State-dependent diffusion: thermodynamic consistency and its path integral formulation

The friction coefficient of a particle can depend on its position as it does when the particle is near a wall. We formulate the dynamics of particles with such state-dependent friction coefficients in terms of a general Langevin equation with multiplicative noise, whose evaluation requires the introduction of specific rules. Two common conventions, the Ito and the Stratonovich, provide alternative rules for evaluation of the noise, but other conventions are possible. We show the requirement that a particle's distribution function approach the Boltzmann distribution at long times dictates that a drift term must be added to the Langevin equation. This drift term is proportional to the derivative of the diffusion coefficient times a factor that depends on the convention used to define the multiplicative noise. We explore the consequences of this result in a number examples with spatially varying diffusion coefficients. We also derive path integral representations for arbitrary interpretation of the noise, and use it in a perturbative study of correlations in a simple system.Comment: 18 pages, 8 figures, Accepted to PR

Viscosity Dependence of the Folding Rates of Proteins

The viscosity dependence of the folding rates for four sequences (the native state of three sequences is a beta-sheet, while the fourth forms an alpha-helix) is calculated for off-lattice models of proteins. Assuming that the dynamics is given by the Langevin equation we show that the folding rates increase linearly at low viscosities \eta, decrease as 1/\eta at large \eta and have a maximum at intermediate values. The Kramers theory of barrier crossing provides a quantitative fit of the numerical results. By mapping the simulation results to real proteins we estimate that for optimized sequences the time scale for forming a four turn \alpha-helix topology is about 500 nanoseconds, whereas the time scale for forming a beta-sheet topology is about 10 microseconds.Comment: 14 pages, Latex, 3 figures. One figure is also available at http://www.glue.umd.edu/~klimov/seq_I_H.html, to be published in Physical Review Letter

Influence of Hydrodynamic Interactions on Mechanical Unfolding of Proteins

We incorporate hydrodynamic interactions in a structure-based model of ubiquitin and demonstrate that the hydrodynamic coupling may reduce the peak force when stretching the protein at constant speed, especially at larger speeds. Hydrodynamic interactions are also shown to facilitate unfolding at constant force and inhibit stretching by fluid flows.Comment: to be published in Journal of Physics: Condensed Matte

Hydrodynamic Coupling of Two Brownian Spheres to a Planar Surface

We describe direct imaging measurements of the collective and relative diffusion of two colloidal spheres near a flat plate. The bounding surface modifies the spheres' dynamics, even at separations of tens of radii. This behavior is captured by a stokeslet analysis of fluid flow driven by the spheres' and wall's no-slip boundary conditions. In particular, this analysis reveals surprising asymmetry in the normal modes for pair diffusion near a flat surface.Comment: 4 pages, 4 figure

Лейшманиоз и ВИЧ-инфекция – актуальная проблема?

The aim of the work is the clinical characteristics of all known cases of combined visceral leishmaniasis (VL) and HIV infection in the Russian Federation.Results. The article contains information on the problem of the combined course of HIV infection and leishmaniasis: a number of statistical and overview data in the world. A brief description of known cases of high blood pressure in patients with HIV infection in the Russian Federation, as well as a detailed description of the last patient diagnosed with VL in 2019 in Moscow. In all cases, the diagnosis of VL was difficult, which was due to clinical features and the lack of alertness of physicians in relation to VL. All but one of the patients contracted VL during their stay in Crimea.Conclusion. The authors point to the need for the formation of diagnostic alertness among doctors on this pathology, especially since with the expansion of tourist routes abroad in endemic countries, as well as in the Crimea, the relevance of this problem increases.Цель: клиническая характеристика всех известных случаев сочетанного течения висцерального лейшманиоза и ВИЧ-инфекции в Российской Федерации.Результаты. Статья содержит сведения по проблеме сочетанного течения ВИЧ-инфекции и лейшманиоза: ряд статистических и обзорных данных в мире. Представлена краткая характеристика известных случаев висцерального лейшманиоза у больных ВИЧ-инфекцией в РФ, а также подробное описание последнего больного с установленным диагнозом висцерального лейшманиоза в 2019 г. в Москве. Во всех случаях установление диагноза висцерального лейшманиоза было затруднительно, что было обусловлено клиническими особенностями и отсутствием настороженности медиков в отношении висцерального лейшманиоза. Все больные, кроме одного, заразились висцеральным лейшманиозом во время пребывания в Крыму.Заключение. Авторы указывают на необходимость формирования у врачей диагностической настороженности по данной патологии, тем более что с расширением туристических маршрутов за рубеж, особенно в эндемичные страны, а также в Крым актуальность этой проблемы возрастает.

