K-ATP channel openers facilitate glutamate uptake by GluTs in rat primary cultured Astrocytes

Increasing evidence, including from our laboratory, has revealed that opening of ATP sensitive potassium channels(K-ATP channels) plays the neuronal protective roles both in vivo and in vitro. Thus K-ATP channel openers(KCOs) have been proposed as potential neuroprotectants. Our previous studies demonstrated that K-ATP channels could regulate glutamate uptake activity in PC12 cells as well as in synaptosomes of rats. Since glutamate transporters(GluTs) of astrocytes play crucial roles in glutamate uptake and KATP channels are also expressed in astrocytes, the present study showed whether and how KATP channels regulated the function of GluTs in primary cultured astrocytes. The results showed that nonselective KCO pinacidil, selective mitochondrial KCO diazoxide, novel, and blood-brain barrier permeable KCO iptakalim could enhance glutamate uptake, except for the sarcolemmal KCO P1075. Moreover pinacidil, diazoxide, and iptakalim reversed the inhibition of glutamate uptake induced by 1-methyl-4-phenylpyridinium(MPP+). These potentiated effects were completely abolished by mitochondrial K-ATP blocker 5-hydroxydecanoate. Furthermore, either diazoxide or iptakalim could inhibit MPP+-induced elevation of reactive oxygen species (ROS) and phosphorylation of protein kinases C(PKC). These findings are the first to demonstrate that activation of K-ATP channel, especially mitochondrial K-ATP channel, improves the function of GluTs in astrocytes due to reducing ROS production and downregulating PKC phosphorylation. Therefore, the present study not only reveals a novel pharmacological profile of KCOs as regulators of GluTs, but also provides a new strategy for neuroprotection.

Neuroprotective effects of a mitochondrial K^+-ATP channel opener (diazoxide) are mediated by Bcl-2 expression upregulation

Mitochondrial K＋-ATP （mito-KATP） channels play an important role in cellular function and survival following ischemic stress. The present results revealed that intervention with diazoxide, a mito-KATP channel opener, led to an increase in Bcl-2 expression in the cerebral cortex of rats subjected to cerebral ischemia reperfusion injury. In addition, the intervention also led to clear improvements in neuronal mitochondrial morphology and consciousness post-injury. Glibenclamide a mito-KATP channel blocker, exhibited the converse effects. Both diazoxide and glibenclamide exerted dose-dependent effects （in particular, at 18 mg/kg diazoxide and 25 mg/kg glibenclamide）. These findings suggest that diazoxide exerts a neuroprotective effect on cerebral ischemia reperfusion injury by opening mito-KATP channels and upregulating Bcl-2 expression.

Fluid Flow and Mixed Heat Transfer in a Horizontal Channel with an Open Cavity and Wavy Wall

Heat exchangers are utilized extensively in different industries and technologies.Consequently,optimizing heat exchangers has been a major concern among researchers.Although various studies have been conducted to improve the heat transfer rate,the use of a wavy wall in the presence of different types of heat transfer mechanisms has not been investigated.This study thus investigates the mixed heat transmission behavior of fluid in a horizontal channel with a cavity and a hot,wavy wall.The fluid flow in the channel is considered laminar,and the governing equations including continuity,momentum,and energy are all solved numerically.The numerical solution is stabilized by using a first-order multi-dimensional characteristic-based scheme in combination with a fifth-order Runge-Kutta method.The flow and heat transfer effects of varying Richardson numbers,Reynolds numbers,wave amplitude,wavelength,channel height,and cavity width are examined.The results indicate that the mean Nusselt number increases with an increase in Reynolds number,wave amplitude,and cavity width,while it decreases with an increase in Richardson number,wavelength,and channel height.The minimum Nusselt number is calculated to be 0.7,whereas the maximum Nusselt number is 27.09.The Nusselt number has only increased by 40%in the higher depths of the cavity,despite the Richardson number being 10,000 times larger.But this figure increases to 130%at lower depths.The mean Nusselt number is thus significantly influenced by channel height and cavity width.The influence of wave amplitude on the mean Nusselt number is twice that of wavelength.

Effect of Mixed Vegetation of Different Heights on Open Channel Flows

Vegetation of different heights commonly grows in natural rivers, canals and wetlands and affects the biodiversity and morphological process. The role of vegetation has drawn great attention in river ecosystems and environmental management. Due to the complexity of the vegetated flow, most previous research focuses on the effect of uniformed one-layered vegetation on the flow structure and morphological process. However, less attention was paid to the impact of the mixing vegetation of different heights, which is more realistic and often occurs in natural riverine environments. This paper aims to investigate the effect of mixing three-layered vegetation on flow characteristics, particularly the velocity distrbution, via a novel experiment. Experiments were performed in a titling water flume fully covered with vegetation of three heights (10, 15 and 20 cm) arranged in a staggered pattern, which is partially submerged. Velocities at different positions along a half cross-section were measured using a mini propeller velocimeter. Observed results showed that the velocity has a distinct profile directly behind vegetation and behind the vegetation gap. The overall profile has two distinct reflections about ? below or near the top of short vegetation (h): the velocity remains almost constant in the bottom layer ( h) the velocities directly behind the middle after short vegetation increase much faster than those directly behind the short after tall vegetation. The finding in this study would help river riparian and ecosystem management. .

Hypoxic pulmonary hypertension and novel ATP-sensitive potassium channel opener: the new hope on the horizon

Hypoxic pulmonary hypertension(HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries.The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance,reverse pulmonary vascular remodeling,and thereby improving right ventricular function.Iptakalim,a lipophilic para-amino compound with a low molecular weight,has been demonstrated to be a new selective ATP-sensitive potassium(K ATP) channel opener via pharmacological,electrophysiological,biochemical studies,and receptor binding tests.In hypoxia-induced animal models,iptakalim decreases the elevated mean pressure in pulmonary arteries,and attenuates remodeling in the right ventricle,pulmonary arteries and airways.Furthermore,iptakalim has selective antihypertensive effects,selective vasorelaxation effects on smaller arteries,and protective effects on endothelial cells,but no effects on the central nervous,respiratory,digestive or endocrine systems at therapeutic dose.Our previous studies demonstrated that iptakalim inhibited the effects of endothelin-1,reduced the intracellular calcium concentration and inhibited the proliferation of pulmonary artery smooth muscle cells.Since iptakalim has been shown safe and effective in both experimental animal models and phase I clinical trials,it can be a potential candidate of HPH in the future.

Utility Impact below Bridge or Culvert Soffit on Open Channel Flow

The background to this research was a flooding incident that occurred in Bridgend, Co. Donegal, Ireland in August 2017. While several properties were flooded, a flooding case study of a single dwelling house adjacent to the Bridgend River at Riverdale, Bunamayne, Co. Donegal, Ireland is used herein. For this study the flooded site shall be referred to as the “Hegarty property”. A structure in the form of a stone arched culvert is located directly adjacent to the two-storey detached dwelling house on the Hegarty Property. While the culvert is referred to locally as a bridge, within this research the word culvert will be used in connection with the structure. The culvert has a concrete surrounded utility (watermain) crossing at a gradient below the culvert soffit on the upstream face of the structure. The utility obstructed flow through the culvert and contributed to the flooding event. Given the implication of climate change and the increased probability of more extreme flooding events, it was decided to explore the case study to ascertain the factors that contribute to flooding events when utilities are positioned at culvert or bridge structures. This work was completed to assist undergraduate students, researchers, and local authorities in a relatively unknown area of flood causation.

Beneficial effects of adenosine triphosphate-sensitive K^+ channel opener on liver ischemia/reperfusion injury

