This research introduces a novel approach to enhancing bucket elevator design and operation through the integration of discrete element method(DEM)simulation,design of experiments(DOE),and metaheuristic optimization a...This research introduces a novel approach to enhancing bucket elevator design and operation through the integration of discrete element method(DEM)simulation,design of experiments(DOE),and metaheuristic optimization algorithms.Specifically,the study employs the firefly algorithm(FA),a metaheuristic optimization technique,to optimize bucket elevator parameters for maximizing transport mass and mass flow rate discharge of granular materials under specified working conditions.The experimental methodology involves several key steps:screening experiments to identify significant factors affecting bucket elevator operation,central composite design(CCD)experiments to further explore these factors,and response surface methodology(RSM)to create predictive models for transport mass and mass flow rate discharge.The FA algorithm is then applied to optimize these models,and the results are validated through simulation and empirical experiments.The study validates the optimized parameters through simulation and empirical experiments,comparing results with DEM simulation.The outcomes demonstrate the effectiveness of the FA algorithm in identifying optimal bucket parameters,showcasing less than 10%and 15%deviation for transport mass and mass flow rate discharge,respectively,between predicted and actual values.Overall,this research provides insights into the critical factors influencing bucket elevator operation and offers a systematic methodology for optimizing bucket parameters,contributing to more efficient material handling in various industrial applications.展开更多
As key components connecting offshore floating production platforms and subsea imports, offshore flexible pipes play significant roles in oil, natural gas, and water injection. It is found that torsional failure is on...As key components connecting offshore floating production platforms and subsea imports, offshore flexible pipes play significant roles in oil, natural gas, and water injection. It is found that torsional failure is one of the failure modes of flexible pipes during transportation and laying. In this paper, a theoretical model(TM) of a flexible pipe section mechanics is established, in which the carcass layer and the pressure armor layer are equivalent to the orthogonal anisotropic layers due to its complex cross-section structure. The calculation results of the TM are consistent with those of a finite element model(FEM), which can accurately describe the torsional response of the flexible pipe.Subsequently, the TM and FEM are used to discuss the influence of boundary conditions on the torsional response.The structure of the flexible pipe is stable when twisted counterclockwise. However, limiting the top axial displacement can improve the axial and radial instability of the tensile armor layer when twisted clockwise. Finally, it is recommended that the flexible pipe can be kept under top fixation during service or installation to avoid torsional failure.展开更多
Ethylene-responsive element binding factors(ERFs)are involved in regulation of various stress responses in plants,but their biological functions in waterlogging stress are largely unclear.In this study,we identified a...Ethylene-responsive element binding factors(ERFs)are involved in regulation of various stress responses in plants,but their biological functions in waterlogging stress are largely unclear.In this study,we identified a petunia(Petunia×hybrida)ERF gene,PhERF2,that was significantly induced by waterlogging in wild-type(WT).To study the regulatory role of PhERF2 in waterlogging responses,transgenic petunia plants with RNAi silencing and overexpression of PhERF2 were generated.Compared with WT plants,PhERF2 silencing compromised the tolerance of petunia seedlings to waterlogging,shown as 96%mortality after 4 days waterlogging and 14 days recovery,while overexpression of PhERF2 improved the survival of seedlings subjected to waterlogging.PhERF2-RNAi lines exhibited earlier and more severe leaf chlorosis and necrosis than WT,whereas plants overexpressing PhERF2 showed promoted growth vigor under waterlogging.Chlorophyll content was dramatically lower in PhERF2-silenced plants than WT or overexpression plants.Typical characteristics of programmed cell death(PCD),DNA condensation,and moon-shaped nuclei were only observed in PhERF2-overexpressing lines but not in PhERF2-RNAi or control lines.Furthermore,transcript abundances of the alcoholic fermentation-related genes ADH1-1,ADH1-2,ADH1-3,PDC1,and PDC2 were reduced in PhERF2-silenced plants,but increased in PhERF2-overexpressing plants following exposure to 12-h waterlogging.In contrast,expression of the lactate fermentation-related gene LDH was up-regulated in PhERF2-silenced plants,but downregulated in its overexpressing plants.Moreover,PhERF2 was observed to directly bind to the ADH1-2 promoter bearing ATCTA motifs.Our results demonstrate that PhERF2 contributes to petunia waterlogging tolerance through modulation of PCD and alcoholic fermentation system.展开更多
The present work aims to assess earthquake-induced earth-retaining(ER)wall displacement.This study is on the dynamics analysis of various earth-retaining wall designs in hollow precast concrete panels,reinforcement co...The present work aims to assess earthquake-induced earth-retaining(ER)wall displacement.This study is on the dynamics analysis of various earth-retaining wall designs in hollow precast concrete panels,reinforcement concrete facing panels,and gravity-type earth-retaining walls.The finite element(FE)simulations utilized a 3D plane strain condition to model full-scale ER walls and numerous nonlinear dynamics analyses.The seismic performance of differentmodels,which includes reinforcement concrete panels and gravity-type and hollowprecast concrete ER walls,was simulated and examined using the FE approach.It also displays comparative studies such as stress distribution,deflection of the wall,acceleration across the wall height,lateral wall displacement,lateral wall pressure,and backfill plastic strain.Three components of the created ER walls were found throughout this research procedure.One is a granular reinforcement backfill,while the other is a wall-facing panel and base foundation.The dynamic response effects of varied earth-retaining walls have also been studied.It was discovered that the facing panel of the model significantly impacts the earthquake-induced displacement of ER walls.The proposed analytical model’s validity has been evaluated and compared with the reinforcement concrete facing panels,gravity-type ER wall,scientifically available data,and American Association of State Highway and Transportation Officials(AASHTO)guidelines results based on FE simulation.The results of the observations indicate that the hollow prefabricated concrete ER wall is the most feasible option due to its lower displacement and high-stress distribution compared to the two types.The methodology and results of this study establish standards for future analogous investigations and professionals,particularly in light of the increasing computational capabilities of desktop computers.展开更多
Understanding the dynamic response of composite material cartridges during the firing process is of great significance for improving their reliability and safety.A theoretical model describing the dynamic response of ...Understanding the dynamic response of composite material cartridges during the firing process is of great significance for improving their reliability and safety.A theoretical model describing the dynamic response of composite material cartridges is established based on the thick-walled cylinder theory and rate-dependent constitutive model of composite materials.The correctness of the theoretical model is validated through finite element simulations of cartridge deformation.The influence of chamber pressure and cartridge wall thickness on the cartridge's deformation process and stress distribution is analyzed.The results indicate that the primary deformation of composite material cartridges inside the chamber is elastic deformation.Compared to metal cartridges,composite material cartridges require higher pressure for touching-chamber and are more prone to developing gaps after unloading to ensure smooth extraction.During the deformation process,the touching-chamber behavior of the cartridge can improve the stress distribution.Under the same chamber pressure,the touching-chamber behavior can reduce the circumferential stress by approximately 30%.The inner wall surface of the cartridge is a critical area that requires attention.The touching-chamber behavior can be facilitated by appropriately reducing the cartridge wall thickness while ensuring overall strength.This study can provide guidance for the optimization design of composite material cartridges.展开更多
As the basic protective element, steel plate had attracted world-wide attention because of frequent threats of explosive loads. This paper reports the relationships between microscopic defects of Q345 steel plate unde...As the basic protective element, steel plate had attracted world-wide attention because of frequent threats of explosive loads. This paper reports the relationships between microscopic defects of Q345 steel plate under the explosive load and its macroscopic dynamics simulation. Firstly, the defect characteristics of the steel plate were investigated by stereoscopic microscope(SM) and scanning electron microscope(SEM). At the macroscopic level, the defect was the formation of cave which was concentrated in the range of 0-3.0 cm from the explosion center, while at the microscopic level, the cavity and void formation were the typical damage characteristics. It also explains that the difference in defect morphology at different positions was the combining results of high temperature and high pressure. Secondly, the variation rules of mechanical properties of steel plate under explosive load were studied. The Arbitrary Lagrange-Euler(ALE) algorithm and multi-material fluid-structure coupling method were used to simulate the explosion process of steel plate. The accuracy of the method was verified by comparing the deformation of the simulation results with the experimental results, the pressure and stress at different positions on the surface of the steel plate were obtained. The simulation results indicated that the critical pressure causing the plate defects may be approximately 2.01 GPa. On this basis, it was found that the variation rules of surface pressure and microscopic defect area of the Q345 steel plate were strikingly similar, and the corresponding mathematical relationship between them was established. Compared with Monomolecular growth fitting models(MGFM) and Logistic fitting models(LFM), the relationship can be better expressed by cubic polynomial fitting model(CPFM). This paper illustrated that the explosive defect characteristics of metal plate at the microscopic level can be explored by analyzing its macroscopic dynamic mechanical response.展开更多
All mammalian metallothionein genes studied to date have several metal responsive elements (MRE) with consensus sequences of TGCRCNC (R, purine) in their regulatory region. MRE-like sequences were also found in many o...All mammalian metallothionein genes studied to date have several metal responsive elements (MRE) with consensus sequences of TGCRCNC (R, purine) in their regulatory region. MRE-like sequences were also found in many other metal-related genes. To see whether there is also such a sequence at the genetic locus (13q14. 3) of Wilson disease, which is a genetic disorder of copper metabolism, junction-trapping method based on the MRE sequence was used. A fragment containing MRE and MRE-like sequences from YAC 27D8 at the WND locus was successfully cloned and mapped back to the YAC by PCR. Presence of such a sequence in the copper transporter gene at the WD locus might imply that it has a possible interesting role in the regulation of WD gene expression.展开更多
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
The reliability of the eddy current testing (ECT) in flaw detection is quantitatively evaluated by theprobability of detection (POD). Precise and efficient modeling of POD gives direction for the implement of ECTon si...The reliability of the eddy current testing (ECT) in flaw detection is quantitatively evaluated by theprobability of detection (POD). Precise and efficient modeling of POD gives direction for the implement of ECTon sites to avoid false or missing flaw detection. Traditional POD analysis focuses on single uncertain factor orsingle response signal with limited credibility in engineering. This paper considers multiple response signals andmultiple flaw parameters to perform POD. The flaw length, the flaw depth, the coil impedance, and the magneticflux density are comprehensively studied under various lift-off distances. A finite element model (FEM) of ECT isestablished and verified with experiments to obtain sufficient simulation data for discrete POD modeling. Thecontinuous POD function is then fitted based on the discrete values to show the superiority of integrating multiplefactors. A comparison with conventional POD analysis further demonstrates the higher reliability of ECT flawdetection considering multiple flaw parameters and multiple response signals, especially for small flaws.展开更多
BACKGROUND: Virological clearance, delayed progression to cirrhosis or liver cancer, and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients. Identification of host factors ...BACKGROUND: Virological clearance, delayed progression to cirrhosis or liver cancer, and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients. Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment. This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha (ESR1) is associated with the initial response to interferon-alpha (IFN-alpha) therapy in chronic hepatitis B patients. METHODS: The initial responses of 100 patients to IFN-alpha therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1: T/T, TIC, and C/C genotype groups. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C. RESULTS: The frequency of initially combined response was markedly higher in both the T/T and TIC groups than in the C/C group (Z=10.326, P=0.006 and Z=26.247, P=0.000, respectively). In addition, the initial virological response was higher in the T/T and T/C groups than the C/C group (chi(2)=5.674, P=0.017 and chi(2)=4.980, P=0.026, respectively). In 78 initially HBeAg-positive patients, however, the frequency of initial e-antigen disappearance or seroconversion among the T/T, T/C, and C/C genotype groups was 34.15%, 27.78% and 15.79%, respectively, which were not significantly different. CONCLUSION. The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-alpha in patients with chronic hepatitis B, and might be a significant marker for predicting the initial response to IFN-alpha, at least in this study population. (Hepatobiliary Pancreat Dis Int 2010; 9: 275-279)展开更多
