Systematic Modeling of Workpiece-Fixture Geometric Default and Compliance for the Prediction of Workpiece Machining Error

Control of workpiece machining error (WME) is a key concern in the design of a fixture system. In this paper, source errors, which are categorized into workpiece-fixture geometric default and workpiece-fixture compliance, are systematically investigated to reveal their effects upon the WME. The underlying mechanism is that source errors lead to the workpiece position error (WPE), the workpiece elastic deformations (WED), and the inconsistent datum error (IDE), and all of them will contribute together to the WME. Here, the IDE refers to the dimension deviation of the processing datum from the locating datum once two references do not coincide. An overall quantitative formulation is proposed for the computing of WME in terms of WPE, WED, and IDE for the first time. In detail, the WPE raised in the workpiece-locating and clamping process is evaluated based on the geometric defaults and local deformations of workpiece-fixture in the contact region. The WED relative to the workpiece-clamping process is determined by solving a nonlinear mathematical programming problem of minimizing the total complementary energy of the frictional workpiece-fixture system. Some numerical tests are finally demonstrated to validate the proposed approach on the basis of both theoretical and experimental data given in the references.

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lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22031407 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1407

Author(s):

Hongxia Liu ◽

Wang Zheng ◽

Qianping Chen ◽

Yuchuan Zhou ◽

Yan Pan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Line ◽

Malignant Tumors ◽

Underlying Mechanism ◽

Mtor Pathway ◽

Rna Seq ◽

Cellular Autophagy ◽

First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

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Marrying Medicine and Materials: Artemisinin (Qinghaosu) Particle is Soft Enough for Scratching Hard SiC Wafer in Water

ScienceOpen Research ◽

10.14293/s2199-1006.1.sor-matsci.amnmzs.v1 ◽

2016 ◽

Author(s):

Yu-rong Zhu ◽

Dan Zhang ◽

Yang Gan ◽

Fei-hu Zhang

Keyword(s):

Pure Water ◽

High Hardness ◽

Underlying Mechanism ◽

Molecular Solids ◽

High Brightness ◽

Force Microscopy ◽

Atomic Force ◽

Chemical Inertness ◽

Sic Wafer ◽

First Time

<p>Silicon carbide (SiC) single crystals, along with sapphire and silicon, are one of most important substrates for high-brightness LED fabrications. Owing to extremely high hardness (Mohs’ scale of 9.5) and chemical inertness, the polishing rate of SiC with conventional chemical mechanical polishing (CMP) methods is not high, and surface scratches are also inevitable because of using slurry containing hard abrasives such as silica particles. Here artemisinin (Qinghaosu) crystals, very soft molecular solids, were found, for the first time to the best of our knowledge, to effectively polish SiC wafers even in pure water as demonstrated by proof-of-concept scratching experiments using atomic force microscopy (AFM). The underlying mechanism is attributed to activated oxidation of SiC by mechanically released reactive ·OH free radicals from the endoperoxide bridges. The preliminary results reported here have important implications for developing novel alternative green and scratch-free polishing methods for hard-brittle substrates including SiC and others.</p>

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The Oxidative Stress Pathway May be an Important Pathway Leading to The Recurrence of Ewing Sarcoma —— Based On Weighted Gene Co-Expression Network Analysis

10.21203/rs.3.rs-21707/v1 ◽

2020 ◽

Author(s):

Jianfeng Li ◽

Shaoyu Hu ◽

Song Hao ◽

Shengjia Huang ◽

Yi Qin ◽

...

Keyword(s):

Oxidative Stress ◽

Network Analysis ◽

Ewing Sarcoma ◽

Underlying Mechanism ◽

Data Sets ◽

Oxidative Stress Pathway ◽

Important Pathway ◽

First Time ◽

Stress Pathway

Abstract Background The role of gene and pathway in recurrence of Ewing sarcoma (ES) was not clear. Thus, we investigated the biological role and underlying mechanism of gene and pathway in recurrence of ES. Methods Data sets of patients with ES were collected from the GEO database. We used dataset GSE63155 and GSE63156 to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). Results We can find that genes with significant interactions in the genes of the recurrence group include SRSF11, TRIM39, SOCS3,NUPL2,COPS5. They work primarily through the oxidative stress pathway. Conclusion Through our research, for the first time found that ES by SRSF11 TRIM39, SOCS3, NUPL2, COPS5 interaction, activation of phosphorylation of bone and oxidative stress is affecting tumor recurrence.

