bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and monomer reactivity ratios of methyl methacrylate and 2‐vinyl‐4,4′‐dimethylazlactone copolymers
Authors: Stanek Lee G. , Heilmann Steven M. , Gleason William B. 
Published: September 2003

AbstractWe report the monomer reactivity ratios for copolymers of methyl methacrylate (MMA) and a reactive monomer, 2‐vinyl‐4,4′‐dimethylazlactone (VDMA), using the Fineman–Ross, inverted Fineman–Ross, Kelen–Tudos, extended Kelen–Tudos, and Tidwell–Mortimer methods at low and high polymer conversions. Copolymers were obtained by radical polymerization initiated by 2,2′‐azobisisobutyronitrile in methyl ethyl ketone solutions and were analyzed by NMR, gas chromatography (GC), and gel permeation chromatography. 1H NMR analysis was used to determine the molar fractions of MMA and VDMA in the copolymers at both low and high conversions. GC analysis determined the molar fractions of the monomers at conversions of less than 27% and greater than 65% for the low‐ and high‐conversion copolymers, respectively. The reactivity ratios indicated a tendency toward random copolymerization, with a higher rate of consumption of VDMA at high conversions. For both low‐ and high‐conversion copolymers, the molecular weights increased with increasing molar fractions of VDMA, and this was consistent with the faster consumption of VDMA (compared with that of MMA). © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3027–3037, 2003
On estimation of frequency data with censored observations
Authors: Menjoge Shailendra S. 
Published: September 2003

AbstractThe problem of the estimation of mean frequency of events in the presence of censoring is important in assessing the efficacy, safety and cost of therapies. The mean frequency is typically estimated by dividing the total number of events by the total number of patients under study. This method, referred to in this paper as the ‘naïve estimator’, ignores the censoring. Other approaches available for this problem require many assumptions that are rarely acceptable. These include the assumption of independence, constant hazard rate over time and other similar distributional assumptions. In this paper a simple non‐parametric estimator based on the sum of the products of Kaplan–Meier estimators is proposed as an estimator of mean frequency, and its approximate variance and standard error are derived. An illustration is provided to show the derivation of the proposed estimator. Although the clinical trial setting is used in this paper, the problem has applications in other areas where survival analysis is used and recurrent events are studied. Copyright © 2003 John Wiley & Sons, Ltd.
Repeated‐measures models in the analysis of QT interval
Authors: Dmitrienko Alex , Smith Brian 
Published: September 2003

AbstractBecause of the recent regulatory emphasis on issues related to drug‐induced cardiac repolarization that can potentially lead to sudden death, QT interval analysis has received much attention in the clinical trial literature. The analysis of QT data is complicated by the fact that the QT interval is correlated with heart rate and other prognostic factors. Several attempts have been made in the literature to derive an optimal method for correcting the QT interval for heart rate; however the QT correction formulae obtained are not universal because of substantial variability observed across different patient populations. It is demonstrated in this paper that the widely used fixed QT correction formulae do not provide an adequate fit to QT and RR data and bias estimates of treatment effect. It is also shown that QT correction formulae derived from baseline data in clinical trials are likely to lead to Type I error rate inflation. This paper develops a QT interval analysis framework based on repeated‐measures models accomodating the correlation between QT interval and heart rate and the correlation among QT measurements collected over time. The proposed method of QT analysis controls the Type I error rate and is at least as powerful as traditional QT correction methods with respect to detecting drug‐related QT interval prolongation. Copyright © 2003 John Wiley & Sons, Ltd.
A constraint‐based approach for the optimum redesign of a packaging operation
Authors: Hicks B. J. , Medland A. J. , Mullineux G. 
Published: September 2003

