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Elastic responses of underground circular arches considering dynamic soil-structure interaction:A theoretical analysis 被引量:10
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作者 Hai-Long Chen Feng-Nian Jin Hua-Lin Fan 《Acta Mechanica Sinica》 SCIE EI CAS CSCD 2013年第1期110-122,共13页
Due to the wide applications of arches in underground protective structures, dynamic analysis of circular arches including soil-structure interactions is important. In this paper, an exact solution of the forced vibra... Due to the wide applications of arches in underground protective structures, dynamic analysis of circular arches including soil-structure interactions is important. In this paper, an exact solution of the forced vibration of circular arches subjected to subsurface denotation forces is obtained. The dynamic soil-structure interaction is considered with the introduction of an interfacial damping between the structure element and the surrounding soil into the equa- tion of motion. By neglecting the influences of shear, rotary inertia and tangential forces and assuming the arch incompressible, the equations of motion of the buried arches were set up. Analytical solutions of the dynamic responses of the protective arches were deduced by means of modal super- position. Arches with different opening angles, acoustic impedances and rise-span ratios were analyzed to discuss their influences on an arch. The theoretical analysis suggests blast loads for elastic designs and predicts the potential failure modes for buried protective arches. 展开更多
关键词 Underground protective arches - Dynamic soilstructure interaction Dynamic responses Analytical solution
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Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C 被引量:2
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作者 Javier García-Samaniego Miriam Romero +6 位作者 Rafael Granados Remedios Alemán Miguel Jorge Juan Dolores Suárez Ramón Pérez Gregorio Castellano Carlos González-Portela 《World Journal of Gastroenterology》 SCIE CAS 2013年第12期1943-1952,共10页
AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter,... AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR. 展开更多
关键词 ANTIVIRAL therapy BASELINE FACTORS Early virological response PEGINTERFERON Α-2A RIBAVIRIN
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Long noncoding RNA negative regulator of antiviral response contributes to pancreatic ductal adenocarcinoma progression via targeting miR-299-3p 被引量:3
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作者 Hai-Quan Wang Chun-Hua Qian +2 位作者 Zeng-Ya Guo Pei-Ming Li Zheng-Jun Qiu 《World Journal of Gastroenterology》 SCIE CAS 2022年第35期5141-5153,共13页
BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance... BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC. 展开更多
关键词 Long noncoding RNA Negative regulator of antiviral response miR-299-3p Proliferation Migration INVASION Pancreatic cancer
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Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response 被引量:1
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作者 Catherine M Greene Noel G McElvaney 《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2010年第5期94-101,共8页
The serine proteinase inhibitor α-1 antitrypsin(AAT) is produced principally by the liver at the rate of 2 g/d.It is secreted into the circulation and provides an antiprotease protective screen throughout the body bu... The serine proteinase inhibitor α-1 antitrypsin(AAT) is produced principally by the liver at the rate of 2 g/d.It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung,where it can neutralise the activity of the serine protease neutrophil elastase.Mutations leading to def iciency in AAT are associated with liver and lung disease.The most notable is the Z AAT mutation,which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine.More than 95% of all individuals with AAT def iciency carry at least one Z allele.ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum(ER) of hepatocytes and other AAT-producing cells.This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT.However,the misfolded protein acquires a toxic gain of function that impacts on the ER.A major function of the ER is to ensure correct protein folding.ZAAT interferes with this function and promotes ER stress responses and inflammation.Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed. 展开更多
