Preliminary design of high power magnet converter for CRAFT

In order to test the superconducting magnet performance for the Comprehensive Research Facility for Fusion Technology(CRAFT)project of China,a power supply converter needs to be designed.In this paper,short circuits upstream and downstream of the direct current(DC)reactor are analyzed,and the thyristor style and the parallel number are determined by the limit analysis of junction temperature and fault current I^2t.On this basis,the over current and voltage verification of fast fuse are finished to protect the thyristor at fault cases by considering the short circuit of the bridge arm.Then,the resistor and capacitor parameters of thyristor snubber are committed to decreasing the reverse over voltage.These analysis results will be used as the preliminary design of high power magnet converter for CRAFT.

基于体细胞突变数据库筛选免疫原性结直肠癌高频新抗原的方法

结直肠癌是世界高发和高致死率的恶性肿瘤。靶向新抗原的免疫治疗已被证实可以诱导癌症患者肿瘤持续消退,但这些特异性新抗原,仅适用于个体精准治疗。随着大量的高频肿瘤基因突变被发现,这些与突变相关的高频新抗原可覆盖更多人群,具有较强的临床意义。然而目前结直肠癌中是否也存在高频新抗原仍不清楚。本研究利用来源于321个结直肠癌患者的体细胞突变数据库,联合1种标准过滤和7种预测算法,筛选并获得了25个基于中国人高频分型HLA-A^*1101限制性的高频新抗原,它们均具有高亲和力(IC50<50 nmol/L)和高呈递分值(>0.90);其中,除了阳性对照多肽KRAS_G12V8-16外,11个高频新抗原能够在体外诱导细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)分泌γ干扰素(interferon gamma,IFN-γ),证实具有免疫原性。选取免疫原性最强的新抗原C1orf170_S418G413-421及阳性对照多肽KRAS_G12V8-16体外刺激T细胞,利用流式细胞分选及单细胞转录组测序技术,获得其特异性CTL的免疫组库信息,所构建的TCR-T(T-cell receptor engineered T cell)能够识别新抗原并分泌细胞因子。以上结果表明,本研究开发了一种利用体细胞数据库预测并体外筛选验证具有免疫原性高频新抗原的方法,为结直肠癌及其他癌种的多肽、DC(dendritic cells)疫苗、TCR-like抗体、TCR-T等免疫治疗提供了重要的多肽靶点和TCR信息,具有实际的临床应用价值。

Regulating dissolution chemistry of nitrates in carbonate electrolyte for high-stable lithium metal batteries

Lithium metal batteries(LMBs)have received increasing attention due to the high energy density.However,the practical application of LMBs is limited due to the incompatibility of ester electrolytes.Transition metal(TM)nitrates have been reported as effective additives in ester electrolyte to improve the stability of lithium anode.Unfortunately,the nitrates are restricted to use due to their poor solubility.We find that the nitrates containing crystal water have high solubility in ester electrolytes.Considering that most TM nitrates contain crystal water and the crystal water can be used as a perfect solubilizer of nitrates,thus,the method is of universality and facile without introducing any solubilizing agent.Herein,In(NO_(3))_(3.6)H_(2)O is chosen as one typical case with increased solubility up to 0.2 M compared with In(NO_(3))_(3)which hardly dissolves in ester electrolyte.The additive promotes the rapid and stable formation of the solid electrolyte interface(SEI),which effectively inhibits the lithium dendrites formation.Moreover,the induced cathode electrolyte interface(CEI)maintains the structural stability of Li Ni_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811).As a result,the electrochemical performance of Li|NCM811 cell is obviously improved.Our study provides a new idea for dissolving nitrates in ester electrolytes and discloses the synergistic function of TM-ions.

Discussions about Modern Standardized Production of Genuine Traditional Chinese Herbal Medicines

In recent years,with the vigorous development of the Chinese herbal medicine market in China,the government and various circles of society pay close attention to the safety of Chinese herbal medicine production. The cultivation and production of traditional Chinese herbal medicine already could not satisfy the current market demands. This paper summarized the forming,changing and the influencing factors of Chinese herbal medicines,and organized the research for the formation of traditional Chinese herbal medicines by modern scholars in China. It reached the following conclusion: the production of modern Chinese herbal medicines should ensure its unique properties,and the more important is to guarantee the quality and safety. With the continuous improvement of science and technology innovation ability and the appraisal method of Chinese medicines,the better management system has been applied in the process of planting. This paper summarized the six attributes of modern production of Chinese herbal medicines,to ensure genuine,safe and standardized production of traditional Chinese medicines.

In situ synthesized homochiral dysprosium-oxo clusters with threonine Schiff bases

Chiral high-nuclearity lanthanide(4f)clusters have shown fantastic properties in various fields.However,their synthesis is still of great challenge.Herein,we report two pairs of enantiomers of highnuclearity Dy-oxo clusters synthesized through in situ strategy.They are[Dy18(^(R/S)Hftp)4(^(R/S)H_(2)btp)4(μ2-OH)_(8)(μ3-OH)20(μ6-O)(NO_(3))_(4)(μ-H_(2)O)_(8)]·[solvents](1R and 1S)and[Dy9(^(R/S)Hftp)2(^(R/S)H_(2)btp)_(2)(OAc)_(6)(μ3-OH)_(10)(H_(2)O)_(6)](OAc)·[solvents](2R and 2S),where^(R/S)Hftp2−and^(R/S)H_(2)btp^(3−)represent in situ formed 2-formyl-6-[N-(threonine)iminomethyl]-4-methylphenol and 2,6-bis[N-(threonine)iminomethyl]-4-methylphenol anions,respectively.These in situ formed clusters were endowed with not only homochirality via introducing^(R/S)Hftp2−and^(R/S)H_(2)btp^(3−)ligands,but also rich oxo-bridges by controlling the hydrolysis of Dy^(III)ions.Different anions from DyIII salts further induced structural variation between two sets of clusters.1R and 1S feature an unprecedent four-blade propeller shaped{Dy18}core,whose centered octahedral{Dy6}unit are surrounded by four triangular{Dy3}units.Strikingly,they represent the second largest chiral 4f cluster species so far.2R and 2S display a sandglass-like{Dy9}skeleton that consist of two square pyramid{Dy5}units sharing a Dy^(III)vertex.Magnetic investigation revealed possible antiferromagnetic interactions between the Dy^(III)centers in these clusters.

