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The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC., Graphical abstract A folate-targeted PEGylated cyclodextrin-based nanoparticle was developed for co-delivery of Rg3 and QTN. The combination of the resultant co-formulation and anti-PD-L1 antibody achieved chemo-immunotherapy for colorectal cancer.Image 1

To address the problem of the weak anti-noise and macro-trend extraction abilities of the current methods for identifying radar antenna scan type, a recognition method for radar antenna scan types based on limited penetrable visibility graph(LPVG) is proposed. Firstly, seven types of radar antenna scans are analyzed, which include the circular scan, sector scan, helical scan, raster scan, conical scan, electromechanical hybrid scan and two-dimensional electronic scan. Then, the time series of the pulse amplitude in the radar reconnaissance receiver is converted into an LPVG network, and the feature parameters are extracted. Finally, the recognition result is obtained by using a support vector machine (SVM) classifier. The experimental results show that the recognition accuracy and noise resistance of this new method are improved, where the average recognition accuracy for radar antenna type is at least 90% when the signal-to-noise ratio (SNR) is 5 dB and above.

Thalassemia is a common monogenic disease in southwestern China, especially in Guizhou province. In this study, 18 309 neonates were examined for thalassemia. The thalassemia carrier rate was 12.90%, which is associated with geographical regions, with carrier frequencies significantly differing between regions (p < 0.0001). The carrier rates for α-thalassemia and β-thalassemia were 8.91% and 3.36%, respectively. There are 22 genotypes identified among 1632 α-thalassemia cases, and 18 genotypes detected among 615 β-thalassemia cases. The birthrates of individuals with intermediate thalassemia and β-thalassemia major were 0.153% and 0.055%, respectively. Methodologically, NGS-Gap-PCR is superior to traditional detection methods, with 65 more cases detected by NGS-Gap-PCR. Since thalassemia-rich genotypes were highly prevalent in this region, early detection of thalassemia carriers would be meaningful for genetic counseling and prevention/treatment of thalassemia. NGS-Gap-PCR provides a powerful tool for neonate genetic testing and clinical diagnosis of thalassemia, especially in high-prevalence regions.

The skin can protect the body from external harm, sense environmental changes, and maintain physiological homeostasis. Cutaneous repair and regeneration associated with surgical wounds, acute traumas, and chronic diseases are a central concern of healthcare. Patients may experience the failure of current treatments due to the complexity of the healing process; therefore, emerging strategies are needed. Hyaluronic acids (HAs, also known as hyaluronan), a glycosaminoglycan (GAG) of the extracellular matrix (ECM), play key roles in cell differentiation, proliferation, and migration throughout tissue development and regeneration. Recently, HA derivatives have been developed as regenerative biomaterials for treating skin damage and injury. In this review, the healing process, namely, hemostasis, inflammation, proliferation, and maturation, is described and the role of HAs in the healing process is discussed. This review also provides recent examples in the development of HA derivatives for wound healing.

According to the discussion of the design method and operational effect for Wuhan Huoshenshan Hospital, this paper summarized the design control points of indoor and outdoor environment of COVID-19 emergency hospital. Based on the design of Wuhan Huoshenshan Hospital, this paper analyzed and discussed the site design, building layout, three-zones and two-passages, the design scheme of the ventilation and air conditioning system for negative pressure ward and negative pressure isolation ward, air distribution, as well as some other key designs for COVID-19 emergency hospital. The design points were summarized and refined. The design methods and technology requirements of the COVID-19 emergency hospital were provided in this study, such as ventilation and air conditioning system setting, ventilation quantity of wards, pressure gradient control measures among different areas, upper and lower air distribution, filter setting mode and distance of air inlet and outlet, which could benefit to provide references for the design of similar projects in the future.

With the development of energy conservation and emission reduction, electric heater in-stead of boiler heating or air conditioning has become a more green choice. Based on electric heater control technology and combined with power line carrier communication technology, this paper studies and designs an electric heater control system. The system realizes the reliable communication of "zero wiring" among electric heater, gateway and server, greatly improves the expansibility and engineering convenience of electric heater control system, and reduces the engineering cost. Comparison between State Grid PLC and G3-PLC has been made via experiment, results show that the State Grid PLC has a better performance in the workspace electric heater controlling scenario.

A comprehensive prediction model of sinter quality based on machine learning algorithm was proposed. First of all, the mass historical data of actual sintering production was collected, cleaned and...

This study presents a high step-up scalable voltage multiple cell (SVMC)-based DC/DC converters, which have the features of high gain, low and adjustable components stresses and automatic input-current sharing in each input phase. In virtue of the above features, the converter is applicable for the DC collection grids for offshore wind farms. In this study, the converter in terms of working principle and property characteristics are analysed with four input phases and three SVMCs. The converter has also been evaluated in terms of the component stress and voltage conversion ratio against some other converters for high-power occasions. Moreover, a 2.5 MW simulation model and a 1.2 kW prototype were constructed for verification.

