Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: chronic activation, normal selection

Autoimmune diseases show high diversity in the affected organs, clinical manifestations and disease dynamics. Yet they all share common features, such as the ectopic germinal centers found in many affected tissues. Lineage trees depict the diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. We previously developed an algorithm for quantifying the graphical properties of IGV gene lineage trees, allowing evaluation of the dynamical interplay between SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we apply this method to ectopic GC B cell clones from patients with Myasthenia Gravis, Rheumatoid Arthritis, and Sjögren’s Syndrome, using data scaling to minimize the effects of the large variability due to methodological differences between groups. Autoimmune trees were found to be significantly larger relative to normal controls. In contrast, comparison of the measurements for tree branching indicated that similar selection pressure operates on autoimmune and normal control clones

Plasmodium yoelii infection of BALB/c mice results in expansion rather than induction of CD4+ Foxp3+ regulatory T cells

Recently, we demonstrated elevated numbers of CD4(+) Foxp3(+) regulatory T (Treg) cells in Plasmodium yoelii‐infected mice contributing to the regulation of anti‐malarial immune response. However, it remains unclear whether this increase in Treg cells is due to thymus‐derived Treg cell expansion or induction of Treg cells in the periphery. Here, we show that the frequency of Foxp3(+) Treg cells expressing neuropilin‐1 (Nrp‐1) decreased at early time‐points during P. yoelii infection, whereas percentages of Helios(+) Foxp3(+) Treg cells remained unchanged. Both Foxp3(+) Nrp‐1(+) and Foxp3(+) Nrp‐1(−) Treg cells from P. yoelii‐infected mice exhibited a similar T‐cell receptor Vβ chain usage and methylation pattern in the Treg‐specific demethylation region within the foxp3 locus. Strikingly, we did not observe induction of Foxp3 expression in Foxp3(−) T cells adoptively transferred to P. yoelii‐infected mice. Hence, our results suggest that P. yoelii infection triggered expansion of naturally occurring Treg cells rather than de novo induction of Foxp3(+) Treg cells

Dense packings of spheres in cylinders: Simulations

We study the optimal packing of hard spheres in an infinitely long cylinder, using simulated annealing, and compare our results with the analogous problem of packing disks on the unrolled surface of a cylinder. The densest structures are described and tabulated in detail up to D/d=2.873 (ratio of cylinder and sphere diameters). This extends previous computations into the range of structures which include internal spheres that are not in contact with the cylinder.Comment: 18 pages, 14 figures, 1 table, to be submitted to PR

Shaped nozzles for cryogenic buffer gas beam sources

Cryogenic buffer gas beams are important sources of cold molecules. In this work we explore the use of a converging-diverging nozzle with a buffer-gas beam. We find that, under appropriate circumstances, the use of a nozzle can produce a beam with improved collimation, lower transverse temperatures, and higher fluxes per solid angle

Model-generated lexical activity predicts graded ERP amplitudes in lexical decision

Recent neurocognitive studies of visual word recognition provide information about neuronal networks correlated with processes involved in lexical access and their time course (e.g., [Holcomb, Ph.J., Grainger J. and O'Rourke, T. (2002). An Electrophysiological Study of the Effects of Orthographic Neighborhood Size on Printed Word Perception, J. of Cogn. Neurosci. 14 938–950; Binder, J.R., McKiernan, K.A., Parsons, M.E., Westbury, C.F., Possing, E.T., Kaufman, J.N. and Buchanan, L. (2003). Neural Correlates of Lexical Access during Visual Word Recognition, J. Cogn. Neurosci. 15 372–393.]). These studies relate the orthographic neighborhood density of letter strings to the amount of global lexical activity in the brain, generated by a hypothetical mental lexicon as speculated in an early paper by [Jacobs, A.M. and Carr, T.H. (1995). Mind mappers and cognitive modelers: Toward cross-fertilization, Behav. Brain. Sci. 18 362–363]. The present study uses model-generated stimuli theoretically eliciting graded global lexical activity and relates this activity to activation of lexical processing networks using event-related potentials (ERPs). The results from a lexical decision task provide evidence for an effect of lexicality around 350 ms post-stimulus and also a graded effect of global lexical activity for nonwords around 500 ms post-stimulus. The data are interpreted as reflecting two different decision processes: an identification process based on local lexical activity underlying the ‘yes’ response to words and a temporal deadline process underlying the ‘no’ response to nonwords based on global lexical activity

On the Prospects for Laser Cooling of TlF

We measure the upper state lifetime and two ratios of vibrational branching fractions f_{v'v} on the B^{3}\Pi_{1}(v') - X^{1}\Sigma^{+}(v) transition of TlF. We find the B state lifetime to be 99(9) ns. We also determine that the off-diagonal vibrational decays are highly suppressed: f_{01}/f_{00} < 2x10^{-4} and f_{02}/f_{00} = 1.10(6)%, in excellent agreement with their predicted values of f_{01}/f_{00} < 8x10^{-4} and f_{02}/f_{00} = 1.0(2)% based on Franck-Condon factors calculated using Morse and RKR potentials. The implications of these results for the possible laser cooling of TlF and fundamental symmetries experiments are discussed.Comment: 5 pages, 2 figure

Shear-Induced Stress Relaxation in a Two-Dimensional Wet Foam

We report on experimental measurements of the flow behavior of a wet, two-dimensional foam under conditions of slow, steady shear. The initial response of the foam is elastic. Above the yield strain, the foam begins to flow. The flow consists of irregular intervals of elastic stretch followed by sudden reductions of the stress, i.e. stress drops. We report on the distribution of the stress drops as a function of the applied shear rate. We also comment on our results in the context of various two-dimensional models of foams

Shot-noise-limited spin measurements in a pulsed molecular beam

Heavy diatomic molecules have been identified as good candidates for use in electron electric dipole moment (eEDM) searches. Suitable molecular species can be produced in pulsed beams, but with a total flux and/or temporal evolution that varies significantly from pulse to pulse. These variations can degrade the experimental sensitivity to changes in spin precession phase of an electri- cally polarized state, which is the observable of interest for an eEDM measurement. We present two methods for measurement of the phase that provide immunity to beam temporal variations, and make it possible to reach shot-noise-limited sensitivity. Each method employs rapid projection of the spin state onto both components of an orthonormal basis. We demonstrate both methods using the eEDM-sensitive H state of thorium monoxide (ThO), and use one of them to measure the magnetic moment of this state with increased accuracy relative to previous determinations.Comment: 12 pages, 6 figure