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  • 1995-1999  (911)
  • 1980-1984
  • 1998  (911)
  • Numerical Methods and Modeling  (582)
  • Cell & Developmental Biology  (273)
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  • pharmacokinetics
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  • 1995-1999  (911)
  • 1980-1984
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  • 1
    ISSN: 1432-2277
    Keywords: Key words Cyclosporin ; pharmacokinetics ; kidney transplantation ; Kidney transplantation ; cyclosporin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This retrospective study served to examine the correlation between the degree of cyclosporin (CyA) exposure, as estimated by a single pharmacokinetic (PK) profile performed at 1 week post-transplant, and the outcome of 290 consecutive renal transplants performed over a 6-year period. For this retrospective analysis patients were stratified into four historical groups based on 12- versus 24-h PK studies and on the use of radioimmunoassay versus fluorescence polarization immunoassay methods for estimates of CyA concentrations. Four PK measures – trough concentration (C0), average concentration values (Cav; i. e., the dosing interval-corrected area under the concentration-time curve), maximum concentration (Cmax), and time to maximum concentration (tmax) – were examined as predictors of patient, graft, and rejection-free survival rates for each of the four groups individually and for all groups combined. Patients with an initial Cav≥ 550 ng/ml had higher 1-year (88 %) and 6-year (66 %) graft survival rates than patients with Cav 〈 550 ng/ml, who had 1- and 6-year graft survival rates of 80 % and 59 %, respectively (P = NS). Statistically significant differences were observed in graft survival rates between patients with Cav 〈 550 versus Cav≥ 550 ng/ml at 30 (88 % vs 96 %; P 〈 0.02), 60 (85 % vs 94 %; P 〈 0.007), 90 (85 % vs 94 %; P 〈 0.02), and 180 (83 % vs 92 %; P 〈 0.05) days. Moreover, patients with Cav 〈 550 ng/ml displayed more severe rejection episodes, as judged by Banff classification, than patients who displayed Cav≥ 550 ng/ml (grades II and III; 71 % vs 50 %; P = 0.036). In contrast, the C0, Cmax, and tmax values did not correlate with patient, graft, or rejection-free survival rates. The pharmacokinetic parameter of Cav correlated strongly with early graft survival and may, therefore, be a useful predictor of those renal transplant patients who may require more intensive post-transplant monitoring of CyA concentrations by serial PK studies to improve graft survival.
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Insulin ; pharmacokinetics ; acylated insulin ; NPH ; insulin therapy ; glucose turnover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary [Ne-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified insulin when infused intravenously (i. v.) secondary to its binding to circulating albumin. The duration and activity profile of the acylated (A) and NPH (B) insulins were assessed following subcutaneous (s. c.) doses of (A) 6 nmol/kg and (B) 1.2 nmol/kg (equivalent to 0.2 U/kg) in 9 subjects with IDDM. After overnight i.v infusion of regular human insulin, morning glucose was (A) 6.9 ± 0.1 and (B) 6.8 ± 0.1 mmol/l. After the s. c. injection, i. v. human insulin or glucose was infused to maintain near-basal glycaemia and tracer glucose to assess hepatic glucose production (HGP). An activity profile was deduced for each study by expressing the glucose infusion rate at each time point, as a fraction (%) of the basal (measured) HGP, and the i. v. insulin infusion rate as a fraction (%) of the basal requirement. The two fractions are combined by adding the fractional glucose infusion rate and subtracting the fractional insulin infusion rate. Infusion rates of i. v. insulin in the morning were (A) 0.96 ± 0.096 and (B) 1.22 ± 0.09 pmol · kg–1· min–1. After insulin injection, i.v insulin requirements decreased and were below 10 % of basal between 100 and 150 min. A constant activity profile of 0 % represents a perfect substitution of the basal i. v. insulin infusion by the s. c. dose. The actual profile is defined by deviations from this (above) and was –17 ± 11, 7 ± 10, –9 ± 6 and –18 ± 18 % for [Ne-palmitoyl Lys (B29)] human insulin and 17 ± 12, 5 ± 6, –9 ± 15, 22 ± 18 % for NPH insulin at 3, 6, 9 and 12 h after s. c. injection. HGP was similar for the two insulins, demonstrating similar metabolic actions and profiles both peripherally and at the liver. [Diabetologia (1998) 41: 116–120]
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  • 3
    ISSN: 1569-8041
    Keywords: CD20 ; chimeric IDEC-C2B8 ; lymphoma ; monoclonal antibody ; pharmacokinetics ; feasibility study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In clinical trials in the USA, IDEC-C2B8 (a mouse-humanchimeric anti-CD20 monoclonal antibody) has demonstrated high response rateswith only mild toxic effects in relapsed B-cell lymphoma at a dose of fourweekly 375 mg/m2 infusions. The aim of the present trial wasto determine whether or not this dose is practically applicable to Japanesepatients with relapsed B-cell lymphoma with respect to safety,pharmacokinetics and efficacy. Patients and methods: Patients with relapsed CD20+ B-cell lymphomareceived intravenous infusions of IDEC-C2B8 once a week for four weeks. Atotal of 12 patients (four at 250 mg/m2 and eight at 375mg/m2) were enrolled. Results: All 11 eligible patients treated with either dose leveltolerated IDEC-C2B8 well. Commonly observed adverse drug reactions weregrades 1 or 2 non-hematologic toxicities during the infusion, consistingmostly of flu-like symptoms and skin reactions. All of the observedhematologic toxicities were of grade 3 or less, and transient. A rapid andsustained B-cell decrease in peripheral blood was observed, but noinfectious episodes were encountered. Human anti-mouse and anti-chimericantibodies were not detected. Of the 11 eligible patients (eight withfollicular, two with diffuse large-cell and one with mantle cell lymphoma),two showed a complete response and five showed a partial response, and allof the seven responders had lymphoma with follicular histology. Apharmacokinetic analysis showed that the elimination half-life (T1/2) ofIDEC-C2B8 was 445 ± 361 hours, and that the serum antibody levelsincreased in parallel with the course of infusions, and in most patients wasstill measurable at three months. Conclusions: The dose of four weekly 375 mg/m2 infusionsof IDEC-C2B8 is safe and effective in Japanese patients with relapsed B-celllymphoma. Further studies evaluating IDEC-C2B8 are warranted.
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  • 4
    ISSN: 1569-8041
    Keywords: DMP 840 ; pharmacodynamics ; pharmacokinetics ; phase I
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: DMP 840, a novel bisnaphthalimide, has demonstrated promising schedule dependent anti-tumor activity in vitro and in vivo against several tumor cell lines. A phase I study was conducted to evaluate the effect of a 24-hour infusion schedule repeated every three weeks, on the therapeutic efficacy of DMP 840. Patients and methods: Fourteen patients with refractory solid tumor malignancies were treated with DMP 840 at doses of 20, 40, 50 and 60 mg/m2. Results: A combination of neutropenia, thrombocytopenia and stomatitis were dose-limiting at doses of 50 and 60 mg/m2 in both minimally- and extensively-pretreated patients. In contrast, all courses at lower dose levels were well tolerated. Pharmacokinetic analysis demonstrated that DMP 840 had a prolonged terminal half life (median 39 hours; range 25–86) and that dose-limiting events were significantly related to several indices of systemic DMP 840 exposure (P 〈 0.01, Wilcoxon Rank Sum test). Conclusion: The recommended dose of DMP 840 for further disease oriented evaluations is 40 mg/m2 administered over 24 hours every three weeks. The infusion duration evaluated in this study did not result in a substantial increase in the tolerable dose compared to shorter, less cumbersome schedules.
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  • 5
    ISSN: 1569-8041
    Keywords: colorectal cancer ; granulocyte-colony stimulating factor ; pharmacokinetics ; phase II ; topotecan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The premise for the study was that topotecan (TPT) resistance in preclinical studies is associated with low level expression of the p-glycoprotein (Pgp) multi-drug transporter conferred by the multi-drug resistant (MDR) phenotype, which might be overcome in clinical practice by administering moderately (2.3-fold) higher doses of TPT that have been shown to be feasible with granulocyte colony-stimulating factor (G-CSF) support. This phase II study evaluated the anti-tumor activity of TPT administered at its highest possible solid tumor dose with G-CSF in patients with fluoropyrimdine-refractory advanced colorectal carcinoma. The study also sought to identify pharmacodynamic (PD) determinants of both activity and toxicity. Patients and methods: TPT was administered as a 30-minute infusion daily for five days every three weeks at a dose of 3.5 mg/m2/day to patients with advanced colorectal carcinoma who developed progressive disease either during treatment with fluoropyrimidine-based chemotherapy for advanced disease or within six months after receiving fluoropyrimdine-based adjuvant chemotherapy. This dose of TPT was previously determined to be the maximal tolerated dose (MTD) with G-CSF support in a phase I study involving solid tumor patients with similar risk factors for myelosuppression. Plasma sampling was performed during course 1 to characterize the pharmacokinetic (PK) and PD behavior of TPT. Results: Seventeen patients who received 89 courses of TPT and G-CSF were evaluable for toxicity; 16 patients were evaluable for anti-tumor response. Toxicity, particularly myelosuppression, was substantial. At the 3.5 mg/m2/day dose level, absolute neutrophil counts (ANC) were less than 500/µl for longer than five days in 17% of courses involving seven of 17 (41%) patients. Severe neutropenia associated with fever occurred in 12.3% of courses; and platelet counts below 25,000/µl were noted in 26.9% of courses. These toxicities resulted in dose reductions in seven of 17 (41%) patients. Nevertheless, 90% of the planned total dose of TPT was administered. No major responses were observed, though minor activity was noted in several patients. Both the median time to progression and the median survival time were short – 2.5 and four months, respectively. Although interindividual variability in the disposition of total TPT was observed, the lack of objective responses precluded PD assessments related to disease activity. Total TPT exposure was significantly higher than drug exposure achieved in similar patients at an identical dose in a previous phase I study of TPT and G-CSF, which may explain why more severe myelosuppressive effects occurred in the present study. There were no PD relationships evident between relevant PK parameters and the percent decrements in platelets and ANCs during course 1, although patients with severe toxic effects (ANC below 500/µl for more than five days and/or platelets 〈25,000/µl) had higher drug exposure than patients with less severe toxicity (P 〈 0.018 and P = 0.09, respectively). Conclusions: Based on these results, the true response rate of TPT at its solid tumor MTD with G-CSF support is unlikely to approach 20%. Although a response rate of less than 20% might be viewed as significant in this disease setting and might be confirmed with sufficient statistical certainty by treating additional patients, the substantial toxicity, inconvenience, and cost associated with this high dose TPT/G-CSF regimen does not warrant the acceptance of a lower level of anti-tumor activity as a criterion for further development.