AbstractThe task of the design engineer is to configure a design such that a predetermined functional requirement is fulfilled, and that it is achieved within a given set of performance criteria. As a design evolves, so these performance criteria change, driven by the ever‐increasing needs of the customer and the inherent competition between manufacturers. It is during this evolutionary process that the engineer demands a CAD system which can represent knowledge about the design and explore solutions regarding the relationship between geometry and behaviour. This is necessary in order to realize the full potential of an existing design, or to examine modifications to an existing design that may achieve the desired performance characteristics. The work described in this paper uses a constraint‐based modelling environment to represent and analyse a high‐speed packaging operation. The goal of the modelling work is to produce an optimal design solution for the given performance requirements, as well as to satisfy the constraints imposed by the existing machine system and packaging process. The construction of the model is described and the identification and representation of the design constraints are discussed. These constraints are then applied to a possible machine modification or redesign and an optimized configuration is developed in the modelling environment. Copyright © 2003 John Wiley & Sons, Ltd.
Decreased enzyme activity of hepatic thioredoxin reductase and glutathione reductase in rabbits by prolonged exposure to inorganic arsenate
Authors: Nikaido Masatoshi , Pi Jingbo , Kumagai Yoshito , Yamauchi Hiroshi , Taguchi Keiko , Horiguchi Satomi , Sun Yang , Sun Guifan , Shimojo Nobuhiro 
Published: September 2003

AbstractChronic exposure of humans to inorganic arsenic, mainly pentavalent arsenate (iAsV), results in drinking water–induced oxidative stress (Pi et al., 2002). Thioredoxin reductase (TR) and glutathione reductase (GR) are the two critical enzymes in the response to oxidative stress in vivo. In the present study we examined alterations in enzyme activities of hepatic TR and GR from prolonged exposure of male New Zealand white rabbits to iAsV. Exposure of rabbits to iAsV in drinking water (5 mg/L) for 18 weeks caused a significant suppression of hepatic TR and GR activities, of approximately 30% and 20%, respectively, below controls. In vitro experiments suggested that trivalent inorganic arsenic (iAsIII) but not pentavalent arsenicals including iAsV, monomethylarsonic acid (MMAsV), and dimethylarsinic acid (DMAsV) affected the hepatic TR activity of rabbit. So it was suggested that in the present study iAsV ingested via drinking water was metabolized to reactive trivalent arsenicals, such as iAsIII, which may play an important role in the decreased TR and GR activities from prolonged exposure to iAsV observed in vivo. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 306–311, 2003.
The fungicide benomyl inhibits differentiation of neural tissue in the Xenopus embryo and animal cap explants
Authors: Yoon Chun‐Sik , Jin Jung‐Hyo , Park Joo‐Hung , Youn Hyun‐Joo , Cheong Seon‐Woo 
Published: September 2003

AbstractThe toxic effect of benomyl on the embryogenesis of Xenopus laevis was investigated, and the tissues most affected by benomyl were identified. The toxicity of benomyl at various concentrations (5–20 μM) was tested with the Xenopus frog embryo teratogenesis assay (FETAX), used with slight modification. All test embryos subjected to 20 μM of benomyl died, and exposure to 10 and 15 μM benomyl produced growth inhibition and 11 types of severe external malformations. Histological examination of the test embryos showed dysplasia of the brain, eyes, intestine, otic vesicle, and muscle and swelling of the pronephric ducts and integuments. Among the tissues and organs affected, malformation of neural tissue was the most severe. The presumptive ectoderm isolated from st. 9 embryo was cultured in 10 ng/mL of activin A to induce neural tissue and mesoderm. When it was cultured with 10 ng/mL of activin A in the presence of 1 and 10 μM of benomyl, neural tissue induction was inhibited more severely than that of any other tissue. The gene expression of cultivated explants was investigated by reverse transcription–polymerase chain reaction (RT‐PCR) assay in order to study the inhibition of neural tissue by benomyl. The results showed that with increasing benomyl concentration, the expression of the neural‐specific marker NCAM (neural cell adhesion molecule), was more strongly inhibited than the muscle‐specific marker muscle actin. Electron micrographs of test explants showed many residual yolk platelets and mitochondrial degeneration. In the present investigation the most severe toxic effects of benomyl were seen in the nerve tissues of the Xenopus embryo. This inhibition of neural development may have been caused by the inhibition of the assembly of neural microtubules and by the effect of benomyl on neuronal proliferation and migration. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 327–337, 2003.
Cell alterations but no DNA strand breaks induced in vitro by cylindrospermopsin in CHO K1 cells
Authors: Fessard Valérie , Bernard Cécile 
Published: September 2003

