Molecular Basis of ß-­arrestin Coupling to Formoterol-­Bound ß1-­adrenoceptor

The β1-adrenoceptor (β1AR) is a G-protein-coupled receptor (GPCR) that couples1 to the heterotrimeric G protein Gs. G-protein-mediated signalling is terminated by phosphorylation of the C terminus of the receptor by GPCR kinases (GRKs) and by coupling of β-arrestin 1 (βarr1, also known as arrestin 2), which displaces Gs and induces signalling through the MAP kinase pathway2. The ability of synthetic agonists to induce signalling preferentially through either G proteins or arrestins-known as biased agonism3-is important in drug development, because the therapeutic effect may arise from only one signalling cascade, whereas the other pathway may mediate undesirable side effects4. To understand the molecular basis for arrestin coupling, here we determined the cryo-electron microscopy structure of the β1AR-βarr1 complex in lipid nanodiscs bound to the biased agonist formoterol5, and the crystal structure of formoterol-bound β1AR coupled to the G-protein-mimetic nanobody6 Nb80. βarr1 couples to β1AR in a manner distinct to that7 of Gs coupling to β2AR-the finger loop of βarr1 occupies a narrower cleft on the intracellular surface, and is closer to transmembrane helix H7 of the receptor when compared with the C-terminal α5 helix of Gs. The conformation of the finger loop in βarr1 is different from that adopted by the finger loop of visual arrestin when it couples to rhodopsin8. β1AR coupled to βarr1 shows considerable differences in structure compared with β1AR coupled to Nb80, including an inward movement of extracellular loop 3 and the cytoplasmic ends of H5 and H6. We observe weakened interactions between formoterol and two serine residues in H5 at the orthosteric binding site of β1AR, and find that formoterol has a lower affinity for the β1AR-βarr1 complex than for the β1AR-Gs complex. The structural differences between these complexes of β1AR provide a foundation for the design of small molecules that could bias signalling in the β-adrenoceptors

Induced Metric And Matrix Inequalities On Unitary Matrices

Recently, Chau [Quant. Inform. & Comp. 11, 721 (2011)] showed that one can define certain metrics and pseudo-metrics on U(n), the group of all $n\times n$ unitary matrices, based on the arguments of the eigenvalues of the unitary matrices. More importantly, these metrics and pseudo-metrics have quantum information theoretical meanings. So it is instructive to study this kind of metrics and pseudo-metrics on U(n). Here we show that any symmetric norm on ${\mathbb R}^n$ induces a metric on U(n). Furthermore, using the same technique, we prove an inequality concerning the eigenvalues of a product of two unitary matrices which generalizes a few inequalities obtained earlier by Chau [arXiv:1006.3614v1].Comment: 6 pages, extensively rewritten with an earlier error fixed. It generalizes and simplifies the mathematical results concerning certain matrix inequalities originally reported in arXiv:1006.3614v1. To appear in J.Phys.

Deformation effects in 56^{56}Ni nuclei produced in 28^{28}Si+28^{28}Si at 112 MeV

Velocity and energy spectra of the light charged particles (protons and $\alpha$-particles) emitted in the $^{28}$Si(E$_{lab}$ = 112 MeV) + $^{28}$Si reaction have been measured at the Strasbourg VIVITRON Tandem facility. The ICARE charged particle multidetector array was used to obtain exclusive spectra of the light particles in the angular range 15 - 150 degree and to determine the angular correlations of these particles with respect to the emission angles of the evaporation residues. The experimental data are analysed in the framework of the statistical model. The exclusive energy spectra of $\alpha$-particles emitted from the $^{28}$Si + $^{28}$Si compound system are generally well reproduced by Monte Carlo calculations using spin-dependent level densities. This spin dependence approach suggests the onset of large deformations at high spin. A re-analysis of previous $\alpha$-particle data from the $^{30}$Si + $^{30}$Si compound system, using the same spin-dependent parametrization, is also presented in the framework of a general discussion of the occurrence of large deformation effects in the A$_{CN}$ ~ 60 mass region.Comment: 25 pages, 6 figure

Dynamical Boson Stars

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201

Scaling of Particle and Transverse Energy Production in 208Pb+208Pb collisions at 158 A GeV

