Long-Term Strength Prediction of Wood Based Composites Using the Kinetic Equations

The existing behaviour models of the structures under constant load (creep) have a fairly wide forecast horizon and low accuracy. As a rule, they consider the transition from an undestroyed state of an element to a destroyed one, in one stage. The purpose of this study is to substantiate and develop a new approach to predicting long-term strength based on kinetic equations, which, in turn, should consider the multistage nature of the process of gradual destruction of structure elements. To achieve this purpose, the study solves the tasks of creating a multistage kinetic transition of individual structure elements from an initially elastic state to a viscoelastic state, and then to a fractured state. When describing this process, the authors employed the methods of formal kinetics and the theory of continuum damage mechanics, including the method of basic diagrams. Wood-based composites were used as the materials under study. Based on the results of the conducted full-scale and computational experiments, the study discovers that a mathematical model based on kinetic equations adequately describes the behaviour of the materials under study for long-term strength; the proposed two-stage model determines the forecast horizon much more accurately than the available one-stage models. The kinetic parameters that determine the rate of transition of a structural element from an elastic state to a viscoelastic state, and then to a destroyed state, were determined based on experimental base chart. The time to fracture was determined at three-point bending at a load equal to 70% of the flexural strength at temperatures of 20°C and 60°C, constant humidity RH 65% and moisture content MC 8%. When building control charts, the load increased by another 15%. The method allows narrowing the forecast horizon and determining the moment of transition of a structure from a stationary state to a blow-up regime with a higher accuracy

On the violation of the zeroth law of turbulence in space plasmas

The zeroth law of turbulence states that, for fixed energy input into large-scale motions, the statistical steady state of a turbulent system is independent of microphysical dissipation properties. This behaviour, which is fundamental to nearly all fluid-like systems from industrial processes to galaxies, occurs because nonlinear processes generate smaller and smaller scales in the flow, until the dissipation – no matter how small – can thermalise the energy input. Using direct numerical simulations and theoretical arguments, we show that in strongly magnetised plasma turbulence such as that recently observed by the Parker Solar Probe spacecraft, the zeroth law is routinely violated. Namely, when such turbulence is ‘imbalanced’ – when the large-scale energy input is dominated by Alfvénic perturbations propagating in one direction (the most common situation in space plasmas) – nonlinear conservation laws imply the existence of a ‘barrier’ at scales near the ion gyroradius. This causes energy to build up over time at large scales. The resulting magnetic-energy spectra bear a strong resemblance to those observed in situ, exhibiting a sharp, steep kinetic transition range above and around the ion-Larmor scale, with flattening at yet smaller scales. The effect thus offers a possible solution to the decade-long puzzle of the position and variability of ion-kinetic spectral breaks in plasma turbulence. The existence of the ‘barrier’ also suggests that, how a plasma is forced at large scales (the imbalance) may have a crucial influence on thermodynamic properties such as the ion-to-electron heating ratio.

Dynamic conformational states of apo and cabozantinib bound TAM kinases to differentiate active-inactive kinetic models

Tyro3, Axl, Mer (TAM) receptor tyrosine kinases (RTKs) are overexpressed in several human cancers. Cabozantinib, a small molecule inhibitor constrains the activity of TAM kinases at nanomolar concentrations. The dynamic active and inactive conformations of kinases play a crucial role in inhibitor binding and the activation of intracellular downstream signalling pathways. The all atom molecular dynamics (MD) simulations at microsecond timescale and longer provide robust insights into the structural details of conformational alterations of proteins due to their role cellular metabolic activities and signaling pathways. In this current study we report microsecond molecular dynamics (MD) simulations of apo, cabozantinib complexed active and inactive TAM RTKs and analysed the post-MD trajectories using the principal component analysis (PCA). Markov State Models (MSM) and transition pathways from Perron-cluster cluster analysis. For consensus, the 1s atomistic simulations with enhanced computational algorithms indicated us to treat tyrosine kinase family by overwhelming dynamic states existence when bound to kinase inhibitors. The dynamic mechanistic pathways intrinsic to the kinase activity and protein conformational landscape in the TAM kinases are revealed due to the alterations in the P-loop, C-helix, activation loop and F-helix that result in breaking the regulatory and catalytic spines. We deciphered the long lived kinetic transition states of distinct active and inactive structural models from MD simulations trajectories of TAM RTKs bound inhibitor complex that have not been revealed so far.

Processivity of molecular motors under vectorial loads

Molecular motors are cellular machines that drive the spatial organisation of the cells by transporting cargoes along intracellular filaments. Although the mechanical properties of single molecular motors are relatively well characterised, it remains elusive how the three-dimensional geometry of a load imposed on a motor affects its processivity, i.e., the average distance that a motor moves per interaction with a filament. Here, we theoretically explore this question for a single kinesin molecular motor by analysing the load-dependence of the stepping and detachment processes. We find that the processivity of kinesin increases with lowering the load angle between kinesin and microtubule filament, due to the deceleration of the detachment rate. When the load angle is large, the processivity is predicted to enhance with accelerating the stepping rate, through an optimal distribution of the load over the kinetic transition rates underlying a mechanical step of the motor. These results provide new insights into understanding of the design of potential synthetic biomolecular machines that can travel long distances with high velocities.

Kinetic Transition in Amyloid Assembly as a Screening Assay for Oligomer-Selective Dyes

Assembly of amyloid fibrils and small globular oligomers is associated with a significant number of human disorders that include Alzheimer’s disease, senile systemic amyloidosis, and type II diabetes. Recent findings implicate small amyloid oligomers as the dominant aggregate species mediating the toxic effects in these disorders. However, validation of this hypothesis has been hampered by the dearth of experimental techniques to detect, quantify, and discriminate oligomeric intermediates from late-stage fibrils, in vitro and in vivo. We have shown that the onset of significant oligomer formation is associated with a transition in thioflavin T kinetics from sigmoidal to biphasic kinetics. Here we showed that this transition can be exploited for screening fluorophores for preferential responses to oligomer over fibril formation. This assay identified crystal violet as a strongly selective oligomer-indicator dye for lysozyme. Simultaneous recordings of amyloid kinetics with thioflavin T and crystal violet enabled us to separate the combined signals into their underlying oligomeric and fibrillar components. We provided further evidence that this screening assay could be extended to amyloid-β peptides under physiological conditions. Identification of oligomer-selective dyes not only holds the promise of biomedical applications but provides new approaches for unraveling the mechanisms underlying oligomer versus fibril formation in amyloid assembly.