Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones

Most anticancer drugs target mitosis as the most crucial and fragile period of rapidly dividing cancer cells. However the limitations of classical chemotherapeutics drive the search for new more effective and selective compounds. For this purpose structural modifications of the previously characterized pyridine analogue (S1) were incorporated aiming to obtain an antimitotic inhibitor of satisfactory and specific anticancer activity. Structure-activity relationship analysis of the compounds against a panel of cancer cell lines allowed to select a compound with a thiophene ring at C5 of a 3,4-dihydropyridine-2(1H)-thione (S22) with promising antiproliferative activity (IC₅₀ equal 1.71 ± 0.58 µM) and selectivity (SI = 21.09) against melanoma A375 cells. Moreover, all three of the most active compounds from the antiproliferative study, namely S1, S19 and S22 showed better selectivity against A375 cells than reference drug, suggesting their possible lower toxicity and wider therapeutic index. As further study revealed, selected compounds inhibited tubulin polymerization via colchicine binding site in dose dependent manner, leading to aberrant mitotic spindle formation, cell cycle arrest and apoptosis. Summarizing, the current study showed that among obtained mitotic-specific inhibitors analogue with thiophene ring showed the highest antiproliferative activity and selectivity against cancer cells.     

基于场效应晶体管的太赫兹探测器中天线设计的一种有效方法

在场效应晶体管太赫兹探测器中,合理的天线设计可以增强晶体管和太赫兹波之间的耦合效率,从而提高太赫兹探测器的响应度.提出一种基于晶体管栅极边缘沟道电场的仿真来设计平面天线的方法.这种方法尤其适用于太赫兹波段晶体管输入阻抗不容易得到的情况.通过流片完成的基于氮化镓高电子迁移率晶体管的太赫兹探测器的响应度测试证实了这种方法的有效性.集成碟形天线和双偶极子天线的太赫兹探测器最大响应度分别在170.7 GHz(1568.4 V/W)和124.3 GHz(1047.2 V/W)频点处测得,这个测试结果接近基于晶体管栅极边缘沟道电场的仿真结果.     

New generalized Newtonian fluid models for quantitative description of complex viscous behavior in shear flows

Two semiempirical models of generalized Newtonian fluid are discussed. Special attention was focused on the stress dependent model based on the free volume theory. However, the strain‐rate dependent model in form of a modified viscosity function resulting from Oldroyd equation is also presented. Both models (along with specific cases) reflecting pseudoplastic or dilatant behavior of liquids in shear flows are generalized to multimode models (defined as products of two or more basic models), which are able to describe quantitatively the behavior of more complex systems, for example, systems with pseudoplastic and dilatant properties in different shear stress (shear rate) ranges. A number of practical examples for viscosity curves of non‐Newtonian fluids described by these models are given. The questions of inverse models and model efficiency are also discussed. POLYM. ENG. SCI., 58:1446–1455, 2018. © 2017 Society of Plastics Engineers     

Fabrication of the self‐reinforced composites using co‐extrusion technique

The results of this work relate to the use of co‐extrusion technology in the preparation of monocomposite pellets. The low‐melting polypropylene copolymer was used as a matrix material. The high strength polypropylene fibers were used as a fibrous reinforcement. Research confirms the possibility to produce the pellets with fibrous structure. The prepared composite material in the form of pellets was processed and shaped using the injection molding technology. Obtained samples were subjected to mechanical testing in the static tensile test and dynamic mechanical analysis. Research complements microscopic observation of scanning electron microscopy. The measurement results confirm the reinforcing effect of the fibers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41180.     

Comparison of the effects of different chemical activation methods on properties of carbonaceous adsorbents obtained from cherry stones

A method for obtaining activated carbons from cherry stones by chemical activation with NaOH is described. Carbonaceous adsorbents were obtained by two methods of activation (physical mixing and impregnation) and two variants of thermal treatment (at a constant or increasing temperature). Cherry stones were proved to be effective cheap precursors of carbon adsorbents, characterised by large pore volume (ranging from 0.22 to 0.47 cm³/g) and good sorption abilities (iodine number from 343 to 996 mg/g). The activated carbons obtained usually have strongly microporous structure and acidic surface character. The best physicochemical properties and adsorption properties towards iodine were found to be shown by the carbon samples obtained by physical mixing of the precursor or char with the activating agent followed by activation at 600 °C.     

