Showing papers by "Radboud University Nijmegen published in 1998"

A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?

Abstract: Summary Recently, we showed that homozygosity for the common 677(C→T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, causing thermolability of the enzyme, is a risk factor for neural-tube defects (NTDs). We now report on another mutation in the same gene, the 1298(A→C) mutation, which changes a glutamate into an alanine residue. This mutation destroys an Mbo II recognition site and has an allele frequency of .33. This 1298(A→C) mutation results in decreased MTHFR activity (one-way analysis of variance [ANOVA] P P P n = 86) of the NTD patients compared with 20% ( n = 403) among controls, resulting in an odds ratio of 2.04 (95% confidence interval: .9–4.7). These data suggest that the combined heterozygosity for the two MTHFR common mutations accounts for a proportion of folate-related NTDs, which is not explained by homozygosity for the 677(C→T) mutation, and can be an additional genetic risk factor for NTDs.

Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.

Abstract: Only a few autoantibodies that are more or less specific for RA have been described so far. The rheumatoid factor most often tested for is not very specific for RA, while the more specific antiperinuclear factor for several reasons is not routinely used as a serological parameter. Here we show that autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue, are specifically present in the sera of RA patients. Using several citrulline-containing peptide variants in ELISA, antibodies could be detected in 76% of RA sera with a specificity of 96%. Sera showed a remarkable variety in the reactivity pattern towards different citrulline-containing peptides. Affinity-purified antibodies were shown to be positive in the immunofluorescence-based antiperinuclear factor test, and in the so-called antikeratin antibody test, and were reactive towards filaggrin extracted from human epidermis. The specific nature of these antibodies and the presence of these antibodies early in disease, even before other disease manifestations occur, are indicative for a possible role of citrulline-containing epitopes in the pathogenesis of RA.

The effects of air‐borne nitrogen pollutants on species diversity in natural and semi‐natural European vegetation

Abstract: Summary The effects of increased atmospheric nitrogen inputs, from both NOy and NHx, on diversity in various semi-natural and natural ecosystems are reviewed The severity of these impacts depends on abiotic conditions (eg buffering capacity, soil nutrient status and soil factors that influence the nitrification potential and nitrogen immobilization rate) in the particular system The sensitivity of fresh water ecosystems, wetlands and bogs, species-rich grasslands, heathlands and field layer of forests, all of which have conservational value, are discussed in detail The most important effects of nitrogen deposition are: (i) accumulation of nitrogenous compounds resulting in enhanced availability of nitrate or ammonium; (ii) soil-mediated effects of acidification; and (iii) increased susceptibility to secondary stress factors Long-term nitrogen enrichment has gradually increased the availability of nitrogen in several vegetation types, leading to competitive exclusion of characteristic species by more nitrophilic plants, especially under oligo- to mesotrophic soil conditions Soil acidification (with losses of buffering capacity and increased concentrations of toxic metals) is especially important after nitrification of ammonium in weakly buffered environments: acid-resistant plant species then become dominant at the expense of the often rare plants typical of intermediate pH The related change in the balance between ammonium and nitrate may also affect the performance of several species The susceptibility of plant species to secondary stress factors (pathogens; frost and drought) may be affected by air-borne nitrogen but data are only available for a few communities (eg dry heathlands) Most global biodiversity is contained within natural and semi-natural vegetation It is thus crucial to control emissions of nitrogenous compounds to the atmosphere, in order to reduce or prevent effects on diversity in these systems Most research has focused on acidification in forestry stands and lakes and on the effects on trees We highlight serious gaps in knowledge of other ecosystems

Predicting behavior from actions in the past : repeated decision making or a matter of habit?