AbstractCylindrospermopsin has been involved in some cyanobacterial blooms associated with animal and human intoxications in different countries. Liver is the main target organ even though thymus and kidney are also affected. Its toxic effect has been shown to be induced by protein synthesis inhibition. However, further research about its toxicological potential is required, as revealed by the U.S. Unregulated Contaminant Monitoring Regulation (US UCMR) meeting in 2001. Induction of DNA damage by cylindrospermopsin has been reported by some authors either by a direct effect on DNA or by an indirect effect on associated macromolecules. This study focused on evaluating its in vitro genotoxic potential using the comet assay coupled to various cell alteration measurements. No DNA damage was detected by the alkaline comet assay on Chinese hamster ovary (CHO) K1 cells after 24 h of treatment with cylindrospermopsin concentrations of 0.5 and 1 μg mL−1. However, inhibition of cell growth was noticed as well as cell blebbing and rounding. These morphological effects were linked to cytoskeletal reorganization (mainly microfilaments) but not to apoptosis. This study concluded that cylindrospermopsin does not obviously react directly with DNA in CHO K1 cells. But the hypothesis of its metabolization into a genotoxic product must be explored further. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 353–359, 2003.
Bcl‐2 family members make different contributions to cell death in hypoxia and/or hyperoxia in rat cerebral cortex
Authors: Hu Xiaoming , Qiu Jingxin , Grafe Marjorie R. , Rea Harriett C. , Rassin David K. , Perez‐Polo J.Regino 
Published: September 2003

AbstractHypoxic brain injury during fetal or neonatal development leads to damaged immature neurons and can result in cognitive or behavioral dysfunction. Hyperoxia therapy (treatment with oxygen) is commonly applied to infants with signs of perinatal hypoxia–anoxia. Both hypoxia and hyperoxia have been shown to result in apoptosis in the brains of rats in several animal models. One determinant of cellular commitment to cell death is the differential expression of the Bcl‐2 family of proteins in response to trauma. Here, we characterize cell death and the expression of Bcl‐2 homologous proteins in 7‐day‐old neonatal rat cerebral cortex after hypoxia (5% O2 for 40 min) and/or hyperoxia (>95% O2 for 2 h after hypoxia). The expression of Bcl‐2 and Bcl‐XL, two anti‐apoptotic proteins, decreased at 24 h after hypoxia. Bcl‐XL increased after either hyperoxia or hypoxia+hyperoxia. We did not detect significant changes in the cytoplasmic levels of pro‐apoptotic protein Bax after any of these three treatments. Using cell death ELISA and DNA FragEL© assays, we observed increased cell death at 24 h after hypoxia, hyperoxia or hypoxia+hyperoxia treatments. At 24 h after either hypoxia, hyperoxia or hypoxia+hyperoxia, caspase 3 activity also increased significantly. Our results suggest that both hypoxia and hyperoxia alone can induce cell death. The Bcl‐2 → cytochrome c → caspase 3 pathway played a role in hypoxia‐induced cell death, while other pathways may be involved in hyperoxia‐induced cell death.
Trawl hangs, baby fish, and closed areas: a win–win scenario
Authors: Link Jason S , Demarest Chad 
Published: September 2003

Abstract
The frequency and geographic distribution of trawlnet hangs from a fishery-independent survey are evaluated. The hangs data were plotted on a substratum map to confirm that many, but not all, were naturally occurring, high relief substrata. The data were also coupled with the occurrence of juvenile cod (Gadus morhua) and haddock (Melanogrammus aeglefinus) to assess the degree of association between juvenile gadoids and high relief substrata. The average minimal distance from a fish occurrence to a hang ranged from 8.1 to 12.0 km (4.4–6.5 nautical miles), well within the reported daily range of movement for these fish. A similar pattern was detected for the sea raven (Hemitripterus americanus), a predator of juvenile gadoids, confirming the location of these microhabitat foodwebs. On average, closing an area 3.7 km (2 nautical miles) around a hang will enclose 17–30% of the populations of these juvenile fish; a wider buffer (18–28 km; 10–15 nautical miles) will close a linearly increasing portion of the populations. Additionally, closing areas surrounding the hangs, particularly regions of high hang density, will help to minimize losses of or damage to fishing gear. We propose a win–win scenario by establishing or evaluating closed areas in regions with high concentrations of known hangs. This approach is widely applicable for many marine ecosystems and may help to achieve simultaneous conservation and resource management goals, whereby one can both protect pre-recruit fish and enhance the effectiveness of a fishery.
Enhancement of alkaline phosphatase synthesis in pulp cells co‐cultured with epithelial cells derived from lower rabbit incisors
Authors: Shiba Hideki , Mouri Yoshihiro , Komatsuzawa Hitoshi , Mizuno Noriyoshi , Xu Wanpeng , Noguchi Takuji , Nakamura Shigeo , Sugai Motoyuki , Kato Yukio , Kurihara Hidemi 
Published: September 2003

