A laser driven pulsed X-ray backscatter technique for enhanced penetrative imaging

X-ray backscatter imaging can be used for a wide range of imaging applications, in particular for industrial inspection and portal security. Currently, the application of this imaging technique to the detection of landmines is limited due to the surrounding sand or soil strongly attenuating the 10s to 100s of keV X-rays required for backscatter imaging. Here, we introduce a new approach involving a 140 MeV short-pulse (< 100 fs) electron beam generated by laser wakefield acceleration to probe the sample, which produces Bremsstrahlung X-rays within the sample enabling greater depths to be imaged. A variety of detector and scintillator configurations are examined, with the best time response seen from an absorptive coated BaF₂ scintillator with a bandpass filter to remove the slow scintillation emission components. An X-ray backscatter image of an array of different density and atomic number items is demonstrated. The use of a compact laser wakefield accelerator to generate the electron source, combined with the rapid development of more compact, efficient and higher repetition rate high power laser systems will make this system feasible for applications in the field.

Phenotype-Based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis

Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge Diverset^TM library and inhibition of hyaloid vessel angiogenesis in Tg(fli1:EGFP) zebrafish. 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4–10 μM in zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants, and retinal revascularization in oxygen-induced retinopathy mice. Quininib is well tolerated in zebrafish, human cell lines, and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed that quininib does not directly target VEGF receptors but antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT_1–2) at micromolar IC₅₀ values. In summary, quininib is a novel anti-angiogenic small-molecule CysLT receptor antagonist. Quininib inhibits angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT signaling. Quininib has potential as a novel therapeutic agent to treat ocular neovascular pathologies and may complement current anti-VEGF biological agents.