关键词 α-1 ANTITRYPSIN Unfolded protein response Endoplasmic reticulum stress APOPTOSIS AUTOPHAGY NFΚB
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Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma
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作者 Dong-Qin Xia Yong Zhou +6 位作者 Shuang Yang Fang-Fei Li Li-Ya Tian Yan-Hua Li Hai-Yan Xu Cai-Zhi Xiao Wei Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第3期798-809,共12页
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19... BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection. 展开更多
关键词 Pancreatic ductal adenocarcinoma Carbohydrate antigen 19-9 Tumor size Pathologic response Biomarkers
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Response Surface Methodology as an Approach for Optimization of the Synthesis of 1-(2-Aminoethyl)-2-imidazolidone
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作者 Yaoyi He Jianguo Cai Yu Zhang 《Journal of Materials Science and Chemical Engineering》 2017年第1期155-167,共13页
Ruthenium loaded on activated carbon pre-treated by HNO3 was used to catalyze the reaction of 1-(2-Aminoethyl)-2-imidazolidone (AEI) synthesized from ethylenediamine, ethanolamine and CO2. Response surface methodology... Ruthenium loaded on activated carbon pre-treated by HNO3 was used to catalyze the reaction of 1-(2-Aminoethyl)-2-imidazolidone (AEI) synthesized from ethylenediamine, ethanolamine and CO2. Response surface methodology (RSM) based on Box-Behnken design (BBD) was employed to optimize the synthesis of AEI. The statistical analysis results showed that the yield of AEI was significantly affected by the CO2 pressure, reaction temperature and reaction time. According to the results of variance analysis, the value of the determination coefficient of 0.9854 was in reasonable agreement with the “Adj R-Squared” of 0.9666, which means this model can predict the yield of AEI well and can be used to optimize reaction conditions for higher AEI yield. The optimal values of AEI yield predicted by RSM was 84.9% under temperature 206.51?C, CO2 pressure 9.35 Mpa, reaction time 10.11 h, and the verification experiment yield of AEI was 83.1%. 展开更多
关键词 1-(2-Aminoethyl)-2-imidazolidone SYNTHESIS Ru/AC response SURFACE DESIGN
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Extreme value of wind-excited response considering influence of bandwidth
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作者 Guoqing Huang Xinzhong Chen +1 位作者 Mingshui Li Liuliu Peng 《Journal of Modern Transportation》 2013年第2期125-134,共10页
This paper addresses the peak factors of wind- excited responses including alongwind, acrosswind tall building responses and vortex-induced vibration considering the bandwidth parameter. The influence of bandwidth par... This paper addresses the peak factors of wind- excited responses including alongwind, acrosswind tall building responses and vortex-induced vibration considering the bandwidth parameter. The influence of bandwidth parameter on the peak factor is investigated using advanced upcrossing theory taking the bandwidth influence into account. Results show that Davenport's formula without consideration of bandwidth parameter servers well in general. However, the advanced upcrossing theory leads to a better prediction of the peak factor of wind-induced response of very lightly damped buildings. 展开更多
关键词 Peak factors Wind-excited responses Upcrossing theory - Bandwidth
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基于“情景-任务-能力”的长三角传染病区域协同处置能力提升
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作者 陈蓉 张放 +2 位作者 管至为 何懿 黄晓燕 《中国卫生资源》 CSCD 北大核心 2023年第6期674-677,共4页
提升传染病区域协同处置能力是深化长三角卫生健康协同发展的重要抓手。卫生应急演练是检验卫生应急体系建设的重要手段。本研究将“情景-任务-能力”的方法引入长三角传染病区域协同处置领域,以构建杭州亚运会测试赛期间发现登革热等... 提升传染病区域协同处置能力是深化长三角卫生健康协同发展的重要抓手。卫生应急演练是检验卫生应急体系建设的重要手段。本研究将“情景-任务-能力”的方法引入长三角传染病区域协同处置领域,以构建杭州亚运会测试赛期间发现登革热等输入传染病病例后区域协查和联动处置情景为例,分析应急处置5个阶段的任务、主要责任单位及任务要点,并以“区域联合风险评估和风险管理”为例,从预案方案、组织领导、人员、设备与系统、物资、培训、演练等7个方面着手,详细分析能力评估的内容。同时,采用“任务分类”的思想,针对属于第二类任务的区域联动涉及的协查、评估和培训等任务,以“区域联合风险评估和风险管理”任务为例,提出制定区域联合风险评估和风险管理协议或方案,成立区域卫生应急专家智库,加强区域公共卫生风险评估交流和统一培训等措施建议。 展开更多
关键词 情景-任务-能力scene-task-ability 应急演练emergency response drill 长三角Yangtze River Delta 区域协同regional collaboration
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Effects ofβ-1,3-glucan and ascorbic acid on the nutritional-immune response and antioxidant signaling pathways of live tiger grouper during simulated transport 被引量:1
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作者 Bo Wu Zhenkun Xu +3 位作者 Jie Cao Qi Wang Jun Mei Jing Xie 《Aquaculture and Fisheries》 CSCD 2024年第2期265-272,共8页
