Cyclic Flow Research Articles

Inhibition of Platelet Glycoprotein β3 by Chimeric Monoclonal Antibody Prevents Arterial Thrombosis in Beagle Dogs,

Abstract 3357In this present study in beagle dogs, we evaluated the antithrombotic efficacy of Pulaimab, the chimeric monoclonal antibodies SZ21-F(ab)2 fragments against platelet glycoprotein (GP) β3, in a modified Folts model. The Folts model is widely accepted to be effective and clinically relevant for testing potential anti-thrombotic agents, in this model the cyclic flow reductions (CFRs) are caused by platelet dependent thrombi that form under high-shear conditions at injured stenosed sites of an artery. Thirty beagle dogs of either sex, weighing 7.5 to 14 kg, were randomly divided into five groups of six (three females and three males), the details were following: negative control group (injected normal saline), positive control group (injected 0.2mg/Kg of Reopro), and three experimental groups [injected 0.2, 0.4, 0.8 mg/Kg of SZ21-F(ab)2, respectively]. A dose range from 0.2 to 0.8 mg/kg of Pulaimab significantly reduced the CFRs by 21–73%, without reduction of platelet numbers and prolongation of the bleeding time. Ex vivo ADP-induced platelet aggregation was equally reduced. The present study demonstrates that the inhibition of platelet GP αIIbβ3function by SZ21-F(ab)2 is a powerful intervention to prevent platelet thrombus formation in injured arteries without thrombocytopenia and prolongation of the bleeding time. We therefore conclude that F(ab)2 fragments of inhibitory anti-GPβ3 antibodies may be useful compounds to prevent thrombosis. Disclosures:No relevant conflicts of interest to declare.

GRAVITY DUAL FOR CYCLIC RENORMALIZATION GROUP FLOW WITHOUT CONFORMAL INVARIANCE

We construct a gravity dual for scale invariant but non-conformal field theories with a cyclic renormalization group flow. A slight modification of our construction gives a gravity dual of discretely scale invariant field theories. The underlying gravitational theory breaks the null energy condition.

Cobalt oxide nanostructure-modified glassy carbon electrode as a highly sensitive flow injection amperometric sensor for the picomolar detection of insulin

Glassy carbon electrode modified with electrodeposited cobalt oxide nanostructure shows an excellent electrocatalytic activity toward insulin oxidation at a wide pH range. Cyclic voltammetry, hydrodynamic amperometry, and flow injection analysis (FIA) were used for insulin determination at a picomolar and higher-concentration range. Amperometric determination of insulin at this modified electrode yielded a calibration curve with the following characteristics; linear range, 100 pM–15 nM; sensitivity of 83.9 nA nM−1 and detection limit 10 pM. FIA yielded the calibration curve with sensitivity and detection limit of 2.0 nA nM−1 and 25 pM, respectively. Furthermore, the RSD of repetitive FIA for 200 pM insulin (n = 13) is 2%. In addition, the interference effect of electroactive existing species (lactic acid, cholesterol, ascorbic acid, uric acid, and glucose) was eliminated by covering the surface of the modified electrode with nafion film. Fast response time, signal stability, high sensitivity, low cost, and ease of preparation are the advantages of the proposed insulin sensor.

Modeling on the cyclic operation of standing column wells under regional groundwater flow

Coupled hydrogeological-thermal simulation of the Standing Column Well (SCW) system is essential to provide an optimized configuration and operation schedule for boreholes on the site. This paper presents numerical investigations and thermo-hydraulic evaluation of standing column well system operating under cyclic flow regime. A three-dimensional numerical model for groundwater flow and heat transport is used to analyze the heat exchange in the ground. The model includes the effects of convective and conductive heat transfer, heat loss to the adjacent confining strata, and hydraulic anisotropy. The operation scenario consists of cyclic injection and recovery and four periods per year to simulate the seasonal temperature conditions. For different parameters of the system, performances have been evaluated in terms of variations in recovery temperature. The calculated temperatures at the producing pipe are relatively constant within a certain range through the year and fluctuating quarterly a year. Pipe-to-pipe distance, injection/production rate, ground thickness, and permeability considered in the model are shown to impact the predicted temperature profiles at each stage and the recovery water temperature. The influence of pressure gradient, which determines the velocity of regional groundwater flow, is most substantial.

Electrochemical sensors for hemoglobin and myoglobin detection based on methylene blue-multiwalled carbon nanotubes nanohybrid-modified glassy carbon electrode

An effective electrochemical sensors for hemoglobin (Hb) and myoglobin (Mb) detection was firstly developed using a simple procedure of self-assembled methylene blue-multiwalled carbon nanotubes (MB-MWNTs) nanohybrid modified on glassy carbon electrode without using any enzymes immobilization. The direct electrochemical and electrocatalytic behaviors of the modified electrode were studied using cyclic voltammetry (CV) and flow injection analysis (FIA) with amperometry. The performance of the sensor was investigated and optimized and the system was evaluated by monitoring Hb and Mb concentrations. The developed MB-MWNTs nanohybrid modified electrode showed excellent electrocatalytic activity for reduction of Hb and Mb with good stability, sensitivity and reproducibility (RSD = 3.05% and 4.5% for 50 successive injections of Hb and Mb, respectively). Under optimal conditions, the catalytic currents are linearly proportional to the concentrations of Hb and Mb in the wide range from 5 nM to 2 μM and 0.1 to 3 μM, and the corresponding detection limits are 1.5 nM and 20 nM (S/N = 3), respectively. This approach provides improved detection limit over other previous works and may provide a novel and efficient platform for the fabrication of sensors for other heme proteins.

Effect of Tonsillar Herniation on Cyclic CSF Flow Studied with Computational Flow Analysis

The Chiari I malformation, characterized by tonsils extending below the foramen magnum, has increased CSF velocities compared with those in healthy subjects. Measuring the effect of tonsillar herniation on CSF flow in humans is confounded by interindividual variation. The goal of this study was to determine the effect of herniated tonsils on flow velocity and pressure dynamics by using 3D computational models. A previously described 3D mathematic model of the normal subarachnoid space was modified by extending the tonsils inferiorly. The chamber created was compared with the anatomy of the subarachnoid space. Pressures and velocities were calculated by CFA methods for sinusoidal flow of a Newtonian fluid. Results were displayed as 2D color-coded plots and 3D animations. Pressure gradients and flow velocities were compared with those in the normal model. Velocity distributions were also compared with those in clinical images of CSF flow. The model represented grossly the subarachnoid space of a patient with Chiari I malformation. Fluid flow patterns in the Chiari model were complex, with jets in some locations and stagnant flow in others. Flow jets, synchronous bidirectional flow, and pressure gradients were greater in the Chiari model than in the normal model. The distribution of flow velocities in the model corresponded well with those observed in clinical images of CSF flow in patients with Chiari I. Tonsillar herniation per se increases the pressure gradients and the complexity of flow patterns associated with oscillatory CSF flow.

Modulation of cyclic AMP and autoregulation of renal blood flow, analysed by the use of forskolin and 1-methyl-3-isobutylxanthine

We have examined the effects of forskolin and 1-methyl-3-isobutylxanthine (IBMX) in relation to cyclic (c)AMP metabolism and renal blood flow autoregulation in anaesthetized dogs. Control observations usually showed excellent autoregulation of renal blood flow over the renal perfusion pressure range of 120-200 mmHg, when the perfusion pressure was changed, stepwise, between 60 and 200 mmHg. Renal blood flow was increased by the infusion of forskolin (10 micrograms min-1) and IBMX (100 micrograms min-1) at the basal perfusion pressure of 100 mmHg, and maintained an increased level while the infusion was continued. Forskolin and IBMX did not inhibit autoregulation, though they shifted the perfusion pressure range evoking autoregulation. These data indicate that vasodilators which may produce the activity through modulating the cAMP level in vascular smooth muscle do not influence the establishment of autoregulation of renal blood flow.

Flow measurement with multi‐instrumentation in a tidal‐affected river

AbstractFlow measurements in a tidal‐affected river provide important information of cyclic flow pattern characteristics in temporal and spatial variations. Reliability and accuracy of measured flow data can provide for numerical model calibration and verification. In the present study, we measured tidally affected river flow in the Danshui River of northern Taiwan during the 2008 summer and fall. The measured flow data, produced by both state of the art and conventional instruments including particle tracking velocimetry (PTV), acoustic Doppler profiler (ADP), horizontal acoustic Doppler current profiler (H‐ADCP) and Price‐type current metre (PCM) were compared and correlated during several tidal cycles. The mean flows by ADP were similar to that by PCM and highly correlated with those by PTV and H‐ADCP. Index velocity rating between ADP and H‐ADCP separately computed during the flood and ebb tides shows good correlation for the ebb tide and poor correlation for the flood tide due to subsurface maximum velocity in the middle‐ to near‐bottom layers.

Washout Control of a Cyclic Vehicular Traffic Flow

AbstractIn this paper, we consider a decentralized control problem for suppressing the traffic jam in a cyclic traffic ow. In recent years, to explain the mechanism that causes the traffic jam, several experiments have been done for multiple vehicles on the circle. The traffic jam can be explained by the so-called optimal velocity model, the optimal velocity function which is a nonlinear function of the headway of the preceding vehicle and describes driver's characteristics. In this paper, we apply washout control to suppress the traffic jam in a cyclic traffic ow not to disturb driver's characteristics. Then, we show a method to select parameters to keep stability of the closed-loop system. We find that our proposed method for selecting parameters is better than the conservative method using the small gain theorem. In addition, we illustrate the effectiveness with several simulations.

Comparison between experimental data and numerical modeling for the natural circulation phenomenon

The study of natural circulation phenomenon has been object of crescent interest in scientific community in recent years. The new generation of compact nuclear reactors uses natural circulation of the fluid as a residual heat removal cooling system in case of accident or shutdown. The objective of this paper is to present a comparison between experimental data and numerical simulation results for the natural circulation phenomenon in single and two-phase flow regime. Experimental data were obtained from a circuit built with glass tubes, through which thermal hydraulic phenomenon visualization was possible. The circuit is composed of an electric heater as the heat source, a heat exchanger as the heat sink and an expansion tank to accommodate fluid density changes. Instrumentation data acquisition is performed through thermocouples and pressure meters, and controlled by a computer interface developed using LABVIEW. Numerical modeling and simulations were done with the thermal hydraulic code RELAP5, which is widely used for this purpose. The cyclic reverse flow observed in the circuit was well represented by the numerical model. The comparison demonstrated that the numerical simulations are very close to the experimental data.

Coupling Between Electroencephalography Pattern and Cyclic Transcranial Doppler Flow During Aortic Root Surgery

van Alfen, Nens MD, PhD*; van Hal, Maarten BSc*; Karmann, Christine MD† Author Information

Efficacy of prothrombin complex concentrate to reverse the anticoagulant effect of the pentasaccharide fondaparinux in a rabbit model

As a potent anticoagulant agent, fondaparinux exposes a risk of bleeding. An effective way to reverse its effects is needed. It was the objective to study efficacy and safety of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of fondaparinux in a rabbit model of bleeding and thrombosis. In anaesthetised and ventilated rabbits, the Folts model was applied: a stenosis (75%) and an injury were carried out on the carotid artery, inducing thrombosis. Blood flow decreased as thrombus size increased until the pressure gradient was such that the thrombus was released and local blood flow was suddenly restored. This is known as a cyclic flow reduction (CFR). After the first CFR, rabbits were randomised into three groups: control (saline and saline after 1 minute), fondaparinux (fondaparinux [3 mg.kg-1] and saline), PCC (fondaparinux and PCC [40 UI.kg-1]). Then CFRs were recorded over 20 minutes. The following were measured: ear immersion bleeding time (BT), haemoglobin blood level (Hb1) and thrombelastometric parameters (ROTEM®). Finally, a hepatosplenic section was performed; 15 minutes later, the amount of blood loss was recorded as primary endpoint and Hb2 was measured. Blood loss was increased with fondaparinux and normalised with PCC. Regarding ROTEM® INTEM, fondaparinux increased clotting time and clotting formation time. PCC normalised these parameters. EXTEM and FIBTEM tests were not modified. Regarding safety, PCC did not increase CFRs. PCC reduced bleeding without increasing thrombosis and was effective to reverse the haemorrhagic effect of fondaparinux in this rabbit model.

Fluid flow within the damage zone of the Boccheggiano extensional fault (Larderello–Travale geothermal field, central Italy): structures, alteration and implications for hydrothermal mineralization in extensional settings

