Clonal analysis of a human antibody response. Quantitation of precursors of antibody-producing cells and generation and characterization of monoclonal IgM, IgG, and IgA to rabies virus.

We quantitated and characterized the changes in the human B cell repertoire, at the clonal level, before and after immunization with rabies virus. Moreover, we generated 10 monoclonal cell lines producing IgM, IgG, and IgA antibodies to the virus. We found that in healthy subjects, not previously exposed to the virus, nearly 2% of the circulating B lymphocytes were committed to the production of antibodies that bound the virus. These B cells expressed the surface CD5 molecule. The antibodies they produced were polyreactive IgM that displayed a relatively low affinity for the virus components (Kd, 1.0-2.4 x 10(-6) g/microliters). After immunization, different anti-virus (IgG and IgA) antibody-producing cells consistently appeared in the circulation and increased from less than 0.005% to greater than 10% of the total B cells committed to the production of IgG and IgA, respectively. Most of such B cells do not express CD5 and produce monoreactive antibodies of high affinity for rabies virus (Kd, 6.5 x 10(-9) to 1.2 x 10(-10) g/microliters). One of these IgG mAbs efficiently neutralized rabies virus in vitro and in vivo, as detailed elsewhere (Dietzschold, B., P. Casali, Y. Ueki, M. Gore, C. E. Rupprecht, A. L. Notkins, and H. Koprowski, manuscript submitted for publication). Hybridization experiments using probes specific for the different human V gene segment families revealed that cell precursors producing low affinity IgM binding to rabies virus utilized a restricted number of VH gene segments (i.e., only members of the VHIIIb subfamily), whereas cell precursors producing high affinity IgG and IgA to rabies virus utilized an assortment of different VH gene segments (i.e., members of the VHI, VHIII, VHIV, and VHVI families and VHIIIb subfamily). In conclusion, our studies show that EBV transformation in conjunction with limiting dilution technology and somatic cell hybridization techniques are useful methods for quantitating, at the B cell clonal level, the human antibody response to foreign Ags and for generating human mAbs of predetermined specificity and high affinity

Low lying spectrum of weak-disorder quantum waveguides

We study the low-lying spectrum of the Dirichlet Laplace operator on a randomly wiggled strip. More precisely, our results are formulated in terms of the eigenvalues of finite segment approximations of the infinite waveguide. Under appropriate weak-disorder assumptions we obtain deterministic and probabilistic bounds on the position of the lowest eigenvalue. A Combes-Thomas argument allows us to obtain so-called 'initial length scale decay estimates' at they are used in the proof of spectral localization using the multiscale analysis.Comment: Accepted for publication in Journal of Statistical Physics http://www.springerlink.com/content/0022-471

Existence and uniqueness of the integrated density of states for Schr\"odinger operators with magnetic fields and unbounded random potentials

The object of the present study is the integrated density of states of a quantum particle in multi-dimensional Euclidean space which is characterized by a Schr\"odinger operator with a constant magnetic field and a random potential which may be unbounded from above and from below. For an ergodic random potential satisfying a simple moment condition, we give a detailed proof that the infinite-volume limits of spatial eigenvalue concentrations of finite-volume operators with different boundary conditions exist almost surely. Since all these limits are shown to coincide with the expectation of the trace of the spatially localized spectral family of the infinite-volume operator, the integrated density of states is almost surely non-random and independent of the chosen boundary condition. Our proof of the independence of the boundary condition builds on and generalizes certain results by S. Doi, A. Iwatsuka and T. Mine [Math. Z. {\bf 237} (2001) 335-371] and S. Nakamura [J. Funct. Anal. {\bf 173} (2001) 136-152].Comment: This paper is a revised version of the first part of the first version of math-ph/0010013. For a revised version of the second part, see math-ph/0105046. To appear in Reviews in Mathematical Physic

Simplified stress analysis on the temporomandibular joint in Class III patients with and without mandibular asymmetry using a rigid body spring model

金沢大学医薬保健研究域医学系To cite this article: Ueki K, Takeuchi N, Nakagawa K, Yamamoto E: Simplified stress analysis on the temporomandibular joint in Class III patients with and without mandibular asymmetry using a rigid body spring model Orthod Craniofac Res 2009;12:312-318 Structured AbstractAuthors - Ueki K, Takeuchi N, Nakagawa K, Yamamoto E Objective - Aim of this study was to investigate the differences in stress on the temporomandibular joint (TMJ) between Class III patients with and without mandibular asymmetry using a rigid body spring model (RBSM). Design - Menton (Me), the centre point of occlusal force on the line that connected the bilateral buccal cusps of the second molars and the most lateral, superior and medial points of the condyle were plotted on frontal cephalograms, and stress on the condyles was calculated with the 2-dimensional RBSM program of fortran. Setting and Sample Population - Eighty Japanese patients with diagnosed mandibular prognathism were divided into two groups, a symmetry group and asymmetry group on the basis of the Mx-Md midline position. Outcome measure - The degree (force partition) of the resultant force, the direction (angulation) and displacement (X, Y) of each condyle were calculated. The horizontal displacement vector (u), the vertical displacement vector (v) and rotation angle (θ) of the mandibular body at Menton were also calculated. Results - There were significant differences between the deviated and non-deviated sides of both groups regarding resultant force (symmetry group: p = 0.0372, asymmetry group: p = 0.0054), X (symmetry group: p < 0.0001, asymmetry group: p = 0.0001) and Y (symmetry group: p = 0.0354, asymmetry group: p = 0.0043). For angulation, there was a significant difference between the deviated and non-deviated sides in the asymmetry group (p = 0.0095). Conclusion - The results of this study suggest that difference in stress angulation on the condyles could be associated with asymmetry in mandibular prognathism. © 2009 John Wiley & Sons A/S

Gene Silencing of Phogrin Unveils Its Essential Role in Glucose-Responsive Pancreatic β-Cell Growth

OBJECTIVE—Phogrin and IA-2, autoantigens in insulin-dependent diabetes, have been shown to be involved in insulin secretion in pancreatic β-cells; however, implications at a molecular level are confusing from experiment to experiment. We analyzed biological functions of phogrin in β-cells by an RNA interference technique

Wegner estimate for discrete alloy-type models

We study discrete alloy-type random Schr\"odinger operators on $\ell^2(\mathbb{Z}^d)$. Wegner estimates are bounds on the average number of eigenvalues in an energy interval of finite box restrictions of these types of operators. If the single site potential is compactly supported and the distribution of the coupling constant is of bounded variation a Wegner estimate holds. The bound is polynomial in the volume of the box and thus applicable as an ingredient for a localisation proof via multiscale analysis.Comment: Accepted for publication in AHP. For an earlier version see http://www.ma.utexas.edu/mp_arc-bin/mpa?yn=09-10

A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment.

The recruitment of substrates by the ser/thr protein phosphatase 2A (PP2A) is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, was identified. However, most validated LxxIxE motifs bind PP2A:B56 with micromolar affinities, suggesting that additional motifs exist to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors, including KIF4A, to facilitate B56 binding via dynamic, electrostatic interactions. Using molecular and cellular experiments, we show that a conserved, negatively charged groove on B56 mediates dynamic binding. We also discovered that this positively charged motif, in addition to facilitating KIF4A dephosphorylation, is essential for condensin I binding, a function distinct and exclusive from PP2A-B56 binding. Together, these results reveal how dynamic, charge-charge interactions fine-tune the interactions mediated by specific motifs, providing a new framework for understanding how PP2A regulation drives cellular signaling