Proteome Analysis of Aflibercept Intervention in Experimental Central Retinal Vein Occlusion

Aflibercept is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the treatment of macular edema following central retinal vein occlusion (CRVO). Retinal proteome changes following aflibercept intervention in CRVO remain largely unstudied. Studying proteomic changes of aflibercept intervention may generate a better understanding of mechanisms of action and uncover aspects related to the safety profile. In 10 Danish Landrace pigs, CRVO was induced in both eyes with an argon laser. Right eyes were treated with intravitreal aflibercept while left control eyes received isotonic saline water. Retinal samples were collected 15 days after induced CRVO. Proteomic analysis by tandem mass tag-based mass spectrometry identified a total of 21 proteins that were changed in content following aflibercept intervention. In retinas treated with aflibercept, high levels of aflibercept components were reached, including the VEGF receptor-1 and VEGF receptor-2 domains. Fold changes in the additional proteins ranged between 0.70 and 1.19. Aflibercept intervention resulted in a downregulation of pigment epithelium-derived factor (PEDF) (fold change = 0.84) and endoplasmin (fold change = 0.91). The changes were slight and could thereby not be confirmed with less precise immunohistochemistry and Western blotting. Our data suggest that aflibercept had a narrow mechanism of action in the CRVO model. This may be an important observation in cases when macular edema secondary to CRVO is resistant to aflibercept intervention.     

Separation of Dihydro-Isocoumarins and Dihydro-Stilbenoids from Hydrangea macrophylla ssp. serrata by Use of Counter-Current Chromatography

Previously, different Hydrangea macrophylla ssp. serrata cultivars were investigated by untargeted LC-MS analysis. From this, a list of tentatively identified and unknown compounds that differ significantly between these cultivars was obtained. Due to the lack of reference compounds, especially for dihydro-isocoumarins, we aimed to isolate and structurally characterise these compounds from the cultivar ‘Yae-no-amacha’ using NMR and LC-MS methods. For purification and isolation, counter-current chromatography was used in combination with reversed-phase preparative HPLC as an orthogonal and enhanced purification workflow. Thirteen dihydro-isocoumarins in combination with other metabolites could be isolated and structurally identified. Particularly interesting was the clarification of dihydrostilbenoid glycosides, which were described for the first time in H. macrophylla ssp. serrata. These results will help us in further studies on the biological interpretation of our data.     

Assemblies from metallic and semiconducting nanocrystals

Optical properties of nanomaterials such as semiconductor and metal quantum dots are important for sensors and photovoltaic applications. We report on optical, microscopic, and AFM investigations on bulk and single nanoobjects such as metal and semiconducting nanoparticles. Firstly, of special interest is the investigation of Ag metal nanoaggregates formed in zeolites. Here, the defined structure of the zeolite serves both as size directing and a stabilizing agent. The size selected Ag aggregates fluoresce in the zeolite cages even after storage under ambient conditions for almost one year. In addition, single Ag particles escape the cages and can be investigated by fluorescence microscopy also with respect to sensor applications. Secondly, with respect to photovoltaic applications, energy transfer among organic dye molecules and semiconductor quantum dots is of great importance. We report on the extension of the optical absorption of ZnSe quantum dots into the UV regime and investigate excitation energy transfer within self-assembled nanoaggregates of surface functionalized QDs and fluorescent styrylpyridine dyes.     

Horizontal bridges in polar dielectric liquids

When a high-voltage direct-current is applied to two beakers filled with polar liquid dielectrica like water or methanol, a horizontal bridge forms between the two beakers. By repeating a version of Pellat’s experiment, it is shown that a horizontal bridge is stable by the action of electrohydrodynamic pressure. Thus, the static and dynamic properties of the phenomenon called a ‘floating water bridge’ can be explained by the gradient of Maxwell pressure, replenishing the liquid within the bridge against any drainage mechanism. It is also shown that a number of liquids can form stable and long horizontal bridges. The stability of such a connection, and the asymmetry in mass flow through such bridges caused by the formation of ion clouds in the vicinity of the electrodes, is also discussed by two further experiments.     

Diffusion effects on the CPMG relaxation rate in a dipolar field

The diffusion in the magnetic dipolar field around a sphere is considered. The diffusion is restricted to the space between two concentric spheres, where the inner sphere is the source of the magnetic dipolar field. Analytical expressions for the CPMG transverse relaxation rate as well as the free induction decay and the spin echo time evolution are given in the Gaussian approximation. The influence of the inter-echo time is analyzed. The limiting cases of small and large inter-echo times as well as the short and long time behavior are evaluated.     

