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Objective The ataxia telangiectasia mutated (ATM) gene is a master regulator in cellular DNA damage response. The dysregulation of ATM expression is frequent in breast cancer, and is known to be involved in the carcinogenesis and prognosis of cancer. However, the underlying mechanism remains unclear. The bioinformatic analysis predicted a potential antisense transcript ATM-antisense (AS) from the opposite strand of the ATM gene. The purpose of this study was to identify ATM-AS and investigate the possible effect of ATM-AS on the ATM gene regulation. Methods Single strand-specific RT-PCR was performed to verify the predicted antisense transcript ATM-AS within the ATM gene locus. qRT-PCR and Western blotting were used to detect the expression levels of ATM-AS and ATM in normal and breast cancer cell lines as well as in tissue samples. Luciferase reporter gene assays, biological mass spectrometry, ChIP-qPCR and RIP were used to explore the function of ATM-AS in regulating the ATM expression. Immunofluorescence and host-cell reactivation (HCR) assay were performed to evaluate the biological significance of ATM-AS in ATM-mediated DNA damage repair. Breast cancer tissue samples were used for evaluating the correlation of the ATM-AS level with the ATM expression as well as prognosis of the patients. Results The ATM-AS significantly upregulated the ATM gene activity by recruiting KAT5 histone acetyltransferase to the gene promoter. The reduced ATM-AS level led to the abnormal downregulation of ATM expression, and impaired the ATM-mediated DNA damage repair in normal breast cells in vitro. The ATM-AS level was positively correlated with the ATM expression in the examined breast cancer tissue samples, and the patient prognosis. Conclusion The present study demonstrated that ATM-AS, an antisense transcript located within the ATM gene body, is an essential positive regulator of ATM expression, and functions by mediating the binding of KAT5 to the ATM promoter. These findings uncover the novel mechanism underlying the dysregulation of the ATM gene in breast cancer, and enrich our understanding of how an antisense transcript regulates its host gene.

Antibiotic resistance genes (ARGs) as emergence contaminations have spread widely in the water environment. Wild fish may be recipients and communicators of ARGs in the water environment, however, the distribution and transmission of ARGs in the wild fish and relevant water environment were rarely reported. Here, we have profiled ARGs and bacterial communities in wild freshwater fish and relevant water in a peri-urban river using high-throughput qPCR and 16S rRNA gene sequence. A total of 80 and 220 unique ARG subtypes were identified in fish and water samples. Fish and water both showed significant ARG seasonal variations (P0.05). The highest absolute abundance of ARGs in fish and water occurred in summer (1.32 × 10

Abuse of antibiotics in aquaculture have been alarming and might aggravate spread of resistance genes in the environment. Holistic ARGs proliferation checks require deeper analyses of coupled absolute abundances in 16S rRNA bacteria communities at the phylum level to detect biomarkers. Sulfanilamide (sul) and copper II sulfate (CuSO4 II) were, therefore, designed and added as separate or combined treatments in 9 replicate engineered goldfish tanks comprising 3 individual sul, 3 CuSO4 II, 3 (sul + CuSO4 II) combinations, and 3 controls within 180 days. The DNA from water and fish guts was sequenced under qPCR to determine 16S rRNA bacteria biomarkers co-occurring with the correspondent ARGs. Combined chemical addition at 0.8–1.5 mg sul + 0.5–1.0 mg CuSO4 II/3 L of tank waters reduced sequenced 16S rRNA bacteria absolute abundances in fish gut and water samples while portraying the biomarkers. Absolute abundances of the entire 16S rRNA bacteria was higher in fish guts (3.4 × 1014–4.9 × 108 copies/g) than water samples (1.5 × 109–2.6 × 1015 copies/L), respectively. Much as sul 1(log) were dominant over intl 1(log) genes, and their fundamental profiles were also higher in the fish guts than water samples; the Spearman’s correlation analyses revealed positive relationship (p Proteobacteria (10–50:15–65%) > Planktomycetes (10–52:8–25%) featured prominently based on LEfSe use as the hot-spotted biomarkers, hence justifying its higher prospects towards innovative environmental microbiological and biotechnological studies.