Toward high‐efficiency dye‐sensitized solar cells with a photoanode fabricated via a simple water‐based formulation

An aqueous formulation containing commercially available P25 nanoparticles and a water‐soluble precursor—titanium (IV) bis(ammonium lactato)dihydroxide (TALH) has been developed and optimized for fabricating photoanodes in dye‐sensitized solar cells. An optimal formulation achieved a power conversion efficiency of 9.2%. Solar cell performance is significantly influenced by precursor concentration impacting the porosity and electron transport of the thin film. The use of TALH during processing is shown to enhance the electron transport in the resulting titanium dioxide nanoparticle network using transient decay measurements. Bridging between neighboring nanoparticles is confirmed using transmission electron microscopy explaining the enhanced electron transport. The developed formulation has several advantages, as it is water‐based, composed of inexpensive, non‐hazardous components, is easy to make, and does not require special handling. The formulation has great potential for industrial applications, in particular for DSC manufacturing using roll‐to‐roll technology. Copyright © 2014 John Wiley & Sons, Ltd.     

Influence of fire retardants on smoke generation from wood and wood derived materials

The influence of three fire retardant agents: Polichron, Pyrolak W-10, and Pyrolak W-10 + Pyrolak W-1 on smoke density of pine wood, plywood, soft hardboard and tough hardboard was investigated. Surface samples of 25 cm² (5 × 5 cm) were used and the heat flux was varied over the range of 1.0 to 4.0 W/cm². Reference: Tadeusz Cisek and Jacek Piechocki, Influence of Fire Retardants on Smoke Generation from Wood and Wood Derived Materials,Fire Technology, Vol. 21, No. 2, May 1985, p. 122.     

Using clinical information in goal-oriented learning.

We have proposed an extension to the Q-learning algorithm that incorporates the existing clinical expertise into the trial-and-error process of acquiring an appropriate administration strategy of rHuEPO to patients with anemia due to ESRD. The specific modification lies in multiple updates of the Q-values for several dose/response combinations during a single learning event. This in turn decreases the risk of administering doses that are inadequate in certain situations and thus increases the speed of the learning process. We have evaluated the proposed method using a simulation test-bed involving an "artificial patient" and compared the outcomes to those obtained by a classical Q-learning and a numerical implementation of a clinically used administration protocol for anemia management. The outcomes of the simulated treatments demonstrate that the proposed method is a more effective tool than the traditional Q-learning. Furthermore, we have observed that it has a potential to provide even more stable anemia management than the AMP.     

Bivalent peptides as models for multimeric targets of PDZ domains

PDZ domains are among the most common modules in eukaryotic, including human, genomes. They are found exclusively in large, multidomain cytosolic proteins--often with other domains that belong to a variety of families--and are involved in a plethora of physiological and pathophysiological events. PDZ domains mediate protein-protein interactions by binding to solvent-exposed and extended C-terminal short fragments of membrane-associated proteins, such as receptors and ion channels. Most of what is known about the mechanisms of target binding by PDZ domains is inferred from studies that involve isolated recombinant PDZ domains and short synthetic peptides that represent the targets. These binary systems constitute an obvious oversimplification and disregard factors such as noncanonical modes of binding and enhanced affinity due to multimeric interactions mediated by clusters and oligomers of PDZ-domain-containing proteins. We have tested whether the interaction between a dimeric form of PDZ domain that mimics a functional dimeric guanine nucleotide exchange factor, PDZ-RhoGEF (PDZ-containing RhoA-specific guanine nucleotide exchange factor) or LARG (leukemia-associated RhoA specific guanine nucleotide exchange factor), and a bivalent peptide that mimics the dimer of the plexin B receptor, could enhance the interaction between the two moieties. Peptide dimerization was achieved by cross-linking the N-terminal ends of peptides attached to Wang resin with poly(ethylene glycol) spacers (30-45 Angstroms in length). The interaction of dimeric PDZ domains with dimeric peptides resulted in an up to 20-fold increase in affinity compared to the simple binary system. This is consistent with the notion that multimerization of both receptors and PDZ-containing proteins might constitute an important regulatory mechanism.     

Comparative analysis of viscosity of complex liquids and cytoplasm of mammalian cells at the nanoscale

We present a scaling formula for size-dependent viscosity coefficients for proteins, polymers, and fluorescent dyes diffusing in complex liquids. The formula was used to analyze the mobilities of probes of different sizes in HeLa and Swiss 3T3 mammalian cells. This analysis unveils in the cytoplasm two length scales: (i) the correlation length ξ (approximately 5 nm in HeLa and 7 nm in Swiss 3T3 cells) and (ii) the limiting length scale that marks the crossover between nano- and macroscale viscosity (approximately 86 nm in HeLa and 30 nm in Swiss 3T3 cells). During motion, probes smaller than ξ experienced matrix viscosity: η(matrix) ≈ 2.0 mPa·s for HeLa and 0.88 mPa·s for Swiss 3T3 cells. Probes much larger than the limiting length scale experienced macroscopic viscosity, η(macro) ≈ 4.4 × 10(-2) and 2.4 × 10(-2) Pa·s for HeLa and Swiss 3T3 cells, respectively. Our results are persistent for the lengths scales from 0.14 nm to a few hundred nanometers.