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Low-density parity-check (LDPC) codes have shown superior error-correcting performance in a variety of data storage system studies, including traditional longitudinal magnetic recording systems. However, perpendicular magnetic recording systems (of increasing interest) exhibit impairments different from longitudinal magnetic recording systems, and thus present new challenges for error-correcting codes. In this effort, we evaluate a structured LDPC code using a perpendicular magnetic recording channel model that includes impairments such as transition noise, nonlinear transition shift, transition percolation, and baseline wander (BLW). The channel model, as well as the LDPC encoder and the decoder are implemented in field-programmable gate array (FPGA) hardware. The LDPC coded system is evaluated down to bit error rate (BER) of [10.sup.-12] and frame error rate (FER) of [10.sup.-8]. The impact of individual impairments on coding performance is studied separately. The soft output Viterbi algorithm (SOVA) + LDPC system maintains its superior error-correcting performance under the perpendicular recording channel. Index Terms--Baseline wander (BLW), EPR4, field-programmable gate array (FPGA), low-density parity-check (LDPC) code, magnetic recording, nonlinear transition shift, partial erasure, perpendicular magnetic recording, transition percolation.

Aiming at the problem of low accuracy of traditional algorithm model, an intelligent recognition model of business English translation based on an improved GLR algorithm is proposed. Through this algorithm, the automatic sentence recognition technology is established, and according to the characteristics of business English, the improved GLR algorithm is used for collection, sorting, and analysis, so as to realize the intelligent recognition of business English. The results show that based on the improved GLR algorithm, the recognition accuracy is high, and the comprehensive score is 92.5 points, which overcomes the disadvantages of the GLR algorithm, and the operation speed and processing are improved. Based on the improved GLR algorithm, the intelligent translation of business English is realized, which is accurate and fast, and greatly promotes the learning and development of business English. [ABSTRACT FROM AUTHOR]

We present the results of performance evaluation of partial response (PR) targets for perpendicular recording by simulation using a field programmable gate array (FPGA). Previous research proposed several PR targets for perpendicular recording channels. We evaluated the bit error rate (BER) performance of those PR targets. Different PR targets led to not only different BERs for given signal-to-noise ratios (SNRs), but also different slopes of BER versus SNR curves. The result can be explained in terms of error event distributions of the corresponding PR targets. In the FPGA simulation, additive white Gaussian noise was used, but no jitter noise was introduced. The soft output Viterbi algorithm is used as the channel detector. A rate-8/9 low-density parity check code with code length 4923 and column weight 3 is used as the error correcting code. Two channel iterations are applied. We attain BERs as low as 10-12. Our results also show that the BER behavior of the PR4 target is significantly different from that of the [1 2 2 1] target. Index Terms--Field programmable gate array (FPGA), partial response (PR) target, perpendicular recording, soft-output Viterbi algorithm (SOVA).

Baseline wander (BLW) is one of major sources of bit errors in perpendicular recording. In this paper, we present a method to compensate for BLW by per-survivor processing (PSP), i.e., along each surviving path in the Viterbi algorithm (VA). We apply the PSP method in VA in timing recovery loop and SOVA for iterative decoding. Simulation results show that the cycle slip rate and bit error rate are lowered and approach ideal case where there is no BLW. Index Terms--Baseline wander (BLW), per-survivor processing (PSP).

Low-density parity check (LDPC) codes have shown near-capacity performance in additive white Gaussian noise (AWGN) channels. However, in magnetic recording systems, the readback signals suffer from various impairments (namely, transition noise, nonlinear transition shift, and partial erasure) in addition to AWGN. In this paper, we describe an FPGA-based advanced magnetic recording channel simulator (that includes these impairments) and an LDPC coding system. The error correcting performances of LDPC codes in the presence of such realistic impairments are investigated down to bit error rate (BER) of [10.sup.-11] and frame error rate (FER) of [10.sup.-8]. Index Terms--EPR4, FPGA, LDPC code, magnetic recording, nonlinear transition shift, partial erasure.

