The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the rat

SummaryObjectiveDuring the development of disease-modifying osteoarthritis (OA) drugs, rat models of OA are frequently used for a first assessment of in vivo efficacy. The most efficacious compound in the rat model may then be tested in a larger animal model before entering human trials. The aim of this study was to describe a histologic scoring system for use in different models of OA in rats that allows standardization and comparison of results obtained by different investigators.MethodsThe experience of the authors with current scoring systems and the range of lesions observed in rat and human OA studies were considered in recommending this common paradigm for rat histologic scoring. Considerations were made for reproducibility and ease of use for new scorers. Additional scoring paradigms may be employed to further identify specific effects of some disease-modifying drugs.ResultsAlthough the described scoring system is more complex than the modified Mankin scores, which are recommended for some other species, the reliability study showed that it is easily understood and can be reproducibly used, even by inexperienced scorers.ConclusionsThe scoring paradigm described here has been found to be sufficiently sensitive to discriminate between treatments and to have high reproducibility. Therefore we recommend its use for evaluation of different rat OA models as well as assessment of disease-modifying effects of treatments in these models

Spatially explicit estimates of N2O emissions from croplands suggest climate mitigation opportunities from improved fertilizer management

With increasing nitrogen (N) application to croplands required to support growing food demand, mitigating N2O emissions from agricultural soils is a global challenge. National greenhouse gas emissions accounting typically estimates N2O emissions at the country scale by aggregating all crops, under the assumption that N2O emissions are linearly related to N application. However, field studies and meta-analyses indicate a nonlinear relationship, in which N2O emissions are relatively greater at higher N application rates. Here we apply a super-linear emissions response model to crop-specific, spatially-explicit synthetic N fertilizer and manure N inputs to provide subnational accounting of global N2O emissions from croplands. We estimate 0.66 Tg of N2O-N direct global emissions circa 2000, with 50% of emissions concentrated in 13% of harvested area. Compared to estimates from the IPCC Tier 1 linear model, our updated N2O emissions range from 20-40% lower throughout Sub-Saharan Africa and Eastern Europe, to >120% greater in some Western European countries. At low N application rates, the weak non-linear response of N2O emissions suggests that relatively large increases in N fertilizer application would generate relatively small increases in N2O emissions. Since aggregated fertilizer data generate underestimation bias in nonlinear models, high-resolution N application data are critical to support accurate N2O emissions estimates

Electronic Collective Modes and Superconductivity in Layered Conductors

A distinctive feature of layered conductors is the presence of low-energy electronic collective modes of the conduction electrons. This affects the dynamic screening properties of the Coulomb interaction in a layered material. We study the consequences of the existence of these collective modes for superconductivity. General equations for the superconducting order parameter are derived within the strong-coupling phonon-plasmon scheme that account for the screened Coulomb interaction. Specifically, we calculate the superconducting critical temperature Tc taking into account the full temperature, frequency and wave-vector dependence of the dielectric function. We show that low-energy plasmons may contribute constructively to superconductivity. Three classes of layered superconductors are discussed within our model: metal-intercalated halide nitrides, layered organic materials and high-Tc oxides. In particular, we demonstrate that the plasmon contribution (electronic mechanism) is dominant in the first class of layered materials. The theory shows that the description of so-called ``quasi-two-dimensional superconductors'' cannot be reduced to a purely 2D model, as commonly assumed. While the transport properties are strongly anisotropic, it remains essential to take into account the screened interlayer Coulomb interaction to describe the superconducting state of layered materials.Comment: Final version (minor changes) 14 pages, 6 figure

The fully differential single-top-quark cross section in next-to-leading order QCD

We present a new next-to-leading order calculation for fully differential single-top-quark final states. The calculation is performed using phase space slicing and dipole subtraction methods. The results of the methods are found to be in agreement. The dipole subtraction method calculation retains the full spin dependence of the final state particles. We show a few numerical results to illustrate the utility and consistency of the resulting computer implementations.Comment: 37 pages, latex, 2 ps figure

