LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration

BACKGROUND: LIM domain only 2 (LMO2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized. METHODS AND RESULTS: In vitro loss‐ and gain‐of‐function studies on LMO2 were performed in human umbilical vein endothelial cells with lentiviral overexpression or short hairpin RNA knockdown (KD) of LMO2, respectively. LMO2 KD significantly impaired endothelial proliferation. LMO2 controls endothelial G1/S transition through transcriptional regulation of cyclin‐dependent kinase 2 and 4 as determined by reverse transcription polymerase chain reaction (PCR), western blot, and chromatin immunoprecipitation, and also influences the expression of Cyclin D1 and Cyclin A1. LMO2 KD also impaired angiogenesis by reducing transforming growth factor‐β (TGF‐β) expression, whereas supplementation of exogenous TGF‐β restored defective network formation in LMO2 KD human umbilical vein endothelial cells. In a zebrafish model of caudal fin regeneration, RT‐PCR revealed that the lmo2 (zebrafish gene) gene was upregulated at day 5 postresection. The KD of lmo2 by vivo‐morpholino injections in adult Tg(fli1:egfp) (y1) zebrafish reduced 5‐bromo‐2′‐deoxyuridine incorporation in endothelial cells, impaired neoangiogenesis in the resected caudal fin, and substantially delayed fin regeneration. CONCLUSIONS: The transcriptional factor LMO2 regulates endothelial proliferation and angiogenesis in vitro. Furthermore, LMO2 is required for angiogenesis and tissue healing in vivo. Thus, LMO2 is a critical determinant of vascular and tissue regeneration

The Life and Death of Dense Molecular Clumps in the Large Magellanic Cloud

We report the results of a high spatial (parsec) resolution HCO+ (J = 1-0) and HCN (J = 1-0) emission survey toward the giant molecular clouds of the star formation regions N105, N113, N159, and N44 in the Large Magellanic Cloud. The HCO+ and HCN observations at 89.2 and 88.6 GHz, respectively, were conducted in the compact configuration of the Australia Telescope Compact Array. The emission is imaged into individual clumps with masses between 10^2 and 10^4 solar masses and radii of <1 pc to ~2 pc. Many of the clumps are coincident with indicators of current massive star formation, indicating that many of the clumps are associated with deeply-embedded forming stars and star clusters. We find that massive YSO-bearing clumps tend to be larger (>1 pc), more massive (M > 10^3 solar masses), and have higher surface densities (~1 g cm^-2), while clumps without signs of star formation are smaller (<1 pc), less massive (M < 10^3 solar masses), and have lower surface densities (~0.1 g cm^-2). The dearth of massive (M >10^3 solar masses) clumps not bearing massive YSOs suggests the onset of star formation occurs rapidly once the clump has attained physical properties favorable to massive star formation. Using a large sample of LMC massive YSO mid-IR spectra, we estimate that ~2/3 of the massive YSOs for which there are Spitzer mid-IR spectra are no longer located in molecular clumps; we estimate that these young stars/clusters have destroyed their natal clumps on a time scale of at least 3 x 10^{5}$ yrs.Comment: Accepted to ApJ 3-19-201

Minimal set of generators of controllability space for singular linear dynamical systems

Due to the significant role played by singular systems in the form E ¿ x ( t ) = Ax ( t ) , on mathematical modeling of science and engineering problems; in the last years recent years its interest in the descriptive analysis of its structural and dynamic properties. However, much less effort has been devoted to studying the exact con- trollability by measuring the minimum set of controls needed to direct the entire system E ¿ x ( t ) = Ax ( t ) to any desired state. In this work, we focus the study on obtaining the set of all matrices B with a minimal number of columns, by making the singular system E ¿ x ( t ) = Ax ( t ) + Bu ( t ) controllable.Postprint (author's final draft

Comparing the performance of published risk scores in Brugada syndrome: a multi-center cohort study.

