H2O2‐induced Microvessel Barrier Dysfunction: The Interplay Between Reactive Oxygen Species, Nitric Oxide, and Peroxynitrite

Elevated H2O2 is implicated in many cardiovascular diseases. We previously demonstrated that H2O2-induced endothelial nitric oxide synthase (eNOS) activation and excessive NO production contribute to vascular cell injury and increases in microvessel permeability. However, the mechanisms of excessive NO-mediated vascular injury and hyperpermeability remain unknown. This study aims to examine the functional role of NO-derived peroxynitrite (ONOO) in H2O2-induced vascular barrier dysfunction by elucidating the interrelationships between H2O2-induced NO, superoxide, ONOO, and changes in endothelial [Ca2+ ]i and microvessel permeability. Experiments were conducted on intact rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (Lp). Endothelial [Ca2+ ]i, NO, and O2 were assessed with fluorescence imaging. Perfusion of vessels with H2O2 (10 µmol/L) induced marked productions of NO and O2, resulting in extensive protein tyrosine nitration, a biomarker of ONOO. The formation of ONOO was abolished by inhibition of NOS with NG-Methyl-L-arginine. Blocking NO production or scavenging ONOO by uric acid prevented H2O2- induced increases in endothelial [Ca2+ ]i and Lp. Additionally, the application of exogenous ONOO to microvessels induced delayed and progressive increases in endothelial [Ca2+ ]i and microvessel Lp, a pattern similar to that observed in H2O2-perfused vessels. Importantly, ONOO caused further activation of eNOS with amplified NO production. We conclude that the augmentation of NOderived ONOO is essential for H2O2-induced endothelial Ca2+ overload and progressively increased microvessel permeability, which is achieved by self-promoted amplifications of NO-dependent signaling cascades. This novel mechanism provides new insight into the reactive oxygen and/or reactive nitrogen species-mediated vascular dysfunction in cardiovascular diseases

Cavity Quantum Electrodynamics Effects with Nitrogen Vacancy Center Spins in Diamond and Microwave Resonators at Room Temperature

Cavity quantum electrodynamics (C-QED) effects, such as Rabi splitting, Rabi oscillations and superradiance, have been demonstrated with nitrogen vacancy center spins in diamond in microwave resonators at cryogenic temperature. In this article we explore the possibility to realize strong collective coupling and the resulting C-QED effects with ensembles of spins at room temperature. Thermal excitation of the individual spins by the hot environment leads to population of collective Dicke states with low symmetry and a reduced collective spin-microwave field coupling. However, we show with simulations that the thermal excitation can be compensated by spin-cooling via optical pumping. The resulting population of Dicke states with higher symmetry implies strong coupling with currently available high-quality resonators and enables C-QED effects at room temperature with potential applications in quantum sensing and quantum information processing.Comment: 9 pages, 6 figure

Spectroscopic visualization of flat bands in magic-angle twisted monolayer-bilayer graphene: localization-delocalization coexisting electronic states

Recent transport studies have demonstrated the great potential of twisted monolayer-bilayer graphene (tMBG) as a new platform to host moir\'e flat bands with a higher tunability than twisted bilayer graphene (tBG). However, a direct visualization of the flat bands in tMBG and its comparison with the ones in tBG remain unexplored. Here, via fabricating on a single sample with exactly the same twist angle of ~1.13{\deg}, we present a direct comparative study between tMBG and tBG using scanning tunneling microscopy/spectroscopy. We observe a sharp density of states peak near the Fermi energy in tunneling spectroscopy, confirming unambiguously the existence of flat electronic bands in tMBG. The bandwidth of this flat-band peak is found to be slightly narrower than that of the tBG, validating previous theoretical predictions. Remarkably, by measuring spatially resolved spectroscopy, combined with continuum model calculation, we show that the flat-band states in tMBG exhibit a unique layer-resolved localization-delocalization coexisting feature, which offers an unprecedented possibility to utilize their cooperation on exploring novel correlation phenomena. Our work provides important microscopic insight of flat-band states for better understanding the emergent physics in graphene moir\'e systems.Comment: 15 pages, 4 figure

