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 ratio of Bˉ→D(∗)τ−νˉτ\bar{B} \to D^{(\ast)} \tau^- \bar{\nu}_\tau relative to Bˉ→D(∗)ℓ−νˉℓ\bar{B} \to D^{(\ast)} \ell^- \bar{\nu}_\ell decays with hadronic tagging at Belle

We report a measurement of the branching fraction ratios R(D(*)) of Bbar -> D(*) tau- nubar_tau relative to Bbar -> D()* l- nubar_l (where l = e or mu) using the full Belle data sample of 772 x 10^6 BBbar pairs collected at the Y(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. The measured values are R(D)= 0.375 +- 0.064(stat.) +- 0.026(syst.) and R(D*) = 0.293 +- 0.038(stat.) +- 0.015(syst.). The analysis uses hadronic reconstruction of the tag-side B meson and purely leptonic tau decays. The results are consistent with earlier measurements and do not show a significant deviation from the standard model prediction.Comment: Accepted for publication in Phys.Rev.

Angular analysis of B0→K∗(892)0ℓ+ℓ−B^0 \to K^\ast(892)^0 \ell^+ \ell^-

We present a measurement of angular observables, $P_4'$, $P_5'$, $P_6'$, $P_8'$, in the decay $B^0 \to K^\ast(892)^0 \ell^+ \ell^-$, where $\ell^+\ell^-$ is either $e^+e^-$ or $\mu^+\mu^-$. The analysis is performed on a data sample corresponding to an integrated luminosity of $711~\mathrm{fb}^{-1}$ containing $772\times 10^{6}$ $B\bar B$ pairs, collected at the $\Upsilon(4S)$ resonance with the Belle detector at the asymmetric-energy $e^+e^-$ collider KEKB. Four angular observables, $P_{4,5,6,8}'$ are extracted in five bins of the invariant mass squared of the lepton system, $q^2$. We compare our results for $P_{4,5,6,8}'$ with Standard Model predictions including the $q^2$ region in which the LHCb collaboration reported the so-called $P_5'$ anomaly.Comment: Conference paper for LHC Ski 2016. SM prediction for $P_{6}'$ corrected and reference for arXiv:1207.2753 adde

In vivo combination of human anti-envelope glycoprotein E2 and -Claudin-1 monoclonal antibodies for prevention of hepatitis C virus infection

Despite the development of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection remains a major cause for liver disease and cancer worldwide. Entry inhibitors block virus host cell entry and, therefore, prevent establishment of chronic infection and liver disease. Due to their unique mechanism of action, entry inhibitors provide an attractive antiviral strategy in organ transplantation. In this study, we developed an innovative approach in preventing HCV infection using a synergistic combination of a broadly neutralizing human monoclonal antibody (HMAb) targeting the HCV E2 protein and a host-targeting anti-claudin 1 (CLDN1) humanized monoclonal antibody. An in vivo proof-of-concept study in human liver-chimeric FRG-NOD mice proved the efficacy of the combination therapy at preventing infection by an HCV genotype 1b infectious serum. While administration of individual antibodies at lower doses only showed a delay in HCV infection, the combination therapy was highly protective. Furthermore, the combination proved to be effective in preventing infection of primary human hepatocytes by neutralization-resistant HCV escape variants selected during liver transplantation, suggesting that a combination therapy is suited for the neutralization of difficult-to-treat variants. In conclusion, our findings suggest that the combination of two HMAbs targeting different steps of virus entry improves treatment efficacy while simultaneously reducing treatment duration and costs. Our approach not only provides a clinical perspective to employ HMAb combination therapies to prevent graft re-infection and its associated liver disease but may also help to alleviate the urgent demand for organ transplants by allowing the transplantation of organs from HCV-positive donors

CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells

Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we generated cell culture infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2 residues W529 or D535 that are critical for binding to CD81 and infectivity. Co-cultivation of these cells with naïve cells expressing enhanced green fluorescent protein (EGFP) resulted in a small number of cells co-expressing both EGFP and HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In contrast, no cell-to-cell transmission from JFH1ΔE1E2-transfected cells occurred, indicating that the HCV glycoproteins are essential for this process. The frequency of cell-to-cell transmission of JFH1W529A was unaffected by the presence of neutralizing antibodies that inhibit E2–CD81 interactions. By using cell lines that expressed little or no CD81 and that were refractive to infection with cell-free virus, we showed that the occurrence of viral cell-to-cell transmission is not influenced by the levels of CD81 on either donor or recipient cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread of HCVcc and that this mode of transmission is shielded from neutralizing antibodies. These data suggest that therapeutic interventions targeting the entry of cell-free HCV may not be sufficient in controlling an ongoing chronic infection, but need to be complemented by additional strategies aimed at disrupting direct cell-to-cell viral transmission

Mediating Solidarity

With the apparent increase in the number of alternative political media, political pluralists are again faced with the question: does the proliferation of subaltern counter-publics lead to a multiplication of forces? Fragmentation in political culture is fuelled by the rise of identity politics that focuses on consumption not production. Party allegiances and class alliances give way to more fluid and informal networks of action. Postmodern theorists celebrate fragmentation because it allows the recognition of diversity in political desires, acknowledges difference between individuals and debunks the myth of homogenous political units leading ultimately to liberation. But for political efficacy there must be more than the apparent freedom that comes with embracing difference and diversity. This article argues that if we accept the description of society as fragmented, in order to create a viable political community then solidarity is crucial. In a global economy, solidarity can be mediated through new communication technologies but the challenge is to articulate the politics online with actual movements and struggles on the ground

‘Forgotten Europeans’: transnational minority activism in the age of European integration

YesThis article examines transnational activism by coalitions of national minorities in Europe from the early 20th century to the present, setting this within the broader ‘security versus democracy dilemma’ that continues to surround international discussions on minority rights. Specifically, we analyse two organisations – the European Nationalities Congress (1925–1938) and the Federal Union of European Nationalities (1949–) – which, while linked, have never been subject to a detailed comparison based on primary sources. In so far as comparisons do exist, they present these bodies in highly negative terms, as mere fronts for inherently particularistic nationalisms that threaten political stability, state integrity and peace. Our more in‐depth analysis provides a fresh and more nuanced perspective: it shows that, in both cases, concepts of European integration and ‘unity in diversity’ have provided the motivating goals and frameworks for transnational movements advocating common rights for all minorities and seeking positive interaction with the interstate world

Efficacy and safety of aripiprazole in the treatment of bipolar disorder: a systematic review

Abstract BACKGROUND: The current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder. METHODS: A systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed, with the combination of the words 'aripiprazole' and 'bipolar'. RESULTS: The search returned 184 articles and was last updated on 15 April 2009. An additional search included repositories of clinical trials and previous systematic reviews specifically in order to trace unpublished trials. There were seven placebo-controlled randomised controlled trials (RCTs), six with comparator studies and one with add-on studies. They assessed the usefulness of aripiprazole in acute mania, acute bipolar depression and during the maintenance phase in comparison to placebo, lithium or haloperidol. CONCLUSION: Aripiprazole appears effective for the treatment and prophylaxis against mania. The data on bipolar depression are so far negative, however there is a need for further study at lower dosages. The most frequent adverse effects are extrapyramidal signs and symptoms, especially akathisia, without any significant weight gain, hyperprolactinaemia or laboratory test changes