The significance of the complement system for the pathogenesis of age-related macular degeneration — current evidence and translation into clinical application

BACKGROUND: Dysregulation of the complement system has been shown to play a major role in the pathogenesis of age-related macular degeneration (AMD). METHODS: The current evidence from human studies derives from immunohistochemical and proteomic studies in donor eyes, genetic association studies, and studies of blood complement protein levels. These lines of evidence are corroborated by in vitro and animal studies. RESULTS: In AMD donor eyes, detection of complement proteins in drusen suggested local inflammatory processes involving the complement system. Moreover, higher levels of complement proteins in the Bruch's membrane/choroid complex could be detected in AMD donor eyes compared to controls. A large number of independent genetic studies have consistently confirmed the association of AMD with risk or protective variants in genes coding for complement proteins, including complement factor H (CFH), CFH-related proteins 1 and 3, factor B/C2, C3 and factor I. Another set of independent studies detected increased levels of complement activation products in plasma of AMD patients, suggesting that AMD may be a systemic disease and the macula a vulnerable anatomic site of minimal resistance to complement activation. Genotype-phenotype correlations, including the impact of genetic variants on disease progression, gene-environment and pharmacogenetic interactions, have been investigated. There is evidence that complement gene variants may be associated with the progression from early to late forms of AMD, whereas they do not appear to play a significant role when late atrophic AMD has already developed. There are indications for an interaction between genetic variants and supplementation and dietary factors. Also, there is some evidence that variants in the CFH gene influence treatment effects in patients with neovascular AMD. CONCLUSIONS: Such data suggest that the complement system may have a significant role for developing new prophylactic and therapeutic interventions in AMD. In fact, several compounds acting on the complement pathway are currently in clinical trials. Therapeutics that modulate the complement system need to balance inhibition with preservation of sufficient functional activity in order to maintain adequate immune responses and tissue homeostasis. Specifically, targeting the dysfunction appears more adequate than a global suppression of complement activation in chronic diseases such as AMD

Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics

We present two prescriptions for broadband (∼77−252GHz), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano–convex elements, the other for densely packed arrays of quasi-optical elements—in our case, 5 mm diameter half-spheres (called “lenslets”). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves (97±2)% transmittance, and the lenslet coating sample achieves (94±3)% transmittance

Friction, wear, and corrosion of laves-hardened nickel alloy hardsurfacing in sodium

This paper represents the results of friction, wear, and corrosion tests on Tribaloy 700 specimens. The Tribaloy alloys are a family of materials typically consisting of a hard, intermetallic Laves phase dispersed in a cobalt or nickel eutectic or solid solution matrix. Only one alloy of the Tribaloy series, Tribaloy 700, is a cobalt-free nickel-base alloy. Tribaloy 700 is therefore of interest for nuclear reactor applications, where cobalt must be restricted. Tribaloy 700 rubbing against itself in sodium exhibited among the lowest friction coefficients measured for metallic materials at high temperature. Detonation-gun coatings had lower friction and lower corrosion rates than plasma coatings, in general. The wear rate of Tribaloy 700 was negligible. Surface damage resistance was good, especially when in contract with itself or other hard materials. The material also exhibited low corrosion rates in sodium

Effect of the multifunctional cosmetic ingredient sphinganine on hair loss in men and women with diffuse hair reduction

Nicole Gerlach,1,* Matthias Mentel,2,* Tim Köhler,2 Benjamin Tuchscherer,2 Birgit Garbe,1 Jasmina Ülker,1 Hagen Tronnier,1 Ulrike Heinrich,1 Mike Farwick2 1DermaTronnier GmbH & Co. KG, Institute for Experimental Dermatology, Witten/Herdecke University, Witten, 2Evonik Nutrition & Care GmbH, Essen, Germany *These authors contributed equally to this work Abstract: Sphingolipids are well known to promote keratinocyte differentiation and to induce ceramide production. In addition, they show anti-inflammatory and antimicrobial activities. Thus, the aim of this study is to investigate the potential effect of sphinganine on prolonging the hair anagen rate and improving the overall hair quality and scalp health. The inhibitory potential of sphinganine toward 5-α-reductase was studied using an in vitro assay. The stimulation of the antimicrobial peptide HBD2 by sphinganine was measured by real-time polymerase chain reaction and immunostaining. Sphinganine bioavailability was studied ex vivo using a pig skin model. A placebo-controlled, double-blind study was designed to evaluate the efficacy of sphinganine on hair loss and hair/scalp quality in vivo. In vitro results showed that sphinganine is a potent inhibitor of 5-α-reductase type I that prevents the conversion of testosterone to dihydrotestosterone, a key factor of androgenetic male baldness. In vivo results demonstrated efficacy in reducing non-illness-related hair loss among males. In terms of expert rating, all hair quality and scalp parameters improved after application of sphinganine. Improved scalp health might be linked to the observed increase of the antimicrobial peptide HBD2. Thus, sphinganine is well suited as a topical alternative for the improvement of scalp health and hair quality and anti-hair loss application. Keywords: sphinganine, 5-α-reductase inhibition, HBD2, hair loss, anagen rate, TrichoScan&reg

Place stratification or spatial assimilation? Neighbourhood quality changes after residential mobility for migrants in Germany

Neighbourhoods provide unequal resources and opportunities. Past research has shown that migrants are less able to move to more resourceful neighbourhoods. For Germany, cross-sectional evidence shows that migrants live in worse neighbourhoods on average, but no longitudinal analysis of changes in neighbourhood quality after residential mobility has been conducted. The present paper closes this gap and tests the place stratification model and the spatial assimilation model. Data from the German Socio-economic Panel and the MICROM dataset are used for the years 2000–09. The data are analysed using fixed-effects panel regression. The analysis shows that Turkish households are less able to improve their neighbourhood quality through moves compared with German households, while households with other ethnic backgrounds do not differ significantly from the native population

Forschung zu Segregation im Elementarbereich: Die Rekonstruktion von Kita-Kompositionen anhand von Daten der Schuleingangsuntersuchung

In dem Beitrag wird das Potenzial von Daten aus der Schuleingangsuntersuchung (SEU) für Sekundäranalysen im Kontext von Segregationsforschung aufgezeigt. Für die Erforschung von differenziellen Lern- und Entwicklungsmilieus im Elementarbereich sind Informationen über die Zusammensetzung von frühkindlichen Betreuungseinrichtungen erforderlich. Diese anhand von Primärdaten zu erheben ist forschungsökonomisch und forschungspraktisch aufwendig, weshalb sich Sekundäranalysen von bereits vorhandenen Daten anbieten. In der jährlichen SEU werden umfangreiche Individualdaten erhoben, anhand derer auch die Zusammensetzung von Kindertageseinrichtungen (Kitas) abgebildet werden kann. Aber auch die Erfassung der Kita-Kompositionen anhand von SEU-Daten steht aufgrund der Altersheterogenität der Kindergruppen und unterschiedlichen Besuchsdauern vor methodischen Herausforderungen, die bislang kaum thematisiert wurden. Anhand des DFG-Projekts „Kompositionseffekte in Kindertageseinrichtungen (KomiK) – Sprachkompetenzen von Kindern zu Schulbeginn“ (HO 5561/1-1