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Alginate oligosaccharide (AOS) is widely used in agriculture because of its many excellent biological properties. However, the possible beneficial effects of AOS and their underlying mechanisms are currently not well known in grass carp (Ctenopharyngodon idellus). Here, grass carp were fed diets supplemented with 5, 10, or 20 g/kg AOS for six weeks. HE and PAS staining showed that the diets of AOS significantly increased the number of goblet cells in the intestinal. According to transcriptome and quantitative real-time PCR (qRT-PCR) data, AOS-supplemented diets activated the expression of fat metabolism-related pathways and genes. The 16S rRNA sequencing results showed that supplementation with AOS affected the distribution and abundance of the gut bacterial assembly. qRT-PCR and activity assays revealed that the AOS diets significantly increased the antioxidant resistance in gut of grass carp, and down-regulated the expression of inflammatory and up-regulated anti-inflammatory cytokines. Finally, the Aeromonas hydrophila infection assay suggested that the mortality in the groups fed dietary AOS was slightly lower than that in the control. Therefore, supplementing the diet of grass carp with an appropriate amount of AOS can improve fat metabolism and immune responses and alter the intestinal bacterial community, which may help to fight bacterial infection.

This paper proposes an extended neuron model with time delay. It aims to investigate the effect of time delay on the dynamical behavior of the system under different conditions. The existence of the Hopf bifurcation of the system and the stability of its periodic solution are proved by the central manifold theorem. Numerical results show that the system has abundant dynamical performance, including chaos, period-adding, and intermittent chaos.

Although proteolysis targeting chimera (PROTAC) technology that hijacking the ubiquitin-proteasome system (UPS) to artificially degrade protein is an emerging promising technology for many undruggable targets, it still faces several challenges, such as the difficulty to select high specificity molecule to protein of interest (POI), and only few of the E3-ligase are suitable for PROTAC mediated protein degradation. Protein-based PROTAC, termed BioPROTAC, owns the advantage of specificity but lacks membrane permeability. Here, we develop a new targeted protein degrading platform, which we termed RiboPROTAC, by encoding BioPROTAC protein degraders with circular mRNA (cmRNA) and delivering intracellularly. In this way, intracellular protein GFP and nuclear protein PCNA were successfully degraded. For PCNA targeting, not only the level of target protein is strongly decreased, but also the cell function related is strongly interfered, such as cell proliferation, apoptosis, as well as the cell cycle. What is more, for the first time, we observed that degrading PCNA with RiboPROTAC causes immunogenic cell death (ICD), although not strong, but was verified in vivo. Importantly, our in vivo results demonstrated that cmRNA encoded PCNA degrader exhibited significant tumor suppression effect, thus we provide the first proof of concept for the application of RiboPROTAC as potential mRNA therapeutic. We consider that RiboPROTAC is a new and superior PROTAC technology for targeting the undruggable targets.

The application of mRNA as a novel kind of vaccine has been proved recently, due to the emergence use authorization (EUA) by FDA for the two COVID-19 mRNA vaccines developed by Moderna and BioNTech. Both of the two vaccines are based on canonical linear mRNA, and encapsulated by lipid nanoparticle (LNP). Circular mRNA, which is found to mediate potent and durable protein expression, is an emerging technology recently. Owing to its simplicity of manufacturing and superior performance of protein expression, circular mRNA is believed to be a disruptor for mRNA area. However, the application of circular mRNA is still at an initiation stage, proof of concept for its usage as future medicine or vaccine is necessary. In the current study, we established a novel kind of circular mRNA, termed C-RNA, based on Echovirus 29 (E29)-derived internal ribosome entry sites (IRES) and newly designed homology arms and RNA spacers. Our results demonstrated that this kind of circular mRNA is able to mediate strong and durable protein expression, compared to typical linear mRNA. Moreover, for the first time, our study demonstrated that direct intratumoral administration of C-RNA encoding a mixture of cytokines achieved successful modulation of intratumoral and systematic anti-tumor immune responses and finally leading to an enhancement of anti-PD-1 antibody-induced tumor repression in syngeneic mouse model. Additionally, after an optimization of the circular mRNA formulation, a significant improvement of C-RNA mediated protein expression was observed. With this optimized formulation, C-RNA induced enhanced anti-tumor effect via intratumoral administration and elicited significant activation of tumor-infiltrated total T cells and CD8+ T cells. Collectively, we established C-RNA, a novel circular mRNA platform, and demonstrated that it can be applied for direct intratumoral administration for cancer therapy.