Nanopore-patterned CuSe drives the realization of PbSe-CuSe lateral heterostructure

Monolayer PbSe has been predicted to be a two-dimensional (2D) topological crystalline insulator (TCI) with crystalline symmetry-protected Dirac-cone-like edge states. Recently, few-layered epitaxial PbSe has been grown on the SrTiO3 substrate successfully, but the corresponding signature of the TCI was only observed for films not thinner than seven monolayers, largely due to interfacial strain. Here, we demonstrate a two-step method based on molecular beam epitaxy for the growth of the PbSe-CuSe lateral heterostructure on the Cu(111) substrate, in which we observe a nanopore patterned CuSe layer that acts as the template for lateral epitaxial growth of PbSe. This further results in a monolayer PbSe-CuSe lateral heterostructure with an atomically sharp interface. Scanning tunneling microscopy and spectroscopy measurements reveal a four-fold symmetric square lattice of such monolayer PbSe with a quasi-particle band gap of 1.8 eV, a value highly comparable with the theoretical value of freestanding PbSe. The weak monolayer-substrate interaction is further supported by both density functional theory (DFT) and projected crystal orbital Hamilton population, with the former predicting the monolayer's anti-bond state to reside below the Fermi level. Our work demonstrates a practical strategy to fabricate a high-quality in-plane heterostructure, involving a monolayer TCI, which is viable for further exploration of the topology-derived quantum physics and phenomena in the monolayer limit.Comment: 26 pagres, 6 Figure

Muscle and Heart Function Restoration in a Limb Girdle Muscular Dystrophy 2I (LGMD2I) Mouse Model by Systemic FKRP Gene Delivery

Mutations in fukutin-related protein (FKRP) gene cause a wide spectrum of disease phenotypes including the mild limb-girdle muscular dystrophy 2I (LGMD2I), the severe Walker-Warburg syndrome, and muscle-eye-brain disease. FKRP deficiency results in α-dystroglycan (α-DG) hypoglycosylation in the muscle and heart, which is a biochemical hallmark of dystroglycanopathies. To study gene replacement therapy, we generated and characterized a new mouse model of LGMD2I harboring the human mutation leucine 276 to isoleucine (L276I) in the mouse alleles. The homozygous knock-in mice (L276IKI) mimic the classic late onset phenotype of LGMD2I in both skeletal and cardiac muscles. Systemic delivery of human FKRP gene by AAV9 vector in the L276IKI mice, at either neonatal age or at the age of 9 months, rendered body wide FKRP expression and restored glycosylation of α-DG in both skeletal and cardiac muscles. FKRP gene therapy ameliorated dystrophic pathology and cardiomyopathy such as muscle degeneration, fibrosis, and myofiber membrane leakage, resulting in restoration of muscle and heart contractile functions. Thus, these results demonstrated that the treatment based on FKRP gene replacement was effective

Associations of HLA-DP Variants with Hepatitis B Virus Infection in Southern and Northern Han Chinese Populations: A Multicenter Case-Control Study

) locus has been reported to be associated with hepatitis B virus (HBV) infection in populations of Japan and Thailand. We aimed to examine whether the association can be replicated in Han Chinese populations. = 0.097∼0.697 and 0.198∼0.615 in northern Chinese population, respectively). loci were strongly associated with HBV infection in southern and northern Han Chinese populations, but not with HBV progression

Physical human-environment interaction via wearable sensors : motion tracking and localization

