Coordinated economic dispatch of the primary and secondary heating systems considering the boiler’s supplemental heating

District heating systems have been widely used in large and medium-sized cities. Typical district heating systems consist of the primary heating system (PHS) and the secondary heating system (SHS) operating in isolation. However, the isolated dispatch of the PHS and the SHS has poor adjustability and large losses, resulting in unnecessary operation costs. To address these issues, a coordinated economic dispatching model (CEDM) for the primary and secondary heating systems considering the boiler’s supplemental heating is proposed in this study, which characterized the physical properties of the PHS and the SHS in detail. Considering that the PHS and the SHS are controlled separately without central operators in practice, it is difficult to dispatch them in a centralized method. Thus, the master-slave splitting algorithm is innovatively introduced to solve the CEDM in a decentralized way. Finally, a P6S12 system is utilized to analyze and verify the effectiveness and optimality of the proposed algorithm

Distributed coordinated reconfiguration with soft open points for resilience-oriented restoration in integrated electric and heating systems

As the coupling between power distribution systems (PDSs) and district heating systems (DHSs) becomes tighter, it is critical to develop a coordinated strategy for load restoration in integrated electric and heating systems (IEHSs) after natural catastrophes. Similar to PDS reconfiguration, DHSs can modify network topology by remotely operating the ties and sectionalizing valves. A coordinated reconfiguration with soft open points (SOPs) is proposed in this paper for resilience-oriented restoration in IEHSs, which mitigates the fault propagation during fault isolation and explores the flexibility of network topology variation with SOPs for load restoration. To guarantee the privacy of electric and heating systems, we propose an adaptive alternating direction method of multipliers (ADMM), which divides the original problem into PDS and DHS subproblems. The proposed algorithm can intelligently dispatch SOPs and switches in the PDS sub-problem and valves in the DHS subproblem. Comprehensive case studies are carried out to illustrate the effectiveness of coordinated reconfiguration with SOPs for load restoration and verify the proposed algorithm. When considering coordinated reconfiguration with SOPs under the PDS fault scenario, the resilience metrics value increases by 9.6% compared to only PDS reconfiguration

Endothelial DR6 in blood-brain barrier malfunction in Alzheimer’s disease

Abstract The impairment of the blood-brain barrier (BBB) has been increasingly recognised as a critical element in the early pathogenesis of Alzheimer’s disease (AD), prompting a focus on brain endothelial cells (BECs), which serve as the primary constituents of the BBB. Death receptor 6 (DR6) is highly expressed in brain vasculature and acts downstream of the Wnt/β-catenin pathway to promote BBB formation during development. Here, we found that brain endothelial DR6 levels were significantly reduced in a murine model of AD (APPswe/PS1dE9 mice) at the onset of amyloid-β (Aβ) accumulation. Toxic Aβ25-35 oligomer treatment recapitulated the reduced DR6 in cultured BECs. We further showed that suppressing DR6 resulted in BBB malfunction in the presence of Aβ25-35 oligomers. In contrast, overexpressing DR6 increased the level of BBB functional proteins through the activation of the Wnt/β-catenin and JNK pathways. More importantly, DR6 overexpression in BECs was sufficient to rescue BBB dysfunction in vitro. In conclusion, our findings provide new insight into the role of endothelial DR6 in AD pathogenesis, highlighting its potential as a therapeutic target to tackle BBB dysfunction in early-stage AD progression

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study

Abstract There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole‐exome sequencing on normal‐tumor‐thrombus‐metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C‐index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501–0.610, 0.667 versus 0.544–0.651, and 0.719 versus 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively). We constructed a risk predicting model, TT‐GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT‐GPS score displayed better discriminatory ability (OS, c‐index: 0.706–0.840, AUC: 0.788–0.874; DFS, c‐index: 0.691–0.717, AUC: 0.771–0.789) than previously reported models in risk assessment. In conclusion, we identified for the first‐time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT‐GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy

Background: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. Objective: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). Design, setting, and participants: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. Outcomes measurements and statistical analysis: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. Results and limitations: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). Conclusions: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. Patient summary: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein