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Non-radiative recombination losses limit the property of perovskite solar cells (PSCs). Here, a synergistic strategy of SnSe2QDs doping into SnO2 and chlorhexidine acetate (CA) coating on the surface of perovskite is proposed. The introduction of 2D SnSe2QDs reduces the oxygen vacancy defects and increases the carrier mobility of SnO2. The optimized SnO2 as a buried interface obviously improves the crystallization quality of perovskite. The CA containing abundant active sites of âNH2/âNHâ, âCâN, CO, âCl groups passivate the defects on the surface and grain boundary of perovskite. The alkyl chain of CA also improves the hydrophobicity of perovskite. Moreover, the synergism of SnSe2QDs and CA releases the residual stress and regulates the energy level arrangement at the top and bottom interface of perovskite. Benefiting from these advantages, the bulk and interface non-radiative recombination loss is greatly suppressed and thereby increases the carrier transport and extraction in devices. As a result, the best power conversion efficiency (PCE) of 23.41% for rigid PSCs and the best PCE of 21.84% for flexible PSCs are reached. The rigid PSC maintains 89% of initial efficiency after storing nitrogen for 3100 h. The flexible PSCs retain 87% of the initial PCE after 5000 bending cycles at a bending radius of 5 mm.
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BACKGROUND: Because of to the removal of subclassification of papillary renal cell carcinoma (pRCC), the survival prognostification of localized pRCC after surgical treatment became inadequate. Sarcopenia was widely evaluated and proved to be a predictive factor for prognosis in RCC patients. Therefore, we comprehensively investigated the survival prediction of the body composition parameters for localized pRCC. METHODS: Patients pathologically diagnosed with pRCC between February 2012 and February 2022 in our center were enrolled. The body composition parameters, including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and perirenal adipose tissue (PRAT), were measured by the images of preoperative computed tomography (CT). The primary outcome was set as progression-free survival (PFS), and the cutoff values of body composition parameters were calculated by using the Youden from receiver operating characteristic curve (ROC) curves. Univariate and multivariate Cox proportional regression analyses were performed to explore independent risk factors for survival prediction. Then, significant factors were used to construct a prognostic nomogram. The performance of the nomogram was evaluated by Harrell's C-index, calibration curves and time-dependent ROC curves. RESULTS: A total of 105 patients were enrolled for analysis. With a median follow-up time of 30.48 months, 25 (23.81%) patients experienced cancer progression. The percentage of sarcopenia was 74.29%. Univariate Cox analysis identified that gender, PRAT, SAT, skeletal muscle (SM), sarcopenia, surgical technique, and tumor diameter were associated with progression. Further multivariate analysis showed that sarcopenia (hazard ratio [HR] 0.15, 95% confidence interval [CI] 0.03-0.66), SAT (HR 6.36, 95% CI 2.39-16.93), PRAT (HR 4.66, 95% CI 1.77-12.27), tumor diameter (HR 0.35, 95% CI 0.14-0.86), and surgical technique (HR 2.85, 95% CI 1.06-7.64) were independent risk factors for cancer progression. Then, a prognostic nomogram based on independent risk factors was constructed and the C-index for progression prediction was 0.831 (95% CI 0.761-0.901), representing a reasonable discrimination, the calibration curves, and the time-dependent ROC curves verified the good performance of the nomogram. CONCLUSIONS: A prognostic nomogram, including sarcopenia, SAT, PRAT, tumor diameter, and surgical technique, was constructed to calculate the probability of progression for localized pRCC patients and needs further external validation for clinical use in the future.
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Carcinoma de Células Renais , Neoplasias Renais , Nomogramas , Sarcopenia , Humanos , Sarcopenia/patologia , Sarcopenia/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/mortalidade , Pessoa de Meia-Idade , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Taxa de Sobrevida , Seguimentos , Prognóstico , Idoso , Curva ROC , Intervalo Livre de Progressão , Composição Corporal , AdultoRESUMO
The power conversion efficiency (PCE) and stability of perovskite solar cells (PSCs) are significantly reduced by defect-induced charge non-radiative recombination. Also, unexpected residual strain in perovskite films leads to an unfavorable impact on the stability and efficiency of PSCs, notably flexible PSCs (f-PSCs). Considering these problems, a thorough and effective strategy is proposed by incorporating phytic acid (PA) into SnO2 as an electron transport layer (ETL). With the addition of PA, the Sn inherent dangling bonds are passivated effectively and thus enhance the conductivity and electron mobility of SnO2 ETL. Meanwhile, the crystallization quality of perovskite is increased largely. Therefore, the interface/bulk defects are reduced. Besides, the residual strain of perovskite film is significantly reduced and the energy level alignment at the SnO2 /perovskite interface becomes more matched. As a result, the champion f-PSC obtains a PCE of 21.08% and rigid PSC obtains a PCE of 21.82%, obviously surpassing the PCE of 18.82% and 19.66% of the corresponding control devices. Notably, the optimized f-PSCs exhibit outstanding mechanical durability, after 5000 cycles of bending with a 5 mm bending radius, the SnO2 -PA-based device preserves 80% of the initial PCE, while the SnO2 -based device only remains 49% of the initial value.
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Due to their tunable wavelength, high color purity, bright emission and low-cost fabrication process, perovskite nanocrystals (PeNCs) have attracted broad interest and exhibited great prospects in application areas such as solar cells, light-emitting diodes, photodetectors, and lasers. Although the fabrication of PeNCs and related optoelectronic devices has witnessed rapid development over the past several years, the poor stability of PeNCs in an external environment still remains a major drawback which severely limits the further improvement and commercialization of PeNC-based devices. Therefore, various techniques and strategies have been developed to enhance the stability of PeNCs. Among them, the encapsulation strategy has been demonstrated to be an effective way to improve the stability of PeNCs. In this review, the origin of the instability of PeNCs is first analyzed to identify the importance of encapsulation, followed by a summary and discussions on recent advances in the encapsulation of PeNCs. The potential applications of encapsulated PeNCs in various optoelectronic devices are also presented to manifest the necessity of encapsulation. Finally, the further development and outlook on encapsulation of PeNCs are analyzed in order to suggest future improvements and commercialization of PeNCs and related optoelectronic devices.
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Saccharina japonica is an ecologically and economically important kelp in cold-temperate regions. When it is cultivated on a large scale in the temperate and even subtropical zones, heat stress is a frequent abiotic stress. This study is the first attempt to reveal the regulatory mechanism of the response to heat stress from the perspective of DNA methylation in S. japonica. We firstly obtained the characteristics of variation in the methylome under heat stress, and observed that heat stress caused a slight increase in the overall methylation level and methylation rate, especially in the non-coding regions of the genome. Secondly, we noted that methylation was probably one of factors affecting the expression of genes, and that methylation within the gene body was positively correlated with the gene expression (rho = 0.0784). Moreover, it was found that among the differentially expressed genes regulated by methylation, many genes were related to heat stress response, such as HSP gene family, genes of antioxidant enzymes, genes related to proteasome-ubiquitination pathway, and plant cell signaling pathways. This study demonstrated that DNA methylation is involved in regulating the response to heat stress, laying a foundation for studying the acclimation and adaptation of S. japonica to heat stress from an epigenetic perspective.
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Metilação de DNA , Laminaria , Epigênese Genética , Resposta ao Choque Térmico/genética , Aclimatação/genéticaRESUMO
BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.
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Antibacterianos/uso terapêutico , Criptosporidiose/tratamento farmacológico , Cryptosporidium/patogenicidade , Diarreia/tratamento farmacológico , Escherichia coli/patogenicidade , Transtornos do Crescimento/etiologia , Shigella/patogenicidade , Estudos de Casos e Controles , Criança , Cryptosporidium/isolamento & purificação , Diarreia/epidemiologia , Diarreia/microbiologia , Escherichia coli/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Shigella/isolamento & purificaçãoRESUMO
BACKGROUND: CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post hoc analysis assessed hospitalized and severe virologically confirmed dengue (VCD) over the complete 6-year follow-up of 3 CYD-TDV efficacy studies (CYD14, CYD15, and CYD23/CYD57). METHODS: The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. Antibody persistence was assessed up to 5 years after the last injection. RESULTS: In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over 6 years compared to placebo (HR [95% confidence interval] multiple imputation from month 0 method, .19 [.12-.30] and .15 [.06-.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6-8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups. CONCLUSIONS: CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire 6-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year-olds. Clinical Trials Registration: NCT00842530, NCT01983553, NCT01373281, NCT01374516.