We here report a genome-editing strategy to correct spinal muscular atrophy (SMA). Rather than directly targeting the pathogenic exonic mutations, our strategy employed Cas9 and guide-sgRNA for the targeted disruption of intronic splicing-regulatory elements. We disrupted intronic splicing silencers (ISSs, including ISS-N1 and ISS + 100) of survival motor neuron (SMN) 2, a key modifier gene of SMA, to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs. Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration. Furthermore, co-injection of Cas9 mRNA from Streptococcus pyogenes (SpCas9) or Cas9 from Staphylococcus aureus (SaCas9) alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56% and 100% of severe SMA transgenic mice (Smn −/−, SMN2 tg/−). The median survival of the resulting mice was extended to >400 days. Collectively, our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs), a class of small non-coding RNAs, have been demonstrated to be involved in the development and progression of human malignancies, including cutaneous squamous cell carcinoma (CSCC). miR-186 serves a suppressive role in certain common types of human cancer; however, its exact function in CSCC has not been reported previously. In the present study, the expression of miR-186 was significantly increased in CSCC tissues compared with adjacent non-tumour tissues. Overexpression of miR-186 significantly promoted CSCC cell proliferation while inhibiting cell apoptosis. Reticulophagy regulator 1 (RETREG1), a gene that is significantly downregulated in CSCC tissues and cell lines, was identified as a novel target of miR-186. In addition, the expression of RETREG1 was inversely correlated with miR-186 expression in CSCC tissues. Furthermore, the expression of RETREG1 was negatively regulated by miR-186 in CSCC cells, and restoration of RETREG1 attenuated the effects of miR-186 on CSCC cells. Taken together, the results of the current study suggest that miR-186 serves an oncogenic role in CSCC and may be used as a potential therapeutic target for the treatment of this disease. [ABSTRACT FROM AUTHOR]

RNA-targeting CRISPR system Cas13 offers an efficient approach for manipulating RNA transcripts in vitro. In this perspective, we provide a proof-of-concept demonstration that Cas13-mediated Vegfa knockdown in vivo could prevent the development of laser-induced CNV in mouse model of Age-related macular degeneration. [ABSTRACT FROM AUTHOR]

The process of neuronal migration is precisely regulated by different molecules during corticogenesis. The FAK (focal adhesion kinase) plays a critical role in embryogenesis and is involved in cell motility through focal adhesions, but the underlying mechanisms on inordinate expression are unclear. To investigate the effect of FAK overexpression on neuronal migration spatiotemporally, mice FAK was transfected into the neurons in vivo by electroporation. Results showed that exogenous FAK distributed in the cytoplasm (in vivo) and co-localized with vinculin (in vitro) and induced aberrant neuronal migration via phosphorylation of FAK at Tyr925 during cerebral cortex development. Meanwhile, FAK Y925F mutant also induced aberrant neuronal migration like inordinate FAK/GFP phenotype. All these results implied that FAK-induced abnormal phenotype depended on phosphorylation of FAK at Tyr925, and this demonstrated that the overexpression of FAK impaired neuronal migration through its phosphorylation and activity of FAK during corticogenesis. [ABSTRACT FROM AUTHOR]

In this article, a novel route for the synthesis of graphene/TiO2 continuous fibers (GTF) using force-spinning combined with water vapor annealing method is reported for the first time. The morphology, structure and optical properties of the composite were fully characterized. With a single step of heat treatment process using steam at ambient conditions, we were able to initiate a series of chemical reactions, such as reduction of graphene oxide (GO), crystallization of TiO2, formation of C-Ti bond, and introduction of oxygen vacancies into TiO2. The incorporation of graphene in TiO2 fibers facilitated bandgap narrowing and improved photo-induced charge separation in the photocatalyst. As a result of synergistic effects, TiO2 fibers-2 wt% graphene (2%GTF) showed the highest photocatalytic activities in the degradation of X-3B under UV irradiation, superior to the benchmark photocatalyst P25. Under visible light irradiation, the same catalyst was about 4 times more efficient compared to pure TiO2 fibers (PTF). A detailed study of involved active species (in particular, ·, h+ and ·OH) unraveled the mechanism regarding photocatalysis. [ABSTRACT FROM AUTHOR]

• AAV based-vaccine could efficiently mediate the RBD protein expression of the SARS-CoV-2 in mammalian cells. • AAV based-vaccine could rapidly induce strong immune responses in mice, which maintaining at least six months. • AAV-3xRBD vaccine could elicit the high level of neutralizing antibodies against SARS-CoV-2 in mice. • AAV-3xRBD vaccine has the ability of inducing the specific antibodies against SARS-CoV-2 in canines. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in catastrophic damage worldwide. Accordingly, the development of powerful, safe, easily accessible vaccines with long-term effectiveness is understood as an urgently needed countermeasure against this ongoing pandemic. Guided by this strong promise of using AAVs, we here designed, optimized, and developed an AAV-based vaccines (including AAV-RBD(max), AAV-RBD(wt), AAV-2xRBD, and AAV-3xRBD) that elicit strong immune responses against the RBD domain of the SARS-CoV-2 S protein. These immunogenic responses have proven long-lived, with near peak levels for at least six months in mice. Notably, the sera immunized with AAV-3xRBD vaccine contains powerful neutralizing antibodies against the SARS-CoV-2 pseudovirus. Further evidence proven that potent specific antibodies could also be elicited in canines after vaccination with AAV-3xRBD vaccine. [ABSTRACT FROM AUTHOR]

