Screening hub genes in coronary artery disease based on integrated analysis

Background: Coronary artery disease (CAD) is the leading cause of mortality worldwide. Identifying key pathogenic genes benefits the understanding molecular mechanism of CAD. Methods: In this study, 5 microarray data sets from the blood sample of 312 CADs and 277 healthy controls were downloaded. Limma and metaMA packages were used to identify differentially expressed genes. The functional enrichment analysis of differentially expressed genes was further performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Additionally, protein–protein interac­tion and transcript factors-target networks were performed based on top 10 up- and down-regulated differentially expressed genes to further study the biological function. Last, real-time quantitative poly­merase chain reaction (RT-qPCR) was used to validate the integrated analysis result. Results: A total of 528 differentially expressed genes were obtained. All differentially expressed genes were significantly involved in signal transduction and the MAPK signaling pathway. Among MAPK signaling pathway, IL1R2, ARRB2 and PRKX were associated with CAD. Furthermore, there were 4 common differentially expressed genes including PLAUR, HSPH1, ZMYND11 and S100A8 in the protein–protein interaction and transcript factors-target networks, which played crucial roles in the development of CAD. In quantitative RT-qPCR, the expression of PRKX, HSPH1 and ZMYND11 was down-regulated and consistent with the integrated analysis. Conclusions: Identified 7 differentially expressed genes (IL1R2, ARRB2, PRKX, PLAUR, HSPH1, ZMYND11 and S100A8) may play crucial roles in the development of CAD

A Biodegradable Polyethylenimine-Based Vector Modified by Trifunctional Peptide R18 for Enhancing Gene Transfection Efficiency In Vivo

Lack of capacity to cross the nucleus membrane seems to be one of the main reasons for the lower transfection efficiency of gene vectors observed in vivo study than in vitro. To solve this problem, a new non-viral gene vector was designed. First, a degradable polyethylenimine (PEI) derivate was synthesized by crosslinking low-molecular-weight (LMW) PEI with N-octyl-N-quaternary chitosan (OTMCS), and then adopting a designed trifunctional peptide (RGDC- TAT-NLS) with good tumor targeting, cell uptake and nucleus transport capabilities to modify OTMCS-PEI. The new gene vector was termed as OTMCS- PEI-R18 and characterized in terms of its chemical structure and biophysical parameters. Gene transfection efficiency and nucleus transport mechanism of this vector were also evaluated. The polymer showed controlled degradation and remarkable buffer capabilities with the particle size around 100–300 nm and the zeta potential ranged from 5 mV to 40 mV. Agraose gel electrophoresis showed that OTMCS-PEI-R18 could effectively condensed plasmid DNA at a ratio of 1.0. Besides, the polymer was stable in the presence of sodium heparin and could resist digestion by DNase I at a concentration of 63U DNase I/DNA. OTMCS-PEI-R18 also showed much lower cytotoxicity and better transfection rates compared to polymers OTMCS-PEI-R13, OTMCS-PEI and PEI 25 KDa in vitro and in vivo. Furthermore, OTMCS-PEI-R18/DNA complexes could accumulate in the nucleus well soon and not rely on mitosis absolutely due to the newly incorporated ligand peptide NLS with the specific nuclear delivery pathway indicating that the gene delivery system OTMCS-PEI-R18 could reinforce gene transfection efficiency in vivo

Multi-dimensional vibration sensing and simultaneous self-homodyne optical transmission of single wavelength net 5.36 Tb/s signal using telecom 7-core fiber

We present a high-capacity self-homodyne optical transmission system that enables simultaneously multidimensional vibration sensing based on a weakly-coupled 7-core fiber. To our knowledge, we demonstrate for the first-time detection of fiber vibration direction along with strength, frequency, and location of the vibration source, while transmitting in the meantime single-carrier 16 QAM signal reaching a net date rate of 5.36 Tb/s over 41.4 km of telecom 7-core fiber.Comment: 5 pages, 4 figure

Binding Affinity, Cellular Uptake, and Subsequent Intracellular Trafficking of the Nano-Gene Vector P123-PEI-R13