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  • 6
    ISSN: 1569-8041
    Keywords: genetic polymorphism ; glucuronidation ; irinotecan ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Irinotecan (CPT-11) is metabolized by esterase to form a SN-38, which is further conjugated by UGT1A1. Genetic polymorphism has been shown in a promoter region of UGT1A1 and is related to its activity. We investigated whether there might be an inter-individual difference in pharmacokinetics of SN-38 and its glucuronide, depending on the genotypes of UGT1A1. Patients and methods: Nine male patients with lung cancer were treated with irinotecan (50 mg/m2) and carboplatin. Pharmacokinetic parameters were calculated with full sampling plasma data. Genotypes were determined by analyzing the sequence of TATA box of UGT1A1 of genomic DNA from the patients. Results: The genotyping analysis revealed one heterozygote (6/7) and one homozygote (7/7) for (TA)7TAA allele (UGT1A1*28). The remaining seven patients were homozygote for (TA)6TAA allele (6/6, wild type). The metabolic ratios (SN-38/SN-38 glucuronide) in the patient with 7/7 genotype were uncharacteristically higher than those in the patients with other genotypes (6/6 and 6/7). Biliary index was 6980 versus 2180 ± 1110 (range 840–3730) in patients with 7/7 versus 6/6 genotypes, respectively. Conclusion: These results support the idea that the patient with 7/7 genotype has an impaired capacity for glucuronidation of SN-38.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of gastroenterology 33 (1998), S. 785-791 
    ISSN: 1435-5922
    Keywords: Key words: gastric emptying rate ; paracetamol (acetaminophen) ; pharmacokinetics ; rate of absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: The paracetamol absorption technique, a widely used method for evaluating the gastric emptying rate of liquids, appears to be performed inappropriately, resulting from a lack of consideration of pharmacokinetics in paracetamol absorption. This review suggests that appropriate study designs and logical choice of the parameters for the rate of paracetamol absorption are the cornerstone of reliable investigation of gastric emptying using the paracetamol method.
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  • 8
    ISSN: 1573-904X
    Keywords: tacrolimus ; bioavailability ; metabolism ; intestine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Tacrolimus, an immunosuppressive agent, has poor and variable bioavailability following oral administration in clinical use. We investigated the contribution of intestinal metabolism to the first pass effect of tacrolimus in rats. Methods. Tacrolimus was administered intravenously, intraportally or intraintestinally to rats. Blood samples were collected over a 240-min period, and blood tacrolimus concentrations were measured. The extraction ratios of tacrolimus in the intestine and liver were investigated. In addition, the metabolism of tacrolimus in the everted sacs of the small intestine was examined. Results. The rate of absorption of tacrolimus in the intestine was rapid, and tacrolimus was almost completely absorbed after intestinal administration. The bioavailability of tacrolimus was about 40% and 25% after intraportal and intraintestinal administration, respectively, indicating that tacrolimus is metabolized in both the intestine and the liver. In addition, tacrolimus was significantly metabolized in the everted sacs of the rat intestine. Conclusions. The present study suggested that the metabolism of tacrolimus in the intestine contributes to its extensive and variable first pass metabolism following the oral administration.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 15 (1998), S. 1888-1894 
    ISSN: 1573-904X
    Keywords: prednisolone ; sirolimus ; immunosuppressant ; interaction ; pharmacokinetics ; pharmacodynamics ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To assess pharmacokinetic and pharmacoimmunodynamic interactions between prednisolone (Pred, 1 mg/kg) and sirolimus (Sir, 0.25 mg/kg) in rabbits. Methods. After intravenous administration, plasma concentrations of Pred and corticosterone, and Sir blood concentrations were followed for 24 hours along with blood granulocyte and T-helper cell counts. Ex vivo and in vitro whole blood lymphocyte proliferation marked lymphocyte reactivity. Results. Pred terminal half-life and clearance were 1.1 hr and 0.72 l/ hr/kg with no difference after Sir. Sir values were 13 hr and 0.16 1/hr/ kg and Pred produced no changes. Corticosterone production (0−12hr) was suppressed by 55% after Pred alone or combined, while Sir did not cause adrenal suppression. Blood T-helper cells and granulocytes displayed circadian rhythms after placebo. Over 12 hr, T-helper cell counts were decreased by Pred (40%) and Sir (19%) while granulocyte numbers increased by 56% and 23%. After coadministration, cell numbers were similar to Pred alone. Pred and Sir decreased lymphocyte reactivity by 41% and 56% over 24 hr and their combination reached 85% inhibition with additive interaction. In vitro studies showed antagonistic or synergistic interactions depending on drug concentration ratios. Conclusions. At therapeutic concentrations, Sir and Pred do not significantly interact pharmacokinetically and have additive pharmacoimmunodynamics. Thus, the therapeutic application of this combination is promising.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 15 (1998), S. 570-575 
    ISSN: 1573-904X
    Keywords: microdialysis ; codeine ; morphine ; blood-brain barrier ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of the study was to investigate the distribution of codeine across the blood-brain barrier (BBB) in rats by micro-dialysis (MD). Methods. Rats were administered intravenous infusion of codeine in doses of (1) 10 mg/kg, (2) 20 mg/kg for 10 min, and (3) an exponential infusion for 2 h aiming at a plasma concentration of 2500 ng/ml, in a crossover design (n = 6). Microdialysis was used to determine codeine unbound concentrations in blood and brain extracellular fluid (ECF). Total brain tissue and plasma concentrations were also determined. Nalorphine was used as a calibrator for measurement of in vivo recovery. Results. Relative recovery and retrodialysis loss of codeine and nalorphine were similar both in vitro and in vivo. Codeine was rapidly transported into the brain ECF with identical influx and efflux clearance across the BBB. The AUC ratios of brain to blood were 0.99 ± 0.25 and 0.95 ± 0.16 for Dose 1 and 2, respectively. The Css ratio of brain to blood was 1.06 ± 0.12 for the exponential infusion. The half-lives were 25 ± 4 min, 22 ± 2 min in blood and 27 ± 5 min, 25 ± 5 min in brain for Dose 1 and Dose 2, respectively. Total brain tissue concentrations were 3.6 ± 1.2-fold higher than the unbound concentrations in brain. Codeine was demethylated to morphine with an unbound AUCbIood,morphine/AUCblood,codeine ratio of 7.7 ± 5.1% in blood. No morphine was detected in brain MD, but total concentrations were possible to measure. Conclusions. Codeine rapidly reached a distributional equilibrium with equal unbound concentrations in blood and brain. The brain transport of codeine did not show any dose-dependency.
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  • 11
    ISSN: 1573-904X
    Keywords: administration ; antisense ; bioavailability ; gastrointestinal ; intra-peritoneal ; intra-tracheal ; ISIS 3521 ; oligonucleotide ; oral ; pharmacokinetics ; subcutaneous
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Phosphorothioate antisense oligodeoxynucleotides are promising therapeutic candidates. When given systemically in clinical trials they are administered via slow intravenous infusion to avoid their putative plasma concentration-dependent haemodynamic side-effects. In this study, we have evaluated alternative parenteral and non-parenteral administration routes which have the potential to enhance the therapeutic and commercial potential of these agents. Methods. The delivery of CGP 64128A by intravenous, subcutaneous, intra-peritoneal, oral and intra-tracheal (pulmonary) routes was investigated in rats using radiolabelled compound and supported by more specific capillary gel electrophoretic analyses. Results. Intravenously administered CGP 64128A exhibited the rapid blood clearance and distinctive tissue distribution which are typical for phosphorothioate oligodeoxynucleotides. Subcutaneous and intra-peritoneal administration resulted in significant bioavailabilities (30.9% and 28.1% over 360 min, respectively) and reduced peak plasma levels when compared with intravenous dosing. Administration via the gastrointestinal tract gave negligible bioavailability (〈2%). Intra-tracheal administration resulted in significant but dose-dependent bioavailabilities of 3.2, 16.5 and 39.8% at 0.06, 0.6 and 6.0 mg/kg, respectively. Conclusions. Significant bioavailabilities of CGP 64128A were achieved following subcutaneous, intra-peritoneal and intra-tracheal administration. Pulmonary delivery represents a promising mode of non-parenteral dosing for antisense oligonucleotides. The dose-dependent increase in pulmonary bioavailability suggests that low doses may be retained in the lungs for local effects whereas higher doses may be suitable for the treatment of a broader spectrum of systemic diseases.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 15 (1998), S. 883-888 
    ISSN: 1573-904X
    Keywords: transdermal access ; skin erosion ; transdermal ; dermal interstitial fluid ; sampling ; glucose ; monitoring ; diabetes mellitus ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe a dermally non-invasive serial sampling technique and to test its clinical feasibility with regard to glucose measurement. Methods. A standardized skin mini-erosion devoid of the epidermal barrier, and covered by an artificial one, was formed by a suctioning technique. Interstitial fluid (IF) was extracted serially by brief application of negative pressure, and its glucose content compared with that in capillary or venous blood samples. Results. The procedure caused no discomfort. The epidermis regenerated rapidly after experimentation. There were no complications. In non-diabetic subjects (n = 13) the mean of all IF values measured daily for 6 days was 6.2 ± 0.1 mmol/1 (±SE). The corresponding capillary blood glucose value was 5.6 ± 0.1 mmol/1, and the venous glucose value was 5.4 ± 0.1 mmol/1. The differences between IF glucose values and invasive control values remained within narrow limits throughout. The 2SD limits of agreement for the differences were 1.44 mmol/1 (IF vs. capillary blood samples) and 1.76 mmol/1 (IF vs venous samples) respectively. The OGTT curves suggested glucose kinetics to be similar in IF and in capillary blood. In diabetic subjects, the mean of IF values determined serially during one day was 15.3 ± 1.0 mmol/1 (range, 6.7−21.8 mmol/1), and the corresponding mean capillary value was 12.0 ± 0.9 mmol/1 (range, 3.3−17.2 mmol/1). The ICC for all paired photometric observations was 0.948. Conclusions. The results suggest the new sampling technique to be a feasible approach for clinical and experimental purposes. A functionally integrated sampling patch is entering the clinical testing stage.
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  • 13
    ISSN: 1573-904X
    Keywords: angiotensin II receptor antagonist ; TH-142177 ; rat tissues ; ex vivo receptor occupancy ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study the relationship between angiotensin II (All) receptor occupancy ex vivo in tissues plasma concentration and hypotensive effect of a novel All receptor antagonist, TH-142177 and losartan in rats. Methods. At 2, 8 and 24 hr after oral administration of TH-142177 and losartan in rats, All receptors in myocardium, adrenal cortex and cerebral cortex were determined by radioligand binding assay using [125I]Sar1,Ile8-AII. Plasma concentrations of both drugs and metabolite in rats were also measured using validated HPLC assays. Further, systolic blood pressure (SBP) in conscious renal hypertensive rats treated orally with TH-142177 and losartan were measured by using a tail cuff plethysmographic method. Results. Oral administration of TH-142177 (1.8 and 5.5 μmol/kg) and losartan (6.5 and 21.7 μmol/kg) in rats brought about dose-dependent decreases in [125I]Sar1,Ile8-AII binding sites (Bmax) in myocardium and adrenal cortex. The extent of receptor occupancy by both drugs in adrenal cortex was maximal at 2 hr later but that in myocardium at 8 hr later. Further, the receptor occupancy was more sustained in myocardium than adrenal cortex. The ex vivo binding affinity of TH-142177 for All receptors in these tissues was roughly three times higher than that of losartan. Also, cerebral cortical [125I]Sar1,Ile8-AII binding was significantly reduced by oral administration of losartan but not by TH-142177. The time course of All receptor occupancy by both drugs in adrenal cortex appeared to be in parallel with that of their plasma concentrations, while the time course in myocardium correlated with that of their hypotensive effects rather than plasma concentrations. Conclusions. TH-142177 produced a relatively selective and sustained occupancy ex vivo of All receptors in myocardium and adrenal cortex of rats with approximately three times greater potency than losartan. Its time course of myocardial receptor occupancy was in parallel with that of hypotensive effect rather than plasma concentration.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 15 (1998), S. 904-910 
    ISSN: 1573-904X
    Keywords: GS522 ; oligodeoxynucleotide ; pharmacokinetics ; tritiated ; biodistribution ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the pharmacokinetic and tissue distribution profiles of a nucleotide-based thrombin inhibitor (GS522, phosphodiester oligonucleotide, GGTTGGTGTGGTTGG) following intravenous administration to rats. Methods. Pharmacokinetic study: 10 mg/kg, 20 mg/kg, 30 mg/kg (6 animals/dose) were administered to rats by rapid injection into the femoral vein. Blood samples were collected over a 45 minute period. Plasma concentrations of GS522 were determined using capillary gel electrophoresis with laser-induced fluorescence detection. Biodistribution Study: l0mg/kg (400μl, 31.46 μCi/ml) of 3H-GS522 was administered to rats by rapid injection into the femoral vein. The animals were sacrificed by decapitation at 1, 5, 10, 30, 60, 360 minutes post-dose (3 rats/point). Brain, blood, duodenum, eyes, heart, kidney, liver, lungs, muscle, pancreas, skin, spleen and vein samples were collected, processed and quantitated using liquid scintillation counting. Results. The pharmacokinetic profile declines in multiexponential manner, exhibiting extremely fast distribution and elimination (t1/2 = 7.6−9.0 min, Cl = 22.0−28.0 ml/min, V = 83.9−132.4 ml/kg). GS522 follows linear pharmacokinetics, with the area under the curve being proportional to the dose (Rsq = 0.9744). Highest radioactivity levels were detected in kidney, liver and blood (39.7, 15.7 and 15.3% dose/ respective organ). Less than 1% of the dose was detected in the heart, spleen and lungs, and 〉0.3% of the dose was found in the brain and eyes. The oligonucleotide associated radioactivity was uniformly distributed between the brain regions (left and right lobe and cerebellum). Six hours following the dose administration a statistically significant increase (p 〈 0.05) in radioactivity levels was observed in the brain, eyes, skin, liver, pancreas and vein. Conclusions. The pharmacokinetic and biodistribution profiles of GS522 following intravenous administration to rats at three doses were characterized. The oligonucleotide associated radioactivity was widely distributed in tissues. The amount of radioactivity sharply decreased with time in most tissues. Kidney, liver and muscle were the main sites of accumulation. The oligonucleotide associated radioactivity did not cross the blood brain barrier to an appreciable extent. In addition, a statistically significant increase (p 〈 0.05) in the radioactivity levels observed in select tissues suggested a re-uptake mechanism for intact oligonucleotide or its degradation products.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 15 (1998), S. 1196-1201 
    ISSN: 1573-904X
    Keywords: guar gum ; sustained release ; extended release ; diltiazem ; dissolution ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study was performed to examine the use of guar gum to sustain the release of diltiazem under in vitro and in vivo conditions. Methods. Guar gum tablet formulations were prepared and evaluated under a variety of in vitro dissolution conditions. The formulations, along with Dilacor XR®, were administered to a group of eight fasted, healthy volunteers in a four period crossover study. Results. Varying the lot of guar gum as well as using guar from different suppliers had little effect on diltiazem dissolution. Also, dissolution of diltiazem from guar gum tablets was essentially independent of stir speed under normal conditions (USP Apparatus II). The stability of guar-based formulations under stressed conditions (40°C/75% relative humidity for 3 months) was also established. All four formulations gave similar plasma concentrations over time in the healthy volunteers pharmacokinetic study. Conclusions. Guar gum-based matrix tablets represent a simple and economical alternative to existing diltiazem sustained release dosage forms.
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  • 16
    ISSN: 1573-904X
    Keywords: risedronate ; gastrointestinal absorption ; gastrointestinal site ; bisphosphonate ; administration rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Two studies were conducted to compare the absorption of risedronate administered as a solution to three different gastrointestinal sites (study A) and to determine the extent of absorption of risedronate solution administered by rapid and slow infusion to the second part of the duodenum (study B). Methods. Each study was designed as a single-dose, crossover (three periods, study A; two periods, study B) trial in healthy male subjects, with a 14-day washout period between dosing. Subjects fasted overnight before drug administration and for 4 hours after drug administration. In study A, a risedronate solution of 40 mg in 30 mL of water was administered directly into the stomach, the second part of the duodenum, or the terminal ileum over 1 minute via a nasoenteral tube in a three-period crossover design. In study B, a risedronate solution of 40 mg in 30 mL of water was administered directly into the second part of the duodenum over 1 minute and over 1 hour in a randomized, two-period crossover design. Serum and urine samples were obtained for 48 hours after dosing for risedronate analysis. Results. Eight subjects completed each study. No statistically significant site-specific differences in any pharmacokinetic parameter were observed (study A). Based on the area under the serum concentration-time profile and the amount of drug excreted in the urine unchanged, the extent of risedronate absorption did not differ significantly following a rapid or a slow infusion (study B). Only minor symptomatic complaints were reported by subjects, such as headaches and body aches. Conclusions. These studies indicate that the rate and extent of risedronate absorption are independent of the site of administration along the gastrointestinal tract, and that the extent of absorption is not affected by the rate of administration.
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  • 17
    ISSN: 1573-904X
    Keywords: propofol ; pharmacokinetics ; pharmacodynamics ; rats ; EEG ; fat emulsion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The influence of different intravenous formulations on the pharmacokinetics and pharmacodynamics of propofol was investigated using the effect on the EEG (11.5-30 Hz) as pharmacodynamic endpoint. Methods. Propofol was administered as an intravenous bolus infusion (30 mg/kg in 5 min) or as a continuous infusion (150 mg/kg in 5 hours) in chronically instrumented male rats. Propofol was formulated as a 1% emulsion in an Intralipid 10%®-like fat emulsion (Diprivan-10®, D) or as a 1%- or 6% emulsion in Lipofundin® MCT/LCT-10% (Pl% and P6%, respectively). EEG was recorded continuously and arterial blood samples were collected serially for the determination of propofol concentrations using HPLC. Results. Following bolus infusion, the pharmacokinetics of the various propofol emulsions could adequately be described by a two-compart-mental pharmacokinetic model. The average values for clearance (Cl), volume of distribution at steady-state (Vd,ss) and terminal half-life (t1/2, λ2) were 107 ± 4 ml/min/kg, 1.38 ± 0.06 l/kg and 16 ± 1 min, respectively (mean ± S.E., n = 22). No significant differences were observed between the three propofol formulations. After continuous infusion these values were 112 ± 11 ml/min/kg, 5.19 ± 0.41 l/kg and 45 ± 3 min, respectively (mean±S.E., n = 20) with again no statistically significant differences between the three propofol formulations. Comparison between the bolus- and the continuous infusion revealed a statistically significant difference for both Vd,ss and t1/2, λ2 (p 〈 0.05), whereas Cl remained unchanged. In all treatment groups infusion of propofol resulted in a burst-suppression type of EEG. A profound hysteresis loop was observed between blood concentrations and EEG effect for all formulations. The hysteresis was minimized by a semi-parametric method and resulted in a biphasic concentration-effect relationship of propofol that was described non-parametrically. For P6% a larger rate constant onset of drug effect (t,1/2, keo) was observed compared to the other propofol formulations (p〈0.05). Conclusions. The pharmacokinetics and pharmacodynamics of propofol are not affected by to a large extent the type of emulsion nor by the concentration of propofol in the intravenous formulation.
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  • 18
    ISSN: 1573-904X
    Keywords: morphine ; morphine-3-glucuronide ; P-glycoprotein ; pharmacokinetics ; pharmacodynamics ; antinociception ; central nervous system ; analgesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The objective of this study was to evaluate the effect of a potent P-gp inhibitor, GF120918, on the systemic pharmacokinetics and antinociceptive pharmacodynamics of a single intravenous dose of morphine in rats. Methods. Male Sprague-Dawley rats received either 500 mg base/kg/d GF120918 or vehicle for 4 days by gavage, or no pretreatment. On day 4, morphine was administered as a 1- or 2-mg/kg i.v. bolus. Antinociception, expressed as percent of maximum possible response (%MPR), was evaluated over 300 min after morphine administration. Serial blood samples were collected and analyzed for morphine and morphine-3-glucuronide (M3G) by HPLC. Results. Morphine clearance and distribution volume were not altered significantly by GF120918. M3G AUC in the GF120918-treated rats was approximately 2-fold higher than in vehicle-treated rats. For both morphine doses, %MPR and the area under the effect-time curve at 300 min were significantly higher in the GF120918-treated rats. A pharmacokinetic/pharmacodynamic effect model accurately described the effect-concentration data for the rats that received 1-mg/kg morphine; ke0 was significantly smaller for GF 120918- vs. vehicle-treated and control rats (0.060 ± 0.028 vs. 0.228 ± 0.101 vs. 0.274 ± 0.026 min−1, p=0.0023). EC50 and γ were similar between treatment groups. Conclusions. Pretreatment with GF 120918 enhanced morphine antinociception, as assessed by the hot-lamp tail-flick assay, and elevated systemic M3G concentrations in rats. The differential pharmacologic response to morphine in the GF120918-treated animals could not be attributed to alterations in systemic morphine pharmacokinetics.
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  • 19
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; tissue-isolated tumor ; liposome ; emulsion ; intratumoral injection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Pharmacokinetic properties of various lipid carriers (liposome and emulsions) after intratumoral injection were studied in perfusion experiments using tissue-isolated tumor preparations of Walker 256 carcinosarcoma. Methods. Four types of lipid carriers, large emulsion (254 nm), small emulsion (85 nm), neutral liposomes (120 nm) and cationic liposomes (125 nm) were prepared. We quantified their recovery from the tumor, leakage from the tumor surface and venous outflow after intratumoral injection into perfused tissue-isolated tumors, and analyzed venous appearance curves based on a pharmacokinetic model. Results. In contrast to the small emulsion and neutral liposomes, which immediately appeared in the venous outflow perfusate following intratumoral injection, the appearance of the cationic liposomes and the large emulsion was highly restricted, clearly demonstrating that intratumoral clearance of these formulations can be greatly retarded by the cationic charge and large particle size, respectively. The venous appearance rate-time profiles were fitted to equations derived from a two-compartment model by nonlinear regression analysis. When the calculated parameters were compared among these four formulations, the venous appearance rate did not exhibit such a large difference; however, the rate of transfer from the injected site to the compartment which involves clearance by venous outflow was all very different. Conclusions. The results of this study indicate that the determining factor which alters the pharmacokinetic properties of these lipid carriers after intratumoral injection is not the rate of transfer from the interstitial space to the vascular side but the rate of intratumoral transfer from the injection site to the well-vascularized region.
