Analysis of B cell selection mechanisms in the adaptive immune response

The essential task of a germinal centre reaction is the selection of those B cells that bind the antigen with high affinity. The exact mechanisms of B cell selection is still unknown and rather difficult to be accessed in experiment. With the help of an already established agent-based model for the space-time-dynamics of germinal centre reactions [1,2] we compare the most important hypotheses for what the limiting factor for B cell rescue may be. We discuss competition for antigen sites on follicular dendritic cells, a refractory time for centrocytes after every encounter with follicular dendritic cells, competition for the antigen itself, the role of antigen masking with soluble antibodies, and competition for T cell help. The unexpected result is that neither competition for interaction sites nor competition for antigen nor antigen masking are in agreement with present experimental data on germinal centre reactions. We show that these most popular selection mechanisms do not lead to sufficient affinity maturation and do not respect the observed robustness against changes of initial conditions. However, the best agreement with data was found for the newly hypothesized centrocyte refractory time and for competition for T cell help. Thus the in silico experiments point towards selection mechanisms that are not in the main focus of current germinal centre research. Possible experiments to test these hypotheses are proposed

An analysis of B cell selection mechanisms in germinal centres

Affinity maturation of antibodies during immune responses is achieved by multiple rounds of somatic hypermutation and subsequent preferential selection of those B cells that express B cell receptors with improved binding characteristics for the antigen. The mechanism underlying B cell selection has not yet been defined. By employing an agent-based model, we show that for physiologically reasonable parameter values affinity maturation can be driven by competition for neither binding sites nor antigen—even in the presence of competing secreted antibodies. Within the tested mechanisms, only clonal competition for T cell help or a refractory time for the interaction of centrocytes with follicular dendritic cells is found to enable affinity maturation while generating the experimentally observed germinal centre characteristics and tolerating large variations in the initial antigen density

Real-Time Monitoring of Beam-Beam Modes at LEP

By slightly exciting one of two colliding bunches in LEP, it is possible to enhance the eigenfrequencies of the resonant system of the two bunches coupled by the space charge force. The LEP Qmeter has been adapted to detect, among these excited frequencies, the so called s- and p- modes, whose distance is proportional to the luminosity. A real time display of these quantities provides the Operators with an effective way of finely optimizing the luminosity

Classical and quantum dynamics of a spin-1/2

We reply to a comment on `Semiclassical dynamics of a spin-1/2 in an arbitrary magnetic field'.Comment: 4 pages, submitted to Journal of Physics

Electrodynamics of Media

Contains reports on two research projects.Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 28-043-AMC-02536(E)U. S. Air Force (ESD) Contract F19628-70-C-006

Quantum Brownian Motion With Large Friction

Quantum Brownian motion in the strong friction limit is studied based on the exact path integral formulation of dissipative systems. In this limit the time-nonlocal reduced dynamics can be cast into an effective equation of motion, the quantum Smoluchowski equation. For strongly condensed phase environments it plays a similar role as master equations in the weak coupling range. Applications for chemical, mesoscopic, and soft matter systems are discussed and reveal the substantial role of quantum fluctuations.Comment: 11 pages, 6 figures, to appear in: Chaos: "100 years of Brownian motion

Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

Geometric diagnostics of complex patterns: Spiral defect chaos

Motivated by the observation of spiral patterns in a wide range of physical, chemical, and biological systems, we present an automated approach that aims at characterizing quantitatively spiral-like elements in complex stripelike patterns. The approach provides the location of the spiral tip and the size of the spiral arms in terms of their arc length and their winding number. In addition, it yields the number of pattern components (Betti number of order 1), as well as their size and certain aspects of their shape. We apply the method to spiral defect chaos in thermally driven Rayleigh- Bénard convection and find that the arc length of spirals decreases monotonically with decreasing Prandtl number of the fluid and increasing heating. By contrast, the winding number of the spirals is nonmonotonic in the heating. The distribution function for the number of spirals is significantly narrower than a Poisson distribution. The distribution function for the winding number shows approximately an exponential decay. It depends only weakly on the heating, but strongly on the Prandtl number. Large spirals arise only for larger Prandtl numbers. In this regime the joint distribution for the spiral length and the winding number exhibits a three-peak structure, indicating the dominance of Archimedean spirals of opposite sign and relatively straight sections. For small Prandtl numbers the distribution function reveals a large number of small compact pattern components

Thermodynamics of phantom black holes in Einstein-Maxwell-Dilaton theory

A thermodynamic analysis of the black hole solutions coming from the Einstein-Maxwell-Dilaton theory (EMD) in 4D is done. By consider the canonical and grand-canonical ensemble, we apply standard method as well as a recent method known as Geometrothermodynamics (GTD). We are particularly interested in the characteristics of the so called phantom black hole solutions. We will analyze the thermodynamics of these solutions, the points of phase transition and their extremal limit. Also the thermodynamic stability is analyzed. We obtain a mismatch of the between the results of the GTD method when compared with the ones obtained by the specific heat, revealing a weakness of the method, as well as possible limitations of its applicability to very pathological thermodynamic systems. We also found that normal and phantom solutions are locally and globally unstable, unless for certain values of the coupled constant of the EMD action. We also shown that the anti-Reissner-Nordstrom solution does not posses extremal limit nor phase transition points, contrary to the Reissner-Nordstrom case.Comment: 23 pages, version accepted for publication in Physical Review