Neurons contain a large number of ions inside and outside the cell, and the transmembrane currents formed by the movement of these ions cause membrane potential fluctuations and induce electromagnetism inside and outside the cell. In addition, any change in external electromagnetic fields can cause changes in the membrane potential of the neurons. Therefore, based on the three-dimensional Hindmarsh — Rose (HR) neuron model, a five-dimensional neuron model with time delay is developed in this paper by introducing flux and electric field variables and considering the resulting time delay. First, the Hopf bifurcation theory is used to demonstrate the local stability of the system at the equilibrium point at different time delays. Then, the stability of the Hopf bifurcation and its direction are proved by using the central flow shape theorem. Finally, the existence of the Hopf bifurcation is proved using the phase diagram and the bifurcation diagram, and the effects of several important parameters on the model are investigated by numerical simulations using time series plots, ISI bifurcation plots and two-parameter bifurcation plots. The model is found to be accompanied by chaotic and chaos-free plus-periodic bifurcation structures, mixed-mode discharges and other phenomena. Also, its discharge pattern can be controlled after adding time delay. The results of this paper provide help to the pathogenic mechanism and control of neurological diseases.

This paper proposes a Dynamic Discontinuous PWM (DDPWM) strategy for Grid Tied Inverter applications utilizing 2 level Voltage Source Inverters (VSIs). DDPWM is a version of Generalized DPWM (GDPWM) optimized for usage with full range of operating power factor values and without need for current feedback signals, such that it provides minimal switching loss. Switching and Conduction Loss expressions are derived, simulated and analyzed for individual transistors and diodes inside inverter module. Simplified thermal model based on available datasheet parameters is presented and used for evaluation of thermal performance of semiconductor devices under DDPWM across full range of power factor and modulation index values. It is demonstrated that high modulation index and low power factor values produce highest overall module losses, but that the individual device temperatures are dependent on module forward and switching characteristics, as well as thermal resistances. Experimental setup is implemented to evaluate thermal performance of DDPWM.

SiC MOSFET switching exhibits high dependence on load current, especially during switch-off. Higher dv/dt from SiC faster switching necessitates installation of output filter when long cables are used for inverter-motor connection. Both long cable and dv/dt filter introduce further deviation on switching performance. Impacts from varying load levels, long cable and output filter are investigated experimentally and compared with Si IGBTs performance in this paper. Among the variables, load current demonstrates dominant effect on turn-off time. Based on detailed characterization results, relationship between load current and turn-off time is derived for control deadtime optimization.

The new generation wide bandgap semiconductor power devices such as silicon carbide MOSFET, which can have much higher switching frequency, have been applied in active frond end rectifiers in recent years. A higher switching frequency may enable a much smaller filter for the the active frond end rectifier. In this paper, the filter design method for active frond end rectifier with high switching frequency up to 40 kHz is studied. A new filter design procedure is presented, and the converter side inductor optimization with different core materials is investigated. For different switching frequencies, different core materials are selected with the optimized cost. Electromagnetic and thermal finite element analysis are carried out and seven inductor prototypes are designed. A 10 horsepower active frond end system based on silicon carbide MOSFET is built and the optimal designs are evaluated through experimental tests.

With the increasing popularity of SiC MOSFET modules, new challenges on overcurrent protection arise due to higher current density than Si based counterparts and modules’ working in Ohmic region, resulting in faster temperature rise. In this paper, FET current mirror based overcurrent detection is evaluated on 1200V 800A Mitsubishi SiC MOSFET Module, with standard IGBT gate drive IC De-Saturation (DeSat) function. A gate driver board is designed utilizing gate current limiting soft turn-off (STO) to turn off gate during overcurrent. Design is experimentally tested under different turn-off currents and operation temperatures. Performance is evaluated and compared with two-stage shutdown (TSS) protection. Experimental results demonstrate the protection effectiveness of both designs and factors that affect the performance.

Pulse width modulation (PWM) technique and micro-processor have been extensively used in power electronics converters. Discontinuous pulse width modulation (DPWM) technique is proposed and applied in industrial drive application where switching loss is of great concern and critical to increasing converter’s power density. In addition, random modulation is gaining more interest because of its potential to alleviate the electromagnetic interference (EMI) problem incurred in power electronics converter. In this paper, discussion is given on digital implementation of carried-based randomized discontinuous PWM for active front end drives. A different scheme of ADC sampling synchronization with randomized DPWM is put forward to achieve improved power quality performance while keeping conducted emission spectrum smoothly spread.

High-resistance grounding (HRG) is preferred in many industrial applications where the operation continuity is critical under ground fault conditions, such as pulp, paper, oil refining, chemical, glass, and metal industries. This is due to: 1) continuity of service; 2) minimized productivity impact with the scheduled system downtime; and 3) improved safety concerns—elimination of phase to ground arc flash hazards, suppression of transient line to ground overvoltages, and minimization of the equipment damage at the point of ground fault. However, there are also some drawbacks in accurately detecting and locating a ground fault in adjustable speed drive (ASD) systems: 1) the HRG fault current (1–10 A) cannot reliably trip the overcurrent protection function in drives; 2) the existing methods are based on the line voltage/frequency (50/60 Hz), making it hard to detect and locate low-voltage/low-frequency ground faults; and 3) with the existing methods, the possible fault locations will be manually checked one by one using an Ammeter by a trained technician. This paper will present a flux linkage detection based HRG fault identification method for ASD systems. The proposed method can solve: 1) reliable HRG fault detection with wide motor speed range; 2) the HRG fault can be easily identified in multiple systems; and 3) the identification process is performed by the proposed system diagnosis method, no trained technician is required during the identification process.

The performance of a novel three-phase four-leg fault-tolerant T-type inverter topology is introduced in this paper. This inverter topology provides a fault-tolerant solution to any open-circuit and certain short-circuit switching faults in the power devices. During any of the fault-tolerant operation modes for these device faults, there is no derating required in the inverter output voltage or output power. In addition, overload capability is increased in this new T-type inverter compared to that in the conventional three-level T-type inverter. Such increase in inverter overload capability is due to the utilization of the redundant leg for overload current sharing with other main phase legs under healthy condition. Moreover, if the redundant phase leg is composed of silicon carbide metal–oxide–semiconductor field-effect transistors, quasi-zero-voltage switching, and zero-current switching of the silicon insulated-gate bipolar transistors (IGBTs) in the conventional main phase legs can be achieved at certain switching states, which can significantly relieve the thermal stress on the outer IGBTs and improve the whole inverter efficiency. Simulation and experimental results are given to verify the efficacy and merits of this high-performance fault-tolerant T-type inverter topology.

Blood-brain barrier (BBB) defects and cerebrovascular dysfunction contribute to amyloid-β (Aβ) brain accumulation and drive Alzheimer disease (AD) pathology. By regulating vascular functions and inflammation in the microvasculature, a disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) plays a significant protective effect in atherosclerosis and stroke. However, whether ADAMTS13 influences AD pathogenesis remains unclear. Using in vivo multiphoton microscopy, histological, behavioral, and biological methods, we determined BBB integrity, cerebrovascular dysfunction, amyloid accumulation, and cognitive impairment in APPPS1 mice lacking ADAMTS13. We also tested the impact of viral-mediated expression of ADAMTS13 on cerebrovascular function and AD-like pathology in APPPS1 mice. We show that ADAMTS13 deficiency led to an early and progressive BBB breakdown as well as reductions in vessel density, capillary perfusion, and cerebral blood flow in APPPS1 mice. We found that deficiency of ADAMTS13 increased brain plaque load and Aβ levels and accelerated cerebral amyloid angiopathy (CAA) by impeding BBB-mediated clearance of brain Aβ, resulting in worse cognitive decline in APPPS1 mice. Virus-mediated expression of ADAMTS13 attenuated BBB disruption and increased microvessels, capillary perfusion, and cerebral blood flow in APPPS1 mice already showing BBB damage and plaque deposition. These beneficial vascular effects were reflected by increase in clearance of cerebral Aβ, reductions in Aβ brain accumulation, and improvements in cognitive performance. Our results show that ADAMTS13 deficiency contributes to AD cerebrovascular dysfunction and the resulting pathogenesis and cognitive deficits and suggest that ADAMTS13 may offer novel therapeutic opportunities for AD., Blood-brain barrier breakdown and cerebrovascular dysfunction contribute to the pathology and cognitive deficits of Alzheimer’s disease. This study shows that ADAMTS13 is an important regulator of cerebrovascular integrity, and can play a role in mitigating Alzheimer-like vascular dysfunction, vascular amyloid pathology and cognitive decline.

