Grain refinement in hypoeutectic Al-Si alloy driven by electric currents

The present thesis investigates the grain refinement in solidifying Al-7wt%Si hypoeutectic alloy driven by electric currents. The grain size reduction in alloys generated by electric currents during the solidification has been intensively investigated. However, since various effects of electric currents have the potential to generate the finer equiaxed grains, it is still argued which effect plays the key role in the grain refinement process. In addition, the knowledge about the grain refinement mechanism under the application of electric currents remains fragmentary and inconsistent. Hence, the research objectives of the present thesis focus on the role of electric current effects and the grain refinement mechanism under the application of electric currents. Chapter 1 presents an introduction with respect to the subject of grain refinement in alloys driven by electric current during the solidification process in particular, including the research objectives; the research motivation; a brief review about the research history; a short introduction on the electric currents effects and a review relevant to the research status of grain refinement mechanism. Chapter 2 gives a description of research methods. This chapter shows the employed experiment materials, experimental setup, experimental procedure, the analysis methods of solidified samples, and numerical method, respectively. Chapter 3 focuses on the role of electric current effects in the grain refinement process. A series of solidification experiments are performed under various values of effective electric currents for both, electric current pulse and direct current. The corresponding temperature measurements and flow measurements are carried out with the increase of effective electric current intensity. Meanwhile, numerical simulations are conducted to present the details of the flow structure and the distribution of electric current density and electromagnetic force. Finally, the role of electric current effects is discussed to find the key effect in the grain refinement driven by electric currents. Chapter 4 investigates the grain refinement mechanism driven by electric currents. This chapter mainly focuses on the origin of finer equiaxed grain for grain refinement under the application of electric current on account of the importance of the origin for understanding the grain refinement mechanism. A series of solidification experiments are carried out in Al-7wt%Si alloy and in high purity aluminum. The main origin of equiaxed grain for grain refinement is concluded based on the experiment results. Chapter 5 presents three further investigations based on the achieved knowledge in chapter 3 and 4 about the role of electric current effects and the grain refinement mechanism. According to the insight into the key electric current effect for the grain refinement shown in chapter 3, this chapter presents a potential approach to promote the grain refinement. In addition, the solute distribution under the influence of electric current is examined based on the knowledge about the electric current effects. Moreover, the grain refinement mechanism under application of travelling magnetic field is investigated by performing a series of solidification experiments to compare with the experiments about the grain refinement mechanism driven by electric currents shown in chapter 4. Chapter 6 summarizes the main conclusions from the presented work.:Abstract VII Contents IX List of figures XI List of tables XVII 1. Introduction 1 1.1 Research objectives 1 1.2 Research motivation 2 1.3 Research history 5 1.4 Electric currents effects 9 1.4.1 Some fundamentals 10 1.4.2 Role of electric currents effects in grain refinement 12 1.5 Grain refinement mechanism 13 1.5.1 Nucleation theory 13 1.5.2 Equiaxed grain formation without the application of external fields 18 1.5.3 Grain refinement mechanism under the application of electric currents 23 1.5.4 Grain refinement mechanism under the application of magnetic field 29 2. Research methods 31 2.1 Introduction 31 2.2 Experimental materials 31 2.2.1 Solidification 31 2.2.2 Similarity of GaInSn liquid metal and Al-Si melt 32 2.3 Experimental setup 33 2.3.1 Solidification 33 2.3.2 Flow measurements 35 2.3.3 External energy fields 36 2.4 Experimental procedure 38 2.4.1 Solidification 38 2.4.2 Flow measurements 39 2.5 Metallography 39 2.6 Numerical method 41 2.6.1 Numerical model 41 2.6.2 Numerical domain and boundary conditions 42 3. Role of electric currents effects in the grain refinement 45 3.1 Introduction 45 3.2 Experimental parameter 45 3.3 Results 46 3.3.1 Solidified structure 46 3.3.2 Forced melt flow 50 3.3.3 Temperature distribution 58 3.4 Discussion 61 3.5 Conclusions 67 4. Grain refinement mechanism driven by electric currents 69 4.1 Introduction 69 4.2 Experimental parameter 69 4.3 Results 73 4.3.1 Solidified structure of Al-Si alloy 73 4.3.2 Cooling curves of Al-Si alloy 77 4.3.3 Solidified structure of high purity aluminum 78 4.4 Discussion 80 4.5 Conclusions 83 5. Supplemental investigations 85 5.1 A potential approach to improve the grain refinement 85 5.1.1 Introduction 85 5.1.2 Experimental parameter 86 5.1.3 Results and discussion 87 5.2 Macrosegregation formation 90 5.2.1 Introduction 90 5.2.2 Experimental parameter 91 5.2.3 Results and discussion 92 5.3 Grain refinement driven by TMF 97 5.3.1 Introduction 97 5.3.2 Experimental parameter 97 5.3.3 Results and discussion 98 5.4 Conclusions 102 6. Summary 103 Bibliography 10