Abstract: This paper summarizes research on determinants of repeated behaviors, and the decision processes underlying them. The present research focuses on travel mode choices as an example of such behaviors. It is proposed that when behavior is performed repeatedly and becomes habitual, it is guided by automated cognitive processes, rather than being preceded by elaborate decision processes (i.e., a decision based on attitudes and intentions). First, current attitude-behavior models are discussed, and the role of habit in these models is examined. Second, research is presented on the decision processes preceding travel mode choices. Based on the present theoretical and empirical overview, it is concluded that frequently performed behavior is often a matter of habit, thereby establishing a boundary condition for the applicability of attitude-behavior models. However, more systematic research is required to disentangle the role of habit in attitude-behavior models and to learn more about the cognitive processes underlying habitual behavior.

Bayesian classification with Gaussian processes

Abstract: We consider the problem of assigning an input vector to one of m classes by predicting P(c|x) for c=1,...,m. For a two-class problem, the probability of class one given x is estimated by /spl sigma/(y(x)), where /spl sigma/(y)=1/(1+e/sup -y/). A Gaussian process prior is placed on y(x), and is combined with the training data to obtain predictions for new x points. We provide a Bayesian treatment, integrating over uncertainty in y and in the parameters that control the Gaussian process prior the necessary integration over y is carried out using Laplace's approximation. The method is generalized to multiclass problems (m>2) using the softmax function. We demonstrate the effectiveness of the method on a number of datasets.

The relation between perception and behavior, or how to win a game of Trivial Pursuit.

Abstract: The authors tested and confirmed the hypothesis that priming a stereotype or trait leads to complex overt behavior in line with this activated stereotype or trait. Specifically, 4 experiments established that priming the stereotype of professors or the trait intelligent enhanced participants' performance on a scale measuring general knowledge. Also, priming the stereotype of soccer hooligans or the trait stupid reduced participants' performance on a general knowledge scale. Results of the experiments revealed (a) that prolonged priming leads to more pronounced behavioral effects and (b) that there is no sign of decay of the effects for at least 15 min. The authors explain their results by claiming that perception had a direct and pervasive impact on overt behavior (cf. J.A. Bargh, M. Chen, & L. Burrows, 1996). Implications for human social behavior are discussed.

Habit versus planned behaviour: A field experiment

Abstract: A field experiment investigated the prediction and change in repeated behaviour in the domain of travel mode choices. Car use during seven days was predicted from habit strength (measured by self-reported frequency of past behaviour, as well as by a more covert measure based on personal scripts incorporating the behaviour), and antecedents of behaviour as conceptualized in the theory of planned behaviour (attitude, subjective norm, perceived behavioural control and behavioural intention). Both habit measures predicted behaviour in addition to intention and perceived control. Significant habit x intention interactions indicated that intentions were only significantly related to behaviour when habit was weak, whereas no intention-behaviour relation existed when habit was strong. During the seven-day registration of behaviour, half of the respondents were asked to think about the circumstances under which the behaviour was executed. Compared to control participants, the behaviour of experimental participants was more strongly related to their previously expressed intentions. However, the habit-behaviour relation was unaffected. The results demonstrate that, although external incentives may increase the enactment of intentions, habits set boundary conditions for the applicability of the theory of planned behaviour.

Helical Superstructures from Charged Poly(styrene)-Poly(isocyanodipeptide) Block Copolymers

Abstract: Amphiphilic block copolymers containing a poly(styrene) tail and a charged helical poly(isocyanide) headgroup derived from isocyano-L-alanine-L-alanine and isocyano-L-alanine-L-histidine were prepared. Analogous to low-molecular mass surfactants, these block copolymers self-assembled in aqueous systems to form micelles, vesicles, and bilayer aggregates. The morphology of these aggregates can be controlled by variation of the length of the poly(isocyanide) block, the pH, and the anion-headgroup interactions. The chirality of the macromolecules results in the formation of helical superstructures that have a helical sense opposite to that of the constituent block copolymers. The great variety of morphologies displayed by these block copolymers and the fact that they are easily accessible from poly(styrene) and different types of peptides open new opportunities for applications in the fields of life and materials sciences.

Low Circulating Folate and Vitamin B6 Concentrations Risk Factors for Stroke, Peripheral Vascular Disease, and Coronary Artery Disease

Abstract: Background—A high plasma homocysteine concentration is a risk factor for atherosclerosis, and circulating concentrations of homocysteine are related to levels of folate and vitamin B6. This study was performed to explore the interrelationships between homocysteine, B vitamins, and vascular diseases and to evaluate the role of these vitamins as risk factors for atherosclerosis. Methods—In a multicenter case-control study in Europe, 750 patients with documented vascular disease and 800 control subjects frequency-matched for age and sex were compared. Plasma levels of total homocysteine (before and after methionine loading) were determined, as were those of red cell folate, vitamin B12, and vitamin B6. Results—In a conditional logistic regression model, homocysteine concentrations greater than the 80th percentile for control subjects either fasting (12.1 μmol/L) or after a methionine load (38.0 μmol/L) were associated with an elevated risk of vascular disease independent of all traditional risk factors. In a...

Producing Words in a Foreign Language: Can Speakers Prevent Interference from Their First Language?.

Abstract: Two picture-word interference experiments were conducted to investigate whether or not words from a first and more dominant language are activated during lexical access in a foreign and less dominant language. Native speakers of Dutch were instructed to name pictures in their foreign language English. Our experiments show that the Dutch name of a picture is activated during initial stages of the process of lexical in English as a foreign language. We conclude that bilingual speakers cannot suppress activation from their first language while naming pictures in a foreign language. The implications for bilingual speech production theories are discussed.

Implementing guidelines and innovations in general practice: which interventions are effective?

Abstract: BACKGROUND: It is crucial that research findings are implemented in general practice if high-quality care is to be achieved. Multifaceted interventions are usually assumed to be more effective than single interventions, but this hypothesis has yet to be tested for general practice care. This review evaluates the effectiveness of interventions in influencing the implementation of guidelines and adoption of innovations in general practice. A systematic literature study was carried out using MEDLINE searches for the period from January 1980 until June 1994, and 21 medical journals were searched manually. Randomized controlled trials and controlled before and after studies (with pre- and post-intervention measurements in all groups) were selected for the analysis. Clinical area, interventions used, methodological characteristics and effects on clinical behaviour were noted independently by two researchers using a standardized scoring form. Of 143 studies found, 61 were selected for the analysis, covering 86 intervention groups that could be compared with a control group without the intervention. Information transfer alone was effective in two out of 18 groups, whereas combinations of information transfer and learning through social influence or management support were effective in four out of eight and three out of seven groups respectively. Information linked to performance was effective in 10 out of 15 groups, but the combination of information transfer and information linked to performance was effective in only three out of 20 groups. Some, but not all, multifaceted interventions are effective in inducing change in general practice. Social influence and management support can improve the effectiveness of information transfer, but information linked to performance does not necessarily do so. The variation in the effectiveness of interventions needs further analysis.

Relearning sound localization with new ears.

Abstract: Because the inner ear is not organized spatially, sound localization relies on the neural processing of implicit acoustic cues. To determine a sound's position, the brain must learn and calibrate these cues, using accurate spatial feedback from other sensorimotor systems. Experimental evidence for such a system has been demonstrated in barn owls, but not in humans. Here, we demonstrate the existence of ongoing spatial calibration in the adult human auditory system. The spectral elevation cues of human subjects were disrupted by modifying their outer ears (pinnae) with molds. Although localization of sound elevation was dramatically degraded immediately after the modification, accurate performance was steadily reacquired. Interestingly, learning the new spectral cues did not interfere with the neural representation of the original cues, as subjects could localize sounds with both normal and modified pinnae.

Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers.

