5,589 research outputs found
Transport Mean Free Path for Magneto-Transverse Light Diffusion
We derive an expression for the transport mean free path
associated with magneto-transverse light diffusion for a random collection of
Faraday-active
Mie scatterers. This expression relates the magneto-transverse diffusion in
multiple scattering directly to the magneto-transverse scattering of a single
scatterer.Comment: 5 pages, 1 figure, Latex, accepted for publication in Europhysics
Letter
Systemic linear polyethylenimine (LâPEI)âmediated gene delivery in the mouse
Background
Several nonviral vectors including linear polyethylenimine(LâPEI) confer a pronounced lung tropism to plasmid DNA when injected into the mouse tail vein in a nonionic solution.
Methods and results
We have optimized this route by injecting 50â”g DNA with excess LâPEI (PEI nitrogen/DNA phosphate=10) in a large volume of 5% glucose (0.4âml). In these conditions, 1â5% of lung cells were transfected (corresponding to 2âng luciferase/mg protein), the other organs remaining essentially refractory to transfection (1â10âpg luciferase/mg protein).ÎČâGalactosidase histochemistry confirmed alveolar cells, including pneumocytes, to be the main target, thus leading to the puzzling observation that the lung microvasculature must be permeable to cationic LâPEI/DNA particles of ca 60ânm. A smaller injected volume, premixing of the complexes with autologous mouse serum, as well as removal of excess free LâPEI, all severely decreased transgene expression in the lung. Arterial or portal vein delivery did not increase transgene expression in other organs.
Conclusions
These observations suggest that effective lung transfection primarily depends on the injection conditions: the large nonionic glucose bolus prevents aggregation as well as mixing of the cationic complexes and excess free LâPEI with blood. This may favour vascular leakage in the region where the vasculature is dense and fragile, i.e. around the lung alveoli. Cationic particles can thus reach the epithelium from the basolateral side where their receptors (heparan sulphate proteoglycans) are abundant
The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes
To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance
Genuine DNA/polyethylenimine (PEI) Complexes Improve Transfection Properties and Cell Survival
Polyethylenimine (PEI) has been described as one of the most efficient cationic polymers for in vitro gene delivery. Systemic delivery of PEI/DNA polyplexes leads to a lung-expression tropism. Selective in vivo gene transfer would require targeting and stealth particles. Here, we describe two strategies for chemically coupling polyethylene glycol (PEG) to PEI, to form protected ligand-bearing particles. Pre-grafted PEGâPEI polymers lost their DNA condensing property, hence their poor performances. Coupling PEG to pre-formed PEI/DNA particles led to the expected physical properties. However, low transfection efficacies raised the question of the fate of excess free polymer in solution. We have developed a straightforward a purification assay, which uses centrifugation-based ultrafiltration. Crude polyplexes were purified, with up to 60% of the initial PEI dose being removed. The resulting purified and unshielded PEI/DNA polyplexes are more efficient for transfection and less toxic to cells in culture than the crude ones. Moreover, the in vivo toxicity of the polyplexes was greatly reduced, without affecting their efficacy
Coherent Backscattering of light in a magnetic field
This paper describes how coherent backscattering is altered by an external
magnetic field. In the theory presented, magneto-optical effects occur inside
Mie scatterers embedded in a non-magnetic medium. Unlike previous theories
based on point-like scatterers, the decrease of coherent backscattering is
obtained in leading order of the magnetic field using rigorous Mie theory. This
decrease is strongly enhanced in the proximity of resonances, which cause the
path length of the wave inside a scatterer to be increased. Also presented is a
novel analysis of the shape of the backscattering cone in a magnetic field.Comment: 27 pages, 5 figures, Revtex, to appear in Phys. Rev.
Anisotropic multiple scattering in diffuse media
The multiple scattering of scalar waves in diffusive media is investigated by
means of the radiative transfer equation. This approach amounts to a
resummation of the ladder diagrams of the Born series; it does not rely on the
diffusion approximation. Quantitative predictions are obtained, concerning
various observables pertaining to optically thick slabs, such as the mean
angle-resolved reflected and transmitted intensities, and the shape of the
enhanced backscattering cone. Special emphasis is put on the dependence of
these quantities on the anisotropy of the cross-section of the individual
scatterers, and on the internal reflections due to the optical index mismatch
at the boundaries of the sample. The regime of very anisotropic scattering,
where the transport mean free path is much larger than the scattering
mean free path , is studied in full detail. For the first time the
relevant Schwarzschild-Milne equation is solved exactly in the absence of
internal reflections, and asymptotically in the regime of a large index
mismatch. An unexpected outcome concerns the angular width of the enhanced
backscattering cone, which is predicted to scale as
, in contrast with the generally
accepted law, derived within the diffusion approximation.Comment: 53 pages TEX, including 2 tables. The 4 figures are sent at reques
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