Human-environment interaction (HEI) is how humans affect and are affected by the surroundings. From the kinematic and kinetic points of view, the motion interaction between the surrounding and the human body can be called physical human-environment interaction (pHEI). Studying pHEI is very useful in understanding human-centered activities in daily live. The objective of this dissertation is to study the tracking of pHEI in daily applications via wearable inertial and contact sensor systems. In body motion tracking, multiple wearable inertial sensors are used to capture the human body kinematics. Meanwhile, contact sensors worn on the body are used to detect the contact interactions with the environment. To determine the precise human kinematic model of a human subject, a quick template-based calibration method is proposed. Subsequently, a three dimensional human motion tracking and localization method termed as simultaneous localization and capture (SLAC) based on the continuous contacts with the environment and the human body kinematics is introduced to record human motions and positions. For tracking of human motions with phases where there is no contact with the environment such as jumping and running, the velocity based SLAC (V-SLAC) and acceleration based SLAC (A-SLAC) are introduced. The proposed SLAC, V-SLAC and A-SLAC methods are able to simultaneously record body motion and track body location over a large space regardless of whether it is indoor and outdoor, or having or not having contacts with the environment. With the proposed quick template-based calibration method, precise human kinematic model can be achieved without using additional external devices. Experimental results and benchmark study with the optical-based Motion Analysis® system showed that the proposed SLAC can control the localization errors within 1% to 2% of the total distance travelled. The velocity errors of the V-SLAC can be controlled within 2% of the moving velocity for daily activities such as walking, jumping and jogging. Experiments on human subjects confirmed that full-body motion and the contact interaction during the pHEI can be properly captured in real-time. With the development of more advanced integrated MEMS inertial sensing technology, SLAC, V-SLAC and A-SLAC can offer great advantage in many daily applications requiring human motion tracking and localization.DOCTOR OF PHILOSOPHY (MAE

Fabrication and applications of graphene-diamond heterostructures

Carbon, which is a common element, has numerous allotropes existing in forms varying from zero-dimension (0D) to three-dimensions (3D). Diamond and graphene are two typical allotropes, in which the carbon atoms bond together with sp3- and sp2hybridisation to form 3D and 2D structures, respectively. With quick development and maturity in synthesis technologies both in the laboratory and industry, diamond and graphene have attracted much interest in many fields. As both diamond and graphene are formed from carbon atoms, the conversion between hybridisation forms are widely investigated. The early synthesis of artificial diamond is prepared from graphite (sp2hybridisation) by high-pressure high-temperature (HPHT) treatment. The sp3- to sp2hybridisation (graphitisation of diamond) is also observed in the mechanical process of using diamond-plated carbide tools in machining transition metal alloys. Recently, with intensive investigation of graphene, researchers have begun to understand the direct conversion of graphene layers on the diamond surface. This thesis firstly gives details on the fabrication of graphene on diamond (graphenediamond) heterostructures. Three different kinds of graphene-diamond heterostructures fabricated by different approaches are introduced as follows. 1) Single layered high quality CVD-grown graphene was transferred directly onto the diamond surface. 2) Thermal treatment of the Ni-coated diamond sample, where the surface of diamond will convert from sp3-bonding to sp2-bonding to form graphene layers on the top. 3) By placing diamond on molten Cu, graphene layers will form on the contact surface of diamond. This thesis also gives details of investigations from three different applications of the fabricated graphene-diamond heterostructures: 1. A diamond detector was fabricated with graphene as the front electrode based on the CVD graphene-diamond heterostructure, which was then characterised. The device shows good Ohmic contact between the graphene and diamond. The device achieves very low dark current and good UV sensitivity. TCAD software is also introduced in this work to simulate the performance of this diamond detector. 2. BasedontheproposedNifilminducedsp3-to-sp2 conversionondiamondsubstrate, a diamond detector was fabricated with graphene layers as electrodes on both sides of the diamond. Density functional theory (DFT) simulations were performed, which demonstrated that the directly converted graphene layer on diamond can achieve Ohmic contact more easily than CVD transferred graphene. Meanwhile, the detector shows good response to the incident X-ray radiation, which indicates a feasible method for the fabrication of an all-carbon detector. 3. The third application reported here is in a graphene-diamond biosensor based on the molten Cu-induced graphene-diamond heterostructure. For traditional graphenebasedbiosensors,thecontactbetweengrapheneandthesubstrateisduetoVanderWaals force, which is not as strong as covalent bonding. As graphene is directly fabricated on the diamond substrate, the contact is based on strong and tight covalent bonding, which ensures high robustness of the graphene-diamond biosensor. When fouled by certain biological detection targets, the performance and sensitivity of the sensor can be fully regeneratedbyasonicationtreatment,whichwouldnothavebeenpossiblefortraditional biosensors. Moreover, the fabricated graphene-diamond biosensor reported in this thesis has high sensitivity and detection range to dopamine. This thesis concludes with a summary of the results, and outlook on future work proposing improvements in graphene-diamond heterostructure fabrication as well as experimental investigations to enhance the understanding of the materials and device physics of diamond UV detectors and X-ray detectors, and opens more opportunities for the development and commercialisation of the photodetectors based on graphenediamond heterostructures

