Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

Objective: Previous studies have shown the importance of somatic mutations and arginine residues in the complementarity-determining regions (CDRs) of pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies in human and murine lupus, and in studies of murine antibodies, a role of mutations at position 53 in VH CDR2 has been demonstrated. We previously demonstrated in vitro expression and mutagenesis of the human IgG1 monoclonal antibody B3. The present study was undertaken to investigate, using this expression system, the importance of the arginine residue at position 53 (R53) in B3 VH. Methods: R53 was altered, by site-directed mutagenesis, to serine, asparagine, or lysine, to create 3 expressed variants of VH. In addition, the germline sequence of the VH3-23 gene (from which B3 VH is derived) was expressed either with or without arginine at position 53. These 5 new heavy chains, as well as wild-type B3 VH, were expressed with 4 different light chains, and the resulting antibodies were assessed for their ability to bind to nucleosomes, -actinin, cardiolipin, ovalbumin, 2-glycoprotein I (2GPI), and the N-terminal domain of 2GPI (domain I), using direct binding assays. Results: The presence of R53 was essential but not sufficient for binding to dsDNA and nucleosomes. Conversely, the presence of R53 reduced binding to -actinin, ovalbumin, 2GPI, and domain I of 2GPI. The combination B3 (R53S) VH/B3 VL bound human, but not bovine, 2GPI. Conclusion: The fact that the R53S substitution significantly alters binding of B3 to different clinically relevant antigens, but that the alteration is in opposite directions depending on the antigen, implies that this arginine residue plays a critical role in the affinity maturation of antibody B3

Asthenosphere-induced melting of diverse source regions for East Carpathian post-collisional volcanism

The occurrence of post-subduction magmatism in continental collision zones is a ubiquitous feature of plate tectonics, but its relation with geodynamic processes remains enigmatic. The nature of mantle sources in these settings, and their interaction with subduction-related components, are difficult to constrain using bulk rocks when magmas are subject to mixing and assimilation within the crust. Here we examine post-collisional magma sources in space and time through the chemistry of olivine-hosted melt inclusions and early-formed minerals (spinel, olivine and clinopyroxene) in primitive volcanic rocks from the Neogene–Quaternary East Carpathian volcanic range in Călimani (calc-alkaline; 10.1–6.7 Ma), Southern Harghita (calc-alkaline to shoshonitic; 5.3–0.03 Ma) and the Perșani Mountains (alkali basaltic; 1.2–0.6 Ma). Călimani calc-alkaline parental magma compositions indicate a lithospheric mantle source metasomatised by ~ 2% sediment-derived melts, and are best reproduced by ~ 2–12% melting. Mafic K-alkaline melts in Southern Harghita originate from a melt- and fluid-metasomatised lithospheric mantle source containing amphibole (± phlogopite), by ~ 5% melting. Intraplate Na-alkaline basalts from Racoș (Perșani) reflect small-degree (1–2%) asthenosphere-derived parental melts which experienced minor interaction with metasomatic components in the lithosphere. An important feature of the East Carpathian post-collisional volcanism is that the lithospheric source regions are located in the lower plate (distal Europe-Moesia), rather than the overriding plate (Tisza-Dacia). The volcanism appears to have been caused by (1) asthenospheric uprise following slab sinking and possibly south-eastward propagating delamination and breakoff, which induced melting of the subduction-modified lithospheric mantle (Călimani to Southern Harghita); and (2) decompression melting as a consequence of minor asthenospheric upwelling (Perșani)

The effect of tranexamic acid on artificial joint materials : a biomechanical study (the bioTRANX study)

Background Tranexamic acid (TXA) has been successfully used to reduce bleeding in joint replacement. Recently local TXA has been advocated to reduce blood loss in total knee or hip replacement; however, this raised concerns about potential adverse effects of TXA upon the artificial joint replacement. Materials and methods In this biomechanical study we compared the effects of TXA and saline upon the following biomechanical properties of artificial joint materials—(1) tensile properties (ultimate strength, stiffness and Young’s modulus), (2) the wear rate using a multi-directional pin-on-plate machine, and (3) the surface topography of pins and plates before and after wear rate testing. Results There were no significant differences in tensile strength, wear rates or surface topography of either ultra-high-molecular-weight polyethylene pins or cobalt chromium molybdenum metal plates between specimens soaked in TXA and specimens soaked in saline. Conclusion Biomechanical testing shows that there are no biomechanical adverse affects on the properties of common artificial joint materials from using topical TXA. Level of evidence

Spring emergence of Canadian Delia radicum and synchronization with its natural enemy, Aleochara bilineata

To characterize time of spring emergence following post-diapause development, Delia radicum (L.) (Diptera: Anthomyiidae) from Saskatchewan, Manitoba, and southwestern Ontario were collected in fall, maintained over winter at 1 °C, then transferred to higher constant temperatures until adult emergence. At each location there were "early” and "late” phenotypes. Truncated normal models of temperature dependency of development rate were fitted for each phenotype from each location. We provide the first evidence of geographic variation in the criteria separating these phenotypes. Separation criteria and models for early and late phenotypes at the two prairie locations, approximately 700 km apart, were indistinguishable, but differed from those for Ontario. Prairie phenotypes developed more slowly than Ontario phenotypes, and more prairie individuals were of the late phenotype. Poor synchronization of spring emergence could impair predation of D. radicum eggs by adult Aleochara bilineata Gyllenhal (Coleoptera: Staphylinidae). Aleochara bilineata from Manitoba were reared and development rates modelled as for D. radicum. Models of development rates for the two species, when combined with simulated soil temperatures for two prairie locations, suggest that emergence of adult A. bilineata is well synchronized with availability of D. radicum eggs in prairie canol