The management of Brugada Syndrome (BrS) patients at intermediate risk of arrhythmic events remains controversial. The present study evaluated the predictive performance of different risk scores in an Asian BrS population and its intermediate risk subgroup. This retrospective cohort study included consecutive patients diagnosed with BrS from January 1 , 1997 to June 20 , 2020 from Hong Kong. The primary outcome is sustained ventricular tachyarrhythmias. Two novel risk risk scores and seven machine learning-based models (random survival forest, Ada boost classifier, Gaussian naïve Bayes, light gradient boosting machine, random forest classifier, gradient boosting classifier and decision tree classifier) were developed. The area under the receiver operator characteristic (ROC) curve (AUC) [95% confidence intervals] was compared between the different models. This study included 548 consecutive BrS patients (7% female, age at diagnosis: 50±16 years, follow-up: 84±55 months). For the whole cohort, the score developed by Sieira et al. showed the best performance (AUC: 0.806 [0.747-0.865]). A novel risk score was developed using the Sieira score and additional variables significant on univariable Cox regression (AUC: 0.855 [0.808-0.901]). A simpler score based on non-invasive results only showed a statistically comparable AUC (0.784 [0.724-0.845]), improved using random survival forests (AUC: 0.942 [0.913-0.964]). For the intermediate risk subgroup (N=274), a gradient boosting classifier model showed the best performance (AUC: 0.814 [0.791-0.832]). A simple risk score based on clinical and electrocardiographic variables showed a good performance for predicting VT/VF, improved using machine learning. Abstract: The management of Brugada Syndrome (BrS) patients at intermediate risk of arrhythmic events remains controversial. This study evaluated the predictive performance of published risk scores in a cohort of BrS patients from Hong Kong (N=548) and its intermediate risk subgroup (N=274). A novel risk score developed by modifying the best performing existing score (by. Sieira et al.) showed an area under the curve of 0.855 and 0.760 for the whole BrS cohort and the intermediate risk subgroup, respectively. The performance of the different scores was significantly improved machine learning-based methods, such as random survival forests and gradient boosting classifier. [Abstract copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

The Tpeak – Tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: a systematic review and meta-analysis

Background: The Tpeak – Tend interval, an electrocardiographic marker reflecting transmural dispersion of repolarization, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD) in different clinical settings. Objective: This systematic review and meta-analysis evaluated the significance of Tpeak – Tend interval in predicting arrhythmic and/or mortality endpoints. Methods: PubMed, Embase, Cochrane Library and CINAHL Plus databases were searched through 30th November 2016.Results: Of the 854 studies identified initially, 33 observational studies involving 155856 patients were included in our meta-analysis. Tpeak – Tend interval prolongation (mean cut-off: 103.3 ± 17.4 ms) was a significant predictor of the arrhythmic or mortality outcomes (odds ratio (OR): 1.14, 95% CI: 1.11 to 1.17, p < 0.001). When different end-points were analyzed, the ORs are as follows: VT/VF (1.10, 95% CI: 1.06 to 1.13, p < 0.0001), SCD (1.27, 95% CI 1.17 to 1.39, p < 0.0001), cardiovascular death (1.40, 95% CI 1.19 to 1.64, p < 0.0001), and all-cause mortality (4.56, 95% CI 0.62 to 33.68, p < 0.0001). Subgroup analysis for each disease revealed that the risk of VT/VF or death was highest for Brugada syndrome (OR: 5.68, 95% CI: 1.57 to 20.53, p < 0.01), followed by hypertension (OR: 1.52, 95% CI: 1.26 to 1.85, p < .0001), heart failure (OR: 1.07, 95% CI: 1.04 to 1.11, p < .0001) and ischemic heart disease (OR: 1.06, 95% CI: 1.02 to 1.10, p = 0.001). In the general population, a prolonged Tpeak – Tend interval also predicted arrhythmic or mortality outcomes (OR: 1.59, 95% CI: 1.21 to 2.09, p < 0.001).Conclusion: The Tpeak – Tend interval is useful risk stratification tool in different diseases and in the general population

