Iron enhances hepatic fibrogenesis and activates TGF-β signaling in murine hepatic stellate cells

Introduction Although excess iron induces oxidative stress in the liver, it is unclear whether it directly activates the hepatic stellate cells (HSC). Methods We evaluated effects of excess iron on fibrogenesis and TGF-β signaling in murine HSC. Cells were treated with holotransferrin (0.005–5 g/L) for 24 h, with or without the iron chelator deferoxamine (10 µM). Gene expressions (α-SMA, Col1-α1, Serpine-1, TGF-β, Hif1-α, Tfrc and Slc40a1) were analyzed by qRT-PCR, while TfR1, ferroportin, ferritin, vimentin, collagen, TGF-β RII and phospho-Smad2 proteins were evaluated by immunofluorescence, western blot and ELISA. Results HSC express the iron-uptake protein TfR1, and the iron-export protein ferroportin. Holotransferrin up-regulated TfR1 expression by 1.8-fold (p<0.03) and ferritin accumulation (iron storage) by 2-fold (p<0.01), and activated HSC with 2-fold elevations (p<0.03) in α-SMA mRNA and collagen secretion, and a 1.6-fold increase (p<0.01) in vimentin protein. Moreover, holotransferrin activated the TGF-β pathway with TGF-β mRNA elevated 1.6-fold (p=0.05), and protein levels of TGF-β RII and phospho-Smad2 increased by 1.8-fold (p<0.01) and 1.6-fold (p<0.01), respectively. By contrast, iron chelation decreased ferritin levels by 30% (p<0.03), inhibited collagen secretion by 60% (p<0.01), repressed fibrogenic genes α-SMA (0.2-fold; p<0.05) and TGF-β (0.4-fold; p<0.01), and reduced levels of TGF-β RII and phospho-Smad2 proteins. Conclusion HSC express iron transport proteins. Holotransferrin (iron) activates HSC fibrogenesis and the TGF-β pathway, while iron depletion by chelation reverses this, suggesting that this could be a useful adjunct therapy for patients with fibrosis. Further studies in primary human HSC and animal models are necessary to confirm this

Mode-Locking in Driven Disordered Systems as a Boundary-Value Problem

We study mode-locking in disordered media as a boundary-value problem. Focusing on the simplest class of mode-locking models which consists of a single driven overdamped degree-of-freedom, we develop an analytical method to obtain the shape of the Arnol'd tongues in the regime of low ac-driving amplitude or high ac-driving frequency. The method is exact for a scalloped pinning potential and easily adapted to other pinning potentials. It is complementary to the analysis based on the well-known Shapiro's argument that holds in the perturbative regime of large driving amplitudes or low driving frequency, where the effect of pinning is weak.Comment: 6 pages, 7 figures, RevTeX, Submitte

A Monitor of Beam Polarization Profiles for the TRIUMF Parity Experiment

TRIUMF experiment E497 is a study of parity violation in pp scattering at an energy where the leading term in the analyzing power is expected to vanish, thus measuring a unique combination of weak-interaction flavour conserving terms. It is desired to reach a level of sensitivity of 2x10^-8 in both statistical and systematic errors. The leading systematic errors depend on transverse polarization components and, at least, the first moment of transverse polarization. A novel polarimeter that measures profiles of both transverse components of polarization as a function of position is described.Comment: 19 pages LaTeX, 10 PostScript figures. To appear in Nuclear Instruments and Methods in Physics Research, Section

ICON 2019: International Scientific Tendinopathy Symposium Consensus: Clinical Terminology

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.Background Persistent tendon pain that impairs function has inconsistent medical terms that can influence choice of treatment.1 When a person is told they have tendinopathy by clinician A or tendinitis by clinician B, they might feel confused or be alarmed at receiving what they might perceive as two different diagnoses. This may lead to loss of confidence in their health professional and likely adds to uncertainty if they were to search for information about their condition. Clear and uniform terminology also assists inter-professional communication. Inconsistency in terminology for painful tendon disorders is a problem at numerous anatomical sites. Historically, the term ‘tendinitis’ was first used to describe tendon pain, thickening and impaired function (online supplementary figure S1). The term ‘tendinosis’ has also been used in a small number of publications, some of which were very influential.2 3 Subsequently, ‘tendinopathy’ emerged as the most common term for persistent tendon pain.4 5 To our knowledge, experts (clinicians and researchers) or patients have never engaged in a formal process to discuss the terminology we use. We believe that health professionals have not yet agreed on the appropriate terminology for painful tendon conditions.Peer reviewedFinal Accepted Versio