A novel color image encryption algorithm based on coarse-grained fractional chaotic system signals is proposed in this paper. First, color images are divided into three channels, which are encrypted based on the corresponding three states of the chaotic system. Second, the chaotic systems are defined as fractional chaotic, in which the fractional order enlarges the parameter space. Third, the fractional chaotic signals are handled with unfixed coarse-grained methods instead of being utilized directly. In addition, the original image and the chaotic signals are divided into bit signals from the pixel values, and the high and low bits are encrypted, respectively. To demonstrate the effectiveness and robustness of the proposed color image encryption algorithm, its properties, including the key space, information entropy, correlation analysis, key sensitivity, and resistance to differential attacks, are provided using a numerical simulation.

In this study, a networked spatiotemporal chaotic map model is proposed based on the traditional coupled map lattice system. In addition, the time delay and variable topology parameters are considered to make the system more practical. The chaotic properties are analyzed using a bifurcation diagram, Lyapunov exponents, and entropies. In addition, institute of standards and technology tests are conducted to further analyze the randomness of the system signal. Based on the proposed system, a three-dimensional encryption algorithm is designed to encrypt multiple color images with scrambling and diffusion at the bit level. Several analyses, including histogram analysis, information entropy analysis, correlation analysis, key sensitivity, differential attack analysis, and resistance analyses, are performed to test the effectiveness and robustness of the proposed multiple image encryption algorithm with a networked chaotic map model.

The significant rise in the number of antibiotic resistance genes (ARGs) that resulted from our abuse of antibiotics could do severe harm to public health as well as to the environment. We investigated removal efficiency and removal mechanism of electrochemical (EC) treatment based on 6 different bacteria isolated from hospital wastewater carrying 3 last resort ARGs including NDM-1, mcr-1 and tetX respectively. We found that the removal efficiency of ARGs increased with the increase of both voltage and electrolysis time while the maximum removal efficiency can reach 90%. The optimal treatment voltage and treatment time were 3 V and 120 min, respectively. Temperature, pH and other factors had little influence on the EC treatment process. The mechanism of EC treatment was explored from the macroscopic and microscopic levels by scanning electron microscopy (SEM) and flow cytometry. Our results showed that EC treatment significantly changed the permeability of cell membrane and caused cells successively experience early cell apoptosis, late cell apoptosis and cell necrosis. Moreover, compared with traditional disinfection methods, EC treatment had less potential risks. The conjugative transfer frequencies of cells were significantly reduced after treatment. Less than 1% of bacteria entered the viable but nonculturable (VBNC) state and less than 5% of intracellular ARGs (iARGs) turned into extracellular ARGs (eARGs). Our findings provide new insights into as well as important reference for future electrochemical treatment in removing ARB from hospital wastewater.

Hospital wastewater contains abundant antibiotics, antibiotic resistance genes (ARGs), and pathogens. Last-resort antibiotic resistance genes (LARGs) include the New Delhi metallo-β-lactamase gene blaNDM, mobile colistin resistance gene mcr and tigecycline resistance gene tet(X) which confers resistance to carbapenems, colistin and tigecycline. The presence and significance of LARGs in hospital wastewater treatment systems (HWTS) have not yet been systematically explored. Here, LARG variants were shown to be prevalent both influents and effluents of HWTS. A total of 989 Enterobacteriaceae isolates that confer resistance to last-resort antibiotics were collected from effluents and multiple genetic contexts of LARGs were analyzed. LARGs-carrying plasmids were confirmed to show high multidrug phenotypes and transferability. We also discovered the co-occurrence of plasmids harboring blaNDM-1 and mcr-1 in single Escherichia coli, as well as E. coli HM016 containing two unique mcr-1-carrying plasmids. This result might accelerate co-dissemination of LARGs under environmental selection pressure. Different core genetic arrangements in these strains suggest several evolutionary pathways in HWTS. The resistance functions of LARGs were confirmed in vitro and in vivo by mass spectrometry. This study provides novel insights into the diversity, genetic context and function of critical ARGs in HWTS. The results raise the concern that LARGs may further spread into the environment, thus, more stringent discharge standards and regulations for hospital wastewater are urgently needed.