Hepatocellular carcinoma (HCC) causes significant morbidity and high fatal outcome globally. Conventional therapeutic strategies for HCC have achieved significant improvements, but they have limitations and are far from ideal. Novel nanoparticulate drug delivery systems have recently presented great therapeutic potential for cancer therapeutics. Appropriate and accurate animal models (main mice) are the basis of preclinical and translational research of nanoparticulate drug formulations in HCC. This review will provide an overview of different animal models of HCC, with a particular emphasis on those applied to assess the clinical potential for drug nanopharmaceutics.

Background/Aims: End-stage renal disease (ESRD), characterized by progressive loss of rental function during the disease course, has been reported to be correlated with immune dysregulation. To date, a majority of previous studies on immune response to ESRD have been focused on the T-cell response. This prospective study was to assess the B-cell receptor (BCR) heavy chain repertoire in ESRD patients. Materials and methods: A total of 10 ESRD patients and six healthy controls were prospectively enrolled in this study. BCR immunoglobulin heavy chain (IGH) repertoire in the peripheral blood from ESRD patients and healthy individuals were analyzed by means of next generation sequencing (NGS) in combination with multiplex PCR, Illumina sequencing, and the international ImMunoGeneTics database (IMGT). Results: Abnormal BCR complementary-determining region 3 (CDR3) sequences were identified in relation to ESRD. We also found that the degree of the B-cell clonal expansion in the ESRD group was significantly greater than that in the control group (p

Background: Thalassemia is highly prevalent hematologic disease in Guizhou, China. This study aims to determine the epidemiological characteristics of thalassemia for couples at childbearing age in this subpopulation.Results: There were 4481 couples at childbearing age recruited for thalassemia-carrier screening through both traditional hematological tests and next-generation sequencing (NGS). Of them, 1314 (14.66%) thalassemia-carriers were identified, including 857 (9.76%) α-thalassemia, 391 (4.36%) β-thalassemia, and 48 (0.54%) composite α and β-thalassemia. Of them, 38 couples were high-risk thalassemia carriers. In addition, 12 a-globin gene alterations and 16 b-globin mutations were detected including four novel thalassemia mutations. SEA is the most common α-thalassemia genotype (26.86%), CD41-42 is the most prevalent β-thalassemia genotype (36.57%); the αα/-α3.7 + CD41-42 is the most frequent composite α and β-thalassemia genotype (18.75%). Ethnically, the Zhuang has the highest rate of thalassemia-gene carriers among the ethnic groups. Geographically, Qiannan presented the highest rate of thalassemia-gene carrier. Conclusion: This result enriched the genetic map of thalassemia and provided thalassemia genetic counseling and fertility-guidance for thalassemia-carriers in Guizhou, China. The NGS is so far the most accurate method for population thalassemia screening.

Fatigue experiments and numerical simulations based on the Linear Elastic Fracture Mechanics (LEFM) theory were conducted on the Even-Matched (EM) and Under-Matched (UM) 10CrNi3MoV Load-carrying Cruciform Welded Joints (LCWJs). The study firstly experimentally investigated the Fatigue Crack Growth Rate (FCGR) of base metal, EM, and UM weldments. The corresponding Paris parameters as essential input data are provided to assess the fatigue crack propagation behavior for weld toe and weld root failure of LCWJs. On the one hand, the Stress Intensity Factors (SIFs) at weld toe and weld root were calculated considering the effects of LCWJ specimen geometries, initial crack types, and sizes. The comparisons between simulated results and standards analytical solutions were executed, which exhibit good accordance. It proved that the fatigue fracture simulation procedure based on LEFM is appropriate for the fatigue assessment of LCWJs. Eventually, it conducted the parametric analysis by predicted S-N curves, which included in the weld length, initial crack shape, initial crack size, penetration length, and materials fracture parameter, to explore some safety assessment reference lines for both failure modes of LCWJ.

Effectively monitoring the location and land use of oil production facilities and production emissions in the oil region is of great significance to the HSE management of oilfields. In the study, we construct a location-based Petroleum Remote Sensing dataset (PetroRS dataset), which consist of 10 thousand labelled high-resolution images in two classes of oil production-related objects. After two distinct forms of data augmentation, the dataset is enlarged 9 times. We applied Faster R-CNN, a deep learning method, to the PetroRS dataset to set up a preliminary result as the baseline. On this basis, we use the model to train the augmented dataset and improve the model by optimized anchor based on scale and aspect-ratio statistics. The results show: (1) Faster R-CNN model could detect two classes of oil production-related object automatically and simultaneously with the accuracy of 76% and 32%, respectively; (2) The model training with augmented dataset gives better result, more than 5% accuracy increments, compared to the baseline; (3) The improved model with optimized anchor returns a better result, more than 10% accuracy increments, compared to the baseline. We believe deep learning could provide a new practical and applicable idea in terms of applying remote sensing technology in the petroleum industry.

