Analysis of the time to sustained progression in Multiple Sclerosis using generalised linear and additive models

The course of multiple sclerosis (MS) is generally difficult to predict. This is due to the great inter-individual variability with respect to symptoms and disability status. An important prognostic endpoint for MS is the expected time to sustained disease progression. Using the Expanded Disability Status Scale (EDSS) this endpoint is here defined as a rise of 1.0 or 0.5 compared to baseline EDSS (5.5) which is confirmed for at least six months. The goal of this paper was threefold. It aimed at identifying covariates which significantly influence sustained progression, determining size and form of the effect of these covariates and estimating the survival curves for given predictors. To this end a piecewise exponential model utilizing piecewise constant hazard rates and a Poisson model were devised. In order to improve and simplify these models a method for piecewise linear parameterization of non-parametric generalized additive models (GAMs) was applied. The models included fixed and random effects, the posterior distribution was estimated using Markov Chain Monte Carlo methods (MCMC) as well as a penalized likelihood approach and variables were selected using Akaikes information criterium (AIC). The models were applied to data of placebo patients from worldwide clinical trials that are pooled in the database of the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR). Only with a pure exponential model and fixed effects, baseline EDSS and the number of relapses in the last 12 month before study entry had an effect on the hazard rate. For the piecewise exponential model with random study effects there was no effect of covariates on the hazard rate other than a slightly decreasing effect of time. This reflects the fact that unstable patients reach the event early and are therefore eliminated from the analysis (selection effect)

Two-Loop QCD Corrections to the Heavy-to-Light Quark Decay

We present an analytic expression for the two-loop QCD corrections to the decay process b -> u W^*, where b and u are a massive and massless quark, respectively, while W^* is an off-shell charged weak boson. Since the W-boson can subsequently decay in a lepton anti-neutrino pair, the results of this paper are a first step towards a fully analytic computation of differential distributions for the semileptonic decay of a b-quark. The latter partonic process plays a crucial role in the study of inclusive semileptonic charmless decays of B-mesons. The three independent form factors characterizing the b W u vertex are provided in form of a Laurent series in (d-4), where d is the space-time dimension. The coefficients in the series are expressed in terms of Harmonic Polylogarithms of maximal weight 4, and are functions of the invariant mass of the leptonic decay products of the W-boson.Comment: 27 pages, 3 figures, References added, version published on JHE

Master integrals with 2 and 3 massive propagators for the 2-loop electroweak form factor - planar case

We compute the master integrals containing 2 and 3 massive propagators entering the planar amplitudes of the 2-loop electroweak form factor. The masses of the $W$, $Z$ and Higgs bosons are assumed to be degenerate. This work is a continuation of our previous evaluation of master integrals containing at most 1 massive propagator. The 1/\epsilon poles and the finite parts are computed exactly in terms of a {\it new} class of 1-dimensional harmonic polylogarithms of the variable x, with \epsilon=2-D/2 and D the pace-time dimension. Since thresholds and pseudothresholds in s=\pm 4m^2 do appear in addition to the old ones in s=0,\pm m^2, an extension of the basis function set involving complex constants and radicals is introduced, together with a set of recursion equations to reduce integrals with semi-integer powers. It is shown that the basic properties of the harmonic polylogarithms are maintained by the generalization. We derive small-momentum expansions |s| << m^2 of all the 6-denominator amplitudes. We also present large momentum expansions |s| >> m^2 of all the 6-denominator amplitudes which can be represented in terms of ordinary harmonic polylogarithms. Comparison with previous results in the literature is performed finding complete agreement.Comment: 68 pages, 7 figure

Boolean versus continuous dynamics on simple two-gene modules

We investigate the dynamical behavior of simple modules composed of two genes with two or three regulating connections. Continuous dynamics for mRNA and protein concentrations is compared to a Boolean model for gene activity. Using a generalized method, we study within a single framework different continuous models and different types of regulatory functions, and establish conditions under which the system can display stable oscillations. These conditions concern the time scales, the degree of cooperativity of the regulating interactions, and the signs of the interactions. Not all models that show oscillations under Boolean dynamics can have oscillations under continuous dynamics, and vice versa.Comment: 8 pages, 10 figure

The infrared structure of e+ e- --> 3 jets at NNLO reloaded

This paper gives detailed information on the structure of the infrared singularities for the process e+ e- --> 3 jets at next-to-next-to-leading order in perturbation theory. Particular emphasis is put on singularities associated to soft gluons. The knowledge of the singularity structure allows the construction of appropriate subtraction terms, which in turn can be implemented into a numerical Monte Carlo program.Comment: 59 pages, additional comments added, version to be publishe

Report of the 2005 Snowmass Top/QCD Working Group

This report discusses several topics in both top quark physics and QCD at an International Linear Collider (ILC). Issues such as measurements at the $t\bar{t}$ threshold, including both theoretical and machine requirements, and the determination of electroweak top quark couplings, are reviewed. New results concerning the potential of a 500 GeV $e^+e^-$ collider for measuring $Wtb$ couplings and the top quark Yukawa coupling are presented. The status of higher order QCD corrections to jet production cross sections, heavy quark form factors, and longitudinal gauge boson scattering, needed for percent-level studies at the ILC, are reviewed. A new study of the measurement of the hadronic structure of the photon at a $\gamma\gamma$ collider is presented. The effects on top quark properties from several models of new physics, including composite models, Little Higgs theories, and CPT violation, are studied.Comment: 39 pages, many figs; typos fixed and refs added. Contributed to the 2005 International Linear Collider Physics and Detector Workshop and 2nd ILC Accelerator Workshop, Snowmass, Colorado, 14-27 Aug 200

Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B

Background: We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner

Hopf algebras, coproducts and symbols: an application to Higgs boson amplitudes

We show how the Hopf algebra structure of multiple polylogarithms can be used to simplify complicated expressions for multi-loop amplitudes in perturbative quantum field theory and we argue that, unlike the recently popularized symbol-based approach, the coproduct incorporates information about the zeta values. We illustrate our approach by rewriting the two-loop helicity amplitudes for a Higgs boson plus three gluons in a simplified and compact form involving only classical polylogarithms.Comment: 46 page

Precision Calculations for Future Colliders

I discuss the motivations for, and the status of, precision calculations for the Large Hadron Collider (LHC) and the planned International Linear Collider (ILC).Comment: latex, uses ws-ijmpe.cls, 19 pages, 9 figures, 1 table, based on a talk given at the symposium "50 Years of High Energy Physics at UB", to appear in International Journal of Modern Physics

The Two Loop Crossed Ladder Vertex Diagram with Two Massive Exchanges

We compute the (three) master integrals for the crossed ladder diagram with two exchanged quanta of equal mass. The differential equations obeyed by the master integrals are used to generate power series expansions centered around all the singular (plus some regular) points, which are then matched numerically with high accuracy. The expansions allow a fast and precise numerical calculation of the three master integrals (better than 15 digits with less than 30 terms in the whole real axis). A conspicuous relation with the equal-mass sunrise in two dimensions is found. Comparison with a previous large momentum expansion is made finding complete agreement.Comment: 42 pages, 1 figur