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Vacinas contra Dengue , Vírus da Dengue , Dengue , Dengue Grave , Anticorpos Antivirais , Ásia/epidemiologia , Criança , Dengue/epidemiologia , Dengue/prevenção & controle , Seguimentos , Humanos , América Latina/epidemiologia , Vacinas Atenuadas , Vacinas CombinadasRESUMO
BACKGROUND: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of nontyphoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. METHODS: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole-genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk-diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing, and whole-genome sequencing was performed to assess the phylogeny of ST313. RESULTS: Of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java, and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar among both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone, but African isolates were susceptible to these antibiotics. CONCLUSIONS: Our data confirm that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multidrug-resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa.
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Infecções por Salmonella , Antibacterianos/farmacologia , Criança , Pré-Escolar , Humanos , Quênia/epidemiologia , Tipagem de Sequências Multilocus , Filogenia , Infecções por Salmonella/epidemiologia , Salmonella typhimurium/genéticaRESUMO
BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (nâ =â 745), culture-negative/qPCR-attributable Shigella cases (nâ =â 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Ageâ <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity.
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Disenteria Bacilar , Shigella , Vacinas , Estudos de Casos e Controles , Criança , Diarreia/epidemiologia , Disenteria Bacilar/diagnóstico , Disenteria Bacilar/epidemiologia , Humanos , Lactente , Reação em Cadeia da Polimerase , Shigella/genéticaRESUMO
In recent years, although the power conversion efficiency (PCE) of thermally stable all-inorganic CsPbI3 perovskite solar cells (PSCs) had shown a great progress, the most reported CsPbI3 PSCs suffered from the large open-circuit voltage (Voc) loss, which is related to severe nonradiative recombination and a mismatch in energy level at the transport layer/perovskite interface. In this work, europium acetate (EuAc3) as a multifunction interface material is chosen to modify the TiO2/perovskite interface, the crystal quality of CsPbI3 perovskite films is improved, and both bulk and interfacial defects are reduced effectively. Meanwhile, the energy levels arrangement between TiO2 and CsPbI3 perovskites is also optimized, corresponding the raised built-in electric field afford a strength force to accelerate the transport and extraction of charge carriers from CsPbI3 perovskites to TiO2. As a result, the performance of CsPbI3 PSCs is largely enhanced with the PCE of 16.76%. When an Ag electrode was replaced by Au, the PCE further improves to 17.92%, which is the highest for CsPbI3 PSCs with P3HT as the HTL ever reported. Besides, the CsPbI3 PSC with the EuAc3 modification layer maintains 84% of the initial PCE under continuous UV irradiation for 250 h in a nitrogen filled glovebox, being obviously higher than the control devices with only 40% of the initial PCE after UV irradiation for 100 h in the same environment.
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This paper explored a pragmatic approach to research the real-time performance of a multiway concurrent multiobject tracking (MOT) system. At present, most research has focused on the tracking of single-image sequences, but in practical applications, multiway video streams need to be processed in parallel by MOT systems. There have been few studies on the real-time performance of multiway concurrent MOT systems. In this paper, we proposed a new MOT framework to solve multiway concurrency scenario based on a tracking-by-detection (TBD) model. The new framework mainly focuses on concurrency and real-time based on limited computing and storage resources, while considering the algorithm performance. For the former, three aspects were studied: (1) Expanded width and depth of tracking-by-detection model. In terms of width, the MOT system can support the process of multiway video sequence at the same time; in terms of depth, image collectors and bounding box collectors were introduced to support batch processing. (2) Considering the real-time performance and multiway concurrency ability, we proposed one kind of real-time MOT algorithm based on directly driven detection. (3) Optimization of system level-we also utilized the inference optimization features of NVIDIA TensorRT to accelerate the deep neural network (DNN) in the tracking algorithm. To trade off the performance of the algorithm, a negative sample (false detection sample) filter was designed to ensure tracking accuracy. Meanwhile, the factors that affect the system real-time performance and concurrency were studied. The experiment results showed that our method has a good performance in processing multiple concurrent real-time video streams.
