Breaking Tolerance to Double Stranded DNA, Nucleosome, and Other Nuclear Antigens Is Not Required for the Pathogenesis of Lupus Glomerulonephritis

In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic glomerulonephritis, severe proteinuria, and early mortality in females. A locus Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti–double stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4 (NZM.C57Lc4), were generated by replacing the respective genetic intervals containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain. The NZM.C57Lc1 females had markedly reduced incidence of chronic glomerulonephritis and severe proteinuria. NZM.C57Lc4 females had chronic glomerulonephritis and severe proteinuria without circulating ANA, anti-dsDNA, and antinucleosome Ab. These data confirm the linkage analysis. Unexpectedly, NZM.C57Lc1 females had little anti-dsDNA and related Ab, suggesting the presence of a second locus Adnz2 on chromosome 1. The diseased NZM.C57Lc4 kidneys had immune complexes by immunofluorescence and electron microscopy. The eluates from these kidneys did not contain ANA, anti-dsDNA, and antinucleosome Ab, indicative of the presence of non–anti-dsDNA nephritogenic Ab. Thus, breaking tolerance to dsDNA and chromatin is not required for the pathogenesis of lupus nephritis. These results reaffirm that anti-dsDNA and related Ab production and chronic glomerulonephritis are under independent genetic control. These findings have significant implications in the pathogenesis of systemic lupus erythematosus

Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes

Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases. In addition, using a microsurgical model, we show how LN metastasis development and dissemination is regulated by the expression of a chromatin modifier, histone deacetylase 11 (HDAC11). Genetic and pharmacologic blockade of HDAC11 decreases LN tumor growth, yet substantially increases migration and distant metastasis formation. Collectively, we reveal a mechanism explaining how HDAC11 plasticity promotes breast cancer growth as well as dissemination from LNs and suggest caution with the use of HDAC inhibitors

Analysis of the radiative decays among the charmonium states

In this article, we study the radiative decays among the charmonium states with the heavy quark effective theory, and make predictions for the ratios among the radiative decay widths of an special multiplet to another multiplet. The predictions can be confronted with the experimental data in the future and put additional constraints in identifying the $X$, $Y$, $Z$ charmonium-like mesons.Comment: 12 pages, revised revisio

Anisotropy in mechanical properties and fracture behavior of an oxide dispersion Fe20Cr5Al alloy

Anisotropy of fracture toughness and fracture behavior of Fe20Cr5Al oxide dispersion-strengthened alloy has been investigated by means of compression tests, hardness tests, and wedge splitting test. The results show a small effect of the compression direction on yield strength (YS) and strain hardening. The YS is minimum for longitudinal direction and maximum for the tangential direction. The transverse plastic strain ratio is similar for tangential and longitudinal directions but very different from that in normal direction. Hardness depends on the indentation plane; it is lower for any plane parallel to the L-T plane and of similar magnitude for the other orthogonal planes, i.e., the L-S and T-S planes. Macroscopically, two failure modes have been observed after wedge-splitting tests, those of LS and TS specimens in which fracture deviates along one or two branches normal to the notch plane, and those of LT, TL, SL, and ST specimens in which fracture propagates along the notch plane. Besides LT and TL specimens present delaminations parallel to L-T plane. Both, the fracture surface of branching cracks and that of the delaminations, show an intergranular brittle fracture appearance. It is proposed that the main cause of the delamination and crack branching is the alignment in the mesoscopic scale of the ultrafine grains structure which is enhanced by the 〈110〉- texture of the material and by the presence in the grain boundaries of both yttria dispersoids and impurity contaminations. An elastoplastic finite element analysis was performed to study what stress state is the cause of the branches and delaminations. It is concluded that the normal to the crack branches and/or the shear stress components could determine the crack bifurcation mechanism, whereas the delamination it seems that it is controlled by the magnitude of the stress component normal to the delamination plane. © The Minerals, Metals & Materials Society and ASM International 2014.Peer Reviewe

Fragmentation Function and Hadronic Production of the Heavy Supersymmetric Hadrons

The light top-squark \sto may be the lightest squark and its lifetime may be `long enough' in a kind of SUSY models which have not been ruled out yet experimentally, so colorless `supersymmetric hadrons (superhadrons)' (\sto \bar{q}) ($q$ is a quark except $t$-quark) may be formed as long as the light top-squark \sto can be produced. Fragmentation function of \sto to heavy `supersymmetric hadrons (superhadrons)' (\sto \bar{Q}) ($\bar{Q}=\bar{c}$ or $\bar{b}$) and the hadronic production of the superhadrons are investigated quantitatively. The fragmentation function is calculated precisely. Due to the difference in spin of the SUSY component, the asymptotic behavior of the fragmentation function is different from those of the existent ones. The fragmentation function is also applied to compute the production of heavy superhadrons at hadronic colliders Tevatron and LHC under the so-called fragmentation approach. The resultant cross-section for the heavy superhadrons is too small to observe at Tevatron, but great enough at LHC, even when all the relevant parameters in the SUSY models are taken within the favored region for the heavy superhadrons. The production of `light superhadrons' (\sto \bar{q}) ($q=u, d, s$) is also roughly estimated. It is pointed out that the production cross-sections of the light superhadrons (\sto \bar{q}) may be much greater than those of the heavy superhadrons, so that even at Tevatron the light superhadrons may be produced in great quantities.Comment: 20 pages, 9 figure

Transverse Beam Spin Asymmetries in Forward-Angle Elastic Electron-Proton Scattering

We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely-polarized 3 GeV electrons from unpolarized protons at Q^2 = 0.15, 0.25 (GeV/c)^2. The results are inconsistent with calculations solely using the elastic nucleon intermediate state, and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A_n provides a direct probe of the imaginary component of the 2-gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.Comment: 5 pages, 3 figures, submitted to Physical Review Letters; shortened to meet PRL length limit, clarified some text after referee's comment

Lepton Dipole Moments and Rare Decays in the CP-violating MSSM with Nonuniversal Soft-Supersymmetry Breaking

We investigate the muon anomalous magnetic dipole moment (MDM), the muon electric dipole moment (EDM) and the lepton-flavour-violating decays of the $\tau-$lepton, $\tau \to \mu \gamma$ and $\tau\to 3\mu$, in the CP-violating Minimal Supersymmetric Standard Model (MSSM) with nonuniversal soft-supersymmetry breaking. We evaluate numerically the muon EDM and the branching ratios $B(\tau \to \mu\gamma)$ and $B(\tau \to 3\mu)$, after taking into account the experimental constraints from the electron EDM and muon MDM. Upon imposition of the experimental limits on our theoretical predictions for the aforementioned branching ratios and the muon MDM, we obtain an upper bound of about $10^{-23} e\cdot cm$ on the muon EDM which lies well within the explorable reach of the proposed experiment at BNL.Comment: Latex, 26 pages, 8 figures, accepted for publication in Phys. Rev.

Strange Quark Contributions to Parity-Violating Asymmetries in the Forward G0 Electron-Proton Scattering Experiment

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < Q^2 < 1.0 GeV^2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange quark contributions to the currents of the proton. The measurements were made at JLab using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate non-zero, Q^2 dependent, strange quark contributions and provide new information beyond that obtained in previous experiments.Comment: 5 pages, 2 figure