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

Experimental and simulated STM images of stoichiometric and partially reduced RuO2(110) surfaces including adsorbates

We present experimental and DFT-simulated STM images of ultrathin RuO2(110) films on Ru(0001), including adsorbates such as oxygen and CO. We are able to identify the under-coordinated O atoms on the RuO2(110) surface with STM, i.e. the bridging O atoms and the on-top O atoms. The partial reduction of the RuO2(110) surface by CO exposure at room temperature leads to a surface where part of the bridging O atoms have been removed and some of the vacancies are occupied by bridging CO. When dosing 10 L of CO at room temperature, the RuO2(110) surface becomes fully mildly reduced in that all bridging 0 atoms are replaced by bridging CO molecules. Annealing the surface to 600 K produces holes on the terraces of such a mildly reduced RuO2(110) surface. These pits are not generated by the recombination of lattice O with CO, but rather these pits are assigned to a complex temperature-induced rearrangement of surface atoms in the topmost RuO2 double layer of RuO2(110). With this process the bridging O atoms are again populated and surplus Ru atoms agglomerate in small islands at the rims of the holes. (C) 2002 Elsevier Science B.V. All rights reserved

On the origin of the Ru-3d(5/2) satellite feature from RuO2(110)

High resolution core level spectroscopy in combination with density functional theory calculations are used to study the satellite feature of the Ru-3d(5/2), core level spectrum whose interpretation is still a matter of debate. We present evidence that the satellite peak is not related to any structural properties of the RuO2(1 1 0) surface. The binding energy shift between the Ru-3d(5/2) component and the satellite peak is close to the electron energy loss due to plasmon excitation. We propose therefore that the satellite peak is due to excitation of the RuO2 plasmon. (C) 2002 Elsevier Science B.V. All rights reserved

On the possible identification of defects using the autocorrelation function approach in double Doppler broadening of annihilation radiation spectroscopy

The recent revived interest in the use of double-Doppler broadening of annihilation radiation (D-DBAR) spectroscopy, which employs two Ge detectors in back-to back geometry has stemmed mainly from its potential in defect identification as a result of its elemental sensitivity through core annihilations in atoms at the defect site. Emphasis has thus largely concentrated on the high momentum spectral range. In contrast the present work emphasizes the need to also focus attention on the low momentum region of the D-DBAr spectra. It is argued that the √2 improved resolving power of D-DBAR, in conjunction with spectral deconvolution, should give future ID (one dimensional) momentum data approaching in quality those obtainable using 1D-ACAR (angular correlation of annihilation radiation), thus formaing an alternative technique for observing the structure containing diffraction patterns that originate from annihilations with localized electron states at positron trapping defects. Rotation of the sample about a specified crystal axis, and the binning of events by angle, is suggested as a means of extending the technique to form a 2D- (two dimensional) DBAR counterpart to 2D-ACAR. The advantages of considering the real space positron electron wavefunction product AF (autocorrelation function), obtained by simple manipulation of the D-DBAR data in Fourier space, are outlined. In particular the possible visualization offered in real space of a defect's physical geometry, with the prospect of building up a library of contour patterns for future defect identification, is discussed, taking the silicon monovacancy in Si and the negative As vacancy in GaAs as examples.link_to_subscribed_fulltex

Quantum ESPRESSO: a modular and open-source software project for quantum simulations of materials

QUANTUM ESPRESSO is an integrated suite of computer codes for electronic-structure calculations and materials modeling, based on density-functional theory, plane waves, and pseudopotentials (norm-conserving, ultrasoft, and projector-augmented wave). The acronym ESPRESSO stands for opEn Source Package for Research in Electronic Structure, Simulation, and Optimization. It is freely available to researchers around the world under the terms of the GNU General Public License. QUANTUM ESPRESSO builds upon newly-restructured electronic-structure codes that have been developed and tested by some of the original authors of novel electronic-structure algorithms and applied in the last twenty years by some of the leading materials modeling groups worldwide. Innovation and efficiency are still its main focus, with special attention paid to massively parallel architectures, and a great effort being devoted to user friendliness. QUANTUM ESPRESSO is evolving towards a distribution of independent and interoperable codes in the spirit of an open-source project, where researchers active in the field of electronic-structure calculations are encouraged to participate in the project by contributing their own codes or by implementing their own ideas into existing codes

Atomically perfect torn graphene edges and their reversible reconstruction

The atomic structure of graphene edges is critical in determining the electrical, magnetic and chemical properties of truncated graphene structures, notably nanoribbons. Unfortunately, graphene edges are typically far from ideal and suffer from atomic-scale defects, structural distortion and unintended chemical functionalization, leading to unpredictable properties. Here we report that graphene edges fabricated by electron beam-initiated mechanical rupture or tearing in high vacuum are clean and largely atomically perfect, oriented in either the armchair or zigzag direction. We demonstrate, via aberration-corrected transmission electron microscopy, reversible and extended pentagon-heptagon (5-7) reconstruction at zigzag edges, and explore experimentally and theoretically the dynamics of the transitions between configuration states. Good theoretical-experimental agreement is found for the flipping rates between 5-7 and 6-6 zigzag edge states. Our study demonstrates that simple ripping is remarkably effective in producing atomically clean, ideal terminations, thus providing a valuable tool for realizing atomically tailored graphene and facilitating meaningful experimental study.close14