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OBJECTIVES: To comprehensively assess the diagnostic performance of Vesical Imaging-Reporting and Data System (VI-RADS) score for detecting the muscle invasion of bladder cancer. METHODS: PubMed, Web of Science, and Embase were searched up to November 20, 2019. QUADAS-2 tool assessed the quality of included studies. The diagnostic estimates including sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and the area under the curve (AUC) of hierarchical summary receiver operating characteristic (HSROC) were calculated. Further subgroup analysis, meta-regression and sensitivity analysis were conducted. RESULTS: Six studies with 1064 patients were finally included. The pooled sensitivity, specificity, and AUC value were 0.90 (95% CI 0.86-0.94), 0.86 (95% CI 0.71-0.94), and 0.93 (95% CI 0.91-0.95) for VI-RADS 3 as the cutoff value. The corresponding estimates were 0.77 (95% CI 0.65-0.86), 0.97 (95% CI 0.88-0.99), and 0.92 (95% CI 0.89-0.94) for VI-RADS 4 as the cutoff value. Meta-regression analysis revealed that study design (p value 0.01) and surgical pattern of reference standard (p value 0.02) were source of the heterogeneity of pooled sensitivity. No publication bias was observed. CONCLUSIONS: The VI-RADS score can provide a good predictive ability for detecting the muscle invasiveness of primary bladder cancer with VI-RADS 3 or VI-RADS 4 as the cutoff value. KEY POINTS: ⢠VI-RADS score has high sensitivity and specificity for predicting muscle invasion. ⢠The diagnostic efficiencies of VI-RADS 3 and VI-RADS 4 as the cutoff value are similar. ⢠VI-RADS score could be used for detecting muscle invasion of bladder cancer in clinical practice.
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Músculo Esquelético/patologia , Radiografia/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Humanos , Invasividade Neoplásica , Curva ROC , Projetos de PesquisaRESUMO
In this study, we analyzed the effects of sludge aging pre-treatment on the stabilization mechanisms of heavy metals during sludge pyrolysis. First, the form of copper (Cu) and chromium (Cr) was conducted using the sequential extraction procedure proposed by the European Community Bureau of Reference (BCR). The stabilization mechanisms for the sludge pyrolysis of Cu and Cr were then analyzed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Results indicate the following: 1) with aging pre-treatment, the improvement in adsorption performance and the formation of newly crystallized materials, like polyhydroxy copper phosphate and chromium phosphate minerals, occur concurrently with the stabilization of heavy metals during pyrolysis; 2) after four weeks of aging, active functional groups like amino and carboxyl groups were significantly sharpened, and caused sustained complexation of the heavy metals. Results suggested that the aging pre-treatment aided the stabilization of heavy metals during sludge pyrolysis. Notably, the aging effect can decrease the potential ecological risk of heavy metals.
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Metais Pesados/química , Pirólise , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Adsorção , Cromo/química , Cobre/química , CristalizaçãoRESUMO
To increase the degree of immobilization of heavy metals subjected to sludge pyrolysis, we investigated the effects of pretreating sludge with Ochrobactrum supplementation on the immobilization of chromium (Cr) and copper (Cu) during sludge pyrolysis. The sequential extraction procedure was used to test the metallic forms of Cr and Cu. The immobilization of Cr and Cu was characterized with X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, etc. Results show that: 1) the addition of Ochrobactrum (1-8%) can accelerate the mineralization process in blank sludge and can accelerate the conversion of the oxidizable forms of Cr and Cu into the residual forms subjected to pyrolysis; 2) pretreatment with Ochrobactrum supplementation can inhibit the volatilization of Cr and Cu during sludge pyrolysis, particularly in the case of a high concentration of Cu. Notably, the pretreatment with Ochrobactrum can reduce 20.38-85.09% of the potential ecological risk of Cr and Cu. The pretreatment with Ochrobactrum contributes to the immobilization of Cr and Cu subjected to sludge pyrolysis and thus can prevent pollution of the environment. The results of this study can be used for harmless disposal of municipal sludge.
