Segregation of granular binary mixtures by a ratchet mechanism

We report on a segregation scheme for granular binary mixtures, where the segregation is performed by a ratchet mechanism realized by a vertically shaken asymmetric sawtooth-shaped base in a quasi-two-dimensional box. We have studied this system by computer simulations and found that most binary mixtures can be segregated using an appropriately chosen ratchet, even when the particles in the two components have the same size, and differ only in their normal restitution coefficient or friction coefficient. These results suggest that the components of otherwise non-segregating granular mixtures may be separated using our method.Comment: revtex, 4 pages, 4 figures, submitte

The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention

Background: When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. Methods: In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na+/K+ pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. Results: We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na+/K+ ATPase elicits SD. Elevated K+ or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Conclusions: Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory. © 2022, The Author(s)

Questioning Glutamate Excitotoxicity in Acute Brain Damage: The Importance of Spreading Depolarization

Background: Within 2 min of severe ischemia, spreading depolarization (SD) propagates like a wave through compromised gray matter of the higher brain. More SDs arise over hours in adjacent tissue, expanding the neuronal damage. This period represents a therapeutic window to inhibit SD and so reduce impending tissue injury. Yet most neuroscientists assume that the course of early brain injury can be explained by glutamate excitotoxicity, the concept that immediate glutamate release promotes early and downstream brain injury. There are many problems with glutamate release being the unseen culprit, the most practical being that the concept has yielded zero therapeutics over the past 30 years. But the basic science is also flawed, arising from dubious foundational observations beginning in the 1950s Methods: Literature pertaining to excitotoxicity and to SD over the past 60 years is critiqued. Results: Excitotoxicity theory centers on the immediate and excessive release of glutamate with resulting neuronal hyperexcitation. This instigates poststroke cascades with subsequent secondary neuronal injury. By contrast, SD theory argues that although SD evokes some brief glutamate release, acute neuronal damage and the subsequent cascade of injury to neurons are elicited by the metabolic stress of SD, not by excessive glutamate release. The challenge we present here is to find new clinical targets based on more informed basic science. This is motivated by the continuing failure by neuroscientists and by industry to develop drugs that can reduce brain injury following ischemic stroke, traumatic brain injury, or sudden cardiac arrest. One important step is to recognize that SD plays a central role in promoting early neuronal damage. We argue that uncovering the molecular biology of SD initiation and propagation is essential because ischemic neurons are usually not acutely injured unless SD propagates through them. The role of glutamate excitotoxicity theory and how it has shaped SD research is then addressed, followed by a critique of its fading relevance to the study of brain injury. Conclusions: Spreading depolarizations better account for the acute neuronal injury arising from brain ischemia than does the early and excessive release of glutamate.Grants to RDA from the Canadian Heart & Stroke Foundation, National Science Engineering and Research Council and the New Frontiers in Research Fund, to E.F from the National Research, Development and Innovation Office of Hungary, grant no. K134377; and the EU’s Horizon 2020 research and innovation program under grant agreement No. 739593, and to JPD from the DFG (German research Council) (DFG DR323/5-1,DFG DR 323/10-1) BMBF Bundesministerium fuer Bildung und Forschung (Era-Net Neuron EBio2, with funds from BMBF 01EW2004)

Analytical and numerical investigation of escape rate for a noise driven bath

We consider a system-reservoir model where the reservoir is modulated by an external noise. Both the internal noise of the reservoir and the external noise are stationary, Gaussian and are characterized by arbitrary decaying correlation functions. Based on a relation between the dissipation of the system and the response function of the reservoir driven by external noise we numerically examine the model using a full bistable potential to show that one can recover the turn-over features of the usual Kramers' dynamics when the external noise modulates the reservoir rather than the system directly. We derive the generalized Kramers' rate for this nonequilibrium open system. The theoretical results are verified by numerical simulation.Comment: Revtex, 25 pages, 5 figures. To appear in Phys. Rev.

Transitions in the Horizontal Transport of Vertically Vibrated Granular Layers

Motivated by recent advances in the investigation of fluctuation-driven ratchets and flows in excited granular media, we have carried out experimental and simulational studies to explore the horizontal transport of granular particles in a vertically vibrated system whose base has a sawtooth-shaped profile. The resulting material flow exhibits novel collective behavior, both as a function of the number of layers of particles and the driving frequency; in particular, under certain conditions, increasing the layer thickness leads to a reversal of the current, while the onset of transport as a function of frequency occurs gradually in a manner reminiscent of a phase transition. Our experimental findings are interpreted here with the help of extensive, event driven Molecular Dynamics simulations. In addition to reproducing the experimental results, the simulations revealed that the current may be reversed as a function of the driving frequency as well. We also give details about the simulations so that similar numerical studies can be carried out in a more straightforward manner in the future.Comment: 12 pages, 18 figure

The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention

Background: When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. Methods: In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na/K pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. Results: We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na/K ATPase elicits SD. Elevated K or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Conclusions: Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory.This work was supported by grants from the Heart and Stroke Foundation of Canada and the National Science and Engineering Research Council of Canada to RDA, an NIH grant (NS106901) to CWS, a National Research, Development and Innovation Office of Hungary grant (K1343777) and EU Horizon 2020 research and innovation program (739953) to EF and from DFG Deutsche Forschungsgemeinschaft (German Research Council) (DFG DR 323/5-1), DFG DR 323/10-1, and BMBF Bundesministerium fuer Bildung und Forschung (EraNet Neuron EBio2, with funds from BMBF 01EW2004) to JPD

Synchronisation in networks of delay-coupled type-I excitable systems

We use a generic model for type-I excitability (known as the SNIPER or SNIC model) to describe the local dynamics of nodes within a network in the presence of non-zero coupling delays. Utilising the method of the Master Stability Function, we investigate the stability of the zero-lag synchronised dynamics of the network nodes and its dependence on the two coupling parameters, namely the coupling strength and delay time. Unlike in the FitzHugh-Nagumo model (a model for type-II excitability), there are parameter ranges where the stability of synchronisation depends on the coupling strength and delay time. One important implication of these results is that there exist complex networks for which the adding of inhibitory links in a small-world fashion may not only lead to a loss of stable synchronisation, but may also restabilise synchronisation or introduce multiple transitions between synchronisation and desynchronisation. To underline the scope of our results, we show using the Stuart-Landau model that such multiple transitions do not only occur in excitable systems, but also in oscillatory ones.Comment: 10 pages, 9 figure

The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention

Background: When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. Methods: In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na+/K+ pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. Results: We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na+/K+ ATPase elicits SD. Elevated K+ or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Conclusions: Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory. © 2022, The Author(s)