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  • 20
    ISSN: 1573-904X
    Keywords: primidone ; bioavailability ; human ; pharmacokinetics ; in vitro dissolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine if large differences in the in vitro dissolution profiles for primidone tablets would result in significant bioavailability differences. Methods. Two separate bioavailability studies were conducted. The first study used 18 healthy subjects and compared the bioavailability of an old 50 mg tablet formulation, a new 50 mg tablet formulation, and a suspension containing 50 mg/ml of primidone. The second study enrolled 24 subjects who were to receive a new 250 mg tablet formulation, two lots of an old 250 mg tablet formulation and a 250 mg tablet from a second manufacturer. In vitro dissolution was conducted over 90 minutes, using USP 23 Apparatus 2 at 50 rpm, with 900 ml of water. Results. Dissolution at 90 minutes for the old and new 50 mg tablets was approximately 20% and 100%, respectively. The dissolution of the four 250 mg tablets ranged from approximately 30% to 100%. The 50 mg tablet that dissolved slower had a longer Tmax and a 14% lower Cmax than the more rapidly dissolving tablet, but the AUC(0−∞) values differed by only 3%. Only nine subjects completed the 250 mg study because of side effects. The differences in Cmax and AUC(0−∞) among the four 250 mg tablets were less than 7%. Conclusions. Even though there were large differences in the in vitro dissolution of the 50 mg and the 250 mg primidone tablets, the two 50 mg tablets were shown to be bioequivalent, as were the four 250 mg tablets.
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  • 21
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    Pharmaceutical research 15 (1998), S. 1782-1786 
    ISSN: 1573-904X
    Keywords: bioavailability ; pharmacokinetics ; squalene synthase inhibitor ; prodrug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To estimate and compare the oral bioavailability of a drug (BMS-187745) administered as single doses of oral solution of either the parent drug or its prodrug (BMS-188494). Methods. A single-dose, two-period, three-treatment, control-balanced, residual-effect, incomplete block crossover study was completed in 16 healthy male subjects. All subjects received a 10 mg IV infusion of BMS-187745, and a single oral dose of either BMS-187745 (PO1) or BMS-188494 (PO2). A model is proposed to calculate the oral bioavailability of BMS-187745 which has a long half-life; incomplete data points were available to characterize its elimination phase. The plasma concentration-time data obtained following IV infusion of parent drug, and after administration of either PO1 or PO2 treatment were fitted simultaneously with systemic pharmacokinetic parameters shared by both the oral and IV routes of administration. Results. The best simultaneous fittings of the plasma concentration-time data were obtained by using a biexponential pharmacokinetic model with a first-order absorption rate constant. The mean bioavailability (F) values of BMS-187745 estimated by the proposed model were 26.5% and 2.6% when given as oral solution of its prodrug and as the parent drug. The coefficient of variation (CV) of these F values are reasonable, ranging from 38−40%. In contrast, F calculated by the model-independent AUC method exhibited high CV, ranging from 111−120%. Conclusions. The oral bioavailability values estimated by the proposed model were more reasonable compared to those calculated by the model-independent AUC method. The proposed approach may be useful for estimating bioavailability of long half-life drugs when incomplete data points are available to characterize their elimination phase.
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  • 22
    ISSN: 1573-904X
    Keywords: pegylation ; blood-brain barrier ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Peptide drug delivery to the brain requires optimization of (a) plasma pharmacokinetics and (b) blood-brain barrier (BBB) permeability. In the present studies, plasma pharmacokinetics are improved with protein pegylation and BBB transport is facilitated with the use of vector-mediated drug delivery using the OX26 monoclonal antibody (MAb) to the rat transferrin receptor, which undergoes receptor-mediated transcytosis through the BBB in vivo. Methods. A conjugate of OX26 and streptavidin (SA), designated OX26/SA, was prepared in parallel with the carboxyl-directed pegylation of brain-derived neurotrophic factor (BDNF). A novel bifunctional polyethyleneglycol (PEG) was used in which a hydrazide (Hz) was attached at one end and a biotin moiety was attached to the other end. This allowed for conjugation of BDNF-PEG-biotin to OX26/SA. Results. The brain uptake of BDNF-PEG-biotin was increased following conjugation to OX26/SA to a level of 0.144 ± 0.004% injected dose per g brain and a BBB permeability-surface area product of 2.0 ± 0.2 μL/min/g. Conclusions. These studies demonstrate that peptide drug delivery to the brain can be achieved with advanced formulation of protein-based therapeutics. The formulation is intended to (a) minimize rapid systemic clearance of the peptide, and (b) allow for vector-mediated drug delivery through the BBB in vivo. Following this dual formulation, the brain uptake of a neurotrophin such as BDNF achieves a value that is approximately 2-fold greater than that of morphine, a neuroactive small molecule.
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  • 23
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    Bulletin of experimental biology and medicine 126 (1998), S. 1098-1099 
    ISSN: 1573-8221
    Keywords: pharmacokinetics ; antipyrine ; individual resistance to hypoxia ; cold stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It is shown that the parameters of antipyrine pharmacokinetics during cold exposure depend on individual resistance to hypoxia. High-resistant rats are characterized by less intense metabolism and more rapid normalization of pharmacokinetic parameters than lowresistant rats characterized by shortened elimination half-time corresponding to a more rapid metabolism of xenobiotics under conditions of cold stress.
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  • 24
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    Veterinary research communications 22 (1998), S. 257-263 
    ISSN: 1573-7446
    Keywords: anthelmintics ; Fasciola ; nutrition ; pharmacokinetics ; sheep ; triclabendazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of two qualities of feed on the kinetic disposition of triclabendazole (TCBZ) metabolites was investigated in sheep (n = 4) following oral administration of TCBZ at 10 mg/kg body weight. The same sheep were given sequentially two qualitatively different diets: a low-quality (LQ) diet based on wheat straw ad libitum, and a high-quality (HQ) diet based on barley+alfalfa. The triclabendazole sulphoxide (TCBZSO) and triclabendazole sulphone (TCBZSO2) concentrations were determined in blood samples taken serially from the jugular vein between 5 min and 9 days after TCBZ administration. The parent drug TCBZ was not detected in any of the samples. The quality of feed affected the kinetics of both TCBZ metabolites. The rate of appearance (Tlag and Tmax) in the jugular blood was slower and the formed amount (AUC) of TCBZSO was slightly higher when the sheep were on the LQ diet (Tlag = 7.74 h; Tmax = 27.91 h; AUC = 1042 μg.h/ml) than when they were offered the HQ diet (Tlag = 1.90 h; Tmax = 16.01 h; AUC = 832.4 μg.h/ml). The MRT of TCBZSO was about 40% longer with the LQ diet than with the HQ diet. Similarly, the rate of appearance of TCBZSO2 in plasma of sheep was slower when they were on the LQ diet than when they were on the HQ diet, suggesting an impairment of the hepatic enzymatic activity involved in the oxidation of TCBZSO to TCBZSO2.
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  • 25
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    Veterinary research communications 22 (1998), S. 533-544 
    ISSN: 1573-7446
    Keywords: calves ; dosage regimen ; oxytetracycline ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A two-way crossover study was conducted in crossbred male calves (6–8 months old) to determine the bioavailability, pharmacokinetics and dosage regimens for a long-acting formulation of oxytetracycline (OTC-LA). The half-lives of oxytetracycline after intravenous and intramuscular administration were 7.8 h and 24 h, respectively. The volume of distribution and total body clearance values of the drug were 0.86±0.07 L and 76.1±3.3 (ml/h)/kg, respectively. The maximum concentration of the drug in the serum (4.7–7.4 μg/ml) was achieved 8–10 h after intramuscular administration. The minimum therapeutic serum concentration of drug of ≥0.5 μg/ml was maintained between 15 min and 84 h after intramuscular administration. The intramuscular bioavailability of the drug was 89.1±4.2%. The dosage regimens to maintain the minimum therapeutic serum concentrations of OTC following intramuscular administration of OTC-LA were computed.
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  • 26
    ISSN: 1573-7446
    Keywords: albendazole ; anthelmintic ; goat ; in-feed ; metabolite ; pharmacokinetics ; sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two trials were conducted against natural and experimentally induced parasitic gastroenteritis in sheep and goats using an in-feed formulation of albendazole to evaluate its therapeutic and prophylactic efficacy. In the first trial, albendazole was incorporated in feed pellets to deliver an average daily dose of 0.7 mg/kg body weight in order to evaluate its prophylactic efficacy. In the second trial, feed pellets were offered to deliver an average total dose of 8.0 mg/kg body weight in two equal split doses in order to evaluate its curative efficacy. Sustained plasma concentrations of the active compound, albendazole sulphoxide, and its metabolite albendazole sulphone, sufficient to prevent establishment of infection, were achieved when the animals were allowed to feed on medicated pellets for 10 consecutive days. The bioavailability of the metabolites of albendazole following the administration of a therapeutic dose in two split doses of the in-feed formulation was sufficient to remove established adult nematodes. The concentrate feed pellets could be used for self-medicating small ruminants for therapeutic use as well as for prophylaxis based on their strategic use appropriate to the epidemiology of the parasitic disease.
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  • 27
    ISSN: 1573-7446
    Keywords: cattle ; nortestosterone ; pharmacokinetics ; residues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The synthetic androgen 19-nortestosterone (β-NT) has been used illegally as a growth promoter in cattle production in the European Union. Elimination of β-NT and its metabolites in plasma, urine and bile was studied in three cattle with cannulated gallbladders following intramuscular injection at a single site of 500 mg of the laurate ester (NTL) containing 300.5 mg β-NT. Using enzyme immunoassay quantification, plasma Cmax of free β-NT was 0.5±0.15 μg/L (mean±SEM). Concentrations of free β-NT in plasma were consistently greater than the assay limit of quantification (0.12 μg/L) for 32.7±13.42 days. Mean residence time for free β-NT in plasma was 68.5±20.75 days. Following sample preparation by immunoaffinity chromatography, high-resolution GC-MS was used to quantify β-NT and α-NT in urine and bile. β-NT was detected irregularly in urine from two of the three animals post injection. The principal metabolite present in the urine, α-NT, was detected for 160.3±22.67 days post injection. Cmax for α-NT in urine was 13.7±5.14 μg/L. Mean urinary AUC0–183 days for α-NT was 845.7±400.90 (μg h)/L. In bile, α-NT was the only metabolite detected for 174.3±8.67 days post treatment. Cmax for α-NT in bile was 40.8±12.70 μg/L and mean biliary AUC0–183 days for α-NT was 1982.6±373.81 (μg h)/L. Concentrations of α-NT in bile samples were greater than those in urine samples taken at the same time. The mean ratio of biliary:urinary AUC0–183 days was 3.0±0.72. It is concluded that bile is a superior fluid for detection of α-NT following injection of NTL, owing to the longer period during which residues may be detected after administration.
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  • 28
    ISSN: 1573-7446
    Keywords: albendazole ; metabolites ; pharmacokinetics ; route of administration ; sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of albendazole was studied in sheep following single oral and intraruminal administration at nematocidal dose rates. The disposition curves of its metabolites indicated increased uptake of the drug in sheep following intraruminal as compared to oral dosing (p〈0.05). The increased bioavailability of benzimidazole anthelmintics given by the intraruminal route could be exploited for optimizing the use of anthelmintic for sustained parasite control in small ruminants.
