One Year Term Review as a Participating Guest in the Detonator and Detonation Physics Group

The one year stay was possible after a long administrative process, because of the fact that this was the first participating guest of B division as a foreign national in HEAF (High Explosives Application Facility) with the Detonator/Detonation Physics Group

The Batten disease protein CLN3 is important for stress granules dynamics and translational activity

The assembly of membrane-less organelles such as stress granules (SGs) is emerging as central in helping cells rapidly respond and adapt to stress. Following stress sensing, the resulting global translational shutoff leads to the condensation of stalled mRNAs and proteins into SGs. By reorganizing cytoplasmic contents, SGs can modulate RNA translation, biochemical reactions, and signaling cascades to promote survival until the stress is resolved. While mechanisms for SG disassembly are not widely understood, the resolution of SGs is important for maintaining cell viability and protein homeostasis. Mutations that lead to persistent or aberrant SGs are increasingly associated with neuropathology and a hallmark of several neurodegenerative diseases. Mutations in CLN3 are causative of juvenile neuronal ceroid lipofuscinosis, a rare neurodegenerative disease affecting children also known as Batten disease. CLN3 encodes a transmembrane lysosomal protein implicated in autophagy, endosomal trafficking, metabolism, and response to oxidative stress. Using a HeLa cell model lacking CLN3, we now show that CLN3KO is associated with an altered metabolic profile, reduced global translation, and altered stress signaling. Furthermore, loss of CLN3 function results in perturbations in SG dynamics, resulting in assembly and disassembly defects, and altered expression of the key SG nucleating factor G3BP1. With a growing interest in SG-modulating drugs for the treatment of neurodegenerative diseases, novel insights into the molecular basis of CLN3 Batten disease may reveal avenues for disease-modifying treatments for this debilitating childhood disease

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Observation of J/ψpJ/\psi p resonances consistent with pentaquark states in Λb0→J/ψK−p{\Lambda_b^0\to J/\psi K^-p} decays

Observations of exotic structures in the $J/\psi p$ channel, that we refer to as pentaquark-charmonium states, in $\Lambda_b^0\to J/\psi K^- p$ decays are presented. The data sample corresponds to an integrated luminosity of 3/fb acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis is performed on the three-body final-state that reproduces the two-body mass and angular distributions. To obtain a satisfactory fit of the structures seen in the $J/\psi p$ mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each describe a resonant state. The significance of each of these resonances is more than 9 standard deviations. One has a mass of $4380\pm 8\pm 29$ MeV and a width of $205\pm 18\pm 86$ MeV, while the second is narrower, with a mass of $4449.8\pm 1.7\pm 2.5$ MeV and a width of $39\pm 5\pm 19$ MeV. The preferred $J^P$ assignments are of opposite parity, with one state having spin 3/2 and the other 5/2.Comment: 48 pages, 18 figures including the supplementary material, v2 after referee's comments, now 19 figure

Observation of the Bs0→J/ψϕϕB_s^0 \rightarrow J/\psi \phi \phi decay

The $B_s^0 \rightarrow J/\psi \phi \phi$ decay is observed in $pp$ collision data corresponding to an integrated luminosity of 3 fb$^{-1}$ recorded by the LHCb detector at centre-of-mass energies of 7 TeV and 8 TeV. This is the first observation of this decay channel, with a statistical significance of 15 standard deviations. The mass of the $B_s^0$ meson is measured to be $5367.08\,\pm \,0.38\,\pm\, 0.15$ MeV/c$^2$. The branching fraction ratio $\mathcal{B}(B_s^0 \rightarrow J/\psi \phi \phi)/\mathcal{B}(B_s^0 \rightarrow J/\psi \phi)$ is measured to be 0.0115\,\pm\, 0.0012\, ^{+0.0005}_{-0.0009}. In both cases, the first uncertainty is statistical and the second is systematic. No evidence for non-resonant $B_s^0 \rightarrow J/\psi \phi K^+ K^-$ or $B_s^0 \rightarrow J/\psi K^+ K^- K^+ K^-$ decays is found.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-2015-033.htm

Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)

The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08 ^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical, the second systematic and the third is associated to the ratio of fragmentation fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/- 0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be (3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table

Measurement of the CKM angle γ from a combination of B±→Dh± analyses

A combination of three LHCb measurements of the CKM angle γ is presented. The decays B±→D K± and B±→Dπ± are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+K−, π+π−, K±π∓, K±π∓π±π∓, K0Sπ+π−, or K0S K+K− final states. All measurements use a dataset corresponding to 1.0 fb−1 of integrated luminosity. Combining results from B±→D K± decays alone a best-fit value of γ =72.0◦ is found, and confidence intervals are set γ ∈ [56.4,86.7]◦ at 68% CL, γ ∈ [42.6,99.6]◦ at 95% CL. The best-fit value of γ found from a combination of results from B±→Dπ± decays alone, is γ =18.9◦, and the confidence intervals γ ∈ [7.4,99.2]◦ ∪ [167.9,176.4]◦ at 68% CL are set, without constraint at 95% CL. The combination of results from B± → D K± and B± → Dπ± decays gives a best-fit value of γ =72.6◦ and the confidence intervals γ ∈ [55.4,82.3]◦ at 68% CL, γ ∈ [40.2,92.7]◦ at 95% CL are set. All values are expressed modulo 180◦, and are obtained taking into account the effect of D0–D0 mixing

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.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-2016-022.html, link to supplemental material inserted in the reference