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Abstract 15873: Novel Contributions of Neutrophil-derived Myeloperoxidase and Hypochlorous Acid to 20-hydroxyeicosatetraenoic Acid Production That Drives Post-ischemic Angiogenesis

Circulation ◽

10.1161/circ.142.suppl_3.15873 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Juan A Azcona ◽

Samantha Tang ◽

Thomas M Jeitner ◽

Michal Schwartzman ◽

Austin M Guo

Keyword(s):

Protein Expression ◽

Hypochlorous Acid ◽

Hypoxia Inducible Factor ◽

Limb Ischemia ◽

Tissue Perfusion ◽

Underlying Mechanism ◽

Arachidonic Acid Metabolite ◽

Micro Vessel Density ◽

First Time ◽

Adequate Tissue

Introduction: Compensatory angiogenic response to ischemia is often insufficient in maintaining adequate tissue perfusion resulting in critical limb ischemia and amputation. Identifying a novel mechanism by which angiogenesis occurs in these conditions is clinically relevant. We recently uncovered that an increase in 20-HETE, an arachidonic acid metabolite of CYP4A/F ω-hydroxylases, regulates post-ischemic angiogenesis. However, the underlying mechanism resulting in this increase is unknown. Hypothesis: Neutrophil-derived myeloperoxidase (MPO) and hypochlorous acid (HOCl) critically contribute to post-ischemic 20-HETE increases that drive angiogenesis. Methods: Hindlimb ischemia was established in mice depleted of neutrophils, macrophages, and MPO (MPO -/- ). Angiogenesis was assessed by laser doppler perfusion imaging and micro-vessel density quantitation in the hindlimb gracilis muscles. MPO and HOCl were detected in these tissues using immunohistochemistry and a HOCl-specific fluorophore. We also determined the effects of MPO and HOCl on 20-HETE production, the expression of 20-HETE synthase CYP4A11, and hypoxia inducible factor-1α in cultured endothelial cells (EC) using LC/MS/MS, real time-PCR and western blot analysis, respectively. Results: We found that ischemia failed to increase 20-HETE production in mice depleted of neutrophils and MPO (13 ± 1.5 vs 35 ± 5 and ~2 ± .25 vs 35 ± 5 pg/mg of protein, respectively), accompanied with a decreased post-ischemic angiogenic phenotype. We also detected the formation of MPO and HOCl in post-ischemic gracilis muscles. MPO and HOCl also significantly stimulate CYP4A11 expression and 20-HETE production (40±12 vs 8±5 pg/mg of protein) in EC. Furthermore, HOCl quickly induces CYP4A11 mRNA/protein expression (2-fold,) and the protein expression of HIF-1α (2-fold) in as little as 15 min. Conclusion: Our studies establish for the first time that neutrophil-derived MPO and HOCl are responsible for promoting 20-HETE increases that critically drive angiogenesis post ischemia. Thus, identifying these novel mediators can further future therapeutic strategies to balance angiogenic responses during ischemia as well as treating diseases that are associated with abnormal angiogenesis.

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A C21-Steroidal Glycoside from Cynanchum atratum Attenuates Concanavalin A-Induced Liver Injury in Mice

Molecules ◽

10.3390/molecules24061087 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1087 ◽

Cited By ~ 2

Author(s):

Jian Yang ◽

Bin Wang ◽

Chao-feng Zhang ◽

Xiang-hong Xu ◽

Mian Zhang

Keyword(s):

