Beta-induced Alfvén eigenmodes and geodesic acoustic modes in presence of strong tearing activity during the current ramp-down on JET

The analysis of the current ramp-down phase of JET plasmas has revealed the occurrence of additional magnetic oscillations in pulses characterized by large magnetic islands. The frequencies of these oscillations range from 5 kHz to 20 kHz, being well below the toroidal gap in the Alfven continuum and of the same order of the low-frequency gap opened by plasma compressibility. The additional oscillations only appear when the magnetic island width exceeds a critical threshold, suggesting that the oscillations could tap their energy from the tearing mode (TM) by a non-linear coupling mechanism. A possible role of fast ions in the excitation process can be excluded, being the pulse phase considered characterized by very low additional heating. The calculation of the coupled Alfven-acoustic continuum in toroidal geometry suggests the possibility of beta-induced Alfven eigenmodes (BAE) rather than beta-induced Alfven acoustic eigenmodes (BAAE). As a main novelty compared to previous works, the analysis of the electron temperature profiles from electron cyclotron emission has shown the simultaneous presence of magnetic islands on different rational surfaces in pulses with multiple magnetic oscillations in the low-frequency gap of the Alfven continuum. This observation supports the hypothesis of different BAE with toroidal mode number n = 1 associated with different magnetic islands. As another novelty, the observation of magnetic oscillations with n = 2 in the BAE range is reported for the first time in this work. Some pulses, characterized by slowly rotating tearing modes, exhibit additional oscillations with n = 0, likely associated with geodesic acoustic modes (GAM), and a cross-spectral bicoherence analysis has confirmed a non-linear interaction among TM, BAE and GAM, with the novelty of the observation of multiple triplets (twin BAEs plus GAM), due to the simultaneous presence of several magnetic islands in the plasma.

A weakly nonlinear framework to study shock–vorticity interaction

Linear interaction analysis (LIA) is routinely used to study the shock–turbulence interaction in supersonic and hypersonic flows. It is based on the inviscid interaction of elementary Kovásznay modes with a shock discontinuity. LIA neglects nonlinear effects, and hence it is limited to small-amplitude disturbances. In this work, we extend the LIA framework to study the fundamental interaction of a two-dimensional vorticity wave with a normal shock. The predictions from a weakly nonlinear framework are compared with high-order accurate numerical simulations over a range of wave amplitudes ( $\epsilon$ ), incidence angles ( $\alpha$ ) and shock-upstream Mach numbers ( $M_1$ ). It is found that the nonlinear generation of vorticity at the shock has a significant contribution from the intermodal interaction between vorticity and acoustic waves. Vorticity generation is also strongly influenced by the curvature of the normal shock wave, especially for high incidence angles. Further, the weakly nonlinear analysis is able to predict the correct scaling of the nonlinear effects observed in the numerical simulations. The analysis also predicts a Mach number dependent limit for the validity of LIA in terms of the maximum possible amplitude of the upstream vorticity wave.

Non-linear interaction of laser light with vacuum: contributions to the energy density and pressure in presence of an intense magnetic field

Recent simulations show that very large electric and magnetic fields near the kilo Tesla strength will likely be generated by ultra-intense lasers at existing facilities over distances of hundreds of microns in underdense plasmas. Stronger ones are even expected in the future although some technical dificulties must be overcome. In addition, it has been shown that vacuum exhibits a peculiar non-linear behaviour in presence of high magnetic and electric field strengths. In this work we are interested in the analysis of thermodynamical contributions of vacuum to the energy density and pressure when radiation interacts with it in the presence of an external magnetic field. Using the Euler-Heisenberg formalism in the regime of weak fields i.e. smaller than critical Quantum Electrodynamics field strength values, we evaluate these magnitudes and analyze the highly anisotropic behaviour we find. Our work has implications for photon-photon scattering with lasers and astrophysically magnetized underdense systems far outside their surface where matter effects are increasingly negligible.

