Biomechanical signals and the C-type natriuretic peptide counteract catabolic activities induced by IL-1β in chondrocyte/agarose constructs

Introduction: The present study examined the effect of C-type natriuretic peptide (CNP) on the anabolic and catabolic activities in chondrocyte/agarose constructs subjected to dynamic compression. Methods: Constructs were cultured under free-swelling conditions or subjected to dynamic compression with low (0.1 to 100 pM) or high concentrations (1 to 1,000 nM) of CNP, interleukin-1? (IL-1?), and/or KT-5823 (inhibits cyclic GMP-dependent protein kinase II (PKGII)). Anabolic and catabolic activities were assessed as follows: nitric oxide (NO) and prostaglandin E2 (PGE2) release, and [3H]-thymidine and 35SO4 incorporation were quantified by using biochemical assays. Gene expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan, and collagen type II were assessed with real-time quantitative PCR (qPCR). Two-way ANOVA and the post hoc Bonferroni-corrected t tests were used to examine data. Results: CNP reduced NO and PGE2 release and partially restored [3H]-thymidine and 35SO4 incorporation in constructs cultured with IL-1?. The response was dependent on the concentration of CNP, such that 100 pM increased [3H]-thymidine incorporation (P &lt; 0.001). This is in contrast to 35SO4 incorporation, which was enhanced with 100 or 1000 nM CNP in the presence and absence of IL-1? (P &lt; 0.001). Stimulation by both dynamic compression and CNP and/or the PKGII inhibitor further reduced NO and PGE2 release and restored [3H]-thymidine and 35SO4 incorporation. In the presence and absence of IL-1?, the magnitude of stimulation for [3H]-thymidine and 35SO4 incorporation by dynamic compression was dependent on the concentration of CNP and the response was inhibited with the PKGII inhibitor. In addition, stimulation by CNP and/or dynamic compression reduced IL-1?-induced iNOS and COX-2 expression and restored aggrecan and collagen type II expression. The catabolic response was not further influenced with the PKGII inhibitor in IL-1?-treated constructs. Conclusions: Treatment with CNP and dynamic compression increased anabolic activities and blocked catabolic effects induced by IL-1?. The anabolic response was PKGII mediated and raises important questions about the molecular mechanisms of CNP with mechanical signals in cartilage. Therapeutic agents like CNP could be administered in conjunction with controlled exercise therapy to slow the OA disease progression and to repair damaged cartilage. The findings from this research provide the potential for developing novel agents to slow the pathophysiologic mechanisms and to treat OA in the young and old. <br/

Balancing Minimum Spanning and Shortest Path Trees

This paper give a simple linear-time algorithm that, given a weighted digraph, finds a spanning tree that simultaneously approximates a shortest-path tree and a minimum spanning tree. The algorithm provides a continuous trade-off: given the two trees and epsilon > 0, the algorithm returns a spanning tree in which the distance between any vertex and the root of the shortest-path tree is at most 1+epsilon times the shortest-path distance, and yet the total weight of the tree is at most 1+2/epsilon times the weight of a minimum spanning tree. This is the best tradeoff possible. The paper also describes a fast parallel implementation.Comment: conference version: ACM-SIAM Symposium on Discrete Algorithms (1993

