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Due to the strong analytical ability of big data, deep learning has been widely applied to model on the collected data in industrial IoT. However, for privacy issues, traditional data-gathering centralized learning is not applicable to industrial scenarios sensitive to training sets, such as face recognition and medical systems. Recently, federated learning has received widespread attention, since it trains a model by only sharing gradients without accessing training sets. But existing researches reveal that the shared gradient still retains the sensitive information of the training set. Even worse, a malicious aggregation server may return forged aggregated gradients. In this paper, we propose the VFL, a verifiable federated learning with privacy-preserving for big data in industrial IoT. Specifically, we use Lagrange interpolation to elaborately set interpolation points for verifying the correctness of the aggregated gradients. Compared with existing schemes, the verification overhead of VFL remains constant regardless of the number of participants. Moreover, we employ the blinding technology to protect the privacy of the privacy gradients. If no more than n-2 of n participants collude with the aggregation server, VFL could guarantee the encrypted gradients of other participants not being inverted. Experimental evaluations corroborate the practical performance of the presented VFL with high accuracy and efficiency.

Bioactive macromolecule mining is important for the functional chemome dissection of traditional Chinese vinegar. Here, saccharide-bearing macromolecules in Shanxi aged vinegar (SBMSAV) were isolated, characterized, and their immunomodulatory activity was evaluated. Four sub-fractions were obtained through ethanol precipitation followed by refining and DEAE-650M column chromatography. All sub-fractions had a maximum molecular weight of more than 2,667 kDa, with 10 types of monosaccharides identified. Comparative analysis of these sub-fractions with melanoidins from real food and model systems showed that all four sub-fractions had similarities with both melanoidins in elemental composition, spectral signature, and pyrolytic characteristics. Immunological assays showed that the four sub-fractions significantly improved macrophage cell viability and phagocytic activity, and promoted the secretion of NO, TNF-α, and IL-6. Immunomodulatory mechanism investigation indicated that SBMSAV enhanced aerobic glycolysis in macrophages and were recognized through TLR2, TLR4, MR, SR, and Dectin-1. Additionally, the MyD88/PI3K/Akt/NF-κB signaling pathway was found to be involved in the activation of macrophages.

This is a dialogue between Paulos Huang (Professor at Shanghai University) and Xianglong Zhang on the cooperation in the Filial Piety of Family between Confucianism and Christianity. It includes the following issues: How has Professor Lin HE influenced Zhang to study philosophy? Zhang’s study on Phenomenology and Daoism in USA. How has Zhang changed his study focus from Phenomenology into Chinese traditions after he returned to China from USA? The cooperation potentiality between Confucianism and Christianity on the filial piety of family. How has Amish in Pennsylvania influenced Zhang to promote similar Confucian special zone in China? The aim of education to study so as to become a real human being in Confucianism and Finland.

Sepsis is a leading cause of mortality in intensive care unit worldwide, it's accompanied by immune cell dysfunction induced by multiple factors. However, little is known about the specific alterations in immune cells in the dynamic pathogenesis of sepsis secondary to bacterial pneumonia. Here, we used single cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) in a healthy control and two patients with sepsis secondary to bacterial pneumonia, including acute, stable and recovery stage. We analyzed the quantity and function of immune cells. During disease course, interferon gamma response was upregulated; T/NK cell subtypes presented activation and exhaustion properties, which might be driven by monocytes through IL-1β signaling pathways; The proportion of plasma cells was increased, which might be driven by NK cells through IFN signaling pathways; Additionally, interferon gamma response was upregulated to a greater degree in sepsis secondary to pneumonia induced by SARS-COV-2 compared with that induced by influenza virus and bacteria.

Background The 15q13.3 microdeletion is associated with several neuropsychiatric disorders, including autism and schizophrenia. Previous association and functional studies have investigated the potential role of several genes within the deletion in neuronal dysfunction, but the molecular effects of the deletion as a whole remain largely unknown. Methods Induced pluripotent stem cells, from 3 patients with the 15q13.3 microdeletion and 3 control subjects, were generated and converted into induced neurons. We analyzed the effects of the 15q13.3 microdeletion on genome-wide gene expression, DNA methylation, chromatin accessibility, and sensitivity to cisplatin-induced DNA damage. Furthermore, we measured gene expression changes in induced neurons with CRISPR (clustered regularly interspaced short palindromic repeats) knockouts of individual 15q13.3 microdeletion genes. Results In both induced pluripotent stem cells and induced neurons, gene copy number change within the 15q13.3 microdeletion was accompanied by significantly decreased gene expression and no compensatory changes in DNA methylation or chromatin accessibility, supporting the model that haploinsufficiency of genes within the deleted region drives the disorder. Furthermore, we observed global effects of the microdeletion on the transcriptome and epigenome, with disruptions in several neuropsychiatric disorder–associated pathways and gene families, including Wnt signaling, ribosome function, DNA binding, and clustered protocadherins. Individual gene knockouts mirrored many of the observed changes in an overlapping fashion between knockouts. Conclusions Our multiomics analysis of the 15q13.3 microdeletion revealed downstream effects in pathways previously associated with neuropsychiatric disorders and indications of interactions between genes within the deletion. This molecular systems analysis can be applied to other chromosomal aberrations to further our etiological understanding of neuropsychiatric disorders.

