Silk Fiber-Reinforced Hyaluronic Acid-Based Hydrogel for Cartilage Tissue Engineering

A continuing challenge in cartilage tissue engineering for cartilage regeneration is the creation of a suitable synthetic microenvironment for chondrocytes and tissue regeneration. The aim of this study was to develop a highly tunable hybrid scaffold based on a silk fibroin matrix (SM) and a hyaluronic acid (HA) hydrogel. Human articular chondrocytes were embedded in a porous 3-dimensional SM, before infiltration with tyramine modified HA hydrogel. Scaffolds were cultured in chondropermissive medium with and without TGF-β1. Cell viability and cell distribution were assessed using CellTiter-Blue assay and Live/Dead staining. Chondrogenic marker expression was detected using qPCR. Biosynthesis of matrix compounds was analyzed by dimethylmethylene blue assay and immuno-histology. Differences in biomaterial stiffness and stress relaxation were characterized using a one-step unconfined compression test. Cell morphology was investigated by scanning electron microscopy. Hybrid scaffold revealed superior chondro-inductive and biomechanical properties compared to sole SM. The presence of HA and TGF-β1 increased chondrogenic marker gene expression and matrix deposition. Hybrid scaffolds offer cytocompatible and highly tunable properties as cell-carrier systems, as well as favorable biomechanical properties.     

Discovery of Covalent Bruton's Tyrosine Kinase Inhibitors with Decreased CYP2C8 Inhibitory Activity

Bruton's tyrosine kinase (BTK) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage. Evidence has shown that inhibition of BTK has clinical benefit for the treatment of a wide array of autoimmune and inflammatory diseases. Previously we reported the discovery of a novel nicotinamide selectivity pocket (SP) series of potent and selective covalent irreversible BTK inhibitors. The top molecule 1 of that series strongly inhibited CYP2C8 (IC₅₀=100 nM), which was attributed to the bridged linker group. However, our effort on the linker replacement turned out to be fruitless. With the study of the X-ray crystal structure of compound 1 , we envisioned the opportunity of removal of this liability via transposition of the linker moiety in 1 from C6 to C5 position of the pyridine core. With this strategy, our optimization led to the discovery of a novel series, in which the top molecule 18 A displayed reduced CYP inhibitory activity and good potency. To further explore this new series, different warheads besides acrylamide, for example cyanamide, were also tested. However, this effort didn't lead to the discovery of molecules with better potency than 18 A . The loss of potency in those molecules could be related to the reduced reactivity of the warhead or reversible binding mode. Further profiling of 18 A disclosed that it had a strong hERG (human Ether-a-go-go Related Gene) inhibition, which could be related to the phenoxyphenyl group.     

Live synthesis

Innovations in Systems and Software Engineering - Synthesis automatically constructs an implementation that satisfies a given logical specification. In this paper, we study the live synthesis...     

Viroids and the Origin of Life

Viroids are non-coding circular RNA molecules with rod-like or branched structures. They are often ribozymes, characterized by catalytic RNA. They can perform many basic functions of life and may have played a role in evolution since the beginning of life on Earth. They can cleave, join, replicate, and undergo Darwinian evolution. Furthermore, ribozymes are the essential elements for protein synthesis of cellular organisms as parts of ribosomes. Thus, they must have preceded DNA and proteins during evolution. Here, we discuss the current evidence for viroids or viroid-like RNAs as a likely origin of life on Earth. As such, they may also be considered as models for life on other planets or moons in the solar system as well as on exoplanets.     

A CO2-Tolerant Perovskite Oxide with High Oxide Ion and Electronic Conductivity

Mixed ionic–electronic conductors (MIECs) that display high oxide ion conductivity (σ_o) and electronic conductivity (σ_e) constitute an important family of electrocatalysts for a variety of applications including fuel cells and oxygen separation membranes. Often MIECs exhibit sufficient σ_e but inadequate σ_o. It has been a long-standing challenge to develop MIECs with both high σ_o and stability under device operation conditions. For example, the well-known perovskite oxide Ba_0.5Sr_0.5Co_0.8Fe_0.2O_3−δ (BSCF) exhibits exceptional σ_o and electrocatalytic activity. The reactivity of BSCF with CO₂, however, limits its use in practical applications. Here, the perovskite oxide Bi_0.15Sr_0.85Co_0.8Fe_0.2O_3−δ (BiSCF) is shown to exhibit not only exceptional bulk transport properties, with a σ_o among the highest for known MIECs, but also high CO₂ tolerance. When used as an oxygen separation membrane, BiSCF displays high oxygen permeability comparable to that of BSCF and much higher stability under CO₂. The combination of high oxide transport properties and CO₂ tolerance in a single-phase MIEC gives BiSCF a significant advantage over existing MIECs for practical applications.     

Hochauflösendes Monitoring von Karst-Grundwasserressourcen beiderseits des Jordangrabens – Konzepte und Anwendungsbeispiele

Grundwasser - Im semiariden östlichen Mittelmeerraum mit ausgeprägter Sommertrockenheit nehmen Karstgrundwasserleiter insgesamt die wichtigste Rolle für die Wasserversorgung ein....     

Synthesis,Biological Evaluation,and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1-Activated Prodrugs as Antiviral Agents

Recent studies indicate that tubulin can be a host factor for vector-borne flaviviruses like dengue (DENV) and Zika (ZIKV), and inhibitors of tubulin polymerization such as colchicine have been demonstrated to decrease virus replication. However, toxicity limits the application of these compounds. Herein we report prodrugs based on combretastatin and colchicine derivatives that contain an ester cleavage site for human carboxylesterase, a highly abundant enzyme in monocytes and hepatocytes targeted by DENV. Relative to their parent compounds, the cytotoxicity of these prodrugs was reduced by several orders of magnitude. All synthesized prodrugs containing a leucine ester were hydrolyzed by the esterase in vitro. In contrast to previous reports, the phenylglycine esters were not cleaved by human carboxylesterase. The antiviral activity of combretastatin, colchicine, and selected prodrugs against DENV and ZIKV in cell culture was observed at low micromolar and sub-micromolar concentrations. In addition, docking studies were performed to understand the binding mode of the studied compounds to tubulin.     

A constraint programming-based approach to a large-scale energy management problem with varied constraints

This paper addresses a large-scale power plant maintenance scheduling and production planning problem, which has been proposed by the ROADEF/EURO Challenge 2010. We develop two lower bounds for the problem: a greedy heuristic and a flow network for which a minimum cost flow problem has to be solved. Furthermore, we present a solution approach that combines a constraint programming formulation of the problem with several heuristics. The problem is decomposed into an outage scheduling and a production planning phase. The first phase is solved by a constraint program, which additionally ensures the feasibility of the remaining problem. In the second phase we utilize a greedy heuristic—developed from our greedy lower bound—to assign production levels and refueling amounts for a given outage schedule. All proposed strategies are shown to be competitive in an experimental evaluation.     

First international Competition on Runtime Verification: rules,benchmarks, tools,and final results of CRV 2014

International Journal on Software Tools for Technology Transfer - The first international Competition on Runtime Verification (CRV) was held in September 2014, in Toronto, Canada, as a satellite...     

Towards an IoT enabled Tourism and Visualization Review on the Relevant Literature in Recent 10 Years

Mobile Networks and Applications - The implementation of IoT related technologies in tourism is promoting the achievement of smart tourism. In this context, Fifth generation (5G) technology, which...