In situ loading and delivery of short single- And double-stranded dna by supramolecular organic frameworks

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double endlabeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF-nucleic acid ratios. In addition to high delivery efficiencies, the watersoluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery

Numerical investigation on particle resuspension in turbulent duct flow via DNS-DEM: Effect of collisions

Particle transportation in a fully developed turbulent duct flow is numerically investigated under the effect of wall-normal gravity force. The hydrodynamic modeling of the fluid phase is based on direct numerical simulation. The kinematics and trajectory of the particles as well as the particle-particle interaction are described by the discrete element method (DEM). By using a soft-sphere DEM where the particles and the walls are specified by material properties in the simulation, the effect of collisions on the particle resuspension rate is discussed. The collisions are found to influence on the particle resuspension rate near the duct floor whereas hardly affect the particle behavior near the duct center

Thickness dependence of microstructures in La0.8Ca0.2MnO3 thin films

The thickness dependence of microstructures of La0.8Ca0.2MnO3 (LCMO)/SrTiO3 (STO) thin films was investigated by high-resolution x-ray diffraction, small angle x-ray reflection, grazing incidence x-ray diffraction, scanning electron microscopy, and atomic force microscopy. The results show that all the LCMO films are well oriented in (00l) direction perpendicular to the substrate surface. Self-organized crystalline grains with a tetragonal shape are uniformly distributed on the film surface, indicating the deposition condition being of benefit to the formation of the crystalline grains. With increasing the film thickness, the crystalline quality of the LCMO film is improved, while the surface becomes rougher. There exists a nondesigned cap layer on the upper surface of the LCMO layer for all the samples. The mechanism is discussed briefly.published_or_final_versio

Minimum Sensitivity Based Robust Beamforming with Eigenspace Decomposition

An enhanced eigenspace-based beamformer (ESB) derived using the minimum sensitivity criterion is proposed with significantly improved robustness against steering vector errors. The sensitivity function is defined as the squared norm of the appropriately scaled weight vector and since the sensitivity function of an array to perturbations becomes very large in the presence of steering vector errors, it can be used to find the best projection for the ESB, irrespective of the distribution of additive noises. As demonstrated by simulation results, the proposed method has a better performance than the classic ESBs and the previously proposed uncertainty set based approach

Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer

Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This “paradox” can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer

Achiral phenolic N-oxides as additives: an alternative strategy for asymmetric cyanosilylation of ketones

The activation of chiral titanium(IV) complexes with additives, phenolic N-oxides, is found to provide an alternative strategy for asymmetric cyanosilylation of ketones in excellent yield With LIP to 82%, ee. (C) 2004 Elsevier Ltd. All rights reserved

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

PIBM: Particulate immersed boundary method for fluid-particle interaction problems

It is well known that the number of particles should be scaled up to enable industrial scale simulation. The calculations are more computationally intensive when the motion of the surrounding fluid is considered. Besides the advances in computer hardware and numerical algorithms, the coupling scheme also plays an important role on the computational efficiency. In this study, a particulate immersed boundary method (PIBM) for simulating the fluid–particle multiphase flow was presented and assessed in both two- and three-dimensional applications. The idea behind PIBM derives from the conventional momentum exchange-based Immersed Boundary Method (IBM) by treating each Lagrangian point as a solid particle. This treatment enables Lattice Boltzmann Method (LBM) to be coupled with fine particles residing within a particular grid cell. Compared with the conventional IBM, dozens of times speedup in two-dimensional simulation and hundreds of times in three-dimensional simulation can be expected under the same particle and mesh number. Numerical simulations of particle sedimentation in Newtonian flows were conducted based on a combined LBM–PIBM–Discrete Element Method (DEM) scheme, showing that the PIBM can capture the feature of particulate flows in fluid and is indeed a promising scheme for the solution of the fluid–particle interaction problems