Significance Turner syndrome (TS) is caused by having only one X chromosome (X0), and Klinefelter syndrome (KS) by having two X chromosomes and one Y chromosome (XXY). In this study we carried out a direct comparison analysis of the effect these chromosome copy number aberrations have on gene expression networks, analyzing genes located on the X chromosome or anywhere else in the genome, in primary samples from KS and TS patients. In both KS and TS, we found gene expression level changes not only in genes on the X chromosome, but also in many genes on all the other chromosomes, revealing a genomewide ripple effect of the chromosome X copy number aberrations., In both Turner syndrome (TS) and Klinefelter syndrome (KS) copy number aberrations of the X chromosome lead to various developmental symptoms. We report a comparative analysis of TS vs. KS regarding differences at the genomic network level measured in primary samples by analyzing gene expression, DNA methylation, and chromatin conformation. X-chromosome inactivation (XCI) silences transcription from one X chromosome in female mammals, on which most genes are inactive, and some genes escape from XCI. In TS, almost all differentially expressed escape genes are down-regulated but most differentially expressed inactive genes are up-regulated. In KS, differentially expressed escape genes are up-regulated while the majority of inactive genes appear unchanged. Interestingly, 94 differentially expressed genes (DEGs) overlapped between TS and female and KS and male comparisons; and these almost uniformly display expression changes into opposite directions. DEGs on the X chromosome and the autosomes are coexpressed in both syndromes, indicating that there are molecular ripple effects of the changes in X chromosome dosage. Six potential candidate genes (RPS4X, SEPT6, NKRF, CX0rf57, NAA10, and FLNA) for KS are identified on Xq, as well as candidate central genes on Xp for TS. Only promoters of inactive genes are differentially methylated in both syndromes while escape gene promoters remain unchanged. The intrachromosomal contact map of the X chromosome in TS exhibits the structure of an active X chromosome. The discovery of shared DEGs indicates the existence of common molecular mechanisms for gene regulation in TS and KS that transmit the gene dosage changes to the transcriptome.

Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present transcriptomic and proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues, such as the liver, kidney, brain, and heart. Immune response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Incorporating human single-cell RNA sequencing findings corroborates the role of macrophages and monocytes in obesity. Moreover, we highlight some potential therapeutic targets including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our findings provide insights into tissue-specific molecular foundations of obesity and T2D and reveal the mechanistic links between these two metabolic disorders.

As the characteristic size of integrated circuits has continued to shrink, there has been increasing interest in using aluminum (Al) as the gate material. In this paper, we have looked at the role ethylenediamine tetraacetic acid dipotassium (EDTA-2K) plays in the chemical mechanical polishing (CMP) of Al for use as a gate material. Currently, the preferred approach to CMP is to use colloidal silica as an abrasive, EDTA-2K as the complexing agent, and H2O2 as the oxidant. We have explored the influence of EDTA-2K and H2O2 on the Al removal rate (RR) during CMP. The results show that when the concentration of EDTA-2K is 1 wt%, the removal rate reaches 3450 Å min−1, and the surface roughness is 0.425 nm. The mechanism of the action of EDTA-2K during CMP was studied through particle size distribution analysis, X-ray photoelectron spectroscopy (XPS), electrochemical tests, and UV–visible (UV–vis) spectroscopy. The results show that EDTA-2K reacts with aluminum ions (Al3+) to form a soluble Al-EDTA complex, which promotes the corrosion rate on the Al surface and thus increases the removal rate of Al.

