bluuebunny/crossref_metadata_2025 huggingface dataset:
Low pass filter/over drop avoidance (LPF/ODA): an algorithm to improve the response time of RED gateways
Authors: Zheng Bing , Atiquzzaman Mohammed
Published: January 2003

The low pass filter (LPF) algorithm, which is used to calculate the average queue length in the random early detection (RED) algorithm, results in a poor response time when RED recovers from congestion. In this paper, we propose a new algorithm, called low pass filter/over drop avoidance (LPF/ODA), to improve the response time of RED. LPF/ODA is based on reducing the time required by RED to recover from long‐term congestion. Simulation results have been used to show that the proposed LPF/ODA algorithm significantly improves the response time, throughput and delay of RED gateways. Copyright © 2002 John Wiley & Sons, Ltd.
Using TCP rate control for queue input‐output rate matching
Authors: Aweya James , Ouellette Michel , Montuno Delfin Y.
Published: January 2003

In explicit TCP rate control, the receiver's advertised window size in acknowledgment (ACK) packets can be modified by intermediate network elements to reflect network congestion conditions. The TCP receiver's advertised window (i.e. the receive buffer of a TCP connection) limits the maximum window and consequently the throughput that can be achieved by the sender. Appropriate reduction of the advertised window can control the number of packets allowed to be sent from a TCP source. This paper evaluates the performance of a TCP rate control scheme in which the receiver's advertised window size in ACK packets are modified in a network node in order to match the generated load to the assigned bandwidth in the node. Using simulation and performance metrics such as the packet loss rates and the cumulative number of TCP timeouts, we examine the service improvement provided by the TCP rate control scheme to the users. The modified advertised windows computed in the network elements and the link utilization are also examined. Copyright © 2002 John Wiley & Sons, Ltd.
Computer visualization and participatory ergonomics as methods in workplace design
Authors: Sundin A. , Medbo L.
Published: January 2003

This case study was carried out at a Volvo plant in Sweden where manual material handling was done in the form of kitting materials for manual assembly workstations. Due to inefficiency as well as ergonomics factors, the management planned a redesign of the kitting area. A group of workers and researchers was formed and a participatory ergonomic approach was used in which 3D CAD visualization presented solutions. Production and mechanical exposure data were used as input to the group. The results showed that the use of computerized visualization was successful in improving participatory ergonomic work. However, characteristics of visualization software, for example, including animation and manikins, seem to be important for reaching improvements. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 1–17, 2003.
An integrated methodology for manufacturing systems design using manual and computer simulation
Authors: Paquet Victor , Lin Li
Published: January 2003

Traditional approaches to manufacturing systems design utilize a sequential procedure that focuses on production capacity requirements, with human operator task design developed late in the systems design phase. Implementing manufacturing systems in this way is difficult when operations management must design flexible and efficient processes, with an often incomplete understanding of how people can best perform within the system. This study developed an integrated methodology that uses both manual and computer simulations to evaluate system performance and ergonomic issues early in the system design process. Information about operator performance and ergonomics is obtained in the manual simulations, while estimates of operator utilization and system throughput is obtained through computer simulations. An iterative design process is used, with the results of manual and computer simulations informing each other during subsequent simulations. An industrial case study is presented here to demonstrate the effectiveness of this methodology. The results show that the methodology can be used to design manufacturing systems with significant savings in labor cost and improved manufacturing system flexibility. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 19–40, 2003.
Ergonomic weighted scores to evaluate critical instructions for improvements in a printed circuit assembly factory
Authors: Sen Rabindra Nath , Yeow Paul H.P.
Published: January 2003

A survey was conducted on the efficacy of the Printed Circuit Assembly operations using newly designed Ergonomic Weighted Scores (EWSs) to evaluate Critical Instructions (CIs) to operators. This helped to choose priorities of problematic operations. Five EWSs were drafted, tried, and finalized by a team of experts, for the purpose of checking the adherence to CIs, failing any of which could cause adverse effects on the quality of products. The top three priority operations were identified and the follow‐up studies resulted in an increase in monthly revenue of US$227,880 and improvements in quality, productivity, occupational health and safety of the operators. © 2003 Wiley Periodicals, Inc. Hum Factors Man 13: 41–58, 2003.
Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases
Authors: Adorini Luciano , Penna Giuseppe , Giarratana Nadia , Uskokovic Milan
Published: January 2003

Dendritic cells (DCs) not only induce but also modulate T cell activation. 1,25‐dihydroxyvitamin D3[1,25(OH)2D3] induces DCs with a tolerogenic phenotype, characterized by decreased expression of CD40, CD80, and CD86 costimulatory molecules, low IL‐12 and enhanced IL‐10 secretion. We have found that a short treatment with 1,25(OH)2D3induces tolerance to fully mismatched mouse islet allografts that is stable to challenge with donor‐type spleen cells and allows acceptance of donor‐type vascularized heart grafts. This effect is enhanced by co‐administration of mycophenolate mofetil (MMF), a selective inhibitor of T and B cell proliferation that has also effects similar to 1,25(OH)2D3on DCs. Graft acceptance is associated with an increased percentage of CD4+CD25+regulatory cells in the spleen and in the draining lymph node that can protect 100% of syngeneic recipients from islet allograft rejection. CD4+CD25+cells, able to inhibit the T cell response to a pancreatic autoantigen and to significantly delay disease transfer by pathogenic CD4+CD25−cells, are also induced by treatment of adult nonobese diabetic (NOD) mice with 1,25‐dihydroxy‐16,23Z‐diene‐26,27‐hexafluoro‐19‐nor vitamin D3(BXL‐698). This treatment arrests progression of insulitis and Th1 cell infiltration, and inhibits diabetes development at non‐hypercalcemic doses. The enhancement of CD4+CD25+regulatory T cells, able to mediate transplantation tolerance and to arrest type 1 diabetes development by a short oral treatment with VDR ligands, suggests possible clinical applications of this approach. J. Cell. Biochem. 88: 227–233, 2003. © 2002 Wiley‐Liss, Inc.
Regulation of 25‐hydroxyvitamin D3‐24‐hydroxylase mRNA by 1,25‐dihydroxyvitamin D3 and parathyroid hormone
Authors: Zierold Claudia , Mings Jamie A. , DeLuca Hector F.
Published: January 2003

The 25‐hydroxyvitamin D3‐24‐hydroxylase mRNA is tightly and reciprocally regulated by 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) and parathyroid hormone (PTH). The upregulation of the 24‐hydroxylase by 1,25(OH)2D3 is well established and occurs at the transcriptional level through two vitamin D response elements in the promoter of the gene. However, this induction is blocked by the protein synthesis inhibitor cycloheximide (CHX) indicating a protein component in the regulation pathway. CHX treatment reduced total vitamin D receptor (VDR) protein levels in cells, but reintroduction of VDR and/or retinoid X receptor protein into cells by transfection did not reduce the inhibition by CHX. This indicates that production of another transcription factor or mRNA‐stabilizing protein synthesized in response to 1,25(OH)2D3 is required for optimal accumulation of 24‐hydroxylase mRNA. PTH downregulates the 24‐hydroxylase mRNA by affecting its stability. The half‐life of 24‐hydroxylase mRNA is reduced 4.2‐fold in AOK‐B50 cells by PTH. Untranslated regions of the 24‐hydroxylase mRNA in reporter gene assays did not confer PTH responsiveness. Further analysis of the coding region of the rat 24‐hydroxylase may reveal sites of action of PTH. J. Cell. Biochem. 88: 234–237, 2003. © 2002 Wiley‐Liss, Inc.
Evidence for tissue‐ and cell‐type selective activation of the vitamin D receptor by Ro‐26‐9228, a noncalcemic analog of vitamin D3
Authors: Peleg Sara , Ismail Ayesha , Uskokovic Milan R. , Avnur Zafrira
Published: January 2003

