Temperature-sensitive gating of TRPV1 channel as probed by atomistic simulations of its trans- and juxtamembrane domains
Heat-activated transient receptor potential channel TRPV1 is one of the most studied eukaryotic proteins involved in temperature sensation. Upon heating, it exhibits rapid reversible pore gating, which depolarizes neurons and generates action potentials. Underlying molecular details of such effects in the pore region of TRPV1 is of a crucial importance to control temperature responses of the organism. Despite the spatial structure of the channel in both open (O) and closed (C) states is known, microscopic nature of channel gating and mechanism of thermal sensitivity are still poorly understood. In this work, we used unrestrained atomistic molecular dynamics simulations of TRPV1 (without N- and C-terminal cytoplasmic domains) embedded into explicit lipid bilayer in its O- and C-states. We found that the pore domain with its neighboring loops undergoes large temperature-dependent conformational transitions in an asymmetric way, when fragments of only one monomer move with large amplitude, freeing the pore upon heating. Such an asymmetrical gating looks rather biologically relevant because it is faster and more reliable than traditionally proposed "iris-like" symmetric scheme of channel opening. Analysis of structural, dynamic, and hydrophobic organization of the pore domain revealed entropy growth upon TRPV1 gating, which is in line with current concepts of thermal sensitivity.
Many environmental stimuli present a quasi-rhythmic structure at different timescales that the brain needs to decompose and integrate. Cortical oscillations have been proposed as instruments of sensory de-multiplexing, i.e., the parallel processing of different frequency streams in sensory signals. Yet their causal role in such a process has never been demonstrated. Here, we used a neural microcircuit model to address whether coupled theta–gamma oscillations, as observed in human auditory cortex, could underpin the multiscale sensory analysis of speech. We show that, in continuous speech, theta oscillations can flexibly track the syllabic rhythm and temporally organize the phoneme-level response of gamma neurons into a code that enables syllable identification. The tracking of slow speech fluctuations by theta oscillations, and its coupling to gamma-spiking activity both appeared as critical features for accurate speech encoding. These results demonstrate that cortical oscillations can be a key instrument of speech de-multiplexing, parsing, and encoding.
This volume collects the referred papers based on plenary, invited, and oral talks, as well on the posters presented at the Third International Conference on Computer Simulations in Physics and beyond (CSP2018), which took place September 24-27, 2018 in Moscow. The Conference continues the tradition started by an inaugural conference in 2015. It took place on the campus of A.N. Tikhonov Moscow Institute of Electronics and Mathematics in Strogino, was jointly organized by the National Research University Higher School of Economics, the Landau Institute for Theoretical Physics and Science Center in Chernogolovka.
The Conference is a multidisciplinary meeting, with a focus on computational physics and related subjects. Indeed, methods of computational physics prove useful in a broad spectrum of research in multiple branches of natural sciences, and this volume provides a sample.
We hope that this volume will interest readers, and we are already looking forward to the next conference in the series.
CSP2018 Conference Chair and Volume Editor
This issue is the collection of the papers based on the talks presented at the extended workshop “Methods of simulations on supercomputers”, which was held at 21–3 April 2014, in Tarusa hotel Interkosmos of the RAS Space Research Institute. It is the workshop in the series of extended workshops, devoted to the computer technologies in natural sciences. Eighth workshop, as a current one, named “Methods of simulations on supercomputers”. The name is connected with the fact that workshops are supported within the research program the grant by Russian Scientific Foundation 14-21-00158 «Algorithms and methods for mathematical simulations on supercomputing systems, including hybrid ones». Important highlight of the workshop is the active participation of the young scientists, and more than half of the talks were done by the young speakers.
In this volume we have collected papers based on the presentations given at the International Conference on Computer Simulations in Physics and beyond (CSP2015), held in Moscow, September 6-10, 2015. We hope that this volume will be helpful and scientifically interesting for readers.
The Conference was organized for the first time with the common efforts of the Moscow Institute for Electronics and Mathematics (MIEM) of the National Research University Higher School of Economics, the Landau Institute for Theoretical Physics, and the Science Center in Chernogolovka. The name of the Conference emphasizes the multidisciplinary nature of computational physics. Its methods are applied to the broad range of current research in science and society. The choice of venue was motivated by the multidisciplinary character of the MIEM. It is a former independent university, which has recently become the part of the National Research University Higher School of Economics.