Objective: To study the effects of resveratrol on apoptosis of rat brain during ischemiareperfusion and on NLRP3 inflammatory bodies, Caspase-1 and ZO-1 in microglia. Methods: According to the random digital table method, forty-five male Sprague-Dawley rats were divided into the sham-operated group (blank control group), cerebral ischemia-reperfusion group (IR control group) and resveratrol treatment group, with 15 rats in each group. After the establishment of cerebral ischemia-reperfusion model by suture method, the effects of different methods on the expression of apoptosis-related molecules (promoters, suppressors) in brain tissue, microglial NLRP3 inflammatory bodies, Caspase-1 and ZO-1 in SD rats were compared. Results: The content of apoptosis-related molecules (CytC, AIF, Caspase-8, Caspase-9, Fas, FasL) in the sham-operated group was significantly lower than that in IR control group and resveratrol group, and the content in IR control group was significantly higher than that in resveratrol group (P

The occurrence of viable but non-culturable (VBNC) bacteria in the wastewater system poses a huge threat to environmental and public health, in particular in hospital wastewater treatment system (HWTS). HWTS-oriented studies have been conducted to assess the effectiveness of chlorination and UV disinfection using indigenous bacteria. Results revealed that the VBNC Escherichia coli and ARGs remained persistent even at high chlorination (12 mg/L for 2.5 h) and UV doses (1000 mJ/cm2). The molecular mechanisms underlying chlorination-/UV-induced VBNC state in E. coli were explored through the transcriptomics and results suggested that most energy-dependent physiological activities (e.g., metabolism) have been suppressed in VBNC E. coli, while the pathogenicity-related genes varied insignificantly compared to the culturable cells, indicating that the VBNC E. coli could potentially display pathogenicity. Further Galleria mellonella model experiment has confirmed that although the disinfection-induced VBNC state made cells less infectious, these cells could regain their pathogenicity after resuscitation. This in vitro study can be used as a reference for studies on infections from VBNC bacteria and highlights the health risk due to VBNC pathogens in hospital effluents. There is a need to develop effluent standards specifically for healthcare facilities, and a stricter downstream disinfection strategy should be considered for the removal of VBNC cells and ARGs in the effluent.

A fully convolutional encoder–decoder network (FCEDN), a deep learning model, was developed and applied to image scanning microscopy (ISM). Super-resolution imaging was achieved with a 78 μm × 78 μm field of view and 12.5 Hz–40 Hz imaging frequency. Mono and dual-color continuous super-resolution images of microtubules and cargo in cells were obtained by ISM. The signal-to-noise ratio of the obtained images was improved from 3.94 to 22.81 and the positioning accuracy of cargoes was enhanced by FCEDN from 15.83 ± 2.79 nm to 2.83 ± 0.83 nm. As a general image enhancement method, FCEDN can be applied to various types of microscopy systems. Application with conventional spinning disk confocal microscopy was demonstrated and significantly improved images were obtained.

