generated increased interest in active‐control trials, particularly those intended to show equivalence or non‐inferiority to the active‐control. A non‐inferiority hypothesis has historically been formulated in terms of a fixed margin. This margin was historically designed to exclude a ‘clinically meaningful difference’, but has become recognized that the margin must also be no larger than the assured effect of the control in the new study. Depending on how this ‘assured effect’ is determined or estimated, the selected margin may be very small, leading to very large sample sizes, especially when there is an added requirement that a loss of some specified fraction of the assured effect must be ruled out. In cases where it is appropriate, this paper proposes non‐inferiority analyses that do not involve a fixed margin, but can be described as a two confidence interval procedure that compares the 95 per cent two‐sided CI for the difference between the treatment and the control to a confidence interval for the control effect (based on a meta‐analysis of historical data comparing the control to placebo) that is chosen to preserve a study‐wide type I error rate of about 0.025 (similar to the usual standard for a superiority trial) for testing for retention of a prespecified fraction of the control effect. The approach assumes that the estimate of the historical active‐control effect size is applicable in the current study. If there is reason to believe that this effect size is diminished (for example, improved concomitant therapies) the estimate of this historical effect could be reduced appropriately. The statistical methodology for testing this non‐inferiority hypothesis is developed for a hazard ratio (rather than an absolute difference between treatments, because a hazard ratio seems likely to be less population dependent than the absolute difference). In the case of oncology, the hazard ratio is the usual way of comparing treatments with respect to time to event (time to progression or survival) endpoints. The proportional hazards assumption is regarded as reasonable (approximately holding). The testing procedures proposed are conditionally equivalent to two confidence interval procedures that relax the conservatism of two 95 per cent confidence interval testing procedures and preserve the type I error rate at a one‐sided 0.025 level. An application of this methodology to Xeloda, a recently approved drug for the treatment of metastatic colorectal cancers, is illustrated. Other methodologies are also described and assessed – including a point estimate procedure, a Bayesian procedure and two delta‐method confidence interval procedures. Published in 2003 by John Wiley & Sons, Ltd.
Identifying high maintenance legacy software
Authors: Harrison Matthew S. , Walton Gwendolyn H. 
Published: January 2003

AbstractLegacy software maintenance is a significant cost item for many engineering organizations. This study is a preliminary report on work to investigate maintenance data, usage, and source code for legacy software used by an engineering design company to support a variety of functions, including electromagnetic, thermal, mechanical loading, vibration, and aerodynamic analysis. The results verify the applicability to legacy engineering software of previous research that concluded that size and structural metrics alone are not good indicators of high maintenance costs. Unlike previous research, the study also evaluates the effect of program usage on maintenance cost. Over the three‐year period of this study of 71 legacy engineering programs, 11 of the programs (15%) accounted for 80% of all maintenance and 67% of all program runs. The highest maintenance programs were not always the largest programs or the worst structured programs. 49% of the programs accounted for only 1% of total maintenance but 42% of the total lines of code (LOC) thus invalidating LOC as an indicator for maintenance cost. While additional work is needed to validate these findings across other organizations and other code sets, these preliminary results provide strong evidence that expected program usage can be a useful indicator of long‐term maintenance cost. Copyright © 2002 John Wiley & Sons, Ltd.
A model of factors affecting an information system's change in state
Authors: Heales Jon 
Published: January 2003

AbstractManagement are keen to maximize the life span of an information system because of the high cost, organizational disruption, and risk of failure associated with the re‐development or replacement of an information system. This research investigates the effects that various factors have on an information system's life span by understanding how the factors affect an information system's stability. The research builds on a previously developed two‐stage model of information system change whereby an information system is either in a stable state of evolution in which the information system's functionality is evolving, or in a state of revolution, in which the information system is being replaced because it is not providing the functionality expected by its users.A case study surveyed a number of systems within one organization. The aim was to test whether a relationship existed between the base value of the volatility index (a measure of the stability of an information system) and certain system characteristics. Data relating to some 3000 user change requests covering 40 systems over a 10‐year period were obtained. The following factors were hypothesized to have significant associations with the base value of the volatility index: language level (generation of language of construction), system size, system age, and the timing of changes applied to a system. Significant associations were found in the hypothesized directions except that the timing of user changes was not associated with any change in the value of thevolatility index. Copyright © 2002 John Wiley & Sons, Ltd.
Three new species of the genus Dactylospora in Spain
Authors: Sarrión F. J. , Hafellner J. , Burgaz A. R. 
Published: January 2003

AbstractThree species of the genus Dactylospora, D. crassa Sarrion & Hafellner, D. mediterranea Sarrión & Hafellner, and D. pseudourceolata Sarrión & Hafellner are described as new from Spain. The morphology, anatomy, and ecology of the three taxa are discussed. A key to the Spanish Dactylospora species is provided.
The Parmeliaceae (Lichenized Ascomycota) of New Caledonia
Authors: Louwhoff Simone H. J. J. , Elix John A. 
Published: January 2003

AbstractA key to forty-one species in ten parmelioid genera [Bulbothrix (4 spp.), Canoparmelia (1 sp.), Hypotrachyna (7 spp.), Myelochroa (1 sp.), Parmelina (2 spp.), Parmelinopsis (1 sp.), Parmotrema (18 spp.), Relicina (2 spp.), Rimelia (3 spp.) and Xanthoparmelia (2 spp.)] from New Caledonia is provided, in addition to brief taxonomic descriptions as well as notes on distribution. Five of the forty-one species are endemic to New Caledonia, and thirteen are new records for the island. Several old names used in the literature are clarified.
The occurrence of biomineralization products in four lichen species growing on sandstone in western Norway
Authors: Bjelland Torbjørg , Sæbø Linda , Thorseth Ingunn H. 
Published: January 2003

AbstractHigh performance thin-layer chromatography/thin-layer chromatography, X-ray diffraction, and scanning electron microscopy analysis of thallus and lichen-rock interface samples, were undertaken to characterize biomineralization products in Fuscidea cyathoides, Ochrolechia tartarea, Ophioparma ventosa, and Pertusaria coralline, growing on sandstone in western Norway. Whewellite (monohydrate form of Ca oxalate) was found in the thallus of all species, but not in any of the weathering rinds beneath the species. A significantly higher amount of whewellite was detected in the thalli of F. cyathoides and O. ventosa than in the other two species. There were only a few differences in whewellite occurrence between the thallus edge and centre samples in the four species. HPTLC/TLC and SEM analysis indicate that lichen compounds occur within the rock beneath some of the lichen specimens. Only divaricatic acid was observed within the weathering rind beneath O. ventosa. No lichen substances were found in the weathering rind beneath F. cyathoides and P. corallina, whereas gyrophoric and lecanoric acids were found in the weathering rind beneath O. tartarea.