AIM: To study the contribution of tonicity response element binding protein(Ton EBP) in retinal ganglion cell(RGC) death of diabetic retinopathy(DR).METHODS: Diabetes was induced in C57BL/6 mice by five consecutive in...AIM: To study the contribution of tonicity response element binding protein(Ton EBP) in retinal ganglion cell(RGC) death of diabetic retinopathy(DR).METHODS: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin(STZ). Control mice received vehicle(phosphate-buffered saline). All mice were killed 2mo after injections, and the extent of cell death and the protein expression levels of Ton EBP and aldose reductase(AR) were examined.RESULTS: The Ton EBP and AR protein levels and the death of RGC were significantly increased in the retinas of diabetic mice compared with controls 2mo after the induction of diabetes. Terminal deoxynucleotidyl transferase(Td T)-mediated d UTP nick end labeling(TUNEL)-positive signals co-localized with Ton EBP immunoreactive RGC. These changes were increased in the diabetic retinas compared with controls.CONCLUSION: The present data show that AR and Ton EBP are upregulated in the DR and Ton EBP may contribute to apoptosis of RGC in the DR.展开更多
The nonlinear finite element(FE) analysis has been widely used in the design and analysis of structural or geotechnical systems.The response sensitivities(or gradients) to the model parameters are of significant i...The nonlinear finite element(FE) analysis has been widely used in the design and analysis of structural or geotechnical systems.The response sensitivities(or gradients) to the model parameters are of significant importance in these realistic engineering problems.However the sensitivity calculation has lagged behind,leaving a gap between advanced FE response analysis and other research hotspots using the response gradient.The response sensitivity analysis is crucial for any gradient-based algorithms,such as reliability analysis,system identification and structural optimization.Among various sensitivity analysis methods,the direct differential method(DDM) has advantages of computing efficiency and accuracy,providing an ideal tool for the response gradient calculation.This paper extended the DDM framework to realistic complicated soil-foundation-structure interaction(SFSI) models by developing the response gradients for various constraints,element and materials involved.The enhanced framework is applied to three-dimensional SFSI system prototypes for a pilesupported bridge pier and a pile-supported reinforced concrete building frame structure,subjected to earthquake loading conditions.The DDM results are verified by forward finite difference method(FFD).The relative importance(RI) of the various material parameters on the responses of SFSI system are investigated based on the DDM response sensitivity results.The FFD converges asymptotically toward the DDM results,demonstrating the advantages of DDM(e.g.,accurate,efficient,insensitive to numerical noise).Furthermore,the RI and effects of the model parameters of structure,foundation and soil materials on the responses of SFSI systems are investigated by taking advantage of the sensitivity analysis results.The extension of DDM to SFSI systems greatly broaden the application areas of the d gradient-based algorithms,e.g.FE model updating and nonlinear system identification of complicated SFSI systems.展开更多
We presented a boundary element method using the approximate analytical Green's function given by Sanchez-Sesma et al. Coordinate transform is introduced to extend the method to deal with the model with constant-grad...We presented a boundary element method using the approximate analytical Green's function given by Sanchez-Sesma et al. Coordinate transform is introduced to extend the method to deal with the model with constant-gradient velocity along oblique direction. The method is validated by comparing the numerical results with other independent methods. This method provides a useful tool for analyzing local site effects. We computed seismic response for two series of models. The results in both frequency and time domains are analyzed and show complex amplification patterns. The fundamental mode of resonance is dependent not only on the velocity at the free surface but also on the velocity distribution of the whole basin. For the higher modes of vibration the heterogeneous basin also has its own characteristic.展开更多
Many high earth-rockfill dams are constructed in the west of China. The seismic intensity at the dam site is usually very high, thus it is of great importance to ensure the safety of the dam in meizoseismal area. A 3D...Many high earth-rockfill dams are constructed in the west of China. The seismic intensity at the dam site is usually very high, thus it is of great importance to ensure the safety of the dam in meizoseismal area. A 3D FEM model is established to analyze the seismic responses of Shiziping earth-rockfill dam. The nonlinear elastic Duncan-Chang constitutive model and the equivalent viscoelastic constitutive model are used to simulate the static and dynamic stress strain relationships of the dam materials, respectively. Four groups of seismic waves are inputted from the top of the bedrock to analyze the dynamic responses of the dam. The numerical results show that the calculated dynamic magnification factors display a good consistency with the specification values. The site spectrum results in larger acceleration response than the specification spectrum. The analysis of relative dynamic displacement indicates that the displacement at the downstream side of the dam is larger than that at the upstream side. The displacement response reduces from the center of river valley to two banks. The displacement responses corresponding to the specification spectrum are a little smaller than those corresponding to the site spectrum. The analysis of shear stress indicates that a large shear stress area appears in the upstream overburden layer, where the shear stress caused by site waves is larger than that caused by specification waves. The analysis of dynamic principal stress indicates that the minimum dynamic stresses in corridor caused by specification and site waves have little difference. The maximum and minimum dynamic stresses are relatively large at two sides. The largest tensile stress occurs at two sides of the floor of grouting corridor, which may result in the crack near the corridor side. The numerical results present good consistency with the observation data of the grouting corridor in Wenchuan earthquake.展开更多
Recent seismic events have raised concerns over the safety and vulnerability of reinforced concrete moment resisting frame "RC-MRF" buildings. The seismic response of such buildings is greatly dependent on the compu...Recent seismic events have raised concerns over the safety and vulnerability of reinforced concrete moment resisting frame "RC-MRF" buildings. The seismic response of such buildings is greatly dependent on the computational tools used and the inherent assumptions in the modelling process. Thus, it is essential to investigate the sensitivity of the response demands to the corresponding modelling assumption. Many parameters and assumptions are justified to generate effective structural finite element(FE) models of buildings to simulate lateral behaviour and evaluate seismic design demands. As such, the present study focuses on the development of reliable FE models with various levels of refinement. The effects of the FE modelling assumptions on the seismic response demands on the design of buildings are investigated. the predictive ability of a FE model is tied to the accuracy of numerical analysis; a numerical analysis is performed for a series of symmetric buildings in active seismic zones. The results of the seismic response demands are presented in a comparative format to confirm drift and strength limits requirements. A proposed model is formulated based on a simplified modeling approach, where the most refined model is used to calibrate the simplified model.展开更多