Search for B+ →μ+νμ and B+ →μ+N with inclusive tagging

We report the result for a search for the leptonic decay of B+→μ+νμ using the full Belle dataset of 711 fb-1 of integrated luminosity at the (4S) resonance. In the Standard Model leptonic B-meson decays are helicity and Cabibbo-Kobayashi-Maskawa suppressed. To maximize sensitivity an inclusive tagging approach is used to reconstruct the second B meson produced in the collision. The directional information from this second B meson is used to boost the observed μ into the signal B-meson rest frame, in which the μ has a monochromatic momentum spectrum. Though its momentum is smeared by the experimental resolution, this technique improves the analysis sensitivity considerably. Analyzing the μ momentum spectrum in this frame we find B(B+→μ+νμ)=(5.3±2.0±0.9)×10-7 with a one-sided significance of 2.8 standard deviations over the background-only hypothesis. This translates to a frequentist upper limit of B(B+→μ+νμ)<8.6×10-7 at 90% confidence level. The experimental spectrum is then used to search for a massive sterile neutrino, B+→μ+N, but no evidence is observed for a sterile neutrino with a mass in a range of 0-1.5 GeV. The determined B+→μ+νμ branching fraction limit is further used to constrain the mass and coupling space of the type II and type III two-Higgs-doublet models. © 2020 authors. Published by the American Physical Society

Long and short paths in uniform random recursive dags

In a uniform random recursive k-dag, there is a root, 0, and each node in turn, from 1 to n, chooses k uniform random parents from among the nodes of smaller index. If S_n is the shortest path distance from node n to the root, then we determine the constant \sigma such that S_n/log(n) tends to \sigma in probability as n tends to infinity. We also show that max_{1 \le i \le n} S_i/log(n) tends to \sigma in probability.Comment: 16 page

Search for leptonic decays of D0 mesons

We search for the flavor-changing neutral current decays D0\to mu+mu- and D0\to e+e-, and for the lepton-flavor violating decays D0\to e\pm mu\mp using 660 fb^-1 of data collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. We find no evidence for any of these decays. We obtain significantly improved upper limits on the branching fractions: B(D0\to mu+mu-)<1.4x10-7, B(D0\to e+e-)<7.9x10-8, and B(D0\to e+mu-)+B(D0\to mu+e-)<2.6x10-7 at 90% confidence level.Comment: 6 pages, 3 figure

Measurements of Branching Fractions and Time-dependent CP Violating Asymmetries in B0→D(∗)±D∓B^{0} \to D^{(*)\pm}D^{\mp} Decays

We report measurements of branching fractions and time-dependent CP asymmetries in $B^{0} \to D^{+}D^{-}$ and $B^{0} \to D^{*\pm}D^{\mp}$ decays using a data sample that contains $(772 \pm 11)\times 10^6 B\bar{B}$ pairs collected at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+ e^-$ collider. We determine the branching fractions to be $\mathcal{B}(B^{0} \to D^{+}D^{-})=(2.12 \pm 0.16 \pm 0.18)\times 10^{-4}$ and $\mathcal{B}(B^{0} \to D^{*\pm}D^{\mp}=(6.14 \pm 0.29 \pm 0.50)\times 10^{-4}$. We measure CP asymmetry parameters $\mathcal{S}_{D^{+}D^{-}} = -1.06_{-0.14}^{+0.21} \pm 0.08$ and $\mathcal{C}_{D^{+}D^{-}} = -0.43 \pm 0.16 \pm 0.05$ in $B^{0} \to D^{+}D^{-}$ and $\mathcal{A}_{D^{*}D} = +0.06 \pm 0.05 \pm 0.02$, $\mathcal{S}_{D^{*}D} = -0.78 \pm 0.15 \pm 0.05$, $\mathcal{C}_{D^{*}D} = -0.01 \pm 0.11 \pm 0.04$, $\Delta\mathcal{S}_{D^{*}D} = -0.13 \pm 0.15 \pm 0.04$ and $\Delta\mathcal{C}_{D^{*}D} = +0.12 \pm 0.11 \pm 0.03$ in $B^{0} \to D^{*\pm}D^{\mp}$, where the first uncertainty is statistical and the second is systematic. We exclude the conservation of CP symmetry in both decays at equal to or greater than $4\sigma$ significance.Comment: 7 pages, 2 figure

Measurement of CP violating asymmetries in B^0 -> K^+K^- K^0_S decays with a time-dependent Dalitz approach

