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.

In this study, a transparent conductive-polymer-based sensor array designed for use in a touch screen panel was fabricated using soft lithography. One of the most promising conductive polymers, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), was used as the conductive material, and the secondary dopant dimethyl sulfoxide (DMSO) was used to increase the conductivity. The experiments were conducted using various DMSO concentrations in PEDOT:PSS in order to identify the optimum conditions to achieve high conductivity and transmittance. The electrical properties of PEDOT:PSS thin films were investigated using a four-point probe, and their transmittance was determined using an UV–vis spectrometer. The surface morphology was observed by field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM). A stable conductivity in the range of 110–204 S/cm was obtained at 0–30% DMSO concentrations, and the transmittances were greater than 92% in the visible range.

Fabrication of a Touch Sensor for Flat Panel Displays Using Poly(3,4-ethylenedioxythiophene):Poly(styrene sulfonate) with Dimethylsulfoxide by Soft Lithography

The flash translation layer (FTL) plays an important role in achieving high performance and reliability for nand flash-based storage devices. To ensure metadata consistency for storage requests, FTL is forced to save its own metadata to nand flash memory. However, a large number of FTL metadata writes can impair the lifetime of nand flash-based storage devices. Even though a small fraction of metadata is updated in the internal memory, FTL should write the whole flash page with the redundant data. In this paper, we utilize the subpage programming (SP) technique to decrease the amount of FTL metadata written to the nand flash memory. We also propose a novel FTL called subpage FTL based on the SP technique to prolong the lifetime of embedded nand flash-based storage. The evaluation results show that SPFTL reduces the written amount of FTL metadata by up to 45.4%, and therefore enhances the lifetime of a storage device by up to 19.3% in real workloads.

Utilizing Subpage Programming to Prolong the Lifetime of Embedded NAND Flash-Based Storage

Background It can be difficult to select an appropriate flap for various defects on the hand Although defects of the hand usually must be covered with a skin flap, some defects require a flap with rich blood supply and adequate additive soft tissue volume The authors present their experience with the anconeus muscle free flap in the reconstruction of various defects and the release of scar contractures of the hand Methods Ten patients underwent reconstruction of the finger or release of the first web space using the anconeus muscle free flap from May 1998 to October 2013 Adequate bed preparations with thorough debridement or contracture release were performed The entire anconeus muscle, located at the elbow superficially, was harvested, with the posterior recurrent interosseous artery as a pedicle The defects were covered with a uniformly trimmed anconeus muscle free flap Additional debulking of the flap and skin coverage using a split-thickness skin graft were performed 3 weeks after the first operation Results The average flap size was 187 cm2 (range, 135-30 cm2) All flaps survived without significant complications Vein grafts for overcoming a short pedicle were necessary in 4 cases Conclusions The anconeus muscle free flap can be considered a reliable reconstructive option for small defects on the hand or contracture release of the web space, because it has relatively consistent anatomy, provides robust blood supply within the same operative field, and leads to no functional loss at the donor site

/pdf/the-anconeus-muscle-free-flap-clinical-application-to-325p6u7n5x.pdf

The Anconeus Muscle Free Flap: Clinical Application to Lesions on the Hand.

Background The introduction of the partial second toe pulp free flap has enabled superior aesthetic and functional results for fingertip reconstruction in adults. Children undergoing fingertip amputation for various reasons have limited options for reconstruction. Conventional treatment could shorten the finger, leading to poor cosmesis and function. We report 18 years of our experiences with fingertip reconstruction using partial second toe pulp free flaps in patients in early childhood. Methods Medical charts of children who had undergone fingertip reconstruction using partial second toe pulp free flaps from 2001 to 2018 were retrospectively reviewed. The surgical procedures were identical to those for adults, except for the usage of 11-0 nylon sutures. Patients' demographic data, vessel size, flap dimensions, length of the distal phalanx, and functional outcomes over the course of long-term follow-up were documented. The statistical analysis was performed with the Student t-test, the Mann-Whitney U test, and Pearson correlation analysis. Results Eighteen toe pulp flaps in 17 patients (mean age, 3.0 years) were identified. All the flaps survived without any major complications. In long-term follow-up, the flap-covered distal phalanges showed growth in line with regular development. There was no donor-site morbidity, and all children adapted to daily life without any problems. In two-point discrimination tests, the fingertip sensation recovered to almost the same level as that in the contralateral finger. Conclusions Partial second toe pulp free flaps are an excellent option for fingertip reconstruction in young children, as well as in adults.

/pdf/partial-second-toe-pulp-free-flaps-in-early-childhood-3rkln4fxpq.pdf

Partial second toe pulp free flaps in early childhood

CANDOR compared the safety/efficacy of carfilzomib with dexamethasone and daratumumab (KdD) to carfilzomib with dexamethasone (Kd) in adults with relapsed/refractory multiple myeloma (RRMM). This CANDOR subgroup analysis evaluated outcomes based on cytogenetic risk. Overall response rates (KdD vs. Kd) were 81% versus 56% in high‐risk and 87% versus 79% in standard‐risk groups. Median progression‐free survival was 11.2 versus 7.4 months in high‐risk (hazard ratio, 0.56 [95% CI, 0.34, 0.93]) and not reached versus 16.6 months in standard‐risk groups (0.56 [95% CI, 0.39, 0.80]). These data support the efficacy of KdD in RRMM treatment, including in patients with high‐risk cytogenetics.

Jin-Soo Kim

Papers

Fabrication of a Touch Sensor for Flat Panel Displays Using Poly(3,4-ethylenedioxythiophene):Poly(styrene sulfonate) with Dimethylsulfoxide by Soft Lithography

Utilizing Subpage Programming to Prolong the Lifetime of Embedded NAND Flash-Based Storage

The Anconeus Muscle Free Flap: Clinical Application to Lesions on the Hand.

Partial second toe pulp free flaps in early childhood

Subgroup analysis based on cytogenetic risk in patients with relapsed or refractory multiple myeloma in the CANDOR study