At 8 weeks after intragastric administration of icariin to senescence-accelerated mice (P8 strain), Morris water maze results showed that escape latency was shortened, and the number of platform crossings was increa...At 8 weeks after intragastric administration of icariin to senescence-accelerated mice (P8 strain), Morris water maze results showed that escape latency was shortened, and the number of platform crossings was increased. Immunohistochemical staining and western blot assay detected significantly increased levels of cyclic adenosine monophosphate response element binding protein These results suggest that icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels and improves learning and memory functions in hippocampus of the senescence-accelerated mouse.展开更多
A new method for optimizing a butterfly-shaped linear ultrasonic motor was proposed to maximize its mechanical output. The finite element analysis technology and response surface methodology were combined together to ...A new method for optimizing a butterfly-shaped linear ultrasonic motor was proposed to maximize its mechanical output. The finite element analysis technology and response surface methodology were combined together to realize the optimal design of the butterfly-shaped linear ultrasonic motor. First, the operation principle of the motor was introduced. Second, the finite element parameterized model of the stator of the motor was built using ANSYS parametric design language and some structure parameters of the stator were selected as design variables. Third, the sample points were selected in design variable space using latin hypercube Design. Through modal analysis and harmonic response analysis of the stator based on these sample points, the target responses were obtained. These sample points and response values were combined together to build a response surface model. Finally, the simplex method was used to find the optimal solution. The experimental results showed that many aspects of the design requirements of the butterfly-shaped linear ultrasonic motor have been fulfilled. The prototype motor fabricated based on the optimal design result exhibited considerably high dynamic performance, such as no-load speed of 873 ram/s, maximal thrust of 27.5 N, maximal efficiency of 43%, and thrust-weight ratio of 45.8.展开更多
Aim: To characterize the matrix metalloproteinases (MMP)-2 promoter and to identify androgen response elements (AREs) involved in androgen-induced MMP-2 expression. Methods: MMP-2 mRNA levels was determined by r...Aim: To characterize the matrix metalloproteinases (MMP)-2 promoter and to identify androgen response elements (AREs) involved in androgen-induced MMP-2 expression. Methods: MMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction (RT-PCR). MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays (EMSA) were used to verify the identified AREs in the MMP-2 promoter. Results: Androgen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1591 to -1259 (relative to the start codon) of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5'-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor (AR) interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay. Conclusion: Two ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.展开更多
In order to study the sliding characteristics when the cable is connected with the other rods in the transmission line structures,a linear sliding cable element based on updated Lagrangian formulation and a sliding ca...In order to study the sliding characteristics when the cable is connected with the other rods in the transmission line structures,a linear sliding cable element based on updated Lagrangian formulation and a sliding catenary element considering the out-of-plane stiffness coefficient are put forward.A two-span and a three-span cable structures are taken as examples to verify the sliding cable elements.By comparing the tensions of the two proposed cable elements with the existing research results,the error is less than 1%,which proves the correctness of the proposed elements.The sliding characteristics should be considered in the practical engineering because of the significant difference between the tensions of sliding cable elements and those of cable element without considering sliding.The out-of-plane stiffness coefficient and friction characteristics do not obviously affect the cable tensions.展开更多
BACKGROUND: cAMP-response element binding protein (CREB) is a key modulator of various signaling pathways. CREB activation initiates a series of intracellular signaling pathways that promote neuronal survival. OBJE...BACKGROUND: cAMP-response element binding protein (CREB) is a key modulator of various signaling pathways. CREB activation initiates a series of intracellular signaling pathways that promote neuronal survival. OBJECTIVE: To investigate the regulatory effects of basic fibroblast growth factor (bFGF) on cerebral neuronal CREB expression following ischemia/reperfusion injury. DESIGN, TIME AND SETTING: An immunohistochemical detection experiment was performed at the Department of Anatomy, Shenyang Medical College, between October 2006 and April 2008. MATERIALS: A total of 60 healthy, adult, Wistar rats were randomly divided into three groups: sham-operated (n =12), ischemia/reperfusion (n = 24), and bFGF-treated (n = 24). Rabbit anti-rat CREB (1: 100) and biotin labeled goat anti-rabbit IgG were purchased from the Wuhan Boster Company, China. MetaMorph-evolution MP5.0-BX51 microscopy imaging system was provided by China Medical University, China. METHODS: Rat models of cerebral ischemia/reperfusion injury were developed using the suture method for right middle cerebral artery occlusion. Two-hour ischemia was followed by reperfusion. Rats from the bFGF-treated and ischemia/reperfusion groups were intraperitoneally administered endogenous bFGF (500 IU/mL, 2 000 IU/kg) or an equal amount of physiological saline. Rats from the sham-operated group underwent a similar surgical procedure, without induction of ischemia/reperfusion injury and drug administration. MAIN OUTCOME MEASURES: After 48-hour reperfusion, hippocampal and parietal cortical neuronal CREB expression was detected by immunohistochemistry, and the absorbance of hippocampal CREB-positive products was determined using MetaMorph-evolutionMP5.0-BX51 microscopy imaging system. RESULTS: The sham-operated group exhibited noticeable CREB expression in hippocampal and parietal cortical neurons. In the ischemia/reperfusion group, the CREB expression was discrete and neurons were poorly arranged. The bFGF-treated group exhibited increased CREB expression and better neuronal arrangement compared with the ischemia/reperfusion group. The mean absorbance of CREB-immunoreactive products in the hippocampus and parietal cortex was significantly higher in the ischemia/reperfusion group than in the sham-operated group (P 〈 0.05), and significantly higher in the bFGF-treated group than in the ischemia/reperfusion group (P 〈 0.05). CONCLUSION: bFGF significantly upregulates CREB expression in hippocampal and parietal cortical neurons following ischemia/reperfusion injury.展开更多
基金This research was funded by the Faculty of Engineering,King Mongkut’s University of Technology North Bangkok.Contract No.ENG-NEW-66-39.