The transcription of eukaryotic genes is regulated by both proximal promoters and distal enhancers. Some promoters also have enhancer activity. NOXA and BCL2 are pro-apoptotic and anti-apoptotic members of the BCL2 family of protein, respectively. Our previous study has found that the NOXA gene promoter and the BCL2 gene promoter interact at the level of three-dimensional chromatin structure. Moreover, the NOXA gene promoter region displays histone modifications characteristic of both promoters and enhancers. This study aimed to explore whether and when the NOXA promoter could act as an active enhancer to regulate BCL2 expression. Based on the apoptosis model of MCF-7 cells induced by camptothecin, we used chromosome conformation capture (3C), quantitative real-time PCR (qRT-PCR) and the luciferase reporter gene technology to demonstrate that the NOXA promoter could function as an active enhancer and physically interact with the BCL2 promoter through chromatin looping. The regulatory properties of the NOXA promoter were closely related to the strength of the apoptosis stimulation. Under weak apoptotic stimulation (1 μmol/L camptothecin treatment), the NOXA promoter mainly functioned as an enhancer; with the enhancement of apoptotic stimulation (10 μmol/L camptothecin treatment), the NOXA promoter activity increased and mainly regulated the expression of the gene itself to promote apoptosis. Chromatin immunoprecipitation (ChIP) confirmed that the dynamic changes of the promoter activity and enhancer activity in the NOXA promoter region are consistent with its histone modification marks. This study provides new clues for further exploring the mechanism underlying cooperative response of BCL2 family member to apoptosis stimuli.真核生物基因的转录受到近端启动子和远端增强子的共同调控,部分基因的启动子可兼具有增强子的活性。NOXA与BCL2分别是BCL2蛋白家族促凋亡和抗凋亡成员。本课题组前期研究发现,NOXA基因启动子与BCL2基因启动子在染色质三维空间结构上存在相互作用,且NOXA基因启动子区兼有启动子和增强子特征性的组蛋白修饰标记。为进一步探究NOXA启动子是否具有增强子活性、能否在细胞凋亡过程中作为增强子调控BCL2基因表达,本研究利用染色质构象捕获(chromosome conformation capture, 3C)、实时荧光定量PCR (quantitative real-time PCR, qRT-PCR)和荧光素酶报告基因等检测技术在喜树碱诱导的MCF-7细胞凋亡模型中证实,NOXA启动子兼具增强子活性,并可通过形成染色质环结构远程调控BCL2基因表达。NOXA启动子的调控属性与凋亡信号强弱密切相关,在较弱凋亡信号刺激下(1 μmol/L喜树碱处理),NOXA启动子主要发挥增强子功能;随着凋亡刺激信号的加强(10 μmol/L喜树碱处理),NOXA启动子活性增强,主要调控其基因自身的表达,促进细胞凋亡。染色质免疫共沉淀(chromatin immunoprecipitation, ChIP)证实NOXA启动子区启动子活性和增强子活性的动态变化与其组蛋白修饰标志一致。本研究为进一步探讨BCL2家族成员对细胞凋亡刺激做出协同反应的机制提供了新的线索。.

Background: Environmental spread of antibiotic resistance has become a public health problem, but the relationship between air quality and antibiotic resistance has not been fully investigated, the effect and mechanism of air pollutants on horizontal genes transfer of antibiotic resistance are rarely mentioned. Results: In the present study, significant correlation ( P < 0.05) between resistance rates of 10 clinical antibiotic-resistant pathogens and number of days when air quality index was below 100 were observed in an extensive survey from 2014 to 2017 in China. In addition, characterization of antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and bacterial communities in airborne particulate matter (PM), dust, and human airway sputum samples were profiled in a hospital. PM 2.5 and PM 10 were shown to contain ARGs and MGEs high relative abundance and diversity index. Importantly, transferable multi-resistant plasmids were identified from air, e.g., pTAir-3 with 26 MGEs and 10 ARGs, using conjugative mating assays and nanopore sequencing . Furthermore, PM 2.5 and PM 10 significantly enhanced the conjugative transfer frequencies between bacteria, via inducing increased levels of reactive oxygen species and cell membrane permeability; upregulated gene expression levels were confirmed by genome-wide RNA sequencing. Conclusions: These findings provide a new perspective on antibiotic resistance research and have profound implications for antibiotic resistance control in clinics and environments.