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

Scale-free static and dynamical correlations in melts of monodisperse and Flory-distributed homopolymers: A review of recent bond-fluctuation model studies

It has been assumed until very recently that all long-range correlations are screened in three-dimensional melts of linear homopolymers on distances beyond the correlation length $\xi$ characterizing the decay of the density fluctuations. Summarizing simulation results obtained by means of a variant of the bond-fluctuation model with finite monomer excluded volume interactions and topology violating local and global Monte Carlo moves, we show that due to an interplay of the chain connectivity and the incompressibility constraint, both static and dynamical correlations arise on distances $r \gg \xi$. These correlations are scale-free and, surprisingly, do not depend explicitly on the compressibility of the solution. Both monodisperse and (essentially) Flory-distributed equilibrium polymers are considered.Comment: 60 pages, 49 figure

Поляризация макрофагов: механизмы, маркеры и факторы индукции

Macrophages  are  key  components  of  the  innate  immune  system. The  variability  of  the  macrophage’s participation in tumor progression, determined by their functional polarization, opens up a wide prospect for modulating their functional profile, primarily in the direction of increasing antitumor activity. The purpose of the study was to provide up-to-date data on the process of macrophage polarization, mechanisms of its regulation, polarization markers and induction factors. Material and methods. A search was made for available literature sources published in Web of Science, Scopus and other databases. more than 160 sources devoted to the study of the process of macrophage polarization were found, of which 121 were included in this review. Results. This review presents data on the molecular mechanisms and gene signatures associated with M1 and M2 polarization of macrophages. We displayed information on metabolic, phenotypic characteristics and cytokine profile of M1- and M2-macrophages, as well as highlighted data on polarization factors and targets of their action. Conclusion. The information presented in the review can serve as an information base for the development of experimental and clinical approaches for editing the functional profile of macrophages in order to control their involvement in various pathological processes.Макрофаги являются ключевыми компонентами врожденной иммунной системы. Вариативность участия макрофагов в различных патологических процессах, определяемая их функциональной поляризацией, открывает широкую перспективу для модуляции их функционального профиля для использования в терапевтических целях. Цель исследования – предоставить современные данные о процессе поляризации макрофагов, механизмах его регуляции, маркерах поляризации и факторах индукции. Материал и методы. Проведен поиск доступных литературных источников, опубликованных в базах данных Web of Science, Scopus и др. Найдено более 160 источников, посвященных изучению процесса поляризации макрофагов, из которых 121 включен в данный обзор. Результаты. В обзоре представлены данные о молекулярных механизмах и генных сигнатурах, ассоциированных с М1- и М2- поляризацией макрофагов, информация о метаболических, фенотипических признаках и цитокиновом профиле М1- и М2-макрофагов, а также освещены данные о факторах поляризации и мишенях их воздействия. Заключение. Представленные в обзоре сведения могут послужить информационной базой для разработки экспериментальных и клинических подходов для редактирования функционального профиля макрофагов с целью управления патологическими процессами с их участием

The CD14+/lowCD16+ monocyte subset is more susceptible to spontaneous and oxidant-induced apoptosis than the CD14+CD16− subset

Human monocytes can be classified into two subsets with distinctive characteristics. In this study, we report a difference in apoptotic potential between these two subsets with CD14+/lowCD16+ monocytes being more susceptible than CD14+CD16− monocytes to undergo spontaneous apoptosis and apoptosis induced by reactive oxygen species (ROS). By global transcriptomic and proteomic approaches, we observed that CD14+/lowCD16+ monocytes expressed higher levels of pro-apoptotic genes and proteins such as TNFα, caspase 3, Bax and cytochrome c and showed more caspases 3 and 7 activities. They also exhibited greater aerobic respiration resulting in a higher production of ROS from the mitochondria. CD14+CD16− monocytes, in contrast, showed higher expression of glutathione (GSH)-metabolizing genes such as GSH peroxidase and microsomal GSH S-transferase and were more resistant to oxidative stress than CD14+/lowCD16+ monocytes. The apoptosis of CD14+/lowCD16+ monocytes was ROS dependent as reducing ROS levels significantly reduced cell death. This is the first report of a differential apoptotic propensity of human monocyte subsets, and gaining a better understanding of this process may help to provide a better understanding of the roles of these subsets during homeostasis and under pathological conditions, particularly in situations in which high levels of oxidants are present

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page