AbstractThe Neogene extensional province of southern Tuscany in central Italy provides an outstanding example of fossil and active structurally controlled fluid flow and epithermal ore mineralization associated with post-orogenic silicic magmatism. Characterization of the hydrodynamic regime leading to the genesis of the polysulphide deposit (known as Filone di Boccheggiano) hosted within the damage zone of the Boccheggiano Fault is a key target to assess modes of fossil hydrothermal fluid circulation in the region and, more generally, to provide inferences on fault-controlled hydrothermal fluid flow in extensional settings. We provide a detailed description of the fault zone architecture and alteration/mineralization associated with the Boccheggiano ore deposit and report the results of fluid inclusion and stable oxygen isotope studies. This investigation shows that the Boccheggiano ore consists of an adularia/illite-type epithermal deposit and that sulphide ore deposition was controlled by channelling of hydrothermal fluids of dominantly meteoric origin within the highly anisotropic permeability structure of the Boccheggiano Fault. The low permeability structure of the fault core compartmentalized the fluid outflow preventing substantial cross-fault flow, with focused fluid flow occurring at the hangingwall of the fault controlled by fracture permeability. Fluid inclusion characteristics indicate that ore minerals were deposited between 280° and 350°C in the upper levels of the brittle extending crust (lithostatic pressure in the order of 0.1 GPa). Abundant vapour-rich inclusions in ore-stage quartz are consistent with fluid immiscibility and boiling, and quartz ore vein textures suggest that mineralization in the Boccheggiano ore deposit occurred during cyclic fluid flow in a deformation regime regulated by transient and fluctuating fluid pressure conditions. Results from this study (i) predict a strongly anisotropic permeability structure of the fault damage zone during crustal extension, and (ii) indicate the rate of secondary (structural) permeability creation and maintenance by active deformation in the hangingwall of extensional faults as the major factor leading to effective hydraulic transmissivity in extensional terranes. These features intimately link ore-grade mineralization in extensional settings to telescoping of hydrothermal flow along the hangingwall block(s) of major extensional fault zones.

Effect on ex vivo platelet aggregation and in vivo cyclic flow with Na+/H+ exchange inhibition

BIIB 513 and EMD 85131 are selective inhibitors of the Na+/H+ exchanger-1 (NHE-1) that are benzoylguanidine derivatives of the clinically employed diuretic amiloride. Prior studies have suggested a role for NHE-1 activity in platelet activation and aggregation using amiloride or its non- benzoylguanidines derivatives. However, the concentrations employed in these prior studies were at levels known to exert effects on other ion transport systems besides the NHE-1. Therefore, the purpose of this study was to examine the effects of more selective NHE-1 inhibitors, BIIB 513 and EMD 85131, on platelet aggregation and in vivo cyclic flow following arterial injury. BIIB 513 and EMD 85131 effects on ex vivo canine and human platelet aggregation in response to various agents was monitored via platelet aggregation. For analysis of in vivo thrombus formation, a femoral artery crush injury model was employed and a flow meter was used to monitor the effect of BIIB 513 on cyclic blood flow. Treatment of either canine or human platelets with up to 1 mM of BIIB 513 had no effect on aggregation induced by platelet activating factor (PAF), thrombin receptor activator peptide (TRAP), or adenosine diphosphate (ADP). Additionally, the structurally related compound EMD 85131 at up to 1 mM failed to inhibit TRAP induced platelet aggregation. In vivo administration of up to 9 mg/kg of BIIB 513 intravenously failed to affect cyclic flow in a canine model of femoral artery injury. These data demonstrate that the specific and selective NHE-1 inhibitors BIIB 513 or EMD 85131 have no effect on ex vivo platelet aggregation or in vivo cyclic flow following arterial injury.

Hydrogen Peroxide Biosensor Based on Hemoglobin Immobilization on Gold Nanoparticle in FFT Continuous Cyclic Voltammetry Flow Injection System

Hydrogen Peroxide Biosensor Based on Hemoglobin Immobilization on Gold Nanoparticle in FFT Continuous Cyclic Voltammetry Flow Injection System

Heat transport in granular materials during cyclic fluid flow

Heat transfer takes place between grains and the fluids that saturate the pore space in granular materials, when the fluid is static or moving. This study explores effective heat transport in granular materials during cyclic fluid flow. Controlled particle-scale experiments, complementary analyses and numerical simulations help us identify the governing variables and ensuing time scales. We show that fluid-grain heat transfer leads to effective heat transport along the granular medium during cyclic fluid flow. At the macro-scale, the process resembles diffusion where the effective diffusion coefficient is proportional to the square of the fluid invasion length in each cycle and inversely proportional to the cycle period. Both experimental and numerical results confirm improved heat transfer by cyclic fluid flow over thermal diffusion under hydrostatic conditions. The formulation can be used to identify optimal operation conditions for maximum transport.

SCH 602539, a Protease-Activated Receptor-1 Antagonist, Inhibits Thrombosis Alone and in Combination With Cangrelor in a Folts Model of Arterial Thrombosis in Cynomolgus Monkeys