Background:It is well established thatretrieved lymph nodes (RLNs) count were positively correlated with better overall survival in gastric cancer (GC). But little is known about the relationship between RLNs count and short-term complications after radical surgery.Methods: A total of 1487 consecutive GC patients between January 2016 and December 2018 at Nanjing Drum Tower Hospital were retrospectively analyzed. Univariate analyses were performed to elucidate the association between RLNs count and postoperative complications. We further identified clinical factors that might affect the RLNs count.Results: Among all of the patients, postoperative complications occurred in 435 (29.3%) patients. The mean RLNs count was 25.1 and 864 (58.1%) patients were diagnosed with lymph node metastasis. Univariate analyses showed no significant difference between RLNscount and postoperative complications (both overall and stratified by CDC grade). We further explored that preoperative serum albumin, type of resection, operation time, tumor invasion, lymph node metastasis, and pTNM stage were associated with RLNs count.Conclusions: The current study demonstrated that RLNs count was not associated with postoperative short-term complications following gastrectomy of GC, which provided a rationale for the determination of a proper RLNs count of curative gastrectomy.

During the operation of the safety digitalized instrument and control system of nuclear power plant, it is necessary to monitor the data of online operation in real time. The communication between the engineer station and the safety level shall ensure the real-time, accuracy, reliability and safety requirements of data monitoring. How to design the maintenance network between non-safety engineer station PC and safety instrument and control system is a difficult problem in the industry of nuclear safety DCS research and design. The FirmSys is the first digital nuclear safety instrument and control system platform successfully developed and appraised in China. This paper is based on the networking characteristics of the data communication network in the FirmSys. A data real-time monitoring design based on 802.3 protocol is proposed. The design is based on standard MAC frame structure, and a new data frame format is formed by adding new data segments to meet the real-time requirement of network node interaction. Then, different communication instruction function codes and fixed communication flow are designed to meet the accuracy requirements of the data, and finally, the communication security requirements are met through CRC check, function code check and communication error check. After testing, the method has the characteristics of high real-time performance, high data accuracy and low configuration requirement, and can meet the requirements of real-time data monitoring of nuclear power instrument and control system, and can also be applied to industrial control fields such as ships and thermal power plants.

We described the clinical and neuroimaging characteristics of seven Chinese patients with anti-GAD65 antibody-associated neurological disorders of whom epileptic seizures were the initial and main symptoms. All patients were given immunotherapy and followed up monthly. The outcome demonstrates that immunotherapy is helpful for non-seizure manifestations of anti-GAD65-associated neurological autoimmunity and is less effective in the treatment of seizures, yet partial responses can still occur in the early stage. Taken together we suggest a trial with immunotherapy in all patients in the early stage of the disease, and in patients with non-epilepsy symptoms in the later stage.

With the objective of improving the construction efficiency and provide excellent performance of railway trackbed, the dry-mixed rubberized epoxy asphalt mixture (DREAM) was proposed to prepare the bi-block precast epoxy asphalt trackbed structure. Based on the coarse aggregate voids filling method combining the similitude method for gradation design of coarse aggregate and Superpave method for gradation design of fine aggregate, the gradation of mixture was determined. To analyze the feasibility of proposed asphalt trackbed material for railway structure, the fatigue test under 3 million repeated loadings and semi-circular bending test under the effect of aging and freeze–thaw cycles were conducted. After comprehensively understanding the test results, it was concluded that the DREAM with 11 wt% crumb rubber (CR) exhibited a better fatigue and fracture resistance compared with another type of DREAM with a lower content of CR, i.e., 9 wt%. Owing to a larger amount of CR, the DREAM with11 wt.% CR owned an outstanding ability of deformation recovery and ductile failure. Therefore, it was determined to be an effective asphalt trackbed material. Once the designed DREAM was selected, the corresponding bi-block precast epoxy asphalt trackbed finite element model was generated by using the ABAQUS software for the life-time deformation analysis through the time–temperature superposition principle. The numerical study and calculation of time–temperature conversion indicated that the train loading was mainly responsible for the permanent deformation. The value of permanent deformation caused by the train loadings was two times higher than that caused by static loading (e.g., steel and fastening).

The impaired wound healing in diabetes is a central concern of healthcare worldwide. However, current treatments often fail due to the complexity of diabetic wounds, and thus, emerging therapeutic approaches are needed. Macrophages, a prominent immune cell in the wound, play key roles in tissue repair and regeneration. Recent evidence has demonstrated that macrophages in diabetic wounds maintain a persistent proinflammatory phenotype that causes the failure of healing. Therefore, modulation of macrophages provides great promise for wound healing in diabetic patients. In this study, the potential of paeoniflorin (PF, a chemical compound derived from the herb Paeonia lactiflora) for the transition of macrophages from M1 (proinflammatory phenotype) to M2 (anti-inflammatory/prohealing phenotype) was confirmed using ex vivo and in vivo experimental approaches. A hydrogel based on high molecular weight hyaluronic acid (HA) was developed for local administration of PF in experimental diabetic mice with a full-thickness wound. The resultant formulation (HA-PF) was able to significantly promote cutaneous healing as compared to INTRASITE Gel (a commercial hydrogel wound dressing). This outcome was accompanied by the amelioration of inflammation, the improvement of angiogenesis, and re-epithelialization, and the deposition of collagen. Our study indicates the significant potential of HA-PF for clinical translation in diabetic wound healing., Graphical abstract Image 1, Highlights • PF modulates the phenotype and function of macrophages from M1 to M2. • The PF-loaded HA-based hydrogel significantly promotes diabetic wound healing. • The healing efficacy results from the capacity of fulfilling the inflammation, proliferation, and maturation stages.