Background: Exacerbated blood-brain barrier (BBB) damage is related with tissue plasminogen activator (tPA)-induced brain hemorrhage after stroke. Platelets have long been recognized as the cellular orchestrators of primary haemostasis. Recent studies have demonstrated further that platelets are required for supporting intact mature blood vessels and play a crucial role in maintaining vascular integrity during inflammation. Therefore, we sought to investigate whether platelets could reduce tPA-induced deterioration of cerebrovascular integrity and lead to less hemorrhagic transformation. Methods: Mice were subjected to models of collagenase-induced intracerebral hemorrhage (ICH) and transient middle cerebral artery (MCA) occlusion. After 2 hours of MCA occlusion, tPA (10 mg/kg) was administered as an intravenous bolus injection of 1 mg/kg followed by a 9 mg/kg infusion for 30 minutes. Immediately after tPA treatment, mice were transfused with platelets. Hemorrhagic volume, infarct size, neurological deficit, tight junction and basal membrane damages, endothelial cell apoptosis, and extravascular accumulation of circulating dextran and IgG, and Evans blue were quantified at 24 hours. Results: Platelet transfusion resulted in a significant decrease in hematoma volume after ICH. In mice after ischemia, tPA administration increased brain hemorrhage transformation and this was reversed by resting but not activated platelets. Consistent with this, we observed that tPA-induced brain hemorrhage was dramatically exacerbated in thrombocytopenic mice. Transfusion of resting platelets ameliorated tPA-induced loss of cerebrovascular integrity and reduced extravascular accumulation of circulating serum proteins and Evans blue, associated with improved neurological functions after ischemia. No changes were found for infarct volume. Inhibition of platelet receptor glycoprotein VI (GPVI) blunted the ability of platelets to attenuate tPA-induced BBB disruption and hemorrhage after ischemia. Conclusions: Our findings demonstrate the importance of platelets in safeguarding BBB integrity and suggest that transfusion of resting platelets may be useful to improve the safety of tPA thrombolysis in ischemic stroke.

Active Front End voltage source converters are widely used in industrial applications. Control loop gain setting is extremely important to maintain reliable operation of these converters to avoid resonance or bus over voltage issues. This paper presents a novel technique to estimate source impedance during drive pre-charge and transient operational mode. The technique can be extended to different drive power architecture which includes SCR/contactor based pre-charge. Transient method is implemented under a single and multiple drive at point of common coupling. Experimental results are used to validate these techniques. It is recommended to use a PQ meter to estimate and communicate grid information to multiple drives at the same time keeping system cost and accuracy of data into account.

This paper presents a standard DC bus conditioner circuit and highlights safety issues with a floating electric drive configuration in a low leakage and ground current environment. A novel circuit is developed for automatic discharge of the bus conditioner capacitor during the drive shut down. It uses DC bus voltage as an input and a control relay to discharge the capacitor across a resistor. Functional tests were conducted on a 480/690VAC system to assess the performance of the system and circuit reliability. The circuit is validated and results are presented.

In active front end (AFE) drive systems, higher switching frequency $(f_{sw})$ is preferred on rectifier to reduce filter size and improve control performance, while the inverter side could reduce switching loss and improve efficiency by adopting a lower switching frequency. Different switching frequencies for rectifier and inverter may cause high common mode voltage in the system, especially under low speed situation. This paper proposes a novel method to reduce the common mode voltage for this scenario. Without hardware change, it is fully implemented in PWM algorithm. Details on algorithm will be elaborated. Simulation results will be presented, which shows a common mode voltage (CMV) reduction from $\pm V_{dc}$ to $\pm 2/3V_{dc}$ .