T Lymphocytes ◽

Concanavalin A ◽

Underlying Mechanism ◽

Dependent Manner ◽

Histopathological Changes ◽

Con A ◽

Concentration Dependent Manner ◽

Steroidal Glycoside ◽

First Time

Cynatratoside A (CyA) is a C21 Steroidal glycoside with pregnane skeleton isolated from the root of Cynanchum atratum Bunge (Asclepiadaceae). This study aimed to investigate the effects of CyA on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) and the underlying mechanism. CyA was orally administered to mice at 10 and 40 mg/kg 8 h before and 1 h after Con A treatment. The effects of CyA on Con A-induced spleen and liver in mice were assessed via histopathological changes, T lymphocyte amounts and the expressions of IL-1β and ICAM-1. Con A-induced L-02 hepatocytes were used to evaluate whether CyA (0.1–10 μM) can directly protect hepatocytes from cytotoxicity and the possible mechanism. The results revealed that CyA treatment could significantly improve the histopathological changes of spleen and liver, reduce the proliferation of splenic T lymphocytes, and decrease the expressions of IL-1β and ICAM-1 in liver. The experiment in vitro showed that CyA inhibited Con A-induced hepatotoxicity in a concentration-dependent manner. CyA (10 μM) significantly increased/decreased the expression of Bcl-2/Bax and reduced the levels of cleaved caspases-9 and -3. Our study demonstrated for the first time that CyA has a significant protective effect on Con A-induced AIH by inhibiting the activation and adhesion of T lymphocytes and blocking hepatocyte apoptosis.

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Improvement the Plasticity via Dual-Amorphous and Nanocrystals Synergistically in a Zr-Cu-Al-Nb Bulk Metallic Glass Composite

Metals ◽

10.3390/met10091158 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1158

Author(s):

Tuo Wang ◽

Xiaohui Yang ◽

Qiang Li ◽

Chuntao Chang

Keyword(s):

Metallic Glass ◽

Bulk Metallic Glass ◽

Underlying Mechanism ◽

Glass Composite ◽

Glass Composites ◽

Bulk Metallic Glass Composites ◽

First Time ◽

Bulk Metallic Glass Composite

In this work, a small amount of Nb has been added in a Zr52Cu42.5Al5.5 bulk metallic glass, and a Zr52Cu42Al5.5Nb0.5 bulk metallic glass composite with dual-amorphous and nanocrystal structures has been developed for the first time. This in situ formed bulk metallic glass composite has a larger room compressive plasticity of above 13% than that of the Zr52Cu42.5Al5.5 bulk metallic glass. The excellent plasticity of the bulk metallic glass composite is attributed to the phase-separated matrix with micro-nanocrystal and the nanocrystallization during the deforming process. This work may give a new sight into design bulk metallic glass composites and the underlying mechanism for deformation.

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MiR-9-5p promotes MSC migration by activating β-catenin signaling pathway

AJP Cell Physiology ◽

10.1152/ajpcell.00232.2016 ◽

2017 ◽

Vol 313 (1) ◽

pp. C80-C93 ◽

Cited By ~ 15

Author(s):

Xianyang Li ◽

Lihong He ◽

Qing Yue ◽

Junhou Lu ◽

Naixin Kang ◽

...

Keyword(s):

Signaling Pathway ◽

Target Genes ◽

Focal Adhesions ◽

Underlying Mechanism ◽

Therapeutic Effects ◽

Migration Ability ◽

Tissue Damages ◽

First Time ◽

Hepatocyte Growth ◽

High Migration

Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate the underlying mechanism, we screened the target genes of miR-9-5p and report for the first time that CK1α and GSK3β, two inhibitors of β-catenin signaling pathway, were direct targets of miR-9-5p in MSCs and that overexpression of miR-9-5p upregulated β-catenin signaling pathway. In line with these data, inhibition of β-catenin signaling pathway by FH535 decreased the miR-9-5p-promoted migration of MSCs, while activation of β-catenin signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR-9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as well as the reorganization of F-actin were affected by the expression of miR-9-5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration by upregulating β-catenin signaling pathway, shedding light on the optimization of MSCs for cell replacement therapy through manipulating the expression level of miR-9-5p.

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Analysis of the Effects of Multi-Clamps Fixture on Workpiece Location Errors

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.375-376.619 ◽

2008 ◽

Vol 375-376 ◽

pp. 619-625 ◽

Cited By ~ 1

Author(s):

Guo Hua Qin ◽

Shi Ping Sun ◽

Zhi Xiong Chen ◽

Tie Jun Wu ◽

Zhi Qiang Ao

Keyword(s):

