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In this study, we report the isomerization of an aspartic acid residue in the complementarity-determining region (CDR) of crizanlizumab as a major degradation pathway. The succinimide intermediate and iso-aspartic acid degradation products were successfully isolated by ion exchange chromatography for characterization. The isomerization site was identified at a DG motif in the CDR by peptide mapping. The biological characterization of the isolated variants showed that the succinimide variant exhibited a loss in target binding and biological activity compared to the aspartic acid and iso-aspartic acid variants of the molecule. The influence of pH on this isomerization reaction was investigated using capillary zone electrophoresis. Below pH 6.3, the succinimide formation was predominant, whereas at pH values above 6.3, iso-aspartic acid was formed and the initial amounts of succinimide dropped to levels even lower than those observed in the starting material. Importantly, while the succinimide accumulated at long-term storage conditions of 2 to 8°C at pH values below 6.3, a complete hydrolysis of succinimide was observed at physiological conditions (pH 7.4, 37°C), resulting in full recovery of the biological activity. In this study, we demonstrate that the critical quality attribute succinimide with reduced potency has little or no impact on the efficacy of crizanlizumab due to the full recovery of the biological activity within a few hours under physiological conditions.

This paper aims to determine the potentials as well as the limitations of digital communication to compensate for the massive decrease in direct social interaction due to the Covid-19 pandemic. The availability of “DorfFunk” – a smartphone app for communication in local rural communities – was expanded in three German federal states during the spring of 2020 to counteract some of the negative consequences of measures taken to contain the spread of the virus (curfews, quarantines, social distancing). Here, we present the results of a survey on the experiences, needs, and perceived benefits/limitations of DorfFunk users in times of the pandemic. The results indicate that DorfFunk can contribute to coping with such a situation, especially in the local sphere. Local information and the connection to the community turned out to be of importance, while functionalities for the interaction with other individuals were regarded as secondary. The benefits of DorfFunk were valued more positively in regions where the service had been established already before the pandemic.

Although Augmented Reality (AR) encourages self-managed learning and enhances the learner’s reflection only few companies and schools use AR glasses in vocational training. In our research project we aim to support the dissemination of AR and speed up the augmentation of existing learning processes. But we did not come across methodologies for transferring a conventional learning processes into learning processes for AR Glasses. Therefore, we developed a methodology to enhance conventional learning processes with AR glasses by supporting the creation of AR enrichments for the individual process steps. We describe a use case of an electro engineering lesson that is enriched with AR elements using our methodology.

The interparticle Coulombic decay is a synchronized decay and ionization phenomenon occurring on two separated and only Coulomb interaction coupled electron binding sites. This publication explores how drastically small environmental changes in between the two sites, basically impurities, can alter the ionization properties and process rate, although the involved electronic transitions remain unaltered. A comparison among the present electron dynamics calculations for the example of different types of quantum dots, accommodating a one- or a two-dimensional continuum for the outgoing electron, and the well-investigated atomic and molecular cases with three-dimensional continuum, reveals that the impurity effect is most pronounced the stronger that electron is confined. This necessarily leads to challenges and opportunities in a quantum dot experiment to prove the interparticle Coulombic decay.

With a focus on elderly people this article puts forward a concept of media generation as athickeningof one or more age groups of people who in their media appropriation share a specific experience space of mediatization and subsequently, based on their personal media biographies, develop a shared self-image as a media generation. Such a conceptualisation grasps media generation as a process. It operates with the central aspects of media relatedness, media-generational specifics of appropriation, and self-positioning. This offers an understanding of elderly people after retirement as members of a mass-media media generation. As the qualitative empirical analysis presented in this article demonstrates, members of this mass-media media generation define themselves in contrast to younger media generations.

