224 research outputs found

    Transmission of pillar-based photonic crystal waveguides in InP technology

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    Waveguides based on line defects in pillar photonic crystals have been fabricated in InP/InGaAsP/InP technology. Transmission measurements of different line defects are reported. The results can be explained by comparison with two-dimensional band diagram simulations. The losses increase substantially at mode crossings and in the slow light regime. The agreement with the band diagrams implies a good control on the dimensions of the fabricated features, which is an important step in the actual application of these devices in photonic integrated circuit

    Tetrodotoxin-sensitive sodium channels mediate action potential firing and excitability in menthol-sensitive Vglut3-lineage sensory neurons

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    © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 39(36), (2019): 7086-7101, doi:10.1523/JNEUROSCI.2817-18.2019.Small-diameter vesicular glutamate transporter 3-lineage (Vglut3lineage) dorsal root ganglion (DRG) neurons play an important role in mechanosensation and thermal hypersensitivity; however, little is known about their intrinsic electrical properties. We therefore set out to investigate mechanisms of excitability within this population. Calcium microfluorimetry analysis of male and female mouse DRG neurons demonstrated that the cooling compound menthol selectively activates a subset of Vglut3lineage neurons. Whole-cell recordings showed that small-diameter Vglut3lineage DRG neurons fire menthol-evoked action potentials and exhibited robust, transient receptor potential melastatin 8 (TRPM8)-dependent discharges at room temperature. This heightened excitability was confirmed by current-clamp and action potential phase-plot analyses, which showed menthol-sensitive Vglut3lineage neurons to have more depolarized membrane potentials, lower firing thresholds, and higher evoked firing frequencies compared with menthol-insensitive Vglut3lineage neurons. A biophysical analysis revealed voltage-gated sodium channel (NaV) currents in menthol-sensitive Vglut3lineage neurons were resistant to entry into slow inactivation compared with menthol-insensitive neurons. Multiplex in situ hybridization showed similar distributions of tetrodotoxin (TTX)-sensitive NaV transcripts between TRPM8-positive and -negative Vglut3lineage neurons; however, NaV1.8 transcripts, which encode TTX-resistant channels, were more prevalent in TRPM8-negative neurons. Conversely, pharmacological analyses identified distinct functional contributions of NaV subunits, with NaV1.1 driving firing in menthol-sensitive neurons, whereas other small-diameter Vglut3lineage neurons rely primarily on TTX-resistant NaV channels. Additionally, when NaV1.1 channels were blocked, the remaining NaV current readily entered into slow inactivation in menthol-sensitive Vglut3lineage neurons. Thus, these data demonstrate that TTX-sensitive NaVs drive action potential firing in menthol-sensitive sensory neurons and contribute to their heightened excitability.This work was supported by NIAMS R01AR051219 (E.A.L.). T.N.G. holds a Postdoctoral Enrichment Program Award from the Burroughs Wellcome Fund and was supported by NHLBI T32HL120826. Core facilities were supported by the Columbia University EpiCURE Center (NIAMS P30AR069632) and the Thompson Family Foundation Initiative in CIPN and Sensory Neuroscience. This project was initiated during the MBL Neurobiology Course with support from NINDS R25NS063307. Dr. Blair Jenkins, Javier Marquina-Solis, and Dr. Adrian Thompson participated in preliminary studies at MBL. We thank Dr. Manu Ben-Johny and Dr. Lori Isom for sharing reagents, Dr. Irina Vetter for peptide toxins, Venesa Cuadrado for technical assistance, Rachel Clary for assistance with custom MATLAB routines, and Dr. Jon Sack and members of the Lumpkin laboratory for helpful discussions.2020-01-0

    Experimental and numerical study of SiON microresonators with air and polymer cladding

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    A systematic experimental and numerical study of the device performance of waveguide-coupled SiON microresonators with air and polymer cladding is presented. Values of device parameters like propagation losses of the microresonator modes, the off-resonance insertion losses, and the straight waveguide to microresonator coupling are determined by applying a detailed fitting procedure to the experimental results and compared to results of detailed numerical simulations. By comparing the propagation losses of the fundamental TE polarized microresonator mode obtained by fitting to the measured spectra to the also experimentally determined propagation losses in the adjacent straight waveguide and the materials losses, it is possible to identify the loss mechanisms in the microresonator. By comparing experimental results for microresonators with air and polymethylmethacrylate cladding and a detailed numerical study, the influence of the cladding index on the bend losses is evaluated. It is demonstrated that the presence of an upper cladding can, under the right conditions, actually be beneficial for loss reduction

    PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

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    Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