Contact Forces ◽

Machining Accuracy ◽

Location Error ◽

Location Errors ◽

Numerical Tests ◽

Proposed Model ◽

One Step ◽

Fixture System ◽

The Impact ◽

Novel Design

Multiple clamps are frequently used to serve the purpose of workholding in a fixture. So multiple clamping forces including their magnitudes, placements and application sequences, greatly influence contact forces and workpiece machining accuracy. In this paper, the impact of multiple clamping forces on workpiece location error is formulated analytically for a workpiece-fixture system. The proposed model takes into account the varying contact forces and friction force during entire clamping operation. It reveals that the historical accumulation of clamping steps influences heavily the final distribution of contact forces in the workpiece-fixture system. In addition, based on effect of contact forces from one step to another on workpiece location, a novel design model is presented to optimize the multiple clamping forces in order to minimize the workpiece location errors. Some numerical tests are finally demonstrated to validate the proposed model and approach.

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Pro-Apoptotic Effect of Lenalidomide (L) in Patients with Chronic Lymphocytic Leukemia (CLL) Is Possibly Mediated through Interruption of the Phosphatidylinositol Pathway.

Blood ◽

10.1182/blood.v108.11.2102.2102 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2102-2102 ◽

Cited By ~ 3

Author(s):

Asher Alban Chanan-Khan ◽

Noreen Ersing ◽

Deborah Krammer ◽

Ralph Bernacki ◽

Lionel Coignet ◽

...

Keyword(s):

Clinical Trial ◽

Tumor Cells ◽

Day Treatment ◽

Underlying Mechanism ◽

Lymphocytic Leukemia ◽

Tnf Alpha ◽

Whole Cell Lysate ◽

Apoptotic Effect ◽

Antileukemic Effect ◽

First Time

Abstract Introduction: In a phase II clinical trial we reported the antileukemic effect of L in CLL pts. In this clinical trial 24/34 (70.5%) pts with detectable tumor cells (ALC > 5,000) in peripheral blood demonstrated a decrease in ALC within 8 days of treatment. Although, the exact molecular mechanism for its antitumor activity remains undetermined, L has been reported to down regulates production of various cytokines including VEGF, IL-6 and TNF-alpha. In order to investigate the underlying mechanism(s) responsible for the antileukemic effects of L in CLL, we examined down stream targets of VEGF and IL-6 signaling pathways in CLL cells obtained from pts pre and post 8 day treatment with L. Method: Pts with accessible tumor cells in blood (ALC > 5000) who received L were identified. Tumor cells were obtained prior to (baseline) and 8 days after treatment with L. Whole cell lysate was prepared and expression of down stream targets of VEGF, AKT and Erk determined through immunobloting assay. Results: In cells obtained from pts who had received 8 days of treatment, we observed that L decreased the expression of pAKT and pErk1/2 without changes in corresponding total protein. Conversely L did not have any effect on protein expression of the Bcl-2 or Bcl-xl, though Mcl-1 was decreased compared to pretreatment control. Conclusion: This is the first time that the antileukemic effect of L in CLL may at least be attributed to down regulation of VEGF and IL-6 mediated prosurvival pathways. Our observation that L does not interrupt the Bcl-2 pathway are clinically intriguing and propose the possibility of combining L with Bcl-2 inhibiting agent(s) to augment the antitumor response in CLL.

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A Kinematic Approach to Locating Error Analysis for Fixture Design

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.431-432.74 ◽

2010 ◽

Vol 431-432 ◽

pp. 74-77 ◽

Cited By ~ 1

Author(s):

Guo Hua Qin ◽

Dong Lu ◽

Shi Ping Sun ◽

Hai Chao Ye

Keyword(s):

Error Analysis ◽

Kinematic Model ◽

Angular Dimension ◽

Fixture Design ◽

Locating Error ◽

Composition Law ◽

Accurate Position ◽

Source Errors ◽

First Time ◽

The Relationship

In order that the required manufacturing processes can be carried out, fixtures are developed to locate and hold a workpiece firmly in the accurate position. However, source errors of fixtures can change the accurate position and in turn, cause the locating error. It follows that the evaluation of locating error is important to fixture design. Therefore, a general approach to the locating error analysis is formulated for the first time. Firstly, a kinematic model and its algorithm of the locating error are proposed to analyzing the linear dimension based on the velocity composition law of particle movement. In addition, according to the relationship between the linear velocity and angular velocity, another kinematic model and its algorithm of the locating error are also formulated to verifying the angular dimension.

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