AbstractDental papilla mesenchymal cells differentiate into odontoblasts through epithelial—mesenchymal interactions. However, the mechanism by which enamel epithelial cells affect the differentiation of dental mesenchymal cells remains unknown. Alkaline phosphatase (ALPase) is a marker for odontoblast‐like differentiation, because odontoblasts show much higher ALPase activity than dental undifferentiated mesenchymal cells. The continuously growing rabbit incisor is a good model for the epithelial—mesenchymal interaction during odontogenesis. In the present study, we isolated and maintained rabbit incisor‐derived epithelial cells and rabbit incisor pulp‐derived fibroblastic cells, and examined the effect of epithelial cells on ALPase activity in fibroblastic cells. Epithelial cells were stained with anti‐cytokeratin 5 and 8 antibodies and showed the expression of tuftelin mRNA. In separate cultures of epithelial cells or fibroblastic cells, ALPase activity and mRNA levels were very low, but were upregulated in co‐cultures of epithelial and fibroblastic cells. Histochemical analysis found high ALPase activity in fibroblastic cells close to epithelial cells. These findings suggest that epithelial cells play an important role in promoting ALPase expression in pulp fibroblastic cells. The co‐culture system developed here will be useful for examining the role of the epithelial—mesenchymal interaction during odontoblast differentiation.
Differential regulation of JNK in caspase‐3‐mediated apoptosis of MPP+‐treated primary cortical neurons
Authors: Sun Der‐Shan , Chang Hsin‐Hou 
Published: September 2003

AbstractMPTP (1‐methyl‐1,2,3,6‐tetrahydropyridine), a chemical contaminant of synthetic heroin, induces neuropathological changes with clinical features similar to idiopathic Parkinson's disease. The mechanism by which MPTP and its metabolite MPP+(1‐methyl‐4‐phenylpyridinium) induces neuronal cell death remains unclear. We employed primary cortical/telencephalon neuronal cultures to investigate the potential role of caspase and stress‐activated protein kinase (SAPK)/c‐Jun N‐terminal kinase (JNK) pathways in MPP+‐induced neuronal death. DNA fragmentation and caspase‐3 activity analysis showed that cortical neuronal cells underwent apoptosis after MPP+treatment. However, a basal level of apoptotic cells was also observed in untreated cultures. Interestingly, JNK activity increased in untreated cultures over time, whereas it was down‐regulated after MPP+treatment. This indicates that the JNK pathways could be differentially regulated in different apoptotic processes.
Effect of sulfated GAGs on the expression and activation of MMP‐2 and MMP‐9 in corneal and dermal explant cultures
Authors: Isnard N. , Robert L. , Renard G. 
Published: September 2003