AIM:To investigate the effect of diazoxide administration on liver ischemia/reperfusion injury.METHODS:Wistar male rats underwent partial liver ischemia performed by clamping the pedicle from the medium and left anterior lateral segments for 1 h under mechanical ventilation.They were divided into 3 groups:Control Group,rats submitted to liver manipulation,Saline Group,rats received saline,and Diazoxide Group,rats received intravenous injection diazoxide(3.5 mg/kg) 15 min before liver reperfusion.4 h and 24 h after reperfusion,blood was collected for determination of aspartate transaminase(AST),alanine transaminase(ALT),tumor necrosis factor(TNF-α),interleukin-6(IL-6),interleukin-10(IL-10),nitrite/nitrate,creatinine and tumor growth factor-β1(TGF-β1).Liver tissues were assembled for mitochondrial oxidation and phosphorylation,malondialdehyde(MDA) content,and histologic analysis.Pulmonary vascular permeability and myeloperoxidase(MPO) were also determined.RESULTS:Four hours after reperfusion the diazoxide group presented with significant reduction of AST(2009 ± 257 U/L vs 3523 ± 424 U/L,P = 0.005); ALT(1794 ± 295 U/L vs 3316 ± 413 U/L,P = 0.005); TNF-α(17 ± 9 pg/mL vs 152 ± 43 pg/mL,P = 0.013; IL-6(62 ± 18 pg/mL vs 281 ± 92 pg/mL); IL-10(40 ± 9 pg/mL vs 78 ± 10 pg/mL P = 0.03),and nitrite/nitrate(3.8 ± 0.9 μmol/L vs 10.2 ± 2.4 μmol/L,P = 0.025) when compared to the saline group.A significant reduction in liver mitochondrial dysfunction was observed in the diazoxide group compared to the saline group(P < 0.05).No differences in liver MDA content,serum creatinine,pulmonary vascular permeability and MPO activity were observed between groups.Twenty four hours after reperfusion the diazoxide group showed a reduction of AST(495 ± 78 U/L vs 978 ± 192 U/L,P = 0.032); ALT(335 ± 59 U/L vs 742 ± 182 U/L,P = 0.048),and TGF-β1(11 ± 1 ng/mL vs 17 ± 0.5 ng/mL,P = 0.004) serum levels when compared to the saline group.The control group did not present alterations when compared to the diazoxide and saline groups.CONCLUSION:Diazoxide maintains liver mitochondrial function,increases liver tolerance to ischemia/reperfusion injury,and reduces the systemic inflammatory response.These effects require further evaluation for using in a clinical setting.

Overbank Flow in a Multi-Staged Open Channel: Zonal and Overall Discharge Studies

An improved divided channel method has been proposed by modelling a parameter using the function of depth ratio for a multi-stage compound channel. Experimental data suggest that as the flow depth increases over the second stage floodplain, fractional contribution of the main channel and first stage floodplain under bankfull height plays a pivotal role in shear layer and momentum distribution. Therefore, a new mathematical model has been suggested for estimating the stage-discharge relationship for staged channels of more than one floodplain using the 1D technique of overall roughness correction. .

Theory of Flexural Shear, Bending and Torsion for a Thin-Walled Beam of Open Section

Aspects of the general Vlasov theory are examined separately as applied to a thin-walled channel section cantilever beam under free-end end loading. In particular, the flexural bending and shear that arise under transverse shear and axial torsional loading are each considered theoretically. These analyses involve the location of the shear centre at which transverse shear forces when applied do not produce torsion. This centre, when taken to be coincident with the centre of twist implies an equivalent reciprocal behaviour. That is, an axial torsion applied concentric with the shear centre will twist but not bend the beam. The respective bending and shear stress conversions are derived for each action applied to three aluminium alloy extruded channel sections mounted as cantilevers with a horizontal principal axis of symmetry. Bending and shear are considered more generally for other thin-walled sections when the transverse loading axes at the shear centre are not parallel to the section = s centroidal axes of principal second moments of area. The fixing at one end of the cantilever modifies the St Venant free angular twist and the free warping displacement. It is shown from the Wagner-Kappus torsion theory how the end constrained warping generates an axial stress distribution that varies with the length and across the cross-section for an axial torsion applied to the shear centre. It should be mentioned here for wider applications and validation of the Vlasov theory that attendant papers are to consider in detail bending and torsional loadings applied to other axes through each of the centroid and the web centre. Therein, both bending and twisting arise from transverse shear and axial torsion applied to each position being displaced from the shear centre. Here, the influence of the axis position upon the net axial and shear stress distributions is to be established. That is, the net axial stress from axial torsional loading is identified with the sum of axial stress due to bending and axial stress arising from constrained warping displacements at the fixing. The net shear stress distribution overlays the distributions from axial torsion and that from flexural shear under transverse loading. Both arise when transverse forces are displaced from the shear centre.

