PRMT5 is upregulated by B-cell receptor signaling and forms a positive-feedback loop with PI3K/AKT in lymphoma cells

PRMT5, which regulates gene expression by symmetric dimethylation of histones and non-histone target proteins, is overexpressed and plays a pathogenic role in many cancers. In diffuse large B cell lymphoma (DLBCL), the mechanisms of PRMT5 dysregulation and its role in lymphomagenesis remain largely unknown. Here we demonstrate that B cell receptor (BCR) signaling regulates PRMT5 expression in DLBCL cells. Immunohistochemical analysis reveals elevated levels of PRMT5 expression in DLBCL cases and in germinal center (GC) B cells when compared to naive B cells. PRMT5 can be induced in naive B cells by BCR stimulation. We discovered that BTK-NF-κB signaling induces PRMT5 transcription in activated B cell-like (ABC) DLBCL cells while BCR downstream PI3K-AKT-MYC signaling upregulates PRMT5 expression in both ABC and GCB DLBCL cells. PRMT5 inhibition inhibits the growth of DLBCL cells in vitro and patient derived xenografts. Genomic and biochemical analysis demonstrate that PRMT5 promotes cell cycle progression and activates PI3K-AKT signaling, suggesting a feedback regulatory mechanism to enhance cell survival and proliferation. Co-targeting PRMT5 and AKT by their specific inhibitors is lethal to DLBCL cell lines and primary cancer cells. Therefore, this study provides a mechanistic rationale for clinical trials to evaluate PRMT5 and AKT inhibitors for DLBCL

Over-Expression of PDGFR-β Promotes PDGF-Induced Proliferation, Migration, and Angiogenesis of EPCs through PI3K/Akt Signaling Pathway

The proliferation, migration, and angiogenesis of endothelial progenitor cells (EPCs) play critical roles in postnatal neovascularization and re-endothelialization following vascular injury. Here we evaluated whether the over-expression of platelet-derived growth factor receptor-β (PDGFR-β) can enhance the PDGF-BB-stimulated biological functions of EPCs through the PDGFR-β/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. We first confirmed the expression of endogenous PDGFR-β and its plasma membrane localization in spleen-derived EPCs. We then demonstrated that the PDGFR-β over-expression in EPCs enhanced the PDGF-BB-induced proliferation, migration, and angiogenesis of EPCs. Using AG1295 (a PDGFR kinase inhibitor), LY294002 (a PI3K inhibitor), and sc-221226 (an Akt inhibitor), we further showed that the PI3K/Akt signaling pathway participates in the PDGF-BB-induced proliferation, migration, and angiogenesis of EPCs. In addition, the PI3K/Akt signaling pathway is required for PDGFR-β over-expression to enhance these PDGF-BB-induced phenotypes

An Investigation of Refrigerant Oil Retention in an Air Conditioning System with Two Inverter Compressors in Parallel

A VRF (variable refrigerant flow) air conditioning, having a number of air handling units connected to an external condensing unit, commonly uses two or more compressors in the system. The complicated piping system of the VRF air conditioning causes difficulties for refrigerant oils to return back to each compressor, especially for compressors operating in different frequencies. Compressors need lubrication in operation process, otherwise the compressor will burn out because of wearing and overheating. Therefore, whether refrigerant oils can successfully return back to each compressor has become a key issue in the VRF air conditioning system. To this regard, this report studied refrigerant oil retention of each compressor operating in different frequencies in an air conditioning system with two compressors in parallel and proposed a simple strategy for the refrigerant oil retention of compressors to keep lubricants balanced in two compressors

Radiated Two-Stage method for LTE MIMO User Equipment Performance Evaluation

Two-stage method for long-term-evolution (LTE) multiple-input-multiple-output (MIMO) wireless user equipment (UE) performance evaluation is one of the methods proposed for standard organizations. However, the conducted two-stage method has been challenged for its lack of support for \u27over-the-air\u27 (OTA) as well as for its negligence of the self-interference in the device under test (DUT) in the throughput test. Self-interference in DUT such as cell phones could significantly reduce receiver sensitivity, thus, if not properly included in the test setup, could affect the test accuracy. In order to solve the problems, a radiated two-stage (RTS) test method for LTE MIMO UE test is presented in this paper. By applying an invert calibration matrix to the input signal of the throughput test, the proposed method performs OTA second-stage test, which eliminates the problems of connecting an RF cable directly to the DUT receiver. The RTS OTA MIMO test method can be executed in a standard single-input-single-output anechoic chamber, reduces overall system cost, and offers high reliability and repeatability. Meanwhile, the measurement provides extensive subcomponent-level performance information and makes it an ideal solution for both research and development (R&D) and certification test

