Current and emerging therapies for the treatment of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV) due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF) therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA) to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary neurotrophic factor is currently being studied for the inhibition of progression of geographic atrophy. Combination therapy has been investigated, and may prove to be more effective in the management of AMD-associated CNV. Ongoing and future studies will be crucial for optimizing the treatment of patients with AMD

Parallel Multi-Hypothesis Algorithm for Criticality Estimation in Traffic and Collision Avoidance

Due to the current developments towards autonomous driving and vehicle active safety, there is an increasing necessity for algorithms that are able to perform complex criticality predictions in real-time. Being able to process multi-object traffic scenarios aids the implementation of a variety of automotive applications such as driver assistance systems for collision prevention and mitigation as well as fall-back systems for autonomous vehicles. We present a fully model-based algorithm with a parallelizable architecture. The proposed algorithm can evaluate the criticality of complex, multi-modal (vehicles and pedestrians) traffic scenarios by simulating millions of trajectory combinations and detecting collisions between objects. The algorithm is able to estimate upcoming criticality at very early stages, demonstrating its potential for vehicle safety-systems and autonomous driving applications. An implementation on an embedded system in a test vehicle proves in a prototypical manner the compatibility of the algorithm with the hardware possibilities of modern cars. For a complex traffic scenario with 11 dynamic objects, more than 86 million pose combinations are evaluated in 21 ms on the GPU of a Drive PX~2

cryoWriter: a blotting free cryo-EM preparation system with a climate jet and cover-slip injector

Electron microscopy (EM) introduced a fast and lasting change to structural and cellular biology. However, the sample preparation is still the bottleneck in the cryogenic electron microscopy (cryo-EM) workflow. Classical specimen preparation methods employ a harsh paper-blotting step, and the protein particles are exposed to a damaging air-water interface. Therefore, improved preparation strategies are urgently needed. Here, we present an amended microfluidic sample preparation method, which entirely avoids paper blotting and allows the passivation of the air-water interface during the preparation process. First, a climate jet excludes oxygen from the sample environment and controls the preparation temperature by varying the relative humidity of the grid environment. Second, the integrated "coverslip injector" allows the modulation of the air-water interface of the thin sample layer with effector molecules. We will briefly discuss the climate jet's effect on the stability and dynamics of the sample thin films. Furthermore, we will address the coverslip injector and demonstrate significant improvement in the sample quality

EPOS : evolving personal to organizational knowledge spaces

EPOS will leverage the user´s personal workspace with its manyfold native information structures to his personal knowledge space and in cooperation with other personal workspaces contribute to the organizational knowledge space which is represented in the organizational memory. This first milestone presents results from the project´s first year in the areas of the personal informational model, user observation for context elicitation, collaborative information retrieval and information visualization

Atomic Force Microscopy-Based Screening of Drug-Excipient Miscibility and Stability of Solid Dispersions

ABSTRACT: Purpose: Development of a method to assess the drug/polymer miscibility and stability of solid dispersions using a melt-based mixing method. Methods: Amorphous fractured films are prepared and characterized with Raman Microscopy in combination with Atomic Force Microscopy to discriminate between homogenously and heterogeneously mixed drug/polymer combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature. Results: Combinations that have the potential to form a molecular disperse mixture are identified. Their potential to phase separate is determined through imaging at molecular length scales, which results in short observation time. De-mixing is quantified by phase separation analysis, and the drug/polymer combinations are ranked to identify the most stable combinations. Conclusions: The presented results demonstrate that drug/polymer miscibility and stability of solid dispersions, with many mechanistic details, can be analyzed with Atomic Force Microscopy. The assay allows to identify well-miscible and stable combinations within hours or a few day

Development of a ³He magnetometer for a neutron electric dipole moment experiment

We have developed a highly sensitive 3He magnetometer for the accurate measurement of the magnetic field in an experiment searching for an electric dipole moment of the neutron. By measuring the Larmor frequency of nuclear spin polarized 3He atoms a sensitivity on the femto-Tesla scale can be achieved. A 3He/Cs-test facility was established at the Institute of Physics of the Johannes Gutenberg University in Mainz to investigate the readout of 3He free induction decay with a lamp-pumped Cs magnetometer. For this we designed and built an ultra-compact and transportable polarizer unit which polarizes 3He gas up to 55% by metastability exchange optical pumping. The polarized 3He was successfully transfered from the polarizer into a glass cell mounted in a magnetic shield and the 3He free induction decay was detected by a lamp-pumped Cs magnetometer.PACS numbers07.55.Ge Magnetometers for magnetic field measurements; 13.40 Electric and magnetic moments; 14.20 Protons and neutrons

Atomic Force Microscopy-Based Screening of Drug-Excipient Miscibility and Stability of Solid Dispersions

PURPOSE: Development of a method to assess the drug/polymer miscibility and stability of solid dispersions using a melt-based mixing method. METHODS: Amorphous fractured films are prepared and characterized with Raman Microscopy in combination with Atomic Force Microscopy to discriminate between homogenously and heterogeneously mixed drug/polymer combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature. RESULTS: Combinations that have the potential to form a molecular disperse mixture are identified. Their potential to phase separate is determined through imaging at molecular length scales, which results in short observation time. De-mixing is quantified by phase separation analysis, and the drug/polymer combinations are ranked to identify the most stable combinations. CONCLUSIONS: The presented results demonstrate that drug/polymer miscibility and stability of solid dispersions, with many mechanistic details, can be analyzed with Atomic Force Microscopy. The assay allows to identify well-miscible and stable combinations within hours or a few days