Breakthroughs in power electronics technology enables the adjustable speed drives widely popular in industrial automation. Most of the adjustable speed drives used in industry are nonregenerative front end adjustable speed drives. During the design and development of the adjustable speed drive, many of the tests need to be performed at rated output frequencies. The dyne test system are used to load the adjustable speed drives for design development and qualification tests. The dyne-systems are expensive, takes significant floor space, and requires precise installation and routine maintenance. In this paper, a novel dyne-less test method of adjustable speed drive is proposed. The propose test method use the inverter of the adjustable speed drive to load the unit and circulate the power through the converter and inverter. There is no mechanical parts and less power conversion stages makes the system energy efficient and maintenance free. This paper includes theory the operation, simulation and experimental results to demonstrate viability of the propose method.

Silicon Carbide (SiC) MOSFETs, which are wide-bandgap semiconductor devices, have the capability to switch at much higher frequency in comparison with their silicon (Si) counterparts. High di/dt during fast switching transients will lead to semiconductor device failure due to overshoot voltage. It is a common belief that a snubber circuit is necessary for implementing the SiC MOSFETs into designs. However, this study shows that if stray inductance in the current commutation loop (CCL) is minimized with the combination of DC film capacitors and a two-layer laminated bus bar, there is not a need for snubber capacitors to suppress voltage overshoots. A 1200V 800A complete SiC MOSFETs based power structure is built for study. Theoretical model and SPICE model are built. The switching performances with DC electrolytic capacitors, film capacitors and snubber capacitors are evaluated with both SPICE based simulation and experiments, which proves that the snubber circuit can be removed.

High Resistance Grounding is preferred in many industrial applications. However, there are some drawbacks for the traditional HRG detection methods to locate a ground fault in Adjustable Speed Drive systems. The existing methods cannot detect or identify which phase faulted once the drive has HRG fault. This paper will present a leakage flux linkage detection based HRG fault identification method to identify the faulted phase of the drive.

Spontaneous intracerebral haemorrhage (ICH) is the most devastating stroke subtype and has no proven treatment. von Willebrand factor (VWF) has recently been demonstrated to promote inflammation processes. The present study investigated the pathophysiological role of VWF after experimental ICH. Functional outcomes, brain edema, blood-brain barrier (BBB) permeability, cerebral inflammation and levels of intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9) were measured in a mouse model of ICH induced by autologous blood injection. We show that VWF were increased in the plasma and was accumulated in the perihematomal regions of mice subjected to ICH. Injection of VWF resulted in incerased expression of proinflammatory mediators and activation of ICAM-1 and MMP-9, associated with elevated myeloperoxidase, recruitment of neutrophils and microglia. Moreover, mice treated with VWF showed dramatically decreased pericyte coverage, more severe BBB damage and edema formation, and neuronal injury was increased compared with controls. In contrast, blocking antibodies against VWF reduced BBB damage and edema formation and improved neurological function. Together, these data identify a critical role for VWF in cerebral inflammation and BBB damage after ICH. The therapeutic interventions targeting VWF may be a novel strategy to reduce ICH-related injury.

Angiogenic response is essential for ischemic brain repair. The von Willebrand factor (VWF)-cleaving protease disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial tube formation in vitro, but there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke. Deficiency of VWF or anti-VWF antibody treatment significantly increased microvessels, perfused capillary length, and reversed pericyte loss and BBB changes in Adamts13-/- mice. Furthermore, we observed that ADAMTS13 deficiency decreased angiopoietin-2 and galectin-3 levels in the isolated brain microvessels, whereas VWF deficiency had the opposite effect. Correlating with this, overexpression of angiopoietin-2 by adenoviruses treatment or administration of recombinant galectin-3 normalized microvascular reductions, pericyte loss, and BBB breakdown in Adamts13-/- mice. The vascular changes induced by angiopoietin-2 overexpression and recombinant galectin-3 treatment in Adamts13-/- mice were abolished by the vascular endothelial growth factor receptor-2 antagonist SU1498. Importantly, treating wild-type mice with recombinant ADAMTS13 at 7 days after stroke markedly increased neovascularization and vascular repair and improved functional recovery at 14 days. Our results suggest that ADAMTS13 controls key steps of ischemic vascular remodeling and that recombinant ADAMTS13 is a putative therapeutic avenue for promoting stroke recovery.

