277 research outputs found
Fms-like tyrosine kinase-3 ligand increases resistance to burn wound infection through effects on plasmacytoid dendritic cells
Equilibrium shapes and energies of coherent strained InP islands
The equilibrium shapes and energies of coherent strained InP islands grown on
GaP have been investigated with a hybrid approach that has been previously
applied to InAs islands on GaAs. This combines calculations of the surface
energies by density functional theory and the bulk deformation energies by
continuum elasticity theory. The calculated equilibrium shapes for different
chemical environments exhibit the {101}, {111}, {\=1\=1\=1} facets and a (001)
top surface. They compare quite well with recent atomic-force microscopy data.
Thus in the InP/GaInP-system a considerable equilibration of the individual
islands with respect to their shapes can be achieved. We discuss the
implications of our results for the Ostwald ripening of the coherent InP
islands. In addition we compare strain fields in uncapped and capped islands.Comment: 10 pages including 6 figures. Submitted to Phys. Rev. B. Related
publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm
Antiproliferative effect of immunoliposomes containing 5-fluorodeoxyuridine-dipalmitate on colon cancer cells
We have investigated the antiproliferative action towards CC531 colon adenocarcinoma cells of target cell-specific immunoliposomes containing the amphiphilic dipalmitoyl derivative of 5-fluorodeoxyuridine (FUdR-dP). FUdR-dP incorporated in immunoliposomes caused a 13-fold stronger inhibition of CC531 cell growth in vitro, during a 72-h treatment, than FUdR-dP in liposomes without antibody, demonstrating that the prodrug is efficiently hydrolysed to yield the active drug, FUdR, intracellularly. The intracellular release of active FUdR was confirmed by determining the fate of H-3-labelled immunoliposomal FUdR-dP. Treatments shorter than 72 h with FUdR-dP in immunoliposomes resulted in anti-tumour activities comparable to, or even higher than, that of free FUdR. The shorter treatments reflect more closely the in vivo situation and illustrate the potential advantage of the use of immunoliposomes over non-targeted liposomal FUdR-dP or free FUdR. Association of tumour cell-specific immunoliposomes with CC531 cells was up to tenfold higher than that of liposomes without antibody or with irrelevant IgG coupled, demonstrating a specific interaction between liposomes and target cells which causes an efficient intracellular delivery of the drug. Since biochemical evidence indicates a lack of internalization or degradation of the liposomes as such; we postulate that entry of the drug most likely involves the direct transfer of the prodrug from the immunoliposome to the cell membrane during its antigen-specific interaction with the cells. followed by hydrolysis of FUdR-dP leading to relatively high intracellular FUdR-levels. In conclusion, we describe a targeted liposomal formulation for the anticancer drug FUdR, which is able to deliver the active drug to colon carcinoma cells with high efficiency, without the need for the cells to internalize the liposomes as such
Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses
Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype
Tuning Nanopore Formation of Oligocholate Macrocycles by Carboxylic Acid Dimerization in Lipid Membranes
Effect of cholesterol incorporation on the sensitivity of liposomes to the polyene antibiotic, filipin
1. 1. A simple spectrophotometric assay has been developed by which the effect of lytic agents on liposomes can be conveniently determined. This method is based on the change in absorbance at 340 mμ which occurs when trapped glucose is liberated in the presence of hexokinase (EC 2.7.1.1) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49). Because the spectrophotometric assay is more sensitive (requiring lower concentrations of liposomes), it possesses several advantages over alternative procedures which have been used to study the release of trapped markers.
2. 2. It has been reported that the polyene antibiotic, filipin, did not produce a greater release of marker when cholesterol was incorporated into the liposomes. This problem has been re-examined with the spectrophotometric assay. Our results indicate that the presence of sterol does increase the sensitivity of the liposomes to the antibiotic. These observations are consistent with previous lipid monolayer and bilayer experiments and the known biological properties of the polyene antibiotic
Effect of immunologic facilitation (enhancement phenomenon) induced both passively and actively on the evolution of runt disease in newborn mice. Abstr.
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