Fluorescence resonance energy transfer (FRET) between a donor (D) and an acceptor (A) at the single-molecule level currently provides qualitative information about distance, and quantitative information about kinetics of distance changes. Here, we used the sorting ability of confocal microscopy equipped with alternating-laser excitation (ALEX) to measure accurate FRET efficiencies and distances from single molecules, using corrections that account for cross-talk terms that contaminate the FRET-induced signal, and for differences in the detection efficiency and quantum yield of the probes. ALEX yields accurate FRET independent of instrumental factors, such as excitation intensity or detector alignment. Using DNA fragments, we showed that ALEX-based distances agree well with predictions from a cylindrical model of DNA; ALEX-based distances fit better to theory than distances obtained at the ensemble level. Distance measurements within transcription complexes agreed well with ensemble-FRET measurements, and with structural models based on ensemble-FRET and x-ray crystallography. ALEX can benefit structural analysis of biomolecules, especially when such molecules are inaccessible to conventional structural methods due to heterogeneity or transient nature.

The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST, also called the Guo Shou Jing Telescope) is a special reflecting Schmidt telescope. LAMOST's special design allows both a large aperture (effective aperture of 3.6 m-4.9 m) and a wide field of view (FOV) (5 • ). It has an innovative active reflecting Schmidt configuration which continuously changes the mirror's surface that adjusts during the observation process and combines thin deformable mirror active optics with segmented active optics. Its primary mirror (6.67 m×6.05 m) and active Schmidt mirror (5.74 m×4.40 m) are both segmented, and composed of 37 and 24 hexagonal sub-mirrors respectively. By using a parallel controllable fiber positioning technique, the focal surface of 1.75 m in diameter can accommodate 4000 optical fibers. Also, LAMOST has 16 spectrographs with 32 CCD cameras. LAMOST will be the telescope with the highest rate of spectral acquisition. As a national large scientific project, the LAMOST project was formally proposed in 1996, and approved by the Chinese government in 1997. The construction started in 2001, was completed in 2008 and passed the official acceptance in June 2009. The LAMOST pilot survey was started in October 2011 and the spectroscopic survey will launch in September 2012. Up to now, LAMOST has released more than 480 000 spectra of objects. LAMOST will make an important contribution to the study of the large-scale structure of the Universe, structure and evolution of the Galaxy, and cross-identification of multiwaveband properties in celestial objects.

The Large sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) general survey is a spectroscopic survey that will eventually cover approximately half of the celestial sphere and collect 10 million spectra of stars, galaxies and QSOs. Objects in both the pilot survey and the first year regular survey are included in the LAMOST DR1. The pilot survey started in October 2011 and ended in June 2012, and the data have been released to the public as the LAMOST Pilot Data Release in August 2012. The regular survey started in September 2012, and completed its first year of operation in June 2013. The LAMOST DR1 includes a total of 1202 plates containing 2 955 336 spectra, of which 1 790 879 spectra have observed signalto-noise ratio (SNR) ≥ 10. All data with SNR ≥ 2 are formally released as LAMOST DR1 under the LAMOST data policy. This data release contains a total of 2 204 696 spectra, of which 1 944 329 are stellar spectra, 12 082 are galaxy spectra and 5017 are quasars. The DR1 not only includes spectra, but also three stellar catalogs with measured parameters: late A,FGK-type stars with high quality spectra (1 061 918 entries), A-type stars (100 073 entries), and M-type stars (121 522 entries). This paper introduces the survey design, the observational and instrumental limitations, data reduction and analysis, and some caveats. A description of the FITS structure of spectral files and parameter catalogs is also provided.

Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with K02288 and LDN-193189 revealed additional contacts in the K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development.