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Low-rate distributed denial of service attacks, as known as LDDoS attacks, pose the notorious security risks in cloud computing network. They overload the cloud servers and degrade network service quality with the stealthy strategy. Furthermore, this kind of small ratio and pulse-like abnormal traffic leads to a serious data scale problem. As a result, the existing models for detecting minority and adversary LDDoS attacks are insufficient in both detection accuracy and time consumption. This paper proposes a novel multi-scale Convolutional Neural Networks (CNN) and bidirectional Long-short Term Memory (bi-LSTM) arbitration dense network model (called MSCBL-ADN) for learning and detecting LDDoS attack behaviors under the condition of limited dataset and time consumption. The MSCBL-ADN incorporates CNN for preliminary spatial feature extraction and embedding-based bi-LSTM for time relationship extraction. And then, it employs arbitration network to re-weigh feature importance for higher accuracy. At last, it uses 2-block dense connection network to perform final classification. The experimental results conducted on popular ISCX-2016-SlowDos dataset have demonstrated that the proposed MSCBL-ADN model has a significant improvement with high detection accuracy and superior time performance over the state-of-the-art models.
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Polyoxymethylene dimethyl ether (PODE) and methanol are important low-carbon substitutable fuels for reducing carbon emissions in internal combustion engines. In the research, the impacts of methanol ratio, injection timing, and intake temperature on HCHO generation and emission were investigated using both engine tests and numerical simulations. Results suggest that an increase in methanol ratio suppresses auto-ignition tendency of PODE, leading to the increase of ignition delay period, pressure peak, and heat release rate peak inside the cylinder. The decrease in in-cylinder combustion temperature contributes to an increase in HCHO emission due to partial oxidation of methanol in the cylinder and exhaust pipe. While the injection timing is gradually postponed from -10 °CA ATDC to 2 °CA ATDC, in-cylinder high-temperature area decreases, the quantity of unburned methanol increases, but part of HCHO is converted to HCO due to H radical influence, resulting in 72% increased HCHO emission. With the increment of intake temperature, the oxidation and decomposition of in-cylinder methanol accelerate, leading to an improvement in combustion stability, more uniform temperature distribution, and a decrease in unburned methanol, which results in lower HCHO emission. When the intake temperature is rose from 30 to 60 °C, HCHO emission decreases by 11.2%.
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Gasolina , Metanol , Éteres Metílicos , Emissões de Veículos , Formaldeído , CarbonoRESUMO
Genome editing mediated by CRISPR/Cas9 is an attractive weapon for cancer therapy. However, in vivo delivery of CRISPR/Cas9 components to achieve therapeutic efficiency is still challenging. Herein, a quaternary ammonium-functionalized poly(L-lysine) and a cholesterol-modified PEG (QNP) were self-assembled with a negatively charged CRISPR Cas9/sgRNA ribonucleoprotein (RNP) to form a ternary complex (QNP/RNP). Such a delivery system of QNP exhibited multiplex genome editing capabilities in vitro (e.g., the GFP gene and the PLK1 gene). In addition, QNP/RNPPLK1 containing PLK1 sgRNA led to 30.99% of genome editing efficiency in MCF-7 cells with negligible cytotoxicity of the carrier. QNP/RNPPLK1, which was capable of simultaneously inhibiting cell proliferation, mediating cell cycle arrest and downregulating expression of PLK1, held great in vitro therapeutic efficiency. Moreover, QNP/RNPPLK1 exhibited outstanding accumulation in tumors and high biocompatibility in vivo. In an MCF-7 xenograft animal model, QNP/RNPPLK1 showed excellent anti-tumor efficacy and achieved 17.75% indels ratio. This work showcases the successful delivery of CRISPR Cas9/sgRNA RNP with enhanced genome editing efficiency and provides a potential on-demand strategy for cancer therapy.
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Compostos de Amônio , Neoplasias , Animais , Humanos , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas , Edição de Genes , Ribonucleoproteínas/genética , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Photocatalysis has the advantages of practical, sustainable and environmental protection, so it plays a significant role in energy transformation and environmental utilization. CeO2 has attracted widespread attention for its unique 4 f electrons, rich defect structures, high oxygen storage capacity and great chemical stability. In this paper, we review the structure of CeO2 and the common methods for the preparation of CeO2-based composites in the first part. In particular, we highlight the co-precipitation method, template method, and sol-gel method methods. Then, in the second part, we introduce the application of CeO2-based composites in photocatalysis, including photocatalytic CO2 reduction, hydrogen production, degradation, selective organic reaction, and photocatalytic nitrogen fixation. In addition, we discuss several modification techniques to improve the photocatalytic performance of CeO2-based composites, such as elemental doping, defect engineering, constructing heterojunction and morphology regulation. Finally, the challenges faced by CeO2-based composites are analyzed and their development prospects are prospected. This review provides a systematic summary of the recent advance of CeO2-based composites in the field of photocatalysis, which can provide useful references for the rational design of efficient CeO2-based composite photocatalysts for sustainable development.
