Myocardial Alternative RNA Splicing and Gene Expression Profiling in Early Stage Hypoplastic Left Heart Syndrome

Hypoplastic Left Heart Syndrome (HLHS) is a congenital defect characterized by underdevelopment of the left ventricle and pathological compensation of the right ventricle. If untreated, HLHS is invariably lethal due to the extensive increase in right ventricular workload and eventual failure. Despite the clinical significance, little is known about the molecular pathobiological state of HLHS. Splicing of mRNA transcripts is an important regulatory mechanism of gene expression. Tissue specific alterations of this process have been associated with several cardiac diseases, however, transcriptional signature profiles related to HLHS are unknown. In this study, we performed genome-wide exon array analysis to determine differentially expressed genes and alternatively spliced transcripts in the right ventricle (RV) of six neonates with HLHS, compared to the RV and left ventricle (LV) from non-diseased control subjects. In HLHS, over 180 genes were differentially expressed and 1800 were differentially spliced, leading to changes in a variety of biological processes involving cell metabolism, cytoskeleton, and cell adherence. Additional hierarchical clustering analysis revealed that differential gene expression and mRNA splicing patterns identified in HLHS are unique compared to non-diseased tissue. Our findings suggest that gene expression and mRNA splicing are broadly dysregulated in the RV myocardium of HLHS neonates. In addition, our analysis identified transcriptome profiles representative of molecular biomarkers of HLHS that could be used in the future for diagnostic and prognostic stratification to improve patient outcome

In-orbit background simulation of a type-B CATCH satellite

The Chasing All Transients Constellation Hunters (CATCH) space mission plans to launch three types of micro-satellites (A, B, and C). The type-B CATCH satellites are dedicated to locating transients and detecting their time-dependent energy spectra. A type-B satellite is equipped with lightweight Wolter-I X-ray optics and an array of position-sensitive multi-pixel Silicon Drift Detectors. To optimize the scientific payloads for operating properly in orbit and performing the observations with high sensitivities, this work performs an in-orbit background simulation of a type-B CATCH satellite using the Geant4 toolkit. It shows that the persistent background is dominated by the cosmic X-ray diffuse background and the cosmic-ray protons. The dynamic background is also estimated considering trapped charged particles in the radiation belts and low-energy charged particles near the geomagnetic equator, which is dominated by the incident electrons outside the aperture. The simulated persistent background within the focal spot is used to estimate the observation sensitivity, i.e. 4.22$\times$10$^{-13}$ erg cm$^{-2}$ s$^{-1}$ with an exposure of 10$^{4}$ s and a Crab-like source spectrum, which can be utilized further to optimize the shielding design. The simulated in-orbit background also suggests that the magnetic diverter just underneath the optics may be unnecessary in this kind of micro-satellites, because the dynamic background induced by charged particles outside the aperture is around 3 orders of magnitude larger than that inside the aperture.Comment: 24 pages, 13 figures, 7 tables, accepted for publication in Experimental Astronom

Simulation Studies for the First Pathfinder of the CATCH Space Mission

The Chasing All Transients Constellation Hunters (CATCH) space mission is an intelligent constellation consisting of 126 micro-satellites in three types (A, B, and C), designed for X-ray observation with the objective of studying the dynamic universe. Currently, we are actively developing the first Pathfinder (CATCH-1) for the CATCH mission, specifically for type-A satellites. CATCH-1 is equipped with Micro Pore Optics (MPO) and a 4-pixel Silicon Drift Detector (SDD) array. To assess its scientific performance, including the effective area of the optical system, on-orbit background, and telescope sensitivity, we employ the Monte Carlo software Geant4 for simulation in this study. The MPO optics exhibit an effective area of $41$ cm$^2$ at the focal spot for 1 keV X-rays, while the entire telescope system achieves an effective area of $29$ cm$^2$ at 1 keV when taking into account the SDD detector's detection efficiency. The primary contribution to the background is found to be from the Cosmic X-ray Background. Assuming a 625 km orbit with an inclination of $29^\circ$, the total background for CATCH-1 is estimated to be $8.13\times10^{-2}$ counts s$^{-1}$ in the energy range of 0.5--4 keV. Based on the background within the central detector and assuming a Crab-like source spectrum, the estimated ideal sensitivity could achieve $1.9\times10^{-12}$ erg cm$^{-2}$ s$^{-1}$ for an exposure of 10$^4$ s in the energy band of 0.5--4 keV. Furthermore, after simulating the background caused by low-energy charged particles near the geomagnetic equator, we have determined that there is no need to install a magnetic deflector

Insight-HXMT observations of Swift J0243.6+6124 during its 2017-2018 outburst

The recently discovered neutron star transient Swift J0243.6+6124 has been monitored by {\it the Hard X-ray Modulation Telescope} ({\it Insight-\rm HXMT). Based on the obtained data, we investigate the broadband spectrum of the source throughout the outburst. We estimate the broadband flux of the source and search for possible cyclotron line in the broadband spectrum. No evidence of line-like features is, however, found up to $\rm 150~keV$. In the absence of any cyclotron line in its energy spectrum, we estimate the magnetic field of the source based on the observed spin evolution of the neutron star by applying two accretion torque models. In both cases, we get consistent results with $B\rm \sim 10^{13}~G$, $D\rm \sim 6~kpc$ and peak luminosity of $\rm >10^{39}~erg~s^{-1}$ which makes the source the first Galactic ultraluminous X-ray source hosting a neutron star.Comment: publishe

Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

As China's first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.Comment: 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech. Astron. arXiv admin note: text overlap with arXiv:1910.0443

신경세포에서 아밀로이드 전구 유사 단백질 2의 C단 단백질의 기능 및 독성 연구

Thesis (doctoral)--서울대학교 대학원 :의학과 약리학 전공,2003.Docto