Tea residue is a by-product of tea processing and contains ∼ 60 % insoluble dietary fiber. We investigated the physicochemical properties and structure of the insoluble dietary fiber of tea (T-IDF), and its defecation function was evaluated. The physical and chemical indexes of the T-IDF, including its water holding, oil holding, swelling, cation exchange, and cholesterol exchange capacities, were measured, while its structure was analyzed by a range of analytical techniques. Furthermore, the related indexes of the animal defecation function were determined, and the in vitro detection of fermented short chain fatty acid was conducted. We found that T-IDF exhibits excellent physical and chemical properties. Moreover, the consumption of T-IDF significantly promoted defecation in slow transit intestinal dyskinesia mice and enhanced the production of short chain fatty acids. Overall, we demonstrated a good correlation between the physicochemical properties and the structure/function of T-IDF.

The traditional method for analyzing the content of instant tea has disadvantages such as complicated operation and being time-consuming. In this study, a method for the rapid determination of instant tea components by near-infrared (NIR) spectroscopy was established and optimized. The NIR spectra of 118 instant tea samples were used to evaluate the modeling and prediction performance of a combination of binary particle swarm optimization (BPSO) with support vector regression (SVR), BPSO with partial least squares (PLS), and SVR and PLS without BPSO. Under optimal conditions, Rp for moisture, caffeine, tea polyphenols, and tea polysaccharides were 0.9678, 0.9757, 0.7569, and 0.8185, respectively. The values of SEP were less than 0.9302, and absolute values of Bias were less than 0.3667. These findings indicate that machine learning can be used to optimize the detection model of instant tea components based on NIR methods to improve prediction accuracy.

Heterozygous NRXN1 deletions constitute the most prevalent currently known single-gene mutation predisposing to schizophrenia. Previous studies showed that engineered heterozygous NRXN1 deletions impaired neurotransmitter release in human neurons, suggesting a synaptic pathophysiological mechanism. Utilizing this observation for drug discovery, however, requires confidence in its robustness and validity. Here, we describe a multi-center effort to test the generality of this pivotal observation, using independent analyses at two laboratories of patient-derived and newly engineered human neurons with heterozygous NRXN1 deletions. We show that in neurons that were trans-differentiated from induced pluripotent stem cells derived from three NRXN1-deletion patients, the same impairment in neurotransmitter release was observed as in engineered NRXN1-deficient neurons. This impairment manifested as a decrease in spontaneous synaptic events and in evoked synaptic responses, and an alteration in synaptic paired-pulse depression. Nrxn1-deficient mouse neurons generated from embryonic stem cells by the same method as human neurons did not exhibit impaired neurotransmitter release, suggesting a human-specific phenotype. NRXN1 deletions produced a reproducible increase in the levels of CASK, an intracellular NRXN1-binding protein, and were associated with characteristic gene expression changes. Thus, heterozygous NRXN1 deletions robustly impair synaptic function in human neurons regardless of genetic background, enabling future drug discovery efforts.

High-fat diet-induced fatty liver is an indolent and chronic disease accompanied by immune dysfunction and metabolic disturbances involving numerous biological pathways. This study investigated how this abnormal metabolic disorder influences sepsis in mice. Mice were fed with normal chow (NC) or high-fat diet (HFD), and palmitic acid (PA) was used to treat hepatocytes to mimic fat accumulation in vitro. Lipopolysaccharide (LPS) was used to induce sepsis and related immune responses. Mice fed on a high-fat diet displayed higher mortality and more severe liver damage but compromised immunoreaction. The supernatant from PA-treated primary hepatocytes markedly diminished the inflammatory cytokine expression of macrophages after LPS stimulation, which showed a state of immunosuppression. Metabolomics analysis indicated the level of many key metabolites with possible roles in immunoreaction was altered in the HFD and PA groups compared with corresponding controls; specifically, β-hydroxybutyric acid (BHB) showed an immunosuppressive effect on Raw264.7 cells during the LPS stimulation. Transcriptomic analysis suggested that several differential signaling pathways may be associated with the alteration of immune function between the NC and HFD groups, as well as in the in vitro model. Our study suggests that the consumption of HFD may alter the hepatic metabolic profile, and that certain metabolites may remold the immune system to immunosuppressive state in the context of sepsis.

Copy number variants (CNVs), either deletions or duplications, at the 16p11.2 locus in the human genome are known to increase the risk for autism spectrum disorders (ASD), schizophrenia, and for several other developmental conditions. Here, we investigate the global effects on gene expression and DNA methylation using a 16p11.2 CNV patient-derived induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system. This approach revealed genome-wide and cell-type specific alterations to both gene expression and DNA methylation patterns and also yielded specific leads on genes potentially contributing to some of the known 16p11.2 patient phenotypes. PCSK9 is identified as a possible contributing factor to the symptoms seen in carriers of the 16p11.2 CNVs. The protocadherin (PCDH) gene family is found to have altered DNA methylation patterns in the CNV patient samples. The iPSC lines used for this study are available through a repository as a resource for research into the molecular etiology of the clinical phenotypes of 16p11.2 CNVs and into that of neuropsychiatric and neurodevelopmental disorders in general.

