High throughput generated micro-aggregates of chondrocytes stimulate cartilage formation in vitro and in vivo

Cell-based cartilage repair strategies such as matrix-induced autologous chondrocyte implantation (MACI) could be improved by enhancing cell performance. We hypothesised that micro-aggregates of chondrocytes generated in high-throughput prior to implantation in a defect could stimulate cartilaginous matrix deposition and remodelling. To address this issue, we designed a micro-mould to enable controlled high-throughput formation of micro-aggregates. Morphology, stability, gene expression profiles and chondrogenic potential of micro-aggregates of human and bovine chondrocytes were evaluated and compared to single-cells cultured in micro-wells and in 3D after encapsulation in Dextran-Tyramine (Dex-TA) hydrogels in vitro and in vivo. We successfully formed micro-aggregates of human and bovine chondrocytes with highly controlled size, stability and viability within 24 hours. Micro-aggregates of 100 cells presented a superior balance in Collagen type I and Collagen type II gene expression over single cells and micro-aggregates of 50 and 200 cells. Matrix metalloproteinases 1, 9 and 13 mRNA levels were decreased in micro-aggregates compared to single-cells. Histological and biochemical analysis demonstrated enhanced matrix deposition in constructs seeded with micro-aggregates cultured in vitro and in vivo, compared to single-cell seeded constructs. Whole genome microarray analysis and single gene expression profiles using human chondrocytes confirmed increased expression of cartilage-related genes when chondrocytes were cultured in micro-aggregates. In conclusion, we succeeded in controlled high-throughput formation of micro-aggregates of chondrocytes. Compared to single cell-seeded constructs, seeding of constructs with micro-aggregates greatly improved neo-cartilage formation. Therefore, micro-aggregation prior to chondrocyte implantation in current MACI procedures, may effectively accelerate hyaline cartilage formation

Measurement of CP observables in B± → D(⁎)K± and B± → D(⁎)π± decays

Measurements of CP observables in B ± →D (⁎) K ± and B ± →D (⁎) π ± decays are presented, where D (⁎) indicates a neutral D or D ⁎ meson that is an admixture of D (⁎)0 and D¯ (⁎)0 states. Decays of the D ⁎ meson to the Dπ 0 and Dγ final states are partially reconstructed without inclusion of the neutral pion or photon, resulting in distinctive shapes in the B candidate invariant mass distribution. Decays of the D meson are fully reconstructed in the K ± π ∓ , K + K − and π + π − final states. The analysis uses a sample of charged B mesons produced in pp collisions collected by the LHCb experiment, corresponding to an integrated luminosity of 2.0, 1.0 and 2.0 fb −1 taken at centre-of-mass energies of s=7, 8 and 13 TeV, respectively. The study of B ± →D ⁎ K ± and B ± →D ⁎ π ± decays using a partial reconstruction method is the first of its kind, while the measurement of B ± →DK ± and B ± →Dπ ± decays is an update of previous LHCb measurements. The B ± →DK ± results are the most precise to date

Measurement of CPCP asymmetries in D±→η′π±D^{\pm}\rightarrow \eta^{\prime} \pi^{\pm} and Ds±→η′π±D_s^{\pm}\rightarrow \eta^{\prime} \pi^{\pm} decays

See paper for full list of authors - 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-2016-041.html - Submitted to Phys. Lett. BInternational audienceA search for CP violation in D±→η′π± and D±s→η′π± decays is performed using proton-proton collision data, corresponding to an integrated luminosity of 3 fb−1, recorded by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The measured CP-violating charge asymmetries are ACP(D±→η′π±)=(−0.61±0.72±0.55±0.12)% and ACP(D±s→η′π±)=(−0.82±0.36±0.24±0.27)%, where the first uncertainties are statistical, the second systematic, and the third are the uncertainties on the ACP(D±→K0Sπ±) and ACP(D±s→ϕπ±) measurements used for calibration. The results represent the most precise measurements of these asymmetries to date

Observation of ηc(2S)→ppˉ\eta_{c}(2S) \to p \bar p and search for X(3872)→ppˉX(3872) \to p \bar p decays

