A novel technique for selective NF-kappa B inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion.

Background and aims: The transcription factor nuclear factor kappa B (NF-kB) has risen as a promising target for anti-inflammatory therapeutics. In the liver, however, NFkB inhibition mediates both damaging and protective effects. The outcome is deemed to depend on the liver cell type addressed. Recent gene knock-out studies focused on the role of NF-kB in hepatocytes, whereas the role of NF-kB in Kupffer cells has not yet been investigated in vivo. Here we present a novel approach, which may be suitable for clinical application, to selectively target NF-kB in Kupffer cells and analyse the effects in experimental models of liver injury. Methods: NF-kB inhibiting decoy oligodeoxynucleotides were loaded upon gelatin nanoparticles (D-NPs) and their in vivo distribution was determined by confocal microscopy. Liver damage, NF-kB activity, cytokine levels and apoptotic protein expression were evaluated after lipopolysaccharide (LPS), D-galactosamine (GalN)/LPS, or concanavalin A (ConA) challenge and partial warm ischaemia and subsequent reperfusion, respectively. Results: D-NPs were selectively taken up by Kupffer cells and inhibited NF-kB activation. Inhibition of NF-kB in Kupffer cells improved survival and reduced liver injury after GalN/LPS as well as after ConA challenge. While anti-apoptotic protein expression in liver tissue was not reduced, pro-apoptotic players such as cJun N-terminal kinase (JNK) were inhibited. In contrast, selective inhibition of NF-kB augmented reperfusion injury. Conclusions: NF-kB inhibiting decoy oligodeoxynucleotide- loaded gelatin nanoparticles is a novel tool to selectively inhibit NF-kB activation in Kupffer cells in vivo. Thus, liver injury can be reduced in experimental fulminant hepatitis, but increased at ischaemia–reperfusion

What is the spatial distribution of magnetic helicity injected in a solar active region?

Copyright © 2006 EDP Sciences. This article appeared in Astronomy & Astrophysics 452 (2006) and may be found at http://www.aanda.org/index.php?option=article&access=doi&doi=10.1051/0004-6361:20054643Context. Magnetic helicity is suspected to play a key role in solar phenomena such as flares and coronal mass ejections. Several investigations have recently computed the photospheric flux of magnetic helicity in active regions. The derived spatial maps of the helicity flux density, called GA, have an intrinsic mixed-sign patchy distribution. Aims. Pariat et al. (2005) recently showed that GA is only a proxy of the helicity flux density, which tends to create spurious polarities. They proposed a better proxy, Gθ. We investigate here the implications of this new approach on observed active regions. Methods. The magnetic data are from MDI/SoHO instrument and the photospheric velocities are computed by local correlation tracking. Maps and temporal evolution of GA and Gθ are compared using the same data set for 5 active regions. Results. Unlike the usual GA maps, most of our Gθ maps show almost unipolar spatial structures because the nondominant helicity flux densities are significantly suppressed. In a few cases, the Gθ maps still contain spurious bipolar signals. With further modelling we infer that the real helicity flux density is again unipolar. On time-scales larger than their transient temporal variations, the time evolution of the total helicity fluxes derived from GA and Gθ show small differences. However, unlike GA, with Gθ the time evolution of the total flux is determined primarily by the predominant-signed flux while the nondominant-signed flux is roughly stable and probably mostly due to noise. Conclusions. Our results strongly support the conclusion that the spatial distribution of helicity injected into active regions is much more coherent than previously thought: on the active region scale the sign of the injected helicity is predominantly uniform. These results have implications for the generation of the magnetic field (dynamo) and for the physics of both flares and coronal mass ejections

In Pursuit of New Physics with B_s Decays

The presence of a sizeable CP-violating phase in B_s^0-B_s^0-bar mixing would be an unambiguous signal of physics beyond the Standard Model. We analyse various possibilities to detect such a new phase considering both tagged and untagged decays. The effects of a sizeable width difference Delta Gamma between the B_s mass eigenstates, on which the untagged analyses rely, are included in all formulae. A novel method to find this phase from simple measurements of lifetimes and branching ratios in untagged decays is proposed. This method does not involve two-exponential fits, which require much larger statistics. For the tagged decays, an outstanding role is played by the observables of the time-dependent angular distribution of the B_s -> J/psi [-> l^+ l^-] \phi [-> K^+K^-] decay products. We list the formulae needed for the angular analysis in the presence of both a new CP-violating phase and a sizeable Delta Gamma, and propose methods to remove a remaining discrete ambiguity in the new phase. This phase can therefore be determined in an unambiguous way.Comment: minor changes, lattice prediction of Delta Gamma updated, appears in PR