// Yingyun Fu 1,3,* , Yazhen Li 1,* , Lan Xu 1 , Shengguo Liu 1 , Minlian Wang 3 , Lu Xiao 1 , Song Liu 2 and Yong Dai 2 1 Department of Respiratory and Critical Care Medicine, The Second Medical College of Jinan University, Shenzhen People’s Hospital, Luohu District, Shenzhen, China 2 Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Luohu District, Shenzhen, China 3 Shenzhen Key Laboratory of Respiratoty Disease, Shenzhen, China * These authors have contributed equally to this work Correspondence to: Yingyun Fu, email: // Keywords : sarcoidosis, immune system, CDR3, TCR BV CDR3, PMBCs, Immunology and Microbiology Section, Immune response, Immunity Received : April 08, 2017 Accepted : July 30, 2017 Published : August 09, 2017 Abstract Sarcoidosis is a systemic granulomatous disorder highly related with immune response. The diversity and stability of the immune system could be measured by hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (TCR). Here we used a combination of multiplex PCR and next-generation sequencing to conduct a good quality analysis of the T-cell receptor BV complementarity-determining region 3 (TCR BV CDR3) gene in peripheral blood mononuclear cells (PBMCs) from 7 sarcoidosis patients and lung sarcoidosis tissue from 6 patients. The length distribution of CDR3 sequences identified a significant difference among CD4+, CD8+ and tissue samples. The analysis of Gini coefficient, Shannon entropy and HEC number showed that they all presents in sarcoidosis tissue group clones in a more skewed manner than that of in PMBCs groups. 2 nucleotide sequences and 2 amino acid sequences were shared by all samples. The comparison of TRBV, TRBJ usage and VJ combination frequency identified 2 TRBV genes, 2 TRBJ genes differentially expressed among different groups and different higher usage and lower usage of V-J combinations between each group.

Recent knowledge of the cellular and molecular mechanisms underlying cutaneous wound healing has advanced the development of medical products. However, patients still suffer from the failure of current treatments, due to the complexity of healing process and thus novel therapeutic approaches are urgently needed. Previously, our laboratories produced a range of low molecular weight hyaluronic acid (LMW-HA) fragments, where a proportion of the glucosamine moieties were chemically N-acyl substituted. Specifically, N-butyrylation results in anti-inflammatory properties in a macrophage system, and we demonstrate the importance of N-acyl substituents in modulating the inflammatory response of LMW-HA. We have set up an inter-institutional collaborative program to examine the biomedical applications of the N-butyrylated LMW-HA (BHA). In this study, the potentials of BHA for dermal healing are assessed in vitro and in vivo. Consequently, BHA significantly promotes dermal healing relative to a commercial wound care product. By contrast, the &ldquo, parent&rdquo, partially de-acetylated LMW-HA (DHA) and the re-acetylated DHA (AHA) significantly delays wound closure, demonstrating the specificity of this N-acylation of LMW-HA in wound healing. Mechanistic studies reveal that the BHA-mediated therapeutic effect is achieved by targeting three phases of wound healing (i.e., inflammation, proliferation and maturation), demonstrating the significant potential of BHA for clinical translation in cutaneous wound healing.

In order to reduce the hydraulic shock and cavitation of micro piston pump, a nonlinear mathematical model of the flow characteristics of micro piston pump was established, considering the leakage of the friction pair. Based on a multi-objective optimization genetic algorithm, with pressure and flow value as optimization targets, the pre-compression and decompression angle of the kidney groove on swashplate was optimized. The computational fluid dynamics (CFD) was used to simulate the flow field of micro piston pump. The simulation results verify the accuracy of the established mathematical model, and flow ripple and pressure overshoot mechanism of micro axial piston pump were analyzed through the CFD visualization technology. This method provides a theoretical support for the structural design optimization of micro piston pump.

Food safety is a big problem. Food traceability can effectively protect food safety. We have designed a complete life cycle food traceability system, using RFID technology to achieve full process supervision from source, circulation and consumption. At the same time, the RFID fault tolerance mechanism is designed to ensure the practicability of the system. Practice has proved that our system effectively provides traceability of food, especially meat, and achieves food safety protection.

