Fluctuations in Stationary non Equilibrium States

In this paper we formulate a dynamical fluctuation theory for stationary non equilibrium states (SNS) which covers situations in a nonlinear hydrodynamic regime and is verified explicitly in stochastic models of interacting particles. In our theory a crucial role is played by the time reversed dynamics. Our results include the modification of the Onsager-Machlup theory in the SNS, a general Hamilton-Jacobi equation for the macroscopic entropy and a non equilibrium, non linear fluctuation dissipation relation valid for a wide class of systems

Exclusion processes with degenerate rates: convergence to equilibrium and tagged particle

Stochastic lattice gases with degenerate rates, namely conservative particle systems where the exchange rates vanish for some configurations, have been introduced as simplified models for glassy dynamics. We introduce two particular models and consider them in a finite volume of size $\ell$ in contact with particle reservoirs at the boundary. We prove that, as for non--degenerate rates, the inverse of the spectral gap and the logarithmic Sobolev constant grow as $\ell^2$. It is also shown how one can obtain, via a scaling limit from the logarithmic Sobolev inequality, the exponential decay of a macroscopic entropy associated to a degenerate parabolic differential equation (porous media equation). We analyze finally the tagged particle displacement for the stationary process in infinite volume. In dimension larger than two we prove that, in the diffusive scaling limit, it converges to a Brownian motion with non--degenerate diffusion coefficient.Comment: 25 pages, 3 figure

Identification and structural characterization of a mutant KRAS‐G12V specific TCR restricted by HLA‐A3

Mutations in KRAS are some of the most common across multiple cancer types and are thus attractive targets for therapy. Recent studies demonstrated that mutant KRAS generates immunogenic neoantigens that are targetable by adoptive T‐cell therapy in metastatic diseases. To expand mutant KRAS‐specific immunotherapies, it is critical to identify additional HLA‐I allotypes that can present KRAS neoantigens and their cognate T‐cell receptors (TCR). Here, we identified a murine TCR specific to a KRAS‐G12V neoantigen (7VVVGAVGVGK16) using a vaccination approach with transgenic mice expressing HLA‐A*03:01 (HLA‐A3). This TCR demonstrated exquisite specificity for mutant G12V and not WT KRAS peptides. To investigate the molecular basis for neoantigen recognition by this TCR, we determined its structure in complex with HLA‐A3(G12V). G12V‐TCR CDR3β and CDR1β formed a hydrophobic pocket to interact with p6 Val of the G12V but not the WT KRAS peptide. To improve the tumor sensitivity of this TCR, we designed rational substitutions to improve TCR:HLA‐A3 contacts. Two substitutions exhibited modest improvements in TCR binding avidity to HLA‐A3 (G12V) but did not sufficiently improve T‐cell sensitivity for further clinical development. Our study provides mechanistic insight into how TCRs detect neoantigens and reveals the challenges in targeting KRAS‐G12V mutations

A pedestrian's view on interacting particle systems, KPZ universality, and random matrices

These notes are based on lectures delivered by the authors at a Langeoog seminar of SFB/TR12 "Symmetries and universality in mesoscopic systems" to a mixed audience of mathematicians and theoretical physicists. After a brief outline of the basic physical concepts of equilibrium and nonequilibrium states, the one-dimensional simple exclusion process is introduced as a paradigmatic nonequilibrium interacting particle system. The stationary measure on the ring is derived and the idea of the hydrodynamic limit is sketched. We then introduce the phenomenological Kardar-Parisi-Zhang (KPZ) equation and explain the associated universality conjecture for surface fluctuations in growth models. This is followed by a detailed exposition of a seminal paper of Johansson that relates the current fluctuations of the totally asymmetric simple exclusion process (TASEP) to the Tracy-Widom distribution of random matrix theory. The implications of this result are discussed within the framework of the KPZ conjecture.Comment: 52 pages, 4 figures; to appear in J. Phys. A: Math. Theo

Interplay between Anomalous Transport and Catalytic Reaction Kinetics in Single-File Nanoporous Systems

Functionalized nanoporous materials have broad utility for catalysis applications. However, the kinetics of catalytic reaction processes in these systems can be strongly impacted by the anomalous transport. The most extreme case corresponds to single-file diffusion for narrow pores in which species cannot pass each other. For conversion reactions with a single-file constraint, traditional mean-field-type reaction-diffusion equations fail to capture the initial evolution of concentration profiles, and they cannot describe the scaling behavior of steady-state reactivity. Hydrodynamic reaction-diffusion equations accounting for the single-file aspects of chemical diffusion can describe such initial evolution, but additional refinements are needed to incorporate fluctuation effects controlling, for example, steady-state reactivity localized near pore openings. For polymerization reactions with a single-file constraint, initial behavior depends strongly on system details such as catalytic site loading and reaction rate. However, long-time behavior often involves the formation of a dominant large polymer near each end of the pore, initially within the pore but subsequently partly extruding. In this partial extrusion regime, the kinetics is governed by the special features of the random walk describing the motion of the end of the partly extruded polymer, noting that this extruded end must return within the pore for further growth

New treatments addressing the pathophysiology of hereditary angioedema

Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation

Control of urea hydrolysis and nitrification in soil by chemicals - Prospects and problems

A review is made of the recent work to assess the prospects of regulating urea hydrolysis and nitrification processes in soils by employing chemicals that can retard urea hydrolysis and nitrification. The possible benefits from control of nitrogen transformations in terms of conserving and enhancing fertilizer nitrogen efficiency for crop production and the problems associated with their use with regard to N metabolism of plants have also been discussed with examples. Prospects of using cheap and effective indigenous materials and chemicals for control of urea hydrolysis and nitrification under specific soil situations appear eminent in improving the fertilizer nitrogen efficiency. Urease inhibitors may be helpful in reducing problems associated with ammonia volatilization if this is not offset by leaching of urea. On the other hand retardation of nitrification appears useful in reducing losses that accompany nitrification due to leaching and denitrification, and with the plants that metabolize equally well with relatively higher amounts of NH4–N may be more effective in improving the utilization of fertilizer N under these situation