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Glioblastoma multiforme (GBM) encompasses brain malignancies marked by phenotypic and transcriptional heterogeneity thought to render these tumors aggressive, resistant to therapy, and inevitably recurrent. However, little is known about how the spatial organization of GBM genomes underlies this heterogeneity and its effects. Here, we compile a cohort of 28 patient-derived glioblastoma stem cell-like lines (GSCs) known to reflect the properties of their tumor-of-origin; six of these were primary-relapse tumor pairs from the same patient. We generate and analyze 5 kbp-resolution chromosome conformation capture (Hi-C) data from all GSCs to systematically map thousands of standalone and complex structural variants (SVs) and the multitude of neoloops arising as a result. By combining Hi-C, histone modification, and gene expression data with chromatin folding simulations, we explain how the pervasive, uneven, and idiosyncratic occurrence of neoloops sustains tumor-specific transcriptional programs via the formation of new enhancer-promoter contacts. We also show how even moderately recurrent neoloops can relate to patient-specific vulnerabilities. Together, our data provide a resource for dissecting GBM biology and heterogeneity, as well as for informing therapeutic approaches. By applying Hi-C to cells derived from the tumors of 24 GBM patients, the authors show pervasive structural variation in GBM chromosomal organization. How such patient-to-patient variation explains the characteristic gene expression patterns in each tumor is investigated. [ABSTRACT FROM AUTHOR]

A new type of rail vibration damping device (NTRVDV), which is arranged between the bottom of the rail and track bed, is proposed in this paper. The finite element model of the rail system with the NTRVDV and tuned rail damper (TRD) was established, respectively. The impact load was applied to the finite element model, and comparison of the set of existing TRD and NTRVDV on the dynamic response of rail and rail vibration decay rate. The effect of the stiffness change of the elastic layer of the NTRVDV on the rail vibration was studied, and a hammering test verified the theoretical research results. The research results show that compared with the traditional TRD, the NTRVDV has a more obvious suppression effect on rail vibration acceleration. The rail vibration decay rate is significantly improved, especially in the low-frequency stage. With the increase of the stiffness of the elastic layer of the vibration suppression device, the vibration suppression effect of the NTRVDV on the rail is improved. The change of the elastic layer stiffness significantly impacts the rail's vibration suppression effect in the range of 0–7 kN/mm. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) represents a set of heterogeneous myeloid malignancies, and hallmarks include mutations in epigenetic modifiers, transcription factors and kinases1–5. The extent to which mutations in AML drive alterations in chromatin 3D structure and contribute to myeloid transformation is unclear. Here we use Hi-C and whole-genome sequencing to analyse 25 samples from patients with AML and 7 samples from healthy donors. Recurrent and subtype-specific alterations in A/B compartments, topologically associating domains and chromatin loops were identified. RNA sequencing, ATAC with sequencing and CUT&Tag for CTCF, H3K27ac and H3K27me3 in the same AML samples also revealed extensive and recurrent AML-specific promoter–enhancer and promoter–silencer loops. We validated the role of repressive loops on their target genes by CRISPR deletion and interference. Structural variation-induced enhancer-hijacking and silencer-hijacking events were further identified in AML samples. Hijacked enhancers play a part in AML cell growth, as demonstrated by CRISPR screening, whereas hijacked silencers have a downregulating role, as evidenced by CRISPR-interference-mediated de-repression. Finally, whole-genome bisulfite sequencing of 20 AML and normal samples revealed the delicate relationship between DNA methylation, CTCF binding and 3D genome structure. Treatment of AML cells with a DNA hypomethylating agent and triple knockdown of DNMT1, DNMT3A and DNMT3B enabled the manipulation of DNA methylation to revert 3D genome organization and gene expression. Overall, this study provides a resource for leukaemia studies and highlights the role of repressive loops and hijacked cis elements in human diseases.Extensive genomic analyses of the chromatin architecture in acute myeloid leukaemia reveals several characteristics, including subtype-specific distal enhancers and silencers, that may represent new anticancer therapeutic targets. [ABSTRACT FROM AUTHOR]

As sequencing depth of chromatin studies continually grows deeper for sensitive profiling of regulatory elements or chromatin spatial structures, aligning and preprocessing of these sequencing data have become the bottleneck for analysis. Here we present Chromap, an ultrafast method for aligning and preprocessing high throughput chromatin profiles. Chromap is comparable to BWA-MEM and Bowtie2 in alignment accuracy and is over 10 times faster than traditional workflows on bulk ChIP-seq/Hi-C profiles and than 10x Genomics' CellRanger v2.0.0 pipeline on single-cell ATAC-seq profiles. As studies continue sequencing with deeper coverage, computational processing of these profiles has become increasingly resource consuming. Here the authors designed an efficient computational method called Chromap to align and preprocess high throughput sequencing data from chromatin profiling techniques, including ChIP-seq, Hi-C, or scATAC-seq, with a major decrease in runtime. [ABSTRACT FROM AUTHOR]

Identifying and analyzing the urban–rural differences of social vulnerability to natural hazards is imperative to ensure that urbanization develops in a way that lessens the impacts of disasters and generate building resilient livelihoods in China. Using data from the 2000 and 2010 population censuses, this study conducted an assessment of the social vulnerability index (SVI) by applying the projection pursuit cluster model. The temporal and spatial changes of social vulnerability in urban and rural areas were then examined during China's rapid urbanization period. An index of urban–rural differences in social vulnerability (SVID) was derived, and the global and local Moran's I of the SVID were calculated to assess the spatial variation and association between the urban and rural SVI. In order to fully determine the impacts of urbanization in relation to social vulnerability, a spatial autoregressive model and Bivariate Moran's I between urbanization and SVI were both calculated. The urban and rural SVI both displayed a steadily decreasing trend from 2000 to 2010, although the urban SVI was always larger than the rural SVI in the same year. In 17.5% of the prefectures, the rural SVI was larger than the urban SVI in 2000, but was smaller than the urban SVI in 2010. About 12.6% of the urban areas in the prefectures became less vulnerable than rural areas over the study period, while in more than 51.73% of the prefectures the urban–rural SVI gap decreased over the same period. The SVID values in all prefectures had a significantly positive spatial autocorrelation and spatial clusters were apparent. Over time, social vulnerability to natural hazards at the prefecture-level displayed a gathering–scattering pattern across China. Though a regional variation of social vulnerability developed during China's rapid urbanization, the overall trend was for a steady reduction in social vulnerability in both urban and rural areas. [ABSTRACT FROM AUTHOR]

Visual processing near the hands is altered compared with stimuli far from the hands. Here, we aimed to test whether this alteration can be found in auditory processing. Participants were required to perform an auditory Simon task either with their hands close to the loudspeakers or far from the loudspeakers. Two experiments consistently showed that the auditory Simon effect was enhanced when the hands were close to the speakers compared with far from the speakers. This is consistent with previous findings of an enhanced visual Simon effect near the hands. Furthermore, the hand-proximity effects in auditory and visual Simon tasks (an enhanced Simon effect near hands compared with far from hands) were comparable, indicating hand-proximity effect is reliable across visual and auditory modalities. Thus, the present study extended the hand-proximity effect from vision to audition by showing that the auditory Simon effect was enhanced near the hands compared with far from the hands. [ABSTRACT FROM AUTHOR]

Understanding and improving the public risk perception have become an important element in the management of flood risk. In China, the risk government is of so-called nationwide catastrophe response mode which is different from the widely adopted "bottom up" risk governance mode in the Western countries. Such a particular mode may make Chinese people perceive risk in a different way from people in other countries. Hence, a further discussion of risk perception is of great value in China. This paper presents a case study on the public perception of flood hazard and flood risk in a city prone to floods. The relationship between risk perception and exposure was examined by spatial analysis. Meanwhile, inferential testing with chi-squared tests was undertaken regarding experience, social trust, and protective behaviors. Our results suggest that (1) the relationship between exposure and risk perception of people in Nanjing is positive and statistically significant, (2) flood experience was strongly related to risk perception, (3) trust showed a significant relationship to risk perception, and (4) people who have perceived the probability of floods and associated loss of life have a higher willingness to take more protective measures. These findings will help local government to develop effective flood risk communication strategies for improving public awareness creation, emergency response and preparedness. [ABSTRACT FROM AUTHOR]