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Cromo/análise , Cobre/análise , Ochrobactrum/química , Pirólise , Esgotos , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Adsorção , China , Microscopia Eletrônica de Varredura , Ochrobactrum/metabolismo , Oxirredução , Esgotos/química , Esgotos/microbiologiaRESUMO
The embedded visual tracking system has higher requirements for real-time performance and system resources, and this is a challenge for visual tracking systems with available hardware resources. The major focus of this study is evaluating the results of hardware optimization methods. These optimization techniques provide efficient utilization based on limited hardware resources. This paper also uses a pragmatic approach to investigate the real-time performance effect by implementing and optimizing a kernel correlation filter (KCF) tracking algorithm based on a vision digital signal processor (vision DSP). We examine and analyze the impact factors of the tracking system, which include DP (data parallelism), IP (instruction parallelism), and the characteristics of parallel processing of the DSP core and iDMA (integrated direct memory access). Moreover, we utilize a time-sharing strategy to increase the system runtime speed. These research results are also applicable to other machine vision algorithms. In addition, we introduced a scale filter to overcome the disadvantages of KCF for scale transformation. The experimental results demonstrate that the use of system resources and real-time tracking speed also satisfies the expected requirements, and the tracking algorithm with a scale filter can realize almost the same accuracy as the DSST (discriminative scale space tracking) algorithm under a vision DSP environment.
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Owing to the constraints of time and space complexity, network intrusion detection systems (NIDSs) based on support vector machines (SVMs) face the "curse of dimensionality" in a large-scale, high-dimensional feature space. This study proposes a joint training model that combines a stacked autoencoder (SAE) with an SVM and the kernel approximation technique. The training model uses the SAE to perform feature dimension reduction, uses random Fourier features to perform kernel approximation, and then random Fourier mapping is explicitly applied to the sub-sample to generate the random feature space, making it possible to apply a linear SVM to uniformly approximate to the Gaussian kernel SVM. Finally, the SAE performs joint training with the efficient linear SVM. We studied the effects of an SAE structure and a random Fourier feature on classification performance, and compared that performance with that of other training models, including some without kernel approximation. At the same time, we compare the accuracy of the proposed model with that of other models, which include basic machine learning models and the state-of-the-art models in other literatures. The experimental results demonstrate that the proposed model outperforms the previously proposed methods in terms of classification performance and also reduces the training time. Our model is feasible and works efficiently on large-scale datasets.
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BACKGROUND Glioblastoma, the most common and malignant glial tumor, often has poor prognosis. Tivantinib has shown its potential in treating c-Met-high carcinoma. No studies have explored whether tivantinib inhibits the development of glioblastoma. MATERIAL AND METHODS The correlation between c-Met expression and clinicopathological characteristics of glioblastoma was investigated. U251 and T98MG glioblastoma cells treated with tivantinib, PI3K inhibitor (LY294002), PI3K activator (740 Y-P), and/or mammalian target of rapamycin (mTOR) inhibitor were subjected to MTT assay or colony formation assay to evaluate cell proliferation. The expression of mTOR signaling and caspase-3 in tivantinib-treated glioblastoma cells was differentially measured by western blotting. RESULTS In a group of Chinese patients, expression of c-Met was elevated with the size of glioblastoma, but not with the other clinicopathological characteristics, including gender, age, grade, IDH status, 1p/19q status, and Ki67 status. High dose of tivantinib (1 µmol/L) obviously repressed the proliferation and colony formation of U251 and T98MG glioblastoma cells, but low dose (0.1 µmol/L) of tivantinib failed to retard cell proliferation. Tivantinib blocked PI3K/Akt/mTOR signaling but did not change the expression of cleaved caspase-3. PI3K activator 740 Y-P (20 µmol/L) significantly rescued tivantinib-induced decrease of cell proliferation. Tivantinib (1 µmol/L) in combination with PI3K inhibitor LY294002 (0.5 µmol/L) and mTOR inhibitor rapamycin (0.1 nmol/L) largely inhibited the proliferation of glioblastoma cells. CONCLUSIONS c-MET inhibitor tivantinib blocks PIKE/Akt/mTOR signaling and hampers the proliferation of glioblastoma cells, which endows the drug a therapeutic effect.