Characterization and validation of somatic mutation spectrum to reveal heterogeneity in gastric cancer by single cell sequencing

Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor prognosis.However, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demonstrated. We performed single-cell whole exome sequencing to detect somatic singlenucleotide variants(SNVs) and significantly mutated genes(SMGs) among 34 tumor cells and 9 normal cells from a patient with GC. The Complete Prediction for Protein Conformation(CPPC) approach directly predicting the folding conformation of the protein 3D structure with Protein Folding Shape Code, combined with functional experiments were used to confirm the characterization of mutated SMGs in GC cells. We identified 201 somatic SNVs, including 117 non-synonymous mutations in GC cells. Further analysis identified 24 significant mutated genes(SMGs) in single cells, for which a single amino acid change might affect protein conformation. Among them, two genes(CDC27 and FLG) that were mutated only in single cells but not in the corresponding tumor tissue, were recurrently present in another GC tissue cohort, and may play a potential role to promote carcinogenesis, as confirmed by functional characterization. Our findings showed a mutational landscape of GC at intra-tumor level for the first time and provided opportunities for understanding the heterogeneity and individualized target therapy for this disease.

Single-cell brain atlas of Parkinson's disease mouse model

Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell types,which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types.Here,we report the application of single-nucleus RNA-seq on midbrain,striatum,and cerebellum of theα-syn-A53 T mouse,a well-established PD mouse model,and matched controls,generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells.Additionally,we comprehensively depicte the dysfunctions in PD pathology,covering the elevation of NF-k B activity,the alteration of ion channel components,the perturbation of protein homeostasis network,and the dysregulation of glutamatergic signaling.Notably,we identify a variety of cell types closely associated with PD risk genes.Taken together,our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution,which facilitates the development of novel approaches for diagnosis and therapies against PD.

Rift Valley Fever Virus and Yellow Fever Virus in Urine: A Potential Source of Infection

Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health(Weaver et al.2018).Yellow fever virus(YFV,family Flaviviridae,genus Flavivirus)is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years(Domingo et al.2018).

A legacy of the “1% program”-The “Chinese Chapter” of the human genome reference sequence

The year of 2018 marks the 65th anniversary of the discovery of DNA double helix and the 15th anniversary of the successful completion of the international Human Genome Project (HGP),the two revolutions in life sciences (Sharp, 2014). The year also sees the effective implementation of the "1%Program", the Chinese contribution to the reference sequence of the human genome,which coincides with the 40th anniversary of the founding of the Genetics Society of China, one of the most influential national academic organizations in China.

3D Genome Tuner:Compare Multiple Circular Genomes in a 3D Context

Circular genomes, being the largest proportion of sequenced genomes, play an important role in genome analysis. However, traditional 2D circular map only provides an overview and annotations of genome but does not offer feature-based comparison. For remedying these shortcomings, we developed 3D Genome Tuner,a hybrid of circular map and comparative map tools. Its capability of viewing comparisons between multiple circular maps in a 3D space offers great benefits to the study of comparative genomics. The program is freely available （under an LGPL licence） at http：//sourceforge.net/projects/dgenometuner.

DNA Copy Number Aberrations in Breast Cancer by Array Comparative Genomic Hybridization

Array comparative genomic hybridization （CGH） has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome （2GH arrays. A number of highly frequent genomic aberrations were discovered, which may act as ＂drivers＂ of tumor progression. Meanwhile, the genomic profiles of four ＂normal＂ breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.

A Novel Approach for Identifying the Heme-Binding Proteins from Mouse Tissues

Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein complexes. Traditionally studies of heme-binding proteins have been approached on a case by case basis, thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues. The procedure described here is aimed at profiling heme-binding proteins in mouse tissues sequentially by 1) purification of heme-binding proteins by heme-agarose, an affinity chromatographic resin; 2) isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis; 3) identification of heme-binding proteins by mass spectrometry. In five mouse tissues, over 600 protein spots were visualized on 2DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF, in which most proteins belong to heme related. This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.

A single-cell approach to engineer CD8+ T cells targeting cytomegalovirus

T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.^(2) CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor(TCR)-engineered T cells(TCR-Ts)provides an encouraging alternative treatment option for patients with CMV reactivation.^(4) However,generating TCR-Ts requires the identification of epitope-specific and functional TCR pairs.Modern single-cell sequencing techniques open up the ability to unravel TCR repertoires,^(5 )which offers a potential opportunity to screen functional TCR pairs for TCR-T therapy.Here,we report an efficient approach that combines ex vivo CD8+T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.

GNL-Scorer: a generalized model for predicting CRISPR on-target activity by machine learning and featurization

CRISPR/Cas9 is an adaptive immunity system in bacteria and most archaea(Koonin and Makarova,2009;Horvath and Barrangou,2010).The CRISPR/Cas9 gene editing system is comprised of two key components,a small guide RNA(gRNA)and a Cas9 endonuclease(Deltcheva etal.,2011;Jineketal.,2012).