The ability of vancomycin-arginine (V-r) to extend the spectrum of activity of glycopeptides to gram-negative bacteria was investigated. Its MIC towards E. coli including β-lactamase expressing Ambler classes A, B, and D was 8-16μg/ml. Addition of 8×MIC V-r to E. coli was acutely bactericidal and associated with a low frequency of resistance (< 2.3×10−10). In vivo, V-r markedly reduced E. coli burden by >7 log10 CFU/g in a thigh muscle model. These data warrant further development of V-r in combatting E. coli, including resistant forms.
Precise direct-write lithography of 3D waveguides or diffractive structures within the volume of a photosensitive material is hindered by the lack of metrology that can yield predictive models for the micron-scale refractive index profile in response to a range of exposure conditions. We apply the transport of intensity equation in conjunction with confocal reflection microscopy to capture the complete spatial frequency spectrum of isolated 10 μm-scale gradient-refractive index structures written by single-photon direct-write laser lithography. The model material, a high-performance two-component photopolymer, is found to be linear, integrating, and described by a single master dose response function. The sharp saturation of this function is used to demonstrate nearly binary, flat-topped waveguide profiles in response to a Gaussian focus.
We demonstrate that multiple exposures of a two-component holographic photopolymer can quadruple the refractive index contrast of the material beyond the single-exposure saturation limit. Quantitative phase microscopy of isolated structures written by laser direct-write lithography is used to characterize the process. This technique reveals that multiple exposures are made possible by diffusion of the chemical components consumed during writing into the previously exposed regions. The ultimate index contrast is shown to be limited by the solubility of fresh components into the multiply exposed region.
The introduction of new and improved antibacterial agents based on facile synthetic modifications of existing antibiotics represents a promising strategy to deliver urgently needed antibacterial candidates to treat multi-drug resistant...
Optically-driven diffusion of high refractive index molecules within a transparent thermoset polymer matrix is a promising platform for hybrid optics that combines a wide range of optical structures from large scale holograms to micron-scale gradient index waveguides in a single integrated optical system. Design of such a system requires characterization of the optical response of the material at a wide range of spatial scales and intensities. While holographic analysis of the photopolymers is appropriate to probe the smaller spatial scales and lower intensity optical response, quantitative phase mapping of isolated structures is needed to probe the response to the higher intensities and lower spatial frequencies used in direct write lithography of waveguides. We apply the transport of intensity equation (TIE) to demonstrate quantitative refractive index measurements of 10 μm-scale localized gradient index structures written into diffusive photopolymer materials using both single-and two-photon polymerization. These quantitative measurements allow us to study the effect of different exposure conditions and material parameters such as writing beam power, exposure time, and wt% loading of the writing monomer on the overall profile of the refractive index structure. We use these measurements to probe the time scales over which diffusion is significant, and take advantage of the diffusion of monomer with a multiple-write scheme that achieves a peak refractive index contrast of 0.025.
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