Abstract Local field potentials recorded from the subthalamic nucleus (STN) in Parkinson’s disease (PD) exhibit a distinctive multiscale spectral signature: exaggerated beta-band oscillations (13-30 Hz) coupled to high-frequency oscillations (HFOs, 200-400 Hz), with HFO amplitude being phase-locked to the beta cycle. This phase-amplitude coupling (PAC) has been identified as a promising biomarker of the parkinsonian state, yet no biophysical model has explained how it emerges, what determines the HFO frequency, or how HFOs can exist without beta modulation in the medicated STN. Here we show that a heterogeneous population of excitatory Izhikevich neurons with recurrent coupling produces three dynamical regimes: (i) asynchronous tonic firing, (ii) asynchronous bursting, in which neurons burst individually producing broadband HFO power but without coherent population-level PAC, and (iii) synchronous bursting, which gives rise to beta-HFO PAC. The regimes are governed by two biophysically interpretable parameters that capture complementary effects of dopamine depletion: one reflecting changes in intrinsic neuronal excitability, the other reflecting changes in synaptic coupling strength. The transition from asynchronous to synchronous bursting in this model captures the emergence of pathological STN neuronal activity in the parkinsonian state. HFO peak frequency varies continuously across the two-parameter landscape, suggesting a possible mechanism of the clinically observed shift from slow (200-300 Hz) to fast (300-400 Hz) HFOs between medication states. The character of the synchronization transition depends on baseline excitability, ranging from a sharp co-emergence of bursting and synchrony at low excitability to a decoupled transition at intermediate excitability, where the bursting fraction saturates while the population synchronization continues to increase with coupling. We also extend the model to include reciprocal coupling to an inhibitory population of globus pallidus externa (GPe)-like neurons and report a similar asynchronous-to-synchronous bursting transition and beta-HFO PAC emerging in the STN population, with the beta rhythm being set by the delay in the synaptic coupling between the two populations. The model generates testable predictions for future clinical and experimental studies, provides a numerical dissection of how mesoscopic LFP features map onto microscopic neuronal dynamics, and serves as a computational building block for future circuit-level models that may inform brain stimulation strategies tailored to the patient-specific dynamical state of the STN. Author summary In Parkinson’s disease, local field potentials (LFP) from the subthalamic nucleus (STN) contain two prominent rhythms: a slow beta rhythm (13-30 Hz) and fast oscillations (200-400 Hz). In the parkinsonian state, these rhythms become coupled, with fast oscillation amplitude varying systematically with beta phase, a relationship absent in the medicated state. We built a biophysical spiking neuron network model that captures two key effects of dopamine depletion on STN neuronal activity: changes in the intrinsic neuronal excitability and changes in synaptic coupling strength. The model produces fast oscillations from rapid intraburst firing, while the slow beta rhythm and its coupling to fast oscillations emerge with the onset of synchronized bursting across the population. Importantly, the frequency of the fast oscillations shifts continuously depending on both parameters, explaining a puzzling clinical observation that these oscillations change frequency between medication states. The model also reproduces the modulation pattern in the spike-triggered average of HFO envelope amplitude reported in patient recordings, confirming consistency with single-unit observations as well as LFP-level spectral features. By mapping how multi-timescale LFP spectral features relate to the dynamical regime of the underlying neuronal population, this work offers a framework for brain stimulation strategies informed by patient-specific dynamical states.

Parkinson's disease (PD) is marked by impairments in voluntary movement, including prolonged movement preparation and execution, yet how parkinsonism alters neural processing to produce these deficits remains unresolved. Prior work examining M1 spiking activity in parkinsonian states has largely characterized firing-rate changes and motor representations at the level of individual neurons, with inconsistent results and limited insight into population-level organization. Here we investigated how parkinsonism reshapes the population-level organization of neural activity in M1 during movement. We simultaneously recorded large populations of neurons from M1 in two nonhuman primates performing reaching tasks before and after induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the parkinsonian state, both preparation and reach durations were significantly prolonged. Population-level analyses revealed that parkinsonism increased the dimensionality of M1 activity during both preparation and movement and reduced the orthogonality between preparatory and movement-related subspaces. Moreover, trial-by-trial variability in reach duration was explained by the alignment of the preparatory and reach subspaces, indicating the functional role of subspace orthogonality. Together, these findings suggest that parkinsonism disrupts the population-level organization of cortical dynamics across computations, providing a population-level framework linking altered cortical dynamics to the movement-related dysfunction observed in PD.