Modality and uncertainty in data visualizations : A corpus approach to the use of connecting lines

publishedVersionPaid Open Acces

Adversarial Sensor Attack on LiDAR-based Perception in Autonomous Driving

In Autonomous Vehicles (AVs), one fundamental pillar is perception, which leverages sensors like cameras and LiDARs (Light Detection and Ranging) to understand the driving environment. Due to its direct impact on road safety, multiple prior efforts have been made to study its the security of perception systems. In contrast to prior work that concentrates on camera-based perception, in this work we perform the first security study of LiDAR-based perception in AV settings, which is highly important but unexplored. We consider LiDAR spoofing attacks as the threat model and set the attack goal as spoofing obstacles close to the front of a victim AV. We find that blindly applying LiDAR spoofing is insufficient to achieve this goal due to the machine learning-based object detection process. Thus, we then explore the possibility of strategically controlling the spoofed attack to fool the machine learning model. We formulate this task as an optimization problem and design modeling methods for the input perturbation function and the objective function. We also identify the inherent limitations of directly solving the problem using optimization and design an algorithm that combines optimization and global sampling, which improves the attack success rates to around 75%. As a case study to understand the attack impact at the AV driving decision level, we construct and evaluate two attack scenarios that may damage road safety and mobility. We also discuss defense directions at the AV system, sensor, and machine learning model levels.Comment: Accepted at the ACM Conference on Computer and Communications Security (CCS), 201

Adjacent Nucleotide Dependence in ncRNA and Order-1 SCFG for ncRNA Identification

Background: Non-coding RNAs (ncRNAs) are known to be involved in many critical biological processes, and identification of ncRNAs is an important task in biological research. A popular software, Infernal, is the most successful prediction tool and exhibits high sensitivity. The application of Infernal has been mainly focused on small suspected regions. We tried to apply Infernal on a chromosome level; the results have high sensitivity, yet contain many false positives. Further enhancing Infernal for chromosome level or genome wide study is desirable. Methodology: Based on the conjecture that adjacent nucleotide dependence affects the stability of the secondary structure of an ncRNA, we first conduct a systematic study on human ncRNAs and find that adjacent nucleotide dependence in human ncRNA should be useful for identifying ncRNAs. We then incorporate this dependence in the SCFG model and develop a new order-1 SCFG model for identifying ncRNAs. Conclusions: With respect to our experiments on human chromosomes, the proposed new model can eliminate more than 50 % false positives reported by Infernal while maintaining the same sensitivity. The executable and the source code of programs are freely available a

Transgenic Mice Over-Expressing ET-1 in the Endothelial Cells Develop Systemic Hypertension with Altered Vascular Reactivity

Endothelin-1 (ET-1) is a potent vasoconstrictor involved in the regulation of vascular tone and implicated in hypertension. However, the role of small blood vessels endothelial ET-1 in hypertension remains unclear. The present study investigated the effect of chronic over-expression of endothelial ET-1 on arterial blood pressure and vascular reactivity using transgenic mice approach. Transgenic mice (TET-1) with endothelial ET-1 over-expression showed increased in ET-1 level in the endothelial cells of small pulmonary blood vessels. Although TET-1 mice appeared normal, they developed mild hypertension which was normalized by the ETA receptor (BQ123) but not by ETB receptor (BQ788) antagonist. Tail-cuff measurements showed a significant elevation of systolic and mean blood pressure in conscious TET-1 mice. The mice also exhibited left ventricular hypertrophy and left axis deviation in electrocardiogram, suggesting an increased peripheral resistance. The ionic concentrations in the urine and serum were normal in 8-week old TET-1 mice, indicating that the systemic hypertension was independent of renal function, although, higher serum urea levels suggested the occurrence of kidney dysfunction. The vascular reactivity of the aorta and the mesenteric artery was altered in the TET-1 mice indicating that chronic endothelial ET-1 up-regulation leads to vascular tone imbalance in both conduit and resistance arteries. These findings provide evidence for the role of spatial expression of ET-1 in the endothelium contributing to mild hypertension was mediated by ETA receptors. The results also suggest that chronic endothelial ET-1 over-expression affects both cardiac and vascular functions, which, at least in part, causes blood pressure elevation