Computer simulation, an active learning technique, is now one of the advanced pedagogical technologies. The use of simulation games in the educational process allows students to gain a firsthand understanding of the processes of real life. Public administration, public policy, and political science courses increasingly adopt simulation games in universities worldwide. Besides person-to-person simulation games, there are computer-based simulations in public administration education. Currently in Russia the use of computer-based simulation games in Master of Public Administration (MPA) curricula is quite limited. This paper focuses on computer-based simulation games for students of MPA programs. Our aim was to analyze outcomes of implementing such games in MPA curricula. We have done so by (1) developing three computer- based simulation games about allocating public finances, (2) testing the games in the learning process, and (3) conducting a posttest examination to evaluate the effect of simulation games on students’ knowledge of municipal finances. This study was conducted in the National Research University Higher School of Economics (HSE) and in the Russian Presidential Academy of National Economy and Public Administration (RANEPA) during the period September to December 2015, in Saint Petersburg, Russia. Two groups of students were randomly selected in each university and then randomly allocated either to the experimental or the control group. In control groups (n=12 in HSE, n=13 in RANEPA) students had traditional lectures. In experimental groups (n=12 in HSE, n=13 in RANEPA) students played three simulation games apart from traditional lectures. This exploratory research shows that the use of computer-based simulation games in MPA curricula can improve students’ outcomes by 38%. In general, the experimental groups had better performance on the posttest examination (figure 2). Students in the HSE experimental group had 27.5% better scores than students in the HSE control group. Students of the RANEPA experimental group had 38.0% better scores than students in the RANEPA control group. Research indicates that lecture-based courses are less effective than courses with more interactive approaches. Therefore, our study highlights the need to implement computer-based simulation games in MPA programs in Russian universities. Computer-based simulation games provide students with practical skills for their future careers.
Computer simulation of mechanical testing is used primarily for the correct interpretation of their results and is particularly relevant in cases, when the properties of the material during deformation are essentially nonlinear. For example: when we study mechanical properties of materials with high rate sensitivity. First of all it is superplastic titanium alloys. Superplastic materials exhibit the ability to severe plastic deformation without discontinuities if forming occurs in a narrow range of strain rates, specific to each alloy and temperature-dependent. In the study of superplastic materials, it’s necessary to maintain a constant rate of deformation of the sample. This is achieved by conducting an experiment with a special program loading, crosshead speed at which change during the experiment.
The article discusses the utility of automated revenue management systems, designed for the needs of civil aviation. The analysis of revenue management systems in Russian airlines and Russian carrier position in the international air transportation market are provided. The need to use the automated revenue management system to increase profits of the operator is identified. A strategy of selling tickets, taking into account overbooking as revenue management strategy, allowing both to increase employment of passenger seats and reduce the loss of the carrier from possible no-show passengers to register, is considered. Creation of the simulator to assess the effectiveness of the commercial activities of the airline is proposed.
Computer simulations of electrostatic discharges (ESD) effect on high-power MOSFET-transistors with built-in protection have been carried out. It was found that the transistors with low gate-source capacitance are more sensitive to the ESD effect.The dependence between printed circuit board (PCB) capacity, causing breakdown of MOSFET-transistor gate dielectric, and ESD voltage was established. It is shown that for transistor haying low gate-source capacitance, the existence of the built-in protection does not prevent gate dielectric breakdown at electrostatic discharges. It is recommended to provide external ESD protection for high-power MOSFET-transistors with built-in protection having low gate-source capacitance, for example, having turned on the ESD protection diode in the electric circuit.
Rigorous nonlinear analysis of the physical model of Costas loop is very difficult task, so for analysis, simplified mathematical models and numerical simulation are widely used. In the work it is shown that the use of simplified mathematical models, and the application of non rigorous methods of analysis may lead to wrong conclusions concerning the operability of Costas loop.
Hypoxia of trophoblast cells is an important regulator of normal development of the placenta. However, some pathological states associated with hypoxia, e.g. preeclampsia, impair the functions of placental cells. Oxyquinoline derivative inhibits HIF-prolyl hydroxylase by stabilizing HIF-1 transcription complex, thus modeling cell response to hypoxia. In human choriocarcinoma cells BeWo b30 (trophoblast model), oxyquinoline increased the expression of a core hypoxia response genes along with up-regulation of NOS3, PDK1, and BNIP3 genes and down-regulation of the PPARGC1B gene. These changes in the expression profile attest to activation of the metabolic cell reprogramming mechanisms aimed at reducing oxygen consumption by enabling the switch from aerobic to anaerobic glucose metabolism and the respective decrease in number of mitochondria. The possibility of practical use of the therapeutic properties of oxyquinoline derivatives is discussed.