A nano-gene vector PEI-P123-R13 was synthesized by cross-linking low molecular weight PEI with P123 and further coupling bifunctional peptide R13 to the polymer for targeting tumor and increasing cellular uptake. The binding assessment of R13 to αvβ3 positive cells was performed by HRP labeling. The internalization pathways of P123-PEI-R13/DNA complexes were investigated based on the effect of specific endocytic inhibitors on transfection efficiency. The mechanism of intracellular trafficking was investigated based on the effect of endosome-lysosome acidification inhibitors, cytoskeleton, and dynein inhibitors on transfection efficiency. The results indicated that the bifunctional peptide R13 had the ability of binding to αvβ3 positive cells in vitro. The modification of P123-PEI-R13 with R13 made it display new property of internalization. P123-PEI-R13/DNA complexes were conducted simultaneously via clathrin-mediated endocytosis, caveolin-mediated endocytosis, macropinocytosis, and possible energy-independent route. After internalization, P123-PEI-R13/DNA complexes could escape from the endosome-lysosome system because of its acidification and further took microtubule as the track and dynein as the dynamic source to be transported toward the microtubule (+) end, to wit nucleus, under the action of microfilament, and with the aid of intermediate filament

PaLM 2 Technical Report

We introduce PaLM 2, a new state-of-the-art language model that has better multilingual and reasoning capabilities and is more compute-efficient than its predecessor PaLM. PaLM 2 is a Transformer-based model trained using a mixture of objectives. Through extensive evaluations on English and multilingual language, and reasoning tasks, we demonstrate that PaLM 2 has significantly improved quality on downstream tasks across different model sizes, while simultaneously exhibiting faster and more efficient inference compared to PaLM. This improved efficiency enables broader deployment while also allowing the model to respond faster, for a more natural pace of interaction. PaLM 2 demonstrates robust reasoning capabilities exemplified by large improvements over PaLM on BIG-Bench and other reasoning tasks. PaLM 2 exhibits stable performance on a suite of responsible AI evaluations, and enables inference-time control over toxicity without additional overhead or impact on other capabilities. Overall, PaLM 2 achieves state-of-the-art performance across a diverse set of tasks and capabilities. When discussing the PaLM 2 family, it is important to distinguish between pre-trained models (of various sizes), fine-tuned variants of these models, and the user-facing products that use these models. In particular, user-facing products typically include additional pre- and post-processing steps. Additionally, the underlying models may evolve over time. Therefore, one should not expect the performance of user-facing products to exactly match the results reported in this report

Stall Mode Transformation in the Wide Vaneless Diffuser of Centrifugal Compressors

A review on the rotating stall in the vaneless diffuser of centrifugal compressors is presented showing that different stall modes characterized by different numbers of cells can be detected within the diffuser even if the operating condition remains unchanged. The interaction between the inlet perturbation and the stall cells near the diffuser outlet is supposed to be the trigger of the stall mode transformation. In order to determine if the inlet perturbation will interact with the downstream stall cells, a characteristic time analysis is proposed to estimate the characteristic time of the perturbation in radial and tangential directions. An additional theoretical model which focused on the development of the vaneless diffuser rotating stall is presented to determine the propagation velocity of the cells. The comparison between the characteristic time in two directions shows that one stall mode is able to evolve into another stall mode if a critical condition is met, and the stall mode transformation is more likely to start from a mode with a higher number of cells and is more likely to occur in the diffuser with a large radius ratio. Experimental results are also employed to validate the proposed critical condition, and good agreements are obtained

Reconstruction of 3D Shapes of Granite Minerals and Generation of Random Numerical Specimens

AbstractThe existing methods of generating random mineral grains in numerical rock specimens mostly adopt random polygons (in 2D) or random polyhedrons (in 3D) to represent mineral grains. Although this simplification is effective and reasonable, the complex three-dimensional (3D) shape of mineral grains can be reconstructed by computed tomography (CT) scan and image processing techniques, and then, random grains with real shape can be generated in a numerical specimen. In this paper, we proposed an improved grain-based model to construct random mineral grains with real 3D shape in numerical specimens. The granite specimens with granular minerals are scanned by CT. After the CT slices are denoised and corrected, the minerals, including biotite, quartz, and feldspar, are segmented from the CT slices to reconstruct the 3D mineral shapes; these shapes are stored in grain library. By importing the grain library in PFC (Particle Follow Code, a simulation software), heterogeneous specimens with random mineral grains are constructed, and uniaxial compression tests are carried out on them. Results show that the ranges of Young’s modulus, Poisson’s ratio, and uniaxial compressive strength of these numerical specimens are similar to those of real specimens measured in the laboratory. Therefore, the proposed method is feasible and reasonable. This work can provide a reference for the study of constructing heterogeneous numerical rock specimens in rock mechanics