The activation of long interspersed nuclear element-1 (LINE-1) leads to genomic instability, which promotes carcinogenesis and drug resistant. Therefore, exploring the mechanism underlying LINE-1 abnormal activation has the theoretical and clinical significance. DNA methylation is an important way to regulate gene expression. DNMT3a, one member of the DNA methyltransferase family, not only inhibits gene expression by inducing promoter hypermethylation, but also activates gene expression by increasing the intragenic DNA methylation. Our previous studies found that the expression of LINE-1 did not increase significantly in the promoter methylation in breast cancer cells treated with paclitaxel (PTX), a first-line chemotherapeutic drug for breast cancer. Here we explored whether DMNMT3a could directly mediate the drug-induced activation of LINE-1 in breast cancer cells through increasing the LINE-1 intragenic methylation. Our ChIP experiments and methyl analysis showed that treatment of breast cancer cells with PTX not only induced DNMT3a expression, but also promoted the binding of DNMT3a to the inner region of the药物诱导的长散在重复序列LINE-1异常激活可促进细胞基因组不稳定,而基因组不稳定是促进肿瘤发生发展和耐药表型形成的重要因素。因此,探索LINE-1异常激活的分子机制具有重要的理论和临床意义。DNA甲基化是调控基因表达的重要方式,已知DNA甲基转移酶家族成员DNMT3a不仅能通过促进基因启动子甲基化抑制基因表达,还可通过增强基因内部甲基化上调基因表达。本实验室前期研究发现,将乳腺癌细胞暴露于化疗药物可诱导LINE-1异常高表达,但LINE-1启动子甲基化水平并无显著改变。本研究进一步探讨了在化疗药物压力下DNMT3a是否可通过增强LINE-1基因内部甲基化水平促进LINE-1在乳腺癌细胞中的异常高表达。ChIP实验和甲基分析结果显示,用化疗药物紫杉醇(PTX)处理乳腺癌细胞,不仅可以诱导DNMT3a表达,而且可以促进DNMT3a与LINE-1基因内部区域的结合,提升其基因内部甲基化水平, 进而上调LINE-1的表达水平。利用表达载体增加细胞内DNMT3a的表达水平,可显著上调LINE-1基因内部的甲基化及基因的表达水平,而下调DNMT3a的表达可有效抑制LINE-1表达。上述研究结果表明,DNMT3a介导的基因非启动子区甲基化在药物诱导的LINE-1异常激活中发挥重要作用,为认识LINE-1在乳腺癌化疗耐药性形成过程中异常激活的机制提供了新思路。.

With the worldwide use and modern development of acupuncture-moxibustion, there is disagreement on its basic definition. There has been an obstacle for clinical practice, research, and legislation. Considering this challenge, the World Federation of Acupuncture-Moxibustion Societies proposes to develop the definition and basic scope of acupuncture-moxibustion with a Delphi study. A reactive Delphi method will be used to ask a group of experts to rate the relevance and clarity of a predesigned initial item list. This list was generated by the steering committee through a literature review and group discussion. Forty experts will be selected from many disciplines and continents to ensure appropriate representation. Predefined rules will be applied to modify the items until a consensus is achieved. After achieving the consensus on all items through the survey round, the steering committee will form the definition and basic scope of acupuncture-moxibustion by organizing a literal statement with a detailed explanation.

Swimming pools are crowd-gathering places that are associated with numerous outbreaks of water-borne diseases. Herein, we investigated the distribution of antibiotic resistance genes (ARGs) and bacterial communities in swimming pools and determined the influencing factors and potential human exposure. Sixteen swimming pools with different bather loads (0.01-0.16 person/m2·h) were investigated. Water samples were collected, before opening and after closing of the facilities, from six swimming pools, and skin samples were collected from volunteers. Comprehensive approaches, high-throughput qPCR and 16S rRNA gene sequencing, were used. The results showed that swimming pools contained a higher relative abundance (0.62 gene copies/16S rRNA) and absolute abundance (6.57×108 gene copies/L) of ARGs on average. Bather loads contributed to the increase of core ARGs, and the absolute abundance of ARGs significantly increased by 1.47-1.94 orders of magnitude when the bather load was more than 0.1 person/m2·h. Dermal contact was estimated as the main exposure route of ARGs. Eighteen ARGs that were not detected before swimming were found on human skin and remained after showering. Furthermore, the event intake burden of ARGs via dermal contact was higher than that via ingestion when swimming. This study provides an assessment of ARGs and antibiotic-resistant bacteria (ARB) in swimming pools and helps to define the health risks to swimmers.

