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.     

Comparison of concentrations and size distributions of fungal spores in buildings with and without mould problems

Concentrations and types of airborne fungal spores and their aerodynamic sizes were studied in nine buildings with mould problems and in matched reference buildings in order to characterize the exposure in buildings with mould problems. Samples were taken with Andersen six-stage impactors in the autumn and winter. In winter, total concentrations of fungal spores in buildings with mould problems were twice those in reference buildings, even though all concentrations were quite small. In the autumn, the differences were less obvious due to the masking effect of outdoor air fungi. Also, the compositions of fungal genera differed in buildings with mould problems from that in reference buildings. The difference was most significant in the size range 2.1-4.7 μm. The size distribution of fungal spores in dwellings with mould problems skewed towards larger particles than in reference dwellings. The observed differences in size distribution indicate differences in airborne behaviour of fungal spores and, consequently, in respiratory exposure.     

The effect of oxygen and the reduction temperature of the Pt/Al2O3 catalyst in enantioselective hydrogenation of 1-phenyl-1,2-propanedione

The effect of oxygen and catalyst reduction temperature in enantioselective hydrogenation of 1-phenyl-1,2-propanedione over commercial Pt/Al₂O₃ catalyst was investigated. Dichloromethane was used as solvent. The catalyst was modified in situ with (−)-cinchonidine. Relatively high enantiomeric excesses (65%) of (R)-1-hydroxy-1-phenyl-2-propanone were obtained with the solvent used as received, i.e. containing traces of dissolved oxygen and other impurities. Dichloromethane dissociated partially on the Pt/Al₂O₃ surface causing desorption of methane, ethene and HCl from the catalyst during TPD according to mass spectrometric analysis. Under anaerobic conditions the reaction rate was low giving only about 40% enantiomeric excesses of (R)-1-hydroxy-1-phenyl-2-propanone. When injecting 5 mm³ of oxygen into the reactor a beneficial effect was observed (i.e. higher reaction rate and enantiomeric excess) in comparison with anaerobic conditions. Poisoning effect of oxygen was observed when injecting 500 mm³ of oxygen into the reactor. Effect of catalyst reduction temperature was studied at three different temperatures (170, 400 and 455°C). Highest reaction rates and enantiomeric excesses were obtained with the catalyst reduced at 400°C. Methane was desorbed from the catalyst at temperatures between 263 and 383°C which could be the explanation for the lower activity of the catalyst reduced at 170°C. It was demonstrated that small amounts of oxygen can have a beneficial effect in enantioselective hydrogenation of 1-phenyl-1,2-propanedione and also that catalyst reduction temperature plays an important role in obtaining high enantiomeric excesses.     

Unique Decipherability in the Monoid of Languages: An Application of Rational Relations

We attack the problem of deciding whether a finite collection of finite languages is a code, that is, possesses the unique decipherability property in the monoid of finite languages. We investigate a few subcases where the theory of rational relations can be employed to solve the problem. The case of unary languages is one of them and as a consequence, we show how to decide for two given finite subsets of nonnegative integers, whether they are the nth root of a common set, for some n≥1. We also show that it is decidable whether a finite collection of finite languages is a Parikh code, in the sense that whenever two products of these sets are commutatively equivalent, so are the sequences defining these products. Finally, we consider a nonunary special case where all finite sets consist of words containing exactly one occurrence of the specific letter.     

The inherent boron dilution mechanism in pressurized water reactors

The purpose of this paper is to describe a mechanism that inherently causes boron dilution in pressurized water reactors (PWRs). The phenomenon is due to the fact that boric acid does not markedly dissolve into steam. This is relevant for transient and accident situations in PWRs where decay heat removal is accomplished by coolant vapourization and condensation, which inherently leads to formation of dilute plugs in the primary. In particular, it is found that inherent dilution will be inevitable for a range of small break loss of coolant accidents (SB LOCAs), with maximum amount of total diluted coolant mass exceeding 20 tonnes for a modern 1300 MWe PWR equipped with U-tube steam generators. A simple analysis of dilute plug motion during the late phases of a SB LOCA and core response to boron dilution shows that the damaging potential might extend to widespread fuel failures. Other transients and accidents are also discussed from the point of view of inherent dilution. Some possible remedies to the problem, as well as suggestions for further research, are presented.