Transport in water is the most common method for transporting live fish in China,however,transport is a strong stressor.Transport stress could lead to a reduced immune and antioxidant system function of tiger grouper,... Transport in water is the most common method for transporting live fish in China,however,transport is a strong stressor.Transport stress could lead to a reduced immune and antioxidant system function of tiger grouper,resulting in sickness and death.Besides,tiger grouper were continuously stressed during transport,which resulted in quality deterioration.It is necessary that find a way to relieve the stress of transportation of tiger grouper.Ascorbic acid is not only a good anti-stress agent,but it is also an effective immunostimulant.β-1,3-glucan is a feed additive that can enhance the immune response of fish.Therefore,this study evaluated the effects ofβ-1,3-glucan and ascorbic acid on the nutritional-immune response and antioxidant signaling pathways of live tiger grouper during simulated transport.Results indicated that addingβ-1,3-glucan and ascorbic acid in transport-water muted the increase of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activity.In addition,β-1,3-glucan and ascorbic acid activated Nrf2 and mediated TOR expression and then up-regulate related mRNA expression of antioxidant and immune enzymes.We concluded that the application ofβ-1,3-glucan and ascorbic acid inhibit the increase of metabolism enzymes and inflammatory factors and activate immune and antioxidant signaling pathways to relieve oxidant stress,immune response,and apoptosis.Reducing the loss of amino acids provided nutrients to relieve oxidative stress and immune response,which demonstrated immune-nutritional response in live tiger grouper during simulated transport.These results may provide a new solution for alleviating the decline of immune and antioxidant function of tiger grouper caused by transportation stress. 展开更多
关键词 Tiger grouper β-1 3-Glucan Ascorbic acid Immune response Antioxidant signaling pathway
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The most important questions in cancer research and clinical oncology Question 2-5.Obesity-related cancers:more questions than answers 被引量:10
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作者 Ajit Venniyoor 《Chinese Journal of Cancer》 SCIE CAS CSCD 2017年第2期53-62,共10页
Obesity is recognized as the second highest risk factor for cancer. The pathogenic mechanisms underlying tobaccorelated cancers are well characterized and efective programs have led to a decline in smoking and related... Obesity is recognized as the second highest risk factor for cancer. The pathogenic mechanisms underlying tobaccorelated cancers are well characterized and efective programs have led to a decline in smoking and related cancers, but there is a global epidemic of obesity without a clear understanding of how obesity causes cancer. Obesity is heterogeneous, and approximately 25% of obese individuals remain healthy(metabolically healthy obese, MHO), so which fat deposition(subcutaneous versus visceral, adipose versus ectopic) is "malignant"? What is the mechanism of carcinogenesis? Is it by metabolic dysregulation or chronic inflammation? Through which chemokines/genes/signaling pathways does adipose tissue influence carcinogenesis? Can selective inhibition of these pathways uncouple obesity from cancers? Do all obesity related cancers(ORCs) share a molecular signature? Are there common(overlapping) genetic loci that make individuals susceptible to obesity, metabolic syndrome, and cancers? Can we identify precursor lesions of ORCs and will early intervention of high risk individuals alter the natural history? It appears unlikely that the obesity epidemic will be controlled anytime soon; answers to these questions will help to reduce the adverse efect of obesity on human condition. 展开更多
关键词 more questions than answers The most important questions in cancer research and clinical oncology Question 2-5.Obesity-related cancers THAN
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Nonlinear dynamic response of beam and its application in nanomechanical resonator 被引量:3
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作者 Yin Zhang Yun Liu Kevin D.Murphy 《Acta Mechanica Sinica》 SCIE EI CAS CSCD 2012年第1期190-200,共11页