The first observation of the decay $\eta_{c}(2S) \to p \bar p$ is reported using proton-proton collision data corresponding to an integrated luminosity of $3.0\rm \, fb^{-1}$ recorded by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The $\eta_{c}(2S)$ resonance is produced in the decay $B^{+} \to [c\bar c] K^{+}$. The product of branching fractions normalised to that for the $J/\psi$ intermediate state, ${\cal R}_{\eta_{c}(2S)}$, is measured to be \begin{align*} {\cal R}_{\eta_{c}(2S)}\equiv\frac{{\mathcal B}(B^{+} \to \eta_{c}(2S) K^{+}) \times {\mathcal B}(\eta_{c}(2S) \to p \bar p)}{{\mathcal B}(B^{+} \to J/\psi K^{+}) \times {\mathcal B}(J/\psi\to p \bar p)} =~& (1.58 \pm 0.33 \pm 0.09)\times 10^{-2}, \end{align*} where the first uncertainty is statistical and the second systematic. No signals for the decays $B^{+} \to X(3872) (\to p \bar p) K^{+}$ and $B^{+} \to \psi(3770) (\to p \bar p) K^{+}$ are seen, and the 95\% confidence level upper limits on their relative branching ratios are % found to be ${\cal R}_{X(3872)}<0.25\times10^{-2}$ and ${\cal R}_{\psi(3770))}<0.10$. In addition, the mass differences between the $\eta_{c}(1S)$ and the $J/\psi$ states, between the $\eta_{c}(2S)$ and the $\psi(2S)$ states, and the natural width of the $\eta_{c}(1S)$ are measured as \begin{align*} M_{J/\psi} - M_{\eta_{c}(1S)} =~& 110.2 \pm 0.5 \pm 0.9 \rm \, MeV, M_{\psi(2S)} -M_{\eta_{c}(2S)} =~ & 52.5 \pm 1.7 \pm 0.6 \rm \, MeV, \Gamma_{\eta_{c}(1S)} =~& 34.0 \pm 1.9 \pm 1.3 \rm \, MeV. \end{align*}Comment: 16 pages, 2 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-2016-016.htm

Measurement of B0B^0, Bs0B^0_s, B+B^+ and Λb0\Lambda^0_b production asymmetries in 7 and 8 TeV proton-proton collisions

See paper for full list of authors - 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-2016-062.html - Submitted to Phys. Lett. B.International audienceThe B0, B0s, B+ and Λ0b hadron production asymmetries are measured using a data sample corresponding to an integrated luminosity of 3.0 fb−1, collected by the LHCb experiment in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. The measurements are performed as a function of transverse momentum and rapidity of the b hadrons within the LHCb detector acceptance. The overall production asymmetries, integrated over transverse momentum and rapidity, are also determined

Search for CPCP violation in the phase space of D0→π+π−π+π−D^0\rightarrow\pi^+\pi^-\pi^+\pi^- decays

A search for time-integrated $CP$ violation in the Cabibbo-suppressed decay \mbox{D^0\rightarrow\pi^+\pi^-\pi^+\pi^-} is performed using an unbinned, model-independent technique known as the energy test. This is the first application of the energy test in four-body decays. The search is performed for $P$-even $CP$ asymmetries and, for the first time, is extended to probe the $P$-odd case. Using proton-proton collision data corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb detector at centre-of-mass energies of $\sqrt{s}=$7 TeV and 8 TeV, the world's best sensitivity to $CP$ violation in this decay is obtained. The data are found to be consistent with the hypothesis of $CP$ symmetry with a $p$-value of $(4.6\pm0.5)\%$ in the $P$-even case, and marginally consistent with a $p$-value of $(0.6\pm0.2)\%$ in the $P$-odd case, corresponding to a significance for $CP$ non-conservation of 2.7 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-2016-044.htm

First observation of forward Z→bbˉZ \rightarrow b \bar{b} production in pppp collisions at s=8\sqrt{s}=8 TeV

The decay Z→bb¯ is reconstructed in pp collision data, corresponding to 2 fb −1 of integrated luminosity, collected by the LHCb experiment at a centre-of-mass energy of s=8 TeV. The product of the Z production cross-section and the Z→bb¯ branching fraction is measured for candidates in the fiducial region defined by two particle-level b -quark jets with pseudorapidities in the range 2.220 GeV and dijet invariant mass in the range 4520$GeV and dijet invariant mass in the range$45 < m_{jj} < 165$GeV. From a signal yield of$5462 \pm 763$$Z \rightarrow b \bar{b}$events, where the uncertainty is statistical, a production cross-section times branching fraction of$332 \pm 46 \pm 59$pb is obtained, where the first uncertainty is statistical and the second systematic. The measured significance of the signal yield is 6.0 standard deviations. This measurement represents the first observation of the$Z \rightarrow b \bar{b}$production in the forward region of$pp$ collisions