Analysis and prediction of VH/VL packing in antibodies

The packing of VH and VL domains in antibodies can vary, influencing the topography of the antigen-combining site. However, until recently, this has largely been ignored in modelling antibody structure. We present an analysis of the degree of variability observed in known structures together with a machine-learning approach to predict the packing angle. A neural network was trained on sets of interface residues and a genetic algorithm designed to perform ‘feature selection' to define which sets of interface residues could be used most successfully to perform the prediction. While this training procedure was very computationally intensive, prediction is performed in a matter of seconds. Thus, not only do we provide a rapid method for predicting the packing angle, but also we define a set of residues that may be important in antibody humanization in order to obtain the correct binding site topograph

Cosmological Perturbations in a Big Crunch/Big Bang Space-time

A prescription is developed for matching general relativistic perturbations across singularities of the type encountered in the ekpyrotic and cyclic scenarios i.e. a collision between orbifold planes. We show that there exists a gauge in which the evolution of perturbations is locally identical to that in a model space-time (compactified Milne mod Z_2) where the matching of modes across the singularity can be treated using a prescription previously introduced by two of us. Using this approach, we show that long wavelength, scale-invariant, growing-mode perturbations in the incoming state pass through the collision and become scale-invariant growing-mode perturbations in the expanding hot big bang phase.Comment: 47 pages, 4 figure

abYsis: Integrated Antibody Sequence and Structure-Management, Analysis, and Prediction

abYsis is a web-based antibody research system that includes an integrated database of antibody sequence and structure data. The system can be interrogated in numerous ways-from simple text and sequence searches to sophisticated queries that apply 3D structural constraints. The publicly available version includes pre-analyzed sequence data from the European Molecular Biology Laboratory European Nucleotide Archive (EMBL-ENA) and Kabat as well as structure data from the Protein Data Bank. A researcher's own sequences can also be analyzed through the web interface. A defining characteristic of abYsis is that the sequences are automatically numbered with a series of popular schemes such as Kabat and Chothia and then annotated with key information such as complementarity-determining regions and potential post-translational modifications. A unique aspect of abYsis is a set of residue frequency tables for each position in an antibody, allowing "unusual residues" (those rarely seen at a particular position) to be highlighted and decisions to be made on which mutations may be acceptable. This is especially useful when comparing antibodies from different species. abYsis is useful for any researcher specializing in antibody engineering, especially those developing antibodies as drugs. abYsis is available at www.abysis.org

Search for Higgs Bosons in e+e- Collisions at 183 GeV

The data collected by the OPAL experiment at sqrts=183 GeV were used to search for Higgs bosons which are predicted by the Standard Model and various extensions, such as general models with two Higgs field doublets and the Minimal Supersymmetric Standard Model (MSSM). The data correspond to an integrated luminosity of approximately 54pb-1. None of the searches for neutral and charged Higgs bosons have revealed an excess of events beyond the expected background. This negative outcome, in combination with similar results from searches at lower energies, leads to new limits for the Higgs boson masses and other model parameters. In particular, the 95% confidence level lower limit for the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA > 72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European Physical Journal

A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays

The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL detector at LEP. Lambda_b are selected by the presence of energetic Lambda particles in bottom events tagged by the presence of displaced secondary vertices. A fit to the momenta of the Lambda particles separates signal from B meson and fragmentation backgrounds. The measured product branching ratio is f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))% Combined with a previous OPAL measurement, one obtains f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European Physical Journal

Measurement of the Michel Parameters in Leptonic Tau Decays

The Michel parameters of the leptonic tau decays are measured using the OPAL detector at LEP. The Michel parameters are extracted from the energy spectra of the charged decay leptons and from their energy-energy correlations. A new method involving a global likelihood fit of Monte Carlo generated events with complete detector simulation and background treatment has been applied to the data recorded at center-of-mass energies close to sqrt(s) = M(Z) corresponding to an integrated luminosity of 155 pb-1 during the years 1990 to 1995. If e-mu universality is assumed and inferring the tau polarization from neutral current data, the measured Michel parameters are extracted. Limits on non-standard coupling constants and on the masses of new gauge bosons are obtained. The results are in agreement with the V-A prediction of the Standard Model.Comment: 32 pages, LaTeX, 9 eps figures included, submitted to the European Physical Journal

