Clinically Applicable Assessment of Tisagenlecleucel CAR T Cell Treatment by Digital Droplet PCR for Copy Number Variant Assessment

Chimeric antigen receptor (CAR) T cell therapy is an innovative immunotherapy for treating cancers in both children and adults with proven utility in numerous clinical trials. Significantly, some CAR T cell therapies have now been approved by relevant national regulatory bodies across numerous countries for clinical therapeutic use outside of clinical trials. One such recently licensed product is tisagenlecleucel, a CAR T therapy approved for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) using autologous T cells from the patient. The genetically engineered T cells target a protein called CD19, common to B cells, through a CAR incorporating a 4-1BB costimulatory domain to improve response. Since tisagenlecleucel is now a standard of care treatment for B-ALL, it is clinically essential to be able to accurately monitor these CAR T cells in patients. Assessment of the copy number variant (CNV) of the CAR T cell products allows this within a clinically acceptable timeframe for optimal patient benefit. However, no standardized method with high reproducibility and efficiency has been described within a routine clinical laboratory setting. Here, we demonstrated a novel digital droplet PCR (ddPCR)-based methodology for the study of CNV (ddPCR-CNV) in 4-1BB CD19-specific CAR T cells with universal applicability across clinical diagnostic laboratories.     

工程数据库动态版本管理模型的研究

本文研究了工程数据库中动态版本管理模型及实现方法,包括设计版本管理,约束及约束传递与控制,版本一致性的管理与控制,完成版的判定等动态版本管理中的基本问题.介绍了一个已投入使用的动态版本管理系统DVMS的结构和设计思想.     

蓝鲸备份系统

业务的全球化使得备份窗口逐渐缩短,如何快速有效地对数据进行统一备份成为数据保护领域亟待解决的关键问题之一。该文设计并实现了一个基于块级备份的分布式数据备份系统(蓝鲸备份系统)。该系统采取块级备份方式,对于不同的文件系统或数据库,都可以采取统一方式进行备份。同时,块级备份能提供更细粒度的备份,与文件级备份相比,在备份性能和空间利用率上都得到了很大提高。蓝鲸备份系统采取策略驱动的自动备份,实现了管理的自动化。     

CVS在小城镇电子政务系统中的应用

介绍了软件配置管理工具CVS的运行机制及其功能特点,以及小城镇电子政务系统的体系结构和运行模式.针对在小城镇电子政务系统开发中产生的问题,CVS规范了软件开发流程,降低了管理难度,提高了开发效率,使整个开发过程在受控制、高效率的情况下进行,提高系统的可靠性、代码及文档的全面性与可追踪性.     

配置产品尺寸参数修改与变型设计方法研究

在大批量定制的产品配置中,有时需要对配置模块进行变型设计或尺寸参数修改,如何快速准确地确定配置模块尺寸之间的相互影响关系,并对配置产品的尺寸参数进行快速准确的修改是配置设计准确性和配置设计效率的关键.将参数化技术和网络理论应用于大批量定制的产品配置领域,在建立产品参数化模型的基础上,建立了配置产品尺寸约束关系网络.提出了基于尺寸参数传递方法的配置产品尺寸参数修改与变型设计方法,开发了与PRO/E集成的产品变型设计模块.最后以联轴器产品为例验证了上述方法的可行性.     

时空数据库变体最近邻查询问题探讨

最近邻查询在地理信息系统、智能交通系统、多媒体应用以及数据挖掘等领域有着广泛的应用,随着对最近邻查询问题研究的深入,其应用前景和发展空间将更为广阔。针对近几年时空数据库中提出的最近邻查询的多种变体查询问题进行了详细地介绍和分析,总结了解决这些变体最近邻查询问题的有效方法,最后对最近邻查询问题的发展方向进行了展望。     

Studies on Lotus Genomics and the Contribution to Its Breeding

Lotus (Nelumbo nucifera), under the Nelumbonaceae family, is one of the relict plants possessing important scientific research and economic values. Because of this, much attention has been paid to this species on both its biology and breeding among the scientific community. In the last decade, the genome of lotus has been sequenced, and several high-quality genome assemblies are available, which have significantly facilitated functional genomics studies in lotus. Meanwhile, re-sequencing of the natural and genetic populations along with different levels of omics studies have not only helped to classify the germplasm resources but also to identify the domestication of selected regions and genes controlling different horticultural traits. This review summarizes the latest progress of all these studies on lotus and discusses their potential application in lotus breeding.     

Identification of Spliceogenic Variants beyond Canonical GT-AG Splice Sites in Hereditary Cancer Genes

Pathogenic/likely pathogenic variants in susceptibility genes that interrupt RNA splicing are a well-documented mechanism of hereditary cancer syndromes development. However, if RNA studies are not performed, most of the variants beyond the canonical GT-AG splice site are characterized as variants of uncertain significance (VUS). To decrease the VUS burden, we have bioinformatically evaluated all novel VUS detected in 732 consecutive patients tested in the routine genetic counseling process. Twelve VUS that were predicted to cause splicing defects were selected for mRNA analysis. Here, we report a functional characterization of 12 variants located beyond the first two intronic nucleotides using RNAseq in APC, ATM, FH, LZTR1, MSH6, PALB2, RAD51C, and TP53 genes. Based on the analysis of mRNA, we have successfully reclassified 50% of investigated variants. 25% of variants were downgraded to likely benign, whereas 25% were upgraded to likely pathogenic leading to improved clinical management of the patient and the family members.     

牛乳清蛋白遗传多态性研究

就牛乳清蛋白遗传多态性及其研究方法以及乳清蛋白多样性与乳品质之间的相关性作以阐述,旨在揭示当前该方向研究现状,并为今后研究提供参考。     

通过轨迹特征根分析时变振荡特性

电力系统受扰轨迹具有非平稳振荡特性,无法由平衡点特征根反映。为此,提出受扰轨迹振荡模式的时变性概念,给出瞬时阻尼的计算式;采用小波脊方法获取轨迹各窗口内的特征根,构成振荡模式的时间序列,以便研究扰动大小和系统时变性对低频振荡的影响。小波变换利用滑动的伸缩窗口在多个尺度空间分析信号的时频特性,有较好的频率适应性。通过追踪小波变换的极大值点可以克服Prony和傅里叶算法不适用于时变系统的困难,反映时变振荡特性。指出由于小波变换反映的是窗口内的平均振荡特性,窗口过宽会掩盖其时变性,因此不能用于时变性太强的场合。