An optimization framework for wind farm layout design using CFD-based Kriging model

Wind farm layout optimization (WFLO) seeks to alleviate the wake loss and maximize wind farm power output efficiency, and is a crucial process in the design of wind energy projects.Since the optimization algorithms typically require thousands of numerical evaluations of the wake effects, conventional WFLO studies are usually carried out with the low-fidelity analytical wake models.In this paper, we develop an optimization framework for wind farm layout design using CFD-based Kriging model to maximize the annual energy production (AEP) of wind farms. This surrogate-based optimization (SBO) framework uses latin hypercube sampling to generate a group of wind farm layout samples, based on which CFD simulations are carried out to obtain the corresponding AEPs.This wind farm layout dataset is used to train the Kriging model, which is then integrated with an optimizer based on genetic algorithm (GA). As the optimization progresses, the intermediate optimal layout designs are again fed into the dataset.Such adaptive update of wind farm layout dataset continues until the algorithm converges.To evaluate the performance of the proposed SBO framework, we apply it to three representative wind farm cases.Compared to the conventional staggered layout, the optimized wind farm produces significantly higher total AEP.In particular, the SBO framework requires significantly smaller number of CFD calls to yield the optimal layouts that generates almost the same AEP with the direct CFD-GA method.Further analysis on the velocity fields show that the optimization framework attempts to locate the downstream turbines away from the the wakes of upstream ones.The proposed CFD-based surrogate model provides a more accurate and flexible alternative to the conventional analytical-wake-model-based methods in WFLO tasks, and has the potential to be used for designing efficient wind farm projects

AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

Backgrounds/Aims: Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor. Methods: Prostate cancer cells were treated with AZD5153. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by [H3] DNA incorporation assay. Cell apoptosis was tested by caspase-3/-9 activity assay, Histone DNA ELISA assay, Annexin V FACS assay and TUNEL staining assay. Cell cycle progression was tested by propidium iodide (PI) FACS assay. Signaling was tested by Western blotting assay. The nude mice PC-3 xenograft model was applied to test AZD5153’s activity in vivo. Results: AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells. AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells. Further studies show that AKT could be the primary resistance factor of AZD5153. Pharmacological inhibition or genetic depletion of AKT induced BRD4 downregulation, sensitizing AZD5153-induced cytotoxicity in PC-3 cells. In vivo, AZD5153 oral administration inhibited PC-3 xenograft tumor growth in nude mice. Its anti-tumor activity was further enhanced with co-treatment of the AKT specific inhibitor MK-2206. Conclusion: Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells

Simulation of microstructure and properties evolution of micro alloyed steel during hot deformation by cellular automaton

A model for prediction of the dynamic recrystallization microstructure and properties evolution of hot deformed austenite for micro alloyed steel by cellular automaton (CA) was developed. The theoretical modeling of dynamic recrystallization was on the basis of dislocation density, and the nucleation and grain growth of dynamic recrystallization were considered. The microstructure evolution of austenite dynamic recrystallization, such as the grain shape, grain size and volume fraction, was predicted quantitatively and visually described. Moreover the distribution and variation of the dislocation density and flow tress were obtained. Meanwhile, the microstructure and variation of the flow tress of micro alloyed\u3c steel during hot deformation were measured by experiments. The measured results were in good agreement with the CA calculation results

Optimal semi‐dynamic traffic and power flow assignment of coupled transportation and power distribution systems for electric vehicles

Abstract As the most promising alternative to internal combustion engines (ICEs), electric vehicles (EVs) have an excellent development outlook. The charging route scheduling of EVs can simultaneously affect traffic congestion in the transportation network (TN) and power flow distribution in the power distribution network (PDN). The research on TN and PDN coupling networks based on the static traffic flow model is relatively mature; however, it ignores that the traffic flow will spread across periods in a short scheduling period. In this paper, a semi‐dynamic traffic flow model is proposed to represent the dynamic propagation characteristics of EVs and ICEs flow. Furthermore, the cost of carbon emission and system operation are combined as the overall goal of system optimisation. Since the model has become a more complex non‐linear model, this paper proposes to combine the heuristic sequential boundary tightening and binary expansion method to linearise the model. The study compared four cases and found that a 20% penetration rate of EVs can reduce carbon emissions by 4.2% while reducing the system's total cost by 10%. Moreover, the impact of network congestion on the spatiotemporal distribution of traffic flow and power flow in the coupled network is alleviated

Clinical characteristics of IgG4-related retroperitoneal fibrosis versus idiopathic retroperitoneal fibrosis.