Nonlinear dynamic response of nanomechanical resonator is of very important characteristics in its application. Two categories of the tension-dominant and curvaturedominant nonlinearities are analyzed. The dynamic non... Nonlinear dynamic response of nanomechanical resonator is of very important characteristics in its application. Two categories of the tension-dominant and curvaturedominant nonlinearities are analyzed. The dynamic nonlinearity of four beam structures of nanomechanical resonator is quantitatively studied via a dimensional analysis approach. The dimensional analysis shows that for the nanomechanical resonator of tension-dominant nonlinearity, its dynamic nonlinearity decreases monotonically with increasing axial loading and increases monotonically with the increasing aspect ratio of length to thickness; the dynamic nonlinearity can only result in the hardening effects. However, for the nanomechanical resonator of the curvature-dominant nonlinearity, its dynamic nonlinearity is only dependent on axial loading. Compared with the tension-dominant nonlinearity, the curvature-dominant nonlinearity increases monotonically with increasing axial loading; its dynamic nonlinearity 展开更多
关键词 Resonator. Dynamic response. Dynamic nonlinearity - Dimensional analysis
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Optimization of Process Parameters of Continuous Microwave Drying Raspberry Puree Based on RSM and ANN-GA
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作者 Zheng Xian-zhe Gao Feng +2 位作者 Fu Ke-sen Lu Tian-lin Zhu Chong-hao 《Journal of Northeast Agricultural University(English Edition)》 CAS 2023年第1期69-84,共16页
To improve drying uniformity and anthocyanin content of the raspberry puree dried in a continuous microwave dryer,the effects of process parameters(microwave intensity,air velocity,and drying time)on evaluation indexe... To improve drying uniformity and anthocyanin content of the raspberry puree dried in a continuous microwave dryer,the effects of process parameters(microwave intensity,air velocity,and drying time)on evaluation indexes(average temperature,average moisture content,average retention rate of the total anthocyanin content,temperature contrast value,and moisture dispersion value)were investigated via the response surface method(RSM)and the artificial neural network(ANN)with genetic algorithm(GA).The results showed that the microwave intensity and drying time dominated the changes of evaluation indexes.Overall,the ANN model was superior to the RSM model with better estimation ability,and higher drying uniformity and anthocyanin retention rate were achieved for the ANN-GA model compared with RSM.The optimal parameters were microwave intensity of 5.53 W•g^(-1),air velocity of 1.22 m·s^(-1),and drying time of 5.85 min.This study might provide guidance for process optimization of microwave drying berry fruits. 展开更多
关键词 raspberry puree continuous microwave drying response surface method(RSM) artificial neural network(ANN) genetic algorithm(GA)CLC number:TG376 Document code:A Article ID:1006-8104(2023)-01-0069-16
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The 5’-Untranslated Region of the C9orf72 mRNA Exhibits a Phylogenetic Alignment to the Cis-Aconitase Iron-Responsive Element;Novel Therapies for Amytrophic Lateral Sclerosis
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作者 Monica A. Lu Susruthi Rajanala +4 位作者 Sohan V. Mikkilineni Catherine M. Cahill Robert Brown James D. Berry Jack T. Rogers 《Neuroscience & Medicine》 2016年第1期15-26,共12页
The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding pla... The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding plays a role in ALS pathogenesis in two ways: non-ATG translation of the repeat can lead to aggregates of the known C9orf72 specific dipeptide polymer, whereas the repeat also can form neurotoxic RNA inclusions that dose-responsively kill motor neurons. We report the presence of a homology in the 5’untranslated region (UTR) of the messenger RNA encoding C9orf72 with the iron responsive elements (IRE) that control expression of iron-associated transcripts and predict that this RNA structure may iron-dependently regulate C9orf72 translation. We previously report altered serum ferritin levels track with severity of ALS in patients. Here, we conduct bioinformatics analyses to determine the secondary structure of the 5’UTR in C9orf72 mRNA and find it aligned with IREs in the human mitochondrial cis-aconitase and L and H-ferritin transcripts. Comparison of the role of RNA repeats in Friedriech’s ataxia and fragile X mental retardation suggests the utility of RNA based therapies for treatment of ALS. Antisense oligonucleotides (ASO) have been reported to therapeutically target these GGGGCC repeats. At the same time, because the function of C9orf72 is unknown, knockdown strategies carry some risk of inducing or compounding haploinsufficiency. We propose, for consideration, an approach that may enhance its therapeutic dynamic range by increasing the 5’UTR driven translation of C9orf72 protein to compensate for any potential ALS-specific or ASO-induced haploinsufficieny. 展开更多