Background Cartilaginous endplate (CEP), a thin layer of hyaline cartilage located between the vertebral endplate and nucleus pulposus, transports the nutrient into the disc. The objective of this study was to evaluate the influence of T140 (polyphemusin II-derived peptide) on the CEP cell growth, apoptosis, and the matrix formation via the stromal cell-derived factor-1 (SDF-1)/cysteine X cysteine (CXC) receptor-4 (CXCR4) signaling pathway. Methods Sprague-Dawley rats were euthanized by cervical dislocation and dissected for the isolation and the appraisal of CEP cells that were extracted from the endplate in rat intervertebral discs and were then added with different concentrations of reagents (SDF-1 and T140). The effect of T140 on CEP cell proliferation and apoptosis were analyzed. The messenger RNA (mRNA) and protein expressions of CXCR4, prominin-1, proteoglycans, type II collagen, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein were analyzed by reverse transcription quantitative polymerase chain reaction and Western blot analysis. Results T140 promoted the proliferation of CEP cells and inhibited the apoptosis of CEP cells. Additionally, T140 suppressed the mRNA and protein expression of CXCR4, prominin-1, and Bcl-2 associated X protein, and increased the mRNA and protein expression of proteoglycans, type II collagen, and Bcl-2. Conclusions T140 promotes the proliferation and matrix formation and inhibits the apoptosis of CEP cells by blocking the SDF-1/CXCR4 signaling pathway in vitro, which provides a certain therapeutic effect on the degeneration of intervertebral discs.

In this paper, a novel method for lossless image encryption based on set partitioning in hierarchical trees and cellular automata. The proposed encryption method embeds the encryption into the compression process, in which a small part of the data is encrypted quickly, while maintaining the good coding characteristics of set partitioning in hierarchical trees (SPIHT). The proposed encryption system adopts three stages of scrambling and diffusion. In each stage of encryption, different chaotic systems are used to generate the plaintext-related key stream to maintain high security and to resist some attacks. Moreover, the channel length of the coded-and-compressed color image is more uncertain, resulting into higher difficulty for attackers to decipher the algorithm. The experimental results indicate that the length of bitstream is compressed to 50% of the original image, showing that our proposed algorithm has higher lossless compression ratio compared with the existing algorithms. Meanwhile, the encryption scheme passes the entropy analysis, sensitivity analysis, lossless recovery test, and SP800-22 test.

In this paper, a novel high dimensional spatiotemporal chaotic system based on 2D non-adjacent coupled map lattice (2DNACML) model is proposed. Each local lattice is influenced by other random lattices in different dimensions and the local map is defined as a fractional-like style. From the theoretical analysis and numerical simulation, it is found that ranges of system parameters are expanded and unfixed in the novel 2DNACML model. As a result, the changed system is improved and been applied in the image encryption with a mixed scrambling scheme with chaotic method and knights tour method and an efficient diffusion scheme for different images to show the effectiveness of the proposed system.

To relieve the traffic congestion in urban areas, one approach is to modify the current planning scheme based on the balance between traffic supply and demand. Based on the proposed GIS platform, this paper analyzes the interactive relationship between land use and traffic system. Feasibility judgment of planning scheme is implemented based on land attribute, represented by urban floor area ratio and road area ratio. TransCAD based simulation is used to evaluate the planning scheme by traffic flow and the saturation of each link. Comparisons between traffic generation and traffic network capacity, based on a two-dimensional model of Space and Time Consuming Method, is presented to verify the coordination between urban traffic and land use. A real-world case study is implemented to test the efficiency and applicability of the proposed model and computing methods.

