Khay See

Valproic acid selectively increases vascular endothelial tissue-type plasminogen activator production and reduces thrombus formation in the mouse

Publisher: Elsevier BV

Date: 12-2016

DOI: 10.1111/JTH.13527

Abstract: Essentials Stimulating endogenous fibrinolysis could be a novel antithrombotic strategy. The effect of valproic acid on endothelial tissue plasminogen activator in mice was investigated. Valproic acid increased tissue plasminogen activator expression in vascular endothelium. Valproic acid reduced fibrin deposition and thrombus formation after vascular injury. Background The endogenous fibrinolytic system has rarely been considered as a target to prevent thrombotic disease. Tissue-type plasminogen activator (t-PA) production is potently increased by histone deacetylase (HDAC) inhibitors in endothelial cells in vitro, but whether this translates into increased vascular t-PA production and an enhanced fibrinolytic capacity in vivo is unknown. Objectives To determine whether the HDAC inhibitor valproic acid (VPA) stimulates production of t-PA in the vasculature of mice, and whether VPA pretreatment affects fibrin deposition and clot formation after mechanical vessel injury. Methods Mice were injected with VPA twice daily for up to 5 days. t-PA mRNA, and antigen expression in the mouse aorta and the circulating levels of t-PA were determined. Fibrin and thrombus dynamics after mechanical vessel injury were monitored with intravital confocal microscopy. Potential effects of VPA on platelets and coagulation were investigated. Results and Conclusions We found that VPA treatment increased vascular t-PA production in vivo and, importantly, that VPA administration was associated with reduced fibrin accumulation and smaller thrombi in response to vascular injury, but still was not associated with an increased risk of bleeding. Furthermore, we observed that higher concentrations of VPA were required to stimulate t-PA production in the brain than in the vasculature. Thus, this study shows that VPA can be dosed to selectively manipulate the fibrinolytic system in the vascular compartment and reduce thrombus formation in vivo.

Calorimetric AC loss measurement of MgB2superconducting tape in an alternating transport current and direct magnetic field

Publisher: IOP Publishing

Date: 03-10-2012

DOI: 10.1088/0953-2048/25/11/115016

Online SoC estimation for Li-ion batteries: A survey explore the distributed secure cloud management to battery packs

Publisher: IEEE

Date: 06-2018

DOI: 10.1109/ICIEA.2017.8283137

Systematic Derivation of Dead-Zone Elimination Strategies for the Noninverting Synchronous Buck–Boost Converter

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 04-2018

DOI: 10.1109/TPEL.2017.2704597

A Single-Switch Quadratic Buck–Boost Converter With Continuous Input Port Current and Continuous Output Port Current

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 05-2018

DOI: 10.1109/TPEL.2017.2717462

Innovative Calorimetric AC Loss Measurement of HTSC for Power Applications

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 06-2011

DOI: 10.1109/TASC.2010.2092741

Analysis of the non-inverting buck-boost converter with four-mode control method

Publisher: IEEE

Date: 10-2017

DOI: 10.1109/IECON.2017.8216151

A Δ-Y Hybrid Impedance Network Boost Converter With Reduced Input Current Ripple

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 04-2018

DOI: 10.1109/TPEL.2017.2751638

Evaluation of persistent-mode operation in a superconducting MgB2 coil in solid nitrogen

Publisher: IOP Publishing

Date: 22-02-2016

DOI: 10.1088/0953-2048/29/4/04LT02

A comprehensive study of the pinning mechanisms of MgB2 wires treated with malic acid and their relationships with lattice defects

Publisher: IOP Publishing

Date: 07-2013

DOI: 10.1088/0953-2048/26/8/085013

An energy storage integrated dual-input PV system with distributed maximum power point tracking

Publisher: IEEE

Date: 10-2017

DOI: 10.1109/IECON.2017.8217434

MgB2 superconducting joints for persistent current operation

Publisher: IOP Publishing

Date: 07-05-2015

DOI: 10.1088/0953-2048/28/6/065017

Transport critical current of MgB2 wires: Pulsed current of varying rate compared to direct current method

Publisher: IOP Publishing

Date: 23-08-2011

DOI: 10.1088/0953-2048/24/10/105009

Tuning the band gap in silicene by oxidation

Publisher: American Chemical Society (ACS)

Date: 30-09-2014

DOI: 10.1021/NN504451T

Abstract: Silicene monolayers grown on Ag(111) surfaces demonstrate a band gap that is tunable by oxygen adatoms from semimetallic to semiconducting type. With the use of low-temperature scanning tunneling microscopy, we find that the adsorption configurations and amounts of oxygen adatoms on the silicene surface are critical for band gap engineering, which is dominated by different buckled structures in √13 × √13, 4 × 4, and 2√3 × 2√3 silicene layers. The Si-O-Si bonds are the most energy-favored species formed on √13 × √13, 4 × 4, and 2√3 × 2√3 structures under oxidation, which is verified by in situ Raman spectroscopy as well as first-principles calculations. The silicene monolayers retain their structures when fully covered by oxygen adatoms. Our work demonstrates the feasibility of tuning the band gap of silicene with oxygen adatoms, which, in turn, expands the base of available two-dimensional electronic materials for devices with properties that is hardly achieved with graphene oxide.

Selective inhibition of brain endothelial Rho-kinase-2 provides optimal protection of an in vitro blood-brain barrier from tissue-type plasminogen activator and plasmin

Publisher: Public Library of Science (PLoS)

Date: 16-05-2017

DOI: 10.1371/JOURNAL.PONE.0177332

Novel Thrombolytic Drug Based on Thrombin Cleavable Microplasminogen Coupled to a Single-Chain Antibody Specific for Activated GPIIb/IIIa

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 02-02-2017

DOI: 10.1161/JAHA.116.004535

Abstract: Thrombolytic therapy for acute thrombosis is limited by life‐threatening side effects such as major bleeding and neurotoxicity. New treatment options with enhanced fibrinolytic potential are therefore required. Here, we report the development of a new thrombolytic molecule that exploits key features of thrombosis. We designed a recombinant microplasminogen modified to be activated by the prothrombotic serine‐protease thrombin (HtPlg), fused to an activation‐specific anti–glycoprotein IIb/ III a single‐chain antibody ( SCE 5), thereby hijacking the coagulation system to initiate thrombolysis. The resulting fusion protein named SCE 5‐HtPlg shows in vitro targeting towards the highly abundant activated form of the fibrinogen receptor glycoprotein IIb/ III a expressed on activated human platelets. Following thrombin formation, SCE 5‐HtPlg is activated to contain active microplasmin. We evaluate the effectiveness of our targeted thrombolytic construct in two models of thromboembolic disease. Administration of SCE 5‐HtPlg (4 μg/g body weight) resulted in effective thrombolysis 20 minutes after injection in a ferric chloride–induced model of mesenteric thrombosis (48±3% versus 92±5% for saline control, P .01) and also reduced emboli formation in a model of pulmonary embolism ( P .01 versus saline). Furthermore, at these effective therapeutic doses, the SCE 5‐HtPlg did not prolong bleeding time compared with saline ( P =0.99). Our novel fusion molecule is a potent and effective treatment for thrombosis that enables in vivo thrombolysis without bleeding time prolongation. The activation of this construct by thrombin generated within the clot itself rather than by a plasminogen activator, which needs to be delivered systemically, provides a novel targeted approach to improve thrombolysis.

Structurally homogeneous MgB2superconducting wires through economical wet mixing process

Publisher: Elsevier BV

Date: 2013

DOI: 10.1016/J.MATLET.2012.09.105

Monash University

Location: Australia

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Discovery Projects - Grant ID: DP230100198

Start Date: 2023

End Date: 12-2025

Amount: $398,530.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP180100722

Start Date: 09-2019

End Date: 09-2023

Amount: $264,192.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP160100273

Start Date: 11-2016

End Date: 08-2021

Amount: $360,000.00

Funder: Australian Research Council

Industrial Transformation Research Hubs - Grant ID: IH200100035

Start Date: 07-2021

End Date: 07-2026

Amount: $5,000,000.00

Funder: Australian Research Council