Our recent studies have shown that the vitamin D analog Ro‐26‐9228 restores bone mineral density without inducing hypercalcemia in osteopenic rats. Our ex vivo experiments demonstrated that the analog upregulated gene expression in trabecular bone but not in the duodenum of female rats. We examined the mechanism for the tissue selectivity of Ro‐26‐9228 in Caco‐2, a human cell line of intestinal origin, and hFOB, and a human fetal osteoblast cell line. We found that the abilities of Ro‐26‐9228 and the natural hormone, 1,25‐dihydroxyvitamin D3 (1,25D3) to induce VDRE‐reporter gene expression in transiently transfected human osteoblasts are similar. In contrast, in Caco‐2 cells, Ro‐26‐9228 induces 40‐fold less reporter gene expression than 1,25D3 does. We also examined the abilities of the vitamin D receptor (VDR)‐ligand complexes from these two cell lines to interact with partners of transcription (glucocorticoid receptor‐interacting protein, VDR‐interacting protein, and retinoid X receptor), in pull‐down assays. These assays revealed that 1,25D3 induces similar levels of interaction of these co‐factors with VDR from both osteoblasts and intestinal cells. In contrast, Ro‐26‐9228 induces significant interaction of VDR from osteoblast cells with these co‐factors, but less of VDR from Caco‐2 cells. These results suggest that the cellular environment of intestinal cells, unlike that of osteoblasts, represses the ability of VDR‐Ro‐26‐9228 complexes to interact with transcription partners. J. Cell. Biochem. 88: 267–273, 2003. © 2002 Wiley‐Liss, Inc.
Role of the vitamin D‐endocrine system in the pathophysiology of postmenopausal osteoporosis
Authors: Riggs B. Lawrence
Published: January 2003

Impaired calcium absorption and impaired adaptation to a low calcium diet are common features of aging in women and these processes are even more severely impaired in patients with osteoporotic fractures. The calcium absorption defects are associated with several abnormalities of the vitamin D‐endocrine system including secondary hyperparathyroidism, intestinal resistance to 1,25‐dihydroxyvitamin D (1,25(OH)2D) action, decreased 1,25(OH)2D production due to impaired 25(OH)D 1α‐hydroxylase activity, and, in some elderly persons, nutritional deficiency of vitamin D. However, in postmenopausal women, most of these abnormalities are normalized by administration of physiologic replacement dosages of estrogen and, thus, appear to be secondary consequences of estrogen deficiency. Nonetheless, a minority of them, especially nutritional vitamin D deficiency and impaired 25(OH)D 1α‐hydroxylase activity late in life, appear to be primary and are independent of estrogen deficiency. J. Cell. Biochem. 88: 209–215, 2003. © 2002 Wiley‐Liss, Inc.
Vitamin D target proteins: Function and regulation
Authors: Christakos S. , Barletta F. , Huening M. , Dhawan P. , Liu Y. , Porta A. , Peng X.
Published: January 2003

Recent findings have indicated that calbindin‐D28k, the first known target of vitamin D action, is present in osteoblasts and protects against TNF and glucocorticoid induced apoptosis of osteoblastic cells. Cytokine mediated destruction of pancreatic β cells, a cause of insulin dependent diabetes, is also inhibited by calbindin‐D28k. In calbindin‐D28k transfected pancreatic β cells free radical formation by cytokines is inhibited by calbindin. Thus, besides its role as a facilitator of calcium diffusion, calbindin has a major role in protecting against cellular degeneration in different cell types. Besides calbindin, the other known pronounced effect of 1,25(OH)2D3 in intestine and kidney is increased synthesis of 25(OH)D3 24‐hydroxylase (24(OH)ase) which is involved in the catabolism of 1,25(OH)2D3. We have noted that CCAAT enhancer binding protein β (C/EBPβ) is induced by 1,25(OH)2D3 in kidney and osteoblastic cells and can enhance the transcriptional response of 24(OH)ase to 1,25(OH)2D3. These studies establish C/EBPβ as a novel 1,25(OH)2D3 target gene and indicate a role for C/EBPβ in 24(OH)ase transcription. These studies extend our previous studies related to factors that affect vitamin D receptor (VDR) mediated 24(OH)ase transcription (YY1, TFIIB, CBP) and the effect of signaling pathways on 24(OH)ase transcription and cofactor recruitment. J. Cell. Biochem. 88: 238–244, 2003. © 2002 Wiley‐Liss, Inc.
Regulation of imprinting: A multi‐tiered process
Authors: Rand Eyal , Cedar Howard
Published: January 2003