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  • 29
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    Geriatric nephrology and urology 8 (1998), S. 29-44 
    ISSN: 1573-7306
    Keywords: aged ; contrast sensitivity ; drug toxicity ; hyperkalemia ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 30
    ISSN: 1573-6903
    Keywords: 5,7-Dihydroxytryptamine ; intracerebroventricular administration ; serotonin release ; in vivo voltammetry ; pharmacokinetics ; striatum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immediate and long-term effects of the selective serotonergic neurotoxin 5,7-dihydroxytryp-tamine (5,7-DHT) on rat striatal serotonergic neurons were examined after its intracerebroventricular administration using in vivo voltammetry. Extracellular concentration of 5-hydroxyindoles increased immediately following intracerebroventricular 5,7-DHT injection (200 μg in 24 μl, 18 min), peaked at 1.5-2 h, and returned to normal by 4 h. 5,7-DHT diffused to the contralateral striatum in detectable amounts 9 to 12 min after the start of injection and returned to basal levels by 1.5 h. Three to 6 days after 5,7-DHT lesions, 5-hydroxytryptophan administration produced an increase in striatal 5-hydroxyindoles that was greater than that produced in pre-lesioned rats. This effect was maximal at 14 to 17 days post-lesion, and remained even after 50 days. The short-term effect of 5,7-DHT may be attributable to increased serotonin release, inhibition of uptake, or monoamine oxidase inhibition. The long-term effect of 5,7-DHT lesions may attributable to increased synthesis of serotonin or decreased reuptake in remaining serotonergic neurons.
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  • 31
    ISSN: 1573-904X
    Keywords: amphotericin B ; pharmacokinetics ; human ; gender-differences ; disposition function differences ; interspecies scaling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To elucidate the pharmacokinetics of amphotericin B in rats, mice and humans, and to perform interspecies scaling to humans using allometry. Methods. Plasma concentrations following intravenous bolus administration in rats, and mice were determined by HPLC. Human pharmacokinetic parameters elucidated from literature data were validated in a preliminary study involving a patient receiving daily infusion dose for 27 days. A critical literature review was conducted to identify appropriate pharmacokinetic parameter values in other species for interspecies scale-up. Interspecies allometric scale-up was performed across mice, rats, rabbits and dogs and the resulting predictions in humans were compared to observed values. Results. A triexponential decline in rat, mouse and human plasma concentrations were observed. No gender differences in rat pharmacokinetics were observed. In contrast to allometry, mouse CL was smaller (82 vs 116 ml/h/kg) and T0.5 (33 vs 20 h) was longer compared to rat. In the preliminary human study, Cpeak and Cmin values remained relatively constant over the duration of therapy, and a CL, MRT, T0.5, Vss and Vdarea of 26 ml/h/kg, 10 and 23 days, 6.2 and 20 L/kg, respectively, were estimated. The relative contributions of the terminal phase area in rat, mouse and human were 75%, 92% and 31%, respectively. Interspecies allometric scale-up predictions of human CL (41 ml/h/kg), CLu (467 ml/h/kg) and Vss (3.3 L/kg) were similar to reported values, whereas poor predictions of human Vuss (33 L/kg), Vdarea (4.1 L/kg) and T0.5 (3 days) were obtained. Conclusions. Insignificant accumulation in humans inspite of the long terminal T0.5 was rationalized to be due to the small terminal-phase area contribution. While human CL and Vss were sucessfully predicted in the interspecies scaling, poor predictions of human Vdarea and T0.5 were obtained, which was attributed to disposition pattern differences between humans and other species, a potential new critical factor affecting interspecies scale-up.
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  • 32
    ISSN: 1573-904X
    Keywords: IL-10 ; cytokines ; protein ; immunosuppression ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study the pharmacokinetics and ex vivo leukocyte responses of recombinant human IL-10 (rHuIL-10) following single SC and IV dosing. Methods. A randomized two-way cross-over study was undertaken in 17 healthy volunteers in which rHuIL-10 was administered as 25 μg/ kg SC and IV doses. Blood samples were collected for 48 hr after dosing to determine serum IL-10 concentrations. Inhibitory activity of IL-10 on ex vivo production of inflammatory cytokines (TNF-α and IL-1β) by LPS-treated peripheral blood cells were measured over 96 hr. Results. A physiologically-relevant modeling approach was developed to determine the pharmacokinetics for two routes of administration (SC and IV). The IV dose showed polyexponential disposition with CL of 65 mL/kg/hr, Vss of 70 mL/kg, and t1/2 of 1.94 hr. Absolute bioavailability averaged 42% for SC dosing which produced lower but sustained concentrations. Substantial and prolonged suppression of TNF-α and IL-1β production was achieved during IL-10 treatment. The Hill Function was used to account for the joint concentration-dependent immunosuppressive action of rHuIL-10 after both IV and SC doses. The IC50 values were about 0.03 ng/mL and Imax values were about 0.85 for both TNF-α and IL-lβ suppression. The degree of change as well as the duration of leukocyte response was greater after SC administration than after IV administration. Conclusions. rHuIL-10 shows favorable PK/PD characteristics especially by theSC route of administration which produced prolonged suppression of cytokine production (ex vivo) which may be applicable in various immune-related disorders.
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  • 33
    ISSN: 1573-904X
    Keywords: magnesium ; absolute bioavailability ; stable isotopes ; pharmacokinetics ; ICP-MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 34
    ISSN: 1573-904X
    Keywords: drug tracer ; labeling ; pharmacokinetics ; erythropoietin ; iodination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Pharmacokinetic (PK) studies assume that the tracer's PK is equivalent to the parent compound. This assumption is often violated. The aim of this work is to present a method enabling the ideal tracer PK, i.e. the PK of the parent compound, to be predicted from the non-ideal tracer. Methods. The procedure uses a disposition decomposition-recomposition (DDR) that assumes that the labeling mainly changes the elimination kinetics while the distribution kinetics is not significantly affected. In the DDR procedure an elimination rate constant correction factor (kCOR) is determined from a simultaneously fitting to plasma concentration data resulting from an i.v. injection of both the tracer and the parent compound. The correction factor is subsequently used to predict the ideal tracer PK behavior from the disposition function (i.v. bolus response) of the non ideal tracer. Results. The DDR method when applied to plasma level data of erythropoietin (r-HuEPO) and its iodinated tracer (l25I-r-HuEPO) from a high (4000U/kg) and a low (400U/kg) dosing of r-HuEPO in newborn lambs (n = 13) resulted in excellent agreements in the elimination rate corrected dispositions in all cases (r = 0.995, SD = 0.0095). The correction factor did not show a dose dependence (p 〉 0.05). The correction factors were all larger than 1 (kCOR = 1.94, SD = 0.519) consistent with a reduction in the EPO elimination by the iodination labeling. Conclusions. The DDR tracer correction methodology produces a better differentiation of the PK of endogenously produced compounds by correcting for the non-ideal PK behavior of chemically produced tracers.
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  • 35
    ISSN: 1573-904X
    Keywords: plasma clearance ; unbound plasma clearance ; inter-species scale-up in plasma clearance ; allometric analysis ; pharmacokinetics ; rat vs. human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate the distribution of allometric exponents for relationship of total plasma clearance of 54 extensively metabolized drugs, with wide-ranging linear clearance values, between humans and rats, to provide a rationale for the observed data, and to discuss potential significance of the findings. Methods. Human and rat plasma clearance values of 54 drugs with markedly different physicochemical properties were obtained from the literature. Standard allometric analysis was performed for each drug using both rat and human data. Unbound vs. total plasma clearances were obtained for 15 out of 54 drugs and their correlations between humans and rats were compared. Results. The mean ± SD of the allometric exponent for the 54 drugs studied is 0.660 ± 0.190. The median clearance ratio based on unit body weight is 7.41 and the median exponent is 0.645. Excluding two outliers the correlation coefficient of plasma clearance between humans and rats was 0.745 (p 〈 0.0001). For the 15 drugs, use of unbound plasma clearance approach seems to significantly improve the correlation coefficient compared to total plasma clearance (0.940 vs. 0.841). Conclusions. The present study indicates that on average, humans and rats may eliminate extensively metabolized drugs at a rate similar to that expected from the allometric or body surface area relationship of basal metabolic rate between the two species. A simple statistical distribution hypothesis is used to rationalize the species difference in plasma drug clearance. Rat may serve as an useful animal model to predict (unbound) plasma clearance of drugs in humans.
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  • 36
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    Space science reviews 84 (1998), S. 199-206 
    ISSN: 1572-9672
    Keywords: Nuclear reactions ; Nucleosynthesis ; Abundances ; Stars:Evolution ; Interior ; Rotation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We first recall the observational and theoretical facts that constitute the so-called 3He problem. We then review the chemical anomalies that could be related to the destruction of 3He in red giants stars. We show how a simple consistent mechanism can lead to the destruction of 3He in low mass stars and simultaneously account for the low 12C/13C ratios and low lithium abundances observed in giant stars of different populations. This process should both naturally account for the recent measurements of 3He/H in galactic HII regions and allow for high values of 3He observed in some planetary nebulae. We propose a simple statistical estimation of the fraction of stars that may be affected by this process.
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  • 37
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    Veterinary research communications 22 (1998), S. 87-96 
    ISSN: 1573-7446
    Keywords: anthelmintic ; albendazole ; buffalo ; cattle ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Concentrations of albendazole sulphoxide and its sulphone metabolite in plasma in cattle and buffalo were measured by high-performance liquid chromatography after single and divided intraruminal administration of albendazole at the recommended nematocidal and fasciolicidal dose rates of 7.5 and 15.0 mg/kg body weight, respectively. No significant differences in the plasma concentrations of the metabolites or their pharmacokinetic parameters were observed between cattle or buffalo at either dose rate. Pharmacokinetic analysis and the disposition curve of the metabolites indicated increased uptake of the drug in both cattle and buffalo when the same total amount of the drug was given in divided doses compared to a single dose (p〈0.05). The divided dose schedules of administration could possibly be exploited to extend the life of the available benzimidazole anthelmintics.
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  • 38
    ISSN: 1573-7446
    Keywords: anti-inflammatory ; cat ; enantiomer ; fenoprofen ; NSAID ; pharmacokinetics ; racemic ; stereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 39
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    Springer
    Veterinary research communications 22 (1998), S. 67-72 
    ISSN: 1573-7446
    Keywords: anthelmintic ; benzimidazole ; calf ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 40
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    Chichester [u.a.] : Wiley-Blackwell
    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 131-131 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: No Abstract
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  • 41
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    Chichester [u.a.] : Wiley-Blackwell
    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 123-130 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: This paper presents the electrode separation method for the boundary condition of a-Si TFT mixed-level simulation. The Poisson equation and the continuity equation are formulated into equivalent circuits. So, a circuit simulator can be used to handle the two-dimensional numerical simulation of a-Si TFT. The boundary condition problem between a semiconductor and an external circuit is solved by the electrode separation method. An electrode is separated into two nodes to fit Kirchhoff's current law and the semiconductor equations, respectively. A simple a-Si TFT/LCD circuit is taken as an example for the electrode separation method. For mixed-level simulation this technique is very useful. © 1998 John Wiley & Sons, Ltd.
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  • 42
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    Chichester [u.a.] : Wiley-Blackwell
    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 133-151 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Most traditional theories of speech production are currently based on plane waves. However, it is well known that, for acoustic waveguides, higher acoustical modes start to propagate and can become predominant above cut-on frequencies. This paper thus presents the transmission line matrix method, a numerical method initially designed for electromagnetic waves, and its adaptation to acoustic waveguides. The method, and in particular the representation of boundary conditions, is validated by comparison with known analytical theories. It is then used to show the dramatic effect of higher order modes upon the radiation characteristics of uniform ducts, as well as the importance of source location. Finally, first applications to bent and bifurcating rectangular ducts are presented, and the transfer function of a vowel [a] is shown to display frequency patterns typical of those measured on human subjects and that cannot be explained by one-dimensional propagation only. © 1998 John Wiley & Sons, Ltd.