The performance of a novel three-phase four-leg fault-tolerant T-Type inverter topology is presented in this paper, which significantly improves the inverter's fault-tolerant capability regarding device switch faults. In this new modular inverter topology, only the redundant leg is composed of Silicon Carbide (SiC) power devices and all other phase legs are constituted by Silicon (Si) devices. The addition of the redundant leg, not only provides fault-tolerant solution to switch faults that could occur in the T-Type inverter, but also can share load current with other phase legs. Moreover, quasi zero-voltage switching (ZVS) and zero-current switching (ZCS) in the Si Insulated-Gate Bipolar Transistors (IGBTs) of the main phase legs can be achieved with the assistance of SiC Metal-Oxide Semiconductor Field-Effect Transistors (MOSFETs) in the redundant leg. Simulation and experimental results are given to verify the efficacy and merits of this high-performance fault-tolerant inverter topology.

Breakthroughs in power electronics devices enabled the utilization of the IGBT as the main power switch in AFE converters and enabled the emergence of the fully controlled Active Front End, “AFE”, and low input harmonic solution. This solution employs voltage and current control loops and switching with relatively high switching frequencies of greater than 2 KHz in most applications. The AFE converter is usually connected to the grid through an LCL filter. In this paper, a hybrid technique is introduced to damp the resonance condition that may result due to the existence of the LCL filter. This technique relies on the concept of hybrid damping which combines the advantages of both active and passive damping previously introduced in literature. It will also be shown that the introduced technique overcomes previous limitations which renders this technique more practical and highly applicable to reliable industrial products.

Active front end rectifiers (AFE) are widely used in various industrial area applications. In these types of systems, AC pre-charge circuit, output LCL filter and power module switches are the three most critical power segments. AC pre-charge circuit design is often related to an overall high component volume and cost. Many manufacturers adopt mechanical contactors or breakers between the utility connection point and the rectifier in order to ensure a smooth pre-charge of the DC bus capacitors. Since these mechanical components are typically associated with lower reliability and increased size, the power density and lifetime of the whole system gets affected significantly. This paper proposes a simple solid state pre-charge circuit for AFE rectifiers. Solid state pre-charge circuit offers a fairly simple control while reducing the inrush current for both LCL filter and DC bus capacitors. This method also demonstrates the following advantages: 1) increased lifetime, 2) smaller foot print 3) lower cost. Basic operating theory and circuit analysis along with simulation and experimental results are presented in the paper to demonstrate the effectiveness of the proposed method.

One of the more difficult problems to solve in industrial plants is how to identify and eliminate ground faults in a high-resistance ground (HRG) system. This is because ground-fault conditions in these systems do not draw enough current to reliably trigger fault current sensors in the drive. This article develops an approach to identify the ground-fault location in HRG systems using voltage sensing, rather than current sensing techniques, inside an adjustable speed drive (ASD). This approach consists of a simple analog circuit and digital signal processing technique to detect a fault condition, as well as to identify the fault location, be it on the load motor side, inside the ASD, or ac line side. The use of this ground-fault identification method is also extended and discussed for application to multiple drive lineups.

This paper investigates the effect of voltage stress on the voltage insulation components inside a regenerative active-front-end adjustable speed drive (ASD). It shows that a high potential voltage insulation issue may exist on various components inside the ASD and cause earlier failures. A simplified system model to describe this phenomenon is described, and the voltage stresses of different components inside the ASD under different grounded conditions are analyzed. It is concluded that a much higher voltage stress may exist in different locations of the drive under different grounding systems. Appropriately designing the insulation components is critical to protect the drive.

Tissue plasminogen activator (tPA) is an effective treatment for ischemic stroke, but its neurotoxicity is a significant problem. Here we tested the hypothesis that recombinant ADAMTS 13 (rADAMTS 13) would reduce tPA neurotoxicity in a mouse model of stroke. We show that treatment with rADAMTS 13 in combination with tPA significantly reduced infarct volume compared with mice treated with tPA alone 48 hours after stroke. The combination treatment significantly improved neurological deficits compared with mice treated with tPA or vehicle alone. These neuroprotective effects were associated with significant reductions in fibrin deposits in ischemic vessels and less severe cell death in ischemic brain. The effect of rADAMTS13 on tPA neurotoxicity was mimicked by the N-methyl-D-aspartate (NMDA) receptor antagonist M-801 and was abolished by injection of NMDA. Moreover, rADAMTS 13 prevents the neurotoxicity effect of tPA, by blocking its interaction with the NMDA receptor NR2B and the attendant phosphorylation of NR2B and activation of ERK1/2. Finally, the NR2B-specific NMDA receptor antagonist ifenprodil abolished tPA neurotoxicity and rADAMTS 13 treatment had no further beneficial effect. Our data suggest that the combination of rADAMTS 13 and tPA may provide a novel treatment of ischemic stroke by diminishing the neurotoxic effects of exogenous tPA.