Abstract: Both homo- and hetero-dimers of ErbB receptor tyrosine kinases mediate signaling by a large group of epidermal growth factor (EGF)-like ligands. However, some ligands are more potent than others, although they bind to the same direct receptor. In addition, signaling by receptor heterodimers is superior to homodimers. We addressed the mechanism underlying these two features of signal tuning by using three ligands: EGF; transforming growth factor alpha (TGFalpha); and their chimera, denoted E4T, which act on cells singly expressing ErbB-1 as a weak, a strong, and a very strong agonist, respectively. Co-expression of ErbB-2, a developmentally important co-receptor whose expression is frequently elevated in human cancers, specifically potentiated EGF signaling to the level achieved by TGFalpha, an effect that was partially mimicked by ErbB-3. Analysis of the mechanism underlying this trans-potentiation implied that EGF-driven homodimers of ErbB-1 are destined for intracellular degradation, whereas the corresponding heterodimers with ErbB-2 or with ErbB-3, dissociate in the early endosome. As a consequence, in the presence of either co-receptor, ErbB-1 is recycled to the cell surface and its signaling is enhanced. This latter route is followed by TGFalpha-driven homodimers of ErbB-1, and also by E4T-bound receptors, whose signaling is further enhanced by repeated cycles of binding and dissociation from the receptors. We conclude that alternative endocytic routes of homo- and hetero-dimeric receptor complexes may contribute to tuning and diversification of signal transduction. In addition, the ability of ErbB-2 to shunt ligand-activated receptors to recycling may explain, in part, its oncogenic potential.

Helical Molecular Programming

Abstract: From hexahelices to nanometer-sized fibers: Helical molecular, macromolecular, and supramolecular structures have moved into the forefront of chemical research in the last years. The information that determines the formation and sense of the helical architecture can be incorporated in the constituent molecular building blocks. The combined use of several complimentary helical assembling techniques in a hierarchical process, a method used by nature, will ultimately allow the design and construction of helical architectures such as 1 with a predefined organization and function.

Recommendations for the presentation of NMR structures of proteins and nucleic acids. IUPAC-IUBMB-IUPAB Inter-Union Task Group on the Standardization of Data Bases of Protein and Nucleic Acid Structures Determined by NMR Spectroscopy.

Abstract: The recommendations presented here are designed to support easier communication of NMR data and NMR structures of proteins and nucleic acids through unified nomenclature and reporting standards. Much of this document pertains to the reporting of data in journal articles; however, in the interest of the future development of structural biology, it is desirable that the bulk of the reported information be stored in computer-accessible form and be freely accessible to the scientific community in standardized formats for data exchange. These recommendations stem from an IUPAC-IUBMB-IUPAB inter-union venture with the direct involvement of ICSU and CODATA. The Task Group has reviewed previous formal recommendations and has extended them in the light of more recent developments in the field of biomolecular NMR spectroscopy. Drafts of the recommendations presented here have been examined critically by more than 50 specialists in the field and have gone through two rounds of extensive modification to incorporate suggestions and criticisms.

Clinical findings with implications for genetic testing in families with clustering of colorectal cancer.

Abstract: Background Germ-line mutations in DNA mismatch-repair genes (MSH2, MLH1, PMS1, PMS2, and MSH6 ) cause susceptibility to hereditary nonpolyposis colorectal cancer. We assessed the prevalence of MSH2...

Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa

Abstract: Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009.

Abstract: The European Group for Blood and Marrow Transplantation regularly publishes special reports on the current practice of haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published. HSCT today includes grafting with allogeneic and autologous stem cells derived from BM, peripheral blood and cord blood. With reduced-intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged, such as autoimmune disorders and AL amyloidosis for autologous HSCT and solid tumours, myeloproliferative syndromes and specific subgroups of lymphomas for allogeneic transplants. The introduction of alternative therapies, such as imatinib for CML, has challenged well-established indications. An updated report with revised tables and operating definitions is presented.

Positional cloning of the gene for X-linked retinitis pigmentosa 2

Abstract: X-linked retinitis pigmentosa (XLRP) results from mutations in at least two different loci, designated RP2 and RP3, located at Xp11.3 and Xp21.1, respectively. The RP3 gene was recently isolated by positional cloning, whereas the RP2 locus was mapped genetically to a 5-cM interval. We have screened this region for genomic rearrangements by the YAC representation hybridization (YRH) technique and detected a LINE1 (L1) insertion in one XLRP patient. The L1 retrotransposition occurred in an intron of a novel gene that consisted of five exons and encoded a polypeptide of 350 amino acids. Subsequently, nonsense, missense and frameshift mutations, as well as two small deletions, were identified in six additional patients. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of s-tubulin folding. Our data provide evidence that mutations in this gene, designated RP2, are responsible for progressive retinal degeneration.

