449 research outputs found

    Almost sure stability of the Euler-Maruyama method with random variable stepsize for stochastic differential equations

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    In this paper, the Euler–Maruyama (EM) method with random variable stepsize is studied to reproduce the almost sure stability of the true solutions of stochastic differential equations. Since the choice of the time step is based on the current state of the solution, the time variable is proved to be a stopping time. Then the semimartingale convergence theory is employed to obtain the almost sure stability of the random variable stepsize EM solution. To our best knowledge, this is the first paper to apply the random variable stepsize (with clear proof of the stopping time) to the analysis of the almost sure stability of the EM method

    Absence of AKT1 Mutations in Glioblastoma

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    Background: Oncogenic activation of the PI3K signalling pathway plays a pivotal role in the development of glioblastoma multiforme (GBM). A central node in PI3K downstream signalling is controlled by the serine-threonine kinase AKT1. A somatic mutation affecting residue E17 of the AKT1 gene has recently been identified in breast and colon cancer. The E17K change results in constitutive AKT1 activation, induces leukaemia in mice, and accordingly, may be therapeutically exploited to target the PI3K pathway. Assessing whether AKT1 is activated by somatic mutations in GBM is relevant to establish its role in this aggressive disease. Methodology/Principal Findings: We performed a systematic mutational analysis of the complete coding sequence of the AKT1 gene in a panel of 109 tumor GBM samples and nine high grade astrocytoma cell lines. However, no somatic mutations were detected in the coding region of AKT1. Conclusions/Significance: Our data indicate that in GBM oncogenic deregulation of the PI3K pathway does not involve somatic mutations in the coding region of AKT1

    Pharmacokinetic and safety profile of raltegravir and ribavirin, when dosed separately and together, in healthy volunteers

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    Results: No statistically significant differences in PK parameters were observed for raltegravir between phases 2 and 3. A statistically significant decrease in maximum plasma concentration (Cmax) and an increase in time to maximum plasma concentration (Tmax) were observed for ribavirin in phase 3 compared with phase 1 [GMR (95% confidence interval) 0.79 (0.62 –1.00) and 1.39 (1.08 –1.78), respectively], whereas no significant differences in other ribavirin PK parameters were observed between study phases. No clinically significant safety concerns were reported. Conclusions: The PK profile of ribavirin is altered when administered with raltegravir (reduced Cmax and increased Tmax), with no safety concerns identified. This is unlikely to be of clinical significance or have an impact on the antiviral effects of ribavirin in HIV-1- and HCV-co-infected subjects

    Coherent transmission through a one dimensional lattice

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    Based on the Keldysh nonequilibrium Green function (NGF) technique, a general formula for the current and transmission coefficient through a one dimensional lattice is derived without the consideration of electron-electron interactions. We obtain an analytical condition for perfect resonant transmission when the levels of sites are aligned, which depends on the parity of the number of sites. Localization-delocalization transition in a generic one dimensional disordered lattice is also analyzed, depending on the correlation among the hopping parameters and the strength of the coupling to reservoirs. The dependence of the number and lineshape of resonant transmission and linear conductance peaks on the structure parameters of the lattice is also given in several site cases.Comment: 22 pages, 3 figures, Revtex, minor revision mad

    Observation of a three-dimensional fractional Hall response in HfTe5

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    Interacting electrons in two dimensions can bind magnetic flux lines to form composite quasiparticles with fractional electric charge, manifesting themselves in the fractional quantum Hall effect (FQHE). Although the FQHE has also been predicted to occur in three dimensions, it has not yet been experimentally observed. Here, we report the observation of fractional plateaus in the Hall conductivity of the bulk semimetal HfTe5 at magnetic fields beyond the quantum limit. The plateaus are accompanied by Shubnikov-de Haas minima of the longitudinal electrical resistivity. The height of the Hall plateaus is given by twice the Fermi wave vector in the direction of the applied magnetic field and scales with integer and particular fractional multiples of the conductance quantum. Our findings are consistent with strong electron-electron interactions, stabilizing a fractionalized variant of the Hall effect in three dimensions.Comment: 35 pages with 17 figure

    Transplantation of Adult Mouse iPS Cell-Derived Photoreceptor Precursors Restores Retinal Structure and Function in Degenerative Mice

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    This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs), could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immune-compromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At 33 days post-differentiation a large proportion of the cells expressed the retinal progenitor cell marker Pax6 and went on to express the photoreceptor markers, CRX, recoverin, and rhodopsin. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for transplantation and treatment of retinal degenerative disease
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