Although most mammalian genes are expressed from both alleles, there is a small group of special genes which are imprinted so that only one of the parental alleles is actually expressed in target cells. This epigenetic process involves regulation at a number of different stages of development and is very complex. In principle, imprinted gene regions must be marked in cis in the gametes using epigenetic features capable of being maintained through cell division and able to direct multigenic monoallelic expression in differentiated cells of the mature organism. The difference between alleles must be erased during early gametogenesis to allow the imprint to be reset in the mature gametes. In this review we will summarize what is currently known about the molecular mechanisms which mediate these steps. J. Cell. Biochem. 88: 400–407, 2003. © 2002 Wiley‐Liss, Inc.
Gene therapy for tissue regeneration
Authors: Cutroneo Kenneth R.
Published: January 2003

Tissue 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

Hepatocyte 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

Rickets 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

In 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

In 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

The 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

The 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

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

The 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

The 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

Legacy 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

Management 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

Three 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

A 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

High 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.
Ecological significance of net photosynthesis activation by water vapour uptake in Ramalina capitata from rain-protected habitats in central Spain
Authors: Pintado Ana , Sancho Leopoldo G.
Published: January 2003

The reactivation of net photosynthesis and dark respiration from water vapour and from liquid water in the lichen Ramalina capitata var. protecta (H. Magn.) Nimis from sheltered habitats in Central Spain was investigated. CO2 gas-exchange response and thallus water content were measured in the laboratory as dry thalli were allowed to equilibrate by water vapour uptake under different relative humidities, and as saturated thalli dried. Water content of thalli from different habitats was also measured in the field during rainfall. The results show that the lichen is very efficient in using water vapour from the air for photosynthesis. Net photosynthetic rates were measured at very low water potentials (up to – 26-9 Megapascal) with water contents of the thalli below 30% dry weight. Maximum net photosynthetic rates measured after water vapour uptake were in some cases similar to those obtained after hydration by liquid water, while respiration rates were always lower after water vapour uptake, indicating a relatively larger activation of the photobiont. Moreover, photosynthetic rates at thallus water contents below 60% dry weight were higher when hydration was achieved through water vapour uptake than with liquid water. Field measurements had shown that this lichen reached water contents through water vapour absorption of 40% dry weight that would allow a positive balance of CO2 uptake. Possible ecological implications of differences in photosynthetic activation depending on the water source are discussed in terms of the carbon gain under natural conditions of this ombrophobous lichen.
The significance of stemflow chemistry for epiphytic lichen diversity in a dieback-affected spruce forest on Mt Brocken, northern Germany
Authors: Hauck Markus , Hesse Volker , Runge Michael
Published: January 2003

