Collapse of transitional wall turbulence captured using a rare events algorithm

This text presents one of the first successful applications of a rare events sampling method for the study of multistability in a turbulent flow without stochastic energy injection. The trajectories of collapse of turbulence in plane Couette flow, and their probability and rate of occurrence are systematically computed using adaptive multilevel splitting (AMS). The AMS computations are performed in a system of size $L_x\times L_z=24\times 18$ at Reynolds number $R=370$ with an acceleration by a factor ${O}(10)$ with respect to direct numerical simulations (DNS) and in a system of size $L_x\times L_z=36\times 27$ at Reynolds number $R=377$ with an acceleration by a factor ${O}(10^3)$ . The AMS results are validated by a comparison with DNS in the smaller system. Visualisations indicate that turbulence collapses because the self-sustaining process of turbulence fails locally. The streamwise vortices decay first in streamwise elongated holes, leaving streamwise invariant streamwise velocity tubes that experience viscous decay. These holes then extend in the spanwise direction. The examination of more than a thousand trajectories in the $(E_{k,x}=\int u_x^2/2\,\textrm {d}^3\boldsymbol {x},E_{k,y-z}=\int (u_y^2/2+u_z^2/2)\,\textrm {d}^3\boldsymbol {x})$ plane in the smaller system confirms the faster decay of streamwise vortices and shows concentration of trajectories. This hints at an instanton phenomenology in the large size limit. The computation of turning point states, beyond which laminarisation is certain, confirms the hole formation scenario and shows that it is more pronounced in larger systems. Finally, the examination of non-reactive trajectories indicates that both the vortices and the streaks reform concomitantly when the laminar holes close.

Optimizing reaction coordinate by flux maximization in the transition path ensemble

Transition path ensemble is a collection of reactive trajectories, all of which largely keep going forward along the transition channel from the reactant state to the product one, and is believed to possess the information necessary for the identification of reaction coordinate. Previously, the full coordinates (both position and momentum) of the snapshots in the transition path ensemble were utilized to obtain the reaction coordinate (J. Chem. Phys. 2016, 144, 114103; J. Chem. Phys. 2018, 148, 084105). Here, with the conformational (or position) coordinates alone, it is demonstrated that the reaction coordinate can be optimized by maximizing the flux of a given coordinate in the transition path ensemble. In the application to alanine dipeptide in vacuum, dihderal angles ϕ and θ were identified to be the two best reaction coordinates, which was consistent with the results in existing studies. A linear combination of these two coordinates gave a better reaction coordinate, which is highly correlated with committor. Most importantly, the method obtained a linear combination of pairwise distances between heavy atoms, which was highly correlated with committor as well. The standard deviation of committor at the transition region defined by the optimized reaction coordinate is as small as 0.08. In addition, the effects of practical factors, such as the choice of transition path sub-ensembles and saving interval between frames in transition paths, on reaction coordinate optimization were also considered.

Determination of Kinetic Properties in Unimolecular Dissociation of Complex Systems from Graph-Theory Based Analysis of an Ensemble of Reactive Trajectories.

<div>We describe and apply a general approach based on graph-theory to obtain kinetic and structural properties from direct dynamics simulations. In particular, we focus on the unimolecular fragmentation of complex systems in which, prior to dissociation, different events can take place, and notably isomerizations and formation of ion-molecule complex.</div><div>3-state and 4-state kinetic models are thus obtained and rate constants for global or specific pathways are obtained from direct counting and flux calculation, both being in agreement.<br />Finally, we show how a theoretical mass spectrum can also be obtained automatically.<br /></div>

Determination of Kinetic Properties in Unimolecular Dissociation of Complex Systems from Graph-Theory Based Analysis of an Ensemble of Reactive Trajectories.

<div>We describe and apply a general approach based on graph-theory to obtain kinetic and structural properties from direct dynamics simulations. In particular, we focus on the unimolecular fragmentation of complex systems in which, prior to dissociation, different events can take place, and notably isomerizations and formation of ion-molecule complex.</div><div>3-state and 4-state kinetic models are thus obtained and rate constants for global or specific pathways are obtained from direct counting and flux calculation, both being in agreement.<br>Finally, we show how a theoretical mass spectrum can also be obtained automatically.<br></div>

Determination of Kinetic Properties in Unimolecular Dissociation of Complex Systems from Graph-Theory Based Analysis of an Ensemble of Reactive Trajectories.

