Search Results (5)

The toolbox of modern antibody engineering allows the design of versatile novel functionalities exceeding nature’s repertoire. Many bispecific antibodies comprise heterodimeric Fc portions recently validated through the approval of several bispecific biotherapeutics. While heterodimerization methodologies have been established for low-throughput large-scale production, few approaches exist to overcome the bottleneck of large combinatorial screening efforts that are essential for the identification of the best possible bispecific antibody. This report presents a novel, robust and miniaturized heterodimerization process based on controlled Fab-arm exchange (cFAE), which is applicable to a variety of heterodimeric formats and compatible with automated high-throughput screens. Proof of applicability was shown for two therapeutic molecule classes and two relevant functional screening read-outs. First, the miniaturized production of biparatopic anti-c-MET antibody–drug conjugates served as a proof of concept for their applicability in cytotoxic screenings on tumor cells with different target expression levels. Second, the automated workflow enabled a large unbiased combinatorial screening of biparatopic antibodies and the identification of hits mediating potent c-MET degradation. The presented workflow utilizes standard equipment and may serve as a facile, efficient and robust method for the discovery of innovative therapeutic agents in many laboratories worldwide. Full article

Background. The COVID-19 lockdown could engender disruption to lifestyle behaviors, thus impairing mental wellbeing in the general population. This study investigated whether sociodemographic variables, changes in physical activity, and sleep quality from pre- to during lockdown were predictors of change in mental wellbeing in quarantined older adults. Methods. A 12-week international online survey was launched in 14 languages on 6 April 2020. Forty-one research institutions from Europe, Western-Asia, North-Africa, and the Americas, promoted the survey. The survey was presented in a differential format with questions related to responses “pre” and “during” the lockdown period. Participants responded to the Short Warwick–Edinburgh Mental Wellbeing Scale, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and the short form of the International Physical Activity Questionnaire. Results. Replies from older adults (aged >55 years, n = 517), mainly from Europe (50.1%), Western-Asia (6.8%), America (30%), and North-Africa (9.3%) were analyzed. The COVID-19 lockdown led to significantly decreased mental wellbeing, sleep quality, and total physical activity energy expenditure levels (all p < 0.001). Regression analysis showed that the change in total PSQI score and total physical activity energy expenditure (F_{(2, 514)} = 66.41 p < 0.001) were significant predictors of the decrease in mental wellbeing from pre- to during lockdown (p < 0.001, R²: 0.20). Conclusion. COVID-19 lockdown deleteriously affected physical activity and sleep patterns. Furthermore, change in the total PSQI score and total physical activity energy expenditure were significant predictors for the decrease in mental wellbeing. Full article

Public health recommendations and governmental measures during the new coronavirus disease (COVID-19) pandemic have enforced numerous restrictions on daily living including social distancing, isolation, and home confinement. While these measures are imperative to mitigate spreading of COVID-19, the impact of these restrictions on psychosocial health is undefined. Therefore, an international online survey was launched in April 2020 to elucidate the behavioral and lifestyle consequences of COVID-19 restrictions. This report presents the preliminary results from more than one thousand responders on social participation and life satisfaction. Methods: Thirty-five research organizations from Europe, North-Africa, Western Asia, and the Americas promoted the survey through their networks to the general society, in 7 languages (English, German, French, Arabic, Spanish, Portuguese, and Slovenian). Questions were presented in a differential format with questions related to responses “before” and “during” confinement conditions. Results: 1047 participations (54% women) from Asia (36%), Africa (40%), Europe (21%), and others (3%) were included in the analysis. Findings revealed psychosocial strain during the enforced COVID-19 home confinement. Large decreases (p < 0.001) in the amount of social activity through family (−58%), friends/neighbors (−44.9%), or entertainment (−46.7%) were triggered by the enforced confinement. These negative effects on social participation were also associated with lower life satisfaction (−30.5%) during the confinement period. Conversely, the social contact score through digital technologies significantly increased (p < 0.001) during the confinement period with more individuals (+24.8%) being socially connected through digital technology. Conclusion: These preliminary findings elucidate the risk of psychosocial strain during the early COVID-19 home confinement period in 2020. Therefore, in order to mitigate the negative psychosocial effects of home confinement, implementation of national strategies focused on promoting social inclusion through a technology-based solution is strongly suggested. Full article

Active Galactic Nuclei emit radiation over the whole electromagnetic spectrum up to TeV energies. Blazars are one subtype with their jets pointing towards the observer. One of their typical features is extreme variability on timescales, from minutes to years. The fractional variability is an often used parameter for investigating the degree of variability of a light curve. Different detection methods and sensitivities of the instruments result in differently binned data and light curves with gaps. As they can influence the physics interpretation of the broadband variability, the effects of these differences on the fractional variability need to be studied. In this paper, we study the systematic effects of completeness in time coverage and the sampling rate. Using public data from instruments monitoring blazars in various energy ranges, we study the variability of the bright TeV blazars Mrk 421 and Mrk 501 over the electromagnetic spectrum, taking into account the systematic effects, and compare our findings with previous results. Especially in the TeV range, the fractional variability is higher than in previous studies, which can be explained by the much longer (seven years compared to few weeks) and more complete data sample. Full article

Blazars are known to show variability on time scales from minutes to years covering a wide range of flux states. Studying the flux distribution of a source allows for various insights. The shape of the flux distribution can provide information on the nature of the underlying variability processes. The level of a possible quiescent state can be derived from the main part of the distribution that can be described by a Gaussian distribution. Dividing the flux states into quiescent and active, the duty cycle of a source can be calculated. Finally, this allows alerting the multi-wavelength and multi-messenger community in case a source is in an active state. To get consistent and conclusive results from flux distributions, unbiased long-term observations are crucial. Only like this is a complete picture of the variability and flux states, e.g., an all-time quiescent state, possible. In seven years of monitoring of bright TeV blazars, the first G-APD Cherenkov telescope (FACT) has collected a total of more than 11,700 hours of physics data with 1500 hours to 3000 hours per source for Mrk 421, Mrk 501, 1ES 1959+650, and 1ES 2344+51. Full article