Qualitative analysis on the diffusive Holling-Tanner predator-prey model

We consider the diffusive Holling–Tanner predator–prey model subject to the homogeneous Neumann boundary condition. We first apply Lyapunov function method to prove some global stability results of the unique positive constant steadystate. And then, we derive a non-existence result of positive non-constant steady-states by a novel approach that can also be applied to the classical Sel’kov model to obtain the non-existence of positive non-constant steady-states if 0 < p ≤ 1

Vanishing diffusion limit and boundary layers for a nonlinear hyperbolic system with damping and diffusion

We consider an initial and boundary value problem for a nonlinear hyperbolic system with damping and diffusion. This system was derived from the Rayleigh–Benard equation. Based on a new observation of the structure of the system, two identities are found; then, the following results are proved by using the energy method. First, the well-posedness of the global large solution is established; then, the limit with a boundary layer as some diffusion coefficient tending to zero is justified. In addition, the $L^2$ convergence rate in terms of the diffusion coefficient is obtained together with the estimation of the thickness of the boundary layer

Determine OWA operator weights using kernel density estimation

Some subjective methods should divide input values into local clusters before determining the ordered weighted averaging (OWA) operator weights based on the data distribution characteristics of input values. However, the process of clustering input values is complex. In this paper, a novel probability density based OWA (PDOWA) operator is put forward based on the data distribution characteristics of input values. To capture the local cluster structures of input values, the kernel density estimation (KDE) is used to estimate the probability density function (PDF), which fits to the input values. The derived PDF contains the density information of input values, which reflects the importance of input values. Therefore, the input values with high probability densities (PDs) should be assigned with large weights, while the ones with low PDs should be assigned with small weights. Afterwards, the desirable properties of the proposed PDOWA operator are investigated. Finally, the proposed PDOWA operator is applied to handle the multicriteria decision making problem concerning the evaluation of smart phones and it is compared with some existing OWA operators. The comparative analysis shows that the proposed PDOWA operator is simpler and more efficient than the existing OWA operator

Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>The human coagulation trigger tissue factor (TF) is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi) technology to silence TF in a lung adenocarcinoma cell line A549 with high-level expression of TF and evaluate its antitumor effects in vitro and in vivo.</p> <p>Methods</p> <p>The specific small interfering RNA (siRNA) designed for targeting human TF was transfected into A549 cells. The expression of TF was detected by reverse transcription-PCR and Western blot. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The metastatic potential of A549 cells was determined by wound healing, the mobility and Matrigel invasion assays. Expressions of PI3K/Akt, Erk1/2, VEGF and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effect of TF-siRNA on the growth of A549 lung adenocarcinoma xenografts in nude mice was investigated.</p> <p>Results</p> <p>TF -siRNA significantly reduced the expression of TF in the mRNA and protein levels. The down-regulation of TF in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis in dose-dependent manner. Erk MAPK, PI3K/Akt pathways as well as VEGF and MMP-2/-9 expressions were inhibited in TF-siRNA transfected cells. Moreover, intratumoral injection of siRNA targeting TF suppressed the tumor growth of A549 cells in vivo model of lung adenocarcinoma.</p> <p>Conclusions</p> <p>Down-regulation of TF using siRNA could provide a potential approach for gene therapy against lung adenocarcinoma, and the antitumor effects may be associated with inhibition of Erk MAPK, PI3K/Akt pathways.</p

Functionalized Double Strain-Promoted Stapled Peptides for Inhibiting the p53-MDM2 Interaction.

The Sondheimer dialkyne reagent has previously been employed in strain-promoted double-click cycloadditions with bis-azide peptides to generate stapled peptide inhibitors of protein-protein interactions. The substituted variants of the Sondheimer dialkyne can be used to generate functionalized stapled peptide inhibitors with improved biological properties; however, this remains a relatively underdeveloped field. Herein, we report the synthesis of new substituted variants of Sondheimer dialkyne and their application in the stapling of p53-based diazido peptides to generate potent stapled peptide-based inhibitors of the oncogenic p53-MDM2 interaction. The functionalized stapled peptide formed from a meta-fluoro-substituted Sondheimer dialkyne was found to be the most potent inhibitor. Furthermore, through experimental studies and density functional theory calculations, we investigated the impact of the substituent on the strain-promoted double-click reactivity of Sondheimer dialkyne

Water-soluble, stable and azide-reactive strained dialkynes for biocompatible double strain-promoted click chemistry.

The Sondheimer dialkyne is extensively used in double strain-promoted azide-alkyne cycloadditions. This reagent suffers with poor water-solubility and rapidly decomposes in aqueous solutions. This intrinsically limits its application in biological systems, and no effective solutions are currently available. Herein, we report the development of novel highly water-soluble, stable, and azide-reactive strained dialkyne reagents. To demonstrate their extensive utility, we applied our novel dialkynes to a double strain-promoted macrocyclisation strategy to generate functionalised p53-based stapled peptides for inhibiting the oncogenic p53-MDM2 interaction. These functionalised stapled peptides bind MDM2 with low nanomolar affinity and show p53 activation in a cellular environment. Overall, our highly soluble, stable and azide-reactive dialkynes offer significant advantages over the currently used Sondheimer dialkyne, and could be utilised for numerous biological applications

First in-depth analysis of the novel Th2-type cytokines in salmonid fish reveals distinct patterns of expression and modulation but overlapping bioactivities

ACKNOWLEDGMENTS The VHSV-infected samples were generated within the Scottish Government funded research project FC1996 and kindly provided by Marine Scotland staff. Thanks to ELANCO for providing the A. davidanieli (Renogen). FINANCIAL SUPPORT T. W. received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. Y.J., W.H. and Q.X. were supported financially by the National Scholarship Council of China. Z.Q. was supported by grants from the National Natural Science Foundation of China (31302221) and the overseas training plan for young and middle-aged teachers and principals of colleges and universities in Jiangsu Province, China. M.M.C. was funded by an Ángeles Alvariño postdoctoral contract from the Consejo Superior de Investigaciones Científicas and the Xunta de Galicia. P.D.-R. was funded by a European Commission (EC) Marie Curie Intra European Fellowship (FP7). J.W.H. was funded by the Biotechnology and Biological Sciences Research Council (BB/K009125/1). This work was also supported financially by the EC, under contract Nos. 222719 (LIFECYCLE) and 311993 (TargetFish), and by the European Research Council Starting Grant 2011 (contract No. 280469).Peer reviewedPublisher PD

Development of Cell-Permeable, Non-Helical Constrained Peptides to Target a Key Protein-Protein Interaction in Ovarian Cancer.

There is a lack of current treatment options for ovarian clear cell carcinoma (CCC) and the cancer is often resistant to platinum-based chemotherapy. Hence there is an urgent need for novel therapeutics. The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in CCC and is seen as an attractive therapeutic target. This was validated through shRNA-mediated knockdown of the target protein, HNF1β, in five high- and low-HNF1β-expressing CCC lines. To inhibit the protein function, cell-permeable, non-helical constrained proteomimetics to target the HNF1β-importin α protein-protein interaction were designed, guided by X-ray crystallographic data and molecular dynamics simulations. In this way, we developed the first reported series of constrained peptide nuclear import inhibitors. Importantly, this general approach may be extended to other transcription factors