Poly(vinyldiaminotriazine) nanoparticles adsorbed 5-fluorouracil, thymine, theobromine, and xanthine in aqueous phase. Each drug molecule formed triple hydrogen bonds with a diaminotriazine moiety at the nanoparticle surface. Adsorption isotherm studies suggested monolayer adsorption while the adsorption capacity was strongly dependent on the drug compositions/structures (0.053 mmol/g 5-fluorouracil, 0.094 mmol/g thymine, 0.0078 mmol/g theobromine, and 0.0065 mmol/g xanthine). The drug compositional/structural effects were also reflected in the adsorption kinetics. In addition to neutral pH adsorption, studies were performed at pH below the polymer's pKa and above the drugs' pKa, separately. Reducing hydrophobicity of the hydrogen bonding sites by protonating the diaminotriazine moieties at pH 4.5 resulted in more than 3 times decrease in adsorption capacities whereas deprotonating the drug molecules at pH 9 increased the adsorption capacity due to electrostatic attraction between the negatively charged drugs and the positively charged nanoparticles, which was supported by strong dependency of the adsorption capacity on ionic strength. The adsorption was reversible for all the four drugs. While increasing temperature caused faster desorption, reducing hydrophobicity of the diaminotriazine moieties by protonation at pH 4.5 had a stronger effect on both cumulative desorption and burst release. The results of this study demonstrated an important role of synergistic interaction between hydrogen bonding and hydrophobic affinity in poly(vinyldiaminotriazine) nanoparticle adsorption of the drugs in the aqueous phase. [ABSTRACT FROM AUTHOR]

The zebrafish (Danio rerio) has been widely used in the study of human disease and development, and about 70% of the protein-coding genes are conserved between the two species1. However, studies in zebrafish remain constrained by the sparse annotation of functional control elements in the zebrafish genome. Here we performed RNA sequencing, assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing, whole-genome bisulfite sequencing, and chromosome conformation capture (Hi-C) experiments in up to eleven adult and two embryonic tissues to generate a comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin, methylomes and 3D genome organization in the zebrafish Tübingen reference strain. A comparison of zebrafish, human and mouse regulatory elements enabled the identification of both evolutionarily conserved and species-specific regulatory sequences and networks. We observed enrichment of evolutionary breakpoints at topologically associating domain boundaries, which were correlated with strong histone H3 lysine 4 trimethylation (H3K4me3) and CCCTC-binding factor (CTCF) signals. We performed single-cell ATAC-seq in zebrafish brain, which delineated 25 different clusters of cell types. By combining long-read DNA sequencing and Hi-C, we assembled the sex-determining chromosome 4 de novo. Overall, our work provides an additional epigenomic anchor for the functional annotation of vertebrate genomes and the study of evolutionarily conserved elements of 3D genome organization. A comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin structure, the methylome and 3D genome organization in the zebrafish (Danio rerio) enables identification of species-specific and evolutionarily conserved regulatory features, and provides a foundation for modelling studies on human disease and development. [ABSTRACT FROM AUTHOR]

