First principles of modelling the stabilization of microturbulence by fast ions

The observation that fast ions stabilize ion-temperature-gradient-driven microturbulence has profound implications for future fusion reactors. It is also important in optimizing the performance of present-day devices. In this work, we examine in detail the phenomenology of fast ion stabilization and present a reduced model which describes this effect. This model is derived from the high-energy limit of the gyrokinetic equation and extends the existing "dilution" model to account for nontrivial fast ion kinetics. Our model provides a physically-transparent explanation for the observed stabilization and makes several key qualitative predictions. Firstly, that different classes of fast ions, depending on their radial density or temperature variation, have different stabilizing properties. Secondly, that zonal flows are an important ingredient in this effect precisely because the fast ion zonal response is negligible. Finally, that in the limit of highly-energetic fast ions, their response approaches that of the "dilution" model; in particular, alpha particles are expected to have little, if any, stabilizing effect on plasma turbulence. We support these conclusions through detailed linear and nonlinear gyrokinetic simulations.Comment: 29 pages, 10 figures, 3 table

On Recurrent Reachability for Continuous Linear Dynamical Systems

The continuous evolution of a wide variety of systems, including continuous-time Markov chains and linear hybrid automata, can be described in terms of linear differential equations. In this paper we study the decision problem of whether the solution $\boldsymbol{x}(t)$ of a system of linear differential equations $d\boldsymbol{x}/dt=A\boldsymbol{x}$ reaches a target halfspace infinitely often. This recurrent reachability problem can equivalently be formulated as the following Infinite Zeros Problem: does a real-valued function $f:\mathbb{R}_{\geq 0}\rightarrow\mathbb{R}$ satisfying a given linear differential equation have infinitely many zeros? Our main decidability result is that if the differential equation has order at most $7$, then the Infinite Zeros Problem is decidable. On the other hand, we show that a decision procedure for the Infinite Zeros Problem at order $9$ (and above) would entail a major breakthrough in Diophantine Approximation, specifically an algorithm for computing the Lagrange constants of arbitrary real algebraic numbers to arbitrary precision.Comment: Full version of paper at LICS'1

Suppression of decoherence via strong intra-environmental coupling

We examine the effects of intra-environmental coupling on decoherence by constructing a low temperature spin--spin-bath model of an atomic impurity in a Debye crystal. The impurity interacts with phonons of the crystal through anti-ferromagnetic spin-spin interactions. The reduced density matrix of the central spin representing the impurity is calculated by dynamically integrating the full Schroedinger equation for the spin--spin-bath model for different thermally weighted eigenstates of the spin-bath. Exact numerical results show that increasing the intra-environmental coupling results in suppression of decoherence. This effect could play an important role in the construction of solid state quantum devices such as quantum computers.Comment: 4 pages, 3 figures, Revtex fil

Can we avoid high coupling?

It is considered good software design practice to organize source code into modules and to favour within-module connections (cohesion) over between-module connections (coupling), leading to the oft-repeated maxim "low coupling/high cohesion". Prior research into network theory and its application to software systems has found evidence that many important properties in real software systems exhibit approximately scale-free structure, including coupling; researchers have claimed that such scale-free structures are ubiquitous. This implies that high coupling must be unavoidable, statistically speaking, apparently contradicting standard ideas about software structure. We present a model that leads to the simple predictions that approximately scale-free structures ought to arise both for between-module connectivity and overall connectivity, and not as the result of poor design or optimization shortcuts. These predictions are borne out by our large-scale empirical study. Hence we conclude that high coupling is not avoidable--and that this is in fact quite reasonable

ParticleStats: open source software for the analysis of particle motility and cytoskeletal polarity

The study of dynamic cellular processes in living cells is central to biology and is particularly powerful when the motility characteristics of individual objects within cells can be determined and analysed statistically. However, commercial programs only offer a limited range of inflexible analysis modules and there are currently no open source programs for extensive analysis of particle motility. Here, we describe ParticleStats (http://www.ParticleStats.com), a web server and open source programs, which input the X,Y coordinate positions of objects in time, and output novel analyses, graphical plots and statistics for motile objects. ParticleStats comprises three separate analysis programs. First, ParticleStats:Directionality for the global analysis of polarity, for example microtubule plus end growth in Drosophila oocytes. Second, ParticleStats:Compare for the analysis of saltatory movement in terms of runs and pauses. This can be applied to chromosome segregation and molecular motor-based movements. Thirdly ParticleStats:Kymographs for the analysis of kymograph images, for example as applied to separation of chromosomes in mitosis. These analyses have provided key insights into molecular mechanisms that are not possible from qualitative analysis alone and are widely applicable to many other cell biology problems

Matrix metalloproteinases in a sea urchin ligament with adaptable mechanical properties

Mutable collagenous tissues (MCTs) of echinoderms show reversible changes in tensile properties (mutability) that are initiated and modulated by the nervous system via the activities of cells known as juxtaligamental cells. The molecular mechanism underpinning this mechanical adaptability has still to be elucidated. Adaptable connective tissues are also present in mammals, most notably in the uterine cervix, in which changes in stiffness result partly from changes in the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). There have been no attempts to assess the potential involvement of MMPs in the echinoderm mutability phenomenon, apart from studies dealing with a process whose relationship to the latter is uncertain. In this investigation we used the compass depressor ligaments (CDLs) of the sea-urchin Paracentrotus lividus. The effect of a synthetic MMP inhibitor - galardin - on the biomechanical properties of CDLs in different mechanical states ("standard", "compliant" and "stiff") was evaluated by dynamic mechanical analysis, and the presence of MMPs in normal and galardin-treated CDLs was determined semi-quantitatively by gelatin zymography. Galardin reversibly increased the stiffness and storage modulus of CDLs in all three states, although its effect was significantly lower in stiff than in standard or compliant CDLs. Gelatin zymography revealed a progressive increase in total gelatinolytic activity between the compliant, standard and stiff states, which was possibly due primarily to higher molecular weight components resulting from the inhibition and degradation of MMPs. Galardin caused no change in the gelatinolytic activity of stiff CDLs, a pronounced and statistically significant reduction in that of standard CDLs, and a pronounced, but not statistically significant, reduction in that of compliant CDLs. Our results provide evidence that MMPs may contribute to the variable tensility of the CDLs, in the light of which we provide an updated hypothesis for the regulatory mechanism controlling MCT mutability

Impact of sequence variation in the ul128 locus on production of human cytomegalovirus in fibroblast and epithelial cells

The human cytomegalovirus (HCMV) virion envelope contains a complex consisting of glycoproteins gH and gL plus proteins encoded by the UL128 locus (UL128L): pUL128, pUL130, and pUL131A. UL128L is necessary for efficient infection of myeloid, epithelial, and endothelial cells but limits replication in fibroblasts. Consequently, disrupting mutations in UL128L are rapidly selected when clinical isolates are cultured in fibroblasts. In contrast, bacterial artificial chromosome (BAC)-cloned strains TB40-BAC4, FIX, and TR do not contain overt disruptions in UL128L, yet no virus reconstituted from them has been reported to acquire mutations in UL128L in vitro. We performed BAC mutagenesis and reconstitution experiments to test the hypothesis that these strains contain subtle mutations in UL128L that were acquired during passage prior to BAC cloning. Compared to strain Merlin containing wild-type UL128L, all three strains produced higher yields of cell-free virus. Moreover, TB40-BAC4 and FIX spread cell to cell more rapidly than wild-type Merlin in fibroblasts but more slowly in epithelial cells. The differential growth properties of TB40-BAC4 and FIX (but not TR) were mapped to single-nucleotide substitutions in UL128L. The substitution in TB40-BAC4 reduced the splicing efficiency of UL128, and that in FIX resulted in an amino acid substitution in UL130. Introduction of these substitutions into Merlin dramatically increased yields of cell-free virus and increased cell-to-cell spread in fibroblasts but reduced the abundance of pUL128 in the virion and the efficiency of epithelial cell infection. These substitutions appear to represent mutations in UL128L that permit virus to be propagated in fibroblasts while retaining epithelial cell tropism

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles