Metastable states in stochastic systems are often characterized by the presence of small eigenvalues in the generator of the stochastic dynamics. We here show that metastability in many-body systems ...is not necessarily associated with small eigenvalues. Instead, many-body explosion of eigenmode expansion coefficients characterizes slow relaxation, which is demonstrated for two models, interacting particles in a double-well potential and the Fredrickson-Andersen model, the latter of which is a prototypical example of kinetically constrained models studied in glass and jamming transitions. Our results provide insights into slow relaxation and metastability in many-body stochastic systems.
Pneumonia is a major cause of death in older people, and the number of such deaths is increasing. Present guidelines for pneumonia management are based on a pathogen‐oriented strategy that relies on ...the optimal application of antibiotics. Older pneumonia inpatients show the high incidence of aspiration pneumonia. The main cause of aspiration pneumonia is an impairment in the swallowing and cough reflexes. These facts suggest a limitation of present management strategies and a requirement for new strategies for aspiration pneumonia. Sarcopenia is the loss of muscle strength and mass, and declining physical function with aging. Recently, a decrease in the mass or strength of the swallowing muscles was suggested to be associated with reduced swallowing function. Accordingly, dysphagia caused by sarcopenia of the systemic and swallowing‐related muscles was named sarcopenic dysphagia. Presently, few studies have shown associations between aspiration pneumonia and sarcopenic dysphagia. As for the cough reflex, strong cough prevents aspiration pneumonia, and its strength is regulated by respiratory muscles. A few studies have reported a relationship between muscles and pneumonia in older people. Sarcopenia is a risk factor for pneumonia in older people, and aspiration pneumonia inpatients with low muscle mass show high mortality rates. Aspiration pneumonia induced muscle atrophy in respiratory, swallowing, and skeletal muscles in an animal model and humans. Associations between respiratory muscle strength and pneumonia are currently under investigation. Evaluation and management of sarcopenia could potentially become a new strategy to prevent and treat pneumonia in older patients, and research has only recently been launched. Geriatr Gerontol Int 2020; 20: 7–13.
This report was written by the Japanese Society of Dysphagia Rehabilitation, the Japanese Association of Rehabilitation Nutrition, the Japanese Association on Sarcopenia and Frailty, and the Society ...of Swallowing and Dysphagia of Japan to consolidate the currently available evidence on the topics of sarcopenia and dysphagia. Histologically, the swallowing muscles are of different embryological origin from somatic muscles, and receive constant input stimulation from the respiratory center. Although the swallowing muscles are striated, their characteristics are different from those of skeletal muscles. The swallowing muscles are inevitably affected by malnutrition and disuse; accumulating evidence is available regarding the influence of malnutrition on the swallowing muscles. Sarcopenic dysphagia is defined as dysphagia caused by sarcopenia of the whole body and swallowing‐related muscles. When sarcopenia does not exist in the entire body, the term “sarcopenic dysphagia” should not be used. Additionally, sarcopenia due to neuromuscular diseases should be excluded; however, aging and secondary sarcopenia after inactivity, malnutrition and disease (wasting disorder and cachexia) are included in sarcopenic dysphagia. The treatment of dysphagia due to sarcopenia requires both dysphagia rehabilitation, such as resistance training of the swallowing muscles and nutritional intervention. However, the fundamental issue of how dysphagia caused by sarcopenia of the swallowing muscles should be diagnosed remains unresolved. Furthermore, whether dysphagia can be caused by primary sarcopenia should be clarified. Additionally, more discussion is required on issues such as the relationship between dysphagia and secondary sarcopenia, as well as the diagnostic criteria and means for diagnosing dysphagia caused by sarcopenia. Geriatr Gerontol Int 2019; 19: 91–97.
In Floquet engineering, periodic driving is used to realize novel phases of matter that are inaccessible in thermal equilibrium. For this purpose, the Floquet theory provides us a recipe for ...obtaining a static effective Hamiltonian. Although many existing works have treated closed systems, it is important to consider the effect of dissipation, which is ubiquitous in nature. Understanding the interplay of periodic driving and dissipation is a fundamental problem of nonequilibrium statistical physics that is receiving growing interest because of the fact that experimental advances have allowed us to engineer dissipation in a controllable manner. In this review, we give a detailed exposition on the formalism of quantum master equations for open Floquet systems and highlight recent work investigating whether equilibrium statistical mechanics applies to Floquet states.
Time-periodic (Floquet) driving is a powerful way to control the dynamics of complex systems, which can be used to induce a plethora of new physical phenomena. However, when applied to many-body ...systems, Floquet driving can also cause heating, and lead to a featureless infinite-temperature state, hindering most useful applications. It is therefore important to find mechanisms to suppress such effects. Floquet prethermalization refers to the phenomenon where many-body systems subject to a high-frequency periodic drive avoid heating for very long times, instead tending to transient states that can host interesting physics. Its key signature is a strong parametric suppression of the heating rate as a function of the driving frequency. Here, we review our present understanding of this phenomenon in both quantum and classical systems, and across various models and methods. In particular, we present rigorous theorems underpinning Floquet prethermalization in quantum spin and fermionic lattice systems and extensions to systems with degrees of freedom that have unbounded local dimension. Further, we briefly describe applications to novel nonequilibrium phases of matter, and recent experiments probing prethermalization with quantum simulators. We close by describing the frontiers of Floquet prethermalization beyond strictly time-periodic drives, including time-quasiperiodic driving and long-lived quasi-conserved quantities enabled by large separation of energy scales.
Amyloid precursor protein (APP) proteolysis is required for production of amyloid-β (Aβ) peptides that comprise β-amyloid plaques in brains of Alzheimer's disease (AD) patients. Recent AD therapeutic ...interest has been directed toward a group of anti-amyloidogenic compounds extracted from plants. We orally administered the brain penetrant, small molecule phenolic compound ferulic acid (FA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) and evaluated behavioral impairment and AD-like pathology. Oral FA treatment for 6 months reversed transgene-associated behavioral deficits including defective: hyperactivity, object recognition, and spatial working and reference memory, but did not alter wild-type mouse behavior. Furthermore, brain parenchymal and cerebral vascular β-amyloid deposits as well as abundance of various Aβ species including oligomers were decreased in FA-treated PSAPP mice. These effects occurred with decreased cleavage of the β-carboxyl-terminal APP fragment, reduced β-site APP cleaving enzyme 1 protein stability and activity, attenuated neuroinflammation, and stabilized oxidative stress. As in vitro validation, we treated well-characterized mutant human APP-overexpressing murine neuron-like cells with FA and found significantly decreased Aβ production and reduced amyloidogenic APP proteolysis. Collectively, these results highlight that FA is a β-secretase modulator with therapeutic potential against AD.
A periodically driven quantum system, when coupled to a heat bath, relaxes to a non-equilibrium asymptotic state. In the general situation, the retrieval of this asymptotic state presents a rather ...non-trivial task. It was recently shown that in the limit of an infinitesimal coupling, using the so-called rotating wave approximation (RWA), and under strict conditions imposed on the time-dependent system Hamiltonian, the asymptotic state can attain the Gibbs form. A Floquet-Gibbs state is characterized by a density matrix which is diagonal in the Floquet basis of the system Hamiltonian with the diagonal elements obeying a Gibbs distribution, being parametrized by the corresponding Floquet quasi-energies. Addressing the non-adiabatic driving regime, upon using the Magnus expansion, we employ the concept of a corresponding effective Floquet Hamiltonian. In doing so we go beyond the conventionally used RWA and demonstrate that the idea of Floquet-Gibbs states can be extended to the realistic case of a weak, although finite system-bath coupling, herein termed effective Floquet-Gibbs states.
This study investigated the relationship between the analgesic efficacy of acetaminophen and the descending noradrenergic systems using rodent models of inflammatory pain.
Inflammatory pain models ...were established by carrageenan injection into rats' paws. The models were defined as acute (4 h after carrageenan injection), subacute (24 h after carrageenan injection), and late (1 week after carrageenan injection) phase. To evaluate intravenous acetaminophen treatment, the withdrawal threshold to mechanical stimuli was assessed simultaneously with in vivo microdialysis assay of noradrenaline levels in the locus coeruleus (LC). Further analyses were performed to observe the effect of yohimbine on the treatment and the impact of AM404 treatment, a metabolite of acetaminophen, on noradrenaline levels in the LC.
In all phases, intravenous acetaminophen had a significant anti-hyperalgesic effect (p < 0.05). There was a significant time-dependent increase in the noradrenaline concentration within the LC (acetaminophen versus saline treatment; at 30 min, p < 0.001; 60 min, p < 0.01) in the subacute pain model, but not in the acute and late phase pain models. Intrathecal pre-injection of yohimbine attenuated the anti-hyperalgesic effect after acetaminophen injection only in the subacute model (p < 0.05). In the subacute pain model, intracerebroventricular administration of AM404 showed the same trend in noradrenaline levels as acetaminophen administration (AM404 versus vehicle group at 30 min, p < 0.001).
We found the descending noradrenergic inhibitory system is involved in the antinociceptive action of acetaminophen in the subacute phase of inflammatory pain.
•Acetaminophen (APAP) is one of the most essential analgesics worldwide.•Coping with chronic pain and the opioid crisis problem, APAP is a desirable option.•Exploring its unclarified analgesic mechanism, noradrenergic system was focused.•The descending noradrenergic system affects APAP's analgesia in inflammatory model.•Time dependent analgesic mechanism during pain chronification may be involved.
Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the ...X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after 5-ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with 5-ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. 5-ALA has been used clinically for photodynamic therapy. Thus, "radiodynamic therapy", using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.
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