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  • 43
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 189-205 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: The atomic mixing model that forms the basis of the IMPETUS software is described in detail. The model simulates the mixing and particle emission that occurs when a solid is bombarded with energetic particles, such as in SIMS or SNMS. The methods employed for computing the deposition of the bombarding particles and their energies along with the modelling of the particle yield and the surface recession speed are described.The material volume concentrations are governed by a set of partial differential equations. A description of the finite element method that is employed for their solution is given. Results from the application of IMPETUS II to a number of typical structures are given. © 1998 John Wiley & Sons, Ltd.
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  • 44
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 3-19 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: This paper presents an efficient space domain integral formulation of planar dielectric structures based on the concepts of multiresolution analysis (MRA) theory. Battle-Lemarie multiresolution expansions are utilized in the moment method solution of a volume integral equation for the unknown electric field. The generation of sparse moment matrices is explained in view of the cancellation property of wavelet basis functions. The formulation is then applied to two- and three-dimensional dielectric structures including waveguides and resonators, and the numerical results and consequences of matrix sparsity are discussed in detail. © 1998 John Wiley & Sons, Ltd.
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  • 45
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 21-40 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: An efficient wavelet-packet-based time-frequency technique is proposed in this paper. This technique has found applications in inverse synthetic aperture radar (ISAR). It combines the Wigner-Ville distribution (WVD) of each sub-band signal partitioned from an input signal by the wavelet-packet transform (WPT). These distributions are used to estimate the parameters in Doppler processing. Similar parametric compensation is carried out in range processing so that a specific scatterer is focused in both range and cross-range. The end result uses the Fourier imaging method to obtain a high-resolution radar image. This technique is primarily based on estimation and compensation of the Doppler scattering parameters of the dominant scatterers for improved focus. It can be of great value to the scattering-oriented ISAR imaging. © 1998 John Wiley & Sons, Ltd.
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  • 46
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 273-274 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: No Abstract
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  • 47
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 255-257 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: We re-examine the potential drop method to give a direct estimation of the absolute error in transmission-line matrix (TLM) diffusion modelling. In particular, the open-circuit boundary is taken into account. Promising results are presented with a structure relevant to thermal analysis of semiconductor devices. © 1998 John Wiley & Sons, Ltd.
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  • 48
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 259-271 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: There is a class of material processing simulators which require solution of the diffusion equation over a surface which is evolving due to some physical or chemical process related to the concentration of the diffusing species. Because of its explicit and unconditionally stable nature, the transmission line matrix (TLM) method is well suited to efficiently solve the diffusion equation in these instances. However, the methodology for using TLM on a dynamic problem space is not well established.This paper describes the development of algorithms to handle the insertion, deletion and motion of TLM nodes along the one-dimensional surface of a two-dimensional thin film process simulator called GROFILMS. These routines are completely compatible with concurrent time scaling to increase computational efficiency. Central to this development is the use of an asymmetric TLM cell which provides more flexibility for representation and minimizes the disturbance effects of these nodal operations. The scaling routines apply conservation of charge and continuity of current into the affected region to recompute the scattered or the incident pulses as a result of the evolving network. Verification of these results through comparison with known analytic solutions is achieved where possible. © 1998 John Wiley & Sons, Ltd.
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  • 49
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 41-54 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: The local support and vanishing moment property of wavelet bases have been recently used to obtain a sparse matrix representation of integral equations in the spatial domain. In this paper, an application of the cubic spline and the corresponding semi-orthogonal wavelets in the spectral domain is proposed for the evaluation of the reflection coefficient for open/short transmission lines. Because of the nearly optimal time (space)-frequency (wavenumber)-window product of the cubic spline and wavelet, the double spectral integrals appearing in the formulation can be computed more efficiently than with the commonly used piecewise sinusoidal (PWS) or triangular basis functions. It is shown that the time-frequency-window product of the triangular and PWS function are close to each other, whereas those of the cubic spline/wavelet are close to 0·5, the lowest possible value corresponding to functions of Gaussian class. Both the PWS and wavelet bases are applied to microstrip and coplanar waveguides with isotropic and anisotropic substrates, and the results are compared with published theoretical and experimental data. It is observed that even though the number of splines/wavelets required for an accurate representation of the current distribution in the transmission line is almost twice as high as the number of PWS functions, the overall computation time decreases significantly in the former case. © 1998 John Wiley & Sons, Ltd.
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  • 50
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 69-84 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: The use of wavelet expansions in numerical solutions of electromagnetic frequency-domain integral equation formulations is steadily growing. In this paper we review the recently suggested impedance matrix compression (IMC) method for a more effective integration of wavelet-based transforms into existing numerical solvers. The difference between the IMC method and the previous approaches to applying wavelets in computational electromagnetics is twofold. Firstly, the transformation is effected by means of a digital filtering approach. This approach renders the transform algorithm adaptive and facilitates the derivation of a basis which best suits the problem at hand. Secondly, the conventional thresholding procedure applied to the impedance matrix is substituted for by a compression process in which only the significant terms in the expansion of the (yet-unknown) current are retained and hence a substantially smaller number of coefficients has to be determined. A few numerical results are included to demonstrate the advantages of the presented method over the currently used ones. The feasibility of ensuring a slow growth in the number of unknowns even when there is a rapid increase in the problem complexity is shown by an illustrative example. © 1998 John Wiley & Sons, Ltd.
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  • 51
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 87-103 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: An efficient novel algorithm is introduced for ground wave propagation problems. First, ground wave propagation characteristics for a vertically polarized short electric dipole over a smooth spherical earth are reviewed, reducing the vector electromagnetic problem for the three-dimensional spherical geometry to an equivalent two-dimensional rectilinear scalar potential problem which is solved by spectral analysis and synthesis. Alternative evaluations of the spectral integral yield ray optical and normal mode solutions, which are conventionally referred to as the Norton and Wait formulations, respectively. Combining these formulations in an efficient manner yields a hybrid algorithm which is constructed so as to account adaptively for the characteristics of ground wave propagation in interference, intermediate and diffraction regions (including mixed paths) for various source and/or receiver heights. Numerical comparisons are made with reference results obtained via the parabolic equation (PE) method, in parametric ranges where PE is reliable; this permits assessment of the effectiveness of the hybrid approach. © 1998 John Wiley & Sons, Ltd.
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  • 52
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 183-184 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: No Abstract
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  • 53
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 153-166 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Most methods for the numerical calculation of inverse Laplace transformations f(t) = L-1[F(s)] have serious limitations concerning the class of functions F(s) that can be inverted or the achievable accuracy. The procedures described in the paper can be used to invert rational as well as irrational or transcendental functions of the complex variable s. The required accuracy of the results can be enhanced without changing the algorithm, only at the cost of a longer computation time. The described methods were verified with many examples including transients in lumped/distributed systems with sections of lossy multiconductor transmission lines or with distributed RC elements. © 1998 John Wiley & Sons, Ltd.
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  • 54
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: No abstract
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  • 55
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 167-181 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: In this study, a software package is described which has been developed for the simulation of detection and tracking in surface wave high frequency (SW-HF) radars. The aim is to investigate the problems related to detection and tracking of surface targets at beyond the horizon ranges. In SW-HF radars target detection and tracking involves stochastic features such as target RCS fluctuations, atmospheric, galactic and/or man-made ambient interference components, and the sea clutter with the dominant resonant Bragg returns which affect target detection are all incorporated in the package. In the model, first, terrain data are fed into the simulator by means of a specially designed graphical user interface. Then, a scenario is prepared where the radar's location, coverage and operational parameters can be defined, together with different targets and their sailing routes. The radial propagation paths for angular resolution cells are extracted from the terrain data with the lengths of (possible) sea-island transitions. The surface wave path losses are calculated over the smooth spherical earth's surface with finite conductivity. Surface roughness and mixed-path propagation effects are also included in these calculations. The target detection is performed in the frequency domain after calculation of the noise floor, signal to noise (SNR) and clutter to noise (CNR) ratios. Since SW-HF radars yield coarse range and azimuth but accurate velocity measurements, different Kalman filter techniques are applied for the target tracking, and algorithms are added to improve the track-measurement data correlation. Various simulation tests are performed and the results are presented. © 1998 John Wiley & Sons, Ltd.
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  • 56
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 187-187 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: No abstract
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  • 57
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 277-287 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: The solution of Maxwell's equations is considered using the finite difference time domain (FDTD) method and the client-server software paradigm on a heterogeneous network of distributed computers. The performance of compilers is evaluated and the PVM 3.3 message-passing harness, in both its conventional and TCP mode of operation, is compared with direct calls to the lesser known TCP/IP routines on the operating system. An example is given showing the impact of using different floating-point representations, in each subdomain, when computing field updates. As far as we are aware to date, there has been no discussion of the actual content of the communication between concurrent FDTD processes; accordingly we have defined one such protocol. © 1998 John Wiley & Sons, Ltd.
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  • 58
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 307-316 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: This paper presents an FE modelling approach for the calculation of transient eddy currents in thin conductive layers, where the complexity of the geometry prohibits both a detailed FE modelling and the use of analytical tools. The method allows an estimation of the maximum values of eddy currents at a highly reduced modelling effort and the use of a commercial FE software package. A prerequisite is a slowly varying magnetic field that can be assumed to be unaffected by the eddy currents. It is shown that neither the source of the magnetic field nor the insulating environment has to be modelled. The model is built up exclusively from 2D elements and is excited via the magnetic vector potential. The spatial distribution of the latter is calculated separately in a magnetostatic calculation based on Biot-Savart's law. It is then applied in time-varying form as a dynamic boundary condition at every node of the model. The method was applied to a simple problem for which the results of a detailed FE calculation were available, to document its validity. Further numerical results are presented for the plasma vessel and the heat radiation shield of the Wendelstein 7-X fusion experiment in the case of an emergency discharge. © 1998 John Wiley & Sons, Ltd.
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  • 59
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 55-68 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Multiresolution time domain (MRTD) analysis is applied directly to Maxwell's equations to model inhomogeneous dielectric material. In our approach, scaling and wavelet functions are used as a complete basis for the method of moments. The MRTD scheme is used to analyze different types of resonant cavity structures with varying dielectric perturbations in one, two and three dimensions. The results presented here agree very well with those obtained by FDTD, FEM and integral equation methods. MRTD allows for considerable savings in memory and computation time in comparison to FDTD, while maintaining the same accuracy of the results. © 1998 John Wiley & Sons, Ltd.
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  • 60
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 1-1 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: No Abstract
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  • 61
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 105-121 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: This paper describes a computationally efficient diakoptic algorithm for the solution of closed-mesh electrical network equations. The algorithm is designed for use with time-varying and/or discontinuous equations describing limited size power supply systems, allowing them to be torn into smaller subdivisions in a manner that is independent of their structure. The efficiency of the algorithm is demonstrated by comparing its performance with that obtained when using a more conventional sparse matrix technique, on the basis of the number of floating point operations required for the solution of a range of typical network problems. Mention is made of the parallel processes inherent in the resultant equation structure. © 1998 John Wiley & Sons, Ltd.
