Introducing Glycolinkers for the Functionalization of Cytotoxic Drugs and Applications in Antibody–Drug Conjugation Chemistry

Antibody–drug conjugates (ADCs) are promising alternatives to naked antibodies for selective drug‐delivery applications and treatment of diseases such as cancer. Construction of ADCs relies upon site‐selective, efficient and mild conjugation technologies. The choice of a chemical linker is especially important, as it affects the overall properties of the ADC. We envisioned that hydrophilic bifunctional chemical linkers based on carbohydrates would be a useful class of derivatization agents for the construction of linker–drug conjugates and ADCs. Herein we describe the synthesis of carbohydrate‐based derivatization agents, glycolinker–drug conjugates featuring the tubulin inhibitor monomethyl auristatin E and an ADC based on an anti‐EGFR antibody. In addition, an initial in vitro cytotoxicity evaluation of the individual components and the ADC is provided against EGFR‐positive cancer cells.     

Simultaneous oxidation of aromatic compounds using Sr-doped lanthanum manganites as catalysts

Strontium-doped lanthanum manganites, La_1-xSr_xMnO₃ (LSMO), are promising and affordable catalysts for oxidative degradation of volatile organic compounds. LSMO catalysts (x = 0, .1, .2, and .3) were prepared by the citrate-nitrate autocombustion (CNA) and coprecipitation synthesis. The phase composition was confirmed by X-ray diffraction and Rietveld refinement analysis, while the oxygen content was determined by Mohr's salt permanganate titration. Morphology and porosity of prepared catalysts was correlated to catalytic oxidation of benzene, toluene, ethylbenzene and o-xylene. It was observed that both synthesis methods yielded catalysts of similar average pore size diameter and specific surface area, but the pore size distribution differed: CNA-prepared catalysts had a multimodal pore size distribution, while the coprecipitated ones had a single maximum at 4 nm. Catalysts prepared by the CNA method have shown a higher catalytic activity in the temperature range 373–723 K, as the presence of Mn³⁺/Mn⁴⁺ mixed valences increased their reducibility.     

Bandwidth limits of luminescent solar concentrators as detectors in free-space optical communication systems

Luminescent solar concentrators(LSCs)have recently emerged as a promising receiver technology in free-space optical communications due to their inherent ability to collect light from a wide field-of-view and concentrate it into small areas,thus leading to high optical gains.Several high-speed communication systems integrating LSCs in their detector blocks have already been demonstrated,with the majority of efforts so far being devoted to maximising the received optical power and the system's field-of-view.However,LSCs may pose a severe bottleneck on the bandwidth of such communication channels due to the comparably slow timescale of the fluorescence events involved,a situation further aggravated by the inherent reabsorption in these systems,and yet,an in-depth study into such dynamic effects remains absent in the field.To fill this gap,we have developed a comprehensive analytical solution that delineates the fundamental bandwidth limits of LSCs as optical detectors in arbitrary free-space optical links,and establishes their equivalence with simple RC low-pass electrical circuits.Furthermore,we demonstrate a time-domain Monte Carlo simulation platform,an indispensable tool in the multiparameter optimisation of LSC-based receiver systems.Our work offers vital insight into LSC system dynamic behaviour and paves the way to evaluate the technology for a wide range of applications,including visible light communications,high-speed video recording,and real-time biological imaging,to name a few.     

Effect of lanthanum-modified magnesium silicate on isotactic polypropylene crystallization in composite materials during shear flow

The activity of isotactic polypropylene (iPP) nucleating additives during shear flow of composite materials is still not entirely explained. In current work the sol-gel method was employed to synthesize MgO·SiO₂ filler, surface-modified with trivalent lanthanum. The crystallization of commercial iPP in the presence of 0.5% by weight La³⁺ modified or unmodified silicates was analyzed. The wide angle X-ray scattering analysis proved that the presence of even small amount of filler influences significantly on supermolecular structure of iPP. The results of microscope observations confirmed that the lanthanum-modified filler shows the nucleating ability for iPP. In that case a significant reduction of crystallization induction time was noticed. The investigation of iPP crystallization in composites after shear treatment confirmed that the increase of shear rate reduces the nucleating ability of additives. Moreover, the flow of filler particles during shearing may impede the shear-induced crystallization phenomenon.     

Redox processes in pressurised smoked salmon studied by resonance Raman spectroscopy

Non-thermal food preservation technology is based on the application of high pressures up to 600 MPa. Here we report a resonance Raman (RR) spectroscopic analysis of smoked salmon meat after high pressure processing. High quality spectra, which can be obtained even from packed salmon without spectral interference of the packing foil, allow determining pressure-dependent irreversible changes of the main RR-active components of salmon meat, astaxanthin and myoglobin/haemoglobin. High pressure-treatment causes a decrease of the relative RR intensities of astaxanthin as probed with 514 nm excitation which is in line with a slight attenuation of the originally intense red colour of the salmon meat. 413-nm excited RR spectra indicate a heterogeneous broadening of astaxanthin bands accompanied by the formation of deoxy-myoglobin or deoxy-haemoglobin. The results suggest that pressure-treatment facilitates the oxidative degradation of astaxanthin coupled to the reduction of metmyoglobin (methaemoglobin).     

Mixture Rules for Critical Shear Values of Extruded Linear PE/Branched PE Blends

Oscillatory flow and elastic turbulence belong to the types of flow instabilities frequently encountered during extrusion of polymer melts. The onset of these defects corresponds to the flow conditions when the critical shear stresses or the critical shear rates are attained. The critical values of shear stresses and shear rates were experimentally determined for linear polyethylene/branched polyethylene blends (IPE/bPE) that were prepared with various weight ratios. Consequently, mixture rules of the logarithmic type are proposed. These rules relate the critical value of shear stress (shear rate) of blend to the critical values of shear stresses (shear rates) of the individual pure components, weight fractions, and interaction parameters. There is a good agreement between the proposed mixture rules and experimentally determined critical values.     

Underapproximation of procedure summaries for integer programs

International Journal on Software Tools for Technology Transfer - We show how to underapproximate the procedure summaries of recursive programs over the integers using off-the-shelf analyzers for...     

Identification of quasi-optimal regions in the design space using surrogate modeling

The use of Surrogate Based Optimization (SBO) is widely spread in engineering design to find optimal performance characteristics of expensive simulations (forward analysis: from input to optimal output). However, often the practitioner knows a priori the desired performance and is interested in finding the associated input parameters (reverse analysis: from desired output to input). A popular method to solve such reverse (inverse) problems is to minimize the error between the simulated performance and the desired goal. However, there might be multiple quasi-optimal solutions to the problem. In this paper, the authors propose a novel method to efficiently solve inverse problems and to sample Quasi-Optimal Regions (QORs) in the input (design) space more densely. The development of this technique, based on the probability of improvement criterion and kriging models, is driven by a real-life problem from bio-mechanics, i.e., determining the elasticity of the (rabbit) tympanic membrane, a membrane that converts acoustic sound wave into vibrations of the middle ear ossicular bones.