Fabry Disease and the Heart: A Comprehensive Review

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.     

基于可调谐珐珀滤波器的光纤珐珀传感解调系统研究

在光纤法珀（Fabry Perot.简称F-P）传感解调系统中,获取传感器反射信号的光谱成分是一种实用的方法,论文从可调谐珐珀滤波器波长选择特性的原理出发,提出使用可调谐珐珀滤波器获取传感器反射信号的光谱,从而实现光纤珐珀传感器的腔长信息解调,并在此基础上使用DSP为控制核心搭建了该系统,实验证明了方案的可行性。     

Micro Fabry Perot light modulator for flat panel display

A new type of Fabry Perot light modulator for displays based on micro-electro-mechanical system technology is proposed. Multiple beam interference theory is used to design the modulator and analyze its characteristics. If Fabry Perot cavity length is one-quarter of the incident wavelength, the transmitted light is blocked by the modulator, and the modulator, which is illuminated from its backside, appears black. If the Fabry Perot cavity length is 0 or one-half of the incident wavelength, light may transmit the Fabry Perot modulator from its backside, and the modulator appears bright. Hence, the modulator may be used for flat panel displays. In this paper one Fabry Perot light modulator based on surface microma-chining technology is introduced. The designed modulator has a contrast ratio of 150 and can theoretically be driven by a voltage of 2.4 V.     

法布里-珀罗型告警器激光入射角度的测量方法分析

分析了法布里-珀罗(Fabry-Perot,F-P)型激光告警器的工作原理,讨论了法布里-珀罗标准具摆动角、激光入射角度与折射角三者之间的关系,分析了计算来袭激光入射角度的方法。以波长为1.064μm的激光为例,针对3种不同的入射角,对透射光强随摆动角的变化情况进行了模拟计算。利用处理软件,对3种来袭激光入射角度进行了模拟测量,结果表明,能够较精确地测量出来袭激光的入射角度。     

Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR/Cas9-Corrected Mutation

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.     

Data erasure in Fabry–Perot Diode Lasers: effects of facet reflectivity

ABSTRACT

In this study, the effects of facet reflectivity on the data erasure ability of injection-locked Fabry Perot Laser Diode (FPLD), based on a remodulation method in wavelength division multiplexed passive optical network (WDM PON), were investigated. For this purpose, the feasible front facet reflectivity of FPLD was determined as between 0.2% and 7%, depending on the specified injected power interval. Firstly, the system carried out analysis without applying data at the user end to comprehensively demonstrate how much downstream data was completely erased in FPLD. Then, 2.5 Gb/s of non-return-to-zero (NRZ) data was applied and the results compared with the erased downstream signal without data. The results show that upstream transmission improved with an increase in facet reflectivity between 0.2% and 7%.     

Metasurface‐based low‐profile high‐gain substrate‐integrated Fabry‐Pérot cavity antenna

A metasurface‐based substrate integrated Fabry‐Pérot cavity (FPC) antenna is presented for improved radiation performance associated with the low profile. A novel partially reflective planar (PRS) artificial magnetic conductor (AMC) structure is proposed as the upper reflector of the substrate integrated FP resonant cavity. A microstrip patch antenna is embedded inside the cavity as a feed. The proposed antenna is designed to operate at 9.35 GHz with the maximum realized gain of 14.2 dBi and the overall profile of λ₀/10 (λ₀ is the operating wavelength in free space). The low‐profile performance of the proposed design outperforms any previous substrate‐integrated FPC antenna design with this gain performance. The influences of the FP cavity on the reduction of the antenna profile and the enhancement of the antenna gain are also investigated. Good agreement between the measured and simulated results validates the feasibility of the analysis and design approach.     

Broadband circularly polarized Fabry‐Perot antenna utilizing Archimedean spiral radiator and multi‐layer partially reflecting surface

This article presents a method to design broadband circularly polarized (CP) Fabry‐Perot Resonator (FPR) antenna. The proposed antenna is based on multi‐layer thin dielectric slabs arranged in close proximity as a partially reflecting surface (PRS) and an Archimedean spiral as a CP radiating source. Experimental results show a broadband operation from 6 to 13 GHz, in which the reflection coefficient is less than ?10 dB and the axial ratio (AR) is lower than 3 dB. In addition, good radiation patterns and high broadside gain of better than 10.8 dBic are achieved over the operating bandwidth. The proposed antenna can be used for C‐ and X‐band satellite communications.     

A new inhomogeneous partially reflecting surface for Fabry‐Perot antenna to reduce side lobe level

In this article, an extension of the spatial filter method to study Fabry‐Perot antennas with homogeneous or inhomogeneous partially reflecting surface (PRS) of finite size is proposed. This tool was subsequently validated through the study of different Fabry‐Perot antennas, with homogeneous PRS and inhomogeneous GRadient‐INdex (GRIN) PRS that present very high side lobe level (SLL). Since they are due to structure truncation, a new inhomogeneous PRS to reduce the SLL is designed with the new analytical tool. The new inhomogeneous PRS for Fabry‐Perot antenna is characterized by simulations and measurements. Compared to the homogeneous PRS antenna, the proposed PRS allows a SLL reduction of 5 dB without decreasing the 14 dBi directivity.     

Fabry病肾脏的超微病理研究

结合临床资料对4例Fabry病进行光镜、电镜观察与分析,探讨Fabry病肾脏的超微病理变化及电镜在其早期诊断中的作用。光镜观察显示肾小球有轻微或呈不同程度局灶节段硬化,在肾小球脏层细胞和肾小管上皮细胞胞质内可观察到数量不等的圆形空泡。这些空泡在半薄切片甲苯胺蓝染色后呈清晰的蓝染颗粒。电镜下可观察到一种特征性的嗜锇“斑马小体”或洋葱皮样小体。小体主要位于肾小球脏层细胞,也可出现在系膜细胞、肾小管上皮细胞、肾问质细胞以及血管内皮细胞和平滑肌细胞胞质内。早期病例只在部分肾小球脏层上皮细胞胞质内观察到嗜锇“斑马小体”。超微病理变化可反应疾病病变程度,特别是可为临床早期诊断提供重要的形态学依据。半薄切片甲苯胺蓝染色在Fabry病诊断中有一定价值。