Lipids are required for directional pollen-tube growth

Abstract: Successful pollination and fertilization are absolute requirements for sexual reproduction in higher plants. Pollen hydration, germination and penetration of the stigma by pollen tubes are influenced by the exudate on wet stigmas and by the pollen coat in species with dry stigmas. The exudate allows pollen tubes to grow directly into the stigma, whereas the pollen coat establishes the contact with the stigma. Pollen tubes then grow into the papillae, which are covered by a cuticle. The components of the exudate or pollen coat that are responsible for pollen tube penetration are not known. To discover the role of the exudate, we tested selected compounds for their ability to act as functional substitutes for exudate in the initial stages of pollen-tube growth on transgenic stigmaless tobacco plants that did not produce exudate. Here we show that lipids are the essential factor needed for pollen tubes to penetrate the stigma, and that, in the presence of these lipids, pollen tubes will also penetrate leaves. We propose that lipids direct pollen-tube growth by controlling the flow of water to pollen in species with dry and wet stigmas.

Sulfate-Induced Eutrophication and Phytotoxicity in Freshwater Wetlands

Abstract: In recent decades, sulfate concentrations in many European freshwater wetlands have increased by 10-fold or more, due mainly to the use of sulfate-polluted river water to compensate for water shortage in these areas. To test the effect of sulfate enrichment, a mesocosm experiment was set up, using waterlogged soil cores, intact with vegetation, from a mesotrophic fen meadow. During sulfate addition at environmentally relevant levels (0, 2, and 4 mmol L -1 ), phosphate concentration and alkalinity of the pore water rapidly rose due to increased sulfate reduction rates. Free sulfide accumulated to levels toxic to several wetland plant species and biomass regrowth after harvesting was significantly lower on treated soils, especially for Carex species. Eventually, the concentrations of ammonium, phosphate, and potassium increased strongly in the treated soils due to reduced uptake by plants and extra mineralization. Sulfate availability was rate limiting, until the supply of readily decomposable organic matter became limited. It is argued that the significance of the observed changes in free sulfide concentrations and in the rate of nutrient mobilization should be recognized, and that these effects can be as important as direct eutrophication caused by the import of nutrients. The reported changes may severely influence the plant species composition of freshwater wetlands.

Interlingual homograph recognition: Effects of task demands and language intermixing

Abstract: A series of three lexical decision experiments showed that interlingual homographs may be recognized faster than, slower than, or as fast as monolingual control words depending on task requirements and language intermixing. In Experiment 1, Dutch bilingual participants performed an English lexical decision task including English/Dutch homographs, cognates, and purely English control words. Reaction times to interlingual homographs were unaffected by the frequency of the Dutch reading and did not differ from monolingual controls. In contrast, cognates were recognized faster than controls. In Experiment 2, Dutch participants again performed an English lexical decision task on homographs, but, apart from nonwords, Dutch words were included which required a “no” reaction. Strong inhibition effects were obtained which depended on the relative frequency difference of the two readings of the homograph. These turned into frequency-dependent facilitation effects in Experiment 3, where participants performed a general lexical decision task, responding “yes” if a word of either language was presented. It is argued that bilingual word recognition models can only account for the series of experiments if they explain how lexical processing is affected by task demands and stimulus list composition.