This paper investigates the power cycling lifetime of a three-phase three-level neutral-point-clamped (NPC) inverter used in a 50-kVA adjustable speed drive (ASD). Considering the short lifetime of NPC inverters under low output frequency conditions, an improved discontinuous pulse width modulation (DPWM) method is introduced to extend the inverter lifetime. This improved DPWM method is achieved by injecting a zero-sequence signal with relative high frequency into the voltage reference signals, which is in order to obtain lower swing value of the junction temperatures in the Insulated Gate Bipolar Transistors (IGBTs). Both simulation and experimental results are presented to verify the effectiveness of this solution.

Reliability of multilevel power converters has received increased attention over the past few years, due to the relatively high component failure probability caused by the large number of switching devices utilized in the converter topologies. Thus, the fault-tolerant operation of multilevel converters plays an essential role in safety-critical industrial applications. This paper introduces an improved fault-tolerant inverter topology based on the conventional three-level T-Type neutral-point-clamped (NPC) inverter. Unlike other existing three-phase four-leg fault-tolerant inverter topologies, the fault-tolerant T-Type inverter topology proposed here can significantly enhance the overall thermal overload capability of the inverter, in addition to providing desired fault-tolerant capability. The operating principle of this proposed fault-tolerant T-Type inverter is detailed in this paper, and simulation results are presented to verify the advantages of this improved inverter topology.

A fixture was designed and built to test power cycling reliability at maximum junction temperatures of 150°C and 175°C. A 1200V, 150A IGBT six pack module was mounted on a single cold plate and three sets of cold plates were connected to DC power supplies controlled by LabView. The IGBTs on each cold plate were cycled to give a junction-to-case temperature rise of 100°C with a maximum junction temperature of 150°C. Every 2000 elapsed power cycles, the cold plates were removed from the test setup and the junction-to-case thermal resistance and collector-emitter saturation voltage was measured. Power cycle tests were run until all IGBT modules exceed the failure criteria (5% change in collector-emitter saturation voltage or 20% change in junction-case thermal resistance). The power cycle test was repeated on a new set of IGBTs with the same temperature rise of 100°C, but at 175°C maximum. Weibull analyses of the power cycle test data resulted in shape parameters of 8.6 and 8.8 for the 150°C and 175°C maximum junction temperature data, respectively, that is indicative of rapid wear out. Inspections of the failed modules indicated wire lift-off. The B5 life at 175°C was found to be 36% lower than the B5 life at 150°C. The power cycling test result at 150°C; however, was over two times higher than the life specified by the manufacturer. High temperature reverse bias testing at 175°C was also performed to stress silicon die and packaging materials under a DC bias in order to accelerate migration of ionic contaminants and silicon die impurities. Die temperatures of 175°C caused no degradation of the key electrical static parameter in 1400 hours, which exceeded industry standard test of 1000 hours.

This paper proposes an H ∞ mixed sensitivity design of output current tracking controller in a stationary reference frame for general microgrid-tied inverter applications. Variations in a microgrid impedance values have been modeled as multiplicative uncertainty in the plant model. Equivalent microgrid voltage has been considered as the output disturbance acting on the plant. Particular weighting functions have been introduced as part of the H ∞ algorithm. Weighting functions have been used for performance tuning by shaping the sensitivity and complementary sensitivity functions of the closed loop system. An 8th order H ∞ controller has been synthesized and system robust stability has been evaluated using modified impedance stability criterion. Controller regulating performance has been validated using PSIM software simulation. Despite the fact that no resonance damping technique is applied, system has shown to be robustly stable under predefined microgrid parameters variations.