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121.
以ABAQUS软件为平台,开发热-弹-塑性有限元方法模拟了V形坡口和K形坡口Q345/SUS304异种钢多层焊对接接头的温度场、残余应力和焊接变形.同时采用试验的方法测量了接头的残余应力和角变形.计算结果与试验测量结果吻合良好,验证了计算方法的妥当性.数值结果表明,不同坡口Q345/SUS304异种钢接头的Q345母材与焊缝交界处的应力分布均出现不连续性,且SUS304侧的高拉伸残余应力区明显宽于Q345侧;K形坡口开口朝向Q345侧相较于开口朝向SUS304侧的接头,Q345/焊缝交界处附近的峰值应力和高拉伸残余应力区均明显较小.试验和数值结果表明,坡口形式对接头的角变形有明显的影响. 相似文献
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针对2.0 mm厚的AZ31B镁合金以及1.0 mm厚的SPHC镀锌钢板,采用KDWJ-17型三相次级整流电阻焊机进行焊接试验,通过光学金相、扫描电镜等方法分析接头各区域的组织结构和成分分布.提出了镁锌低熔点化合物挤压机制,分析了Zn元素在镁合金和镀锌钢板电阻点焊中的作用.结果表明,Zn与Mg元素形成的低熔点化合物MgZn2在电极压力的作用下能填满由于焊接变形引起的间隙,使反应界面密封,促进Fe,Al元素在界面发生处扩散,Fe与Al元素在界面处发生反应生成Fe2Al5化合物,从而形成高强度的镁合金与镀锌钢板的电阻点焊接头. 相似文献
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Cynthia M. Simbulan-Rosenthal Yogameenakshi Haribabu Sahar Vakili Li-Wei Kuo Havens Clark Ryan Dougherty Ryyan Alobaidi Bonnie Carney Peter Sykora Dean S. Rosenthal 《International journal of molecular sciences》2022,23(4)
Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC) implicated in tumorigenesis, invasion, and drug resistance, and is characterized by the elevated expression of stem cell markers, including CD133. The siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133’s anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRASQ61K and NRASQ61R drivers, after CRISPR-Cas9 CD133 knockout or Dox-inducible expression of CD133. MACS-sorted CD133(+) BAKP cells were conditionally reprogrammed to derive BAKR cells with sustained CD133 expression and MIC features. Compared to BAKP, CD133(+) BAKR exhibit increased cell survival and reduced apoptosis in response to trametinib or the chemotherapeutic dacarbazine (DTIC). CRISPR-Cas9-mediated CD133 knockout in BAKR cells (BAKR-KO) re-sensitized cells to trametinib. CD133 knockout in BAKP and POT cells increased trametinib-induced apoptosis by reducing anti-apoptotic BCL-xL, p-AKT, and p-BAD and increasing pro-apoptotic BAX. Conversely, Dox-induced CD133 expression diminished apoptosis in both trametinib-treated cell lines, coincident with elevated p-AKT, p-BAD, BCL-2, and BCL-xL and decreased activation of BAX and caspases-3 and -9. AKT1/2 siRNA knockdown or inhibition of BCL-2 family members with navitoclax (ABT-263) in BAKP-KO cells further enhanced caspase-mediated apoptotic PARP cleavage. CD133 may therefore activate a survival pathway where (1) increased AKT phosphorylation and activation induces (2) BAD phosphorylation and inactivation, (3) decreases BAX activation, and (4) reduces caspases-3 and -9 activity and caspase-mediated PARP cleavage, leading to apoptosis suppression and drug resistance in melanoma. Targeting nodes of the CD133, AKT, or BCL-2 survival pathways with trametinib highlights the potential for combination therapies for NRAS-mutant melanoma stem cells for the development of more effective treatments for patients with high-risk melanoma. 相似文献
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Matthew K. Boag Angus Roberts Vladimir N. Uversky Linlin Ma Des R. Richardson Dean L. Pountney 《International journal of molecular sciences》2022,23(4)
A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated α-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation. 相似文献
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Automata theory, algorithmic deduction and abstract interpretation provide the foundation behind three approaches to implementing program verifiers. This article is a first step towards a mathematical translation between these approaches. By extending Büchi’s theorem, we show that reachability in a control flow graph can be encoded as satisfiability in an extension of the weak, monadic, second-order logic of one successor. Abstract interpreters are, in a precise sense, sound but incomplete solvers for such formulae. The three components of an abstract interpreter: the lattice, transformers and iteration algorithm, respectively represent a fragment of a first-order theory, deduction in that theory, and second-order constraint propagation. By inverting the Lindenbaum–Tarski construction, we show that lattices used in practice are subclassical first-order theories. 相似文献
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