Plasma-based microwave power limitation in a printed transmission line: a self-consistent model compared with experimental data

Plasma-based microwave power limitation in a suspended microstrip transmission line integrating a micro hollow cathode discharge (MHCD) in its center is experimentally and numerically studied. Transient and steady state microwave power measurements exhibit a limitation threshold of 28 dBm and time responses of 25 microseconds. Intensified charge-coupled device (ICCD) imaging shows that microwave breakdown occurs at the top of the MHCD. The plasma then extends towards the microwave source within the suspended microstrip transmission line. Besides, a self-consistent model is proposed to simulate the non-linear interaction between microwave and plasma. It gives numerical results in great agreement with the measurements, and show that the plasma expansion during the transient response is related to a shift between the ionization source term and the electron density maximum. The propagation speed, under the tested conditions, depends mainly on the stepwise ionization from the excited states.

A Comparison of Covariate Adjustment Approaches Under Model Misspecification In Individually Randomized Trials

Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on small to medium-sized individually randomized trials, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, Inverse Probability of Treatment Weighting ( IPTW ), Augmented Inverse Probability of Treatment Weighting ( AIPTW ) and Targeted Maximum Likelihood Estimation ( TMLE ) offer improvement over the commonly used Analysis of Covariance ( ANCOVA ). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW ) show improved results compared to ANCOVA . When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; development of small sample corrections is needed.

Developing Society Integrity and Cultural Code by Means of Social and Cultural Activity as Factor of Ensuring National Security

Trends of developing relations in today’s society, spread of digital technologies and restrictions in movement during the last year showed a rising diffusion of society, split of opinions and weakening of the cultural code of the Russian population. The article studies sources of these changes and searches for solutions based on means of social and cultural activity. It is well known that cultural code is formed for decades and it is the social and cultural sphere that can concentrate this process and direct it to strengthening of national self-identification, rise in the rate of patriotism, education and wellbeing of the population. The process of shaping the civil society in the post-soviet period is based on pursuing cultural policy financed at the expense of the country budget, in contrast to western countries. This aspect makes us think about the necessity to change means and methods of social and cultural activity with due regard to processes of society digitalization. At the same time cultural policy acts as a significant section of the system of national security, as a way of shaping civil society, keeping cultural values and traditions. The research showed that non-linear interaction of such tensors, as sustainable development, corporate social responsibility, national security, digitalization, technologization of society can seriously affect the processes of diffusion of society integrity, destruction of its cultural code and sovereignty of state as it is. Preserving the cultural code as a foundation of national culture and overcoming problems of society diffusion are possible in case the state participation in reforming approaches to pursuing cultural policy is extended. A separate aspect is developing the HR potential of cultural institutions of the future oriented to advanced technologies, continuous learning the achievements of psychology as a science, which can create patriotic feelings in society promoting values of cultural inheritance as a foundation of national identification.

Structural-bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild-type reference.

To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread came in several pandemic waves characterized by the emergence of new SARS-CoV-2 variants. Here, we report on a sequence- and structural-bioinformatics analysis by which we estimate the impact of amino acid exchanges on the affinity of the SARS-CoV-2 spike receptor-binding domain (RBD) to the human receptor hACE2. This is carried out by qualitative electrostatics and hydrophobicity analysis as well as through molecular dynamics simulations used for the development of a highly accurate linear interaction energy (LIE) binding affinity model that was calibrated on a large set of experimental binding energies. For the newest variant of concern (VOC), B.1.1.529 Omicron, our Halo difference point cloud studies reveal the largest impact on the RBD binding interface compared to any other VOC. Moreover, according to our LIE model, Omicron achieved a substantially higher ACE2 binding affinity than the wild-type and in particular the highest among all VOCs except for Alpha and therefore requires special attention and monitoring. Using this prediction model we provide early structural insight and binding properties before experimentally determined complex structures and binding affinity data become available in the upcoming months.

A minimal model demonstrates the control of mouse sperm capacitation by a positive feedback loop between sNHE and SLO3

When mammalian spermatozoa are released in the female reproductive tract, they are incapable of fertilizing the oocyte. They need a prolonged exposure to the alkaline medium of the female genital tract before their flagellum gets hyperactivated and the acrosome reaction can take place, allowing the sperm to interact with the oocyte. Ionic fluxes across the sperm membrane are involved in two essential aspects of capacitation: the increase in intracellular pH and the membrane hyperpolarization. In particular, it has been shown that the SLO3 potassium channel and the sNHE sodium-proton transporter, two sperm-specific transmembrane proteins, are necessary for the capacitation process to occur. As the SLO3 channel is activated by an increase in intracellular pH and sNHE is activated by hyperpolarization, they act together as a positive feedback system. Mathematical modeling provides a unique tool to capture the essence of a molecular mechanism and can be used to derive insight from the existing data. We have therefore developed a theoretical model formalizing the positive feedback loop between SLO3 and sHNE in mouse epididymal sperm to see if this non-linear interaction can provide the core mechanism explaining the existence of uncapacited and capacitated states. We show that the proposed model can fully explain the switch between the uncapacitated and capacited states and also predicts the existence of a bistable behaviour. Furthermore, our model indicates that SLO3 inhibition, above a certain threshold, is effective to completely abolish capacitation.