文摘This research introduces a novel approach to enhancing bucket elevator design and operation through the integration of discrete element method(DEM)simulation,design of experiments(DOE),and metaheuristic optimization algorithms.Specifically,the study employs the firefly algorithm(FA),a metaheuristic optimization technique,to optimize bucket elevator parameters for maximizing transport mass and mass flow rate discharge of granular materials under specified working conditions.The experimental methodology involves several key steps:screening experiments to identify significant factors affecting bucket elevator operation,central composite design(CCD)experiments to further explore these factors,and response surface methodology(RSM)to create predictive models for transport mass and mass flow rate discharge.The FA algorithm is then applied to optimize these models,and the results are validated through simulation and empirical experiments.The study validates the optimized parameters through simulation and empirical experiments,comparing results with DEM simulation.The outcomes demonstrate the effectiveness of the FA algorithm in identifying optimal bucket parameters,showcasing less than 10%and 15%deviation for transport mass and mass flow rate discharge,respectively,between predicted and actual values.Overall,this research provides insights into the critical factors influencing bucket elevator operation and offers a systematic methodology for optimizing bucket parameters,contributing to more efficient material handling in various industrial applications.
基金financially supported by the Natural Science Starting Project of SWPU (Grant No. 2022QHZ002)Sichuan Natural Science Foundation Youth Fund Project (Grant No. 2023NSFC0918)。
文摘As key components connecting offshore floating production platforms and subsea imports, offshore flexible pipes play significant roles in oil, natural gas, and water injection. It is found that torsional failure is one of the failure modes of flexible pipes during transportation and laying. In this paper, a theoretical model(TM) of a flexible pipe section mechanics is established, in which the carcass layer and the pressure armor layer are equivalent to the orthogonal anisotropic layers due to its complex cross-section structure. The calculation results of the TM are consistent with those of a finite element model(FEM), which can accurately describe the torsional response of the flexible pipe.Subsequently, the TM and FEM are used to discuss the influence of boundary conditions on the torsional response.The structure of the flexible pipe is stable when twisted counterclockwise. However, limiting the top axial displacement can improve the axial and radial instability of the tensile armor layer when twisted clockwise. Finally, it is recommended that the flexible pipe can be kept under top fixation during service or installation to avoid torsional failure.
基金supported by the National Science Foundation of China(grant numbers 31701963 and 31801895)United States Department of Agriculture(USDA)CRIS project 5306-21000-019-00D.
文摘Ethylene-responsive element binding factors(ERFs)are involved in regulation of various stress responses in plants,but their biological functions in waterlogging stress are largely unclear.In this study,we identified a petunia(Petunia×hybrida)ERF gene,PhERF2,that was significantly induced by waterlogging in wild-type(WT).To study the regulatory role of PhERF2 in waterlogging responses,transgenic petunia plants with RNAi silencing and overexpression of PhERF2 were generated.Compared with WT plants,PhERF2 silencing compromised the tolerance of petunia seedlings to waterlogging,shown as 96%mortality after 4 days waterlogging and 14 days recovery,while overexpression of PhERF2 improved the survival of seedlings subjected to waterlogging.PhERF2-RNAi lines exhibited earlier and more severe leaf chlorosis and necrosis than WT,whereas plants overexpressing PhERF2 showed promoted growth vigor under waterlogging.Chlorophyll content was dramatically lower in PhERF2-silenced plants than WT or overexpression plants.Typical characteristics of programmed cell death(PCD),DNA condensation,and moon-shaped nuclei were only observed in PhERF2-overexpressing lines but not in PhERF2-RNAi or control lines.Furthermore,transcript abundances of the alcoholic fermentation-related genes ADH1-1,ADH1-2,ADH1-3,PDC1,and PDC2 were reduced in PhERF2-silenced plants,but increased in PhERF2-overexpressing plants following exposure to 12-h waterlogging.In contrast,expression of the lactate fermentation-related gene LDH was up-regulated in PhERF2-silenced plants,but downregulated in its overexpressing plants.Moreover,PhERF2 was observed to directly bind to the ADH1-2 promoter bearing ATCTA motifs.Our results demonstrate that PhERF2 contributes to petunia waterlogging tolerance through modulation of PCD and alcoholic fermentation system.
基金supported by Supported by the Science and Technology Research Program of the Institute of Mountain Hazards and Environment,CAS(IMHE-ZDRW-01)the National Natural Science Foundation of China,China(Grant Numbers:42077275&42271086)the Special Project of Basic Research-Key Project,Yunnan(Grant Number:202301AS070039).
文摘The present work aims to assess earthquake-induced earth-retaining(ER)wall displacement.This study is on the dynamics analysis of various earth-retaining wall designs in hollow precast concrete panels,reinforcement concrete facing panels,and gravity-type earth-retaining walls.The finite element(FE)simulations utilized a 3D plane strain condition to model full-scale ER walls and numerous nonlinear dynamics analyses.The seismic performance of differentmodels,which includes reinforcement concrete panels and gravity-type and hollowprecast concrete ER walls,was simulated and examined using the FE approach.It also displays comparative studies such as stress distribution,deflection of the wall,acceleration across the wall height,lateral wall displacement,lateral wall pressure,and backfill plastic strain.Three components of the created ER walls were found throughout this research procedure.One is a granular reinforcement backfill,while the other is a wall-facing panel and base foundation.The dynamic response effects of varied earth-retaining walls have also been studied.It was discovered that the facing panel of the model significantly impacts the earthquake-induced displacement of ER walls.The proposed analytical model’s validity has been evaluated and compared with the reinforcement concrete facing panels,gravity-type ER wall,scientifically available data,and American Association of State Highway and Transportation Officials(AASHTO)guidelines results based on FE simulation.The results of the observations indicate that the hollow prefabricated concrete ER wall is the most feasible option due to its lower displacement and high-stress distribution compared to the two types.The methodology and results of this study establish standards for future analogous investigations and professionals,particularly in light of the increasing computational capabilities of desktop computers.
