The expression and signalling patterns of CD180 toll like receptor in Chronic Lymphocytic Leukaemia (CLL)

Chronic lymphocytic leukaemia (CLL) is characterised by a progressive accumulation of mature CD5+CD20+CD23+ lymphocytes. Despite the remarkable progress in our understanding of the immunobiology of CLL, the aetiology of the disease remains unknown. The consensus is that CLL cells are driven by (auto)antigen(s) through the B cell receptor (BCR) and are regulated by a variety of signals received from the microenvironment, including toll-like receptors (TLR).Our group has previously shown that engagement of the CD180 orphan TLR expressed by approximately 60% of CLL cells, can re-wire the sIgM-mediated signalling from a pro-survival pathway, involving phosphatidylinositol-4,5-bisphosphate3-kinase (PI3K) and protein kinase B (AKT) to the potentially pro-apoptotic pathway through mitogen-activated protein kinase (p38MAPK). However, little is known about the function of the other BCR - sIgD in CLL and its possible interaction with CD180. Here we studied intracellular signalling and apoptosis of CLL cells following sole or sequential ligation of CD180 and sIgD. Our data indicated that following sequential ligation of CD180 and sIgD, CLL samples demonstrated enhanced p38MAPK phosphorylation leading to increased apoptosis of CLL cells indicating synergistic relationship between CD180 and sIgD. To better understand the prognostic importance of CD180 expression we sought to determine whether CD180 and other prognostic markers such as CD38 and ZAP70 displayed any correlation with the known cytogenetic aberrations:TP53 and DLEU1. Our results suggested that CLL cells with DLEU1 deletion are characterised by the negative expression of both, CD180 and CD38, and this might have a significance for CLL prognosis. To explain this correlation, we hypothesised that interaction of CLL cells with their microenvironment through TLRs leads to the expansion of leukaemic clones, in vivo, in lymph nodes. Our results indicated that CD180 is heterogeneously expressed in the paraffin tissue sections of the lymph nodes of CLL patients and its expression positively correlates with the expression of Ki-67. Our data demonstrated, that although CD180 expression and signaling might have negative prognostic importance in CLL due to the enhanced proliferation of leukaemic cells, its interaction with sIgD would re-direct leukaemic cells towards apoptosis thus opening new opportunities for the disease immunotherapy

Unregulated Desires: Anomie, the “Rainbow Underclass” and Second-generation Alevi Kurdish Gangs in London

This article offers a case study of the adaptation strategies of a section of second-generation young male Alevi Kurds in London and the social conditions which make some of them more prone to join gangs and to reject mainstream institutions in their search for instant material rewards. It is instructive to use Durkheim’s analysis of society’s integrative and regulative functions and particularly his concept of anomie to understand a situation where the legitimate means in the pursuit of material wealth and comfort are out of balance with the demand, calling into question the legitimacy of the institutions which provide these functions. Those who cannot compete through existing institutions are more likely to seek alternative means to achieve these ends. Durkheim identified youth as more vulnerable to such unregulated desires and I argue that his approach offers valuable insights into the anomic pressures confronting second-generation migrant young men in particular

Microscopic theory of absorption and emission in nanostructured solar cells: Beyond the generalized Planck formula

Absorption and emission in inorganic bipolar solar cells based on low dimensional structures exhibiting the effects of quantum confinement is investigated in the framework of a comprehensive microscopic theory of the optical and electronic degrees of freedom of the photovoltaic system. In a quantum-statistical treatment based on non-equilibrium Green's functions, the optical transition rates are related to the conservation of electronic currents, providing a quantum version of the balance equations describing the operation of a photovoltaic device. The generalized Planck law used for the determination of emission from an excited semiconductor in quasi-equilibrium is replaced by an expression of extended validity, where no assumptions on the distribution of electrons and photons are made. The theory is illustrated by the numerical simulation of single quantum well diodes at the radiative limit.Comment: 6 pages, 5 figures, extended LaTeX version of the EUPVSEC09 proceedings articl

On the influence of the cosmological constant on gravitational lensing in small systems

The cosmological constant Lambda affects gravitational lensing phenomena. The contribution of Lambda to the observable angular positions of multiple images and to their amplification and time delay is here computed through a study in the weak deflection limit of the equations of motion in the Schwarzschild-de Sitter metric. Due to Lambda the unresolved images are slightly demagnified, the radius of the Einstein ring decreases and the time delay increases. The effect is however negligible for near lenses. In the case of null cosmological constant, we provide some updated results on lensing by a Schwarzschild black hole.Comment: 8 pages, 1 figure; v2: extended discussion on the lens equation, references added, results unchanged, in press on PR

Testing the Space-Time Structure of Event Generators

We report on work done in collaboration with Klaus Kinder-Geiger and John Ellis which aims at connecting the space-time structure of event generator simulations with observable output.Comment: 16 pages LaTeX, including 5 postscript figures. To appear in the Proceedings of ``RHIC Physics and Beyond - Kay Kay Gee Day'' (Brookhaven National Laboratory, 23 Oct 1998), ed. by B. Muller and R.D. Pisarski, AIP Conference Proceeding

A Method for the Precision Mass Measurement of the Stop Quark at the International Linear Collider

Many supersymmetric models predict new particles within the reach of the next generation of colliders. For an understanding of the model structure and the mechanism(s) of symmetry breaking, it is important to know the masses of the new particles precisely. In this article the measurement of the mass of the scalar partner of the top quark (stop) at an e+e- collider is studied. A relatively light stop is motivated by attempts to explain electroweak baryogenesis and can play an important role in dark matter relic density. A method is presented which makes use of cross-section measurements near the pair-production threshold as well as at higher center-of-mass energies. It is shown that this method not only increases the statistical precision, but also greatly reduces the systematic uncertainties, which can be important. Numerical results are presented, based on a realistic event simulation, for two signal selection strategies: using conventional selection cuts, and using an Iterative Discriminant Analysis (IDA). Our studies indicate that a precision of \Delta\mstop = 0.42 GeV can be achieved, representing a major improvement over previous studies. While the analysis of stops is particularly challenging due to the possibility of stop hadronization, the general procedure could be applied to the mass measurement of other particles as well. We also comment on the potential of the IDA to discover a stop quark in this scenario, and we revisit the accuracy of the theoretical predictions for the neutralino relic densityComment: 41 pages, 14 figures, in JHEP forma

Dynamical realizations of N=1 l-conformal Galilei superalgebra

Dynamical systems which are invariant under N=1 supersymmetric extension of the l-conformal Galilei algebra are constructed. These include a free N=1 superparticle which is governed by higher derivative equations of motion and an N=1 supersymmetric Pais-Uhlenbeck oscillator for a particular choice of its frequencies. A Niederer-like transformation which links the models is proposed.Comment: 12 pages. New material and references added. Published versio