<div>We describe and apply a general approach based on graph-theory to obtain kinetic and structural properties from direct dynamics simulations. In particular, we focus on the unimolecular fragmentation of complex systems in which, prior to dissociation, different events can take place, and notably isomerizations and formation of ion-molecule complex.</div><div>3-state and 4-state kinetic models are thus obtained and rate constants for global or specific pathways are obtained from direct counting and flux calculation, both being in agreement.<br>Finally, we show how a theoretical mass spectrum can also be obtained automatically.<br></div>

A Relaxation Time Approximation method for the efficient detection of critical states in reactive trajectories

We present a bespoke theoretical framework aimed at the computationally efficient Monte Carlo generation of reactive trajectories based on an ab initio potential (Density Functional Theory or higher level of theory), perturbed by a time-dependent force, within the Relaxation Time Approximation (RTA) scope. As a case study, we traced the RTA evolution of Stearic acid adsorbed on a CaCO3 surface, for which we submit an initial set of results on the determination of preferred bonding. Generalization of the RTA method may eventually accommodate kinetic Monte Carlo-based approaches for the analysis of the reactive mesoscale.

TAMI-53. THE ONCOMETABOLITE D-2HG INDUCE INFLAMMATORY ASTROGLIOSIS CAUSING NEUROTOXICITY AND SEIZURES IN IDH MUTATED GLIOMA

The role of tumor-associated astrocytes in the microenvironment of glioma has long been underestimated but is moving into the focus of current research. We explored the role of reactive astrocytes in IDH-mutated glioma using RNA-sequencing of purified astrocytes and microglia and single-nucleus RNA-sequencing of infiltrating tumor regions. Mapping of the transcriptional phenotype of astrocytes along developmental and reactive trajectories revealed an inflammatory transformation of IDH-mutated associated astrocytes. The major proportion of astrocytes is marked by complement-activation similar to findings in neuroinflammatory diseases. A human neocortical slices model with injected IDH-mutated patient-derived cells or D-2HG treatment (+/- microglia depletion) was used to map shared and unique transcriptional adaptation in astrocytes promoted by either tumor cells or metabolic alteration. High-dimensional electrophysiological profiling was used to investigate alterations in neural response to tumor-induced microenvironmental transformation. We showed that 2HG alone promote the inflammatory pattern of astrocytes, which causes neurotoxicity and seizures in our neocortical slice model. Depletion of microglia rescued the neurotoxicity suggesting that microglia predominantly drive inflammatory astrogliosis as a response to metabolic alteration the tumor environment. We showed that neurotoxic astrogliosis induced by the oncometabolite D-2HG via distinct microglia activation promote the evolution of frequently observed seizures in IDH-mutated glioma patients.

Collisional Dynamics Simulations Revealing Fragmentation Properties of Zn(II)-Bound Poly-Peptide

<div> <div> <div> <p>Chemical dynamics simulations are performed to study the collision induced gas phase unimolecular fragmentation of a model peptide with the sequence acetyl-His1-Cys2-Gly3-Pro4-Tyr5-His6-Cys7 (analogue methanobactin peptide-5, amb5) and in particular to explore the role of zinc binding on reactivity. Fragmentation pathways, their mechanisms, and collision energy transfer are discussed. The probability distributions of the pathways are compared with the results of the experimental IM-MS, MS/MS spectrum and previous thermal simulations. Collisional activation gives both statistical and non-statistical fragmentation pathways with non-statistical shattering mechanisms accounting for a relevant percentage of reactive trajectories, becoming dominant at higher energies. The tetra-coordination of zinc changes qualitative and quantitative fragmentation, in particular the shattering. The collision energy threshold for the shattering mechanism was found to be 118.9 kcal/mol which is substantially higher than the statistical Arrhenius activation barrier of 35.8 kcal/mol identified previously during thermal simulations. This difference can be attributed to the tetra-coordinated zinc complex that hinders the availability of the sidechains to undergo direct collision with the Ar projectile. </p> </div> </div> </div>

Collisional Dynamics Simulations Revealing Fragmentation Properties of Zn(II)-Bound Poly-Peptide

<div> <div> <div> <p>Chemical dynamics simulations are performed to study the collision induced gas phase unimolecular fragmentation of a model peptide with the sequence acetyl-His1-Cys2-Gly3-Pro4-Tyr5-His6-Cys7 (analogue methanobactin peptide-5, amb5) and in particular to explore the role of zinc binding on reactivity. Fragmentation pathways, their mechanisms, and collision energy transfer are discussed. The probability distributions of the pathways are compared with the results of the experimental IM-MS, MS/MS spectrum and previous thermal simulations. Collisional activation gives both statistical and non-statistical fragmentation pathways with non-statistical shattering mechanisms accounting for a relevant percentage of reactive trajectories, becoming dominant at higher energies. The tetra-coordination of zinc changes qualitative and quantitative fragmentation, in particular the shattering. The collision energy threshold for the shattering mechanism was found to be 118.9 kcal/mol which is substantially higher than the statistical Arrhenius activation barrier of 35.8 kcal/mol identified previously during thermal simulations. This difference can be attributed to the tetra-coordinated zinc complex that hinders the availability of the sidechains to undergo direct collision with the Ar projectile. </p> </div> </div> </div>