Probabilistic Counting-Out Game on a Line

This thesis attempts to solve a novel problem originally posted on a question-and-answer website. In a counting-out game, there are n people in a line at positions 1, 2, . . . , n. For each round, we randomly select a person at position k, where k is odd, to leave the line, and shift the people at each position i such that i > k to position i − 1. We continue to select people until there is only one person left, who then becomes the winner. We are interested in two questions: which initial position has the greatest chance to win and which has the longest expected time to stay in the line. To answer the two questions above, we use a recursive approach to solve for exact values of the winning probabilities and the expected survival time, prove the exact formula for the winning probabilities and derive the asymptotic behaviors of the expected survival time for some locations. We have also considered a variation of the problem, where people are grouped into triples, quadruples, etc., and the first person in each group is at the risk of being selected. Recursive equations are constructed for this generalized case, and a proof of the exact formula for the winning probabilities is provided as well. Finally, we present other possible extensions and discuss future research directions concerning this problem

Comprehensive identification of alternative back-splicing in human tissue transcriptomes

Circular RNAs (circRNAs) are covalently closed RNAs derived from back-splicing of genes across eukaryotes. Through alternative back-splicing (ABS), a single gene produces multiple circRNAs sharing the same back-splice site. Although many ABS events have recently been discovered, to what extent ABS involves in circRNA biogenesis and how it is regulated in different human tissues still remain elusive. Here, we reported an in-depth analysis of ABS events in 90 human tissue transcriptomes. We observed that ABS occurred for about 84% circRNAs. Interestingly, alternative 5\u27 back-splicing occurs more prevalently than alternative 3\u27 back-splicing, and both of them are tissue-specific, especially enriched in brain tissues. In addition, the patterns of ABS events in different brain regions are similar to each other and are more complex than the patterns in non-brain tissues. Finally, the intron length and abundance of Alu elements positively correlated with ABS event complexity, and the predominant circRNAs had longer flanking introns and more Alu elements than other circRNAs in the same ABS event. Together, our results represent a resource for circRNA research-we expanded the repertoire of ABS events of circRNAs in human tissue transcriptomes and provided insights into the complexity of circRNA biogenesis, expression, and regulation

Wafer-scale heterogeneous integration InP on trenched Si with a bubble-free interface

Heterogeneous integration of compound semiconductors on a Si platform leads to advanced device applications in the field of Si photonics and high frequency electronics. However, the unavoidable bubbles formed at the bonding interface are detrimental for achieving a high yield of dissimilar semiconductor integration by the direct wafer bonding technology. In this work, lateral outgassing surface trenches (LOTs) are introduced to efficiently inhibit the bubbles. It is found that the chemical reactions in InP-Si bonding are similar to those in Si-Si bonding, and the generated gas can escape via the LOTs. The outgassing efficiency is dominated by LOTs\u27 spacing, and moreover, the relationship between bubble formation and the LOT\u27s structure is well described by a thermodynamic model. With the method explored in this work, a 2-in. bubble-free crystalline InP thin film integrated on the Si substrate with LOTs is obtained by the ion-slicing and wafer bonding technology. The quantum well active region grown on this Si-based InP film shows a superior photoemission efficiency, and it is found to be 65% as compared to its bulk counterpart

Depletion of TRRAP induces p53-independent senescence in liver cancer by downregulating mitotic genes

Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer with few effective treatments and the underlying mechanisms that drive HCC pathogenesis remain poorly characterized. Identifying genes and pathways essential for HCC cell growth will aid the development of new targeted therapies for HCC. Using a kinome CRISPR screen in three human HCC cell lines, we identified transformation/transcription domain-associated protein (TRRAP) as an essential gene for HCC cell proliferation. TRRAP has been implicated in oncogenic transformation, but how it functions in cancer cell proliferation is not established. Here, we show that depletion of TRRAP or its co-factor, histone acetyltransferase KAT5, inhibits HCC cell growth via induction of p53- and p21-independent senescence. Integrated cancer genomics analyses using patient data and RNA-sequencing identified mitotic genes as key TRRAP/KAT5 targets in HCC, and subsequent cell cycle analyses revealed that TRRAP- and KAT5-depleted cells are arrested at G2/M phase. Depletion of TOP2A, a mitotic gene and TRRAP/KAT5 target, was sufficient to recapitulate the senescent phenotype of TRRAP/KAT5 knockdown. CONCLUSION: Our results uncover a role for TRRAP/KAT5 in promoting HCC cell proliferation via activation of mitotic genes. Targeting the TRRAP/KAT5 complex is a potential therapeutic strategy for HCC

Uterine perivascular epithelioid tumors (PEComas) with lung metastasis showed good responses to mTOR and VEGFR inhibitors: A case report