Accurately predicting chromatin loops from genome-wide interaction matrices such as Hi-C data is critical to deepening our understanding of proper gene regulation. Current approaches are mainly focused on searching for statistically enriched dots on a genome-wide map. However, given the availability of orthogonal data types such as ChIA-PET, HiChIP, Capture Hi-C, and high-throughput imaging, a supervised learning approach could facilitate the discovery of a comprehensive set of chromatin interactions. Here, we present Peakachu, a Random Forest classification framework that predicts chromatin loops from genome-wide contact maps. We compare Peakachu with current enrichment-based approaches, and find that Peakachu identifies a unique set of short-range interactions. We show that our models perform well in different platforms, across different sequencing depths, and across different species. We apply this framework to predict chromatin loops in 56 Hi-C datasets, and release the results at the 3D Genome Browser. Predicting chromatin loops from genome-wide interaction matrices such as Hi-C data provides insight into gene regulation events. Here, the authors present Peakachu, a Random Forest classification framework that predicts chromatin loops from genome-wide contact maps, and apply it to systematically predict chromatin loops in 56 Hi-C datasets, with results available at the 3D Genome Browser. [ABSTRACT FROM AUTHOR]

Polystyrene crosslinked microspheres were prepared by soap-free emulsion polymerization using styrene (St) and divinylbenzene (DVB) as monomers; then, the microporous structure was knitted by the Friedel-Crafts alkylation reaction, and the Au nanoparticles (AuNPs) were loaded into the pores through thermal reduction, to obtain AuNPs/hyper-crosslinked microporous polymer composite microspheres. SEM and particle-size test results show that the microspheres show good monodispersity. The micropore analysis indicates that the specific surface area and the pore volume of the microporous polymer microspheres decrease with increasing DVB content, and when the DVB content is 0.1%, the specific surface area reaches a maximum of 1 174.6 m2/g. After loading AuNPs, the specific surface area and the amount of micropores of the composite microspheres decrease obviously. The results of XRD and XPS analyses suggest that HAuCl4 is reduced to AuNPs. The composite microspheres show a good catalytic performance for the reduction catalyst of 4-nitrophenol. [ABSTRACT FROM AUTHOR]

It has been reported that human visual perception and attention are altered when the hands are nearby. Previous studies indicate that placing hands near stimuli enhances a subject's temporal sensitivity. However, few researchers have investigated the effect of hand proximity on reproducing temporal duration. Moreover, the delayed attentional disengagement and enhanced magnocellular visual processing theories provide two distinct predictions of the hand proximity effect on reproduced duration. Delayed attentional disengagement near hands will cause prolonged reproductions, whereas enhanced magnocellular visual processing predicts more accurate reproduction in the peri-hand space. The current study is the first to show that a short temporal duration is reproduced for a longer period near hands than far from hands in the dual-responding-hand condition, and this hand-proximity effect is attenuated in the single-responding-hand condition. These findings together with two further studies suggest that reproducing a temporal duration is modulated by hand proximity through prolonged attentional switch. [ABSTRACT FROM AUTHOR]

To take advantage of the polymer’s special properties, we synthesized PVDAT coated polystyrene (PVDAT@PS) microspheres through semi-continuous precipitation polymerization, and demonstrated the possibility of controlling the size of microspheres by using different sized PS cores. Mechanism of the microsphere synthesis was investigated. Preliminary application studies indicated that the synthesized microspheres adsorbed double-stranded DNAs (dsDNAs) comprising A-T base pairs in pH7.4 phosphate buffered saline, and the adsorption capacity was in a range of 3.28mg to 5.58mg per gram PVDAT@ PS microspheres depending on A-T base pair percentage and chain length of the dsDNAs. [ABSTRACT FROM AUTHOR]

A facile approach has been developed to synthesize Fe3O4@PAM (polyacrylamide) nanoparticles (NPs) with carboxyl groups on the surfaces by copolymerization with acrylamide and acrylic acid in Fe3O4 NPs aqueous suspension. Nitrilotriacetic acid (NTA) was conjugated to the magnetic NPs via well-known carboniimide chemistry using EDC and NHS. The Ni2+ ions loaded on the surface of NPs provide abundant docking sites for immobilization of His-tagged green fluorescent proteins (His-tagged GFP). The high magnetic property of Fe3O4@PAM@NTA-Ni2+ allows an easy separation of the NPs from solution under an external magnetic field, with high His-tagged protein binding capacity (42 μg protein/mg of NPs). The NPs can be recycled for at least four times without significant loss of binding capacity to proteins. These materials show great potential to separate His-tagged protein with low-cost purification at industrial scale. [ABSTRACT FROM AUTHOR]

