Suppression of experimental arthritis through AMP-activated protein kinase activation and autophagy modulation

Autophagy plays a central role in various disease processes. However, its contribution to inflammatory arthritides such as rheumatoid arthritis (RA) is unclear. We observed that autophagy is engaged in the K/BxN serum transfer model of RA but autophagic flux is severely impaired. Metformin is an anti-diabetic drug that has been shown to stimulate autophagy. Induction of autophagic flux, through metformin-mediated AMP-activated protein kinase (AMPK) activation and interruption of mammalian target of rapamycin (mTOR) signaling mitigated the inflammation in experimental arthritis. Further investigation into the effects of metformin suggest that the drug directly activates AMPK and dose-dependently suppressed the release of TNF-α, IL-6, and MCP-1 by macrophages while enhancing the release of IL-10 in vitro. In vivo, metformin treatment significantly suppressed clinical arthritis and inflammatory cytokine production. Mechanistic studies suggest that metformin exerts its anti-inflammatory effects by correcting the impaired autophagic flux observed in the K/BxN arthritis model and suppressing NF-κB-mediated signaling through selective degradation of IκB kinase (IKK). These findings establish a central role for autophagy in inflammatory arthritis and argue that autophagy modulators such as metformin may represent potential therapeutic agents for the treatment of RA

Signal for CP violation in B±→PPˉπ±B^{\pm} \to P {\bar P} \pi^{\pm} decays

We analyze the partial rate asymmetry in $B^{\pm} \to P {\bar P} \pi^{\pm}$ decays ($P = \pi^+, K ^+, \pi^0, \eta$) which results from the interference of the nonresonant decay amplitude and the resonant amplitude for $B^{\pm} \to \chi_{c0} \pi^{\pm}$ followed by the decay $\chi_{c0} \to P {\bar P}$. The CP violating phase $\gamma$ can be extracted from the measured asymmetry. We find that the partial rate asymmetry for $B^\pm \to \pi^+ \pi^- \pi^\pm$ is $0.33~sin \gamma$, while for $B^\pm \to K^+ K^-\pi^\pm$ it amounts $0.45~ sin \gamma$.Comment: 3 pages, latex, no figures, Talk given by S. Fajfer at the Hyperons, Charm and Beauty Hadrons, Genova, Italy, 30 June -3 July 1998, to appear as proceedings in Nucl. Phys.

B -> K1 gamma and tests of factorization for two-body non leptonic Bdecays with axial-vector mesons

The large branching ratio for B-> K1 gamma recently measured at Belle implies a large B -> K1 transition form factor and large branching ratios for non leptonic B decays involving an axial-vector meson. In this paper we present an analysis of two-body B decays with an axial-vector meson in the final state using naive factorization and the B -> K1 form factors obtained from the measured radiative decays. We find that the predicted B -> J/psi K1 branching ratio is in agreement with experiment. We also suggest that the decay rates of B -> K1 pi, B -> a1 K and B -> b1 K could be used to test the factorization ansatz.Comment: 8 pages; 7 new references included and a comment on K2(1430) in the final state adde

FACTORS AFFECTING ECOTOURISM LOYALTY WITH THE MODERATING ROLE OF SOCIAL INFLUENCE - EMPIRICAL EVIDENCE IN VIETNAM

Today, ecotourism has become more common and attractive for tourists who love to explore nature and experience the cultural heritage. In the 4.0 age of technology, social networking not only helps visitors find suitable destinations to visit easily but also provides visitors with a place to leave comments or reviews after the trips. This study aims to qualify the relationships between electronic-worth-of-mouth (eWOM), social influence (SI), destination image (DI), tourist satisfaction (SAT), and ecotourism loyalty (EL). The study applied the PLS-SEM model to estimate 499 observations at ecotourism sites in Vietnam as empirical evidence. The research results show that all the factors in the research model have positive and significant effects on EL. In particular, DI and SAT, directly and indirectly, affect EL; while eWOM and SI only have direct effects on EL. Additionally, it was found that the effect of eWOM on EL increased with the moderating role of SI

B => \pi \pi \ell \nu decays in a QCD relativistic potential model

In the framework of a QCD relativistic potential model we evaluate the form factors describing the exclusive decay B => \pi\pi \ell \nu. The calculation is performed in a phase space region far away from the resonances and therefore is complementary to other decay mechanisms where the pions are produced by intermediate particles, e.g. in the chiral approach. We give an estimate of the contribution of the non resonant channel of the order of BR(B- => \pi+ \pi- \ell \nu) \approx 2.2 x 10^(-4).Comment: 14 pages LaTeX2e + 3 figures, Napoli Preprint DSF 99/3

Final State Interactions in B−>DρB -> D \rho and B−>D∗πB -> D^{*}\pi Decays

We analyze final state strong interaction effects in $B -> D \rho$ and $B -> D^{*}\pi$ decays using the Regge model. We find that, due to the smallness of the contributions from the non-leading Regge trajectories ($\rho$, $f$, $\pi$ etc.), final state interaction phases are small if the Pomeron coupling to the charm quark is suppressed in comparison to lighter quarks. Our conclusion is that for $B$ decays into states containing charm, final state interaction effects should play a minor role.Comment: 10 pages, LaTeX, accepted for Physics Letters

Neutrinos in 5D SO(10) Unification

We study neutrino physics in a 5D supersymmetric SO(10) GUT. We analyze several different choices for realizing the See-Saw mechanism. We find that the "natural" scale for the Majorana mass of right-handed neutrinos depends critically on whether the right-handed neutrinos are located in the bulk or localized on a brane. In the former case, the effective Majorana mass is "naturally" of order the compactification scale, about 10^{14} GeV. Note, this is the value necessary for obtaining a light tau neutrino mass approximately 10^{-2} eV which, within the context of hierarchical neutrino masses, is the right order of magnitude to explain atmospheric neutrino oscillations. On the other-hand when the right-handed neutrino is localized on the brane, the effective Majorana mass is typically larger than the compactification scale. Nevertheless with small parameters of order 1/10 - 1/30, an effective Majorana mass of order 10^{14} GeV can be accommodated. We also discuss the constraints on model building resulting from the different scenarios for locating the right-handed neutrinos.Comment: 24 page

Charming penguin and direct CP-violation in charmless B decays

In the study of two-body charmless B decays as a mean of looking for direct CP-violation and measuring the CKM mixing parameters in the Standard Model, the short-distance penguin contribution with its absorptive part generated by charm quark loop seems capable of producing sufficient $B \to K\pi$ decays rates, as obtained in factorization and QCD-improved factorization models. However there are also long-distance charming penguin contributions which could give rise to a strong phase due to the rescattering $D^{*}D^{*}_{s} \to K\pi$ etc. In this talk, I would like to discuss recent works on the charming penguin contribution as a different approach to the calculation of these contributions in two-body charmless B decays. We find that the charming penguin contribution is significant for $B\to K\pi$ decays and, together with the tree and penguin terms, produces large branching ratios in agreement with data, though the analysis is affected by large theoretical uncertainties. The absorptive part due to the charmed meson intermediate states is found to produce large CP asymmetries for $B \to K\pi, \pi\pi$ decays.Comment: Talk given at the QCD Euroconference 2002, Montpellier 2-9 July 2002, LaTex, 7 pages, Misprint in the Tables correcte