Molecular Modeling Studies of N-phenylpyrimidine-4-amine Derivatives for Inhibiting FMS-like Tyrosine Kinase-3

Overexpression and frequent mutations in FMS-like tyrosine kinase-3 (FLT3) are considered risk factors for severe acute myeloid leukemia (AML). Hyperactive FLT3 induces premature activation of multiple intracellular signaling pathways, resulting in cell proliferation and anti-apoptosis. We conducted the computational modeling studies of 40 pyrimidine-4,6-diamine-based compounds by integrating docking, molecular dynamics, and three-dimensional structure–activity relationship (3D-QSAR). Molecular docking showed that K644, C694, F691, E692, N701, D829, and F830 are critical residues for the binding of ligands at the hydrophobic active site. Molecular dynamics (MD), together with Molecular Mechanics Poison–Boltzmann/Generalized Born Surface Area, i.e., MM-PB(GB)SA, and linear interaction energy (LIE) estimation, provided critical information on the stability and binding affinity of the selected docked compounds. The MD study suggested that the mutation in the gatekeeper residue F691 exhibited a lower binding affinity to the ligand. Although, the mutation in D835 in the activation loop did not exhibit any significant change in the binding energy to the most active compound. We developed the ligand-based comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models. CoMFA (q2= 0.802, r2= 0.983, and = 0.698) and CoMSIA (q2= 0.725, r2= 0.965 and = 0.668) established the structure–activity relationship (SAR) and showed a reasonable external predictive power. The contour maps from the CoMFA and CoMSIA models could explain valuable information about the favorable and unfavorable positions for chemical group substitution, which can increase or decrease the inhibitory activity of the compounds. In addition, we designed 30 novel compounds, and their predicted pIC50 values were assessed with the CoMSIA model, followed by the assessment of their physicochemical properties, bioavailability, and free energy calculation. The overall outcome could provide valuable information for designing and synthesizing more potent FLT3 inhibitors.

The influence of somatosensory and auditory evoked potentials on concurrent transcranial-magnetic stimulation electroencephalography recordings

Background: Transcranial magnetic stimulation (TMS) evoked potentials (TEPs) can be used to index cortical excitability. However, it remains unclear to what extent TEPs reflect somatosensory and auditory-evoked potentials which arise from the scalp sensation and click of the TMS coil, as opposed to transcranial stimulation of cortical circuits. Objectives: The present study had two aims; a) to determine the extent to which sensory potentials contaminate TEPs using a spatially matched sham condition, and b) to determine whether sensory potentials reflect auditory or somatosensory potentials alone, or a combination of the two. Methods: Twenty healthy participants received active or sham stimulation, with the latter consisting of the click of a sham coil combined with scalp electrical stimulation. Earplugs/headphones were used to suppress the TMS click noise. Two additional control conditions i) electrical stimulation alone and ii) auditory stimulation alone were included in a subset of 13 participants. Results: Signals from active and sham stimulation were correlated in spatial and temporal domains, especially >70ms post-stimulation. Relative to auditory or electrical stimulation alone, combined (sham) stimulation resulted in a) larger evoked responses b) stronger correlations with active stimulation and c) a signal that could not be explained by the linear sum of electrical and auditory stimulation alone. Conclusions: Sensory potentials can confound data interpretations of TEPs at timepoints >70ms post-TMS, while earlier timepoints appear reflective of cortical excitability. Furthermore, contamination of TEPs cannot be explained by auditory or somatosensory potentials alone, but instead reflects a non-linear interaction between both sources. Future studies may benefit from controlling for sensory contamination using sham conditions that are spatially matched to active TMS, and which consist of combined auditory and somatosensory stimulation.