基金supported by the National Defense National Defense Pre-Research Foundation of China(Grant no.301030102)。
文摘Understanding the dynamic response of composite material cartridges during the firing process is of great significance for improving their reliability and safety.A theoretical model describing the dynamic response of composite material cartridges is established based on the thick-walled cylinder theory and rate-dependent constitutive model of composite materials.The correctness of the theoretical model is validated through finite element simulations of cartridge deformation.The influence of chamber pressure and cartridge wall thickness on the cartridge's deformation process and stress distribution is analyzed.The results indicate that the primary deformation of composite material cartridges inside the chamber is elastic deformation.Compared to metal cartridges,composite material cartridges require higher pressure for touching-chamber and are more prone to developing gaps after unloading to ensure smooth extraction.During the deformation process,the touching-chamber behavior of the cartridge can improve the stress distribution.Under the same chamber pressure,the touching-chamber behavior can reduce the circumferential stress by approximately 30%.The inner wall surface of the cartridge is a critical area that requires attention.The touching-chamber behavior can be facilitated by appropriately reducing the cartridge wall thickness while ensuring overall strength.This study can provide guidance for the optimization design of composite material cartridges.
基金Science and Technology Project of Fire Rescue Bureau of Ministry of Emergency Management(Grant No.2022XFZD05)S&T Program of Hebei(Grant No.22375419D)National Natural Science Foundation of China(Grant No.11802160).
文摘As the basic protective element, steel plate had attracted world-wide attention because of frequent threats of explosive loads. This paper reports the relationships between microscopic defects of Q345 steel plate under the explosive load and its macroscopic dynamics simulation. Firstly, the defect characteristics of the steel plate were investigated by stereoscopic microscope(SM) and scanning electron microscope(SEM). At the macroscopic level, the defect was the formation of cave which was concentrated in the range of 0-3.0 cm from the explosion center, while at the microscopic level, the cavity and void formation were the typical damage characteristics. It also explains that the difference in defect morphology at different positions was the combining results of high temperature and high pressure. Secondly, the variation rules of mechanical properties of steel plate under explosive load were studied. The Arbitrary Lagrange-Euler(ALE) algorithm and multi-material fluid-structure coupling method were used to simulate the explosion process of steel plate. The accuracy of the method was verified by comparing the deformation of the simulation results with the experimental results, the pressure and stress at different positions on the surface of the steel plate were obtained. The simulation results indicated that the critical pressure causing the plate defects may be approximately 2.01 GPa. On this basis, it was found that the variation rules of surface pressure and microscopic defect area of the Q345 steel plate were strikingly similar, and the corresponding mathematical relationship between them was established. Compared with Monomolecular growth fitting models(MGFM) and Logistic fitting models(LFM), the relationship can be better expressed by cubic polynomial fitting model(CPFM). This paper illustrated that the explosive defect characteristics of metal plate at the microscopic level can be explored by analyzing its macroscopic dynamic mechanical response.
基金The sequence described in this paper has been deposited in Gen-Bank with the accession number U90431. This work was supporte
文摘All mammalian metallothionein genes studied to date have several metal responsive elements (MRE) with consensus sequences of TGCRCNC (R, purine) in their regulatory region. MRE-like sequences were also found in many other metal-related genes. To see whether there is also such a sequence at the genetic locus (13q14. 3) of Wilson disease, which is a genetic disorder of copper metabolism, junction-trapping method based on the MRE sequence was used. A fragment containing MRE and MRE-like sequences from YAC 27D8 at the WND locus was successfully cloned and mapped back to the YAC by PCR. Presence of such a sequence in the copper transporter gene at the WD locus might imply that it has a possible interesting role in the regulation of WD gene expression.
文摘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.
基金supported by the Key Research and Development Project of Zhejiang Province(Grant No.2023C01248,2023C01069)and the National Natural Science Foundation of China(Grant No.52375135,52305137).
文摘The reliability of the eddy current testing (ECT) in flaw detection is quantitatively evaluated by theprobability of detection (POD). Precise and efficient modeling of POD gives direction for the implement of ECTon sites to avoid false or missing flaw detection. Traditional POD analysis focuses on single uncertain factor orsingle response signal with limited credibility in engineering. This paper considers multiple response signals andmultiple flaw parameters to perform POD. The flaw length, the flaw depth, the coil impedance, and the magneticflux density are comprehensively studied under various lift-off distances. A finite element model (FEM) of ECT isestablished and verified with experiments to obtain sufficient simulation data for discrete POD modeling. Thecontinuous POD function is then fitted based on the discrete values to show the superiority of integrating multiplefactors. A comparison with conventional POD analysis further demonstrates the higher reliability of ECT flawdetection considering multiple flaw parameters and multiple response signals, especially for small flaws.
基金supported by grants from the National Natural Science Foundation of China(No.30771907)the Foundation of Pre-973 Program Projects(No.2009CB526411)
文摘BACKGROUND: Virological clearance, delayed progression to cirrhosis or liver cancer, and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients. Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment. This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha (ESR1) is associated with the initial response to interferon-alpha (IFN-alpha) therapy in chronic hepatitis B patients. METHODS: The initial responses of 100 patients to IFN-alpha therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1: T/T, TIC, and C/C genotype groups. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C. RESULTS: The frequency of initially combined response was markedly higher in both the T/T and TIC groups than in the C/C group (Z=10.326, P=0.006 and Z=26.247, P=0.000, respectively). In addition, the initial virological response was higher in the T/T and T/C groups than the C/C group (chi(2)=5.674, P=0.017 and chi(2)=4.980, P=0.026, respectively). In 78 initially HBeAg-positive patients, however, the frequency of initial e-antigen disappearance or seroconversion among the T/T, T/C, and C/C genotype groups was 34.15%, 27.78% and 15.79%, respectively, which were not significantly different. CONCLUSION. The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-alpha in patients with chronic hepatitis B, and might be a significant marker for predicting the initial response to IFN-alpha, at least in this study population. (Hepatobiliary Pancreat Dis Int 2010; 9: 275-279)
基金Supported by the Basic Research Program of the Korea Science & Engineering Foundation (No. 2009-0068732)the Basic Research Program of the National Research Foundation of Korea (No.2011-0020163)+1 种基金the Bio-Industry Technology Development Program funded by the Korea Institute of Planning & Evaluation for Technology in Food, Agriculture Forestry & Fisheries (No.112005-3)the BK21 Program and by the MRC program of KRF (R13-2005-012-01001-1)
文摘AIM: To study the contribution of tonicity response element binding protein(Ton EBP) in retinal ganglion cell(RGC) death of diabetic retinopathy(DR).METHODS: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin(STZ). Control mice received vehicle(phosphate-buffered saline). All mice were killed 2mo after injections, and the extent of cell death and the protein expression levels of Ton EBP and aldose reductase(AR) were examined.RESULTS: The Ton EBP and AR protein levels and the death of RGC were significantly increased in the retinas of diabetic mice compared with controls 2mo after the induction of diabetes. Terminal deoxynucleotidyl transferase(Td T)-mediated d UTP nick end labeling(TUNEL)-positive signals co-localized with Ton EBP immunoreactive RGC. These changes were increased in the diabetic retinas compared with controls.CONCLUSION: The present data show that AR and Ton EBP are upregulated in the DR and Ton EBP may contribute to apoptosis of RGC in the DR.
