A comprehensive pan-cancer analysis of CDH5 in immunological response

BackgroundCadherin 5 (CDH5) functions critically in maintaining cell adhesion and integrity of endothelial and vascular cells. The expression of CDH5 is abnormal in tumor cells, which may have great potential to serve as a new immune checkpoint. The current pan-cancer analysis was performed to better understand the role of CDH5 in tumor.MethodsThe clinical significance and immunological function of CDH5 in pan-cancers were comprehensively analyzed based on the correlations between CDH5 and clinicopathologic features, prognosis values, tumor mutation burden (TMB), microsatellite instability (MSI), immune cells infiltration and immune response genes using 33 datasets from The Cancer Genome Atlas (TCGA). We further confirmed the expression of CDH5 in bladder cancer (BCa) tissues and cell lines. The CD8+ T cells were screened from peripheral blood of healthy controls and activated. BCa cell-CD8+ T cell co-culture assay and ELISA assay were carried out to verify the immunological function of CDH5.ResultsThe expression of CDH5 was down-regulated in 8 types of tumors including in BCa but up-regulated in 4 types of tumors. CDH5 was significantly correlated with tumor stage in 6 types of tumors. In addition, CDH5 was positively or negatively correlated with tumor prognosis. Furthermore, CDH5 was closely associated with TMB in 15 types of tumors and with MSI in 9 types of tumors. KEGG-GSEA and Hallmarks-GSEA analyses results indicated that CDH5 was positively related to immune response in most tumor types. In many tumors, CDH5 showed a positive correlation with immune cell infiltration. Enrichment analyses demonstrated that CDH5 was significantly related to the expression of many immunomodulators and chemokines. Further experiments showed that CDH5 was low-expressed in BCa tissues and cell lines in comparison to adjacent normal tissues and normal urothelial cell line, but it was positively associated with a better prognosis of BCa patients. The results of in vitro co-culture assay and ELISA assay demonstrated that CDH5 could promote the function of CD8+ T cells in TME of BCa.ConclusionIn summary, CDH5 was positively associated with a favorable prognosis and effective immune response in tumors, showing a great potential to serve as a novel tumor biomarker and immune checkpoint

Active arc suppression device based on voltage-source convertor with consideration of line impedance in distribution networks

Abstract In the non‐effectively grounding distribution system, residual current under single‐line‐to‐ground (SLG) fault threatens the safety of human being and power supply equipment. Active arc suppression device has been proved to be effective for SLG fault arc suppression when the line impedance is ignored. However, in practice, line impedance varies with the fault location and the load current flowing through the impedance brings about additional voltage drop, which increases the fault current and is not dealt with by the conventional methods. To achieve accurate SLG fault arc suppression with the existence of line impedance, the neutral‐to‐ground voltage reference for full ground‐fault current compensation is firstly derived and a detection method is then proposed. The pre‐fault and post‐fault line currents are used to eliminate the influence of load current on the line impedance voltage drop. A dual‐loop voltage and current controller is then designed. The prototype of active arc suppression device was developed. The results of simulation and prototype experiment validate the effectiveness of the proposed method

The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons

Degrons are minimal elements that mediate the interaction of proteins with degradation machineries to promote proteolysis. Despite their central role in proteostasis, the number of known degrons remains small and a facile technology to characterize them is lacking. Using a strategy combining Global Protein Stability (GPS) profiling with a synthetic human peptidome, we identify thousands of peptides containing degron activity. Using CRISPR screening, we established that the stability of many proteins is regulated through degrons located at their C-terminus. We characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complexes adaptors that regulate C-terminal degrons including six CRL2 and two CRL4 complexes and computationally implicate multiple non-CRLs in end recognition. Human proteome analysis revealed that the C-termini of eukaryotic proteins are depleted for C-terminal degrons, suggesting an E3 ligase-dependent modulation of proteome composition. Thus, we propose that a series of ‘C-end rules’ operate to govern protein stability and shape the eukaryotic proteome

Feasibility and reliability analysis of LCC DC grids and LCC/VSC hybrid DC grids

Power system interconnections using high-voltage direct-current (HVDC) technologies between different areas can be an effective solution to enhance system efficiency and reliability. Particularly, the multi-terminal DC grids, that could balance and ensure resource adequacy, increase asset utilization and reduce costs. In this paper, the technical feasibility of building DC grids using the line commutated converter based (LCC) and voltage source converter based (VSC) HVDC technologies are discussed. Apart from presenting the technical challenges of building LCC DC grids and LCC/VSC hybrid DC grids, the reliability modeling and analysis of these DC grids are also presented. First, the detailed reliability model of the modular multi-level converters (MMCs) with series connected high-voltage and low-voltage bridges are developed. The active mode redundancy design is considered for the reliability model. To this end, a comprehensive whole system reliability model of the studied systems is developed. The reliability model of each subsystem is modeled in detail. Various reliability indices are calculated using this whole system reliability model. The impacts of the redundancy design of the MMCs on these indices are presented. The studies of this paper provide useful guidance for DC grid design and reliability analysis

Control strategies of full-voltage to half-voltage operation for LCC and hybrid LCC/MMC based UHVDC systems