This paper presents a sequential coupled thermo-metallurgical-mechanical finite element model for low alloy steel quenching which can be used to predict temperature history, evolution of microstructure, internal stress and distortion. The main efforts are to develop a series of subroutines which consider the latent heat released due to phase transformation and numerical implementation of a thermo-metallurgical-mechanical constitute equation. The effectiveness of developed computational method is confirmed by a immersion quenching. Simulations of immersion quenching demonstrate that transformation induce plasticity has significant effect of the evolution of residual stress, distortion and can not be neglected for low alloy steel during immersion quenching.

Technology innovation, knowledge innovation and talent development were treated as a mutually embedded parallel process. Technological innovation as the carrier , it analyzed knowledge innovation, talent development and the coupling evolution mechanism in the different stages of technology innovation.

Background An adductor canal block (ACB) provides recognized analgesia following total knee arthroplasty (TKA). This meta-analysis compared the single-injection ACB (SACB) with the continuous-injection ACB (CACB). Method Relevant studies were searched from PubMed (1996-October 2018), Embase (1980-October 2018), and Cochrane Library (CENTRAL, October 2018). Four randomized controlled trials (RCTs), which compared SACB with CACB, were included in our meta-analysis. Results Four RCTs met the inclusion criteria. Our pooled data indicated that the SACB group had similar efficacy compared with the CACB group in terms of morphine consumption (P = .19), time to first opioid request (P = .32), range of motion (P = .97), and visual analogue scale (VAS) scores at 24 hours at rest (P = .12) and movement (P = .24), without increasing the risk of complications (P = .97) and length of stay (P = .54). Conclusion The SACB technique provides similar analgesia in the 24 hours following TKA compared with CACB, while the CACB method was better over 48 hours.

The objective of this paper provides a numerical implementation procedure of thermo-metallurgical-mechanical constitute equation based on additively decomposition of strain rate. Together with phase transformation kinetics, the macro material properties are determined by assigning temperature dependent material properties to each phase and by applying mixture rule to combine. Then the constitute equation is implemented into general purpose implicit finite element program via user material subroutine. The effectiveness of developed computational method is confirmed by a Satoh test simulation. Simulation of Satoh test demonstrates that transformation induce plasticity has significant effect of the evolution of residual stress and can not be neglected for alloy steel during hot working process.

The objective of this paper is to investigate the effects of solid-state phase transformation on welding residual stress in high stress low alloy steel. In this study, based on commercial finite element software, a sequentially coupled thermal, metallurgical, mechanical plane strain finite element model is developed. The main effort is to develop a series of subroutines which consider the heat transfer from welding arc and numerical implementation of a thermo-metallurgical-mechanical constitute equation. The effectiveness of developed computational method is confirmed by a butt welding simulation. Simulation of butt welding demonstrates that the distribution pattern of longitudinal residual stresses perpendicular to weld centerline at the upper surface of weldment has two peak and transformation plasticity has significant effect on the evolution of residual stress.

The multidrug resistance 1 (MDR1) gene product P-glycoprotein is an ATP-dependent efflux pump associated with chemotherapy failure in breast cancer. In the present study, we show that paclitaxel induces MDR1 expression in the MCF-7 breast cancer cell line in a MAPK/Egr-1-dependent manner. Paclitaxel exposure activated the Erk1/2/MAPK pathway and promoted the accumulation of the early response transcription factor Egr-1 in MCF-7 cells. Egr-1 binds to the GC element on the proximal MDR1 promoter to enhance MDR1 transcription. Loss of Egr-1 function in paclitaxel-resistant MCF-7 cells decreased MDR1 expression, whereas inhibiting Erk1/2 activity reduced both Egr-1 accumulation and MDR1 expression. These findings suggest that Erk1/2-induced Egr-1 accumulation activates MDR1 transcription and thereby induces the drug resistance observed in paclitaxel-resistant MCF-7 cells. Further mechanistic studies indicate that Egr-1 most likely does not induce the constitutive activation of Erk1/2 through its target gene geranylgeranyl diphosphate synthase (GGPPS), which regulates Ras prenylation. Indeed, our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.