Epiphytic lichen diversity in a boggy stand of Norway spruce (Picea abies) was studied in the eastern Harz Mountains, northern Germany. Spruce trees at wet sites were affected by forest dieback, whereas trees on drier sites remained unaffected. Lichen diversity was higher on diebackaffected trees than on healthy ones. The foliose lichen Hypogymnia physodes was significantly more frequent on dead trees, whereas the crustose, extremely toxitolerant Lecanora conizaeoides occurred more frequently on healthy trees. Stemflow concentrations of NH⊂4⊃+, NO⊂3⊃-, PO⊂3⊃-, and SO⊂4⊃2- were lower on affected trees. This is attributed to reduced interception from the atmosphere due to needle loss. Cover of H. physodes decreased with increasing mean SO⊂4⊃2- concentration in stemflow. The total of lichen species per sample tree also decreased with increasing SO⊂4⊃2- concentration in stemflow, indicating that most species reacted in a similar way as H. physodes. Cover of L. conizaeoides increased with increasing SO⊂4⊂2- concentration, but decreased at higher SO⊂4⊃2- concentrations. Bark chemistry had a minor influence on lichen diversity.
Isolation of embryonic stem‐like cells from equine blastocysts and their differentiation in vitro1
Authors: Saito Shigeo , Ugai Hideyo , Sawai Ken , Yamamoto Yusuke , Minamihashi Akira , Kurosaka Kahori , Kobayashi Yoshiro , Murata Takehide , Obata Yuichi , Yokoyama Kazunari
Published: January 2003

Embryonic stem (ES) cells are pluripotent cells with the potential capacity to generate any type of cell. We describe here the isolation of pluripotent ES‐like cells from equine blastocysts that have been frozen and thawed. Our two lines of ES‐like cells (E‐1 and E‐2) appear to maintain a normal diploid karyotype indefinitely in culture in vitro and to express markers that are characteristic of ES cells from mice, namely, alkaline phosphatase, stage‐specific embryonic antigen‐1, STAT‐3 and Oct 4. After culture of equine ES‐like cells in vitro for more than 17 passages, some ES‐like cells differentiated to neural precursor cells in the presence of basic fibroblast growth factor (bFGF), epidermal growth factor and platelet‐derived growth factor. We also developed a protocol that resulted in the differentiation of ES‐like cells in vitro to hematopoietic and endothelial cell lineages in response to bFGF, stem cell factor and oncostatin M. Our observations set the stage for future developments that may allow the use of equine ES‐like cells for the treatment of neurological and hematopoietic disorders.
Homocysteine promotes the LDL oxidase activity of ceruloplasmin
Authors: Exner M , Hermann M , Hofbauer R , Hartmann B , Kapiotis S , Gmeiner B
Published: January 2003

Ceruloplasmin (CP) oxidises low density lipoprotein (LDL). The oxidising potential depends on the formation of Cu+‐CP which is redox‐cycled during oxidation. Homocysteine (HCY) reduces free Cu2+, potentiating its cell‐damaging property. We show that HCY enhanced LDL oxidation by CP, but did not activate the LDL oxidising potential of Cu2+‐diamine oxidase. Selective removal of the redox‐active Cu2+ abolished the LDL oxidase activity of CP. However, HCY partially restored the LDL oxidase activity of redox‐copper depleted CP, indicating that the remaining six copper atoms in CP may also be involved in the process. Spectroscopic and oxidation inhibition studies using the Cu+‐reagent bathocuproine revealed that HCY induced Cu+‐CP formation, thus promoting its LDL oxidase activity.
N‐terminal PDZ‐binding domain in Kv1 potassium channels
Authors: Eldstrom Jodene , Doerksen Kyle W , Steele David F , Fedida David
Published: January 2003

We have investigated the interactions of prototypical PDZ domains with both the C‐ and N‐termini of Kv1.5 and other Kv channels. A combination of in vitro binding and yeast two‐hybrid assays unexpectedly showed that PDZ domains derived from PSD95 bind both the C‐ and N‐termini of the channels with comparable avidity. From doubly transfected HEK293 cells, Kv1.5 was found to co‐immunoprecipitate with the PDZ protein, irrespective of the presence of the canonical C‐terminal PDZ‐binding motif in Kv1.5. Imaging analysis of the same HEK cell lines demonstrated that co‐localization of Kv1.5 with PSD95 at the cell surface is similarly independent of the canonical PDZ‐binding motif. Deletion analysis localized the N‐terminal PDZ‐binding site in Kv1.5 to the T1 region of the channel. Co‐expression of PSD95 with Kv1.5 N‐ and C‐terminal deletions in HEK cells had contrasting effects on the magnitudes of the potassium currents across the membranes of these cells. These findings may have important implications for the regulation of channel expression and function by PDZ proteins like PSD95.
Local inhibition of Drosophila homeobox‐containing neural dorsoventral patterning genes by Dpp
Authors: Oh Chun Taek , Kwon Seung Hae , Jeon Kyoung Ja , Han Pyung-Lim , Kim Sang Hee , Jeon Sang-Hak
Published: January 2003