低空智联网中基于多质心OpenMax的无人机开集识别方法

随着网络化、智能化的发展,无人机(Unmanned aerial vehicles, UAVs)逐渐成为低空智联网(Low-altitude intelligent network, LAIN)的重要组成部分,但如何对低空智联网中的无人机平台进行有效的管理仍面临严峻挑战。基于无人机信号中的细微特征可对无人机进行个体识别,并检测是否为非法无人机,从而实现低空智联网中无人机的身份识别和管理。针对低空领域信道环境复杂且无法提前获取非法无人机信号样本的问题,本文提出了基于差值时频和多质心OpenMax的无人机开集识别方法。首先,提出了与信道无关的差值时频特征来降低多径信道环境对射频指纹(Radio frequency fingerprinting, RFF)特征的影响,并利用数据增强提高了识别模型的准确率和鲁棒性。其次,利用多质心OpenMax替代神经网络Softmax层,以实现无人机个体的开集识别。最后,对神经网络的损失函数进行了改进,提高了开集识别准确率。本文利用真实环境采集的数据对所提算法进行了验证,在多径信道环境中开放度为0.087时,开集识别准确率达到了93.23%,与基准算法相比,准确率分别提高了7.61%和13.4%。本文提出的算法可在复杂信道环境中有效识别无人机个体并检测出首次出现的非法无人机。

Protective effect and mechanism of K_(ATp) channel opener on the sinoatrial node cells of neonatal rat cultured in simulated ischemia-reperfusion

Objective: To study the effect of KATP channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoatrial node (SAN) cells of neonatal rats were purified and cultured for 2 d, and then they were randomly divided into the control, simulated ischemia-reperfusion group (I/R group), group intervened with KATP channel opener pinacidil (P+I/R group), KATP Channel blocking agent 5-HD (5-HD+I/R group), and group with the 2 agents at same time (5-HD+P+I/R group). The survival rate of cells was measured by flow cytometry and the content of intracellular calcium in the cells of each group was detected with laser confocal microscopy. Results: ① The survival rate of SAN cells in I/R group [(51.79±6.28)%] was remarkably significantly lower than in control [(95.08±10.48)%] (P<0.001), and very significantly lower than in P+I/R group [(63.77±5.35)%] (P<0.01), however, those of 5-HD+P+I/R group [(52.88±6.25)%] and 5-HD+I/R group [(53.16±5.35)%] was significantly lower compared with that in P+I/R group (P<0.01); ② When the average fluorescence intensity of sinoatrial node cells in the control was regarded as 100%, the relative fluorescence intensities of each group were: (374±52)% in I/R group, significantly higher than that of control (P<0.01); (162±20)% in P+I/R group, declining significantly than that of I/R group (P<0.01); (385±56)% in 5-HD+P+I/R group and (379±44)% in 5-HD+I/R group, increasing significantly than that of I/R group (P<0.01). Conclusion: ① Simulated ischemia-reperfusion can significantly reduce the survival rate of SAN cells, and can also lead to the overload of intracellular calcium in them. ② KATP channel opener, pinacidil, exerts protective effect on the cells under simulated ischemia-reperfusion, which may be associated with the decrease of intracellular calcium loading in them.

Influence of bed elevation discordance on flow patterns and head losses in an open-channel confluence

Confluences play a major role in the dynamics of networks of natural and man-made open channels, and field measurements on river confluences reveal that discordance in bed elevation is common.Studies of schematized confluences with a step at the interface between the tributary and the main channel bed reveal that bed elevation discordance is an important additional control for the confluence hydrodynamics.This study aimed to improve understanding of the influence of bed elevation discordance on the flow patterns and head losses in a right-angled confluence of an open channel with rectangular cross-sections.A large eddy simulation (LES)-based numerical model was set up and validated with experiments by others.Four configurations with different bed discordance ratios were investigated.The results confirm that, with increasing bed elevation discordance, the tributary streamlines at the confluence interface deviate less from the geometrical confluence angle, the extent of the recirculation zone (RZ) gets smaller, the ratio of the water depth upstream to that downstream of the confluence decreases, and the water level depression reduces.The bed elevation discordance also leads to the development of a large-scale structure in the lee of the step.Despite the appearance of the large-scale structure, the reduced extent of the RZ and associated changes in flow deflection/contraction reduce total head losses experienced by the main channel with an increase of the bed discordance ratio.It turns out that bed elevation discordance converts the lateral momentum from the tributary to streamwise momentum in the main channel more efficiently.