基金National Key Research and Development Program of China under Grant No.2016YFC0701106Natural Sciences and Engineering Research Council of Canada via Discovery under Grant No.NSERC RGPIN-2017-05556 Li
文摘The nonlinear finite element(FE) analysis has been widely used in the design and analysis of structural or geotechnical systems.The response sensitivities(or gradients) to the model parameters are of significant importance in these realistic engineering problems.However the sensitivity calculation has lagged behind,leaving a gap between advanced FE response analysis and other research hotspots using the response gradient.The response sensitivity analysis is crucial for any gradient-based algorithms,such as reliability analysis,system identification and structural optimization.Among various sensitivity analysis methods,the direct differential method(DDM) has advantages of computing efficiency and accuracy,providing an ideal tool for the response gradient calculation.This paper extended the DDM framework to realistic complicated soil-foundation-structure interaction(SFSI) models by developing the response gradients for various constraints,element and materials involved.The enhanced framework is applied to three-dimensional SFSI system prototypes for a pilesupported bridge pier and a pile-supported reinforced concrete building frame structure,subjected to earthquake loading conditions.The DDM results are verified by forward finite difference method(FFD).The relative importance(RI) of the various material parameters on the responses of SFSI system are investigated based on the DDM response sensitivity results.The FFD converges asymptotically toward the DDM results,demonstrating the advantages of DDM(e.g.,accurate,efficient,insensitive to numerical noise).Furthermore,the RI and effects of the model parameters of structure,foundation and soil materials on the responses of SFSI systems are investigated by taking advantage of the sensitivity analysis results.The extension of DDM to SFSI systems greatly broaden the application areas of the d gradient-based algorithms,e.g.FE model updating and nonlinear system identification of complicated SFSI systems.
基金supported by the National Science Foundation of China(Nos. D40444002 and D40521002)National Key Basic Research Program(No.2006CB705803)
文摘We presented a boundary element method using the approximate analytical Green's function given by Sanchez-Sesma et al. Coordinate transform is introduced to extend the method to deal with the model with constant-gradient velocity along oblique direction. The method is validated by comparing the numerical results with other independent methods. This method provides a useful tool for analyzing local site effects. We computed seismic response for two series of models. The results in both frequency and time domains are analyzed and show complex amplification patterns. The fundamental mode of resonance is dependent not only on the velocity at the free surface but also on the velocity distribution of the whole basin. For the higher modes of vibration the heterogeneous basin also has its own characteristic.
基金Foundation item: Project(IRTl125) supported by the Program for Changjiang Scholars and Innovative Research Team in Universities of China Project(B13024) supported by the "111" Project Project(BK2012811) supported by the Natural Science Foundation of Jiangsu Province, China
文摘Many high earth-rockfill dams are constructed in the west of China. The seismic intensity at the dam site is usually very high, thus it is of great importance to ensure the safety of the dam in meizoseismal area. A 3D FEM model is established to analyze the seismic responses of Shiziping earth-rockfill dam. The nonlinear elastic Duncan-Chang constitutive model and the equivalent viscoelastic constitutive model are used to simulate the static and dynamic stress strain relationships of the dam materials, respectively. Four groups of seismic waves are inputted from the top of the bedrock to analyze the dynamic responses of the dam. The numerical results show that the calculated dynamic magnification factors display a good consistency with the specification values. The site spectrum results in larger acceleration response than the specification spectrum. The analysis of relative dynamic displacement indicates that the displacement at the downstream side of the dam is larger than that at the upstream side. The displacement response reduces from the center of river valley to two banks. The displacement responses corresponding to the specification spectrum are a little smaller than those corresponding to the site spectrum. The analysis of shear stress indicates that a large shear stress area appears in the upstream overburden layer, where the shear stress caused by site waves is larger than that caused by specification waves. The analysis of dynamic principal stress indicates that the minimum dynamic stresses in corridor caused by specification and site waves have little difference. The maximum and minimum dynamic stresses are relatively large at two sides. The largest tensile stress occurs at two sides of the floor of grouting corridor, which may result in the crack near the corridor side. The numerical results present good consistency with the observation data of the grouting corridor in Wenchuan earthquake.
基金Scientific Research Deanship,Taibah University Grant No.6363/436
文摘Recent seismic events have raised concerns over the safety and vulnerability of reinforced concrete moment resisting frame "RC-MRF" buildings. The seismic response of such buildings is greatly dependent on the computational tools used and the inherent assumptions in the modelling process. Thus, it is essential to investigate the sensitivity of the response demands to the corresponding modelling assumption. Many parameters and assumptions are justified to generate effective structural finite element(FE) models of buildings to simulate lateral behaviour and evaluate seismic design demands. As such, the present study focuses on the development of reliable FE models with various levels of refinement. The effects of the FE modelling assumptions on the seismic response demands on the design of buildings are investigated. the predictive ability of a FE model is tied to the accuracy of numerical analysis; a numerical analysis is performed for a series of symmetric buildings in active seismic zones. The results of the seismic response demands are presented in a comparative format to confirm drift and strength limits requirements. A proposed model is formulated based on a simplified modeling approach, where the most refined model is used to calibrate the simplified model.
文摘At 8 weeks after intragastric administration of icariin to senescence-accelerated mice (P8 strain), Morris water maze results showed that escape latency was shortened, and the number of platform crossings was increased. Immunohistochemical staining and western blot assay detected significantly increased levels of cyclic adenosine monophosphate response element binding protein These results suggest that icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels and improves learning and memory functions in hippocampus of the senescence-accelerated mouse.
基金Projects(51275235, 50975135) supported by the National Natural Science Foundation of ChinaProject(U0934004) supported by the Natural Science Foundation of Guangdong Province, ChinaProject(2011CB707602) supported by the National Basic Research Program of China
文摘A new method for optimizing a butterfly-shaped linear ultrasonic motor was proposed to maximize its mechanical output. The finite element analysis technology and response surface methodology were combined together to realize the optimal design of the butterfly-shaped linear ultrasonic motor. First, the operation principle of the motor was introduced. Second, the finite element parameterized model of the stator of the motor was built using ANSYS parametric design language and some structure parameters of the stator were selected as design variables. Third, the sample points were selected in design variable space using latin hypercube Design. Through modal analysis and harmonic response analysis of the stator based on these sample points, the target responses were obtained. These sample points and response values were combined together to build a response surface model. Finally, the simplex method was used to find the optimal solution. The experimental results showed that many aspects of the design requirements of the butterfly-shaped linear ultrasonic motor have been fulfilled. The prototype motor fabricated based on the optimal design result exhibited considerably high dynamic performance, such as no-load speed of 873 ram/s, maximal thrust of 27.5 N, maximal efficiency of 43%, and thrust-weight ratio of 45.8.
基金Acknowledgment We thank Dr Etty N. Benveniste (University of Alabama at Birmingham, Birmingham, AL, USA) for the truncated MMP-2 promoter-driven luciferase constructs and Ms Donna Barnes for excellent secretarial assistance. This study was supported by KU William L.Valk Endowment and Kansas Mason's Foundation, and a grant from KUMC Lied Foundation to Dr Ben-Yi Li. This study was also partially supported by grants from the National Natural Science Foundation of China (No. 30370509 and No. 30370645) to Dr Ping-Yi Xu.
文摘Aim: To characterize the matrix metalloproteinases (MMP)-2 promoter and to identify androgen response elements (AREs) involved in androgen-induced MMP-2 expression. Methods: MMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction (RT-PCR). MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays (EMSA) were used to verify the identified AREs in the MMP-2 promoter. Results: Androgen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1591 to -1259 (relative to the start codon) of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5'-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor (AR) interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay. Conclusion: Two ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.
基金Project(51308193)supported by the National Natural Science Foundation of ChinaProject(SGKJ[2007]116)supported by the Science and Technology Program of State Grid Corporation of China
文摘In order to study the sliding characteristics when the cable is connected with the other rods in the transmission line structures,a linear sliding cable element based on updated Lagrangian formulation and a sliding catenary element considering the out-of-plane stiffness coefficient are put forward.A two-span and a three-span cable structures are taken as examples to verify the sliding cable elements.By comparing the tensions of the two proposed cable elements with the existing research results,the error is less than 1%,which proves the correctness of the proposed elements.The sliding characteristics should be considered in the practical engineering because of the significant difference between the tensions of sliding cable elements and those of cable element without considering sliding.The out-of-plane stiffness coefficient and friction characteristics do not obviously affect the cable tensions.
基金Scientific Research Foundation of Liaoning Provincial Education Department for Higher Education Institutions, No.05L442
文摘BACKGROUND: cAMP-response element binding protein (CREB) is a key modulator of various signaling pathways. CREB activation initiates a series of intracellular signaling pathways that promote neuronal survival. OBJECTIVE: To investigate the regulatory effects of basic fibroblast growth factor (bFGF) on cerebral neuronal CREB expression following ischemia/reperfusion injury. DESIGN, TIME AND SETTING: An immunohistochemical detection experiment was performed at the Department of Anatomy, Shenyang Medical College, between October 2006 and April 2008. MATERIALS: A total of 60 healthy, adult, Wistar rats were randomly divided into three groups: sham-operated (n =12), ischemia/reperfusion (n = 24), and bFGF-treated (n = 24). Rabbit anti-rat CREB (1: 100) and biotin labeled goat anti-rabbit IgG were purchased from the Wuhan Boster Company, China. MetaMorph-evolution MP5.0-BX51 microscopy imaging system was provided by China Medical University, China. METHODS: Rat models of cerebral ischemia/reperfusion injury were developed using the suture method for right middle cerebral artery occlusion. Two-hour ischemia was followed by reperfusion. Rats from the bFGF-treated and ischemia/reperfusion groups were intraperitoneally administered endogenous bFGF (500 IU/mL, 2 000 IU/kg) or an equal amount of physiological saline. Rats from the sham-operated group underwent a similar surgical procedure, without induction of ischemia/reperfusion injury and drug administration. MAIN OUTCOME MEASURES: After 48-hour reperfusion, hippocampal and parietal cortical neuronal CREB expression was detected by immunohistochemistry, and the absorbance of hippocampal CREB-positive products was determined using MetaMorph-evolutionMP5.0-BX51 microscopy imaging system. RESULTS: The sham-operated group exhibited noticeable CREB expression in hippocampal and parietal cortical neurons. In the ischemia/reperfusion group, the CREB expression was discrete and neurons were poorly arranged. The bFGF-treated group exhibited increased CREB expression and better neuronal arrangement compared with the ischemia/reperfusion group. The mean absorbance of CREB-immunoreactive products in the hippocampus and parietal cortex was significantly higher in the ischemia/reperfusion group than in the sham-operated group (P 〈 0.05), and significantly higher in the bFGF-treated group than in the ischemia/reperfusion group (P 〈 0.05). CONCLUSION: bFGF significantly upregulates CREB expression in hippocampal and parietal cortical neurons following ischemia/reperfusion injury.