Perivascular epithelioid cell tumors (PEComas) are extremely rare mesenchymal neoplasms for which the uterus is the most common site. The prognosis of malignant PEComa is poor as it is characterized by resistance to classical chemotherapies. Both mTOR inhibitors and VEGFR inhibitors exhibited clinical utility in treating malignant PEComas, but the combination of these two regimens has rarely been reported. In the present case, a uterine PEComa patient developed lung and bone metastases after the failure of chemotherapies and derived benefit from the combination regimen of an mTOR inhibitor (everolimus) and a VEGFR inhibitor (apatinib), achieving a 15-month progression-free survival. Targeted NGS revealed TP53 and TSC2 mutations in the patient’s primary uterine tumors and plasma ctDNA at disease progression. Plasma ctDNA clearance was consistent with a radiologic partial response determined by RECIST 1.1 and a reduction of neuron-specific enolase (NSE) and cancer antigen 125 (CA125) levels. Thus, we provided clinical evidence supporting the administration of combined therapy of mTOR and VEGFR inhibitors to metastatic uterine PEComa patients and highlighted the application of serial plasma ctDNA profiling for dynamic disease monitoring

Investigation on a new hole-flanging approach by incremental sheet forming through a featured tool

One of the major challenges in conventional incremental sheet forming (ISF) is the extreme sheet thinning resulted in an uneven thickness distribution of formed part. This is also the case for incrementally formed parts with hole-flanging features. To overcome this problem, a new ISF based hole-flanging processing method is proposed by developing a new ISF flanging tool. Comparative studies are conducted by performing hole-flanging tests using both ISF conventional ball-nose tool and the new flanging tool to evaluate the sheet deformation behavior and the quality of the final part. Stress distribution and strain variation are investigated by analytical approach and numerical simulation. Experiments have been conducted to validate the analytical model and simulation results, and to further study the fracture behavior. Results show that the new flanging tool generates greater meridional bending than stretching deformation in conventional ISF. The combination of bending-dominated deformation mode with localized deformation of ISF ensures more uniform thickness distribution on hole-flanging part with better resistance to fracture

Tissue engineered corneal epithelium derived from clinical-grade human embryonic stem cells

角膜上皮位于角膜最表层，对维持角膜的透明性发挥非常重要的作用。角膜上皮细胞处于不断更新之中，它们更新的源泉在于角膜缘处的上皮干细胞，即角膜缘干细胞。眼表面化学伤、热烧伤以及部分先天性遗传疾病可以引起角膜缘干细胞缺乏，或者使干细胞丧失向正常角膜上皮细胞分化的能力，导致经久不愈的角膜上皮缺损、角膜新生血管、角膜上皮结膜化、角膜溃疡等病理改变，严重影响患者视力，甚至导致失明。由于眼表面的严重破坏，这类患者的治疗具有很大的挑战性，目前比较理想的治疗方法是进行组织工程角膜上皮移植。 厦门大学眼科研究所和中国科学院动物研究所干细胞与生殖生物学国家重点实验室合作研究采用中科院动物研究所研发的我国第一个临床级胚胎干细胞系Q-CTS-hESC-1，体外诱导分化为角膜上皮祖细胞，在此基础上构建组织工程角膜上皮，移植于兔角膜缘干细胞缺乏动物模型，成功重建眼表面。 厦门大学眼科研究所博士研究生贺佳和欧尚坤为该论文的共同第一作者，厦门大学眼科研究所李炜教授、刘祖国教授以及中科院动物所郝捷副研究员为共同通讯作者。【Abstract】Purpose: To construct tissue engineered corneal epithelium from a clinical-grade human embryonic stem cells (hESCs) and investigate the dynamic gene profile and phenotypic transition in the process of differentiation.Methods: A stepwise protocol was applied to induce differentiation of clinical-grade hESCs Q-CTS-hESC-1 and construct tissue engineered corneal epithelium. Single cell RNA sequencing (scRNA-seq) analysis was performed to monitor gene expression and phenotypic changes at different differentiation stages. Immunostaining, realtime quantitative PCR and Western blot analysis were conducted to detect gene and protein expressions. After subcutaneous transplantation into nude mice to test the biosafety, the epithelial construct was transplanted in a rabbit corneal limbal stem cell deficiency (LSCD) model and followed up for eight weeks. Results: The hESCs were successfully induced into epithelial cells. scRNA-seq analysis revealed upregulation of ocular surface epithelial cell lineage related genes such as TP63, Pax6, KRT14, and activation of Wnt, Notch,Hippo, and Hedgehog signaling pathways during the differentiation process. Tissue engineered epithelial cell sheet derived from hESCs showed stratified structure and normal corneal epithelial phenotype with presence of clonogenic progenitor cells. Eight weeks after grafting the cell sheet onto the ocular surface of LSCD rabbit model, a full-thickness continuous corneal epithelium developed to fully cover the damaged areas with normal limbal and corneal epithelial phenotype. Conclusion: The tissue engineered corneal epithelium generated from a clinical-grade hESCs may be feasible in the treatment of limbal stem cell deficiency.This study was supported in part by the National Key R&D Program of China (2018YFA0107301 [to WL], 2018YFA0107304 [to ZL], 2013CB967003 [to WL]), the National Natural Science Foundation of China (NSFC, No.81770894, No.81470602 [to WL], and No.81330022 [to ZL]). 该论文获得了国家重点研发计划项目和国家自然科学基金项目的资助