To determine the antithrombotic effects of SCH 602539, an analog of the selective protease-activated receptor (PAR)-1 antagonist vorapaxar (formerly SCH 530348) currently in advanced clinical development, and the P2Y(12) ADP receptor antagonist cangrelor, alone and in combination. Multiple platelet activation pathways contribute to thrombosis. The effects of SCH 602539 and cangrelor alone and in combination on cyclic flow reductions were evaluated in a Folts model of thrombosis in cynomolgus monkeys. The effects of these treatments on ex vivo platelet aggregation and coagulation parameters were also monitored. Dose-dependent inhibition of cyclic flow reductions was observed after treatment with SCH 602539 alone and cangrelor alone (P<0.05 versus vehicle for the 2 highest concentrations of each agent). The combination of SCH 602539 and cangrelor was associated with synergistic antithrombotic effects (P<0.05 versus vehicle for all combinations tested). The 2 highest doses of SCH 602539 inhibited platelet aggregation in response to PAR-1-selective high-affinity thrombin receptor agonist peptide by greater than 80% but did not affect platelet aggregation induced by other agonists; also, they did not affect any coagulation parameters. The combined inhibition of the PAR-1 and the P2Y(12) ADP platelet activation pathways had synergistic antithrombotic and antiplatelet effects. The addition of a PAR-1 antagonist to a P2Y(12) ADP receptor antagonist may provide incremental clinical benefits in patients with atherothrombotic disease, both in short- and long-term settings. These hypotheses need to be tested clinically.

Numerical Analysis of a Periodically Forced Dyeing Process

In this work, a forcing strategy based on a cyclic flow reversal of a dyeing process of bobbin threads is investigated through numerical simulation. Convection, dispersion, and adsorption of dye on the threads are modeled considering that the system is operated by a cyclic reversal of the flow direction through the bobbins. The periodic forcing is modeled by an ad hoc discontinuous periodic function, and a mathematical model that takes it into account is developed. The mathematical model is a set of partial differential equations that is reduced to a system of ordinary differential equations by an orthogonal collocation on finite elements technique. The comparison between forced and unforced processes has been carried out analyzing the dye distribution factor and the total amount of adsorbed dye during the transient regime for both of the processes. The main effect of periodic forcing is to enhance a more even dye distribution.

Electrochemical detection of propofol at the preanodized carbon electrode

Preanodized screen printed carbon electrode (SPCE) has been utilized for the detection of propofol. Here the preanodized SPCE possess the specific functional groups which help the detection and determination of propofol. The proposed SPCE shows a clear oxidation peak for the detection of propofol in pH 7.0 phosphate buffer solutions. Interestingly, it shows a well-defined individual oxidation peak for the detection of propofol in the presence interferences (mixture of ascorbic acid, dopamine, and uric acid). This type of pretreated SPCE successfully enhances the electrooxidation current and overcomes the interference effects and clearly exhibits the signals for the propofol detection using cyclic voltammetry and flow injection analysis techniques. The preanodized SPCE shows the electrooxidation signals for the propofol detection in the linear range of 0.09 to 0.90 μM, respectively. Further, the sensitivity of the proposed electrode for the propofol detection is found to be 3.6 μA μM−1.

Airflow and nanoparticle deposition in rat nose under various breathing and sniffing conditions—A computational evaluation of the unsteady and turbulent effect

Accurate prediction of nanoparticle (1–100 nm) deposition in the rat nasal cavity is important for assessing the toxicological impact of inhaled nanoparticles as well as for potential therapeutic applications. A quasi-steady assumption has been widely adopted in the past investigations on this topic, yet the validity of such simplification under various breathing and sniffing conditions has not been carefully examined. In this study, both steady and unsteady computational fluid dynamics (CFD) simulations were conducted in a published rat nasal model under various physiologically realistic breathing and sniffing flow rates. The transient airflow structures, nanoparticle transport and deposition patterns in the whole nasal cavity and the olfactory region were investigated and compared with steady state simulation of equivalent flow rate. The results showed that (1) the quasi-steady flow assumption for cyclic flow was valid for over 70% of the cycle period during all simulated breathing and sniffing conditions in the rat nasal cavity, or the unsteady effect was only significant during the transition between the respiratory phases; (2) yet the quasi-steady assumption for nanoparticle transport was not valid, except in the vicinity of peak respiration. In general, the total deposition efficiency of nanoparticle during cyclic breathing would be lower than that of steady state due to the unsteady effect on particle transport and deposition, and further decreased with the increase of particle size, sniffing frequency, and flow rate. In the contrary, previous study indicated that for micro-scale particles (0.5–4 μm), the unsteady effect would increase deposition efficiencies in rat nasal cavity. Combined, these results suggest that the quasi-steady assumption of nasal particle transport during cycling breathing should be used with caution for an accurate assessment of the toxicological and therapeutic impact of particle inhalation. Empirical equations and effective steady state approximation derived in this study are thus valuable to estimate such unsteady effects in future applications. Finally, through large eddy simulations, turbulent effects were found to be negligible for all breathing/sniff conditions in rat nasal cavity.