BackgroundCopy number variation (CNV) analysis is an integral component of the study of human genomes in both research and clinical settings. Array-based CNV analysis is the current first-tier approach in clinical cytogenetics. Decreasing costs in high-throughput sequencing and cloud computing have opened doors for the development of sequencing-based CNV analysis pipelines with fast turnaround times. We carry out a systematic and quantitative comparative analysis for several low-coverage whole-genome sequencing (WGS) strategies to detect CNV in the human genome.MethodsWe compared the CNV detection capabilities of WGS strategies (short insert, 3 kb insert mate pair and 5 kb insert mate pair) each at 1×, 3× and 5× coverages relative to each other and to 17 currently used high-density oligonucleotide arrays. For benchmarking, we used a set of gold standard (GS) CNVs generated for the 1000 Genomes Project CEU subject NA12878.ResultsOverall, low-coverage WGS strategies detect drastically more GS CNVs compared with arrays and are accompanied with smaller percentages of CNV calls without validation. Furthermore, we show that WGS (at ≥1× coverage) is able to detect all seven GS deletion CNVs >100 kb in NA12878, whereas only one is detected by most arrays. Lastly, we show that the much larger 15 Mbp Cri du chat deletion can be readily detected with short-insert paired-end WGS at even just 1× coverage.ConclusionsCNV analysis using low-coverage WGS is efficient and outperforms the array-based analysis that is currently used for clinical cytogenetics.

LANGUAGE NOTE | Document text in Chinese; abstract also in English.首先闡明儒家與基督教及古希臘文化各自對於同性戀的態度。儒家與基督教的嚴厲排斥和古希臘人的某種鼓勵皆不同，對同性戀持一種有保留的寬容態度，對於同性戀個人的評價更是以其道德行為為依據。為了理解儒耶在這個問題上分歧的深層原因，審視了西方的二元分叉和古代中國陰陽互補對生的不同思想方式。儒家因此將同性戀人群的產生歸為陰陽發生過程的可能產物，有其自然的原因，並不是一種罪惡。但是，也正是由於儒家信持這樣一個陰陽生發的結構，她不可能贊許同性婚姻的合法化，因為同性戀者的結合畢竟不是陰陽化生的原真形態，將它與異性婚姻在法律地位上等同看待會導致一些對於人類社群長久延續不利的後果。它們包括：這種合法化會從道理上打開通向群婚制的缺口；它還可能會傷害一些無辜者；它具有的某種示範效應可能會引導那些在性別取向上的徘徊者走上他們本來不一定要選擇的性道路。本文的第三部分第一節還依據中英原文，考訂了美國最高法院的甘迺迪法官所引用的孔子話語，說明它在表達形式上的不嚴格和內容上的大致可行。又闡述了此法官的基本思想與這段引文及其上下文所代表的儒家思路的衝突。First, the various attitudes towards homosexuality among Confucianism, Christianity and ancient Greek culture are considered. Distinguished from the Christian harsh repulsion and the Greek slight encouragement, Confucianism has been guardedly tolerant of homosexuality and judged homosexuals according to their personal moral behavior. To reveal the deep reasons for the distinction between Confucianism and Christianity on this issue, the paper examines the differences in thinking between the Western dichotomy and the Confucian genesis by the co-opposites of yin-yang. Confucianism explains homosexuality as one of the possible results of the yin-yang process. It is thereby a natural phenomenon, not an evil thing. However, it is due to this understanding that Confucianism cannot advocate the legalization of homosexual marriage, because a union between homosexuals does not belong to a true yin-yang means of combination and production. To treat it legitimately as being the same as a marriage between heterosexuals could lead to consequences that would be unfavorable to the longevity of human communities, which include, for instance, opening up the possibility of group marriage; hurting innocent people; and leading those who do not have a definite sexual tendency to make a homosexual decision. The third part of the paper refers to the Confucian saying cited by Anthony Kennedy, the Chief Justice of the Supreme Court of the USA, in his statement on the ruling on same-sex marriage, and shows that his citation was inaccurate, but its content was not far from the original meaning of Confucius’ saying. Further, the conflict between Kennedy’s basic thinking and the Confucian thought demonstrated in the citation and its context is exposed.DOWNLOAD HISTORY | This article has been downloaded 329 times in Digital Commons before migrating into this platform.

Heterozygous deletions in the 15q13.3 region are associated with several neuropsychiatric disorders including autism, schizophrenia, and attention deficit hyperactivity disorder. Several genes within the 15q13.3 deletion region may play a role in neuronal dysfunction, based on association studies in humans and functional studies in mice, but the intermediate molecular mechanisms remain unknown. We analyzed the genome-wide effects of the 15q13.3 microdeletion on the transcriptome and epigenome. Induced pluripotent stem cell (iPSC) lines from three patients with the typical heterozygous 15q13.3 microdeletion and three sex-matched controls were generated and converted into induced neurons (iNs) using the neurogenin-2 induction method. We analyzed genome-wide gene expression using RNA-Seq, genome-wide DNA methylation using SeqCap-Epi, and genome-wide chromatin accessibility using ATAC-Seq, in both iPSCs and iNs. In both cell types, gene copy number change within the 15q13.3 microdeletion was accompanied by significantly decreased gene expression and no compensatory changes in DNA methylation or chromatin accessibility, supporting the model that haploinsufficiency of genes within the deleted region drives the disorder. Further, we observed global effects of the deletion on the transcriptome and epigenome, with the effects being cell type specific and occurring at discrete loci. Several genes and pathways associated with neuropsychiatric disorders and neuronal development were significantly altered, including Wnt signaling, ribosome biogenesis, DNA binding, and clustered protocadherins. This molecular systems analysis of a large neuropsychiatric microdeletion can also be applied to other brain relevant chromosomal aberrations to further our etiological understanding of neuropsychiatric disorders.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, with a high prevalence and a presumed high heterogeneity. Copy number variants (CNVs) could contribute to the heritable component of risk, but the two previous genome-wide association studies of rare CNVs did not report significant findings. METHODS: In this meta-analysis of four cohorts (5780 patients and 6626 control subjects), we analyzed the association of MDD to 1) genome-wide burden of rare deletions and duplications, partitioned by length (,100 kb or .100 kb) and other characteristics, and 2) individual rare exonic CNVs and CNV regions. RESULTS: Patients with MDD carried significantly more short deletions than control subjects (p = .0059) but not long deletions or short or long duplications. The confidence interval for long deletions overlapped with that for short deletions, but long deletions were 70% less frequent genome-wide, reducing the power to detect increased burden. The increased burden of short deletions was primarily in intergenic regions. Short deletions in cases were also modestly enriched for high-confidence enhancer regions. No individual CNV achieved thresholds for suggestive or significant association after genome-wide correction. p values , .01 were observed for 15q11.2 duplications (TUBGCP5, CYFIP1, NIPA1, and NIPA2), deletions in or near PRKN or MSR1, and exonic duplications of ATG5. CONCLUSIONS: The increased burden of short deletions in patients with MDD suggests that rare CNVs increase the risk of MDD by disrupting regulatory regions. Results for longer deletions were less clear, but no large effects were observed for long multigenic CNVs (as seen in schizophrenia and autism). Further studies with larger sample sizes are warranted., This work was supported by a joint grant from the United Kingdom Medical Research Council and GlaxoSmithKline (Grant No. G0701420) and the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service (NHS) Foundation Trust and Institute of Psychiatry, King’s College London. This work presents independent research in part funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This work was also supported by the Wellcome Trust Grant No. 086635 (JJHR); NIHR Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King’s College London (SC-W); a Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme; European Commission Grant Agreement No. 115008); and Canada Research Chairs program

A scheme of closed-loop distribution network by a midvoltage flexible high-temperature superconducting (HTS) dc system is proposed and analyzed. This midvoltage (10-kV) scheme is compared, in terms of capital costs, with that of the closed-loop distribution network by a high-voltage (110-kV) flexible conventional dc system. Based on the HTS cables that are made of the first-generation Bi2223 tapes with a length of 2.5 km, the total investment cost of the 10-kV flexible superconducting dc system with a power capacity of 42 MVA is estimated about 1% lower than that of the 110-kV flexible conventional dc system with the same power capacity, owing to the substantial cost reduction of the voltage-source converter stations with the reduced voltage level. According to the “N - 1” principle of distribution networks, with the interconnecting flexible HTS dc system of 42 MVA, the total power to supply loads of the connected substations can be increased by the same power capacity of the interconnecting system. The simulation results of a three-phase short-circuit fault reveal that the voltage recovery time of the critical loads in the closed-loop distribution network can be reduced to less than 0.1 s, which is much faster than that in open-loop distribution networks.