4040 Background: PD-1 inhibitor and chemotherapy have shown significant clinical benefits in 1L-treatment of G/GEJ. While it is not clear for locally advanced stage. The aim of this single-arm phase Ib trial is to assess the feasibility of sintilimab (PD-1 inhibitor) in combination with cCRT in locally advanced GC. Methods: Patients (pts) with initial histopathologically confirmed G/GEJ adenocarcinoma, diagnosed as locally advanced III-IVA per AJCC 8th and ECOG PS of 0-1 were eligible. Sintilimab (200mg, iv, Q3W) was given with CRT sandwich in sequence of one induction chemotherapy (S-1+Nab-PTX), weekly Nab-PTX(80-100mg/m2, d1, d8, d15, d22), concurrent radiotherapy (45Gy/1.8Gy*25f), and one consolidation chemotherapy (S-1+Nab-PTX). Pts received three additional combinations of sintilimab and chemotherapy after surgery or investigator’s best choice for unresectable pts after planned therapy. The primary endpoint was pCR and a Simon two-stage was employed at first 9 pts. This interim analysis was pre-planned after finishing stage I assessment. Accrual is ongoing with another 25 in next stage. Results: In the first stage, 5 out of 9 pts achieved pCR and passed to next stage. As of 7th Feb 2021, 28 pts met inclusion criteria with median age 67 yrs (range 47-81), men 86%, PS 1 25%, cT3/4a/4b 28%/54%/18%, cN1/N2/N3 7%/50%/43% and Borrmann II/III/IV 57%/18%/25%. The location on GEJ and G was 14% and 86%. Of 23 pts completed neoadjuvant, all were evaluated as D2-surgery feasibility. 19 pts had completed gastrectomy (4 pts waiting for surgery) with pCR 42.1% (8/19), MPR (≤10% viable tumor cells) 73.7% (14/19) and R0 resection 94.7% (18/19). Down-staging to pT0 and pN0 were both observed in 42.1%. The median follow-up was 5.8m unavailable for survival evaluation at present. Grade (gr) 3-4 TRAE occurred in 39.3% (11/28) pts with most common events as myelosuppression (39.3%) and increased transaminase (10.7%). IrAEs occurred in 21.4% (6/28) pts with one gr 4 hepatitis and others gr 1-2. Peri-operative complications occurred in 3 pts with gr 1-2 pneumonia, increased transaminase, and ileus. No death or unexpected toxicity observed. Conclusions: SHARED interim analysis demonstrated a promising feasibility of sintilimab in combination with cCRT with preliminary impressive pCR & MPR and acceptable toxicity in phase III-IVA G/GEJ cancer. These results warrant further accrual and evaluation. Clinical trial information: ChiCTR1900024428.

e16098 Background: Systemic therapy options for patients with advanced gastric cancer (GC) are limited. We here presented the efficacy results for advanced GC patients matched to targeted therapies or immunotherapies based on the identification of tumor tissue genotypes. Methods: We selected 30 patients diagnosed between 2014 and 2020 with advanced GC at Nanjing Drum Tower Hospital, the affiliated Hospital of Nanjing University Medical School identified with actionable alterations and received ≥1 matched therapies. Tumor biopsy specimens from the patients were analyzed using NGS and/or selected immunohistochemistry and fluorescence in situ hybridization. Results: In these 30 patients, median age at diagnosis was 63 years (range 28-83) and 6 (20%) were female. In total, 11 (37%) harbored c-MET amplification/overexpression (received savolitinib or crizotinib, cohort A), 9 (30%) harbored HER2 mutation/overexpression (received RC48-ADC or trastuzumab, cohort B), 6 (20%) dMMR/MSI-H/TMB-H (received sintilimab, pembrolizumab, tislelizumab or nivolumab, combined with antivascular or not, cohort C), 2 (7%) KIT mutation/amplification (received imatinib or anlotinib, cohort D), 1 (3%) BRAF V600E mutation (received vemurafenib, cohort E) and 1 (3%) EGFR mutation (received afatinib, cohort F). Except for three patients in cohort C, all patients received at least one previous line systemic therapy. In cohort A, three of 11 patients had an objective response (1 complete response and 2 partial responses, objective response rate (ORR) 27%), disease control rate (DCR) was 45%, median progression-free survival (mPFS) was 2.1 months, and median overall survival (mOS) was 3.7 months. In cohort B, ORR was 44% (4/9), DCR was 78% (7/9), mPFS and mOS was 3.1 months and 5.5 months, respectively. In cohort C, ORR was 17% (1/6), DCR was 67% (4/6), mPFS and mOS was 1.9 months and 6.8 months, respectively. In cohort D, no patient had objective response or disease control. In cohort E, the one patient had PR. Stable disease was observed in the patient in cohort F. In all cohorts, ORR was 30% (9/30), DCR was 60% (18/30), mPFS and mOS was 2.7 months and 5.8 months, respectively. Conclusions: Overall, 30 patients with advanced GC were treated with matched therapies according to specific genotype. These real-world outcomes suggested that matched therapies for advanced GC has promising efficacy, supporting the adoption of genotyping in treatment determination.

The problem of suppression of nonlinear random impulse disturbance in grid-connected wind power generation is studied in this paper. The mathematical model of grid side converter of wind power system is obtained by using Kirchhoff law. A feedback synchronization controller is designed to suppress the disturbance of current. With the help of Lyapunov stability theory, the effectiveness of the synchronization controller is verified. Further effectively restrain the nonlinear random disturbance caused by the current connected to the grid, so that the current generated by the wind turbine is synchronized with the current generated by the power grid. Finally, the simulation verification is carried out. The simulation results show that the effectiveness of the proposed control method.

The emerging construction of China’s industry park requires for a specific evaluation method for the local energy internet’s power utilization efficiency. This article focuses on the solar power exploitation from power supply reliability, energy utilization efficiency, solar power general efficiency, established a complete energy internet evaluation index system using improved analytic hierarchy process (AHP). Such method was proved to be more delicate to evaluate the solar-involved park energy internet comparing to traditional methods. The energy internet of a certain industry park was taken as an example for verification. It was found that the improved AHP method can objectively reflect the planning’s efficiency from multi-indicators. When evaluating from different perspective, focusing on a different characteristic of the regional power grid will lead to changes in the AHP evaluation weighting and the results. According to the evaluation result, the relevant suggestions to improve energy efficiency were also proposed.

Because of the lag in sinter composition detection, fluctuations in production conditions are not conducive to making timely adjustments to sintering. In this paper, the characteristics of sintering production data are studied, and three core conclusions are drawn. We find that these data have (1) noise, (2) high dimensionality, and (3) time correlation. Based on these findings, an integrated model based on a deep neural network (DNN) and a long short-term memory (LSTM) network is proposed; using a DNN and an LSTM network solves the problem of developing a system model according to the given input and output data to predict the chemical composition of sinter. Specifically, first, we use a box plot and an isolated forest (iForest) algorithm to detect and filter noise in the data preparation stage and then propose using key feature selection and the Pearson correlation coefficient to reduce the high dimensionality of the data. Then, both an online component monitoring model based on a DNN and an advance component prediction model based on an LSTM are proposed to help the field operators to control the change of the sinter composition in real time. The results of many experiments show that the proposed method performs better than the current methods: the goodness of fit (R2) score of the better model is above 0.92, and both the mean square error (MSE) and mean absolute error (MAE) are approximately zero. The deep neural network-based method proposed in this paper is more suitable for the online monitoring and advance prediction of sinter components.

Background Tuberculosis (TB) is a major global health problem and has replaced HIV as the leading cause of death from a single infectious agent. Methods Here, we applied high throughput sequencing to study the immune repertoire of nine pulmonary tuberculosis patients and nine healthy control samples. Results Tuberculosis patients and healthy controls displayed significantly different high express clones and distinguishable sharing of CDR3 sequences. The TRBV and TRBJ gene usage showed higher expression clones in patients than in controls and we also found specific high express TRBV and TRBJ gene clones in different groups. In addition, six highly expressed TRBV/TRBJ combinations were detected in the CD4 group, 21 in the CD8 group and 32 in the tissue group. Conclusion In conclusion, we studied the patients with tuberculosis as well as healthy control individuals in order to understand the characteristics of immune repertoire. Sharing of CDR3 sequences and differential expression of genes was found among the patients with tuberculosis which could be used for the development of potential vaccine and targets treatment.

Chiral plasmonic nanostructures with giant and tunable chiral optical responses hold great potential in chiral sensing applications for chemistry, biology, and pharmacy, etc. For the origin of the chiral optical response of artificial plasmonic chiral assemblies, resonant and off-resonant coupling mechanisms have been figured out. However, most existing chiral plasmonic assemblies are based on only one mechanism, where strong optical chirality always compromises with spectral tunability. To release the trade-off between the strength and spectral tunability, we employ a combination of resonant and off-resonant coupling mechanisms and demonstrate a pronounced and tailorable chiral optical response based on plasmonic meta-atoms with distinct shapes. We anticipate that our strategy provides more flexibility in designing chiral plamsonic nanostructures and promotes the field further towards customized chiral plasmonic platforms.

The correlation between coronary artery disease (CAD) and obstructive sleep apnea syndrome (OSAS) was investigated to analyze its risk factors. A total of 84 patients with suspected CAD due to chest tightness and pain or nocturnal angina, were selected. They were admitted and received coronary angiography in The Affiliated Hospital of Medical College Qingdao University from March, 2016 to June, 2017. The vital signs were monitored, and the sleep monitoring was performed before and after coronary angiography. Before angiography, the fasting blood was drawn for blood biochemical detection, followed by routine electrocardiogram and echocardiographic examination. In addition, the body mass index was calculated and whether patients suffered from hypertension and diabetes mellitus was observed. The patients were divided into the control group (patients with a negative coronary angiography) and the CAD group (patients with a positive coronary angiography). There were 34 cases in the control group, including 21 cases of OSAS (61.76%), and 50 in the CAD group, including 40 cases of OSAS (80.00%). Statistical analysis revealed that there were statistically significant differences in the apnea hypopnea index (AHI), lowest oxygen saturation, degree of coronary stenosis (Gensini score) and triglyceride level between the two groups (P20 were the risk factors of CAD (OR=7.036 and 5.377). Thus, CAD is closely correlated with OSAS and AHI >20 is one of the risk factors of CAD.

The anti-seismic performance of fuel assembly is mainly determined by the critical crush load and the stiffness of spacer grids. To comprehensive know about the influence of fuel rods on the spacer grid, a 5×5 spacer grid FEM model which including fuel rods is established. Basing the fact that the grid spring has remarkable influence on the grid crush strength which is found in experiment, some cases are carried out, which are used to analyze effects of grid with/without fuel rod, friction between the grid spring/dimple and the fuel rod, the deflection of grid spring on the static buckling strength. Results show that grids with fuel rods will have higher crush strength than those without fuel rods; at certain range, increasing grid spring deflection at working point will do help to increase the grid crush strength; higher friction coefficient of grid spring and fuel rod can enhance the crush strength. Comparing with experimental results in literatures, results from simulations show the same tendency with the experimental results. The conclusion and the simulation method involved in this paper can provide some guidelines to optimize the performance of spacer grid assembly.

Interactive image segmentation method plays a vital role in various applications, such as image processing, computer vision and other fields. Traditional interactive image segmentation methods focus on using the way of manually adding interactive information, such as sketching the edges, distinguishing foreground backgrounds with dotted frames, and so on. The information acquisition and decoding technology has become more mature, such as in eye movement and electroencephalogram, and based on which, this paper presents an interactive image segmentation method that uses eye movement trajectory and EEG as interactive information. While observing the image, it collects the data from EEG and eye movement, based on these physiological signals to establish a more natural interactive image object segmentation method. The results show that the method of brain-computer interaction based image segmentation has advantages in the following aspects: first, it is hand-free, and can be applied to special occasions; second, there will be higher efficiency and better results in multi-target image segmentation. This research provides a new way to establish a new method of image segmentation based on human-computer cooperation.

Radioactive source terms at nuclear power plants varies due to different operation condition. During cold shutdown process, oxygenation operation is taken to reduce the radioactive source term activity raised by sharpen pressure and temperature changes in pipes and equipments, thus factors such as oxygenation process, working condition, significant time point need to be considered for a conservative yet reasonable result of shielding source term calculation. Taking RHR system for example, this paper focuses on the theoretical analysis of appropriate shielding source terms considering oxygenation operation under cold shutdown condition. The effects of oxygenation operation on source terms especially on corrosion products are analyzed, and an acceptable result consisting with the principle-optimization of radiation protection is suggested.

Pulsed laser ablation of solid target has very wide applications in many areas at present. However, most theoretical and experimental investigations focus on the interaction between pulsed laser and solid target with flat surface. It is significant for practical application of pulsed laser to research it interact with a non-smooth target surface. In this paper, time-resolved observation using ICCD camera has been performed to research process of plasma induced by nanosecond laser pulse ablation of copper target with a rough plaque. The experiment result shows the copper target is ionized at first and plasma plume then produce. Moreover, the plasma plume produce again at the end of the laser pulse because large amount of particles moves towards the target and transfer energy to the surface resulted in ionization.

With the development of electrified railway, there produced more andmore electromagnetic compatibility problems. It will affect the safety of trainoperation and personnel safety. This paper introduces electromagneticinterference analysis about our electrified railway on the traction powersupply system, the signal equipment, the train structure and the surroundingenvironment in our country.