Mutation of Ser172 in Yeast β Tubulin Induces Defects in Microtubule Dynamics and Cell Division

Ser172 of β tubulin is an important residue that is mutated in a human brain disease and phosphorylated by the cyclin-dependent kinase Cdk1 in mammalian cells. To examine the role of this residue, we used the yeast S. cerevisiae as a model and produced two different mutations (S172A and S172E) of the conserved Ser172 in the yeast β tubulin Tub2p. The two mutants showed impaired cell growth on benomyl-containing medium and at cold temperatures, altered microtubule (MT) dynamics, and altered nucleus positioning and segregation. When cytoplasmic MT effectors Dyn1p or Kar9p were deleted in S172A and S172E mutants, cells were viable but presented increased ploidy. Furthermore, the two β tubulin mutations exhibited synthetic lethal interactions with Bik1p, Bim1p or Kar3p, which are effectors of cytoplasmic and spindle MTs. In the absence of Mad2p-dependent spindle checkpoint, both mutations are deleterious. These findings show the importance of Ser172 for the correct function of both cytoplasmic and spindle MTs and for normal cell division

Muon anomalous magnetic moment in the standard model with two Higgs doublets

The muon anomalous magnetic moment is investigated in the standard model with two Higgs doublets (S2HDM) motivated from spontaneous CP violation. Thus all the effective Yukawa couplings become complex. As a consequence of the non-zero phase in the couplings, the one loop contribution from the neutral scalar bosons could be positive and negative relying on the CP phases. The interference between one and two loop diagrams can be constructive in a large parameter space of CP-phases. This will result in a significant contribution to muon anomalous magnetic moment even in the flavor conserving process with a heavy neutral scalar boson ($m_h \sim$ 200 GeV) once the effective muon Yukawa coupling is large ($|\xi_\mu|\sim 50$). In general, the one loop contributions from lepton flavor changing scalar interactions become more important. In particular, when all contributions are positive in a reasonable parameter space of CP phases, the recently reported 2.6 sigma experiment vs. theory deviation can be easily explained even for a heavy scalar boson with a relative small Yukawa coupling in the S2HDM.Comment: 8 pages, RevTex file, 5 figures, published version Phys. Rev. D 54 (2001) 11501

Single Top Quark at Future Hadron Colliders. Complete Signal and Background Study

We perform a detail theoretical study including decays and jet fragmentation of all the important modes of the single top quark production and all basic background processes at the upgraded Tevatron and LHC colliders. Special attention was paid to the complete tree level calculation of the QCD fake background which was not considered in the previous studies. Analysis of the various kinematical distributions for the signal and backgrounds allowed to work out a set of cuts for an efficient background suppression and extraction of the signal. It was shown that the signal to background ratio after optimized cuts could reach about 0.4 at the Tevatron and 1 at the LHC. The remaining after cuts rate of the signal at the LHC for the $lepton+jets$ signature is expected to be about 6.1 pb and will be enough to study the single top physics even during the LHC operation at a low luminosity.Comment: 15 pages, LaTex, 7 figure

Polarized Single Top Quark Production in e\gamma Collision and Anomalous Wtb Couplings

We investigate the potential of $e\gamma$ collisions to probe anomalous $Wtb$ couplings via the polarized single top quark production process $e^{+} \gamma \to t \bar{b} \bar{\nu_{e}}$. We find 95% confidence level limits on the anomalous coupling parameters $F_{2L}$ and $F_{2R}$ with an integrated luminosity of $500 fb^{-1}$ and $\sqrt{s}=0.5, 1$ and 1.5 TeV energies. The effects of top quark spin polarization on the anomalous $Wtb$ couplings are discussed. It is shown that polarization leads to a considerable improvement in the sensitivity limits.Comment: published versio