Molecular Characterization of a Novel Intracellular ADP-Ribosyl Cyclase

Background. ADP-ribosyl cyclases are remarkable enzymes capable of catalyzing multiple reactions including the synthesis of the novel and potent intracellular calcium mobilizing messengers, cyclic ADP-ribose and NAADP. Not all ADP-ribosyl cyclases however have been characterized at the molecular level. Moreover, those that have are located predominately at the outer cell surface and thus away from their cytosolic substrates. Methodology/Principal Findings. Here we report the molecular cloning of a novel expanded family of ADP-ribosyl cyclases from the sea urchin, an extensively used model organism for the study of inositol trisphosphate-independent calcium mobilization. We provide evidence that one of the isoforms (SpARC1) is a soluble protein that is targeted exclusively to the endoplasmic reticulum lumen when heterologously expressed. Catalytic activity of the recombinant protein was readily demonstrable in crude cell homogenates, even under conditions where luminal continuity was maintained. Conclusions/Significance. Our data reveal a new intracellular location for ADP-ribosyl cyclases and suggest that production of calcium mobilizing messengers may be compartmentalized

A Study of One-Prong Tau Decays with a Charged Kaon

From an analysis of the ionisation energy loss of charged particles selected from 110326 e+e- -> tau+tau- candidates recorded by the OPAL detector at e+e- centre-of-mass energies near the Z0 resonance, we determine the one-prong tau decay branching ratios: Br(tau- -> nu_tau K- >=0h0) = 1.528 +- 0.039 +- 0.040 % Br(tau- -> nu_tau K-) = 0.658 +- 0.024 +- 0.029 % where the h0 notation refers to a pi0, an eta, a K^0_S, or a K^0_L, and where the first uncertainty is statistical and the second is systematic.From an analysis of the ionisation energy loss of charged particles selected from 110326 e+e- -> tau+tau- candidates recorded by the OPAL detector at e+e- centre-of-mass energies near the Z0 resonance, we determine the one-prong tau decay branching ratios: Br(tau- -> nu_tau K- >=0h0) = 1.528 +- 0.039 +- 0.040 % Br(tau- -> nu_tau K-) = 0.658 +- 0.024 +- 0.029 % where the h0 notation refers to a pi0, an eta, a K^0_S, or a K^0_L, and where the first uncertainty is statistical and the second is systematic

Multiplicities of π0\pi^{0}, η\eta, K0K^{0} and of charged particles in quark and gluon jets

We compared the multiplicities of pizero, eta, Kzero and of charged particles in quark and gluon jets in 3-jet events, as measured by the OPAL experiment at LEP. The comparisons were performed for distributions unfolded to 100% pure quark and gluon jets, at an effective scale Qjet which took into account topological dependences of the 3-jet environment. The ratio of particle multiplicity in gluon jets to that in quark jets as a function of Qjet for pizero, eta and Kzero was found to be independent of the particle species. This is consistent with the QCD prediction that the observed enhancement in the mean particle rate in gluon jets with respect to quark jets should be independent of particle species. In contrast to some theoretical predictions and previous observations, we observed no evidence for an enhancement of eta meson production in gluon jets with respect to quark jets, beyond that observed for charged particles. We measured the ratio of the slope of the average charged particle multiplicity in gluon jets to that in quark jets, C, and we compared it to a next-to-next-to-next-to leading order calculation. Our result, C=2.27+-0.20(stat+syst),is about one standard deviation higher than the perturbative prediction.We compared the multiplicities of pizero, eta, Kzero and of charged particles in quark and gluon jets in 3-jet events, as measured by the OPAL experiment at LEP. The comparisons were performed for distributions unfolded to 100% pure quark and gluon jets, at an effective scale Qjet which took into account topological dependences of the 3-jet environment. The ratio of particle multiplicity in gluon jets to that in quark jets as a function of Qjet for pizero, eta and Kzero was found to be independent of the particle species. This is consistent with the QCD prediction that the observed enhancement in the mean particle rate in gluon jets with respect to quark jets should be independent of particle species. In contrast to some theoretical predictions and previous observations, we observed no evidence for an enhancement of eta meson production in gluon jets with respect to quark jets, beyond that observed for charged particles. We measured the ratio of the slope of the average charged particle multiplicity in gluon jets to that in quark jets, C, and we compared it to a next-to-next-to-next-to leading order calculation. Our result, C=2.27+-0.20(stat+syst),is about one standard deviation higher than the perturbative prediction