AbstractIt has been shown previously that hyaluronan (HA) added to fibroblast and keratocyte cell cultures or corneal explant cultures produces an up‐regulation of MMP‐2 and MMP‐9 expression and activation. Here, we examine the effect of sulfated GAG‐s, chondroitin 4 and 6 sulfate (CS4, CS6), dermatan sulfate (DS), keratan sulfate (KS) and heparan sulfate (HS) on MMP‐2 and 9 expression and activation under the same culture conditions. It appears that CS4 has only minor effects, KS inhibits MMP‐2 activation and CS6, DS and HS increase MMP‐2 activation in corneal explant cultures. For skin explant cultures, DS, KS and HS strongly increase MMP‐9 activation, whereas KS inhibits and DS increases MMP‐2 activation. All these effects can be strongly inhibited by the addition of an antibody to CD44, except CS6 and DS. Activation by these two GAGs was only slightly affected, supporting the contention that the effects of HA, CS4, KS and HS are mediated by one of the isoforms of this CD44 receptor. The physio‐pathological significance of these results is discussed for cornea and skin ageing, because of the divergent evolution with in vitro ageing of the relative proportions of GAGs synthesised by these two cell types.
The mitochondrial acetoacetyl‐CoA thiolase (T2) deficiency in Japanese patients: urinary organic acid and blood acylcarnitine profiles under stable conditions have subtle abnormalities in T2‐deficient patients with some residual T2 activity
Authors: Fukao T. , Zhang G.‐X. , Sakura N. , Kubo T. , Yamaga H. , Hazama A. , Kohno Y. , Matsuo N. , Kondo M. , Yamaguchi S. , Shigematsu Y. , Kondo N. 
Published: September 2003

AbstractMitochondrial acetoacetyl‐CoA thiolase (T2) deficiency is an inborn error of metabolism affecting isoleucine and ketone bodies in the catabolic process. Mutation analysis and expression analysis of mutant cDNAs have facilitated the division of T2‐deficient patients into two groups: those with null mutations in either allele (group I) and those with mutation(s) retaining some residual T2 activity in at least one of two mutant alleles (group II). Among 5 Japanese T2‐deficient patients, GK01 belonged to group I and the other patients (GK19, GK19B, GK30 and GK31) to group II. As we have suggested previously, the severity of ketoacidotic episodes in the group II patients was similar to that in the group I patient. However, the urinary organic acid and blood spot acylcarnitine profiles under stable conditions differed between the two groups. The group I patient had typical profiles for the T2 deficiency. In contrast, in all four patients in group II, tiglylglycine was not or was only faintly detected and the 2‐methyl‐3‐hydroxybutyrate levels were less than the cutoff value. Their tiglylcarnitine levels were within the normal range and 2‐methyl‐3‐hydroxybutyrylcarnitine was detected just around the cutoff value in our newborn screening pilot test. Hence, these analyses under stable conditions are not reliable for diagnosing the T2 deficiency in the group II patients. The T2 deficiency (group II) can be misdiagnosed as normal if these analyses are performed under nonepisodic conditions and possibly during the newborn screening for inborn errors of metabolism.
Maternal methionine adenosyltransferase I/III deficiency: Reproductive outcomes in a woman with four pregnancies
Authors: Mudd S. H. , Tangerman A. , Stabler S. P. , Allen R. H. , Wagner C. , Zeisel S. H. , Levy H. L. 
Published: September 2003

AbstractFour pregnancies in a women with moderately severe deficiency of methionine adenosyltransferase I/III (MAT I/III) activity are reported. She is an apparent homozygote for apointmutation inMAT1A,the gene that encodes the catalytically active subunit of MAT I/III. This mutation reduces the activity of her expressed enzyme to some 11% of wild‐type. She was the first such individual identified in the United States, and these are the first pregnancies known in anyone with this extent of MAT I/III deficiency. No adverse effects were noted in the mother. Three normal babies resulted, but fetal arrest was detected in one embryo at 10–11 weeks gestation. Plasma methionine concentrations remained virtually constant at their elevated levels of 300–350 µmol/L throughout the pregnancies. Plasma free choline was below the reference range. In view of the evidence that maternal choline delivery to the fetus is important for brain development, it was suggested the patient ingest two eggs daily from gestation week 17. Plasma choline and phosphatidylcholine tended to rise during such supplementation. Plasma cystathionine concentrations rose progressively to far above normal during these pregnancies, but not during pregnancies in control women. This may be explained by delivery of excessive methionine to the fetus, with consequent increased cystathionine synthesis by fetal tissues. Because fetal tissues lack γ‐cystathionase, presumably cystathionine accumulated abnormally in the fetus and was transferred in abnormal amounts back to the mother. Plasma and urinary concentrations of methionine transamination metabolites rose during pregnancy for reasons that remain obscure.