We report a measurement of $CP$ violating asymmetries in $B^0(\overline{B}^0) \to K^+ K^- K^0_S$ decays with a time-dependent Dalitz approach. This analysis is based on a data sample of $657\times 10^6$ $B\overline{B}$ pairs accumulated at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. As the result of an unbinned maximum likelihood fit to the selected candidates, the mixing-induced and direct $CP$ violation parameters, $\phi^{\rm eff}_1$ and ${\cal A}_{CP}$ are obtained for $B^0 \to \phi(1020) K^0_S$, $B^0 \to f_0(980) K^0_S$ and other $B^0 \to K^+ K^- K^0_S$ decays. We find four solutions that describe the data. There are \{eqnarray*} \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (32.2 \pm 9.0 \pm 2.6 \pm 1.4)^{\circ}; \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (26.2 \pm 8.8 \pm 2.7 \pm 1.2)^{\circ};\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (27.3 \pm 8.6 \pm 2.8 \pm 1.3)^{\circ}\; {\rm and}\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (24.3 \pm 8.0 \pm 2.9 \pm 5.2)^{\circ}.{eqnarray*}\ The values for the $CP$ violating phase in $B^0\to \phi(1020) K^0_S$ are similar but other properties of the Dalitz plot are quite different for the four solutions. These four solutions have consistent $\phi^{\rm eff}_1$ values for all three $B$ meson decay channels and none of them deviates significantly from the values measured in $B \to (c\bar{c}) K^0$ decays with the currently available statistics. In addition, we find no significant direct $CP$ violation.Comment: submitted to PR

Measurement of CP violating asymmetries in B^0 -> K^+K^- K^0_S decays with a time-dependent Dalitz approach

We report a measurement of $CP$ violating asymmetries in $B^0(\overline{B}^0) \to K^+ K^- K^0_S$ decays with a time-dependent Dalitz approach. This analysis is based on a data sample of $657\times 10^6$ $B\overline{B}$ pairs accumulated at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. As the result of an unbinned maximum likelihood fit to the selected candidates, the mixing-induced and direct $CP$ violation parameters, $\phi^{\rm eff}_1$ and ${\cal A}_{CP}$ are obtained for $B^0 \to \phi(1020) K^0_S$, $B^0 \to f_0(980) K^0_S$ and other $B^0 \to K^+ K^- K^0_S$ decays. We find four solutions that describe the data. There are \{eqnarray*} \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (32.2 \pm 9.0 \pm 2.6 \pm 1.4)^{\circ}; \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (26.2 \pm 8.8 \pm 2.7 \pm 1.2)^{\circ};\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (27.3 \pm 8.6 \pm 2.8 \pm 1.3)^{\circ}\; {\rm and}\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (24.3 \pm 8.0 \pm 2.9 \pm 5.2)^{\circ}.{eqnarray*}\ The values for the $CP$ violating phase in $B^0\to \phi(1020) K^0_S$ are similar but other properties of the Dalitz plot are quite different for the four solutions. These four solutions have consistent $\phi^{\rm eff}_1$ values for all three $B$ meson decay channels and none of them deviates significantly from the values measured in $B \to (c\bar{c}) K^0$ decays with the currently available statistics. In addition, we find no significant direct $CP$ violation.Comment: submitted to PR

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

Evidence for B- -> tau- nu_bar with a Semileptonic Tagging Method

We present a measurement of the decay B- -> tau- nu_bar using a data sample containing 657 million BB_bar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. A sample of BB_bar pairs are tagged by reconstructing one B meson decaying semileptonically. We detect the B- -> tau- nu_bar candidate in the recoil. We obtain a signal with a significance of 3.6 standard deviations including systematic uncertainties, and measure the branching fraction to be Br(B- -> tau- nu_bar) = [1.54+0.38-0.37(stat)+0.29-0.31(syst)]*10^-4. This result confirms the evidence for B- -> tau- nu_bar obtained in a previous Belle measurement that used a hadronic B tagging method.Comment: 7 pages, 3 figures, corrected references, to appear in PRD-R