2,510 research outputs found
Remote and reversible inhibition of neurons and circuits by small molecule induced potassium channel stabilization
Manipulating the function of neurons and circuits that translate electrical and chemical signals into behavior represents a major challenges in neuroscience. In addition to optogenetic methods using light-activatable channels, pharmacogenetic methods with ligand induced modulation of cell signaling and excitability have been developed. However, they are largely based on ectopic expression of exogenous or chimera proteins. Now, we describe the remote and reversible expression of a Kir2.1 type potassium channel using the chemogenetic technique of small molecule induced protein stabilization. Based on shield1-mediated shedding of a destabilizing domain fused to a protein of interest and inhibition of protein degradation, this principle has been adopted for biomedicine, but not in neuroscience so far. Here, we apply this chemogenetic approach in brain research for the first time in order to control a potassium channel in a remote and reversible manner. We could show that shield1-mediated ectopic Kir2.1 stabilization induces neuronal silencing in vitro and in vivo in the mouse brain. We also validated this novel pharmacogenetic method in different neurobehavioral paradigms. The DD-Kir2.1 may complement the existing portfolio of pharmaco- and optogenetic techniques for specific neuron manipulation, but it may also provide an example for future applications of this principle in neuroscience research
Observation of an Excited Bc+ State
Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+Ï+Ï- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bcâ(2S31)+ state reconstructed without the low-energy photon from the Bcâ(1S31)+âBc+Îł decay following Bcâ(2S31)+âBcâ(1S31)+Ï+Ï-. A second state is seen with a global (local) statistical significance of 2.2Ï (3.2Ï) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date
Observation of two new baryon resonances
Two structures are observed close to the kinematic threshold in the mass spectrum in a sample of proton-proton collision data, corresponding
to an integrated luminosity of 3.0 fb recorded by the LHCb experiment.
In the quark model, two baryonic resonances with quark content are
expected in this mass region: the spin-parity and
states, denoted and .
Interpreting the structures as these resonances, we measure the mass
differences and the width of the heavier state to be
MeV,
MeV,
MeV, where the first and second
uncertainties are statistical and systematic, respectively. The width of the
lighter state is consistent with zero, and we place an upper limit of
MeV at 95% confidence level. Relative
production rates of these states are also reported.Comment: 17 pages, 2 figure
Measurement of the mass and lifetime of the baryon
A proton-proton collision data sample, corresponding to an integrated
luminosity of 3 fb collected by LHCb at and 8 TeV, is used
to reconstruct , decays. Using the , decay mode for calibration, the lifetime ratio and absolute
lifetime of the baryon are measured to be \begin{align*}
\frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\
\tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the
uncertainties are statistical, systematic and from the calibration mode (for
only). A measurement is also made of the mass difference,
, and the corresponding mass, which
yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm
MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2.
\end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm
Measurement of the lifetime
Using a data set corresponding to an integrated luminosity of ,
collected by the LHCb experiment in collisions at centre-of-mass energies
of 7 and 8 TeV, the effective lifetime in the
decay mode, , is measured to be ps. Assuming
conservation, corresponds to the lifetime of the light
mass eigenstate. This is the first measurement of the effective
lifetime in this decay mode.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-017.htm
Observation of associated production of a boson with a meson in the~forward region
A search for associated production of a boson with an open charm meson is
presented using a data sample, corresponding to an integrated luminosity of
of proton--proton collisions at a centre-of-mass energy
of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for
associated production of a boson with a meson and four candidate
events for a boson with a meson are observed with a combined
significance of 5.1standard deviations. The production cross-sections in the
forward region are measured to be where the first uncertainty is statistical and the
second systematic.Comment: 18 pages, 2 figure
Study of charmonium production in b -hadron decays and first evidence for the decay Bs0
Using decays to Ï-meson pairs, the inclusive production of charmonium states in b-hadron decays is studied with pp collision data corresponding to an integrated luminosity of 3.0 fbâ1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. Denoting byBC ⥠B(b â C X) Ă B(C â ÏÏ) the inclusive branching fraction of a b hadron to a charmonium state C that decays into a pair of Ï mesons, ratios RC1C2 ⥠BC1 /BC2 are determined as RÏc0ηc(1S) = 0.147 ± 0.023 ± 0.011, RÏc1ηc(1S) =0.073 ± 0.016 ± 0.006, RÏc2ηc(1S) = 0.081 ± 0.013 ± 0.005,RÏc1 Ïc0 = 0.50 ± 0.11 ± 0.01, RÏc2 Ïc0 = 0.56 ± 0.10 ± 0.01and Rηc(2S)ηc(1S) = 0.040 ± 0.011 ± 0.004. Here and below the first uncertainties are statistical and the second systematic.Upper limits at 90% confidence level for the inclusive production of X(3872), X(3915) and Ïc2(2P) states are obtained as RX(3872)Ïc1 < 0.34, RX(3915)Ïc0 < 0.12 andRÏc2(2P)Ïc2 < 0.16. Differential cross-sections as a function of transverse momentum are measured for the ηc(1S) andÏc states. The branching fraction of the decay B0s â ÏÏÏ is measured for the first time, B(B0s â ÏÏÏ) = (2.15±0.54±0.28±0.21B)Ă10â6. Here the third uncertainty is due to the branching fraction of the decay B0s â ÏÏ, which is used for normalization. No evidence for intermediate resonances is seen. A preferentially transverse Ï polarization is observed.The measurements allow the determination of the ratio of the branching fractions for the ηc(1S) decays to ÏÏ and p p asB(ηc(1S)â ÏÏ)/B(ηc(1S)â p p) = 1.79 ± 0.14 ± 0.32
Measurements of the , , meson and baryon lifetimes
Measurements of -hadron lifetimes are reported using collision data,
corresponding to an integrated luminosity of 1.0fb, collected by the
LHCb detector at a centre-of-mass energy of Tev. Using the exclusive decays
, , ,
and the average decay
times in these modes are measured to be = 0.004 0.003 ps, =
0.006 0.004 ps, = 0.013
0.005 ps, = 0.027
0.006 ps and = 0.011
0.005 ps, where the first uncertainty is statistical and the second is
systematic. These represent the most precise lifetime measurements in these
decay modes. In addition, ratios of these lifetimes, and the ratio of the
decay-width difference, , to the average width, , in
the system, , are
reported. All quantities are found to be consistent with Standard Model
expectations.Comment: 28 pages, 4 figures. Updated reference
Study of J /Ï production in Jets
The production of J/Ï mesons in jets is studied in the forward region of proton-proton collisions using data collected with the LHCb detector at a center-of-mass energy of 13 TeV. The fraction of the jet transverse momentum carried by the J/Ï meson, z(J/Ï)âĄpT(J/Ï)/pT(jet), is measured using jets with pT(jet)>20 GeV in the pseudorapidity range 2.5<η(jet)<4.0. The observed z(J/Ï)distribution for J/Ï mesons produced in b-hadron decays is consistent with expectations. However, the results for prompt J/Ï production do not agree with predictions based on fixed-order nonrelativistic QCD. This is the first measurement of the pT fraction carried by prompt J/Ï mesons in jets at any experiment
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