Genomic analyses of the immune system

Project 1. Genetic variation in key immune system components Genes underpinning the diversity and plasticity of the human adaptive immune system, such as the HLA and immunoglobulins, are known for their complex structures and polymorphism. The emergence of long-read sequencing technologies has revolutionised genomics research, in particular the characterisation of segmental duplications and structural variation. Here, using long-read sequencing and additional genomics data from a healthy donor identified as HV31, I built two iterations of de novo personal genome assemblies for HV31 as a foundation to study the genetic variation of the immune system. I analysed complex structural variants found in genomic regions encoding key immune system components, and validated them against sequencing data. I also evaluated long-read sequencing accuracy and developed a tool for genomic data visualisation. Collectively, these efforts demonstrate the applications of personal genome assemblies in studying the immune system. Project 2. Effects of low-dose IL-2 immunotherapy in T and NK cells Low-dose interleukin-2 (IL-2) immunotherapy is a promising treatment for type 1 diabetes (T1D). IL-2 supresses autoimmune reactions by increasing the number of regulatory T cells (Tregs). To better understand the mechanism of action of low- dose IL-2 immunotherapy, I analysed single-cell multiomics data of T and NK cells collected from T1D patients before and after low-dose IL-2 treatment. I confirmed that low-dose IL-2 selectively expanded thymic-derived FOXP3+ HELIOS+ regulatory T cells and CD56br NK cells, and showed that the treatment reduced the frequency of IL-21-producing CD4+ T cells. In addition, I identified a long-lived gene expression signature induced by IL-2, which featured the upregulation of CISH and downregulation of AREG. Notably, I found that the signature remained detectable one month after the treatment. Further analyses of publicly available COVID-19 cohort data revealed that SARS-CoV-2 infection induced opposite changes that persisted for several months after recovery. These findings suggested potential mechanisms of long COVID and longer-term benefits of IL-2 immunotherapy

Therblig-embedded value stream mapping method for lean energy machining

To improve energy efficiency, extensive studies have focused on the cutting parameters optimization in the machining process. Actually, non-cutting activities (NCA) occur frequently during machining and this is a promising way to save energy through optimizing NCA without changing the cutting parameters. However, it is difficult for the existing methods to accurately determine and reduce the energy wastes (EW) in NCA. To fill this gap, a novel Therblig-embedded Value Stream Mapping (TVSM) method is proposed to improve the energy transparency and clearly show and reduce the EW in NCA. The Future-State-Map (FSM) of TVSM can be built by minimizing non-cutting activities and Therbligs. By implementing the FSM, time and energy efficiencies can be improved without decreasing the machining quality, which is consistent with the goal of lean energy machining. The method is validated by a machining case study, the results show that the total energy is reduced by 7.65%, and the time efficiency of the value-added activities is improved by 8.12% , and the energy efficiency of value-added activities and Therbligs are raised by 4.95% and 1.58%, respectively. This approach can be applied to reduce the EW of NCA, to support designers to design high energy efficiency machining processes during process planning

Bayesian Formula and Its Application Analysis

Bayesian formula is a very important and widely used formula in probability and statistics courses, which can simplify the probability calculation of certain complex events. This article not only introduces the relevant theories of Bayesian formula, but also explores its practical applications in daily life through examples

Several Methods on the Limit Problem of Integration

If the expression of a limit contains definite integral, we call this kind of limit as the limit of integration. This paper takes the graduate entrance exams of some famous universities in China as examples, and gives several methods to solve the limit problem of integration by comprehensively utilizing the characteristics and operational properties of integral