Phenylene-Bridged Perylene Monoimides as Acceptors for Organic Solar Cells: A Study on the Structure–Property Relationship

A series of non-fullerene acceptors based on perylene monoimides coupled in the peri position through phenylene linkers were synthesized via Suzuki-coupling reactions. Various substitution patterns were investigated using density functional theory (DFT) calculations in combination with experimental data to elucidate the geometry and their optical and electrochemical properties. Further investigations of the bulk properties with grazing incidence wide angle X-ray scattering (GIWAXS) gave insight into the stacking behavior of the acceptor thin films. Electrochemical and morphological properties correlate with the photovoltaic performance of devices with the polymeric donor PBDB-T and a maximum efficiency of 3.17 % was reached. The study gives detailed information about structure–property relationships of perylene-linker-perylene compounds.     

Scaling laws for transverse relaxation times

Simple scaling laws are useful tools in understanding the effect of changing parameters in MRI experiments. In this paper the general scaling behavior of the transverse relaxation times is discussed. We consider the dephasing of spins diffusing around a field inhomogeneity inside a voxel. The strong collision approximation is used to describe the diffusion process. The obtained scaling laws are valid over the whole dynamic range from motional narrowing to static dephasing. The dependence of the relaxation times on the external magnetic field, diffusion coefficients of the surrounding medium, and the characteristic scale of the field inhomogeneity is analyzed. For illustration the generally valid scaling laws are applied to the special case of a capillary, usually used as a model of the myocardial BOLD effect.     

Enzymatic Conversion of Flavonoids using Bacterial Chalcone Isomerase and Enoate Reductase

Flavonoids are a large group of plant secondary metabolites with a variety of biological properties and are therefore of interest to many scientists, as they can lead to industrially interesting intermediates. The anaerobic gut bacterium Eubacterium ramulus can catabolize flavonoids, but until now, the pathway has not been experimentally confirmed. In the present work, a chalcone isomerase (CHI) and an enoate reductase (ERED) could be identified through whole genome sequencing and gene motif search. These two enzymes were successfully cloned and expressed in Escherichia coli in their active form, even under aerobic conditions. The catabolic pathway of E. ramulus was confirmed by biotransformations of flavanones into dihydrochalcones. The engineered E. coli strain that expresses both enzymes was used for the conversion of several flavanones, underlining the applicability of this biocatalytic cascade reaction.     

On the 3-Torsion Part of the Homology of the Chessboard Complex

Let 1 ≤ m ≤ n. We prove various results about the chessboard complex M _m,n , which is the simplicial complex of matchings in the complete bipartite graph K _m,n . First, we demonstrate that there is nonvanishing 3-torsion in [(H)\tilde]_d(\sf M_m,n; \mathbb Z){{\tilde{H}_d({\sf M}_{m,n}; {\mathbb Z})}} whenever \fracm+n-43 ￡ d ￡ m-4{{\frac{m+n-4}{3}\leq d \leq m-4}} and whenever 6 ≤ m < n and d = m − 3. Combining this result with theorems due to Friedman and Hanlon and to Shareshian and Wachs, we characterize all triples (m, n, d ) satisfying [(H)\tilde]_d (\sf M_m,n; \mathbb Z) 1 0{{\tilde{H}_d \left({\sf M}_{m,n}; {\mathbb Z}\right) \neq 0}}. Second, for each k ≥ 0, we show that there is a polynomial f _k (a, b) of degree 3k such that the dimension of [(H)\tilde]_k+a+2b-2 (\sf M_{k+a+3b-1,k+2a+3b-1}; \mathbb Z₃){{\tilde{H}_{k+a+2b-2}}\,\left({{\sf M}_{k+a+3b-1,k+2a+3b-1}}; \mathbb Z_{3}\right)}, viewed as a vector space over \mathbbZ₃{\mathbb{Z}_3}, is at most f _k (a, b) for all a ≥ 0 and b ≥ k + 2. Third, we give a computer-free proof that [(H)\tilde]₂ (\sf M_5,5; \mathbb Z) @ \mathbb Z₃{{\tilde{H}_2 ({\sf M}_{5,5}; \mathbb {Z})\cong \mathbb Z_{3}}}. Several proofs are based on a new long exact sequence relating the homology of a certain subcomplex of M _m,n to the homology of M _m-2,n-1 and M _m-2,n-3.     

Quantitative Imaging by Optical Diffraction Tomography

Optical diffraction tomography (ODT) is applied to reconstruct the cross-sectional, complex refractive index distribution of cylindrical objects. Experimental reconstructions showing noticeable image contrast for refractive index variations of about 0.001, and having a spatial resolution of about 2 μm, are obtained for objects with cross-sectional diameters of about 100 μm. The results demonstrate that ODT can be used for quantitative imaging of semitransparent fibers.Presented at the International Commission of Optics Topical Meeting, Kyoto, 1994.