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  • 62
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 207-219 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: The IMPETUS II code simulates the atomic mixing and particle emission that occurs when a solid is bombarded by energetic particles (as in SIMS or SNMS). The underlying model consists of a system of partial differential equations that are solved by a finite difference method (FDM). Special techniques are also employed to model thin layers and sharp interfaces, to deal efficiently with wide homogeneous layers (when the solution is tending to a steady state), to model linear diffusion in order to smooth the sharp interfaces before they enter to domain of the FDM.In this paper the special techniques are described in detail. Results from test problems, demonstrating these techniques, are shown. An algorithm that describes the way the IMPETUS II code is structured is given. © 1998 John Wiley & Sons, Ltd.
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  • 63
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 221-229 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: This paper presents a physical-mathematical model for abrupt heterojunction transistors and its solution using numerical methods with application to InP/InGaAs HBTs. The physical model is based on the combination of the drift-diffusion transport model in the bulk with thermionic emission and tunnelling transmission through the emitter-base interface. Fermi-Dirac statistics and bandgap narrowing distribution between the valence and conduction bands are considered in the model. A compact formulation is used that makes it easy to take into account other effects such as the non-parabolic nature of the bands or the presence of various subbands in the conduction process. The simulator has been implemented for distributed memory multicomputers, making use of the MPI message-passing standard library. In order to accelerate the solution process of the linear system, iterative methods with parallel incomplete factorization-based preconditioners have been used. © 1998 John Wiley & Sons, Ltd.
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  • 64
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 273-273 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: No Abstract
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  • 65
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 233-242 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: The propagation factors of buried microstrip lines are considered. The associated eigenvalue problems are solved by the edge-based vectorial finite element method (VFEM). To improve the higher-order VFEM solutions, the problem infinite domain is truncated by second-order absorbing boundary conditions (ABCs). This reduces the number of unknowns and, consequently, the numerical effort. Owing to the many advantages of both the edge-based VFEM and the second-order ABCs, this full-wave method is implemented by a general computer program for solving unbounded domain problems involving complex geometries and inhomogeneous media. The examples presented show the validity of this technique. © 1998 John Wiley & Sons, Ltd.
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  • 66
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 243-254 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Various local absorbing boundary conditions are implemented in the TLM method and their corresponding reflections are compared as a waveguide termination. The instability in different ABCs is discussed and reflections from the terminating walls are computed. An improvement for the matched termination wall is proposed and reflection of this absorbing condition is compared with ordinary matched termination. © 1998 John Wiley & Sons, Ltd.
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  • 67
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 317-318 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: No Abstract
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  • 68
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 289-298 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Oscillatory flow present in the melt during InSb single crystal growth using an RF-heating Czochralski method has been numerically investigated by means of the finite difference method using the HSMAC algorithm. The thermal boundary conditions required for the numerical simulation model were obtained experimentally by measuring the temperature profile along the crucible of a Czochralski system by means of thermocouples mounted in the crucible. Results of numerical simulations showed that the use of a third-order upwind discretization scheme was necessary to catch the oscillatory behaviour of the fluid flow in the melt. It was shown that this oscillatory behaviour strongly depends on the crystal rotation rate. Indeed, the oscillation period increases when the crystal rotation rate is above a critical rotation rate. In order to avoid such oscillations, crystal rotation rates lower than this critical value of crystal rotation rate must be selected for the growth of high quality crystals free of striations. © 1998 John Wiley & Sons, Ltd.
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    International Journal of Numerical Modelling: Electronic Networks, Devices and Fields 11 (1998), S. 299-306 
    ISSN: 0894-3370
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: The application of the FDTD algorithm on generalized non-orthogonal meshes, following the basic ideas of Holland (1983), has been investigated by many authors for several years now, and detailed dispersion analysis as well as convergence studies have been published. Already in 1992 also a general stability criterion was given for the time integration using the standard leap-frog scheme (Lee et al.). Many authors, however, still propose some damped time stepping algorithms to work around unexpected instabilities in the discretization method. In this paper the origin of this type of instability is revealed, and a technique to obtain a stable discretization of Maxwell's equations on non-orthogonal grids is proposed. To obtain more insight into the stability properties of the method, it is reformulated according to the matrix-vector notation of the Finite Integration Technique. © 1998 John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 25-42 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: Considered is the rotation of a robot arm or rod in a horizontal plane about an axis through the arm's fixed end and driven by a motor whose torque is controlled. The model was derived and investigated computationally by Sakawa and co-authors in [7] for the case that the arm is described as a homogeneous Euler beam. The resulting equation of motion is a partial differential equation of the type of a wave equation which is linear with respect to the state, if the control is fixed, and non-linear with respect to the control.Considered is the problem of steering the beam, within a given time interval, from the position of rest for the angle zero into the position of rest under a certain given angle.At first we show that, for every L2-control, there is exactly one (weak) solution of the initial boundary value problem which describes the vibrating system without the end condition.Then we show that the problem of controllability is equivalent to a non-linear moment problem. This, however, is not exactly solvable. Therefore, an iteration method is developed which leads to an approximate solution of sufficient accuracy in two steps. This method is numerically implemented and demonstrated by an example. © 1998 by B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 59-91 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: A time-dependent Ginzburg-Landau-type model of a superconducting-normal-superconducting junction is presented. The existence and the uniqueness of the solutions are proved. When the data of the model are symmetric of some kinds, the solutions turns out to be symmetric of some kinds. In this symmetric case, an approximate model with the small thickness of the normal material in the middle of the junction as coefficients of a differential system is established for the sake of numerical computations. And also the existence and the uniqueness of the solution to this approximate model are set up. © 1998 by B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 165-185 
    ISSN: 0170-4214
    Keywords: boundary integral equations ; boundary finite element ; free edge polygonal plate ; hypersingular kernels ; Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We consider the problem of a polygonal plate with free edges. It is a boundary value problem for the biharmonic operator on a polygon with Neumann boundary conditions. Its resolution is studied via boundary integral equations. A variational formulation of the boundary problem obtained by a double-layer potential is given. Finally, we implement the method and give numerical results. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 227-249 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: Integral equations associated with the basic boundary value problems for the Laplace and Stokes equations are considered. The integral operators for these integral equations are interpreted as the pseudodifferential operators, and their principal symbols are calculated. The symbols are obtained in terms of the principal curvatures and the coefficients of the first quadratic form of the boundary. As a consequence, the initial approximation is suggested for the iterative methods solving the integral equations. © 1998 by B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 375-392 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In this work we analyse a model for radiative heat transfer in materials that are conductive, grey and semitransparent. Such materials are for example glass, silicon, water and several gases. The most important feature of the model is the non-local interaction due to exchange of radiation. This, together with non-linearity arising from the well-known Stefan-Boltzmann law, makes the resulting heat equation non-monotone. By analysing the terms related to heat radiation we prove that the operator defining the problem is pseudomonotone. Hence, we can prove the existence of weak solution in the cases where coercivity can be obtained. In the general case, we prove the solvability of the system using the technique of sub and supersolutions. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 463-477 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We consider the time-harmonic Maxwell equations in the high-frequency case for a heterogeneous medium, i.e., a medium which is composed by a conductor and a perfect insulator, or, in other words, a loaded cavity. As a consequence of a suitable compactness result, we prove that Fredholm alternative holds for such a problem. Since the kernels of the considered operator and of its adjoint are proven to be trivial, a unique solution exists for each given datum. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 501-517 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In this paper an initial-boundary-value problem in one-space dimension is studied for the Broadwell model extended to a gas mixture undergoing bimolecular reactions. Techniques of semigroup of bounded positive operators in a suitable Banach space are used to prove existence and uniqueness of the solution on bounded time intervals whose length depends on the initial data. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 589-603 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In the paper we study the problem of control by means of a heat source g for a thermoelastic system of equationsutt - ρ∇·p(θ, ∇u) - νΔut + DΔ2 u = f, cv(θ, ∇u)θt - κΔθ - ρθ[pθ (θ, ∇u)·∇ut] - ν∣∇ut∣2 = g, in a two-dimensional domain, where both viscosity ν and rigidity D are positive. Such a system has been considered in our former papers, and existence of solutions as well as uniqueness have been obtained. Here we prove the continuity and differentiability of solutions under somewhat stronger assumptions. An example of a control problem and necessary optimality conditions are presented. The system has an interpretation as a plate reinforced with shape memory alloy (SMA) wire mesh. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 619-651 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We consider acoustic scattering from an obstacle inside an inhomogeneous structure. We prove in the paper that if the outside inhomogeneity is known then the obstacle and possible inside inhomogeneity are uniquely determined by the fixed energy far field data. The proof is based on new mapping properties of layer potentials in spaces that specify one point. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 685-700 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In the present work, the problem of electromagnetic wave propagation in three-dimensional stratified media is studied. The method of decoupling the electric and magnetic fields is implemented, and the spectral approach is adopted, componentwise, to the vector equation involving the electric field. Operational calculus of self-adjoint, positive operators in suitable Hilbert spaces is used to solve the corresponding initial value problems. The spectral families of these operators for the cases of the whole space and of a finite layer are constructed. A discussion on the applicability of the obtained results to physical problems is also included. © 1998 B.G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 757-780 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In this paper we prove under the assumption of small initial data the global existence of a classical solution to the equations in viscoelasticity, associated with a free damping boundary condition. We also show that if we choose the initial data large enough, blow up will occur in finite time. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1115-1148 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We apply the Child-Langmuir asymptotics of the Vlasov-Poisson system to the case of a bipolar diode, i.e. a vacuum diode where two species of particles of opposite electric charge are flowing. This leads to a simplified model which, if at least one of the two injected currents is not too large, has a unique solution. Moreover, in that case, the currents flowing inside the diode are limited by the so-called bipolar Child-Langmuir currents. In the case of large currents, other solutions may appear, and the formation of virtual electrodes may occur inside the diode. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1149-1183 
    ISSN: 0170-4214
    Keywords: free boundary fluid motion ; Cauchy problem ; Hamilton structure ; Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: The Cauchy problem for the motion of a liquid drop under surface tension is solved locally in time on the basis of a general abstract existence theorem for Hamiltonian systems which seems to be of interest also in other areas. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 969-983 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We study the problem of the scattering by a periodic, inhomogeneous, penetrable medium. Using the Dirichlet-to-Neumann operator from the classical formulation of the problem we derive a variational equation and give regularity result to show the equivalence of both formulations. We present certain uniqueness results, which by the Fredholm alternative yield existence of the solution and its continuous dependence on the incoming wave. We prove existence of a solution for special incident waves even if there is no uniqueness. A result about analytical dependence of the solution on the wave number and the incident angle is given. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1185-1194 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In this paper we prove the global existence and study decay property of the solutions to the initial boundary value problem for the quasi-linear wave equation with a dissipative term without the smallness of the initial data. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1207-1226 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: Reaction random-walk systems are hyperbolic models to describe spatial motion (in one dimension) with finite speed and reactions of particles. Here we present two approaches which relate reaction random-walk equations with reaction diffusion equations. First, we consider the case of high particle speeds (parabolic limit). This leads to a singular perturbation analysis of a semilinear damped wave equation. A initial layer estimate is given. Secondly, we consider the case of a transcritical bifurcation. We use techniques similar to that of the Ginzburg-Landau method to find a modulation equation for the amplitude of the first unstable mode. It turns out that the modulation equation is Fisher's equation, hence near the bifurcation point travelling wave solutions are obtained. The approximation result and the corresponding estimate is given in terms of the bifurcation parameter. Both results are based on an a priori estimate for classical solutions which follows from explicit representations of the solution of the linear telegraph equation. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1365-1377 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In the article the problem of regulation of the cardiovascular system is investigated from the point of view of control process theory. This problem was reduced to finding the optimal control in the sense of speed in a bilinear system. In the first part of the article the possibility of applying Saburov's method for the solution to bilinear control problems is considered. The second part of the article is devoted to the application of this method to a concrete problem from practical medicine. The method has allowed the complete synthesis of an optimal control to be carried out  -  the sliding mode takes place and it was investigated completely. The results obtained are interesting from the point of view of control process theory, and testify to the high efficiency of the method. The final results allow concrete recommendations about the regulation of the cardiovascular system. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1399-1413 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: The steady-state equations for a charged gas or fluid consisting of several components, exposed to an electric field, are considered. These equations form a system of strongly coupled, quasilinear elliptic equations which in some situations can be derived from the Boltzmann equation. The model uses the duality between the thermodynamic fluxes and the thermodynamic forces. Physically motivated mixed Dirichlet-Neumann boundary conditions are prescribed. The existence of generalized solutions is proven. The key of the proof is a transformation of the problem by using the entropic variables, or electro-chemical potentials, which symmetrize the equations. The uniqueness of weak solutions is shown under the assumption that the boundary data are not far from the thermal equilibrium. A general uniqueness result cannot be expected for physical reasons. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1343-1363 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We consider an elastic plate with the non-deformed shape ΩΣ := Ω \ Σ, where Ω is a domain bounded by a smooth closed curve Γ and Σ ⊂ Ω is a curve with the end points {γ1, γ2}. If the force g is given on the part ΓN of Γ, the displacement u is fixed on ΓD := Γ \ ΓN and the body force f is given in Ω, then the displacement vector u(x) = (u1(x), u2(x)) has unbounded derivatives (stress singularities) near γk, k = 1, 2   u(x) = ∑2k, l=1 Kl(γk)r1/2kSCkl(θk) + uR(x)     near γk.Here (rk, θk) denote local curvilinear polar co-ordinates near γk, k = 1, 2, SCkl (θk) are smooth functions defined on [-π, π] and uR(x) ∊ {H2(near γk)}2. The constants Kl(γk),   l = 1, 2, which are called the stress intensity factors at γk (abbr. SIFs), are important parameters in fracture mechanics. We notice that the stress intensity factors Kl(γk) (l = 1, 2;  k = 1, 2) are functionals Kl(γk) = Kl(γk; L, Ω, Σ) depending on the load L, the shape of the plate Ω and the shape of the crack Σ. We say that the crack Σ is safe, if Kl(γk; Ω)2 + K2(γk; Ω)2 〈 RẼ. By a small change of Ω the shape Σ can change to a dangerous one, i.e. we have K1(γk; Ω)2 + K2(γk; Ω)2 ≥ RẼ. Therefore it is important to know how Kl(γk) depends on the shape of Ω.For this reason, we calculate the Gâteaux derivative of Kl(γk) under a class of domain perturbations which includes the approximation of domains by polygonal domains and the Hadamard's parametrization Γ(τ) := {x + τφ(x)n(x);  x ∊ Γ}, where φ is a function on Γ and n is the outward unit normal on Γ. The calculations are quite delicate because of the occurrence of additional stress singularities at the collision points {γ3, γ4} = ΓD ∩ ΓN.The result is derived by the combination of the weight function method and the Generalized J-integral technique (abbr. GJ-integral technique). The GJ-integrals have been proposed by the first author in order to express the variation of energy (energy release rate) by extension of a crack in a 3D-elastic body. This paper begins with the weak solution of the crack problem, the weight function representation of SIF's, GJ-integral technique and finish with the shape sensitivity analysis of SIF's. GJ-integral Jω(u; X) is the sum of the P-integral (line integral) Pω(u, X) and the R-integral (area integral) Rω(u, X). With the help of the GJ-integral technique we derive an R-integral expression for the shape derivative of the potential energy which is valid for all displacement fields u ∊ H1. Using the property that the GJ-integral vanishes for all regular fields u ∊ H2 we convert the R-integral expression for the shape derivative to a P-integral expression. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1495-1517 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: Inverse problems for identification of the four memory kernels in one-dimensional linear thermoviscoelasticity are reduced to a system of non-linear Volterra integral equations using Fourier's method for solving the direct problem. To this system of equations the contraction principle in weighted norms is applied. In this way global in time existence of a solution to the inverse problems is proved and stability estimates for it are derived. In analogous way inverse problems for the memory kernels in linear poroviscoelasticity can be handled. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1467-1477 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In this paper, the existence, both locally and globally in time, the uniqueness of solutions and the non-existence of global solutions to the initial boundary value problem of a generalized Modification of the Improved Boussinesq equation utt-uxx-uxxtt=σ(u)xx are studied and a few examples are discussed. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 1619-1635 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We consider the two-parameter non-linear Sturm-Liouville problems. By using the variational method on general level sets, the variational eigenvalues are obtained. The purpose of this paper is to study the properties of these variational eigenvalues with respect to the parameter of general level sets. © 1998 B. G. Teubner Stuttgart - John Wiley & Sons, Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 187-226 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We study the limit behaviour of solution of Poisson's equation in a class of thin two-dimensional domains, both simply connected or single-hollowed, as its thickness becomes very small. The method is based on a transformation of the original problem into another posed on a fixed domain, obtention of a priori estimates and convergence results when thickness parameter tends to zero. As an important application of abstract results we obtain the limit expressions for functions appearing in elastic beam theories as torsion and warping functions. In this way, we provide a mathematical justification and a correct definition of torsion, warping and Timoshenko functions and constants that should be used in the open and closed thin-walled elastic beam theories. © 1998 by B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 269-279 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: The generalized Möbius function and Möbius inversion formula are applied to a multiplicative semigroup. A general mathematical method based on this Möbius inversion is presented to solve inversion problems of expansions with unequally weighted terms. By this method, all the inverse lattice problems in physics can be solved concisely. The solutions of four inverse lattice problems: the Fibonacci structure, the square lattice structure, the bcc and the hcp lattice structures are given. These are difficult to be solved by other methods. © 1998 by B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 361-374 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We use the eigenfunction expansion of Green's function of Dirichlet problems to obtain sampling theorems. The analytic properties of the sampled integral transforms as well as the uniform convergence of the sampling series are proved without any restrictions on the integral transforms. We obtain a one- and multi-dimensional versions of sampling theorems. In both cases the sampling series are written in terms of Lagrange-type interpolation expansions. Some examples and the truncation error as well as the stability of the obtained sampling expansions are discussed at the end of the paper. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 393-416 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We consider a dynamical von Kármán system in the presence of thermal effects. Our model includes the possibility of a rotational inertia term in the system. We show that the total energy of the solution of such system decays exponentially as t→+∞. The decay rates we obtain are uniform on bounded sets of the energy space. The main ingredients of our method of proof are suitable properties of a decoupled system, the energy method and the compactness of the nonlinear map associated to the von Kármán system. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
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    Mathematical Methods in the Applied Sciences 21 (1998), S. 479-488 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: This short article discusses the spectrum of the Neumann Laplacian in the infinite domain Ω⊂∝n, n ≥2 created by inserting a compact obstacle P into the uniform cylinder Ω0 =(-∞, ∞)×Ω′. The main result is the existence of at least one embedded eigenvalue when P is an (n -2)-dimensional surface whose unit normal is parallel to Ω′ at each point of P . The special case when P is symmetric about {0}×Ω′ is also treated. It is shown that there is at least one symmetric eigenvector and, when P is sufficiently long, at least one antisymmetric eigenvector. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 97
    Electronic Resource
    Electronic Resource
    Chichester, West Sussex : Wiley-Blackwell
    Mathematical Methods in the Applied Sciences 21 (1998), S. 551-564 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: We prove the existence of solutions to the three-dimensional elastoplastic problem with Hencky's law and Neumann boundary conditions by elliptic regularization and the penalty method, both for the case of a smooth boundary and of an interior two dimensional crack. It is shown, in particular, that the variational solution satisfies all boundary conditions. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
    Type of Medium: Electronic Resource
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  • 98
    Electronic Resource
    Electronic Resource
    Chichester, West Sussex : Wiley-Blackwell
    Mathematical Methods in the Applied Sciences 21 (1998), S. 565-588 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: New explicit stability conditions are derived for a linear integro-differential equation with periodic operator coefficients. The equation under consideration describes oscillations of thin-walled viscoelastic structural members driven by periodic loads. To develop stability conditions two approaches are combined. The first is based on the direct Lyapunov method of constructing stability functionals. It allows stability conditions to be derived for unbounded operator coefficients, but fails to correctly predict the critical loads for high-frequency excitations. The other approach is based on transforming the equation under consideration in such a way that an appropriate ‘differential’ part of the new equation would possess some reserve of stability. Stability conditions for the transformed equation are obtained by using a technique of integral estimates. This method provides acceptable estimates of the critical forces for periodic loads, but can be applied to equations with bounded coefficients only. Combining these two approaches, we derive explicit stability conditions which are close to the Floquet criterion when the integral term vanishes. These conditions are applied to the stability problem for a viscoelastic bar compressed by periodic forces. The effect of material and structural parameters on the critical load is studied numerically. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 99
    Electronic Resource
    Electronic Resource
    Chichester, West Sussex : Wiley-Blackwell
    Mathematical Methods in the Applied Sciences 21 (1998), S. 653-664 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: In order to maintain spectrally accurate solutions, the grids on which a non-linear physical problem is to be solved must also be obtained by spectrally accurate techniques. The purpose of this paper is to describe a pseudospectral computational method of solving integro-differential systems with quadratic performance index. The proposed method is based on the idea of relating grid points to the structure of orthogonal interpolating polynomials. The optimal control and the trajectory are approximated by the m th degree interpolating polynomial. This interpolating polynomial is spectrally constructed using Legendre-Gauss-Lobatto grid points as the collocation points, and Lagrange polynomials as trial functions. The integrals involved in the formulation of the problem are calculated by Gauss-Lobatto integration rule, thereby reducing the problem to a mathematical programming one to which existing well-developed algorithms may be applied. The method is easy to implement and yields very accurate results. An illustrative example is included to confirm the convergence of the pseudospectral Legendre method, and a comparison is made with an existing result in the literature. © 1998 B. G. Teubner Stuttgart-John Wiley & Sons Ltd.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
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  • 100
    Electronic Resource
    Electronic Resource
    Chichester, West Sussex : Wiley-Blackwell
    Mathematical Methods in the Applied Sciences 21 (1998), S. 701-718 
    ISSN: 0170-4214
    Keywords: Engineering ; Numerical Methods and Modeling
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics
    Notes: This article establishes the existence of a trapped-mode solution to a linearized water-wave problem. The fluid occupies a symmetric horizontal channel that is uniform everywhere apart from a confined region which either contains a thin vertical plate spanning the depth of the channel or has indentations in the channel walls; the forces of gravity and surface tension are operative. A trapped mode corresponds to an eigenvalue of the composition of an inverse differential operator and a Neumann-Dirichlet operator for an elliptic boundary-value problem in the fluid domain. The existence of such an eigenvalue is established by extending previous results dealing with the case when surface tension is absent. © 1998 B.G. Teubner Stuttgart-John Wiley & Sons, Ltd.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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