Bistability in sine-Gordon: the ideal switch

The sine-Gordon equation, used as the representative nonlinear wave equation, presents a bistable behavior resulting from nonlinearity and generating hysteresis properties. We show that the process can be understood in a comprehensive analytical formulation and that it is a generic property of nonlinear systems possessing a natural band gap. The approach allows to discover that sine-Gordon can work as an it ideal switch by reaching a transmissive regime with vanishing driving amplitude.Comment: Phys. Rev. E, (to be published, May 2005

CYP3A5 polymorphisms and their effects on tacrolimus exposure in an ethnically diverse South African renal transplant population

Background. Tacrolimus forms the cornerstone for immunosuppression in solid-organ transplantation. It has a narrow therapeutic window with wide inter- and intra-patient variability (IPV). Cytochrome P-450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The rs776746A>G (i.e. CYP3A5*3) single-nucleotide polymorphism in CYP3A5 alters tacrolimus predose trough concentration (C0) and may also affect IPV, which may lead to immune- and/or drug-mediated allograft injury. CYP3A5*3 may result in absent (*3/*3), partial (*1/*3) or normal (*1/*1) CYP3A5 expression. The effect of CYP3A5*3 on tacrolimus exposure and variability has not been examined in South African (SA) transplant recipients.Objectives. To determine the frequencies and effect of CYP3A5 and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms on tacrolimus C0/dose ratios in different ethnic groups attending a tertiary renal transplant clinic in SA, and other factors that may explain inter- and IPV in tacrolimus C0.Methods. All consenting stable renal transplant recipients on tacrolimus at the Livingstone Hospital Renal Unit in Port Elizabeth, SA, were included. Tacrolimus concentrations were obtained using a microparticle enzyme immunoassay method (ARCHITECT analyser, Abbott Laboratories). Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 and *6 allelic variants.Results. There were 43 participants (35% black African, 44% mixed ancestry and 21% white), with a mean age of 44.5 years, median duration post-transplant of 47 months and median (interquartile range) creatinine and estimated glomerular filtration rate levels of 118 (92 - 140) µmol/L and 62 (49 - 76) mL/min at study inclusion. The mean tacrolimus C0 in the study was 6.7 ng/mL, with no difference across the different ethnic groups. However, the mean total daily dose of tacrolimus required was 9.1 mg (0.12 mg/kg), 7.2 mg (0.09 mg/kg) and 4.3 mg (0.06 mg/kg) in black, mixed-ancestry and white patients, respectively (p=0.017). The frequencies for CYP3A5 expressors (i.e. CYP3A5*1/*1 + CYP3A5*1/*3 genotypes) were 72%, 100%, 76% and 12% for all patients combined and black, mixed-ancestry and white patients, respectively. The frequencies for CYP3A5 non-expressors (i.e. CYP3A5*3/*3 genotypes) were 0%, 24% and 88% among the black, mixed-ancestry and white patients, respectively. None of the patients carried the CYP3A5*6 allele. CYP3A5*1/*1 and CYP3A5*1/*3 genotype carriers required a two-fold increase in dose compared with the non-expressor genotype carriers, CYP3A5*3/*3 (p<0.05). CYP3A5*3/*3 carriers also demonstrated higher IPV than CYP3A5*1/*1 and *1/*3 carriers (18.1% v. 14.2%; p=0.125).Conclusions. Compared with global transplant populations, SA renal transplant recipients demonstrated a very high rate of CYP3A5 expression, with a significant impact on tacrolimus pharmacokinetics. Genetic variation in CYP3A5 expression affects tacrolimus dosing requirements, and knowing the CYP3A5 genotype of transplant patients may allow better dose prediction compared with current standard dosing recommendations in a multi-ethnic population. Overall, black African patients required higher doses of tacrolimus than their white counterparts. While further prospective studies are needed to better evaluate dosing algorithms, it would appear that the starting dose of tacrolimus should be higher in black and mixed-race patients.

Rapidly progressive post-transplant lymphoproliferative disease following withdrawal of sirolimus

Sirolimus, a potent inhibitor of B- and T-cell activation, is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder following the withdrawal of sirolimus

COMPRESSION OF ENVELOPE SOLITONS IN NONLINEAR ELECTRICAL LINES

La propagation des solitons enveloppe dans les lignes non linéaires de transmission électrique et de transmission Josephson est étudiée sous l'aspect théorique et en simulation numérique. Dans l'approximation des milieux continus et la limite des faibles amplitudes, les équations caractéristiques de ces lignes se ramènent à l'équation NLS . La solution "à deux solitons enveloppe" se propage parfaitement dans les lignes considérées avec des phénoménes de récurrence et de compression d'enveloppe. Ceci est observé également pour des profils d'excitation non solution de NLS, ce qui est d'un grand intérêt pour les applications pratiques.We study theoretically and numerically the properties of envelope solitons in a nonlinear electrical transmission line and in a Josephson transmission line, in a small amplitude limit. In the continuum limit and weak amplitude limit, we reduce the characteristic equations of these systems to NLS equation and we study "the two solitons envelope" solutions which propagate with recurrence phenomena along the two types of lines. Compression of envelope is observed for the academic solutions but we show that, even with a non-academic profile, the full width at half maximum is reduced, which is of a great interest for practical applications

Thermal influence on friction losses of an axle gear set

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