Characterization and monitoring of post-translational modifications (PTMs) are key analytical requirements during the development of biologics. Top and middle-down (MD) approaches aim at capturing a direct snapshot of all proteoforms with their combinatorial distribution. However, classical MD data analysis is predominantly limited to the interpretation of terminal ion series and PTMs matched by mass. In this study, time-resolved deconvolution (TRD) maps were produced to detect variants and impurities in Fd, Fc/2, and LC subunits of an IgG1 consistently across multiple samples. Classical MD analysis retrieved terminal ions, suggesting a deamidation at a NN motif for a LC+1 Da species, and inconclusive information for a LC+40 Da species. Additionally, we performed differential analysis of all MS2 ions across unmodified and variant subunit spectra to focus data analysis on spectral differences and reveal diagnostic ions (present, absent, enriched, or depleted ions) before fragment assignment. This sensitive methodology was able to detect diagnostic ions in a chimeric spectrum pointing at a proline-to-histidine sequence variant (+40 Da) missed by classical MD analysis. This methodology was pivotal to unravel relevant terminal ions and internal fragments N-terminal to proline as diagnostic ions to confirm the deamidation site. Moreover, different cleavage propensities were revealed at the deamidated DN site compared to the native NN motif for terminal and internal fragments, which may be tracked as a diagnostic behavior. Differential analysis may refine the detection of novel diagnostic ions and leverage the sequence information on internal fragments for the characterization of product-related variants and impurities by MD mass spectrometry.

We have conducted a comprehensive investigation of the optical and vibrational properties of the binary semiconductor SnSe as a function of temperature and pressure by means of experimental and ab initio probes. Our high-temperature investigations at ambient pressure have successfully reproduced the progressive enhancement of the free carrier concentration upon approaching the Pnma → Bbmm transition, whereas the pressure-induced Pnma → Bbmm transformation at ambient temperature, accompanied by an electronic semiconductor → semi-metal transition, has been identified for bulk SnSe close to 10 GPa. Modeling of the Raman-active vibrations revealed that three-phonon anharmonic processes dominate the temperature-induced mode frequency evolution. In addition, SnSe was found to exhibit a pressure-induced enhancement of the Born effective charge. Such behavior is quite unique and cannot be rationalized within the proposed effective charge trends of binary materials under pressure.

We investigate electronic quantum fluxes during large amplitude nuclear vibrations of hydrocarbon (HnCCHn), hydrosilicon (HnSiSiHn) and organosilicon (HnSiCHn) compounds with n = 1, 2, 3. The total electronic fluxes are analysed in terms of contributions from localised molecular orbital densities. Furthermore, the vibrationally induced charge transfer in the polar compounds is investigated in terms of the underlying fluxes.

The interparticle Coulombic decay process in paired quantum dots is studied by electron dynamics calculations. We consider a pair of Coulomb-coupled one-electron charged gallium arsenide quantum dots embedded in a nanowire. The two-electron decay process is approximately described by a single active electron model. Within this model, we employ the time-dependent wavepacket approach to the Fermi golden rule (introduced in the context of vibrational predissociation) to calculate autoionization rates, which are compared to exact rates obtained from fully correlated two-electron dynamics calculations. We found that the approximate decay rates agree well with the exact results in the limit of sufficiently separated quantum dots. Finally, we explore whether the short-range behavior of the new model can be further enhanced by the inclusion of local exchange effects by means of regularization of the Coulomb-potential based on a Jastrow-Slater wavefunction. The proposed method may open a route to study the interparticle Coulombic decay in more intricate systems, e.g., paired metal-nanoparticle—quantum dot systems.The interparticle Coulombic decay process in paired quantum dots is studied by electron dynamics calculations. We consider a pair of Coulomb-coupled one-electron charged gallium arsenide quantum dots embedded in a nanowire. The two-electron decay process is approximately described by a single active electron model. Within this model, we employ the time-dependent wavepacket approach to the Fermi golden rule (introduced in the context of vibrational predissociation) to calculate autoionization rates, which are compared to exact rates obtained from fully correlated two-electron dynamics calculations. We found that the approximate decay rates agree well with the exact results in the limit of sufficiently separated quantum dots. Finally, we explore whether the short-range behavior of the new model can be further enhanced by the inclusion of local exchange effects by means of regularization of the Coulomb-potential based on a Jastrow-Slater wavefunction. The proposed method may open a route to study the interpa...