Experimental study on influence of boundary on location of maximum velocity in open channel flows

The velocity dip phenomenon may occur in a part of or in the whole flow field of open channel flows due to the secondary flow effect. Based on rectangular flume experiments and the laser Doppler velocimetry, the influence of the distance to the sidewall and the aspect ratio on the velocity dip is investigated. Through application of statistical methods to the experimental results, it is proposed that the flow field may be divided into two regions, the relatively strong sidewall region and the relatively weak sidewall region. In the former region, the distance to the sidewall greatly affects the location of maximum velocity, and, in the latter region, both the distance to the sidewall and the aspect ratio influence the location of the maximum velocity.

Lateral Shear Layer and Its Velocity Distribution of Flow in Rectangular Open Channels

The lateral velocity distribution of flow in the shear layer of open channel is required to many problems in river and eco-environment engineering, e.g. distribution of pollutant dispersion, sediment transport and bank erosion, and aquatic habitat. It is not well understood about how the velocity varies laterally in the wall boundary layer. This paper gives an analytical solution of lateral velocity distribution in a rectangular open channel based on the depth-averaged momentum equation proposed by Shiono & Knight. The obtained lateral velocity distributions in the wall shear layer are related to the two hydraulic parameters of lateral eddy viscosity (λ) and depth-averaged secondary flow (Γ) for given roughened channels. Preliminary relationships between the above two parameters and the aspect ratio of channel, B/H, are obtained from two sets of experimental data. The lateral width (δ) of the shear layer was investigated and found to relate to the λ and the bed friction factor (f), as described by Equation (26). This study indicates that the lateral shear layer near the wall can be very wide (δ/H = 14.6) for the extreme case (λ = 0.6 and f = 0.01).

Flow characteristics in curved open channel with partial suspended vegetation

Suspended vegetation in open channels such as natural river,lake,reservoir usually affect the flow structure,causing the change of the water environment,sediment transport,bed deformation.In order to study the water flow behavior in curved open channels under the influence of suspended vegetation,experiments were conducted in a Ushaped flume with 180°bend where the suspended vegetation substituted by cylindrical glass rods were partially placed.The particle image velocimeter(PIV)system was employed to measure the flow velocities of various cases with different vegetation arrangements and roots length.Comparison and analysis were conducted for measured data,such as water level,velocity,head loss,Reynolds stress,and turbulence kinetic energy(TKE)to obtain certain general rules of water flow in open curved channels with suspended vegetation.It can be found from the measured data that the water level and the head loss in the vegetation area are closely related to the arrangements of the suspended vegetation.Furthermore,the drag force of the vegetation can not only lead to smaller increments of longitudinal TKE above the vegetation tail than that below it,but also lead to the flow velocities in vegetation area much smaller than areas without vegetation.In addition,suspended vegetation weakens the vortex strength near the water surface and increases the vortex strength below the vegetation tail,and the flow velocity in the vegetation area has a close relationship with the suspended vegetation length in the water.Therefore,it can be concluded that the reasonable arrangements of suspended vegetation group in curved open channel can protect the concave bank from being scoured,and protect the convex bank from being deposited.

Prediction of boundary shear stress distribution in straight open channels using velocity distribution

Conventional methods for measuring local shear stress on the wetted perimeter of open channels are related to the measurement of the very low velocity close to the boundary.Measuring near-zero velocity values with high fluctuations has always been a difficult task for fluid flow near solid boundaries.To solve the observation problems,a new model was developed to estimate the distribution of boundary shear stress from the velocity distribution in open channels with different cross-sectional shapes.To estimate the shear stress at a point on the wetted perimeter by the model,the velocity must be measured at a point with a known normal distance to the boundary.The experimental work of some other researchers on channels with various cross-sectional shapes,including rectangular,trapezoidal,partially full circular,and compound shapes,was used to evaluate the performance of the proposed model.Optimized exponent coefficients for the model were found using the multivariate Newton method with the minimum of the mean absolute percentage error(MAPE)between the model and experimental data as the objective function.Subsequently,the calculated shear stress distributions along the wetted perimeter were compared with the experimental data.The most important advantage of the proposed model is its inherent simplicity.The mean MAPE value for the seven selected cross-sections was 6.9%.The best results were found in the cross-sections with less discontinuity of the wetted perimeter,including the compound,trapezoidal,and partially full circular pipes.In contrast,for the rectangular cross-section with an angle between the bed and walls of 90°,MAPE increased due to the large discontinuities.

Uniform Flow of Molten Metals in Rectangular Open Channels

The flow of liquids in open channels has been studied since ancient Rome. However, the vast majority of published reports on flow in open channels are focused on the transport of drinking water and sewage disposal. The literature on the transport of molten metals in open channels is quite scarce. In this work, the uniform flow of pig iron and molten aluminum in rectangular open channels is studied. Specific energy curves are constructed and critical heights are analytically determined. The transition from subcritical to supercritical flow is analyzed as a function of the angle of inclination of the channel and the roughness of its walls. Manning’s equation is applied to the pig iron flow using data reported in the literature for molten aluminum. The need to correct the roughness coefficient for pig iron is observed in order to obtain results consistent with those previously reported.

A Pair of 3D Homochiral Coordination Polymers with Open Channels Constructed by Lactic Acid Derivative Ligands and In-situ Formed Anions

With the help of in-situ formed CH_3COO- anion, a pair of 3D homochiral coordination polymers with open channels were constructed by the assembly of lactic acid derivative ligands, 1.4-DIB ligands and Cd（II） ions, namely [Cd3（（R）-CIA）2（CH3CO2）_2（1.4-DIB）2（H2O）2]·x（Guest）（1-D） and [Cd3（（S）-CIA）2（CH3CO2）2（1.4-DIB）2（H2O）2]·x（Guest）（1-L）. They contain 1D interesting ladder-like Cd-（R）-CIA（3-） chains and exhibit SHG-active behavior and photoluminescent property.

Influence of deflection angles on flow behaviours in openchannel bends

The deflection angle of a river bend plays an important role on behaviours of the flow within it, and a clear understanding of the angle's influence is significant in both theoretical study and engineering application. This paper presents a systematic numerical investigation on effects of deflection angles(30°, 60°, 90°, 120°, 150°, and 180°) on flow phenomena and their evolution in open-channel bends using a Re-Normalization Group(RNG) κ-ε model and a volume of fluid(VOF) method. The numerical results indicate that the deflection angle is a key factor for flows in bends. It is shown that the maximum transverse slope of water surface occurs at the middle cross section of a bend, and it increases with the deflection angle. Besides a major vortex, or, the primary circulation cell near the channel bottom, a secondary vortex, or, an outer bank cell, may also appear above the former and near the outer bank when the deflection angle is sufficiently large, and it will gradually migrate towards the inner bank and evolve into an inner bank cell. The strength of the secondary circulations increases with the deflection angle. The simulation demonstrates that there is alow-stress zone on the bed near the outer bank and a high-stress zone on the bed near the inner bank, and both of them increase in size with the deflection angle. The maximum of shear stress on the inner bank increases nonlinearly with the angle, and its maximums on the outer bank and on the bed take place when the deflection angle becomes 120°.

BASIC EQUATIONS OF TURBULENT FLOW FOR VARIABLE DENSITY AND VARIABLE VISCOSITY NEWTONIAN FLUID IN OPEN CHANNEL

In this paper, using Navier-Stokes equations and Reynolds time-averaged rules, the turbulent motional differential equations of variable density and variable viscosity Newtonian fluid have been presented, and the turbulent motional differential equations of variable density and variable viscosity Newtonian fluid in open channel have been further proposed. The concepts of the density turbulence stress and the viscosity turbulence stress have been firstly presented in the paper.