Based on interviews with 21 young Chinese tobacco users, this study explores the gendered symbolic meanings of conventional cigarette smoking and electronic cigarette vaping in the background of a traditionally patriarchal society. The theoretical frameworks of hegemonic masculinity and symbolic interactionism reveal that smoking and cigarette-sharing as performances of masculinity are embedded in men’s dominant positions in the gender system. In China, conventional cigarettes are not only a symbol of masculinity but also a carrier of patriarchy and its reproduction. Women smoking is seen as challenging hegemonic masculinity and thus still firmly disapproved. Electronic cigarettes are not sharable and thus not labeled as male activities in socializing; their popularity among Chinese women is observed nowadays. However, female tobacco users in China still carefully consider the suitableness of smoking and vaping on different occasions and actively negotiate how to express their smoker identity in the gender system. [ABSTRACT FROM AUTHOR]

By means of distillation precipitation polymerization, the silica-hybrid particles with polyazobenzene shell (PAzo@SiO2) microspheres were prepared with 6-(4-methoxy-4'-oxy-azobenzene) hexyl methacrylate (Azo-M) as monomer, divinylbenzene (DVB) as cross-linker, and ~250 nm vinylated sol-gel silica particles as template. Hollow polyazobenzene microspheres were further developed after selective removal of the silica cores with HF solution. When the content of DVB related to Azo-M is 20 wt%, the acetonitrile is 200 mL, and the polymerization time is 4.5 h, the hollow PAzo microspheres with about 20 nm shell are successfully fabricated. These hollow PAzo microspheres have excellent reversible photoisomerization, and their first-order rate constant of trans-cis isomerization only decreases 11.8% compared with homopolymer of azobenzene (Homo-PAzo). [ABSTRACT FROM AUTHOR]

The inertance tube is one of the key components of a pulse tube cryocooler. It has great influence not only on the efficiency of the pulse tube cryocooler, but also on the efficiency of the linear compressor. Meanwhile, it is very difficult to predict the impedance of an inertance tube because of the turbulent flow. In this paper, using a quasi-turbulent model, the inertance tube is optimized to match a linear compressor driven pulse tube cryocooler. Experimental results show that this model can predict the impedance quite well. With 127 W input electric power, the pulse tube cryocooler obtains 9.4 W cooling power at a temperature of 77 K. The relative Carnot efficiency of the whole system reaches 19.8%. [ABSTRACT FROM AUTHOR]

Individuals with a history of childhood abuse (CA, including neglect and abuse by caregivers before the age of 18 years) have more severe substance dependence problems than those without a history of childhood abuse. However, whether a history of CA exacerbates craving and the mechanism of this effect remain largely unknown. The aim of this study was to explore the role of alexithymia in the effects of CA on craving in a large sample of methamphetamine-dependent individuals based on latent vulnerability theory. A total of 324 methamphetamine-dependent individuals who met DSM-5 criteria for substance use disorder were recruited. CA, alexithymia, and craving data were collected from the Childhood Trauma Questionnaire, the Toronto Alexithymia Scale-20, and the Obsessive Compulsive Drug Use Scale, respectively. t tests and ANCOVA were conducted to compare variables between the CA and non-CA groups, while partial correlation and mediation analyses were conducted to examine the potential mediating role of alexithymia in the relationship between CA and craving. Abused methamphetamine-dependent individuals reported higher levels of craving and higher levels of alexithymia than those of non-abused methamphetamine-dependent individuals. Alexithymia partially mediated the link between CA and craving, especially the effect of CA on craving frequency was fully mediated by alexithymia. Our findings reveal that a history of childhood abuse has a lasting effect on craving in stimulant-dependent individuals, and alexithymia contributes to some extent to the severity of substance abuse problems in abused methamphetamine-dependent individuals. [ABSTRACT FROM AUTHOR]