Diffusion of impurities in a granular gas

Diffusion of impurities in a granular gas undergoing homogeneous cooling state is studied. The results are obtained by solving the Boltzmann--Lorentz equation by means of the Chapman--Enskog method. In the first order in the density gradient of impurities, the diffusion coefficient $D$ is determined as the solution of a linear integral equation which is approximately solved by making an expansion in Sonine polynomials. In this paper, we evaluate $D$ up to the second order in the Sonine expansion and get explicit expressions for $D$ in terms of the restitution coefficients for the impurity--gas and gas--gas collisions as well as the ratios of mass and particle sizes. To check the reliability of the Sonine polynomial solution, analytical results are compared with those obtained from numerical solutions of the Boltzmann equation by means of the direct simulation Monte Carlo (DSMC) method. In the simulations, the diffusion coefficient is measured via the mean square displacement of impurities. The comparison between theory and simulation shows in general an excellent agreement, except for the cases in which the gas particles are much heavier and/or much larger than impurities. In theses cases, the second Sonine approximation to $D$ improves significantly the qualitative predictions made from the first Sonine approximation. A discussion on the convergence of the Sonine polynomial expansion is also carried out.Comment: 9 figures. to appear in Phys. Rev.

A direct numerical simulation method for complex modulus of particle dispersions

We report an extension of the smoothed profile method (SPM)[Y. Nakayama, K. Kim, and R. Yamamoto, Eur. Phys. J. E {\bf 26}, 361(2008)], a direct numerical simulation method for calculating the complex modulus of the dispersion of particles, in which we introduce a temporally oscillatory external force into the system. The validity of the method was examined by evaluating the storage $G'(\omega)$ and loss $G"(\omega)$ moduli of a system composed of identical spherical particles dispersed in an incompressible Newtonian host fluid at volume fractions of $\Phi=0$, 0.41, and 0.51. The moduli were evaluated at several frequencies of shear flow; the shear flow used here has a zigzag profile, as is consistent with the usual periodic boundary conditions

Exploring the performance of the spectrometer prisma in heavy zirconium and xenon mass regions

We present results from two recent runs which illustrate the performance of the PRISMA spectrometer in the proximity of the upper limit of its operational interval, namely 96Zr + 124Sn at Elab = 500 MeV and 136Xe + 208Pb at Elab = 930 MeV. In the latter run, the γ array CLARA also allowed us to identify previously unknown γ transitions in the nuclides 136Cs and 134I

Synthesis of accelerograms compatible with the Chinese GB 50011-2001 design spectrum via harmonic wavelets: artificial and historic records

A versatile approach is employed to generate artificial accelerograms which satisfy the compatibility criteria prescribed by the Chinese aseismic code provisions GB 50011-2001. In particular, a frequency dependent peak factor derived by means of appropriate Monte Carlo analyses is introduced to relate the GB 50011-2001 design spectrum to a parametrically defined evolutionary power spectrum (EPS). Special attention is given to the definition of the frequency content of the EPS in order to accommodate the mathematical form of the aforementioned design spectrum. Further, a one-to-one relationship is established between the parameter controlling the time-varying intensity of the EPS and the effective strong ground motion duration. Subsequently, an efficient auto-regressive moving-average (ARMA) filtering technique is utilized to generate ensembles of non-stationary artificial accelerograms whose average response spectrum is in a close agreement with the considered design spectrum. Furthermore, a harmonic wavelet based iterative scheme is adopted to modify these artificial signals so that a close matching of the signals’ response spectra with the GB 50011-2001 design spectrum is achieved on an individual basis. This is also done for field recorded accelerograms pertaining to the May, 2008 Wenchuan seismic event. In the process, zero-phase high-pass filtering is performed to accomplish proper baseline correction of the acquired spectrum compatible artificial and field accelerograms. Numerical results are given in a tabulated format to expedite their use in practice

Grain boundary pinning and glassy dynamics in stripe phases

We study numerically and analytically the coarsening of stripe phases in two spatial dimensions, and show that transient configurations do not achieve long ranged orientational order but rather evolve into glassy configurations with very slow dynamics. In the absence of thermal fluctuations, defects such as grain boundaries become pinned in an effective periodic potential that is induced by the underlying periodicity of the stripe pattern itself. Pinning arises without quenched disorder from the non-adiabatic coupling between the slowly varying envelope of the order parameter around a defect, and its fast variation over the stripe wavelength. The characteristic size of ordered domains asymptotes to a finite value $R_g \sim \lambda_0\ \epsilon^{-1/2}\exp(|a|/\sqrt{\epsilon})$, where$\epsilon\ll 1$is the dimensionless distance away from threshold,$\lambda_0$the stripe wavelength, and$a$ a constant of order unity. Random fluctuations allow defect motion to resume until a new characteristic scale is reached, function of the intensity of the fluctuations. We finally discuss the relationship between defect pinning and the coarsening laws obtained in the intermediate time regime.Comment: 17 pages, 8 figures. Corrected version with one new figur

Measuring CMB Polarization with BOOMERANG

BOOMERANG is a balloon-borne telescope designed for long duration (LDB) flights around Antarctica. The second LDB Flight of BOOMERANG took place in January 2003. The primary goal of this flight was to measure the polarization of the CMB. The receiver uses polarization sensitive bolometers at 145 GHz. Polarizing grids provide polarization sensitivity at 245 and 345 GHz. We describe the BOOMERANG telescope noting changes made for 2003 LDB flight, and discuss some of the issues involved in the measurement of polarization with bolometers. Lastly, we report on the 2003 flight and provide an estimate of the expected results.Comment: 12 pages, 8 figures, To be published in the proceedings of "The Cosmic Microwave Background and its Polarization", New Astronomy Reviews, (eds. S. Hanany and K.A. Olive). Fixed typos, and reformatted citation