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Glioblastoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/metabolismo , Pirrolidinonas/farmacologia , Quinolinas/farmacologia , Adulto , Idoso , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , China , Cromonas/farmacologia , Feminino , Expressão Gênica , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/fisiologia , Pirrolidinonas/metabolismo , Quinolinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
Photothermal therapy at the NIR-II biowindow (1000-1350â nm) is drawing increasing interest because of its large penetration depth and maximum permissible exposure. Now, the supramolecular radical dimer, fabricated by N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole radical cation (MPT.+ ) and cucurbit[8]uril (CB[8]), achieves strong absorption at NIR-II biowindow. The supramolecular radical dimer (2MPT.+ -CB[8]) showed highly efficient photothermal conversion and improved stability, thus contributing to the strong inhibition on HegG2 cancer cell under 1064â nm irradiation even penetrating through chicken breast tissue. This work provides a novel approach to construct NIR-II chromophore by tailor-made assembly of organic radicals. It is anticipated that this study provides a new strategy to achieve NIR-II photothermal therapy and holds promises in luminescence materials, optoelectronic materials, and also biosensing.
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Hidrocarbonetos Aromáticos com Pontes/química , Radicais Livres/química , Imidazóis/química , Raios Infravermelhos , Substâncias Macromoleculares/química , Tiazóis/química , Adsorção , Cátions/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cristalografia por Raios X , Dimerização , Células Hep G2 , Humanos , Hipertermia Induzida/métodos , Substâncias Macromoleculares/farmacologia , Microscopia Confocal , Conformação Molecular , Teoria QuânticaRESUMO
BACKGROUND: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). METHODS: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. FINDINGS: We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1·5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89·3% (95% CI 83·2-96·0) at the population level, compared with 51·5% (48·0-55·0) in the original GEMS analysis. The top six pathogens accounted for 77·8% (74·6-80·9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42·5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38·9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. INTERPRETATION: A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. FUNDING: Bill & Melinda Gates Foundation.
Assuntos
Efeitos Psicossociais da Doença , Diarreia/microbiologia , Diarreia/virologia , Adenoviridae/isolamento & purificação , Adenoviridae/patogenicidade , África/epidemiologia , Ásia/epidemiologia , Bactérias/isolamento & purificação , Bactérias/patogenicidade , Infecções Bacterianas/diagnóstico , Campylobacter/isolamento & purificação , Campylobacter/patogenicidade , Estudos de Casos e Controles , Pré-Escolar , Coinfecção , Cryptosporidium/isolamento & purificação , Cryptosporidium/patogenicidade , Diarreia/epidemiologia , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Feminino , Humanos , Incidência , Lactente , Masculino , Rotavirus/isolamento & purificação , Rotavirus/patogenicidade , Shigella/isolamento & purificação , Shigella/patogenicidade , Viroses/diagnóstico , Vírus/isolamento & purificação , Vírus/patogenicidadeRESUMO
A novel deep-blue emitter PhImPOTD based on phenathroimidazole was synthesized, which is incorporated by an electron-donating dibenzothiophene unit and electron-withdrawing phenanthroimidazole and diphenylphosphine oxide moieties. Furthermore, the weak π-π stacking and intermolecular aggregation render the photoluminescence quantum yield is as high as 0.34 in the solid state. Non-doped organic light emitting diodes (OLEDs) based on PhImPOTD emitter exhibits a low turn-on voltage of 3.6 V, a favorable efficiency of 1.13 cd A-1 and a deep blue emission with Commission Internationale de l'Eclairage (CIE) coordinates of (0.15, 0.08). The CIE is very close to the NTSC (National Television Standards Committe) blue standard (CIE: 0.14, 0.08). PhImPOTD is also utilized as blue emitter and the host for a yellow emitter (PO-01) to fabricate white organic light-emitting diodes (WOLEDs). This gives a forward-viewing maximum CE of 4.83 cd A-1 and CIE coordinates of (0.32, 0.32) at the luminance of 1000 cd m-2. Moreover, the single-carrier devices unambiguously demonstrate that typical bipolar-dominant characteristics of PhImPOTD. This work demonstrates not only that the phenanthroimidazole unit is an excellent building block to construct deep blue emission materials, but also the introduction of a diphenylphosphine oxide deprotonation substituent is an efficient tactic for harvesting deep-blue emitting devices.