A Novel Positional Calibration Method for an Underwater Acoustic Beacon Array Based on the Equivalent Virtual Long Baseline Positioning Model

The performance of long baseline (LBL) positioning systems is significantly impacted by the distribution and positional calibration accuracy of underwater acoustic beacon arrays. In previous calibration methods for beacon arrays based on autonomous underwater vehicle (AUV) platforms, the slant range information of each beacon was processed independently, and each beacon was calibrated one at a time. This approach not only decreases the calibration efficiency but also leaves the positional calibration accuracy of each beacon highly susceptible to the navigation trajectory of the AUV. To overcome these limitations, an equivalent virtual LBL (EVLBL) positioning model is introduced in this paper. This model operates by adjusting the positions of each beacon according to the dead reckoning increments computed during the AUV’s reception of positioning signals, effectively forming a virtual beacon array. Consequently, the AUV is capable of mitigating LBL positioning errors that arise from its motion by simultaneously receiving positioning signals from all beacons. Additionally, an overall calibration method for beacon arrays based on particle swarm optimization (PSO) is proposed. In this approach, the minimization of the deviation between the EVLBL trajectory and the dead reckoning trajectory is set as the optimization objective, and the coordinates of each beacon are iteratively optimized. The simulation results demonstrate that the proposed EVLBL-based PSO algorithm (EVPSO) significantly enhanced the calibration efficiency and positional accuracy of the beacon array. Compared with conventional methods, the estimation error of the beacon positions was reduced from 6.40 m to within 1.00 m. After compensating for the beacon array positions, the positioning error of the LBL system decreased from approximately 5.00 m (with conventional methods) to around 1.00 m (with EVPSO), demonstrating the effectiveness of the proposed approach

Peer-regarding fairness in supply chain

<p>People exhibit peer-regarding fairness concern when others who are in similar circumstances are treated unfairly. The fairness concern derives from a sense of sympathy or schadenfreude. We study it in a distribution channel where a supplier deals with two retailers located at independent markets. Sympathy means the decrease of the retailer’s utility because he believes that his peer’s unfair treatment is undeserved, while schadenfreude indicates the utility increase as the unfair treatment is perceived deserved. The two retailers are offered wholesale prices sequentially and set their retail prices if they accept the offers. In our paper, the second retailer has the peer-regarding fairness concern. We show the following in regards to this idea: (i) the retailers’ profits and the distribution channel performance can be improved by the peer-regarding fairness concern for sympathy; (ii) the retailers’ profits and the channel performance can be reduced by the peer-regarding fairness concern for schadenfreude; and (iii) the peer-regarding fairness concern for sympathy is unfavourable to the supplier, and the second retailer may be punished separately if the concern is not strong enough, while the supplier benefits from the peer-regarding fairness concern for schadenfreude and may exploit the second retailer solely if the schadenfreude parameter is large.</p

Expression Analysis of Retinal G Protein-coupled Receptor and its Correlation with Regulation of the Balance between Proliferation and Aberrant Differentiation in Cutaneous Squamous Cell Carcinoma

Retinal G protein-coupled receptor (RGR), a photosensitive protein, functions as a retinal photoisomerase under light conditions in humans. Cutaneous squamous cell carcinoma (cSCC) is linked to chronic ultraviolet exposure, which suggests that the photoreceptor RGR may be associated with tumorigenesis and progression of squamous cell carcinoma (SCC). However, the expression and function of RGR remain uncharacterized in SCC. This study analysed RGR expression in normal skin and in lesions of actinic keratosis, Bowen’s disease and invasive SCC of the skin with respect to SCC initiation and development. A total of 237 samples (normal skin (n = 28), actinic keratosis (n = 42), Bowen’s (n = 35) and invasive SCC (n = 132) lesions) were examined using immunohistochemistry. Invasive SCC samples had higher expression of RGR protein than the other samples. A high immunohistochemical score for RGR was associated with increased tumour size, tumour depth, Clark level, factor classification, and degree of differentiation and a more aggressive histological subtype. In addition, RGR expression was inversely correlated with involucrin expression and positively correlated with proliferating cell nuclear antigen (PCNA) and Ki67 expression. Furthermore, RGR regulates SCC cell differentiation through the PI3K-Akt signalling pathway, as determined using molecular biology approaches in vitro, suggesting that high expression of RGR is associated with aberrant proliferation and differentiation in SCC