Omiganan Enhances Imiquimod-Induced Inflammatory Responses in Skin of Healthy Volunteers

Omiganan (OMN; a synthetic cationic peptide) and imiquimod (IMQ; a TLR7 agonist) have synergistic effects on interferon responses in vitro. The objective of this study was to translate this to a human model for proof-of-concept, and to explore the potential of OMN add-on treatment for viral skin diseases. Sixteen healthy volunteers received topical IMQ, OMN, or a combination of both for up to 4 days on tape-stripped skin. Skin inflammation was quantified by laser speckle contrast imaging and 2D photography, and molecular and cellular responses were analyzed in biopsies. IMQ treatment induced an inflammatory response of the skin. Co-treatment with OMN enhanced this inflammatory response to IMQ, with increases in perfusion (+17.1%; 95% confidence interval (CI) 5.6%–30%; P < 0.01) and erythema (+1.5; 95% CI 0.25%–2.83; P = 0.02). Interferon regulatory factor-driven and NFκB-driven responses following TLR7 stimulation were enhanced by OMN (increases in IL-6, IL-10, MXA, and IFNɣ), and more immune cell infiltration was observed (in particular CD4+, CD8+, and CD14+ cells). These findings are in line with the earlier mechanistic in vitro data, and support evaluation of imiquimod/OMN combination therapy in human papillomavirus-induced skin diseases

Neuropsychological intervention in kindergarten children with subtyped risks of reading retardation

Kindergarten children at risk of developing language problems were administered the Florida Kindergarten Screening Battery. A principal components analysis revealed a verbal and a visual-spatial component and subsequent discriminant function analyses a high verbal/low visual-spatial group (LAL: Latent L) and a high visual-spatial/low verbal group (LAP: Latent P). LAL- and LAP-children were considered at risk for developing an L- or P-type of dyslexia, respectively. As is common practice with children suffering from manifest L- or Pdyslexia, the LAL- and LAP-kindergartners received right and left hemisphere stimulation, respectively. The outcomes were compared with those of bilateral hemispheric stimulation and no intervention. Reading tests were administered in primary school Grades 1 and 5/6; teachers' evaluation of reading took place in Grade 5/6. Overall, the LAL- and LAP- groups showed significant backwardness in word and text reading, both at early and late primary school. Types of intervention made a difference though: not significantly backward in early word, late word, and late text reading were the LAL-children who had received right hemisphere stimulation. Nonintervened LAP-children did not show significant backwardness in early word reading and late text reading, nor did LAP-children who had received left hemisphere or bilateral stimulation. Early text reading was not affected by any treatment. Teacher's evaluations were in support of these findings. Copyright © 2005 by The International Dyslexia Association®

Supplement 1: Subnanometer-accuracy optical distance ruler based on fluorescence quenching by transparent conductors

Supplemental document Originally published in Optica on 20 February 2016 (optica-3-2-112

Probing the negative permittivity perfect lens at optical frequencies using near-field optics and single molecule detection

Recently, the existence of a perfect lens has been predicted, made of an artificial material that has a negative electric permittivity and a negative magnetic permeability. For optical frequencies a poormans version is predicted to exist in the sub-wavelength limit. Then, only the permittivity has to be negative, a demand that metals fulfill at optical frequencies. We propose a new measurement scheme to verify the performance of such a negative permittivity near-perfect lens at optical frequencies. The scheme is based on near-field scanning optical microscopy and single molecule detection. Prerequisite near-field single molecule data, necessary to assess the performance of the lens, is presented. A numerical evaluation, which includes absorption, of the expected performance of a slab of a realistic negative permittivity material confirms the merits of the scheme

Reversible Polarization Control of Single Photon Emission

We present reversible and a-priori control of the polarization of a photon emitted by a single molecule by introducing a nanoscale metal object in its near field. It is experimentally shown that, with the metal close to the emitter, the polarization ratio of the emission can be varied by a factor of 2. The tunability of polarization decays, when the metal is displaced by typically 30 nm. Calculations based on the multiple multipole method agree well with our experiments and predict even further enhancement with a suitable nanoantenna desig

Fluorescence Polarization Control for On-Off Switching of Single Molecules at Cryogenic Temperatures

Light microscopy, allowing sub-diffraction-limited resolution, has been among the fastest developing techniques at the interface of biology, chemistry, and physics. Intriguingly no theoretical limit exists on how far the underlying measurement uncertainty can be lowered. In particular data fusion of large amounts of images can reduce the measurement error to match the resolution of structural methods like cryo-electron microscopy. Fluorescence, although reliant on a reporter molecule and therefore not the first choice to obtain ultraresolution structures, brings highly specific labeling of molecules in a large assembly to the table and inherently allows the detection of multiple colors, which enables the interrogation of multiple molecular species at the same time in the same sample. Here, the problems to be solved in the coming years, with the aim of higher resolution, are discussed, and what polarization depletion of fluorescence at cryogenic temperatures can contribute for fluorescence imaging of biological samples, like whole cells, is described

Near-field driving of a optical monopole antenna \ud

Nanosized optical antennas have the potential to confine and enhance optical electromagnetic fields, making nano-antennas essential tools for applications in integrated nano-optical devices and high-resolution microscopy. The size, shape and material of the nano-antenna, together with the optical frequency, determine the antenna response and its resonances. Here, we discuss a λ/4 long optical nano-antenna, analogous to the radio frequency monopole antenna. The antenna is fabricated at the end of a near-field aperture-type fibre probe by focused-ion-beam milling in two sequential steps. Illumination through the fibre creates a localized evanescent excitation source, with the advantage of a lower background compared to 'apertureless' techniques, which require far-field excitation. Previously, we have studied the field localization, antenna excitation conditions and antenna resonances, both in experiment, by near-field single-molecule detection experiments, and in theory, by finite integration technique simulations. In this study we investigate the importance of both polarization conditions and antenna position in creating an efficient local driving field for the monopole antenna. It is shown that the antenna is driven by the field component along the antenna axis. Next we show the advantage of the antenna over the aperture: upon reduction of the diameter the antenna gains local field intensity, while the aperture field decreases rapidly. Finally, the highly localized field near the antenna apex is probed by single molecules and detected molecular emission features below 30 nm FWHM are presented.\u

Nanoscale Imaging of Light-Matter Coupling Inside Metal-Coated Cavities with a Pulsed Electron Beam

Many applications in (quantum) nanophotonics rely on controlling light-matter interaction through strong, nanoscale modification of the local density of states (LDOS). All-optical techniques probing emission dynamics in active media are commonly used to measure the LDOS and benchmark experimental performance against theoretical predictions. However, metal coatings needed to obtain strong LDOS modifications in, for instance, nanocavities, are incompatible with all-optical characterization. So far, no reliable method exists to validate theoretical predictions. Here, we use subnanosecond pulses of focused electrons to penetrate the metal and excite a buried active medium at precisely defined locations inside subwavelength resonant nanocavities. We reveal the spatial layout of the spontaneous-emission decay dynamics inside the cavities with deep-subwavelength detail, directly mapping the LDOS. We show that emission enhancement converts to inhibition despite an increased number of modes, emphasizing the critical role of optimal emitter location. Our approach yields fundamental insight in dynamics at deep-subwavelength scales for a wide range of nano-optical systems