Excessive daytime sleepiness, i.e., the inability to sustain wakefulness during the day, is a common Parkinson’s disease (PD) non-motor symptom. Elevated cortico-basal ganglia beta oscillatory power (8-35 Hz) is a pathophysiological signature of PD motor signs. The relationship between beta oscillatory power and daytime sleepiness, however, remains unclear. Here, we examined the relationship between beta power and daytime vigilance in parkinsonian nonhuman primates. We administered dopaminergic medication to alter cortico-basal ganglia beta power and measured its effect on daytime vigilance. The beta power from motor cortex (MC) and subthalamic nucleus (STN), and wake quantity were derived in the following conditions: OFF-medication, ON-medication, and decay of medication effect. STN low-beta (8-20 Hz) power negatively correlated with wake quantity, suggesting that elevated STN low-beta power could disrupt sustenance of wakefulness. The cortical low-beta power did not correlate with wakefulness. Interestingly, STN and MC high-beta (21-35 Hz) power positively correlated with wake quantity. Our data provide evidence for an association between beta power and daytime vigilance in parkinsonism in addition to its known relationship with PD motor signs. These findings could inform targeted treatments to promote wakefulness in PD by selectively suppressing (e.g., low-beta) and/or amplifying (e.g., high-beta) cortico-basal ganglia beta oscillatory power. The neurophysiology of excessive daytime sleepiness in Parkinson’s disease (PD) remains unclear. Here, the authors found that beta oscillatory activity, a pathophysiological signature of PD motor signs, is also associated with daytime vigilance in parkinsonism

The mechanical properties of soil in soft soil area are poor, and the settlement of the underlying layer in the composite foundation accounts for a large proportion of the total settlement. At present, most of the research focuses on the settlement of the reinforced area, and the research on the settlement of the underlying layer is of great significance for the settlement of soft soil composite foundation. The differences in load transfer modes of soil and pile are analyzed, and based on the Boussinesq solution and Mindlin solution, a calculation method for the stress and settlement of the underlying layer in flexible and rigid pile composite foundation is proposed. The relative displacement of soil and pile in flexible pile composite foundation is small, and the negative friction can be ignored, but the influence of effective pile length should be considered. The relative displacement of soil and pile in rigid pile composite foundation is large, so the negative friction should be considered. Part of soil top stress is transmitted to the pile via negative friction, and then the pile axial force is transmitted back to the soil via positive friction. In addition to effective pile length, the change of stress transfer path caused by negative friction should also be considered in settlement calculation.

Pretreatment is a key step in lignocellulosic biorefinery. In this study, the combination of organosolv pretreatment and lignin repolymerization inhibitor was put forward to fractionate the lignocellulosic biomass, providing readily hydrolyzed substrate. Results showed that, acidic 1,4-butanediol pretreatment extensively removed lignin from softwood, reducing the physical blockage effect of lignin. Besides, lignin repolymerization inhibitors were employed to modify lignin, giving rise to lower unproductive binding effect of lignin. As a result, maximum 79.9 +/- 0.3 % of original lignin in raw biomass could be removed, and 97.9 +/- 0.5 % of glucan in pretreated solid could be converted into fermentable sugars after acidic butanediol pretreatment assisted by sodium 2-naphthol7-sulphonate and enzymatic hydrolysis at 2 % glucan loading. Furthermore, a modified pre-hysrolysis simultaneous saccharification and fermentation process at 10 % glucan loading produced 45.6 +/- 1.7 g/L ethanol, with ethanol yield of 18.7 +/- 0.4 g/100 g raw biomass. Finally, the mass balance revealed that the lignocellulosic biorefinery based on acidic butanediol pretreatment assisted by sodium 2-naphthol-7-sulphonate could achieve full utilization of lignocellulosic components to co -produce ethanol, lignin materials and hemicellulose-derived mono-saccharides.

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson’s disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8–35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however. To address this question, we used a within-subject design in a nonhuman primate (NHP) model of PD to record local field potentials from the primary motor cortex (MC) during sleep across normal and mild parkinsonian states. The MC is a critical node in the BGTC network, exhibits pathological oscillations with depletion in dopamine tone, and displays high amplitude slow oscillations during SWS. The MC is therefore an appropriate recording site to understand the neurophysiology of SWS dysfunction in parkinsonism. We observed a reduction in SWS quantity (p = 0.027) in the parkinsonian state compared to normal. The cortical delta (0.5–3 Hz) power was reduced (p = 0.038) whereas beta (8–35 Hz) power was elevated (p = 0.001) during SWS in the parkinsonian state compared to normal. Furthermore, SWS quantity positively correlated with delta power (r = 0.43, p = 0.037) and negatively correlated with beta power (r = −0.65, p < 0.001). Our findings support excessive beta oscillations as a mechanism for SWS dysfunction in mild parkinsonism and could inform the development of neuromodulation therapies for enhancing SWS in people with PD.

This study analyzes the effects of heat release rate (HRR), fire position, smoke exhaust velocity, shaft diameter, and ambient pressure on the smoke exhaust efficiency in a rescue station with semi-transverse ventilation. The results demonstrate that the shaft close to the fire source has higher smoke exhaust efficiency, but the fire location has little effect on the overall smoke exhaust efficiency. The smoke exhaust efficiency decreases with the increase of HRR and is proportional to the -1/3 power of the dimensionless HRR. Before the smoke is overall controlled in the rescue station, increasing the smoke exhaust velocity can improve smoke exhaust efficiency, and the smoke exhaust efficiency is proportional to the 2/3 power of the dimensionless smoke exhaust velocity. When the smoke in the rescue station is overall controlled, increasing the exhaust velocity can reduce the smoke spread distance. Moreover, the smoke exhaust efficiency is proportional to the 9/5 power of the dimensionless shaft diameter and 0.3 power of the pressure ratio. Finally, combined with theoretical analysis, a prediction model of the smoke exhaust efficiency is obtained. Therefore, this study can guide the design of the semi-transverse ventilation system in extra-long railway tunnel rescue stations at different altitudes.

Shengxian decoction (SXT) is a traditional Chinese medicine that is clinically used for treating cardiovascular diseases. It is known for its beneficial effect on cardiomyocyte injuries, some of which can be induced by anticancer agents including doxorubicin (DOX). To determine the molecular mechanisms involved in the cardioprotective effects of SXT, DOX-induced H9c2 cells were analyzed for apoptosis and expression levels of apoptosis biomarkers. Cell viability and apoptosis were measured by CCK-8 and flow cytometry. Triggering receptors expressed on myeloid cells 1 (TREM1), cleaved caspase-3, survivin and NF-κBp65 expression levels were measured by reverse transcription-quantitative PCR and/or western blotting. A total of 30 adult male Sprague-Dawley rats were randomly allocated into five groups (n=6 each); control group receiving 0.9% saline, 1 DOX group receiving 2.5 mg/kg of DOX and 3 DOX + SXT groups, receiving a DOX dose equivalent to the DOX-only group and either 0.4, 0.8 or 1.6 g/kg of SXT. It was found that DOX increased apoptosis and NF-κB activation of H9c2 cells by increasing TREM1 expression and that SXT inhibited apoptosis and NF-κB activation of H9c2 cells induced by DOX or Trem1 overexpression. SXT also significantly reversed DOX-induced cardiotoxicity in rats. The results suggested that the protective effects of SXT against DOX-induced apoptosis may be attributed to its downregulation of TREM1.

At present, the cushion thickness of composite foundation under rigid base is mostly selected by the experience of the engineer, which is of great arbitrariness.In order to improve this problem, the optimum design method of cushion thickness is proposed by theoretical research.First, the stress diffusion line in the cushion is assumed to be a quadratic curve, and the critical diffusion thickness of the pile top stress is obtained.Then, by analyzing the relative deformation between soil and pile, pile top penetration into the critical cushion thickness is proposed.Finally, based on the relationship between stress ratio of pile to soil and cushion thickness, the calculation method of optimum cushion thickness is put forward.The application of engineering cases shows that the proposed method has better calculation results, which attests to the correctness of the method.The method can be used for the optimal design of cushion thickness of single-type-pile or multi-type-pile composite foundation.

The existence of the ultra-wide road tunnels improves the transportation efficiency and promotes economic development. However, fire hazards cannot be ignored. Thus, a single entrance 4-lane road tunnel is selected to explore the fire smoke control effect of an ultra-wide road tunnel with lateral exhaust. First, a scale model experiment is utilized to verify the accuracy of the numerical model and then in the influence of the most unfavorable position of the fire source, the number of open smoke outlets and the amount of smoke exhaust volumes on the smoke control effect of tunnel fire under the lateral exhaust mode is simulated by a three-dimensional model. The results show that the distribution pattern of fire smoke in an ultra-wide road tunnel under the lateral exhaust mode is affected by the lateral position of the fire source. When the fire source is closer to the sidewall of the exhaust duct, the smoke distribution that is inclined to the sidewall of the tunnel is more obvious. Based on the comparison among the time of the smoke spreading to the tunnel entrance, the spreading distance of 60 °C smoke, and the smoke exhaust efficiency under various working conditions, it is concluded that the most unfavorable lateral fire source location is in the middle of the tunnel. What’s more, 4 open smoke exhaust ports with 200 m3/s exhaust volume near the fire source can achieve the best smoke control effect.

Introduction:Coordinated Reset Deep Brain Stimulation (CR DBS) is a novel DBS approach for treating Parkinson's disease (PD) that uses lower levels of burst stimulation through multiple contacts of the DBS lead. Though CR DBS has been demonstrated to have sustained therapeutic effects on rigidity, tremor, bradykinesia, and akinesia following cessation of stimulation, i.e., carryover effect, its effect on Parkinsonian gait has not been well studied. Impaired gait is a disabling symptom of PD, often associated with a higher risk of falling and a reduced quality of life. The goal of this study was to explore the carryover effect of subthalamic CR DBS on Parkinsonian gait.Methods:Three non-human primates (NHPs) were rendered Parkinsonian and implanted with a DBS lead in the subthalamic nucleus (STN). For each animal, STN CR DBS was delivered for several hours per day across five consecutive days. A clinical rating scale modified for NHP use (mUPDRS) was administered every morning to monitor the carryover effect of CR DBS on rigidity, tremor, akinesia, and bradykinesia. Gait was assessed quantitatively before and after STN CR DBS. The stride length and swing speed were calculated and compared to the baseline, pre-stimulation condition.Results:In all three animals, carryover improvements in rigidity, bradykinesia, and akinesia were observed after CR DBS. Increased swing speed was observed in all the animals; however, improvement in stride length was only observed in NHP B2. In addition, STN CR DBS using two different burst frequencies was evaluated in NHP B2, and differential effects on the mUPDRS score and gait were observed.Discussion:Although preliminary, our results indicate that STN CR DBS can improve Parkinsonian gait together with other motor signs when stimulation parameters are properly selected. This study further supports the continued development of CR DBS as a novel therapy for PD and highlights the importance of parameter selection in its clinical application.

To explore the hydrolysis rules of the methoxysilane coupling agents (MSCA), the Fourier transform near infrared (FTNIR) spectroscopy combined with the partial least squares (PLS) model were successfully applied to study the hydrolysis kinetics of the phenyltrimethoxysilane, vinyltrimethoxysilane, 3-mercaptopropyltrimethoxysilane, 3-chloropropyltrimethoxysilane, (3, 3, 3-trifluoropropyl)trimethoxysilane and (1H, 1H, 2H, 2H-perfluorooctyl)trimethoxysilane in a HCl-catalyzed EtOH system. The fluorinated silicone resin was synthesized by the hydrolysis and copolycondensation reactions of the 1H, 1H, 2H, 2H-perfluorooctyltrimethoxysilane and methyltrimethoxysilane. The results were listed as follows: (1) the fast scanning speed, no sampling characters of the FTNIR spectroscopy, and the data processing ability of the PLS, enabled the method to “catch” the fast changing [H2O] accurately in real time with the resolution of 23 s. (2) The hydrolysis reactions were second-order reactions, the measured results were in good agreement with the theoretical kinetic equations in the primeval stage. Both temperature and acidity could promote the hydrolysis reactions. The applicable pH of this method was 3 7. The rate constant of the PTMS was sensitive to the temperature. The phenyl was unfavorable while the vinyl was favorable to the hydrolysis reaction. (3) The fluorinated silicone resins could hardly be cured without catalysis when the n(PFOTMS)/(n(MTMS) + n(PFOTMS)) was higher than 75

Personal safety risk management is one of the important components of power enterprise safety management. The key is to quantify the risk value. Based on the accident cause theory, combined with the particularity of the subject, object and environment of power supply operation, as well as the theory

纳米流体作为一种高效传热工质,在最近20多年受到广泛关注.根据纳米流体的发展,本文总结了纳米流体的制备方法,在汽车冷却系统中应用的现状以及面临的挑战.

Electrically evoked compound action potentials (ECAPs) generated in the subthalamic nucleus (STN) contain features that may be useful for titrating deep brain stimulation (DBS) therapy for Parkinson's disease. Delivering a strong therapeutic effect with DBS therapies, however, relies on selectively targeting neural pathways to avoid inducing side effects. In this study, we investigated the spatiotemporal features of ECAPs in and around the STN across parameter sweeps of stimulation current amplitude, pulse width, and electrode configuration, and used a linear classifier of ECAP responses to predict electrode location. Four non-human primates were implanted unilaterally with either a directional (n = 3) or non-directional (n = 1) DBS lead targeting the sensorimotor STN. ECAP responses were characterized by primary features (within 1.6 ms after a stimulus pulse) and secondary features (between 1.6 and 7.4 ms after a stimulus pulse). Using these features, a linear classifier was able to accurately differentiate electrodes within the STN versus dorsal to the STN in all four subjects. ECAP responses varied systematically with recording and stimulating electrode locations, which provides a subject-specific neuroanatomical basis for selecting electrode configurations in the treatment of Parkinson's disease with DBS therapy.

Steel-concrete composite beams can give full play to the material properties of concrete and steel, and have been widely used in bridge structures. The two are connected by shear joints, so that the two materials form a single unit, allowing the composite beam to make full use of the advantages of both. In this paper, a fatigue analysis model is established to analyze the fatigue parameters of steel-cement composite beams. From the results of the analysis, it can be seen that the initial maximum value of shear force is assumed by the studs at the beam ends at the intersection of the composite beam, and then decreases non-linearly with fatigue loading, and vice versa for the studs near the middle of the span.

BACKGROUND:Excessive subthalamic nucleus (STN) β-band (13-35 Hz) synchronized oscillations has garnered interest as a biomarker for characterizing disease state and developing adaptive stimulation systems for Parkinson's disease (PD). OBJECTIVES:To report on a patient with abnormal treatment-responsive modulation in the β-band. METHODS:We examined STN local field potentials from an externalized deep brain stimulation (DBS) lead while assessing PD motor signs in four conditions (OFF, MEDS, DBS, and MEDS+DBS). RESULTS:The patient presented here exhibited a paradoxical increase in β power following administration of levodopa and pramipexole (MEDS), but an attenuation in β power during DBS and MEDS+DBS despite clinical improvement of 50% or greater under all three therapeutic conditions. CONCLUSIONS:This case highlights the need for further study on the role of β oscillations in the pathophysiology of PD and the importance of personalized approaches to the development of β or other biomarker-based DBS closed loop algorithms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Ultra-wide road tunnel plays an important role in relieving traffic pressure. The lateral smoke exhaust system was used to control the fire smoke in the ultra-wide road tunnel. This study conducted a series of experiments in a 1:20 scale tunnel to explore the effects of lateral smoke exhaust volume and heat release rate (HRR) on the ceiling temperature in the ultra-wide road tunnel. The results demonstrate that the ceiling temperature in the ultra-wide road tunnel with the lateral smoke exhaust is obliquely distributed along the longitudinal direction, which is different from the other smoke exhaust modes. The lateral smoke exhaust system can create a better evacuation environment for the tunnel space near the exhaust duct. As the HRR increases or the lateral smoke exhaust volume decreases, the ceiling temperature decays more slowly along the longitudinal direction of the tunnel. Finally, a longitudinal attenuation prediction model of the ceiling temperature is proposed based on a nondimensional analysis. The prediction model conforms to a double exponential function and is suitable for ultra-wide road tunnels with lateral smoke exhaust. Therefore, the research results of this study can provide references for ultra-wide road tunnel fire research and the design of lateral smoke exhaust systems.

Background Organosolv pretreatment is one of the most efficient methods for delignification and boosting biomass saccharification. As compared to typical ethanol organosolv pretreatments, 1,4-butanediol (BDO) organosolv pretreatment is a high-boiling-point solvent pretreatment, which can generate low pressure in the reactor during high temperature cooking that improves the operation safety. Although several studies showed that organosolv pretreatment can lead to effective delignification and enhancement in glucan hydrolysis, there has been no studies on acid- and alkali-catalyzed BDO pretreatment, as well as their comparison on promoting biomass saccharification and lignin utilization. Results It was shown that BDO organosolv pretreatment was more effective in removing lignin from poplar as compared with typical ethanol organosolv pretreatment under the same pretreatment conditions. HCl-BDO pretreatment with 40 mM acid loading led to 82.04% of original lignin removed from biomass, as compared to the lignin removal of 59.66% in HCl-Ethanol pretreatment. Besides, acid-catalyzed BDO pretreatment was more effective in improving the enzymatic digestibility of poplar than alkali-catalyzed BDO pretreatment. As a result, HCl-BDO with acid loading of 40 mM provided a good enzymatic digestibility of cellulose (91.16%) and the maximum sugar yield of 79.41% from original woody biomass. The linear correlations between physicochemical structure (e.g., fiber swelling, cellulose crystallinity, crystallite size, surface lignin coverage and cellulose accessibility) changes of BDO pretreated poplar and enzymatic hydrolysis were plotted to figure out the main factors that influenced biomass saccharification. Moreover, acid-catalyzed BDO pretreatment mainly brought about the phenolic hydroxyl (PhOH) groups formation in lignin structure, while alkali-catalyzed BDO pretreatment mostly led to the lower molecular weight of lignin. Conclusions Results indicated that the acid-catalyzed BDO organosolv pretreatment could significantly improve enzymatic digestibility of the highly recalcitrant woody biomass. The great enzymatic hydrolysis of glucan resulted from increased cellulose accessibility, which mostly associated with the higher degree of delignification and hemicellulose solubilization, as well as the more increase in fiber swelling. Besides, lignin was recovered from the organic solvent, which could be used as natural antioxidants. The formation of phenolic hydroxyl groups in lignin structure and the lower molecular weight of lignin contributed to its greater radical scavenging capacity.