Retroperitoneal fibrosis (RPF) is an uncommon condition characterized by inflammation and fibrosis in the retroperitoneal space. More than two-thirds of RPF are idiopathic, with the remaining stemed from a variety of secondary causes. It was suggested that IgG4-related RPF is a secondary form of RPF. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-related RPF and IRPF in a large Chinese cohort. We retrospectively reviewed the medical records of 132 RPF patients diagnosed at Peking University People's Hospital between March 2010 and March 2018. Among the 132 patients, the mean age at disease onset was 54.8 years. IgG4-related RPF group showed greater male predominance compared to IRPF group. IgG4-related RPF patients showed a longer interval between symptom onset and diagnosis, and allergic diseases were more common in this group. Sixty-four patients (48.4%) had lower back pain, which was more common in IRPF group than that in IgG4-related RPF patients. In terms of organ involvement, although 42 of 47 patients (89.3%) with IgG4-related RPF had other organ involvement, there were no patients in the IRPF group with other organ involvement. In addition, the serum IgG4 level, elevated eosinophils counts and IgE level were significantly higher in IgG4-related RPF patients. We described the demographic, clinical and laboratory differences between IgG4-related RPF and IRPF patients, indicating their potential differences in pathogenesis, which was of great importance to diagnose and manage the two phenotypes

SERD-NHC-Au(I) complexes for dual targeting ER and TrxR to induce ICD in breast cancer

The development of selective estrogen receptor degraders (SERDs) has brought new ideas for the clinical treatment of ER-positive advanced breast cancer. The successful application of combinational therapy inspired the exploration of other targets to prevent breast cancer progression. Thioredoxin reductase (TrxR) is an important enzyme that can regulate redox balance in cells and it was considered as a potential target for anticancer treatment. In this study, we firstly combine a clinical SERD candidate——G1T48 (NCT03455270), with a TrxR inhibitor——N-heterocyclic carbene gold(I) [NHC-Au(I)] to form dual targeting complexes that can regulate both signaling pathways. The most efficacious complex 23 exhibited significant antiproliferative profile through degrading ER and inhibiting TrxR activity. Interestingly, it can induce immunogenic cell death (ICD) caused by ROS. This is the first evidence to elucidate the role of ER/TrxR-ROS-ICD axis in ER positive breast cancer and this research may inspire new drug development with novel mechanisms. The in vivo xenograft study demonstrated that complex 23 had excellent antiproliferative activity toward MCF-7 cells in mice model

Circular RNA CDR1as Mediated by Human Antigen R (HuR) Promotes Gastric Cancer Growth via miR-299-3p/TGIF1 Axis

Background: Gastric cancer (GC) remains a common malignancy worldwide with a limited understanding of the disease mechanisms. A novel circular RNA CDR1as has been recently reported to be a crucial regulator of human cancer. However, its biological role and mechanism in the GC growth are still far from clear. Methods: Small interfering RNAs (siRNAs), lentivirus or plasmid vectors were applied for gene manipulation. The CDR1as effects on the GC growth were evaluated in CCK8 and colony formation assays, a flow cytometry analysis and mouse xenograft tumor models. A bioinformatics analysis combined with RNA immunoprecipitation (RIP), RNA pull-down assays, dual-luciferase reporter gene assays, Western blot, reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and functional rescue experiments were used to identify the CDR1as target miRNA, the downstream target gene and its interaction with human antigen R (HuR). Results: The CDR1as overexpression promoted the GC growth in vitro and in vivo and reduced the apoptotic rate of GC cells. Its knockdown inhibited the GC cell proliferation and viability and increased the cell apoptotic rate. Proliferation-related proteins PCNA and Cyclin D1 and apoptosis-related proteins Bax, Bcl-2, Caspase-3 and Caspase-9 were regulated. Mechanically, the cytoplasmic CDR1as acted as a miR-299-3p sponge to relieve its suppressive effects on the GC cell growth. Oncogenic TGIF1 was a miR-299-3p downstream target gene that mediated the promotive effects of CDR1as and regulated the PCNA and Bax levels. HuR interacted with CDR1as via the RRM2 domain and positively regulated the CDR1as level and its oncogenic role as well as downstream target TGIF1. Conclusions: CDR1as promotes the GC growth through the HuR/CDR1as/miR-299-3p/TGIF1 axis and could be used as a new therapeutic target for GC

Simultaneous Activation of Immunogenic Cell Death and cGAS-STING Pathway by Liver- and Mitochondria-Targeted Gold(I) Complexes for Chemoimmunotherapy of Hepatocellular Carcinoma

Induction of immunogenic cell death (ICD) and activation of the cyclic GMP-AMP synthase stimulator of interferon gene (cGAS-STING) pathway are two potent anticancer immunotherapeutic strategies in hepatocellular carcinoma (HCC). Herein, 12 liver- and mitochondria-targeting gold(I) complexes (9a–9l) were designed and synthesized. The superior complex 9b produced a considerable amount of reactive oxygen species (ROS) and facilitated DNA excretion, the ROS-induced ICD and DNA activated the cGAS-STING pathway, both of which evoked an intense anticancer immune response in vitro and in vivo. Importantly, 9b strongly inhibited tumor growth in a patient-derived xenograft model of HCC. Overall, we present the first case of simultaneous ICD induction and cGAS-STING pathway activation within the same gold-based small molecule, which may provide an innovative strategy for designing chemoimmunotherapies for HCC