Androgen receptor (AR) is the major driver of prostate cancer (CaP) progression. Despite initially inducing remissions, androgen deprivation therapy (ADT) does not cure CaP and the majority of CaP that recurs under ADT continues to rely on AR. In a subset of patients, administration of novel, more potent ADT drugs leads to emergence of a neuroendocrine (NE) CaP phenotype that is AR-indifferent and even harder to treat. The molecular mechanisms by which AR regulates cell cycle progression and that can be developed into alternative targets to inhibit CaP growth, overcome acquired resistance to ADT, or prevent NE progression, however, remain largely unknown. Here, we identify citron kinase (CIT), which controls cell division, as a novel drugabble target that acts downstream of AR. In multiple CaP models, CIT protein expression was stimulated selectively by low doses of androgens that promote CaP cell proliferation and decreased by AR silencing or short-term administration of AR-antagonist enzalutamide, confirming its AR dependence. Silencing of CIT significantly reduced CaP cell viability and cell proliferation, delayed cell progression, increased the number of multinucleated cells in ADT-naïve and -recurrent CaP cells, and attenuated CaP growth in xenograft models. Overexpression of CIT, transiently or stably, stimulated CaP cell proliferation in androgen-supplemented conditions and under ADT, and this depended entirely on an intact CIT kinase domain. In 2 independent clinical CaP datasets, CIT mRNA levels increased during CaP progression and higher CIT expression correlated with shorter disease-free and overall survival. Using CaP tissue microarrays that contain more than 200 patient specimens, CIT protein expression was significantly higher in primary CaP when compared to adjacent non-neoplastic prostate tissues and correlated with increasing Gleason scores, validating the relevance of CIT overexpression to CaP aggressiveness. Integrated RNA-Seq, MSigDB and GSEA analyses confirmed that the AR- and CIT-dependent transcriptome preferentially controlled CaP cell cycle progression and proliferation. Mechanistically, the use of inhibitors of gene transcription, mRNA translation and proteasome indicated that the androgen-dependence of CIT expression is regulated at the post-transcriptional level. Specifically, CIT protein expression was controlled by the E2F family of cell cycle regulators, with androgen-responsive E2F2 as the major determinant of CaP CIT expression. Our work, thus, isolated a novel role for the mitotic kinase CIT in AR-dependent CaP cell proliferation and clinical progression and identified CIT’s kinase moiety as a novel target for CaP therapy. Funding: NIH/NCI, Case Comprehensive Cancer Center Pilot Research Award Citation Format: Salma Ben-Salem, Salam Bachour, Varadha Balaji Venkadakrishnan, Yixue Su, Eduardo Cortes Gomez, Qiang Hu, Eric Klein, Nicolas Marlo, Cristina Magi-Galluzzi, Liu Song, Hannelore V. Heemers. Prostate cancer progression depends on the activity of the mitotic kinase citron kinase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 390.

Sensing of leakage at an early stage is crucial for the safe utilization of hydrogen. Optical hydrogen sensors eliminate the potential hazard of ignition caused by electrical sparks but achieve a detection limit far higher than their electrical counterparts so far. To essentially improve the performance of optical hydrogen sensors in terms of detection limit, we demonstrate in this work a plasmonic hydrogen sensor based on aluminum-palladium (Al-Pd) hybrid nanorods. Arranged into high-density regular arrays, the hybrid nanorods are capable of sensing hydrogen at a concentration down to 40 ppm, i.e., one thousandth of the lower flammability limit of hydrogen in air. Different sensing behaviors are found for two sensor configurations, where Pd-Al nanorods provide larger spectral shift and Al-Pd ones exhibit shorter response time. In addition, the plasmonic hydrogen sensors here utilize exclusively CMOS-compatible materials, holding the potential for real-world, large-scale applications.

The mechanical vibration transfer path model of the axial piston pump was established for aiming at the aviation hydraulic vibration that it has been more intense with the development trend of high speed and high pressure. In this paper, firstly, based on the first-order trajectory sensitivity method to solve the time-domain sensitivity function curves, the system parameters that have influence on the vibration response of the pump were determined. Secondly, two sensitivity measure indexes were defined to quantitative analysis of the effect that various parameters on the rear shell vibration displacement. We hope that the work in this paper can have some benefit for controlling the aircraft hydraulic system machinery vibration coming from the pump, optimizing the structure of aviation hydraulic pump and promoting the development of domestic large aircraft, providing theoretical and technical basis.

We investigated the cardioprotective effect of renal ischemic postconditioning (RI-PostC) and its mechanisms in a rabbit model. Rabbits underwent 60 min of left anterior descending coronary artery occlusion (LADO) and 6 h of reperfusion. The ischemia-reperfusion (IR) group underwent LADO and reperfusion only. In the RI-PostC group, the left renal artery underwent 3 cycles of occlusion for 30 seconds and release for 30 seconds, before the coronary artery was reperfused. In the RI-PostC + GF109203X group, the rabbits received 0.05 mg/kg GF109203X (protein kinase C inhibitor) intravenously for 10 min followed by RI-PostC. Light microscopy and electron microscopy demonstrated that the RI-PostC group showed less pronounced changes, a smaller infarct region, and less apoptosis than the other two groups. Bcl-2 and Bax protein expression did not differ between the IR and RI-PostC + GF109203X groups. However, in the RI-PostC group, Bcl-2 protein expression was significantly higher and Bax protein expression was significantly lower than in the other two groups (P<0.05). Changes in heart rate and mean arterial pressure were also smaller in the RI-PostC group than in the other two groups. These results indicate that RI-PostC can ameliorate myocardial ischemia-reperfusion injury and increase the Bcl-2/Bax ratio through a mechanism involving protein kinase C.

Detailed energy consumption information of household appliance is meaningful for the demand side management (DSM) and home energy conservation. In this paper, a novel non-intrusive load monitoring (NILM) method is proposed for residential energy management systems(REMS). Unlike existing NILM techniques, this method works effectively with very few smart meter measurementparameters obtained at a low sampling rate. A neural network pattern recognition (NNPR) model is utilized in the NILM system for the first time. The proposed method can detect finite-state appliances by changing the number of output neurons. Experimental results indicate that the proposed method provides a very high identification accuracy. Moreover, this method can estimate each appliance detail energy consumption effectively, which is ideal for scheduling the household appliances and participation in the demand respond (DR).