Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term

The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG is primarily metabolized by UGT1A4 and this isozyme is shown to be present in placenta at term, it may be hypothesized that the placenta is involved in the fall of LTG serum concentrations during pregnancy

A beta 2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation

beta 2-integrins are essential for immune system function because they mediate immune cell adhesion and signaling. Consequently, a loss of beta(2)-integrin expression or function causes the immunodeficiency disorders, Leukocyte Adhesion Deficiency (LAD) type I and III. LAD-III is caused by mutations in an important integrin regulator, kindlin-3, but exactly how kindlin-3 regulates leukocyte adhesion has remained incompletely understood. Here we demonstrate that mutation of the kindlin-3 binding site in the beta 2-integrin (TTT/AAA-beta 2-integrin knock-in mouse/KI) abolishes activation of the actin-regulated myocardin related transcription factor A/serum response factor (MRTF-A/SRF) signaling pathway in dendritic cells and MRTF-A/SRF-dependent gene expression. We show that Ras homolog gene family, member A (RhoA) activation and filamentous-actin (F-actin) polymerization is abolished in murine TTT/AAA-beta 2-integrin KI dendritic cells, which leads to a failure of MRTF-A to localize to the cell nucleus to coactivate genes together with SRF. In addition, we show that dendritic cell gene expression, adhesion and integrin-mediated traction forces on ligand coated surfaces is dependent on the MRTF-A/SRF signaling pathway. The participation of beta 2-integrin and kindlin-3-mediated cell adhesion in the regulation of the ubiquitous MRTF-A/SRF signaling pathway in immune cells may help explain the role of beta 2-integrin and kindlin-3 in integrin-mediated gene regulation and immune system function

Spatial Division Multiplexed Microwave Signal processing by selective grating inscription in homogeneous multicore fibers

[EN] The use of Spatial Division Multiplexing for Microwave Photonics signal processing is proposed and experimentally demonstrated, for the first time to our knowledge, based on the selective inscription of Bragg gratings in homogeneous multicore fibers. The fabricated devices behave as sampled true time delay elements for radiofrequency signals offering a wide range of operation possibilities within the same optical fiber. The key to processing flexibility comes from the implementation of novel multicavity configurations by inscribing a variety of different fiber Bragg gratings along the different cores of a 7-core fiber. This entails the development of the first fabrication method to inscribe high-quality gratings characterized by arbitrary frequency spectra and located in arbitrary longitudinal positions along the individual cores of a multicore fiber. Our work opens the way towards the development of unique compact fiber-based solutions that enable the implementation of a wide variety of 2D (spatial and wavelength diversity) signal processing functionalities that will be key in future fiber-wireless communications scenarios. We envisage that Microwave Photonics systems and networks will benefit from this technology in terms of compactness, operation versatility and performance stability.We thank Prof. Jose Capmany for the thoughtful discussions and recommendations that greatly contribute to this work. This research was supported by the Spanish MINECO Projects TEC2014-60378-C2-1-R and TEC2015-62520-ERC, the Valencian Research Excellency Award Program GVA PROMETEO 2013/012, the Spanish MECD FPU Scholarship (FPU13/04675) for J. Hervas, and the Spanish MINECO Ramon y Cajal Program (RYC-2014-16247) for I. Gasulla.Gasulla Mestre, I.; Barrera Vilar, D.; Hervás-Peralta, J.; Sales Maicas, S. (2017). Spatial Division Multiplexed Microwave Signal processing by selective grating inscription in homogeneous multicore fibers. Scientific Reports. 7(41727):1-10. https://doi.org/10.1038/srep41727S110741727Samsung Electronics Co, “5G Vision”, available at http://www.samsung.com/global/business-images/insights/2015/Samsung-5G-Vision-0.pdf (2015).Technology Focus on Microwave Photonics. Nat. Photonics 5, 723 (2011).J. Capmany, J. Mora, I. Gasulla, J. Sancho, J. Lloret & S. Sales . Microwave photonic signal processing. IEEE J. Lightw. Technol. 31, 571–586 (2013).Y. Long & J. Wang . Ultra-high peak rejection notch microwave photonic filter using a single silicon microring resonator. Opt. Express 23, 17739–17750 (2015).Y. Long & J. Wang . All-optical tuning of a nonlinear silicon microring assisted microwave photonic filter: theory and experiment. Opt. Express 23, 17758–17771 (2015).Y. Long, L. Zhou & J. Wang . Photonic-assisted microwave signal multiplication and modulation using a silicon Mach–Zehnder modulator. Sci. Reports 6, 20215 (2016).J. Sancho, J. Bourderionnet, J. Lloret, S. Combrié, I. Gasulla, S. Xavier, S. Sales, P. Colman, G. Lehoucq, D. Dolfi, J. Capmany & A. De Rossi . Integrable microwave filter based on a photonic crystal delay line. Nat. Commun. 3, 1075 (2012).F. Ohman, K. Yvind & J. Mørk . Slow Light in a Semiconductor Waveguide for True-Time Delay Applications in Microwave Photonics. IEEE Photon. Technol. Lett. 19, 1145–1157 (2007).P. A. Morton & J. B. Khurgin. Microwave photonic delay line with separate tuning of the optical carrier. IEEE Photon. Technol. Lett. 21, 1686–1688 (2009).D. Marpaung, C. Roeloffzen, R. Heideman, A. Leinse, S. Sales & J. Capmany . Integrated microwave photonics. Lasers Photon. Rev. 7, 506–538 (2013).I. Gasulla & J. Capmany . Microwave photonics applications of multicore fibers. Photonics J. 4, 877–888 (2012).S. Garcia & I. Gasulla . Design of Heterogeneous Multicore fibers as sampled True Time Delay Lines. Opt. Lett. 40, 621–624 (2015).F. Zeng & J. Yao . All-optical microwave filters using uniform fiber Bragg gratings with identical reflectivities. IEEE J. Lightw. Technol. 23, 1410 (2005).C. Wang & J. Yao . Fiber Bragg gratings for microwave photonics subsystems. Opt. Express 21, 22868–22884 (2013).I. Gasulla, D. Barrera & S. Sales . Microwave photonic devices based on multicore fibers. 16th International Conference on Transparent Optical Networks (ICTON), Graz, Austria, 2014.I. Gasulla, D. Barrera, J. Hervás, S. García & S. Sales . Multi-cavity Microwave Photonics devices built upon multicore fibres. 18th International Conference on Transparent Optical Networks (ICTON), Trento (Italy), pp. 1–4, 2016.K. O. Hill & G. Meltz . Fiber Bragg grating technology fundamentals and overview. IEEE J. Lightw. Technol. 15, 1263–1276 (1997).T. Erdogan . Fiber grating spectra. IEEE J. Lightw. Technol. 15, 1277–1294 (1997).D. Barrera, I. Gasulla & S. Sales . Multipoint two-dimensional curvature optical fiber sensor based on a non-twisted homogeneous four-core fiber. IEEE J. Lightw. Technol. 33, 2445–2450 (2015).T. Birks, B. Mangan, A. Diez, J. Cruz, S. Leon-Saval, J. Bland-Hawthorn & D. Murphy . Multicore optical fibres for astrophotonics. In CLEO/Europe and EQEC 2011 Conference Digest, OSA Technical Digest (CD)d (Optical Society of America, 2011), paper JSIII2_1.C. Wang, Z. Yan, Q. Sun, Z. Sun, C. Mou, J. Zhang, A. Badmos & L. Zhang . Fibre Bragg gratings fabrication in four core fibres. Proc. SPIE 9886, Micro-Structured and Specialty Optical Fibres IV, 98860H (2016).M. J. Cole, W. H. Loh, R. I. Laming, M. N. Zervas & S. Barcelos . Moving fibre/phase mask-scanning beam technique for enhanced flexibility in producing fibre gratings with uniform phase mask. Electron. Lett. 31, 1488–1490 (1995).M. Gallagher & U. Österberg . Time resolved 3.10 eV luminescence in germanium-doped silica glass. Appl. Phys. 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Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)

Using gene expression profiles from peripheral blood to identify asymptomatic responses to acute respiratory viral infections

<p>Abstract</p> <p>Background</p> <p>A recent study reported that gene expression profiles from peripheral blood samples of healthy subjects prior to viral inoculation were indistinguishable from profiles of subjects who received viral challenge but remained asymptomatic and uninfected. If true, this implies that the host immune response does not have a molecular signature. Given the high sensitivity of microarray technology, we were intrigued by this result and hypothesize that it was an artifact of data analysis.</p> <p>Findings</p> <p>Using acute respiratory viral challenge microarray data, we developed a molecular signature that for the first time allowed for an accurate differentiation between uninfected subjects prior to viral inoculation and subjects who remained asymptomatic after the viral challenge.</p> <p>Conclusions</p> <p>Our findings suggest that molecular signatures can be used to characterize immune responses to viruses and may improve our understanding of susceptibility to viral infection with possible implications for vaccine development.</p

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Measurement of the top pair production cross section in 8 TeV proton-proton collisions using kinematic information in the lepton plus jets final state with ATLAS

A measurement is presented of the $t\bar{t}$ inclusive production cross-section in $pp$ collisions at a center-of-mass energy of $\sqrt{s}=8$ TeV using data collected by the ATLAS detector at the CERN Large Hadron Collider. The measurement was performed in the lepton+jets final state using a data set corresponding to an integrated luminosity of 20.3 fb$^{-1}$. The cross-section was obtained using a likelihood discriminant fit and $b$-jet identification was used to improve the signal-to-background ratio. The inclusive $t\bar{t}$ production cross-section was measured to be $260\pm 1{\textrm{(stat.)}} ^{+22}_{-23} {\textrm{(syst.)}}\pm 8{\textrm{(lumi.)}}\pm 4{\mathrm{(beam)}}$ pb assuming a top-quark mass of 172.5 GeV, in good agreement with the theoretical prediction of $253^{+13}_{-15}$ pb. The $t\bar{t}\to (e,\mu)+{\mathrm{jets}}$ production cross-section in the fiducial region determined by the detector acceptance is also reported.Comment: Published version, 19 pages plus author list (35 pages total), 3 figures, 2 tables, all figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2013-06

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model