LncRNA RUNX1-IT1 is downregulated in gastric cancer and suppresses the maturation of miR-20a by binding to its precursor

Background. RUNX1-IT1 has been characterized as a tumor suppressive long non-coding RNA (lncRNA) in several types of cancer but not gastric cancer (GC). This study aimed to explore the role of RUNX1-IT1 in GC. Methods. The expression of RUNX1-IT1, microRNA (miR)-20a precursor and mature miR-20a in GC and healthy tissues donated by GC patients (n=62) were measured by RT-qPCR. Correlation analysis was performed by linear regression. The expression of mature miR-20a and miR-20a precursor in cells with overexpression of RUNX1-IT1 was also determined by RT-qPCR. Cell invasion and migration were evaluated by Transwell assays. Results. RUNX1-IT1 was downregulated in GC. Across GC tissues, RUNX1-IT1 and mature miR-20a were inversely correlated. However, RUNX1-IT1 and miR-20a precursor were not closely correlated. RUNX1- IT1 and miR-20a precursor were predicted to interact with each other, and overexpression of RUNX1-IT1 in GC cells decreased the expression levels of mature miR20a. Transwell assay showed that the enhancing effect of miR-20a on cell invasion and migration was reduced by overexpression of RUNX1-IT1. Conclusions. RUNX1-IT1 may suppress the GC cell movement by inhibiting the maturation of miR-20

Heterogeneous nucleation of pure Al on MgO single crystal substrate accompanied by a MgAl2O4 buffer layer

This paper investigates the correlations between interfacial reaction, crystallographic orientation relationship on the interface and the required undercooling for nucleation on different crystallographic planes of MgO. Thermal analysis and high resolution transmission electron microscopy were used to study the nucleation behavior of liquid, high-purity Al droplet on single crystal MgO substrates using a DSC with an integrated image capture system and a sessile drop apparatus. The results showed that the original substrate MgO would be completely replaced by the reaction product MgAlO at the interface owing to the chemical reaction between liquid Al and the MgO substrates. In addition, the same crystal structure with the original MgO substrate is achieved in the new MgAlO layer. The orientation relationship between MgAlO and Al is consistent with the theoretical prediction according to the Bramfitt's lattice misfit theory and Edge-to-Edge model. Consequently, the generated MgAlO significantly influences the detected undercooling

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Dual modification of Alzheimer’s disease PHF-tau protein by lysine methylation and ubiquitylation: a mass spectrometry approach

In sporadic Alzheimer’s disease (AD), neurofibrillary lesion formation is preceded by extensive post-translational modification of the microtubule associated protein tau. To identify the modification signature associated with tau lesion formation at single amino acid resolution, immunopurified paired helical filaments were isolated from AD brain and subjected to nanoflow liquid chromatography–tandem mass spectrometry analysis. The resulting spectra identified monomethylation of lysine residues as a new tau modification. The methyl-lysine was distributed among seven residues located in the projection and microtubule binding repeat regions of tau protein, with one site, K254, being a substrate for a competing lysine modification, ubiquitylation. To characterize methyl lysine content in intact tissue, hippocampal sections prepared from post mortem late-stage AD cases were subjected to double-label confocal fluorescence microscopy using anti-tau and anti-methyl lysine antibodies. Anti-methyl lysine immunoreactivity colocalized with 78 ± 13% of neurofibrillary tangles in these specimens. Together these data provide the first evidence that tau in neurofibrillary lesions is post-translationally modified by lysine methylation

Integrated Molecular Characterization of Uterine Carcinosarcoma

SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies