RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease

Receptor for AGE (RAGE) is a member of the immunoglobulin superfamily that engages distinct classes of ligands. The biology of RAGE is driven by the settings in which these ligands accumulate, such as diabetes, inflammation, neurodegenerative disorders and tumors. In this review, we discuss the context of each of these classes of ligands, including advance glycation end-products, amyloid beta peptide and the family of beta sheet fibrils, S100/calgranulins and amphoterin. Implications for the role of these ligands interacting with RAGE in homeostasis and disease will be considered.     

An inhibitor of Bcl-2 family proteins induces regression of solid tumours

Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.     

利用光纤光栅实现压力和温度同时测量

结合光纤光栅弹簧管压力传感器的结构特点 ,在悬臂梁的上下两面分别粘贴两个应力和温度灵敏系数基本相同的光纤光栅 ,通过分别测量光纤光栅对的波长位移 ,实现了压力和温度的同时测量 ,压力和温度测量的分辨率分别为 0 .1 4 MPa和 0 .5℃ .     

Totally synthetic (±)-13-Alkyl-3-hydroxy and methoxy-gona-1,3,5(10)-trien-17-ones and related compounds

Zusammenfassung Von mehreren (±) 3-Oxy- und (±) 3-Methoxy-13-alkylgona-1,3,5(10)trien-17-onen und verwandten Verbindungen, einschliesslich von Vertretern der (±) 13-Alkylgon-4-en-3-on-Reihe, werden Totalsynthese und biologische Wirksamkeit beschrieben.     

Three-dimensional control of light in a two-dimensional photonic crystal slab

Optoelectronic devices are increasingly important in communication and information technology. To achieve the necessary manipulation of light (which carries information in optoelectronic devices), considerable efforts are directed at the development of photonic crystals--periodic dielectric materials that have so-called photonic bandgaps, which prohibit the propagation of photons having energies within the bandgap region. Straightforward application of the bandgap concept is generally thought to require three-dimensional (3D) photonic crystals; their two-dimensional (2D) counterparts confine light in the crystal plane, but not in the perpendicular z direction, which inevitably leads to diffraction losses. Nonetheless, 2D photonic crystals still attract interest because they are potentially more amenable to fabrication by existing techniques and diffraction losses need not seriously impair utility. Here we report the fabrication of a waveguide-coupled photonic crystal slab (essentially a free-standing 2D photonic crystal) with a strong 2D bandgap at wavelengths of about 1.5 microm, yet which is capable of fully controlling light in all three dimensions. These features confirm theoretical calculations on the possibility of achieving 3D light control using 2D bandgaps, with index guiding providing control in the third dimension, and raise the prospect of being able to realize unusual photonic-crystal devices, such as thresholdless lasers.