HepG2 is one of the most widely used human cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher-order structural features of its genome beyond its karyotype were only cursorily known. The high degree of aneuploidy in HepG2 renders traditional genome variant analysis methods challenging and partially ineffective. Correct and complete interpretation of the extensive functional genomics data from HepG2 requires an understanding of the cell line's genome sequence and genome structure. We performed deep whole-genome sequencing, mate-pair sequencing and linked-read sequencing to identify a wide spectrum of genome characteristics in HepG2: copy numbers of chromosomal segments, SNVs and Indels (both corrected for copy-number), phased haplotype blocks, structural variants (SVs) including complex genomic rearrangements, and novel mobile element insertions. A large number of SVs were phased, sequence assembled and experimentally validated. Several chromosomes show striking loss of heterozygosity. We re-analyzed HepG2 RNA-Seq and whole-genome bisulfite sequencing data for allele-specific expression and phased DNA methylation. We show examples where deeper insights into genomic regulatory complexity could be gained by taking knowledge of genomic structural contexts into account. Furthermore, we used the haplotype information to produce an allele-specific CRISPR targeting map. This comprehensive whole-genome analysis serves as a resource for future studies that utilize HepG2.

In this paper, Tungsten Inert Gas Welding (TIG) and single-sided welding and double-sided forming have been used to weld the 7A05-T6/5A06-O dissimilar aluminum alloy circular welded joint of a ring-stiffened closed cylindrical sandwich shell. Microstructural characterization and mechanical properties of welded joints were investigated by use of scanning electron microscopy (SEM), backscatter electron diffraction (EBSD) and transmission electron microscopy (TEM), respectively. Hardness distribution and tensile properties of the welded joints were examined. The results showed the failure of the welded joints produced in the fusion zone (FZ). The tensile strength and yield strength of the welded joints were, respectively, 78.87% and 97.24% of the 5A06-O base metal (BM), and the elongation reached 84.29% of 7A05-T6 base metal. Welding high heat input led to the coarse grain size in the fusion zone, and the long-term similar quenching effect can lead to the full dissolution of the strengthening zone of the fusion zone resulting in the reductions of strength and hardness. Around 7A05 heat-affected zone (HAZ), there is an obvious hardening zone and softening zone, the solid solution precipitates into the Rayleigh brilliant &eta, &prime, (MgZn2) phase, which results in natural aging strengthening, thus obtaining high hardness. &eta, (MgZn2) enhanced phase dissolved fully and the dislocation density decreased rapidly in the HAZ region resulted in a softening zone with a lower hardness at about (10&ndash, 18) mm from the center of the weld center.

Microduplication of chromosome 1q21.1 is observed in ~0.03% of adults. It has a highly variable, incompletely penetrant phenotype that can include intellectual disability, global developmental delay, specific learning disabilities, autism, schizophrenia, heart anomalies and dysmorphic features. We evaluated a 10-year-old-male with a 1q21.1 duplication by CGH microarray. He presented with major attention deficits, phonological dysphasia, poor fine motor skills, dysmorphia and mild autistic features, but not the typical macrocephaly. Neuropsychiatric evaluation demonstrated a novel phenotype: an unusually large discrepancy between non-verbal capacities (borderline-impaired WISC-IV index scores of 70 for Working Memory and 68 for Processing Speed) vs. strong verbal skills – scores of 126 for Verbal Comprehension (superior) and 111 for Perceptual Reasoning (normal). HYDIN2 has been hypothesized to underlie macrocephaly and perhaps cognitive deficits in this syndrome, but assessment of HYDIN2 copy number by microarray is difficult because of extensive segmental duplications. We performed whole-genome sequencing which supported HYDIN2 duplication (chr1:146,370,001-148,590,000, 2.22 Mb, hg38). To evaluate copy number more rigorously we developed droplet digital PCR assays of HYDIN2 (targeting unique 1 kb and 6 kb insertions) and its paralog HYDIN (targeting a unique 154 bp segment outside the HYDIN2 overlap). In an independent cohort, ddPCR was concordant with previous microarray data. Duplication of HYDIN2 was confirmed in the patient by ddPCR. This case demonstrates that a large discrepancy of verbal and non-verbal abilities can occur in 1q21.1 duplication syndrome, but it remains unclear whether this has a specific genomic basis. These ddPCR assays may be useful for future research on HYDIN2 copy number.