    HETEAC – the Hybrid End-To-End Aerosol Classification model for EarthCARE

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    The Hybrid End-To-End Aerosol Classification (HETEAC) model for the Earth Clouds, Aerosols and Radiation Explorer (EarthCARE) mission is introduced. The model serves as the common baseline for the development, evaluation, and implementation of EarthCARE algorithms. It guarantees the consistency of different aerosol products from the multi-instrument platform and facilitates the conformity of broad-band optical properties needed for EarthCARE radiative-closure assessments. While the hybrid approach ensures that the theoretical description of aerosol microphysical properties is consistent with the optical properties of the measured aerosol types, the end-to-end model permits the uniform representation of aerosol types in terms of microphysical, optical, and radiative properties. Four basic aerosol components with prescribed microphysical properties are used to compose various natural and anthropogenic aerosols of the troposphere. The components contain weakly and strongly absorbing fine-mode and spherical and non-spherical coarse-mode particles and thus are representative for pollution, smoke, sea salt, and dust, respectively. Their microphysical properties are selected such that good coverage of the observational phase space of intensive, i.e., concentration-independent, optical aerosol properties derived from EarthCARE measurements is obtained. Mixing rules to calculate optical and radiative properties of any aerosol blend composed of the four basic components are provided. Applications of HETEAC in the generation of test scenes, the development of retrieval algorithms for stand-alone and synergistic aerosol products from EarthCARE's atmospheric lidar (ATLID) and multi-spectral imager (MSI), and for radiative-closure assessments are introduced. Finally, the implications of simplifying model assumptions and possible improvements are discussed, and conclusions for future validation and development work are drawn.</p

    Small business economics: A perspective from The Netherlands

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    In the analysis of economic phenomena either within or across industries there is room for integrating the role of small business. This contribution can be made by aggregation or generalization of the findings at the meso level, which again are partly based upon analyses at the micro level. The Netherlands has a long history in macro model building. A recent discussion among Dutch macro-economists considered the future of econometric model building at the macro level, and considered how best to improve this model building. The explicit integration of scale effects, however, was not mentioned. I am convinced that improvements in this respect are possible. In particular, I have in mind the role which small businesses play in certain areas such as wage structure, employment or investments. The dissection of macro prognoses into a small business component and a remaining component is a traditional practice in The Netherlands.1 Finally, there is much concern in The Netherlands for the calculation of regulatory effects, decomposed into effects for small and large businesses. If anywhere in the world there is a solid foundation for studying scale effects in both macro and sectoral models, it most certainly has been in The Netherlands. There is a strong tradition of macro-econometric model building; groups of econometricians specialized in small business research exist; Dutch policymakers show concern and the required research apparatus is available

    Relating circulating thyroid hormone concentrations to serum interleukins-6 and -10 in association with non-thyroidal illnesses including chronic renal insufficiency

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    <p>Abstract</p> <p>Background</p> <p>Because of the possible role of cytokines including interleukins (IL) in systemic non-thyroidal illnesses' (NTI) pathogenesis and consequently the frequently associated alterations in thyroid hormone (TH) concentrations constituting the euthyroid sick syndrome (ESS), we aimed in this research to elucidate the possible relation between IL-6 & IL-10 and any documented ESS in a cohort of patients with NTI.</p> <p>Methods</p> <p>Sixty patients and twenty healthy volunteers were recruited. The patients were subdivided into three subgroups depending on their underlying NTI and included 20 patients with chronic renal insufficiency (CRI), congestive heart failure (CHF), and ICU patients with myocardial infarction (MI). Determination of the circulating serum levels of IL-6 and IL-10, thyroid stimulating hormone (TSH), as well as total T4 and T3 was carried out.</p> <p>Results</p> <p>In the whole group of patients, we detected a significantly lower T3 and T4 levels compared to control subjects (0.938 ± 0.477 vs 1.345 ± 0.44 nmol/L, p = 0.001 and 47.9 ± 28.41 vs 108 ± 19.49 nmol/L, p < 0.0001 respectively) while the TSH level was normal (1.08+0.518 μIU/L). Further, IL-6 was substantially higher above controls' levels (105.18 ± 72.01 vs 3.35 ± 1.18 ng/L, p < 0.00001) and correlated negatively with both T3 and T4 (r = -0.620, p < 0.0001 & -0.267, p < 0.001, respectively). Similarly was IL-10 level (74.13 ± 52.99 vs 2.64 ± 0.92 ng/ml, p < 0.00001) that correlated negatively with T3 (r = -0.512, p < 0.0001) but not T4. Interestingly, both interleukins correlated positively (r = 0.770, p = <0.001). Moreover, IL-6 (R<sup>2 </sup>= 0.338, p = 0.001) and not IL-10 was a predictor of low T3 levels with only a borderline significance for T4 (R<sup>2 </sup>= 0.082, p = 0.071).</p> <p>By subgroup analysis, the proportion of patients with subnormal T3, T4, and TSH levels was highest in the MI patients (70%, 70%, and 72%, respectively) who displayed the greatest IL-6 and IL-10 concentrations (192.5 ± 45.1 ng/L & 122.95 ± 46.1 ng/L, respectively) compared with CHF (82.95 ± 28.9 ng/L & 69.05 ± 44.0 ng/L, respectively) and CRI patients (40.05 ± 28.9 ng/L & 30.4 ± 10.6 ng/L, respectively). Surprisingly, CRI patients showed the least disturbance in IL-6 and IL-10 despite the lower levels of T3, T4, and TSH in a higher proportion of them compared to CHF patients (40%, 45%, & 26% vs 35%, 25%, & 18%, respectively).</p> <p>Conclusion</p> <p>the high prevalence of ESS we detected in NTI including CRI may be linked to IL-6 and IL-10 alterations. Further, perturbation of IL-6 and not IL-10 might be involved in ESS pathogenesis although it is not the only key player as suggested by our findings in CRI.</p
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