Search for B→hννˉ\boldsymbol{B\to h\nu\bar{\nu}} decays with semileptonic tagging at Belle

We present the results of a search for the rare decays $B\to h\nu\overline{\nu}$, where $h$ stands for $K^+,\:K^0_{\mathrm{S}},\:K^{\ast +},\:K^{\ast 0},\:\pi^+,\:\pi^0,\:\rho^+$ and $\rho^{0}$. The results are obtained with $772\times10^{6}$ $B\overline{B}$ pairs collected with the Belle detector at the KEKB $e^+ e^-$ collider. We reconstruct one $B$ meson in a semileptonic decay and require a single $h$ meson but nothing else on the signal side. We observe no significant signal and set upper limits on the branching fractions. The limits set on the $B\to K^0_{\mathrm{S}}\nu\overline{\nu}$, $B^0\to K^{*0}\nu\overline{\nu}$, $B\to \pi^+\nu\overline{\nu}$, $B^0\to\pi^0\nu\overline{\nu}$, $B^+\to\rho^+\nu\overline{\nu}$, and $B^0\to\rho^0\nu\overline{\nu}$ channels are the world's most stringent.Comment: Submitted to PR

Measurement of the branching fraction and CPCP asymmetry in B0→π0π0B^{0} \to \pi^{0}\pi^{0} decays, and an improved constraint on ϕ2\phi_{2}

We measure the branching fraction and $CP$ violation asymmetry in the decay $B^{0}\to \pi^{0}\pi^{0}$, using a data sample of $752\times 10^{6}$ $B\bar{B}$ pairs collected at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB $e^{+}e^{-}$ collider. The obtained branching fraction and direct $CP$ asymmetry are $\mathcal{B}(B\to \pi^{0}\pi^{0}) = [1.31 \pm 0.19~ \text{(stat.)} \pm 0.19~ \text{(syst.)}] \times 10^{-6}$ and $A_{CP} = +0.14 \pm 0.36~ \text{(stat.)} \pm 0.10~ \text{(syst.)},$ respectively. The signal significance, including the systematic uncertainty, is 6.4 standard deviations. We combine these results with Belle's earlier measurements of $B^{0}\to \pi^{+} \pi^{-}$ and $B^{\pm} \to \pi^{\pm} \pi^{0}$ to exclude the $CP$-violating parameter $\phi_{2}$ from the range $15.5^{\circ} < \phi_{2} < 75.0^{\circ}$ at 95\% confidence level.Comment: 8 pages, 2 figure

Search for CPCP Violation and Measurement of the Branching Fraction in the Decay D0→KS0KS0D^{0} \to K^0_S K^0_S

We report a study of the decay $D^0 \to K^0_S K^0_S$ using 921~fb$^{-1}$ of data collected at or near the $\Upsilon(4S)$ and $\Upsilon(5S)$ resonances with the Belle detector at the KEKB asymmetric energy $e^+e^-$ collider. The measured time-integrated $CP$ asymmetry is $A_{CP}(D^0 \to K^0_S K^0_S) = (-0.02 \pm 1.53 \pm 0.02 \pm 0.17) \%$, and the branching fraction is $\mathcal{B} (D^{0}\rightarrow K_{S}^{0}K_{S}^{0})$ = (1.321 $\pm$ 0.023 $\pm$ 0.036 $\pm$ 0.044) $\times$ 10$^{-4}$, where the first uncertainty is statistical, the second is systematic, and the third is due to the normalization mode ($D^0 \to K_S^0 \pi^0$). These results are significantly more precise than previous measurements available for this mode. The $A_{CP}$ measurement is consistent with the standard model expectation.Comment: 7 pages,1 figure, Submitted to PR

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Isolation of Monoclonal Antibodies with Predetermined Conformational Epitope Specificity

Existing technologies allow isolating antigen-specific monoclonal antibodies (mAbs) from B cells. We devised a direct approach to isolate mAbs with predetermined conformational epitope specificity, using epitope mimetics (mimotopes) that reflect the three-dimensional structure of given antigen subdomains. We performed differential biopanning using bacteriophages encoding random peptide libraries and polyclonal antibodies (Abs) that had been affinity-purified with either native or denatured antigen. This strategy yielded conformational mimotopes. We then generated mimotope-fluorescent protein fusions, which were used as baits to isolate single memory B cells from rhesus monkeys (RMs). To amplify RM immunoglobulin variable regions, we developed RM-specific PCR primers and generated chimeric simian-human mAbs with predicted epitope specificity. We established proof-of-concept of our strategy by isolating mAbs targeting the conformational V3 loop crown of HIV Env; the new mAbs cross-neutralized viruses of different clades. The novel technology allows isolating mAbs from RMs or other hosts given experimental immunogens or infectious agents

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

Search for B−→μ−¯νμ Decays at the Belle Experiment

We report the results of a search for the rare, purely leptonic decay B$^{-}$ → μ− ¯ν$_{μ}$ performed with a 711 fb$^{-1}$ data sample that contains 772 × 10$^{6}$ BB¯ pairs, collected near the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e$^{+}$e$^{-}$ collider. The signal events are selected based on the presence of a high momentum muon and the topology of the rest of the event showing properties of a generic B-meson decay, as well as the missing energy and momentum being consistent with the hypothesis of a neutrino from the signal decay. We find a 2.4 standard deviation excess above background including systematic uncertainties, which corresponds to a branching fraction of B(B$^{-}$ → μ$^{-}$ ¯ν$_{μ}$) = (6.46 $\pm$ 2.22 $\pm$ 1.60) × 10$^{-7}$ or a frequentist 90% confidence level interval on the B$^{-}$ → μ$^{-}$ ¯ν$_{μ}$ branching fraction of [2.9,10.7] × 10$^{-7}$