Background Large Copy Number Variants (CNVs) in the human genome are strongly associated with common neurodevelopmental, neuropsychiatric disorders such as schizophrenia and autism. However, given that these large CNVs each affect many genes directly and an often even larger number of genes indirectly, understanding the molecular mechanisms that connect these loci with the clinical phenotypes is a considerable challenge. Methods Using Hi-C for the genome-wide analysis of long-range chromosome interactions and ChIP-Seq for the analysis of regulatory histone marks we studied the epigenomic effects of the prominent large deletion CNV on chromosome 22q11.2, in a cohort of Lymphoblastoid Cell Lines (LCLs), and also replicated a subset of the findings in LCLs with the common large deletion CNV on chromosome 1q21.1. Results We found that, in addition to local and global gene expression changes, there are pronounced and multilayered effects on chromatin states, chromosome folding and topological domains of the chromatin that emanate from the large CNV locus. Regulatory histone marks are altered in the deletion proximal regions, and in opposing directions for activating and repressing marks. There are also significant changes of histone marks elsewhere along chromosome 22q and genome wide. Chromosome interaction patterns are weakened within the deletion boundaries and strengthened between the deletion proximal regions. We detected a change in the manner in which chromosome 22q folds onto itself, namely by increasing the long-range contacts between the telomeric end and the deletion proximal region. Further, the large CNV affects the topological domain that is spanning its genomic region. Finally, there is a widespread and complex effect on chromosome interactions genome-wide, i.e. involving all other autosomes, with some of the effect directly tied to the deletion region on 22q11.2. Discussion These findings outline novel principles of how such large genomic deletions can alter nuclear organization and affect genomic molecular activity. Our work demonstrates that there are molecular mechanisms other than the gene expression changes that result from the alteration of the copy number of a given gene, that should be taken into account when studying this problem. Multiple molecular levels of control should be assayed and analyzed in an integrated fashion when studying this essential phenomenon of human genome biology and pathophysiology.

K562 is widely used in biomedical research. It is one of three tier-one cell lines of ENCODE and also most commonly used for large-scale CRISPR/Cas9 screens. Although its functional genomic and epigenomic characteristics have been extensively studied, its genome sequence and genomic structural features have never been comprehensively analyzed. Such information is essential for the correct interpretation and understanding of the vast troves of existing functional genomics and epigenomics data for K562. We performed and integrated deep-coverage whole-genome (short-insert), mate-pair, and linked-read sequencing as well as karyotyping and array CGH analysis to identify a wide spectrum of genome characteristics in K562: copy numbers (CN) of aneuploid chromosome segments at high-resolution, SNVs and Indels (both corrected for CN in aneuploid regions), loss of heterozygosity, mega-base-scale phased haplotypes often spanning entire chromosome arms, structural variants (SVs) including small and large-scale complex SVs and non-reference retrotransposon insertions. Many SVs were phased, assembled, and experimentally validated. We identified multiple allele-specific deletions and duplications within the tumor suppressor geneFHIT. Taking aneuploidy into account, we re-analyzed K562 RNA-seq and whole-genome bisulfite sequencing data for allele-specific expression and allele-specific DNA methylation. We also show examples of how deeper insights into regulatory complexity are gained by integrating genomic variant information and structural context with functional genomics and epigenomics data. Furthermore, using K562 haplotype information, we produced an allele-specific CRISPR targeting map. This comprehensive whole-genome analysis serves as a resource for future studies that utilize K562 as well as a framework for the analysis of other cancer genomes.

LANGUAGE NOTE | Document text in Chinese; abstract also in English.本文首先介紹王鳳儀的人生，說明其開悟體驗如何塑成他的倫理療病術，並闡釋這種不尋常醫術的特點、哲理基礎、具體方法和一些案例，繼而分析倫理療病的作用機制和條件、它與中醫和西醫的相通與不同處，以及它的適用範圍。另外，本文還集中介紹王鳳儀的追隨者――劉有生對此術的繼承和發展。最後，文章總述這種倫理療病術的儒家性，表明倫理療病可以直接作用於人的生命倫理學。First, this paper presents the life of Feng-yi Wang (1864-1937), a peasant thinker who lived in northeastern China and shows how Wang’s experiences of enlightenment enabled him to invent an ethical cure. A serious disease with which Wang had been afflicted for more than 10 years was healed overnight by his sudden recognition that the origin of his illness was not the immorality of his brothers but his own hatred for them and by his profound repentance for this mistake. As a result of this experience, he realized that no universal principles exist for family relationships. Wang underwent two more experiences of enlightenment: the first during a desperate attempt to save a moral friend, and the second during three years spent besides his father’s tomb as an expression of filial love.Second, the characteristics, philosophical foundations and concrete applications of this unusual therapy are explained and some examples are provided. Wang identified the causes of illnesses in disorders of family and other ethical relations, and treated these illnesses by correcting the corresponding ethical disorders. Wang proposed that every human life has three dimensions, heavenly, psychological and desirous. Disease occurs when an individual’s heavenly disposition is obscured or damaged by passionate emotions arising from psychological states and/or desire. It has been argued that Wang regarded the heavenly dimension of human nature as embodied in family bonds, exemplified by the parent-child relationship. Wang’s method of treatment had three steps. First, the patient was encouraged to recognize the potentially fatal nature of her/his situation, and thus to speak with complete sincerity and commitment to finding a cure. Second, the patient’s way of life, especially her/his familial and other ethical relationships, were examined to determine the cause of her/his illness. Third, the patient was told why his/her behavior toward others was immoral and urged to repent thoroughly in front of the offended party, whether a living family member or an ancestor’s memorial tablet. Physical reactions to the treatment such as vomiting and weeping were taken as signs that the method had worked and the illness had been alleviated or cured.The third aim of this paper is to identify the mechanisms of Wang’s ethical treatment, the conditions for its success and the scope of its application. According to the Doctrine of the Mean, complete sincerity is the necessary condition for Wang’s treatment to succeed. A timely and skillful diagnosis arouses a patient’s conscience and encourages her/him to speak sincerely. Therefore, adequate communication is necessary between the diagnostician and the patient. Although Wang’s ethical treatment may seem better suited to psychic than physical ailments, Wang’s followers argue that it can be used to cure physical injuries. In the third section of the paper, Wang’s ethical approach is briefly compared with traditional Chinese medicine and modern Western medicine.Fourth, attention is paid to one of Wang’s followers, You-sheng Liu. In the fifth and final section of the paper, the Confucian properties of Wang’s ethical treatment are described and his approach to medicine is shown to directly affect the ethics of human life.DOWNLOAD HISTORY | This article has been downloaded 468 times in Digital Commons before migrating into this platform.

The adsorbent H8Nb22O59·8H2O and its precursor Rb8Nb22O59 were prepared to produce high-purify NaCl. Their characteristics were studied by X-ray diffraction (XRD), thermogravimetric and differential scanning calorimetry (TG-DSC) and scanning electron microscope (SEM). Two main calcinations factors of calcinations time and temperature were investigated. Results suggest that calcination time rarely influenced the crystal structure probably owing to the high calcination temperature. Furthermore, the high calcination temperature contributed to the stronger crystallinity of precursor Rb8Nb22O59, which shows that the structure of Rb8Nb22O59 was not changed by the extraction of Rb from Rb8Nb22O59 and this process is topotactical. Finally, the present absorbent of H8Nb22O59·8H2O exhibited the excellent selectivity for K ion, indicating that it can be considered as a promising adsorbent for the selective removal of K from sodium chloride solutions.

Confucianism is a rather typical non-universalism, even though it does believe that its own doctrines are indeed the ultimate truth, and denies the validity of any higher, universalist meta-standard. Therefore, when facing the contemporary culture intercourse, Confucianism advocates genuine discourse: It rejects any cultural conflict to-the-death, refuses to engage in universalist competition and antagonism, and maintains a mutually-beneficial interaction with other cultures. However, it also adheres to a “free-to-terminate-relations” principle, which implies that any side is free to terminate, at any time, all potential and actual interactions, whenever it feels that its original cultural vitality is threatened. In other words, cultural interactions must only occur when the cultural uniqueness and independence of all participating sides is guaranteed.

Background Generally, SNPs are abundant in the genome; however, they display low power in linkage analysis because of their limited heterozygosity. Haplotype markers, on the other hand, which are composed of many SNPs, greatly increase heterozygosity and have superiority in linkage statistics. Results Here we developed Haplo2Ped to automatically transform SNP data into haplotype markers and then to compute the logarithm (base 10) of odds (LOD) scores of regional haplotypes that are homozygous within the disease co-segregation haploid group. The results are reported as a hypertext file and a 3D figure to help users to obtain the candidate linkage regions. The hypertext file contains parameters of the disease linked regions, candidate genes, and their links to public databases. The 3D figure clearly displays the linkage signals in each chromosome. We tested Haplo2Ped in a simulated SNP dataset and also applied it to data from a real study. It successfully and accurately located the causative genomic regions. Comparison of Haplo2Ped with other existing software for linkage analysis further indicated the high effectiveness of this software. Conclusions Haplo2Ped uses haplotype fragments as mapping markers in whole genome linkage analysis. The advantages of Haplo2Ped over other existing software include straightforward output files, increased accuracy and superior ability to deal with pedigrees showing incomplete penetrance. Haplo2Ped is freely available at: http://bighapmap.big.ac.cn/software.html.