Fabrication and applications of graphene-diamond heterostructures

Carbon, which is a common element, has numerous allotropes existing in forms varying from zero-dimension (0D) to three-dimensions (3D). Diamond and graphene are two typical allotropes, in which the carbon atoms bond together with sp3- and sp2hybridisation to form 3D and 2D structures, respectively. With quick development and maturity in synthesis technologies both in the laboratory and industry, diamond and graphene have attracted much interest in many fields. As both diamond and graphene are formed from carbon atoms, the conversion between hybridisation forms are widely investigated. The early synthesis of artificial diamond is prepared from graphite (sp2hybridisation) by high-pressure high-temperature (HPHT) treatment. The sp3- to sp2hybridisation (graphitisation of diamond) is also observed in the mechanical process of using diamond-plated carbide tools in machining transition metal alloys. Recently, with intensive investigation of graphene, researchers have begun to understand the direct conversion of graphene layers on the diamond surface. This thesis firstly gives details on the fabrication of graphene on diamond (graphenediamond) heterostructures. Three different kinds of graphene-diamond heterostructures fabricated by different approaches are introduced as follows. 1) Single layered high quality CVD-grown graphene was transferred directly onto the diamond surface. 2) Thermal treatment of the Ni-coated diamond sample, where the surface of diamond will convert from sp3-bonding to sp2-bonding to form graphene layers on the top. 3) By placing diamond on molten Cu, graphene layers will form on the contact surface of diamond. This thesis also gives details of investigations from three different applications of the fabricated graphene-diamond heterostructures: 1. A diamond detector was fabricated with graphene as the front electrode based on the CVD graphene-diamond heterostructure, which was then characterised. The device shows good Ohmic contact between the graphene and diamond. The device achieves very low dark current and good UV sensitivity. TCAD software is also introduced in this work to simulate the performance of this diamond detector. 2. BasedontheproposedNifilminducedsp3-to-sp2 conversionondiamondsubstrate, a diamond detector was fabricated with graphene layers as electrodes on both sides of the diamond. Density functional theory (DFT) simulations were performed, which demonstrated that the directly converted graphene layer on diamond can achieve Ohmic contact more easily than CVD transferred graphene. Meanwhile, the detector shows good response to the incident X-ray radiation, which indicates a feasible method for the fabrication of an all-carbon detector. 3. The third application reported here is in a graphene-diamond biosensor based on the molten Cu-induced graphene-diamond heterostructure. For traditional graphenebasedbiosensors,thecontactbetweengrapheneandthesubstrateisduetoVanderWaals force, which is not as strong as covalent bonding. As graphene is directly fabricated on the diamond substrate, the contact is based on strong and tight covalent bonding, which ensures high robustness of the graphene-diamond biosensor. When fouled by certain biological detection targets, the performance and sensitivity of the sensor can be fully regeneratedbyasonicationtreatment,whichwouldnothavebeenpossiblefortraditional biosensors. Moreover, the fabricated graphene-diamond biosensor reported in this thesis has high sensitivity and detection range to dopamine. This thesis concludes with a summary of the results, and outlook on future work proposing improvements in graphene-diamond heterostructure fabrication as well as experimental investigations to enhance the understanding of the materials and device physics of diamond UV detectors and X-ray detectors, and opens more opportunities for the development and commercialisation of the photodetectors based on graphenediamond heterostructures