Mutational patterns along different evolution paths of follicular lymphoma

Follicular lymphoma (FL) is an indolent disease, characterized by a median life expectancy of 18-20 years and by intermittent periods of relapse and remission. FL frequently transforms into the more aggressive diffuse large B cell lymphoma (t-FL). In previous studies, the analysis of immunoglobulin heavy chain variable region (IgHV) genes in sequential biopsies from the same patient revealed two different patterns of tumor clonal evolution: direct evolution, through acquisition of additional IgHV mutations over time, or divergent evolution, in which lymphoma clones from serial biopsies independently develop from a less-mutated common progenitor cell (CPC). Our goal in this study was to characterize the somatic hypermutation (SHM) patterns of IgHV genes in sequential FL samples from the same patients, and address the question of whether the mutation mechanisms (SHM targeting, DNA repair or both), or selection forces acting on the tumor clones, were different in FL samples compared to healthy control samples, or in late relapsed/transformed FL samples compared to earlier ones. Our analysis revealed differences in the distribution of mutations from each of the nucleotides when tumor and non-tumor clones were compared, while FL and transformed FL (t-FL) tumor clones displayed similar mutation distributions. Lineage tree measurements suggested that either initial clone affinity or selection thresholds were lower in FL samples compared to controls, but similar between FL and t-FL samples. Finally, we observed that both FL and t-FL tumor clones tend to accumulate larger numbers of potential N-glycosylation sites due to the introduction of new SHM. Taken together, these results suggest that transformation into t-FL, in contrast to initial FL development, is not associated with any major changes in DNA targeting or repair, or the selection threshold of the tumor clone

Quantum kinetic approach to the calculation of the Nernst effect

We show that the strong Nernst effect observed recently in amorphous superconducting films far above the critical temperature is caused by the fluctuations of the superconducting order parameter. We employ the quantum kinetic approach for the derivation of the Nernst coefficient. We present here the main steps of the calculation and discuss some subtle issues that we encountered while calculating the Nernst coefficient. In particular, we demonstrate that in the limit T=0 the contribution of the magnetization ensures the vanishing of the Nernst signal in accordance with the third law of thermodynamics. We obtained a striking agreement between our theoretical calculations and the experimental data in a broad region of temperatures and magnetic fields.Comment: 24 pages, 13 figure

Nernst effect as a probe of superconducting fluctuations in disordered thin films

In amorphous superconducting thin films of $Nb_{0.15}Si_{0.85}$ and $InO_x$, a finite Nernst coefficient can be detected in a wide range of temperature and magnetic field. Due to the negligible contribution of normal quasi-particles, superconducting fluctuations easily dominate the Nernst response in the entire range of study. In the vicinity of the critical temperature and in the zero-field limit, the magnitude of the signal is in quantitative agreement with what is theoretically expected for the Gaussian fluctuations of the superconducting order parameter. Even at higher temperatures and finite magnetic field, the Nernst coefficient is set by the size of superconducting fluctuations. The Nernst coefficient emerges as a direct probe of the ghost critical field, the normal-state mirror of the upper critical field. Moreover, upon leaving the normal state with fluctuating Cooper pairs, we show that the temperature evolution of the Nernst coefficient is different whether the system enters a vortex solid, a vortex liquid or a phase-fluctuating superconducting regime.Comment: Submitted to New. J. Phys. for a focus issue on "Superconductors with Exotic Symmetries

Quantum kinetic approach for studying thermal transport in the presence of electron-electron interactions and disorder

A user friendly scheme based on the quantum kinetic equation is developed for studying thermal transport phenomena in the presence of interactions and disorder. We demonstrate that this scheme is suitable for both a systematic perturbative calculation as well as a general analysis. We believe that we present an adequate alternative to the Kubo formula, which for the thermal transport is rather cumbersome.Comment: 30 pages, 16 figure

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

Micro-manufacturing : research, technology outcomes and development issues

Besides continuing effort in developing MEMS-based manufacturing techniques, latest effort in Micro-manufacturing is also in Non-MEMS-based manufacturing. Research and technological development (RTD) in this field is encouraged by the increased demand on micro-components as well as promised development in the scaling down of the traditional macro-manufacturing processes for micro-length-scale manufacturing. This paper highlights some EU funded research activities in micro/nano-manufacturing, and gives examples of the latest development in micro-manufacturing methods/techniques, process chains, hybrid-processes, manufacturing equipment and supporting technologies/device, etc., which is followed by a summary of the achievements of the EU MASMICRO project. Finally, concluding remarks are given, which raise several issues concerning further development in micro-manufacturing

NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth

Mitochondria are emerging as important players in the transformation process of cells, maintaining the biosynthetic and energetic capacities of cancer cells and serving as one of the primary sites of apoptosis and autophagy regulation. Although several avenues of cancer therapy have focused on mitochondria, progress in developing mitochondria-targeting anticancer drugs nonetheless has been slow, owing to the limited number of known mitochondrial target proteins that link metabolism with autophagy or cell death. Recent studies have demonstrated that two members of the newly discovered family of NEET proteins, NAF-1 (CISD2) and mitoNEET (mNT; CISD1), could play such a role in cancer cells. NAF-1 was shown to be a key player in regulating autophagy, and mNT was proposed to mediate iron and reactive oxygen homeostasis in mitochondria. Here we show that the protein levels of NAF-1 and mNT are elevated in human epithelial breast cancer cells, and that suppressing the level of these proteins using shRNA results in significantly reduced cell proliferation and tumor growth, decreased mitochondrial performance, uncontrolled accumulation of iron and reactive oxygen in mitochondria, and activation of autophagy. Our findings highlight NEET proteins as promising mitochondrial targets for cancer therapy

Nonlinear Lattice Waves in Random Potentials

Localization of waves by disorder is a fundamental physical problem encompassing a diverse spectrum of theoretical, experimental and numerical studies in the context of metal-insulator transition, quantum Hall effect, light propagation in photonic crystals, and dynamics of ultra-cold atoms in optical arrays. Large intensity light can induce nonlinear response, ultracold atomic gases can be tuned into an interacting regime, which leads again to nonlinear wave equations on a mean field level. The interplay between disorder and nonlinearity, their localizing and delocalizing effects is currently an intriguing and challenging issue in the field. We will discuss recent advances in the dynamics of nonlinear lattice waves in random potentials. In the absence of nonlinear terms in the wave equations, Anderson localization is leading to a halt of wave packet spreading. Nonlinearity couples localized eigenstates and, potentially, enables spreading and destruction of Anderson localization due to nonintegrability, chaos and decoherence. The spreading process is characterized by universal subdiffusive laws due to nonlinear diffusion. We review extensive computational studies for one- and two-dimensional systems with tunable nonlinearity power. We also briefly discuss extensions to other cases where the linear wave equation features localization: Aubry-Andre localization with quasiperiodic potentials, Wannier-Stark localization with dc fields, and dynamical localization in momentum space with kicked rotors.Comment: 45 pages, 19 figure