When do diffusion-limited trajectories become memoryless?

Stochastic description of cellular dynamics by the chemical master equation assumes the exponential distribution of intervals between reaction events. Diffusion-limited reactions violate this assumption. Using the example of the target search we investigate the conditions under which a peaked waiting-time distribution can be approximated by the exponential function. We link the steady-state flux and the dynamic property of the diffusion, the mean first-passage time

Comparison of formaldehyde and methanol fixatives used in the detection of ion channel proteins in isolated rat ventricular myocytes by immunofluorescence labelling and confocal microscopy

In this study, a fixation protocol using a 10% neutral buffered formalin (FA) solution and another protocol using a methanol (MeOH) solution were compared for detection of ion channels, Kv1.5, Kv4.2, Cav1.2, Kir6.2, Nav1.5 and Nav1.1 in rat myocytes by immunolabelling. Kv1.5 and Kv4.2 at intercalated discs and Cav1.2 at transverse tubules were not detected by FA but were detected by MeOH. Kir6.2 at transverse tubules and Nav1.5 at sarcolemma were detected by FA but not by MeOH. It is suggested that both FA and MeOH fixation protocols should be used for the detection of cardiac ion channels by immunolabellin

Resonant states in GaAs/Ga1-xAlxAs Multi-Quantum-Wells

The effect of buffer layers on resonant states in a Multi-Quantum-Well (MQW) sandwiched between two substrates is investigated here theoretically. These resonances appear as well-defined peaks in the density of states (DOS). The local and total densities of states are obtained from an analytical determination of the Green functions. Due to the substrate/buffer layer/ MQW /substrate interaction, different kinds of resonant states are found and their properties are investigated. We show in particular that an incident electron in the left-hand side substrate is transmitted in the right hand side substrate of the structure with large time delays in the phase time. The peaks in the phase time associated with the transmission coefficient are found to be similar to those corresponding to the DOS. The intensity of these peaks associated with extended states in MQW’s and Tamm like states lying at the MQW/buffer layer interface, strongly depends on the width of the buffer layer.The effect of buffer layers on resonant states in a Multi-Quantum-Well (MQW) sandwiched between two substrates is investigated here theoretically. These resonances appear as well-defined peaks in the density of states (DOS). The local and total densities of states are obtained from an analytical determination of the Green functions. Due to the substrate/buffer layer/ MQW /substrate interaction, different kinds of resonant states are found and their properties are investigated. We show in particular that an incident electron in the left-hand side substrate is transmitted in the right hand side substrate of the structure with large time delays in the phase time. The peaks in the phase time associated with the transmission coefficient are found to be similar to those corresponding to the DOS. The intensity of these peaks associated with extended states in MQW’s and Tamm like states lying at the MQW/buffer layer interface, strongly depends on the width of the buffer layer

Méthode de pénalization basée sur une approche d’adaptation enformalisme résidu distribué ALE pour des objets mobiles en écoulement laminaire

The coupling of anisotropic unstructured mesh adaptation techniques with an immersed boundary method (IBM) called penalization is studied for time dependent flow simulations involving moving objects. To extend Residual Distribution (RD) method to the penalized Navier Stokes equations, a new formulation based on a Strang splitting is developed. To reduce the error on solid boundaries, unstructured mesh adaptation based on an elasticity model is used. Keeping a constant connectivity, the mesh evolves in time according to the solid position, and the new formulation is proposed in an ALE framework.Le couplage des techniques d’adaptation de maillages non structurés anisotropes avec une méthode de frontière immergée (IBM) appelée Pénalization est étudié pour des simulations instationnaires impliquant des objents en mouvement. Pour étendre les méthodes de distribution du résidu (RD) aux équations de Navier Stokes pénalisées, une nouvelle formulation basée sur un splitting de Strang est développée. Pour réduire l’erreur sur les frontières du solide, une adaptation de maillage non structuré est utilisée, basée sur un modèle d’élasticité. Gardant une connectivité constante, le maillage évolue en temps en accord avec la position du solide, et la nouvelle formulation est proposée dans un formalisme ALE

Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors

BACKGROUND: Male germ cell tumor (GCT) is a highly curable malignancy, which exhibits exquisite sensitivity to cisplatin treatment. The genetic pathway(s) that determine the chemotherapy sensitivity in GCT remain largely unknown. RESULTS: We studied epigenetic changes in relation to cisplatin response by examining promoter hypermethylation in a cohort of resistant and sensitive GCTs. Here, we show that promoter hypermethylation of RASSF1A and HIC1 genes is associated with resistance. The promoter hypermethylation and/or the down-regulated expression of MGMT is seen in the majority of tumors. We hypothesize that these epigenetic alterations affecting MGMT play a major role in the exquisite sensitivity to cisplatin, characteristic of GCTs. We also demonstrate that cisplatin treatment induce de novo promoter hypermethylation in vivo. In addition, we show that the acquired cisplatin resistance in vitro alters the expression of specific genes and the highly resistant cells fail to reactivate gene expression after treatment to demethylating and histone deacetylase inhibiting agents. CONCLUSIONS: Our findings suggest that promoter hypermethylation of RASSF1A and HIC1 genes play a role in resistance of GCT, while the transcriptional inactivation of MGMT by epigenetic alterations confer exquisite sensitivity to cisplatin. These results also implicate defects in epigenetic pathways that regulate gene transcription in cisplatin resistant GCT