Likelihood-based inference of B-cell clonal families

The human immune system depends on a highly diverse collection of antibody-making B cells. B cell receptor sequence diversity is generated by a random recombination process called "rearrangement" forming progenitor B cells, then a Darwinian process of lineage diversification and selection called "affinity maturation." The resulting receptors can be sequenced in high throughput for research and diagnostics. Such a collection of sequences contains a mixture of various lineages, each of which may be quite numerous, or may consist of only a single member. As a step to understanding the process and result of this diversification, one may wish to reconstruct lineage membership, i.e. to cluster sampled sequences according to which came from the same rearrangement events. We call this clustering problem "clonal family inference." In this paper we describe and validate a likelihood-based framework for clonal family inference based on a multi-hidden Markov Model (multi-HMM) framework for B cell receptor sequences. We describe an agglomerative algorithm to find a maximum likelihood clustering, two approximate algorithms with various trade-offs of speed versus accuracy, and a third, fast algorithm for finding specific lineages. We show that under simulation these algorithms greatly improve upon existing clonal family inference methods, and that they also give significantly different clusters than previous methods when applied to two real data sets

String Breaking in Four Dimensional Lattice QCD

Virtual quark pair screening leads to breaking of the string between fundamental representation quarks in QCD. For unquenched four dimensional lattice QCD, this (so far elusive) phenomenon is studied using the recently developed truncated determinant algorithm (TDA). The dynamical configurations were generated on an Athlon 650 MHz PC. Quark eigenmodes up to 420 MeV are included exactly in these TDA studies performed at low quark mass on large coarse (but O($a^2$) improved) lattices. A study of Wilson line correlators in Coulomb gauge extracted from an ensemble of 1000 two-flavor dynamical configurations reveals evidence for flattening of the string tension at distances R $\geq$ approximately 1 fm.Comment: 16 pages, 5 figures, Latex (deleted extraneous eps figure file

Improved Pseudofermion Approach for All-Point Propagators

Quark propagators with arbitrary sources and sinks can be obtained more efficiently using a pseudofermion method with a mode-shifted action. Mode-shifting solves the problem of critical slowing down (for light quarks) induced by low eigenmodes of the Dirac operator. The method allows the full physical content of every gauge configuration to be extracted, and should be especially helpful for unquenched QCD calculations. The method can be applied for all the conventional quark actions: Wilson, Sheikoleslami-Wohlert, Kogut-Susskind, as well as Ginsparg-Wilson compliant overlap actions. The statistical properties of the method are examined and examples of physical processes under study are presented.Comment: LateX, 26 pages, 10 eps figure

A Damping of the de Haas-van Alphen Oscillations in the superconducting state

Deploying a recently developed semiclassical theory of quasiparticles in the superconducting state we study the de Haas-van Alphen effect. We find that the oscillations have the same frequency as in the normal state but their amplitude is reduced. We find an analytic formulae for this damping which is due to tunnelling between semiclassical quasiparticle orbits comprising both particle-like and hole-like segments. The quantitative predictions of the theory are consistent with the available data.Comment: 7 pages, 5 figure

Direct administration of 2-hydroxypropyl-beta-cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements

<p>Cochlear response measurements from two different animals made before (red) and after (blue) treatment with HPβCD (Panel A) and TTX (Panel B) to 80 dB SPL 4 kHz tone bursts. Cochlear response waveform maintained CAP-like morphology after HPβCD treatment, consistent with reduced mechanical drive to neural excitation (Panel B, blue). In contrast, response waveform is EPSP-like following TTX treatment. Unlike TTX, results from HPβCD do not support the hypothesis that the auditory nerve is a site of action for 13 mM HPβCD.</p

The FADE mass-stat:A technique for inserting or deleting particles in molecular dynamics simulations

The emergence of new applications of molecular dynamics (MD) simulation calls for the development of mass-statting procedures that insert or delete particles on-the-fly. In this paper we present a new mass-stat which we term FADE, because it gradually “fades-in” (inserts) or “fades-out” (deletes) molecules over a short relaxation period within a MD simulation. FADE applies a time-weighted relaxation to the intermolecular pair forces between the inserting/deleting molecule and any neighbouring molecules. The weighting function we propose in this paper is a piece-wise polynomial that can be described entirely by two parameters: the relaxation time scale and the order of the polynomial. FADE inherently conserves overall system momentum independent of the form of the weighting function. We demonstrate various simulations of insertions of atomic argon, polyatomic TIP4P water, polymer strands, and C60 Buckminsterfullerene molecules. We propose FADE parameters and a maximum density variation per insertion-instance that restricts spurious potential energy changes entering the system within desired tolerances. We also demonstrate in this paper that FADE compares very well to an existing insertion algorithm called USHER, in terms of accuracy, insertion rate (in dense fluids), and computational efficiency. The USHER algorithm is applicable to monatomic and water molecules only, but we demonstrate that FADE can be generally applied to various forms and sizes of molecules, such as polymeric molecules of long aspect ratio, and spherical carbon fullerenes with hollow interiors

Unquenched QCD with Light Quarks

We present recent results in unquenched lattice QCD with two degenerate light sea quarks using the truncated determinant approximation (TDA). In the TDA the infrared modes contributing to the quark determinant are computed exactly up to some cutoff in quark off-shellness (typically 2$\Lambda_{QCD}$). This approach allows simulations to be performed at much lighter quark masses than possible with conventional hybrid MonteCarlo techniques. Results for the static energy and topological charge distributions are presented using a large ensemble generated on very coarse (6$^4$) but physically large lattices. Preliminary results are also reported for the static energy and meson spectrum on 10$^3$x20 lattices (lattice scale $a^{-1}$=1.15 GeV) at quark masses corresponding to pions of mass $\leq$ 200 MeV. Using multiboson simulation to compute the ultraviolet part of the quark determinant the TDA approach becomes an exact with essentially no increase in computational effort. Some preliminary results using this fully unquenched algorithm are presented.Comment: LateX, 39 pages, 16 eps figures, 1 ps figur

No Shortcuts to Progress: An Assessment of Agricultural Research Planning and Priority Setting in Africa

Research and Development/Tech Change/Emerging Technologies, Downloads July 2008-June 2009: 7,

EEG–fMRI of idiopathic and secondarily generalized epilepsies

We used simultaneous EEG and functional MRI (EEG–fMRI) to study generalized spike wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE). Recent studies have demonstrated thalamic and cortical fMRI signal changes in association with GSW in idiopathic generalized epilepsy (IGE). We report on a large cohort of patients that included both IGE and SGE, and give a functional interpretation of our findings. Forty-six patients with GSW were studied with EEG–fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in 25 of 36 individual patients who had GSW during EEG–fMRI. This was seen in thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%), and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were predominantly positive and cortical changes predominantly negative. Group analysis showed a negative BOLD response in the cortex in the IGE group and to a lesser extent a positive response in thalamus. Thalamic activation was consistent with its known role in GSW, and its detection in individual cases with EEG–fMRI may in part be related to the number and duration of GSW epochs recorded. The spatial distribution of the cortical fMRI response to GSW in both IGE and SGE involved areas of association cortex that are most active during conscious rest. Reduction of activity in these regions during GSW is consistent with the clinical manifestation of absence seizures