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The first measurement of jet shapes, defined as the fractional transverse momentum radial distribution, for inclusive jets produced in heavy-ion collisions is presented. Data samples of PbPb and pp collisions, corresponding to integrated luminosities of 150 mu b(-1) and 5.3 pb(-1) respectively, were collected at a nucleon-nucleon centre-of-mass energy of root s(NN) = 2.76 TeV with the CMS detector at the LHC. The jets are reconstructed with the anti-k(T) algorithm with a distance parameter R = 0.3, and the jet shapes are measured for charged particles with transverse momentum P-T > 1 GeV/c. The jet shapes measured in PbPb collisions in different collision centralities are compared to reference distributions based on the pp data. A centrality-dependent modification of the jet shapes is observed in the more central PbPb collisions, indicating a redistribution of the energy inside the jet cone. This measurement provides information about the parton shower mechanism in the hot and dense medium produced in heavy-ion collisions. (C) 2014 The Authors. Published by Elsevier B.V.

Mechanosensitive ion channels underlie neuronal responses to physical forces in the sensation of touch, hearing, and other mechanical stimuli. The fundamental basis of force transduction in eukaryotic mechanosensitive ion channels is unknown. Are mechanical forces transmitted directly from membrane to channel as in prokaryotic mechanosensors or are they mediated through macromolecular tethers attached to the channel? Here we show in cells that the K+ channel TRAAK (K2P4.1) is responsive to mechanical forces similar to the ion channel Piezo1 and that mechanical activation of TRAAK can electrically counter Piezo1 activation. We then show that the biophysical origins of force transduction in TRAAK and TREK1 (K2P2.1) two-pore domain K+ (K2P) channels come from the lipid membrane, not from attached tethers. These findings extend the "force-from-lipid" principle established for prokaryotic mechanosensitive channels MscL and MscS to these eukaryotic mechanosensitive K+ channels.

In this work we analyze electro-corticography (ECoG) recordings in human subjects during induction of anesthesia with propofol. We hypothesize that the decrease in responsiveness that defines the anesthetized state is concomitant with the stabilization of neuronal dynamics. To test this hypothesis, we performed a moving vector autoregressive analysis and quantified stability of neuronal dynamics using eigenmode decomposition of the autoregressive matrices, independently fitted to short sliding temporal windows. Consistent with the hypothesis we show that while the subject is awake, many modes of neuronal activity oscillations are found at the edge of instability. As the subject becomes anesthetized, we observe statistically significant increase in the stability of neuronal dynamics, most prominently observed for high frequency oscillations. Stabilization was not observed in phase randomized surrogates constructed to preserve the spectral signatures of each channel of neuronal activity. Thus, stability analysis offers a novel way of quantifying changes in neuronal activity that characterize loss of consciousness induced by general anesthetics.

The transcription factors c-Myc and N-Myc-encoded by Myc and Mycn, respectively-regulate cellular growth(1) and are required for embryonic development(2,3). A third paralogue, Mycl1, is dispensable for normal embryonic development but its biological function has remained unclear(4). To examine the in vivo function of Mycl1 in mice, we generated an inactivating Mycl1(gfp) allele that also reports Mycl1 expression. We find that Mycl1 is selectively expressed in dendritic cells (DCs) of the immune system and controlled by IRF8, and that during DC development, Mycl1 expression is initiated in the common DC progenitor(5) concurrent with reduction in c-Myc expression. Mature DCs lack expression of c-Myc and N-Myc but maintain L-Myc expression even in the presence of inflammatory signals such as granulocyte-macrophage colony-stimulating factor. All DC subsets develop in Mycl1-deficient mice, but some subsets such as migratory CD103(+) conventional DCs in the lung and liver are greatly reduced at steady state. Importantly, loss of L-Myc by DCs causes a significant decrease in in vivo T-cell priming during infection by Listeria monocytogenes and vesicular stomatitis virus. The replacement of c-Myc by L-Myc in immature DCs may provide for Myc transcriptional activity in the setting of inflammation that is required for optimal T-cell priming(6).

The photophysical properties of a chlorin, isobacteriochlorin and bacteriochlorin built on a core tetrapentafluorophenylporphyrin (TPPF20) and the nonhydrolyzable para thioglycosylated conjugates of these chromophores are presented. The photophysical characterization of these compounds was done in three different solvents to correlate with different environments in cells and tissues. Compared with TPPF20 other dyes have greater absorption in the red region of the visible spectrum and greater fluorescence quantum yields. The excited state lifetimes are from 3 to 11ns. The radiative and nonradiative rate constants for deactivation of the excited state were estimated from the fluorescence quantum yield and excited state lifetime. The data indicate that the bacteriochlorin has strong absorption bands near 730nm and efficiently enters the triplet manifold. The isobacteriochlorin has a 40-70% fluorescence quantum yield depending on solvent, so it may be a good fluorescent tag. The isobacteriochlorins also display enhanced two-photon absorption, thereby allowing the use of 860nm light to excite the compound. While the two-photon cross section of 25GM units is not large, excitation of low chromophore concentrations can induce apoptosis. The glycosylated compounds accumulate in cancer cells and a head and neck squamous carcinoma xenograft tumor model in mice. These compounds are robust to photobleaching.

