The sensitivity of molecular fingerprinting is dramatically improved when placing the absorbing sample in a high-finesse optical cavity, thanks to the large increase of the effective path-length. As demonstrated recently, when the equidistant lines from a laser frequency comb are simultaneously injected into the cavity over a large spectral range, multiple trace-gases may be identified within a few milliseconds. Analyzing efficiently the light transmitted through the cavity however still remains challenging. Here, a novel approach, cavity-enhanced frequency comb Fourier transform spectroscopy, fully overcomes this difficulty and measures ultrasensitive, broad-bandwidth, high-resolution spectra within a few tens of $\mu$s. It could be implemented from the Terahertz to the ultraviolet regions without any need for detector arrays. We recorded, within 18 $\mu$s, spectra of the 1.0 $\mu$m overtone bands of ammonia spanning 20 nm with 4.5 GHz resolution and a noise-equivalent-absorption at one-second-averaging per spectral element of 3 10^-12 cm^-1Hz^-1/2, thus opening a route to time-resolved spectroscopy of rapidly-evolving single-events

We demonstrated single-shot measurements of spectral interference between a white-light continuum generated in a hollow-fiber and its second harmonic. The interference has information on the carrier-envelope phase of an input pulse to the fiber and the time delay of the blue wing of the continuum. By analyzing the observed spectral interference, we estimated shot-by-shot changes of the carrier-envelope phase. This method is useful for determining the carrier-envelope phase changes of a low-repetition-rate, high-intensity laser.

FLASH has been shown to be required for S phase progression and to interact with a nuclear protein, ataxia-telangiectasia locus (NPAT), a component of Cajal bodies in the nucleus and an activator of histone transcription. We investigated the role of human FLASH by using an inducible FLASH knockdown system in the presence or absence of various mutant forms of mouse FLASH. While carboxyl-terminal deletion mutants of FLASH, which do not interact with NPAT, can support S phase progression, its amino-terminal deletion mutants, which are unable to self associate, cannot support S phase progression, replication-dependent histone transcription, or the formation of Cajal bodies. Furthermore, FLASH was shown to be associated with arsenite resistance protein 2 (ARS2) through its central region, which is composed of only 13 amino acids. The expression of ARS2 and the interaction between FLASH and ARS2 are required for S phase progression. Taking these results together, FLASH functions in S phase progression through interaction with ARS2.FADD-like interleukin-1␤-converting enzyme/caspase-8-associated huge protein (FLASH)/CASP8AP2, originally identified as a component of the Fas-caspase-8-mediated apoptosis-inducing pathway (13), was reported to be involved in Fas-mediated apoptotic signaling through translocation from the nucleus to the cytoplasm (20). FLASH also was shown to act in the nucleus as an enhancer and/or repressor of steroid hormone receptor-mediated transcription (14,15,21). On the other hand, FLASH was found to be essential for cell division by the high-throughput screening of a genome-scale library of short interfering RNAs (16). FLASH also was reported to be a potential prognostic marker in cases of acute lymphoblastic leukemia (10). Recently, it was shown that FLASH is an essential component of Cajal bodies in the nucleus, playing an important role in histone transcription and S phase progression (3, 4). In addition, these reports indicated that FLASH interacts with a nuclear protein, ataxia-telangiectasia locus (p220 NPAT [NPAT]), a component of Cajal bodies. The phosphorylation of NPAT by cyclin E/Cdk2 was reported to regulate the activation of histone gene transcription in S phase and to be necessary to maintain the structure of Cajal bodies during the cell cycle (7,19,27,29,30). Therefore, FLASH has been thought to play an essential role in S phase progression, probably through interaction with NPAT. However, the molecular mechanisms underlying the role of FLASH in cell cycle progression largely have remained unknown.Cajal bodies are small subnuclear organelles, originally described by Santiago Ramon Y Cajal in 1903, that are involved in several nuclear functions, including the biogenesis and trafficking of small nuclear and nucleolar ribonucleoprotein particles (snRNPs and snoRNPs, respectively) and the processing of pre-rRNA and replication-dependent histone mRNA (6, 11). Recently, a number of Cajal bodies were found to contain FLASH and NPAT but not coilin, a conventional marker of such bodies, sugges...

(HT) † These authors contributed equally to this work. Running title: LBP mediates LPS-induced TLR4 internalization and signalingKeywords: CD14, cell surface receptor, endotoxin, innate immunity, LPS, LPS-binding protein (LBP), pathogen-associated molecular pattern (PAMP), pattern recognition receptor (PRR), TIR-domaincontaining adapter-inducing interferon-β (TRIF), Toll-like receptor 4 (TLR4), AbstractToll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKε, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NFκB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces LBP mediates LPS-induced TLR4 internalization and signaling 1 http://www.jbc.org/cgi

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