Modeling magnetospheric fields in the Jupiter system

The various processes which generate magnetic fields within the Jupiter system are exemplary for a large class of similar processes occurring at other planets in the solar system, but also around extrasolar planets. Jupiter's large internal dynamo magnetic field generates a gigantic magnetosphere, which is strongly rotational driven and possesses large plasma sources located deeply within the magnetosphere. The combination of the latter two effects is the primary reason for Jupiter's main auroral ovals. Jupiter's moon Ganymede is the only known moon with an intrinsic dynamo magnetic field, which generates a mini-magnetosphere located within Jupiter's larger magnetosphere including two auroral ovals. Ganymede's magnetosphere is qualitatively different compared to the one from Jupiter. It possesses no bow shock but develops Alfv\'en wings similar to most of the extrasolar planets which orbit their host stars within 0.1 AU. New numerical models of Jupiter's and Ganymede's magnetospheres presented here provide quantitative insight into the processes that maintain these magnetospheres. Jupiter's magnetospheric field is approximately time-periodic at the locations of Jupiter's moons and induces secondary magnetic fields in electrically conductive layers such as subsurface oceans. In the case of Ganymede, these secondary magnetic fields influence the oscillation of the location of its auroral ovals. Based on dedicated Hubble Space Telescope observations, an analysis of the amplitudes of the auroral oscillations provides evidence that Ganymede harbors a subsurface ocean. Callisto in contrast does not possess a mini-magnetosphere, but still shows a perturbed magnetic field environment. Callisto's ionosphere and atmospheric UV emission is different compared to the other Galilean satellites as it is primarily been generated by solar photons compared to magnetospheric electrons.Comment: Chapter for Book: Planetary Magnetis

Model-independent constraints on Delta F=2 operators and the scale of New Physics

We update the constraints on new-physics contributions to Delta F=2 processes from the generalized unitarity triangle analysis, including the most recent experimental developments. Based on these constraints, we derive upper bounds on the coefficients of the most general Delta F=2 effective Hamiltonian. These upper bounds can be translated into lower bounds on the scale of new physics that contributes to these low-energy effective interactions. We point out that, due to the enhancement in the renormalization group evolution and in the matrix elements, the coefficients of non-standard operators are much more constrained than the coefficient of the operator present in the Standard Model. Therefore, the scale of new physics in models that generate new Delta F=2 operators, such as next-to-minimal flavour violation, has to be much higher than the scale of minimal flavour violation, and it most probably lies beyond the reach of direct searches at the LHC.Comment: 32 pages, 11 figures, 6 tables. v2: error in the implementation of D0 untagged Bs->J/Psi phi correlation matrix corrected. Improved presentation of the results and discussion of ambiguities in untagged Bs->J/Psi phi. Results for NP in Bs oscillations changed. Final version to appear in JHE

Averages of b-hadron, c-hadron, and tau-lepton properties as of 2018 Heavy Flavor Averaging Group (HFLAV)

This paper reports world averages of measurements of b-hadron, c-hadron, and τ -lepton properties obtained by the Heavy Flavour Averaging Group using results available through September 2018. In rare cases, significant results obtained several months later are also used. For the averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters, C P violation parameters, parameters of semileptonic decays, and Cabibbo–Kobayashi–Maskawa matrix elements

Measurement of the effective B0s→K+K− lifetime

A measurement of the effective lifetime is presented using approximately 37 pb−1 of data collected by LHCb during 2010. This quantity can be used to put constraints on contributions from processes beyond the Standard Model in the meson system and is determined by two complementary approaches as τKK=1.440±0.096 (stat)±0.008 (syst)±0.003 (model) ps