Modiff: Action-Conditioned 3D Motion Generation with Denoising Diffusion Probabilistic Models

Diffusion-based generative models have recently emerged as powerful solutions for high-quality synthesis in multiple domains. Leveraging the bidirectional Markov chains, diffusion probabilistic models generate samples by inferring the reversed Markov chain based on the learned distribution mapping at the forward diffusion process. In this work, we propose Modiff, a conditional paradigm that benefits from the denoising diffusion probabilistic model (DDPM) to tackle the problem of realistic and diverse action-conditioned 3D skeleton-based motion generation. We are a pioneering attempt that uses DDPM to synthesize a variable number of motion sequences conditioned on a categorical action. We evaluate our approach on the large-scale NTU RGB+D dataset and show improvements over state-of-the-art motion generation methods

Risk assessment of complex engineering project based on fuzzy Petri net under the perspective of vulnerability

Traditional engineering risk management has been unable to adapt to the complexity and variability due to its constituent elements and dynamic nature of internal and external environments. Vulnerability, as a concept closely related to risk, has been neglected in the traditional risk management due to its hidden characteristics. This study attempts to quantify and evaluate vulnerabilities of complex engineering projects independently and explore the transmission mechanism between risk and vulnerability factors. Twenty different types of large-scale engineering projects in China were selected as case studies from the Mega Project Case Study Center (MPCSC) of Tongji University. Vulnerability and risk factors of each project were identified and analysed. A mechanism model was developed to explore the impacts of vulnerabilities and risks through ta Fuzzy Petri Net. Four main vulnerability-risk critical paths were identified through the reverse labelling method. The overall evaluation of engineering project risks considering the impacts of vulnerabilities is the highlight of this paper. This study interprets the cognition and evaluation of complex engineering risks from a new perspective, enriches the connotation of engineering risk management, and provides a reference for risk management and decisionmaking of complex engineering projects

Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers.

Although promoter-associated CpG islands have been established as targets of DNA methylation changes in cancer, previous studies suggest that epigenetic dysregulation outside the promoter region may be more closely associated with transcriptional changes. Here we examine DNA methylation, chromatin marks, and transcriptional alterations to define the relationship between transcriptional modulation and spatial changes in chromatin structure. Using human papillomavirus-related oropharyngeal carcinoma as a model, we show aberrant enrichment of repressive H3K9me3 at the transcriptional start site (TSS) with methylation-associated, tumor-specific gene silencing. Further analysis identifies a hypermethylated subtype which shows a functional convergence on MYC targets and association with CREBBP/EP300 mutation. The tumor-specific shift to transcriptional repression associated with DNA methylation at TSSs was confirmed in multiple tumor types. Our data may show a common underlying epigenetic dysregulation in cancer associated with broad enrichment of repressive chromatin marks and aberrant DNA hypermethylation at TSSs in combination with MYC network activation

Publisher Correction: Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers.

The original version of this Article contained an error in the author affiliations. Trey Ideker was incorrectly associated with 'Department of Medicine (Oncology), Stanford University School of Medicine, 875 Blake Wilbur Dr, Palo Alto, CA 94304, USA.' This has now been corrected in both the PDF and HTML versions of the Article

Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing.

BACKGROUND:Rapidly growing evidence suggests that microRNAs (miRNAs) are involved in a wide range of cancer malignant behaviours including radioresistance. Therefore, the present study was designed to investigate miRNA expression patterns associated with radioresistance in NPC. METHODS:The differential expression profiles of miRNAs and mRNAs associated with NPC radioresistance were constructed. The predicted target mRNAs of miRNAs and their enriched signaling pathways were analyzed via biological informatical algorithms. Finally, partial miRNAs and pathways-correlated target mRNAs were validated in two NPC radioreisitant cell models. RESULTS:50 known and 9 novel miRNAs with significant difference were identified, and their target mRNAs were narrowed down to 53 nasopharyngeal-/NPC-specific mRNAs. Subsequent KEGG analyses demonstrated that the 53 mRNAs were enriched in 37 signaling pathways. Further qRT-PCR assays confirmed 3 down-regulated miRNAs (miR-324-3p, miR-93-3p and miR-4501), 3 up-regulated miRNAs (miR-371a-5p, miR-34c-5p and miR-1323) and 2 novel miRNAs. Additionally, corresponding alterations of pathways-correlated target mRNAs were observed including 5 up-regulated mRNAs (ICAM1, WNT2B, MYC, HLA-F and TGF-β1) and 3 down-regulated mRNAs (CDH1, PTENP1 and HSP90AA1). CONCLUSIONS:Our study provides an overview of miRNA expression profile and the interactions between miRNA and their target mRNAs, which will deepen our understanding of the important roles of miRNAs in NPC radioresistance

Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks

Precise gene editing is—or will soon be—in clinical use for several diseases, and more applications are under development. The programmable nuclease Cas9, directed by a single-guide RNA (sgRNA), can introduce double-strand breaks (DSBs) in target sites of genomic DNA, which constitutes the initial step of gene editing using this novel technology. In mammals, two pathways dominate the repair of the DSBs—nonhomologous end joining (NHEJ) and homology-directed repair (HDR)—and the outcome of gene editing mainly depends on the choice between these two repair pathways. Although HDR is attractive for its high fidelity, the choice of repair pathway is biased in a biological context. Mammalian cells preferentially employ NHEJ over HDR through several mechanisms: NHEJ is active throughout the cell cycle, whereas HDR is restricted to S/G2 phases; NHEJ is faster than HDR; and NHEJ suppresses the HDR process. This suggests that definitive control of outcome of the programmed DNA lesioning could be achieved through manipulating the choice of cellular repair pathway. In this review, we summarize the DSB repair pathways, the mechanisms involved in choice selection based on DNA resection, and make progress in the research investigating strategies that favor Cas9-mediated HDR based on the manipulation of repair pathway choice to increase the frequency of HDR in mammalian cells. The remaining problems in improving HDR efficiency are also discussed. This review should facilitate the development of CRISPR/Cas9 technology to achieve more precise gene editing

Spatial heterogeneity in summer phytoplankton communities shaped by anthropogenic and natural effects in typical coastal bay-river systems in South China

Phytoplankton community spatial scales vary in typical coastal bay-river systems under natural and anthropogenic effects. However, their relative importance in shaping phytoplankton spatial heterogeneity has been largely uncharacterized in the literature. In this study, we performed comprehensive analyses using field monitoring, meteorological, and remote sensing datasets from a coastal bay-river system in South China (the Guangdong-Hong Kong-Macao Greater Bay-Pearl River tributaries) to examine phytoplankton spatial heterogeneity and main effects. We showed that water quality in the four water bodies of the typical coastal bay-river system in South China were relatively poor. Phytoplankton community abundance, taxonomic grouping, dominant species, and species similarity varied significantly in response to environmental gradients. We showed that Cyanophyta, Bacillatiophyta, and Chlorophyta were dominant phyla, and we observed regional variations in taxonomic groups and dominant species. Phytoplankton abundance was significantly higher in Dongjiang River and water bodies in branched bays when compared with other regions due to nutrient input from extensive agricultural and urban development, where the dominant phylum was Cyanophyta. Cyclotella (Bacillariophyta) had relatively high abundance and was widely distributed throughout the coastal bay-river system, except in the Dongjiang River. Melosira (Bacillariophyta) had relatively high abundance in Dongjiang and Xijiang Rivers, Merismopedia (Cyanophyta) dominated in the Dongjiang River and highly urbanized branched bay areas, while Microcystis (Cyanophyta) only dominated in Beijiang and Xijiang Rivers. Dominant species distributions showed apparent spatial heterogeneity in phytoplankton community composition. Species similarities between different water bodies were generally low, but phytoplankton species similarities between the Dongjiang River and water bodies in the branched bay area were relatively high, which indicated that water exchange associated with freshwater and nutrient inputs may have profoundly influenced species dispersal and dominant phytoplankton species. Redundancy analyses (RDA) demonstrated that pH, elevation, photosynthetically active radiation (PAR), dissolved active phosphorus (SRP), total dissolved phosphorus (TP), total nitrogen (TN), and nitrate nitrogen (NO3−-N) values - associated with nutrient and climate indicators were the main factors explaining structured phytoplankton spatial distributions. Variance partitioning analyses (VPA) showed that phytoplankton community variations were explained by anthropogenic factors (eutrophication) in summer. Our study improves our understanding of the natural and anthropogenic effects on phytoplankton spatial heterogeneity and provides basic study data for long-term phytoplankton evolution from river to bay areas