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

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

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

PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

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

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

<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 (R²= 0.338, p = 0.001) and not IL-10 was a predictor of low T3 levels with only a borderline significance for T4 (R²= 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

In vivo degeneration and the fate of inorganic nanoparticles

What happens to inorganic nanoparticles (NPs), such as plasmonic gold or silver, superparamagnetic iron oxide, or fluorescent quantum dot NPs after they have been administrated to a living being? This review discusses the integrity, biodistribution, and fate of NPs after in vivo administration. The hybrid nature of the NPs is described, conceptually divided into the inorganic core, the engineered surface coating comprising of the ligand shell and optionally also bio-conjugates, and the corona of adsorbed biological molecules. Empirical evidence shows that all of these three compounds may degrade individually in vivo and can drastically modify the life cycle and biodistribution of the whole heterostructure. Thus, the NPs may be decomposed into different parts, whose biodistribution and fate would need to be analyzed individually. Multiple labeling and quantification strategies for such a purpose will be discussed. All reviewed data indicate that NPs in vivo should no longer be considered as homogeneous entities, but should be seen as inorganic/organic/biological nanohybrids with complex and intricately linked distribution and degradation pathwaysThis work was partly funded by the European Commission (grant FutureNanoNeeds to WJP), the MINECO (MAT2013-48169-R, NanoFATE, to WJP and PdP), BMBF-MRCyte/NanoBEL, Zeiss-ChemBioMed, Stiftung Rheinland-Pfalz (NanoScreen), Peter und Traudl Engelhorn foundation, BIOMATICS (grants to RS, DD), DFG SPP1313 (grants to RS, PN, WJP), the CNRS (Centre National de la Recherche Scientifique, Defi Nano program), the ANR (Agence Nationale de la Recherche) and CGI (Commissariat à l'Investissement d'Avenir) through the LabEx SEAM (Science and Engineering for Advanced Materials and devices; ANR 11 LABX 086, ANR 11 IDEX 05 02) (grants to DA and FG). SA acknowledges the Alexander von Humboldt Foundation for a PostDoc fellowship and NF the Lars Hierta Memorial FoundationS

The 243 steps of making photonic integrated circuits in InP Citation for published version (APA): The 243 Steps of Making Photonic Integrated Circuits in InP

The fabrication ofInP-based Photonic Integrated Circuits (PICs) is a complex process. The process used in the COBRA cleanroom in Eindhoven consists of 13 deposition, 10 lithography, 14 dry-and 7 wet-etching steps. Together with the intermediate cleaning, preparation and inspection procedures, the total process flow consists of 243 steps. In this paper we show how we created a robust modular process flow that can be usedfor a large variety of active-and passive circuits. These circuits can be fabricated together in multi-project wafer runs, allowing a drastic reduction of the fabrication costs making even small-volume production economicallyfeasible