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Biomedical subjects

M Lücke

Publications and source records attributed to M Lücke.

At least 19 recordsLinked to original sources

Growth of binary fluid convection: role of the concentration field.

The growth of convection in binary fluid mixtures out of different perturbations of the quiescent conductive state is investigated using finite-difference numerical simulations for realistic ethanol-water parameters with strong negative Soret coupling between temperature and concentration fluctuations. Several different analysis tools are used to elucidate the complex spatiotemporal behavior associated with the dramatic concentration redistribution during the transients. It shows first the competition between counterpropagating waves that initially superimpose to form standing wave perturbations. Having reached a critical amplitude an advective breaking of the concentration wave triggers a very fast flow-induced transition from standing to traveling wave convection with large phase velocity and large concentration field amplitudes. Strongly nonlinear advective mixing and weak long-time diffusive homogenization then slow down the waves.

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Influence of inlet and bulk noise on Rayleigh-Bénard convection with lateral flow.

Spatiotemporal properties of convective fluctuations and of their correlations are investigated theoretically in the vicinity of the threshold for onset of convection in the presence of a lateral through-flow using the full linearized equations of fluctuating hydrodynamics. The effect of external forcing by inlet boundary conditions on the downstream evolution of convective fields is separated from the effect of internal bulk thermal forcing with the use of spatial Laplace transformations. They show how the spatial variation of fluctuations and of their correlations are governed by the six spatial characteristic exponents of the field equations.

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Localized perturbations in binary fluid convection with and without throughflow.

Dynamics and structure of spatially localized convective perturbations in binary fluid layers heated from below and the effect of a plane horizontal Poiseuille throughflow on them are investigated. Fronts and pulse-like wave packets formed out of the three relevant perturbations-two oscillatory ones and a stationary one-are analyzed after evaluating the appropriate saddle points of the three respective dispersion relations of the linear field equations over the complex wave number plane. Front and pulse properties are elucidated in quantitative detail as a function of small throughflow Reynolds numbers for different Soret coupling strengths psi including the pure fluid limit psi=0 in comparison with the appropriate Ginzburg-Landau amplitude equation approximations. Furthermore, small amplitude pulses and fronts obtained from solving the full nonlinear field equations numerically are presented to check and compare with the linear results.

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The rate of homozygous CDKN2A/p16 deletions in glioma cell lines and in primary tumors.

The rate of homozygous deletions of CDKN2A/p16 is variable between different tumor entities, and in addition it is higher in established cell lines in comparison with primary tumors. Such incongruencies may reflect statistical sampling errors, true differences depending on tissue derivatisation and CDKN2A/p16 loss under selective pressure in tissue culture. Clarification of these issues is warranted in the context of defining tumor suppressor genes such as CDKN2A/p16 as targets for gene replacement therapies. We therefore compared established cell lines derived from human glioblastomas and their corresponding primary tumors by multiplex PCR methodology. Archival early passages were included to determine the time point at which the p16 status of a cell line changes if it is different from the original tumor. It was found that in 2 of 11 cases (18%) the primary tumor had no p16 alteration whereas the corresponding cell lines had a homozygous p16 deletion. Tracking the in vitro evolution of these two cell lines we found that CDKN2A/p16 was lost already in the earliest passages. This suggests a clonal outgrowth advantage of a subpopulation of p16 deleted tumor cells rather than instability of the CDKN2A/p16 genotype in vitro. Including 20 additional glioblastoma-derived cell lines we detected that in 19 of the total 31 lines at least one exon was lost bringing the rate of p16 loss in the whole panel to 61%. This compares to a rate of 49% which was found in original glioma tissue from 47 unselected other patients. It is concluded, that in cell culture selective pressure favours the outgrowth of pre-existing CDKN2A/p16 negative clones, which account for the difference of CDKN2A/p16 status between cell lines and tumors. In no case did we see a change of the CDKN2A/p16 status during prolonged tissue culture periods of up to 8 years.

Adult↗

Foamy virus vectors for suicide gene therapy.

To improve the delivery of so-called suicide genes into tumors, recombinant retroviruses were constructed by inserting the herpes virus type 1 (HSV-1) thymidine kinase (tk), the E. coli cytosine deaminase (cd) and polynucleoside phosphorylase (pnp), or the jellyfish gene for the green fluorescent protein (gfp) into a foamy virus (FV)-derived replication-competent vector (pFOV-7). Expression and stability of the inserted foreign gene was analyzed by immunoblot and polymerase chain reaction (PCR). The functionality of the suicide genes was determined by a metabolic assay on virus vector infected cells and treatment with the respective prodrugs. In terms of vector stability and effectiveness of specific cell killing a virus transducing the pnp gene (FOV-7/pnp) was superior to those using the other two suicide genes. FOV-7/pnp is a candidate virus for suicide gene delivery into solid tumors.

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