With the increasing demand of transmitting bulk-power over long-distance, the ultra high-voltage direct-current (UHVDC) transmission systems become an attractive option. Nowadays, not only the line commutated converter (LCC) based systems, but also the modular multilevel converter (MMC) based systems have reached UHVDC levels. The converter stations of UHVDC systems normally utilize two series-connected valve-groups to reduce the difficulties of device manufacturing and transportation. This high-voltage and low-voltage valve-group configuration allows the UHVDC systems to achieve a full-voltage to half-voltage operation which increases the flexibility of the systems. However, the existing research only focuses on the full-voltage to half-voltage control of LCC-UHVDC systems. The control strategies for hybrid LCC/MMC UHVDC systems are underresearched. Moreover, the approaches to reduce the load-shedding caused by the full-voltage to half-voltage control for both LCC and hybrid LCC/MMC based UHVDC systems have not been investigated. In this paper, full-voltage to half-voltage control strategies for both LCC and hybrid LCC/MMC based UHVDC systems have been proposed. Moreover, to avoid load-shedding caused by the half-voltage operation, a power rescheduling method that re-sets the power references of the half-voltage operating and full-voltage operating poles has been proposed. The proposed full-voltage to half-voltage control strategies and power rescheduling method can achieve a stable and fast control process with a minimum power loss. The proposed methods have been verified through the time-domain simulations conducted in PSCAD/EMTDC

Hypertensive intracerebral hemorrhage: Which one should we choose between laser navigation and 3D navigation mold?

BackgroundHypertensive intracerebral hemorrhage (HICH) is a severe life-threatening disease, and its incidence has gradually increased in recent years. Due to the particularity and diversity of its bleeding sites, the early treatment of hematoma needs to be more meticulous and accurate, and minimally invasive surgery is often one of the measures that are commonly adopted now. The lower hematoma debridement and the navigation template created by 3D printing technology were compared in the external drainage of a hypertensive cerebral hemorrhage. Then the effect and feasibility of the two operations were explicitly evaluated.Material and methodsWe performed a retrospective analysis of all eligible patients with HICH who underwent laser-guided hematoma evacuation or hematoma puncture under 3D-navigated molds at the Affiliated Hospital of Binzhou Medical University from January 2019 to January 2021. A total of 43 patients were treated. Twenty-three patients were treated with laser navigation-guided hematoma evacuation (group A); 20 patients were treated with 3D navigation minimally invasive surgery (group B). A comparative study was conducted between the two groups to evaluate the preoperative and postoperative conditions.ResultsThe preoperative preparation time of the laser navigation group was significantly shorter than that of the 3D printing group. The operation time of the 3D printing group was better than that of the laser navigation group (0.73 ± 0.26 h vs. 1.03 ± 0.27 h P = 0.00070). In the improvement in the short-term postoperatively, there was no statistically significant difference between the laser navigation group and the 3D printing group (Median hematoma evacuation rate P = 0.14); And in the three-month follow-up NIHESS score, there was no significant difference between the two (P = 0.82).ConclusionLaser-guided hematoma removal is more suitable for emergency operations, with real-time navigation and shortened preoperative preparation time; hematoma puncture under a 3D navigation mold is more personalized and shortens the intraoperative time course. There was no significant difference in therapeutic effect between the two groups

Influence Pathway Discovery on Social Media

This paper addresses influence pathway discovery, a key emerging problem in today's online media. We propose a discovery algorithm that leverages recently published work on unsupervised interpretable ideological embedding, a mapping of ideological beliefs (done in a self-supervised fashion) into interpretable low-dimensional spaces. Computing the ideological embedding at scale allows one to analyze correlations between the ideological positions of leaders, influencers, news portals, or population segments, deriving potential influence pathways. The work is motivated by the importance of social media as the preeminent means for global interactions and collaborations on today's Internet, as well as their frequent (mis-)use to wield influence that targets social beliefs and attitudes of selected populations. Tools that enable the understanding and mapping of influence propagation through population segments on social media are therefore increasingly important. In this paper, influence is measured by the perceived ideological shift over time that is correlated with influencers' activity. Correlated shifts in ideological embeddings indicate changes, such as swings/switching (among competing ideologies), polarization (depletion of neutral ideological positions), escalation/radicalization (shifts to more extreme versions of the ideology), or unification/cooldown (shifts towards more neutral stances). Case-studies are presented to explore selected influence pathways (i) in a recent French election, (ii) during political discussions in the Philippines, and (iii) for some Russian messaging during the Russia/Ukraine conflict.Comment: This paper is accepted by IEEE CIC as an invited vision pape

QTL Mapping Combined With Bulked Segregant Analysis Identify SNP Markers Linked to Leaf Shape Traits in Pisum sativum Using SLAF Sequencing

Leaf shape is an important trait that influences the utilization rate of light, and affects quality and yield of pea (Pisum sativum). In the present study, a joint method of high-density genetic mapping using specific locus amplified fragment sequencing (SLAF-seq) and bulked segregant analysis (BSA) was applied to rapidly detect loci with leaf shape traits. A total of 7,146 polymorphic SLAFs containing 12,213 SNP markers were employed to construct a high-density genetic map for pea. We conducted quantitative trait locus (QTL) mapping on an F2 population to identify QTLs associated with leaf shape traits. Moreover, SLAF-BSA was conducted on the same F2 population to identify the single nucleotide polymorphism (SNP) markers linked to leaf shape in pea. Two QTLs (qLeaf_or-1, qLeaf_or-2) were mapped on linkage group 7 (LG7) for pea leaf shape. Through alignment of SLAF markers with Cicer arietinum, Medicago truncatula, and Glycine max, the pea LGs were assigned to their corresponding homologous chromosomal groups. The comparative genetic analysis showed that pea is more closely related to M. truncatula. Based on the sequencing results of two pools with different leaf shape, 179 associated markers were obtained after association analysis. The joint analysis of SLAF-seq and BSA showed that the QTLs obtained from mapping on a high-density genetic map are convincing due to the closely associated map region with the BSA results, which provided more potential markers related to leaf shape. Thus, the identified QTLs could be used in marker-assisted selection for pea breeding in the future. Our study revealed that joint analysis of QTL mapping on a high-density genetic map and BSA-seq is a cost-effective and accurate method to reveal genetic architecture of target traits in plant species without a reference genome