关键词 Amyotrophic Lateral Sclerosis (ALS) Iron-responsive Element (IRE) C9orf72 mRNA Mitochondrial Aconitase (mACO) Frontotemporal Dementia (FTD) Amyloid Precursor Protein (APP) HIV Trans-Activation response Element (TAR) Antisense Oligonucleotides (ASO) Iron-Regulatory Proteins-1 and -2 (IRP1 and IRP2)
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浅析课堂话语的典型交际模式——I-R-F三分结构 被引量:6
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作者 陈艳 《山东外语教学》 2004年第3期52-54,共3页
外语课堂交际活动有它自身特定的方式、规律和规则.师生间为完成某种教学目标所进行的交际明显不同于人们日常生活中的交际活动.在课堂上,学生使用语言参与课堂交际的积极性和能力发挥得好坏,在很大程度上取决于课堂交际模式的引导.本... 外语课堂交际活动有它自身特定的方式、规律和规则.师生间为完成某种教学目标所进行的交际明显不同于人们日常生活中的交际活动.在课堂上,学生使用语言参与课堂交际的积极性和能力发挥得好坏,在很大程度上取决于课堂交际模式的引导.本文重点探讨了I-R-F三分结构这一典型的课堂话语交际模式以及教师在这一模式中应起的作用. 展开更多
关键词 I—R—F结构 参与 提问 回答 反馈
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行政机关负责人出庭应诉制度的现状及完善研究
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作者 李晓虹 《信阳农林学院学报》 2024年第1期25-31,共7页
行政机关负责人出庭应诉作为一项具有中国特色的制度,自产生以来在维护司法权威、解决行政争议和推进法治政府建设方面具有重要作用。但通过搜集整理各地的规范性文件并进行分析之后,可以发现该制度在司法实践中,存在行政机关负责人应... 行政机关负责人出庭应诉作为一项具有中国特色的制度,自产生以来在维护司法权威、解决行政争议和推进法治政府建设方面具有重要作用。但通过搜集整理各地的规范性文件并进行分析之后,可以发现该制度在司法实践中,存在行政机关负责人应当出庭应诉的案件范围划分模糊,现有规范对负责人不出庭应诉的责任制约性弱,出庭负责人级别不统一以及各地普遍追求高应诉率的问题,需要通过完善出庭应诉范围、统一出庭应诉负责人级别、强化行政机关负责人出庭应诉的考核监督、增强负责人的应诉能力等方式进一步规范具体的实践做法,最后还应当改变单一追求行政机关负责人出庭应诉率的做法,正确引导新闻媒体作正面宣传,以此激发该项制度所蕴含的功能,推进行政审判的进步。 展开更多
关键词 行政机关负责人 出庭应诉 负责人范围 考核监督
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A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses
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作者 Yuhan Li Xiangqing Ding +8 位作者 Xianxian Wu Longfei Ding Yuhui Yang Xiaoliang Jiang Xing Liu Xu Zhang Jianrong Su Jianqing Xu Zhiwei Yang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第11期4461-4476,共16页
Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to ... Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to inflammatory sites,blockade of PSGL-1 might confer potent anti-inflammatory effects.In this study,we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1,RH001-6 and RH001-22,which were screened from immunized rhesus macaques.We found that RH001-6,can effectively block the binding of P-selectin to PSGL-1,and abolish the adhesion of leukocytes to endothelial cells in vitro.In vivo,we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and L-arginine induced AP models.We also evaluated the safety profile after RH001-6 treatment in mice,and verified that RH001-6 did not cause any significant pathological damages in vivo.Taken together,we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity,named RH001-6,which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP.Therefore,RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases,such as AP. 展开更多
关键词 Acute pancreatitis PSGL-1 Non-human primate Monoclonal antibody Therapeutic antibody RH001-6 Adhesion of leukocytes to endothelial cells Inflammatory responses Pancreatic injury
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Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B 被引量:18
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作者 Ji Chen,Yan Wang,Xue-Jie Wu,Jun Li,Feng-Qin Hou,Gui-Qiang Wang,Department of Infectious Diseases,Center for Liver Diseases,Peking University First Hospital,Beijing 100034,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第48期6145-6150,共6页
AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. ... AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines. 展开更多
关键词 CHRONIC HEPATITIS B Pegylated INTERFERON Α-2B therapy IMMUNE response CYTOKINE
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MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein 被引量:10
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作者 Min Li Qi Wang +7 位作者 Shun-Ai Liu Jin-Qian Zhang Wei Ju Min Quan Sheng-Hu Feng Jin-Ling Dong Ping Gao Jun Cheng 《World Journal of Gastroenterology》 SCIE CAS 2015年第15期4517-4525,共9页
AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cell... AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGCR) was measured by quantitative real-time PCR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi RNA.RESULTS: HCV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGCR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HCV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HCV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HCV core protein. CONCLUSION: HCV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein. 展开更多
关键词 CHOLESTEROL HEPATITIS C VIRUS core protein miR-185-5p STEATOSIS STEROL response ELEMENT bindingproteins
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LNCaP衍生的雄激素非依赖型前列腺癌细胞系C4-2对辐射的应答反应 被引量:4
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作者 Bang-Xiang Xie Hui Zhang +8 位作者 Lan Yu Jian Wang Bo Pang Rui-Qin Wu Xiao-Long Qian Shan-Hu Li Qing-Guo Shi Le-Le Wang Jian-Guang Zhou 《Asian Journal of Andrology》 SCIE CAS CSCD 2010年第3期405-414,I0011,共11页
Radiation therapy is a relatively effective therapeutic method for localized prostate cancer (PCa) patients. However, radioresistance occurs in nearly 30% of patients treated with potentially curative doses. Therape... Radiation therapy is a relatively effective therapeutic method for localized prostate cancer (PCa) patients. However, radioresistance occurs in nearly 30% of patients treated with potentially curative doses. Therapeutic synergy between radiotherapy and androgen ablation treatment provides a promising strategy for improving the clinical outcome. Accordingly, the androgen deprivation-induced signaling pathway may also mediate radiosensitivity in PCa cells. The C4-2 cell line was derived from the androgen-sensitive LNCaP parent line under androgen-depleted condition and had acquired androgen-refractory characteristics. In our study, the response to radiation was evaluated in both LNCaP and C4-2. Results showed that C4-2 cells were more likely to survive from irradiation and appeared more aggressive in their resistance to radiation treatment compared with LNCaP, as measured by clonogenic assays and cell viability and cell cycle analyses. Gene expression analyses revealed that a set of genes involved in cell cycle arrest and DNA repair were differentially regulated in LNCaP and C4-2 in response to radiation, which was also consistent with the radiation-resistant property observed in C4-2 cells. These results strongly suggested that the radiation-resistant property may develop with progression of PCa to androgen- independent status. Not only can the LNCaP and C4-2 PCa progression model be applied for investigating androgen-refractory progression, but it can also be used to explore the development of radiation resistance in PCa. 展开更多
关键词 LNCAP C4-2 prostate cancer radiation response
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Nonlinear study of the dynamic behavior of a string-beam coupled system under combined excitations 被引量:3
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作者 Y.S. Hamed M. Sayed +1 位作者 D.-X. Cao W. Zhang 《Acta Mechanica Sinica》 SCIE EI CAS CSCD 2011年第6期1034-1051,共18页
In this paper,the nonlinear dynamic behavior of a string-beam coupled system subjected to external,parametric and tuned excitations is presented.The governing equations of motion are obtained for the nonlinear transve... In this paper,the nonlinear dynamic behavior of a string-beam coupled system subjected to external,parametric and tuned excitations is presented.The governing equations of motion are obtained for the nonlinear transverse vibrations of the string-beam coupled system which are described by a set of ordinary differential equations with two degrees of freedom.The case of 1:1 internal resonance between the modes of the beam and string,and the primary and combined resonance for the beam is considered.The method of multiple scales is utilized to analyze the nonlinear responses of the string-beam coupled system and obtain approximate solutions up to and including the second-order approximations.All resonance cases are extracted and investigated.Stability of the system is studied using frequency response equations and the phase-plane method.Numerical solutions are carried out and the results are presented graphically and discussed.The effects of the different parameters on both response and stability of the system are investigated.The reported results are compared to the available published work. 展开更多
关键词 1:1 internal resonance - String-beam - Multiple scales Chaotic response Stability
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