抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Targeted nucleases are powerful tools for mediating genome alteration with high precision. The RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system can be used to facilitate efficient genome engineering in eukaryotic cells by simply specifying a 20-nt targeting sequence within its guide RNA. Here we describe a set of tools for Cas9-mediated genome editing via nonhomologous end joining (NHEJ) or homology-directed repair (HDR) in mammalian cells, as well as generation of modified cell lines for downstream functional studies. To minimize off-target cleavage, we further describe a double-nicking strategy using the Cas9 nickase mutant with paired guide RNAs. This protocol provides experimentally derived guidelines for the selection of target sites, evaluation of cleavage efficiency and analysis of off-target activity. Beginning with target design, gene modifications can be achieved within as little as 1-2 weeks, and modified clonal cell lines can be derived within 2-3 weeks.

/pdf/genome-engineering-using-the-crispr-cas9-system-4x8nw03mgu.pdf

Genome engineering using the CRISPR-Cas9 system

The advent of facile genome engineering using the bacterial RNA-guided CRISPR-Cas9 system in animals and plants is transforming biology. We review the history of CRISPR (clustered regularly interspaced palindromic repeat) biology from its initial discovery through the elucidation of the CRISPR-Cas9 enzyme mechanism, which has set the stage for remarkable developments using this technology to modify, regulate, or mark genomic loci in a wide variety of cells and organisms from all three domains of life. These results highlight a new era in which genomic manipulation is no longer a bottleneck to experiments, paving the way toward fundamental discoveries in biology, with applications in all branches of biotechnology, as well as strategies for human therapeutics.

The new frontier of genome engineering with CRISPR-Cas9

http://knockout.cwru.edu/publications/hsucrisprreview.pdf

Development and applications of CRISPR-Cas9 for genome engineering.

https://limlab.ucsf.edu/papers/pdfs/lsq_2013.pdf

Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression.

Interim Results of the Phase 1 Study of Tnb-486, a Novel CD19xCD3 T-Cell Engager, in Patients with Relapsed/Refractory (R/R) B-NHL

NVMeVirt: A Versatile Software-defined Virtual NVMe Device

We report the performance and compatibility of our new organic BARC materials (HEART004) designed to work for lithographic applications at 193 nm. The new organic BARC material has approximately an optical density of 12.1 /spl mu/m/sup -1/ at 193 nm. Its plasma etch rate is higher than that of ArF resists depending on the etch conditions. We evaluated typical two kinds of ArF resists on the organic BARCs, one is DHA1001 based on cycloolefin/maleic anhydride copolymer and the other is PAR710 based on acrylic copolymer. The PAR710 shows good compatibility with HEART004 at 210/spl deg/C of baking temperature.

Novel organic bottom anti-reflective coating materials for 193 nm lithography

Early evaluation of the corticospinal tract (CST) is critical for patients with acute hypertensive intracerebral hemorrhage (ICH) to predict long-term motor functional outcome. Therefore, we investigated motor functional outcome of an ICH using diffusion tensor imaging (DTI) in patients with hypertensive ICH. Thirty six patients with hemiparesis due to hypertensive ICH underwent DTI within 3 days after onset. Fractional anisotropy (FA) was measured within the CST at levels of the posterior limbs of the internal capsules, and motor impairment was assessed on admission and 8 weeks after ICH by manual muscle test. The correlation between FA ratio and improvement of motor function was analyzed by Pearson’s correlation analysis. The FA ratio from the initial DTI showed a correlation with motor function improvement. The amount of hematoma correlated with motor function on admission, but did not show correlation with the degree of motor recovery. Therefore, FA ratio analysis calculated from FA values of DTI could be a prognostic factor of motor function improvement in patients with hypertensive ICH.

https://www.longdom.org/open-access/diffusion-tensor-imaging-predicts-motor-functional-outcome-after-acute-hypertensive-intracerebral-hemorrhage-2157-7013-1000203.pdf

Jin-Soo Kim

Papers

Interim Results of the Phase 1 Study of Tnb-486, a Novel CD19xCD3 T-Cell Engager, in Patients with Relapsed/Refractory (R/R) B-NHL

NVMeVirt: A Versatile Software-defined Virtual NVMe Device

Novel organic bottom anti-reflective coating materials for 193 nm lithography

Diffusion Tensor Imaging Predicts Motor Functional Outcome after Acute Hypertensive Intracerebral Hemorrhage

Experimental study of bump void formation according to process conditions