Rotation-induced 3D vorticity in 4He superfluid films adsorbed on a porous glass

Detailed study of torsional oscillator experiments under steady rotation up to 6.28 rad/sec is reported for a 4He superfluid monolayer film formed in 1 micrometer-pore diameter porous glass. We found a new dissipation peak with the height being in proportion to the rotation speed, which is located to the lower temperature than the vortex pair unbinding peak observed in the static state. We propose that 3D coreless vortices ("pore vortices") appear under rotation to explain this new peak. That is, the new peak originates from dissipation close to the pore vortex lines, where large superfluid velocity shifts the vortex pair unbinding dissipation to lower temperature. This explanation is confirmed by observation of nonlinear effects at high oscillation amplitudes.Comment: 4pages, 5figure

Suppression of Superfluidity of 4^4He in a Nanoporous Glass by Preplating a Kr Layer

Helium in nanoporous media has attracted much interest as a model Bose system with disorder and confinement. Here we have examined how a change in porous structure by preplating a monolayer of krypton affects the superfluid properties of $^4$He adsorbed or confined in a nanoporous Gelsil glass, which has a three-dimensional interconnected network of nanopores of 5.8 nm in diameter. Isotherms of adsorption and desorption of nitrogen show that monolayer preplating of Kr decreases the effective pore diameter to 4.7 nm and broadens the pore size distribution by about eight times from the sharp distribution of the bare Gelsil sample. The superfluid properties were studied by a torsional oscillator for adsorbed film states and pressurized liquid states, both before and after the monolayer Kr preplating. In the film states, both the superfluid transition temperature $T_{\mathrm c}$ and the superfluid density decrease about 10 percent by Kr preplating. The suppression of film superfluidity is attributed to the quantum localization of $^4$He atoms by the randomness in the substrate potential, which is caused by the preplating--induced broadening of the pore size distribution. In the pressurized liquid states, the superfluid density $\rho_{\mathrm s}$ is found to increase by 10 percent by Kr preplating, whereas $T_{\mathrm c}$ is decreased by 2 percent at all pressures. The unexpected enhancement of $\rho_{\mathrm s}$ might indicate the existence of an unknown disorder effect for confined $^4$He.Comment: 27 pages, 8 figures, submitted to J. Phys. Soc. Jp

Tolerance and rebound with zafirlukast in patients with persistent asthma

<p>Abstract</p> <p>Background</p> <p>The potential for tolerance to develop to zafirlukast, a cysteinyl leukotriene (CysLT) receptor antagonist (LRA) in persistent asthma, has not been specifically examined.</p> <p>Objective</p> <p>To look for any evidence of tolerance and potential for short-term clinical worsening on LRA withdrawal. Outcome measures included changes in; airway hyperresponsiveness to inhaled methacholine (PD₂₀FEV₁), daily symptoms and peak expiratory flows (PEF), sputum and blood cell profiles, sputum CysLT and prostaglandin (PG)E₂and exhaled nitric oxide (eNO) levels.</p> <p>Methods</p> <p>A double blind, placebo-controlled study of zafirlukast, 20 mg twice daily over 12 weeks in 21 asthmatics taking β₂-agonists only (Group I), and 24 subjects treated with ICS (Group II).</p> <p>Results</p> <p>In Group I, zafirlukast significantly improved morning PEF and FEV₁compared to placebo (p < 0.01), and reduced morning waking with asthma from baseline after two weeks (p < 0.05). Similarly in Group II, FEV₁improved compared to placebo (p < 0.05), and there were early within-treatment group improvements in morning PEF, β₂-agonist use and asthma severity scores (p < 0.05). However, most improvements with zafirlukast in Group I and to a lesser extent in Group II deteriorated toward baseline values over 12 weeks. In both groups, one week following zafirlukast withdrawal there were significant deteriorations in morning and evening PEFs and FEV₁compared with placebo (p ≤ 0.05) and increased nocturnal awakenings in Group II (p < 0.05). There were no changes in PD₂₀FEV₁, sputum CysLT concentrations or exhaled nitric oxide (eNO) levels. However, blood neutrophils significantly increased in both groups following zafirlukast withdrawal compared to placebo (p = 0.007).</p> <p>Conclusion</p> <p>Tolerance appears to develop to zafirlukast and there is rebound clinical deterioration on drug withdrawal, accompanied by a blood neutrophilia.</p

Chronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathways

Maladaptive changes in the carotid body (CB) induced by chronic intermittent hypoxia (IH) account for the pathogenesis of cardiovascular morbidity in patients with sleep-disordered breathing. We postulated that the proinflammatory cytokines, namely interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and cytokine receptors (IL-1r1, gp130 and TNFr1) locally expressed in the rat CB play a pathophysiological role in IH-induced CB inflammation. Results showed increased levels of oxidative stress (serum 8-isoprostane and nitrotyrosine in the CB) in rats with 7-day IH treatment resembling recurrent apneic conditions when compared with the normoxic control. Local inflammation shown by the amount of ED1-containing cells (macrophage infiltration) and the gene transcripts of NADPH oxidase subunits (gp91phox and p22phox) and chemokines (MCP-1, CCR2, MIP-1α, MIP-1β and ICAM-1) in the CB were significantly more in the hypoxic group than in the control. In addition, the cytokines and receptors were expressed in the lobules of chemosensitive glomus cells containing tyrosine hydroxylase and the levels of expressions were significantly increased in the hypoxic group. Exogenous cytokines elevated the intracellular calcium ([Ca2+]i) response to acute hypoxia in the dissociated glomus cells. The effect of cytokines on the [Ca2+]i response was significantly greater in the hypoxic than in the normoxic group. Moreover, daily treatment of IH rats with anti-inflammatory drugs (dexamethasone or ibuprofen) attenuated the levels of oxidative stress, gp91phox expression and macrophage infiltration in the CB. Collectively, these results suggest that the upregulated expression of proinflammatory cytokine pathways could mediate the local inflammation and functional alteration of the CB under chronic IH conditions

The Translation Initiation Factor 3f (eIF3f) Exhibits a Deubiquitinase Activity Regulating Notch Activation

The translation initiation factor complex eIF3f has an intrinsic deubiquitinase activity and regulates the Notch signaling pathway

Notch and Presenilin Regulate Cellular Expansion and Cytokine Secretion but Cannot Instruct Th1/Th2 Fate Acquisition

Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4+ T or reporter cells, the presence of Lunatic Fringe in CD4+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4+ T cells lacking γ-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch) independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation

Notch and Presenilin Regulate Cellular Expansion and Cytokine Secretion but Cannot Instruct Th1/Th2 Fate Acquisition

Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4+ T or reporter cells, the presence of Lunatic Fringe in CD4+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4+ T cells lacking γ-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch) independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation