Improvements in the Synthesis of the Third-Generation EGFR Inhibitor Osimertinib

Osimertinib, a third generation potent and specific EGFR inhibitor is an important drug against many forms of cancer. It was synthesized by an improved and highly efficient protocol, revisiting the classical synthetic process and modifying parameters, such as solvents, temperature, reagents, and reaction time. A cost-effective, environmentally friendly methodology for the synthesis of osimertinib was established, which gave shorter reaction times, saved labor by eliminating purification steps through column chromatography, and enhanced yields. Four of the seven steps in total, were proceeded quantitatively or almost quantitatively (ca. 98 %). This synthetic protocol provides a very high overall yield, up to 68 %. In addition, the entire approach enables the preparation of osimertinib analogues and could be extended in the synthesis of other structurally similar bioactive compounds.     

A proposal for a convertible stadium roof structure derived from Watt-I linkage

In this paper, a novel convertible stadium roof structure is introduced, which has been derived from a special geometric configuration of Watt-I linkage, a 1-DoF mechanism used in robot technologies as anthropomorphic fingers. The proposed structure can offer a wide range of different shape configurations according to the environmental conditions and spatial needs, thus offering several aesthetic and functional advantages over existing solutions. This paper serves as a feasibility investigation of this concept, mainly from geometric and structural point of view. To that affect, first kinematic analysis and geometric design of this linkage are introduced. Then, structural analyses of the proposed structure with realistic dimensions and loading conditions are performed in three different geometric configurations, in order to discuss strength and stiffness limitations. Finally, potential cover materials and actuators are briefly discussed.     

Operations research in the space industry

Operations research techniques have been used in the space industry since its infancy, and various competing methods and codes, with widely varying characteristics, have been used over time. This survey is intended to give an overview of current application cases of different operations research techniques and methodologies in the domain of space engineering and space science.     

Diblock copolymers of polystyrene‐b‐poly(1,3‐cyclohexadiene) exhibiting unique three‐phase microdomain morphologies

The synthesis and molecular characterization of a series of conformationally asymmetric polystyrene‐block‐poly(1,3‐cyclohexadiene) (PS‐b‐PCHD) diblock copolymers (PCHD: ～90% 1,4 and ～10% 1,2), by sequential anionic copolymerization high vacuum techniques, is reported. A wide range of volume fractions (0.27 ≤ ?_PS ≤ 0.91) was studied by transmission electron microscopy and small‐angle X‐ray scattering in order to explore in detail the microphase separation behavior of these flexible/semiflexible diblock copolymers. Unusual morphologies, consisting of PCHD core(PCHD‐1,4)–shell(PCHD‐1,2) cylinders in PS matrix and three‐phase (PS, PCHD‐1,4, PCHD‐1,2) four‐layer lamellae, were observed suggesting that the chain stiffness of the PCHD block and the strong dependence of the interaction parameter χ on the PCHD microstructures are important factors for the formation of this unusual microphase separation behavior in PS‐b‐PCHD diblock copolymers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1564–1572     

Evaluating the impact of functional groups on membrane-mediated CO2/N2 gas separations using a common polymer backbone

Polymeric membranes have shown tremendous promise for the separation of CO₂ from flue gas streams. However, few systematic studies have been conducted to better understand the impact that chemical functionalities have on membrane-based gas separation performance. To address this gap, we herein describe the synthesis and gas separation performance of a series of vinyl-addition polynorbornenes bearing various CO₂-philic functional groups. To facilitate direct comparison between functional groups, each material was designed to maintain a common polymer backbone. Though the incorporation of CO₂-philic moieties within a dense polymeric membrane is frequently hypothesized to enhance CO₂ solubility, and thereby increase CO₂/N₂ selectivity, our results demonstrate that the incorporation of CO₂-philic groups onto a common polymer backbone do not necessarily result in increased gas separation performance. Experimental and computational results demonstrate that the incorporation of amidoxime groups onto a polynorbornene backbone increase CO₂/N₂ selectivity, whereas commonly employed ethereal side chains only increased permeability.     

Nonlinear Poisson autoregression

We study statistical properties of a class of non-linear models for regression analysis of count time series. Under mild conditions, it is shown that a perturbed version of the model is geometrically ergodic and possesses moments of any order. This result turns out to be instrumental on deriving large sample properties of the maximum likelihood estimators of the regression parameters. The theory is illustrated with examples.     

Production of antibodies from chicken egg yolk to phenyl- N -methylcarbamate insecticides for analytical purposes

With the aim of developing polyclonal antibodies binding as many phenyl-N-methylcarbamate insecticides (PNMCs) as possible, IgY antibodies were produced in laying hens. Two haptens (3-(2,6-dimethyl-4-(methylcarbamoyl)phenylaminocarbonyl)propanoic acid and 4-((2,6-dimethyl-4-(methylcarbamoyl)phenylaminocarbonyl)-3,3-dimethyl)butanoic acid) were synthesized preserving the major structural features of PNMCs, by a novel synthetic pathway. These haptens differed only in the spacer arm incorporated. Immunizing antigen and coating antigen were prepared by coupling the first hapten with bovine serum albumin and the second with thyroglobulin, from porcine thyroid glands, respectively. The titre and maturation increase in the developed antibodies, in the egg yolk, were assessed by non-competitive ELISA. Avidity and cross-reactivity of the antibodies with selected pesticides were estimated by means of competitive ELISA. The produced IgYs exhibited a high binding capacity to carbaryl, trimethacarb, metolcarb, aminocarb, and promecarb. These antibodies can be used for immunosorbent preparation for analytical purposes.