Recent advances in high-throughput omics technologies have enabled biomedical researchers to collect large-scale genomic data. As a consequence, there has been growing interest in developing methods ...to integrate such data to obtain deeper insights regarding the underlying biological system. A key challenge for integrative studies is the heterogeneity present in the different omics data sources, which makes it difficult to discern the coordinated signal of interest from source-specific noise or extraneous effects.
We introduce a novel method of multi-modal data analysis that is designed for heterogeneous data based on non-negative matrix factorization. We provide an algorithm for jointly decomposing the data matrices involved that also includes a sparsity option for high-dimensional settings. The performance of the proposed method is evaluated on synthetic data and on real DNA methylation, gene expression and miRNA expression data from ovarian cancer samples obtained from The Cancer Genome Atlas. The results show the presence of common modules across patient samples linked to cancer-related pathways, as well as previously established ovarian cancer subtypes.
The source code repository is publicly available at https://github.com/yangzi4/iNMF.
gmichail@umich.edu
Supplementary data are available at Bioinformatics online.
Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage tracing and clinical trials have ...demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis. Several signaling pathways, that are associated with the inflammatory response, have been implicated within atherosclerosis such as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch and Wnt signaling pathways, which are of importance for atherosclerosis development and regression. Targeting inflammatory pathways, especially the NLRP3 inflammasome pathway and its regulated inflammatory cytokine interleukin-1β, could represent an attractive new route for the treatment of atherosclerotic diseases. Herein, we summarize the knowledge on cellular participants and key inflammatory signaling pathways in atherosclerosis, and discuss the preclinical studies targeting these key pathways for atherosclerosis, the clinical trials that are going to target some of these processes, and the effects of quelling inflammation and atherosclerosis in the clinic.
The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past ...two decades.Here,we review the evolutionariiy conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development,homeostasis and diseases.In the early stages of embryonic limb development,Sonic Hedgehog（Shh） acts as a major morphogen in patterning the limb buds.Indian Hedgehog（Ihh） has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium.Hh signalling is also involved intramembrane ossification.Interactions between Hh and Wnt signalling regulate cartilage development,endochondral bone formation and synovial joint formation.Hh also plays an important role in bone homeostasis,and reducing Hh signalling protects against age-related bone loss.Disruption of Hh signalling regulation leads to multiple bone diseases,such as progressive osseous heteroplasia.Therefore,understanding the signalling mechanisms and functions of Hh signalling in bone development,homeostasis and diseases will provide important insights into bone disease prevention,diagnoses and therapeutics.
Recent efforts have promoted programmable wireless environments (PWEs) to enhance the reception quality in high-frequency bands via reconfigurable intelligent surfaces (RISs). However, relevant ...research efforts are limited to setups with stationary users. This paper shows that crowd mobility in indoor PWEs induces spatio-temporal shadows on the surfaces, resulting in spatio-temporal sparsity in channel gains due to signal blockages. This overlooked aspect impacts the operation strategy of PWEs as the shadowed RIS tiles would contribute to the overheads while offering almost no improvement to the reception quality. Hence, this paper proposes an optimal strategy that excludes the shadowed tiles, which maximizes the utilization efficiency of RISs while minimizing the overheads. Since signal blockage is tied with the details of user mobility, a general model does not exist to identify such shadowed tiles for exclusion. Hence, we follow a data-driven approach that capitalizes on a realistic indoor mobility model and ray-tracing to generate the channel data. However, conventional ray-tracing presents high complexity that hinders data generation. So, we propose an approach to identify the shadow regions with a nine-order of magnitude reduction in complexity to efficiently generate the channel data. Furthermore, we present two exclusion strategies that offer guaranteed and best-effort quality-of-service support, and each can identify the tiles to be excluded via a search method with a complexity of <inline-formula> <tex-math notation="LaTeX">\mathcal {O}(N) </tex-math></inline-formula> for <inline-formula> <tex-math notation="LaTeX">N </tex-math></inline-formula> tiles. The results indicate that the proposed strategies reduce the overheads by <inline-formula> <tex-math notation="LaTeX">45-50\% </tex-math></inline-formula> while maintaining optimal service quality in various environments, operation frequencies, and user and access point density.
Based on the path integral formulation of the reduced density matrix, we develop a scheme to overcome the exponential growth of computational complexity in reliably extracting low-lying entanglement ...spectrum from quantum Monte Carlo simulations. We test the method on the Heisenberg spin ladder with long entangled boundary between two chains and the results support the Li and Haldane's conjecture on entanglement spectrum of topological phase. We then explain the conjecture via the wormhole effect in the path integral and show that it can be further generalized for systems beyond gapped topological phases. Our further simulation results on the bilayer antiferromagnetic Heisenberg model with 2D entangled boundary across the (2 + 1)D O(3) quantum phase transition clearly demonstrate the correctness of the wormhole picture. Finally, we state that since the wormhole effect amplifies the bulk energy gap by a factor of β, the relative strength of that with respect to the edge energy gap will determine the behavior of low-lying entanglement spectrum of the system.
The palladium‐catalyzed asymmetric 4+3 cyclization of trimethylenemethane donors with benzofuran‐derived azadienes furnishes chiral benzofuro3,2‐bazepine frameworks in high yields (up to 98 %) with ...exclusive regioselectivities and excellent stereoselectivities (up to >20:1 d.r., >99 % ee). This catalytic asymmetric 4+3 cyclization of Pd‐trimethylenemethane can enrich the arsenal of Pd‐TMM reactions in organic synthesis. In addition, this strategy provides an alternative approach to chiral azepines by a transition‐metal‐catalyzed asymmetric 4+3 cyclization.
A wide range of chiral benzofuro3,2‐bazepine skeletons can be synthesized in excellent yields, high diastereoselectivities, and excellent enantioselectivities through the title reaction. The diastereoselectivity of the reaction can be controlled through ligand R1, with a cyano group affording trans products and a diphenyl ketimine group affording cis products.
Halide perovskite quantum dots (QDs), primarily regarded as optoelectronic materials for LED and photovoltaic devices, have not been applied for photochemical conversion (e.g., water splitting or CO2 ...reduction) applications because of their insufficient stability in the presence of moisture or polar solvents. Herein, we report the use of CsPbBr3 QDs as novel photocatalysts to convert CO2 into solar fuels in nonaqueous media. Under AM 1.5G simulated illumination, the CsPbBr3 QDs steadily generated and injected electrons into CO2, catalyzing CO2 reduction at a rate of 23.7 μmol/g h with a selectivity over 99.3%. Additionally, through the construction of a CsPbBr3 QD/graphene oxide (CsPbBr3 QD/GO) composite, the rate of electron consumption increased 25.5% because of improved electron extraction and transport. This study is anticipated to provide new opportunities to utilize halide perovskite QD materials in photocatalytic applications.
: A comprehensive investigation was carried out to determine the changes that occurred in water‐stressed cucumber (Cucumis sativus L.) in response to melatonin treatment. We examined the potential ...roles of melatonin during seed germination and root generation and measured its effect on reactive oxygen species (ROS) levels, antioxidant enzyme activities, and photosynthesis. Melatonin alleviated polyethylene glycol induced inhibition of seed germination, with 100 μm melatonin‐treated seeds showing the greatest germination rate. Melatonin stimulated root generation and vitality and increased the root:shoot ratio; therefore, melatonin may have an effect on strengthening cucumber roots. Melatonin treatment significantly reduced chlorophyll degradation. Seedlings treated with 100 μm melatonin clearly showed a higher photosynthetic rate, thus reversing the effect of water stress. Furthermore, the ultrastructure of chloroplasts in water‐stressed cucumber leaves was maintained after melatonin treatment. The antioxidant levels and activities of the ROS scavenging enzymes, i.e., superoxide dismutase, peroxidase, and catalase, were also increased by melatonin. These results suggest that the adverse effects of water stress can be minimized by the application of melatonin.
Catalytic asymmetric transformations by dearomatization have developed into a widely applicable synthetic strategy, but heavily relied on the use of arenes bearing a heteroatom. In this case, the ...dearomatization is facilitated by the involvement of a p‐orbital electron of the heteroatom. Different from the conventional substrate‐dependent model, here we demonstrate that the activation by a d‐orbital electron of the transition‐metal center can serve as a driving force for dearomatization, and is applied to the development of a novel asymmetric alkynyl copper facilitated remote substitution reaction. A newly modified PyBox chiral ligand enables the construction of valuable diarylmethyl and triarylmethyl skeletons in high enantioselectivities. An unexpected tandem process involving sequential remote substitution/cyclization/1,5‐H shift leads to the formation of the enantioenriched C−N axis. A gram‐scale reaction and various downstream transformations highlight the robustness of this method and the potential transformations of the products. Preliminary mechanistic studies reveal a mononuclear Cu‐catalyzed remote substitution process.
Alkynyl copper facilitates dearomatization through the involvement of a d‐orbital electron of the transition metal, and was applied to a novel remote substitution reaction. A newly modified PyBox ligand enabled the construction of diarylmethyl and triarylmethyl skeletons with high enantioselectivities.
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