Background: The CRISPR/Cas9 system has become an efficient gene editing method for generating cells carrying precise gene mutations, including the rearrangement and deletion of chromosomal segments. However, whether an entire chromosome could be eliminated by this technology is still unknown., Results: Here we demonstrate the use of the CRISPR/Cas9 system to eliminate targeted chromosomes. Using either multiple cleavages induced by a single-guide RNA (sgRNA) that targets multiple chromosome-specific sites or a cocktail of multiple sgRNAs, each targeting one specific site, we found that a sex chromosome could be selectively eliminated in cultured cells, embryos, and tissues in vivo. Furthermore, this approach was able to produce a targeted autosome loss in aneuploid mouse embryonic stem cells with an extra human chromosome and human induced pluripotent stem cells with trisomy 21, as well as cancer cells., Conclusions: CRISPR/Cas9-mediated targeted chromosome elimination offers a new approach to develop animal models with chromosome deletions, and a potential therapeutic strategy for human aneuploidy diseases involving additional chromosomes.

The CRISPR/Cas9 system is an efficient gene-editing method, but the majority of gene-edited animals showed mosaicism, with editing occurring only in a portion of cells. Here we show that single gene or multiple genes can be completely knocked out in mouse and monkey embryos by zygotic injection of Cas9 mRNA and multiple adjacent single-guide RNAs (spaced 10-200 bp apart) that target only a single key exon of each gene. Phenotypic analysis of F0 mice following targeted deletion of eight genes on the Y chromosome individually demonstrated the robustness of this approach in generating knockout mice. Importantly, this approach delivers complete gene knockout at high efficiencies (100% on Arntl and 91% on Prrt2) in monkey embryos. Finally, we could generate a complete Prrt2 knockout monkey in a single step, demonstrating the usefulness of this approach in rapidly establishing gene-edited monkey models.

Targeted integration of transgenes can be achieved by strategies based on homologous recombination (HR), microhomology-mediated end joining (MMEJ) or non-homologous end joining (NHEJ). The more generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and ∼800 bp of homology arms, and the targeted genome. We found no significant improvement of the targeting efficiency by the HMEJ-based method in either mouse embryonic stem cells or the neuroblastoma cell line, N2a, compared to the HR-based method. However, the HMEJ-based method yielded a higher knock-in efficiency in HEK293T cells, primary astrocytes and neurons. More importantly, this approach achieved transgene integration in mouse and monkey embryos, as well as in hepatocytes and neurons in vivo, with an efficiency much greater than HR-, NHEJ- and MMEJ-based strategies. Thus, the HMEJ-based strategy may be useful for a variety of applications, including gene editing to generate animal models and for targeted gene therapies.

Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely targeted gene integration in transfected neurons and hepatocytes in vivo with efficiencies up to 20%, much higher (up to 10 fold) than HDR-based strategy in adult mouse tissues. As a proof of concept of its therapeutic potential, we demonstrate the efficacy of MMEJ-based strategy in correction of Fah mutation and rescue of Fah -/- liver failure mice, offering an efficient approach for precisely targeted gene therapies., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis.

Molecular mechanisms underlying the effects of Fyn on cell morphology, pseudopodium movement, and cell migration were investigated. The Fyn gene was subcloned into pEGFP-N1 to produce pEGFP-N1-Fyn. Chinese hamster ovary (CHO) cells were transfected with pEGFP-N1-Fyn. The expression of Fyn mRNA and proteins was monitored by reverse transcription-PCR and Western blotting. Additionally, transfected cells were stained with 4',6-diamidino-2-phenylindole and a series of time-lapse images was taken. Sequences of the recombinant plasmids pMD18-T-Fyn and pEGFP-N1-Fyn were confirmed by sequence identification using National Center for Biotechnology Information in USA, and Fyn expression was detected by RT-PCR and Western blotting. The morphology of CHO cells transfected with the recombinant vector was significantly altered. Fyn expression induced filopodia and lamellipodia formation. Based on these results, we concluded that overexpression of mouse Fyn induces the formation of filopodia and lamellipodia in CHO cells, and promotes cell movement.