Transverse energy, charged particle pseudorapidity distributions and photon transverse momentum spectra have been studied as a function of the number of participants (N_{part}) and the number of binary nucleon-nucleon collisions (N_{coll}) in 158 A GeV Pb+Pb collisions over a wide impact parameter range. A scaling of the transverse energy pseudorapidity density at midrapidity as N_{part}^{1.08 \pm 0.06} and N_{coll}^{0.83 \pm 0.05} is observed. For the charged particle pseudorapidity density at midrapidity we find a scaling as N_{part}^{1.07 \pm 0.04} and N_{coll}^{0.82 \pm 0.03}. This faster than linear scaling with N_{part} indicates a violation of the naive Wounded Nucleon Model.Comment: 13 pages, 16 figures, submitted to European Physical Journal C (revised results for scaling exponents

Systematics of Inclusive Photon Production in 158 AGeV Pb Induced Reactions on Ni, Nb, and Pb Targets

The multiplicity of inclusive photons has been measured on an event-by-event basis for 158 AGeV Pb induced reactions on Ni, Nb, and Pb targets. The systematics of the pseudorapidity densities at midrapidity (rho_max) and the width of the pseudorapidity distributions have been studied for varying centralities for these collisions. A power law fit to the photon yield as a function of the number of participating nucleons gives a value of 1.13+-0.03 for the exponent. The mean transverse momentum, , of photons determined from the ratio of the measured electromagnetic transverse energy and photon multiplicity, remains almost constant with increasing rho_max. Results are compared with model predictions.Comment: 16 pages including 4 figure

Highly deformed 40^{40}Ca configurations in 28^{28}Si + 12^{12}C

The possible occurrence of highly deformed configurations in the $^{40}$Ca di-nuclear system formed in the $^{28}$Si + $^{12}$C reaction is investigated by analyzing the spectra of emitted light charged particles. Both inclusive and exclusive measurements of the heavy fragments (A $\geq$ 10) and their associated light charged particles (protons and $\alpha$ particles) have been made at the IReS Strasbourg {\sc VIVITRON} Tandem facility at bombarding energies of $E_{lab} (^{28}$Si) = 112 MeV and 180 MeV by using the {\sc ICARE} charged particle multidetector array. The energy spectra, velocity distributions, and both in-plane and out-of-plane angular correlations of light charged particles are compared to statistical-model calculations using a consistent set of parameters with spin-dependent level densities. The analysis suggests the onset of large nuclear deformation in $^{40}$Ca at high spin.Comment: 33 pages, 11 figure

Centrality Dependence of Neutral Pion Production in 158 A GeV Pb + Pb Collisions

The production of neutral pions in 158AGeV Pb+Pb collisions has been studied in the WA98 experiment at the CERN SPS. Transverse momentum spectra are studied for the range 0.3 GeV/c < mT-m0 < 4.0 GeV/c. The results for central collisions are compared to various models. The centrality dependence of the neutral pion spectral shape and yield is investigated. An invariance of the spectral shape and a simple scaling of the yield with the number of participating nucleons is observed for centralities with greater than about 30 participating nucleons which is most naturally explained by assuming an equilibrated system.Comment: 5 pages, Latex, including 3 eps figures, submitted to Phys.Rev.Lett; updated pQCD comparison due to new input from the author, updated references, corrected plotting error in figure

Central Pb+Pb Collisions at 158 A GeV/c Studied by Pion-Pion Interferometry

Two-particle correlations have been measured for identified negative pions from central 158 AGeV Pb+Pb collisions and fitted radii of about 7 fm in all dimensions have been obtained. A multi-dimensional study of the radii as a function of kT is presented, including a full correction for the resolution effects of the apparatus. The cross term Rout-long of the standard fit in the Longitudinally CoMoving System (LCMS) and the vl parameter of the generalised Yano-Koonin fit are compatible with 0, suggesting that the source undergoes a boost invariant expansion. The shapes of the correlation functions in Qinv and Qspace have been analyzed in detail. They are not Gaussian but better represented by exponentials. As a consequence, fitting Gaussians to these correlation functions may produce different radii depending on the acceptance of the experimental setup used for the measurement.Comment: 13 pages including 10 figure

Search for DCC in 158A GeV Pb+Pb Collisions

A detailed analysis of the phase space distributions of charged particles and photons have been carried out using two independent methods. The results indicate the presence of nonstatistical fluctuations in localized regions of phase space.Comment: Talk at the PANIC99 Conference, June 9-16, 199