A search for three-jet hadronic resonance production in pp collisions at a centre-of-mass energy of 8 TeV has been conducted by the CMS Collaboration at the LHC with a data sample corresponding to an integrated luminosity of 19.4 fb(-1). The search method is model independent, and events are selected that have high jet multiplicity and large values of jet transverse momenta. The signal models explored assume R-parity-violating supersymmetric gluino pair production and have final states with either only light-flavour jets or both light- and heavy-flavour jets. No significant deviation is found between the selected events and the expected standard model multijet and t (t) over bar background. For a gluino decaying into light-flavour jets, a lower limit of 650 GeV on the gluino mass is set at a 95% confidence level, and for a gluino decaying into one heavy- and two light-flavour jets, gluino masses between 200 and 835 GeV are, for the first time, likewise excluded. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

While gastrulation movements offer mechanistic paradigms for how collective cellular movements shape developing embryos, far less is known about coordinated cellular movements that occur later in development. Studying eyelid closure, we explore a case where an epithelium locally reshapes, expands, and moves over another epithelium. Live imaging, gene targeting, and cell-cycle inhibitors reveal that closure does not require overlying periderm, proliferation, or supracellular actin cable assembly. Laser ablation and quantitative analyses of tissue deformations further distinguish the mechanism from wound repair and dorsal closure. Rather, cell intercalations parallel to the tissue front locally compress it perpendicularly, pulling the surrounding epidermis along the closure axis. Functional analyses in vivo show that the mechanism requires localized myosin-IIA- and alpha 5 beta 1 integrin/fibronectin-mediated migration and E-cadherin downregulation likely stimulated by Wnt signaling. These studies uncover a mode of epithelial closure in which forces generated by cell intercalation are leveraged to tow the surrounding tissue.

Total internal reflection fluorescence microscopy (TIRFM) is becoming an increasingly common methodology to narrow the illumination excitation thickness to study cellular process such as exocytosis, endocytosis, and membrane dynamics. It is also frequently used as a method to improve signal/noise in other techniques such as in vitro single-molecule imaging, stochastic optical reconstruction microscopy/photoactivated localization microscopy imaging, and fluorescence resonance energy transfer imaging. The unique illumination geometry of TIRFM also enables a distinct method to create an excitation field for selectively exciting fluorophores that are aligned either parallel or perpendicular to the optical axis. This selectivity has been used to study orientation of cell membranes and cellular proteins. Unfortunately, the coherent nature of laser light, the typical excitation source in TIRFM, often creates spatial interference fringes across the illuminated area. These fringes are particularly problematic when imaging large cellular areas or when accurate quantification is necessary. Methods have been developed to minimize these fringes by modulating the TIRFM field during a frame capture period; however, these approaches eliminate the possibility to simultaneously excite with a specific polarization. A new, to our knowledge, technique is presented, which compensates for spatial fringes while simultaneously permitting rapid image acquisition of both parallel and perpendicular excitation directions in similar to 25 ms. In addition, a back reflection detection scheme was developed that enables quick and accurate alignment of the excitation laser. The detector also facilitates focus drift compensation, a common problem in TIRFM due to the narrow excitation depth, particularly when imaging over long time courses or when using a perfusion flow chamber. The capabilities of this instrument were demonstrated by imaging membrane orientation using DiO on live cells and on lipid bilayers that were supported on a glass slide (supported lipid bilayer). The use of the approach to biological problems was illustrated by examining the temporal and spatial dynamics of exocytic vesicles.

Recent research on long noncoding RNAs (IncRNAs) has expanded our understanding of gene transcription regulation and the generation of cellular complexity. Depending on their genomic origins, IncRNAs can be transcribed from intergenic or intragenic regions or from introns of protein-coding genes. We have recently reported more than 6000 intergenic lncRNAs in Arabidopsis. Here, we systematically identified long noncoding natural antisense transcripts (IncNATs), defined as lncRNAs transcribed from the opposite DNA strand of coding or noncoding genes. We found a total of 37,238 sense-antisense transcript pairs and 70% of annotated mRNAs to be associated with antisense transcripts in Arabidopsis. These IncNATs could be reproducibly detected by different technical platforms, including strand-specific tiling arrays, Agilent custom expression arrays, strand-specific RNA-seq, and qRT-PCR experiments. Moreover, we investigated the expression profiles of sense-antisense pairs in response to light and observed spatial and developmental-specific light effects on 626 concordant and 766 discordant NAT pairs. Genes for a large number of the light-responsive NAT pairs are associated with histone modification peaks, and histone acetylation is dynamically correlated with light-responsive expression changes of NATs.

Several risk groups are known for the rare but serious, frequently fatal, viscerotropic reactions following live yellow fever virus vaccine (YEL-AVD). Establishing additional risk groups is hampered by ignorance of the numbers of vaccinees in factor-specific risk groups thus preventing their use as denominators in odds ratios (ORs). Here, we use an equation to calculate ORs using the prevalence of the factor-specific risk group in the population who remain well. The 95% confidence limits and P values can also be calculated. Moreover, if the estimate of the prevalence is imprecise, discrimination analysis can indicate the prevalence at which the confidence interval results in an OR of similar to 1 revealing if the prevalence might be higher without yielding a non-significant result. These methods confirm some potential risk groups for YEL-AVD and cast doubt on another. They should prove useful in situations in which factor-specific risk group denominator data are not available.