Aspects of Bifurcation Theory for Piecewise-Smooth, Continuous Systems

Systems that are not smooth can undergo bifurcations that are forbidden in smooth systems. We review some of the phenomena that can occur for piecewise-smooth, continuous maps and flows when a fixed point or an equilibrium collides with a surface on which the system is not smooth. Much of our understanding of these cases relies on a reduction to piecewise linearity near the border-collision. We also review a number of codimension-two bifurcations in which nonlinearity is important.Comment: pdfLaTeX, 9 figure

Study of the production of Λb0\Lambda_b^0 and B‾0\overline{B}^0 hadrons in pppp collisions and first measurement of the Λb0→J/ψpK−\Lambda_b^0\rightarrow J/\psi pK^- branching fraction

The product of the $\Lambda_b^0$ ($\overline{B}^0$) differential production cross-section and the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ ($\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$) is measured as a function of the beauty hadron transverse momentum, $p_{\rm T}$, and rapidity, $y$. The kinematic region of the measurements is $p_{\rm T}<20~{\rm GeV}/c$ and $2.0<y<4.5$. The measurements use a data sample corresponding to an integrated luminosity of $3~{\rm fb}^{-1}$ collected by the LHCb detector in $pp$ collisions at centre-of-mass energies $\sqrt{s}=7~{\rm TeV}$ in 2011 and $\sqrt{s}=8~{\rm TeV}$ in 2012. Based on previous LHCb results of the fragmentation fraction ratio, $f_{\Lambda_B^0}/f_d$, the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ is measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4}, \end{equation*} where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay $\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$, and the fourth is due to the knowledge of $f_{\Lambda_b^0}/f_d$. The sum of the asymmetries in the production and decay between $\Lambda_b^0$ and $\overline{\Lambda}_b^0$ is also measured as a function of $p_{\rm T}$ and $y$. The previously published branching fraction of $\Lambda_b^0\rightarrow J/\psi p\pi^-$, relative to that of $\Lambda_b^0\rightarrow J/\psi pK^-$, is updated. The branching fractions of $\Lambda_b^0\rightarrow P_c^+(\rightarrow J/\psi p)K^-$ are determined.Comment: 29 pages, 19figures. 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-2015-032.htm

Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_{\text{NN}}}=5$TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, $\Delta\eta$, and relative azimuthal angle, $\Delta\phi$, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, $\Delta\phi \approx 0$, is observed in the pseudorapidity range $2.0<\eta<4.9$. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to $\eta=4.9$. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.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-2015-040.htm

Evidence for the strangeness-changing weak decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

Using a $pp$ collision data sample corresponding to an integrated luminosity of 3.0~fb$^{-1}$, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay $\Xi_b^-\to\Lambda_b^0\pi^-$. No $b$ hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be ${{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}$, where $f_{\Xi_b^-}$ and $f_{\Lambda_b^0}$ are the $b\to\Xi_b^-$ and $b\to\Lambda_b^0$ fragmentation fractions, and ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ is the branching fraction. Assuming $f_{\Xi_b^-}/f_{\Lambda_b^0}$ is bounded between 0.1 and 0.3, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ would lie in the range from $(0.57\pm0.21)\%$ to $(0.19\pm0.07)\%$.Comment: 7 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-2015-047.htm

Potential for comparative public opinion research in public administration

The public administration and public services have always taken a marginal place in the political scientists’ behavioural research. Public administration students on the other hand tend to focus on political and administrative elites and institutions, and largely ignored citizens in comparative research. In this article we make a plea for international comparative research on citizens’ attitudes towards the public administration from an interdisciplinary perspective. Available international survey material is discussed, and main trends in empirical practice and theoretical approaches are outlined, especially those with a potential impact on public sector reform

Search for B⁺c decays to the pp‾π⁺ final state

A search for the decays of the B + c meson to pp-π + is performed for the first time using a data sample corresponding to an integrated luminosity of 3.0 fb -1 collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV. No signal is found and an upper limit, at 95% confidence level, is set, fcfu×B(B + c →ppπ + ) < 3.6×10-8 in the kinematic region m(pp) < 2.85 GeV/c2, p T (B) < 20 GeV/c and 2.0 < y(B) < 4.5, where B is the branching fraction and f c (f u ) is the fragmentation fraction of the b quark into a B c + (B + ) meson