Job characteristics and employee well-being: a test of Warr's Vitamin Model in health care workers using structural equation modelling

Abstract: Warr's (1987) Vitamin Model was investigated in a representative sample of 1437 Dutch health care workers (i.e. nurses and nurses' aides). According to this model, it was hypothesized that three job characteristics (i.e. job demands, job autonomy, and workplace social support) are curvilinearly related with three key indicators of employee well-being (i.e. job satisfaction, job-related anxiety, and emotional exhaustion). Structural equation modelling (LISREL 8) was employed to test the comprehensive Vitamin Model. The results showed that the fit of the non-linear model is superior to that of the linear model. Except for the relationship between job autonomy and emotional exhaustion, the curvilinear relationships followed the predicted U-shaped or inverted U-shaped curvilinear pattern. Moreover, it appeared that the three job characteristics are differentially related with various indicators of employee well-being. In conclusion, this study partially supports the assertion of the Vitamin Model that non-linear relationships exist between job characteristics and employee well-being. © 1998 John Wiley & Sons, Ltd.

The First Nuclear-Encoded Complex I Mutation in a Patient with Leigh Syndrome

Abstract: Nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase (complex I) is the largest multiprotein enzyme complex of the respiratory chain. The nuclear-encoded NDUFS8 (TYKY) subunit of complex I is highly conserved among eukaryotes and prokaryotes and contains two 4Fe4S ferredoxin consensus patterns, which have long been thought to provide the binding site for the iron-sulfur cluster N-2. The NDUFS8 cDNA contains an open reading frame of 633 bp, coding for 210 amino acids. Cycle sequencing of amplified NDUFS8 cDNA of 20 patients with isolated enzymatic complex I deficiency revealed two compound heterozygous transitions in a patient with neuropathologically proven Leigh syndrome. The first mutation was a C236T (P79L), and the second mutation was a G305A (R102H). Both mutations were absent in 70 control alleles and cosegregated within the family. A progressive clinical phenotype proceeding to death in the first months of life was expressed in the patient. In the 19 other patients with enzymatic complex I deficiency, no mutations were found in the NDUFS8 cDNA. This article describes the first molecular genetic link between a nuclear-encoded subunit of complex I and Leigh syndrome.

Covered by Equality: The Gender Subtext of Organizations

Abstract: This paper describes the results of an empirical study of the gender subtext in organizations. We examine the divergence of practice and impression of gender distinctions: gender inequality is still persistent in organizational practices while a dominant perception of equality occurs at the same time. Our analysis focuses on the processes (re)producing this divergence. We argue that both the persistency of gender inequality and the perception of equality emerge from a so-called gender subtext: the set of often concealed, power-based gendering processes, i.e. organizational and individual arrangements (objectives, measures, habits), systematically (re)producing gender distinctions. These gendering processes are examined in five departments in the Dutch banking sector. We explore the gender subtext in three organizational settings: show pieces (the token position of the few women in top functions), the mommy track (the side track many women with young children are shunted to) and the importance of being ask...

Orientation of ECM protein deposition, fibroblast cytoskeleton, and attachment complex components on silicone microgrooved surfaces.

Abstract: The microfilaments and vinculin-containing attachment complexes of rat dermal fibroblasts (RDF) incubated on microtextured surfaces were investigated with confocal laser scanning microscopy (CLSM) and digital image analysis (DIA). In addition, depositions of bovine and endogenous fibronectin and vitronectin were studied. Smooth and microtextured silicone substrata were produced that possessed parallel surface grooves with a groove and ridge width of 2.0, 5.0, and 10.0 μm. The groove depth was approximately 0.5 μm. CLSM and DIA make it possible to visualize and analyze intracellular and extracellular proteins and the underlying surface simultaneously. It was observed that the microfilaments and vinculin aggregates of the RDFs on the 2.0 μm grooved substrata were oriented along the surface grooves after 1, 3, 5, and 7 days of incubation while these proteins were significantly less oriented on the 5.0 and 10.0 μm grooved surfaces. Vinculin was located mainly on the surface ridges on all textured surfaces. In contrast, bovine and endogenous fibronectin and vitronectin were oriented along the surface grooves on all textured surfaces. These proteins did not seem to be hindered by the surface grooves since many groove-spanning filaments were found on all the microgrooved surfaces. In conclusion, it can be said that microtextured surfaces influence the orientation of intracellular and extracellular proteins. Although results corroborate three earlier published hypotheses, they do not justify a specific choice of any one of these hypotheses. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 291–300, 1998.