An important step in Drosophila neurogenesis is to establish the neural dorsoventral (DV) patterning. Here we describe how dpp loss‐of‐ and gain‐of‐function mutation affects the homeobox‐containing neural DV patterning genes expressed in the ventral neuroectoderm. Ventral nervous system defective (vnd), intermediate neuroblast defective (ind), muscle‐specific homeobox (msh), and orthodenticle (otd) genes participate in development of the central nervous system and peripheral nervous system, and encode homeodomain proteins. otd and msh genes were ectopically expressed in dpp loss‐of‐function mutation, but vnd and ind were not affected. However, when dpp was ectopically expressed in the ventral neuroectoderm by rho‐GAL4/UAS‐dpp system, it caused the repression of vnd, and msh expressions in ventral and dorsal columns of the neuroectoderm, respectively, but not that of ind. The later expression pattern of otd was also restricted by Dpp. The expression pattern of msh, vnd and otd in dpp loss‐of‐function and gain‐of‐function mutation indicates that Dpp activity does not reach to the ventral midline and it works locally to establish the dorsal boundary of the ventral neuroectoderm.
Novel human G protein‐coupled receptors with long N‐terminals containing GPS domains and Ser/Thr‐rich regions
Authors: Fredriksson Robert , Lagerström Malin C , Höglund Pär J , Schiöth Helgi B
Published: January 2003

We report eight novel members of the superfamily of human G protein‐coupled receptors (GPCRs) found by searches in the human genome databases, termed GPR97, GPR110, GPR111, GPR112, GPR113, GPR114, GPR115 and GPR116. Phylogenetic analysis shows that these are additional members of a family of GPCRs with long N‐termini, previously termed EGF‐7TM, LNB‐7TM, B2 or LN‐7TM. Five of the receptors form their own phylogenetic cluster, while three others form a cluster with the previously reported HE6 and GPR56 (TM7XN1). All the receptors have a GPS domain in their N‐terminus and long Ser/Thr‐rich regions forming mucin‐like stalks. GPR113 has a hormone binding domain and one EGF domain. GPR112 has over 20 Ser/Thr repeats and a pentraxin domain. GPR116 has two immunoglobulin‐like repeats and a SEA box. We found several human EST sequences for most of the receptors showing differential expression patterns, which may indicate that some of these receptors participate in reproductive functions while others are more likely to have a role in the immune system.
Cerivastatin enhances the cytotoxicity of 5‐fluorouracil on chemosensitive and resistant colorectal cancer cell lines
Authors: Wang Weiguang , Collie-Duguid Elaina , Cassidy James
Published: January 2003

Cerivastatin is one of the synthetic 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors used for the treatment and prevention of hypercholesterolaemia. The observation that patients receiving this drug had a lower incidence at cancer led to our interest in using it as a putative anticancer agent. In this study, we tested the cytotoxicity of cerivastatin on a panel of 5‐fluorouracil (5FU) sensitive and resistant cell lines in vitro. Cerivastatin was cytotoxic to both 5FU sensitive and resistant cells. Cerivastatin significantly augmented the cytotoxic effect of 5FU on drug sensitive (6–22‐fold) and resistant (229–310‐fold) cell lines. Cerivastatin and 5FU acted synergistically. Cerivastatin inhibited nuclear factor κB DNA binding activity. The enhancing effect of cerivastatin on 5FU was partially mevalonate pathway independent. Cerivastatin may allow successful 5FU therapy in chemoresistant patients.