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Background: Concurrent programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors with sequential chemoradiotherapy (SCRT) have been reported in only a limited number of studies involving patients with unresectable stage III non-small-cell lung cancer (NSCLC). A retrospective study was conducted to systematically analyze the efficacy and safety of the emerging therapy among Chinese patients. Materials and methods: We included patients with unresectable, stage III NSCLC who received concurrent sintilimab with chemotherapy or chemotherapy alone for 3-6 cycles, followed by radical radiotherapy at the First Hospital of Jilin University from Dec 15, 2019, to Jul 15, 2022. The primary end point was the objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), 12-month and 18-month PFS rates, the duration of response (DoR), and safety. Results: The retrospective study involved 77 patients, of which 49 receiving concurrent sintilimab with SCRT were assigned to cohort A, and 28 receiving SCRT alone were assigned to cohort B. The ORR was significantly higher in cohort A (79.6%, 95% CI 65.7-89.8) than in cohort B (35.7%, 95% CI 18.6-55.9) (p<0.001). Median PFS was significantly longer in cohort A than in cohort B (NR [95% CI 21.4-NR] vs. 16.0 months [13.0-22.5]; HR 0.375, 95% CI 0.192-0.735; p=0.003). The PFS rates at 12 and 18 months were 84.8% (95% CI 75.0-95.9) and 71.3% (95% CI 58.7-86.7) in cohort A and 75.0% (95% CI 60.6-92.9) and 38.3% (95% CI 23.7-61.7) in cohort B, respectively. Grade 3 or 4 adverse events (AEs) were reported in 19 patients (38.8%) and seven patients (25.0%) in two cohorts, respectively. Grade 3 or 4 pneumonitis or immune-mediated pneumonitis, radiation pneumonitis, and pneumonia occurred in five (10.2%), four (8.2%), and two (4.1%) cohort A patients, and zero, two (7.1%), and two (7.1%) cohort B patients, respectively. Only cohort A reported AE leading to death in one (2.0%) patient (immune-mediated pneumonitis). Conclusion: Concurrent sintilimab with SCRT resulted in a significantly better ORR and longer PFS than SCRT alone, with manageable safety profiles in Chinese patients with unresectable stage III NSCLC.
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Boosted by mobile communication technologies, Human Activity Recognition (HAR) based on smartphones has attracted more and more attentions of researchers. One of the main challenges is the classification time and accuracy in processing long-time dependent sequence samples with noisy or missed data. In this paper, a 1-D Convolution Neural Network (CNN)-based bi-directional Long Short-Term Memory (LSTM) parallel model with attention mechanism (ConvBLSTM-PMwA) is proposed. The original features of sensors are segmented into sub-segments by well-designed equal time step sliding window, and fed into 1-D CNN-based bi-directional LSTM parallel layer to accelerate feature extraction with noisy and missed data. The weights of extracted features are redistributed by attention mechanism and integrated into complete features. At last, the final classification results are obtained with the full connection layer. The performance is evaluated on public UCI and WISDM HAR datasets. The results show that the ConvBLSTM-PMwA model performs better than the existing CNN and RNN models in both classification accuracy (96.71%) and computational time complexity (1.1 times faster at least), even if facing HAR data with noise.
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Atividades Humanas , Redes Neurais de Computação , Humanos , Memória de Longo Prazo , Reconhecimento Psicológico , SmartphoneRESUMO
This pilot study (NCT03958097; https://www.clinicaltrials.gov/ct2/show/NCT03958097) was aimed to evaluate the efficacy and safety of PD-1 antibody combined autologous NK cells in the treatment of patients with stage IIIB/IIIC or IV non-small-cell lung cancer (NSCLC) who failed the first-line platinum-based chemotherapy. All patients received both sintilimab 200mg and 3×109 NK cells every 3 weeks. 20 patients were enrolled, median follow up time was 22.6 months. The median PFS was 11.6 months, ORR was 45%. Median OS was 17.7 months, 6-month OS rate and 12-month OS rate was 95.0% and 80.0%. Unexpected adverse events were not observed. 2 patients reported grade 3 adverse events (hypertriglyceridemia, neutropenia and increased creatine kinase). The autologous NK cells did not add extra adverse events to the ICI treatment. Autologous NK plus sintilimab showed promising antitumor activity and an acceptable safety profile in advanced driven-mutation negative NSCLC who failed on the first line treatment.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Células Matadoras Naturais/patologia , Neoplasias Pulmonares/tratamento farmacológico , Projetos Piloto , Platina/uso terapêuticoRESUMO
Primary peripheral nerve sheath tumors (PNSTs) of the thyroid gland are rare, with fewer than 30 cases reported in the medical literature to date. Primary PNSTs of the thyroid gland are classiï¬ed into malignant and benign PNSTs. The benign PNSTs may be further subclassified into neuroï¬bromas and Schwannomas. This is the case report of a 51-year-old male patient presenting with multiple primary PNSTs involving the left lobe of the thyroid gland. The patient underwent total excision of the thyroid gland and the pathological results indicated a Schwannoma with Antoni type A and B cells. The literature was reviewed briefly and, to the best of our knowledge, this is the first case report of multiple primary PNSTs of the thyroid gland.
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It has been shown that overexpression of signal transducer and activator of transcription 3 (Stat3) contribute to the progression and metastasis of various solid tumors and that silencing Stat3 inhibits tumor growth in several types of cancer. Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), a Stat3-inhibitory protein, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis by targeting the transcription factor Stat3 for inhibition. However, little is known about Stat3 and GRIM-19 roles in the tumor growth of thyroid carcinoma cells. In the present study, we developed a dual expression plasmid that co-expressed Stat3-specific siRNA and GRIM-19 (pSi-Stat3-GRIM-19) and transfected it into SW579 cells (thyroid carcinoma cell line) to evaluate its effects on cell proliferation, cell apoptosis, cell migration and cell invasion in vitro and tumor growth in vivo. Simultaneous expression of pSi-Stat3-GRIM-19 in SW579 cancer cells was found to significantly suppress the proliferation, migration and invasion in vitro and tumor growth in vivo, when compared to the controls either Stat3-specific siRNA or GRIM-19 alone. In conclusion, our data demonstrated that a combined strategy of co-expressed Stat3-specific siRNA and GRIM19 synergistically and more effectively suppressed thyroid tumor growth, and have therapeutic potential for the treatment of thyroid cancer.