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- team creativity (1)
- intrapreneurship (1)
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"Briefe wie gemahlt"
(2007)
Am 19. Dezember 1831 wurde der verdienstvolle Mikrobiologe Christian Gottfried Ehrenberg zum korrespondierenden Mitglied des Institut de France gewählt. Alexander von Humboldt, der Ehrenberg als Wissenschaftler hoch schätzte, hat sich energisch für diese Wahl eingesetzt. Ein Zeugnis seines Engagements ist ein Brief an den Mediziner Antoine Baron Portal (1742-1832), den er um seine Stimme bei der bevorstehenden Wahl bat. Die Geschichte der Wahl Ehrenbergs in Verbindung mit diesem Brief und die Gründe für Humboldts Interesse daran sollen hier kurz skizziert werden.
Daniel Kehlmann gibt vor, mit seinem Roman Die Vermessung der Welt „verschwiegene oder übersehene Wahrheiten sichtbar“ zu machen. Dadurch, dass er die Leser bewusst im Zweifel lässt, was historisch belegt und was erfunden ist, entstehen Missverständnisse. Der Beitrag analysiert die wichtigsten Charakteristika des Kehlmann‘schen und des historischen Alexander von Humboldt und weist nach, dass diese nicht übereinstimmen. Der Aufsatz fragt nach Kehlmanns Rolle, der in der Öffentlichkeit gerne die Pose des Gelehrten einnimmt, seine Erfindungen jedoch nicht offenlegt und sie als angebliches Humboldt-Zitat sogar in einem wissenschaftlichen Text publiziert. Der Beitrag kommt zu dem Schluss, dass alle, die etwas für ihre Allgemeinbildung tun möchten, bei Die Vermessung der Welt an der falschen Adresse sind.
Background:
Cyberhate is a growing form of online aggression against a person or a group based on race, ethnicity, nationality, sexual orientation, gender, religion, or disability. The present study aims to examine psychometric properties of the Coping with Cyberhate Questionnaire, the prevalence of coping strategies in Spanish adolescents, differences in coping strategies based in sex, age, and victim status, and the association between coping with cyberhate and adolescents' mental well-being.
Method:
The sample consisted of 1,005 adolescents between 12 and 18 years old (Mage = 14.28 years, SD = 1.63; 51.9% girls) who completed self-report measures on coping strategies, victimization status, and mental well-being.
Results:
The results of confirmatory factor analyses showed a structure for the Coping with Cyberhate Questionnaire composed of six factors, namely Distal advice, Assertiveness, Helplessness/Selfblame, Close support, Technical coping, and Retaliation. It demonstrated acceptable internal consistency. The three most frequently endorsed coping strategies were Technical coping, Close support, and Assertiveness. In addition, lower Helplessness/Self-blame, and higher Close-support, Assertiveness, and Distal advice were significantly related to adolescents' better mental well-being.
Conclusion:
Prevention programs that educate adolescents about how to deal with cyberhate are needed.
"Orfeo out of Care"
(2022)
The paper focuses on an example of multiple-step reception: the contribution of the classical story of Orpheus and Eurydice and the mediaeval lay Sir Orfeo to Tolkien’s work.
In the first part, I compare the lay with Virgilian and Ovidian versions of Orpheus’ myth. This comparison shows the anonymous author’s deep knowledge of the ancient texts and complex way of rewriting them through stealing and hybridization.
The lay was highly esteemed by Tolkien, who translated it and took inspiration from it while describing the Elven kingdom in The Hobbit and building the storyline of Beren and Lúthien in The Silmarillion. Through this key tale, Orpheus/Orfeo’s romance has a deep influence also on Aragorn and Arwen’s story in The Lord of the Rings. The most important element that Tolkien takes from the Sir Orfeo figuration of the ancient story is undoubtedly the insertion of political theme: the link established between the recovery of the main character’s beloved and the return to royal responsability.
The second part of the paper is, thus, dedicated to the reception of Sir Orfeo and the classical myth in Tolkien. It shows how in his work the different steps of the tradition of Orpheus’ story are co-present, creating an inextricable substrate of inspiration that nourishes his imagination.
Empirical evidence of the relationship between social support and post-disaster mental health provides support for a general beneficial effect of social support (main-effect model; Wheaton, 1985). From a theoretical perspective, a buffering effect of social support on the negative relationship between disaster-related stress and mental health also seems plausible (stress-buffering model; Wheaton, 1985). Previous studies, however, (a) have paid less attention to the buffering effect of social support and (b) have mainly relied on interpersonal support (but not collective-level support such as community resilience) when investigating this issue. This previous work might have underestimated the effect of support on post-disaster mental health. Building on a sample of residents in Germany recently affected by flooding (N = 118), we show that community resilience to flooding (but not general interpersonal social support) buffered against the negative effects of flooding on post-disaster mental health. The results support the stress-buffering model and call for a more detailed look at the relationship between support and resilience and post-disaster adjustment, including collective-level variables.
"Writing with my professors”
(2023)
Kollaboratives Forschen quer zu hegemonialen Wissensordnungen gilt als wichtiger Baustein dekolonialer Wissenspraxis. Gemeinsame Schreibprozesse von Wissenschaftler*innen und ihren nicht-wissenschaftlichen Forschungspartner*innen sind allerdings selten und eine methodologische und forschungspraktische Reflexion fehlt. Die Beiträger*innen widmen sich diesen Lücken, indem sie erfolgreiche, aber auch gescheiterte Projekte kollaborativer Textproduktion zwischen Universität und Feld vorstellen und auf ihr Potenzial als transformative und dekoloniale Wissenspraxis befragen. So entsteht eine praktische Orientierungshilfe, die gleichzeitig die interdisziplinäre Diskussion anregt.
(Auf) Humboldts Spuren
(2021)
Vor seiner Besteigung des Antisana in Ecuador verbrachte Alexander von Humboldt mit seinem Expeditionsteam die Nacht vom 15. auf den 16. März 1802 in einer Hacienda am Fuße des Vulkangipfels, deren letztes bauliches Zeugnis eine steinerne Hütte darstellt. Bauforscherische Untersuchungen eines internationalen Forscherteams konnten die mehrschichtige Bau- und Reparaturgeschichte dieses Baudenkmals ermitteln und über eine Auswertung von Reiseberichten mehrerer Andenforscher die Nutzungsgeschichte des einzelnen Gebäudes und des gesamten Anwesens klären. Schließlich ergaben sich daraus neue Erkenntnisse zu Humboldts Aufenthalt am Antisana.
The paper investigates Tolkien’s narratives of decline through the lens of their classical ancestry. Narratives of decline are widespread in ancient culture, in both philosophical and literary discourses. They normally posit a gradual degradation (moral and ontological) from an idealized Golden Age, which went hand-in-hand with increasing detachment of gods from mortal affairs. Narratives of decline are also at the core of Tolkien’s mythology, constituting yet another underresearched aspect of classical influence on Tolkien. Such Classical narratives reverberate e.g. in Tolkien’s division of Arda’s history into ages, from an idealized First Age filled with Joy and Light to a Third Age, described as “Twilight Age (…) the first of the broken and changed world” (Letters 131). More generally, these narratives are related to Tolkien’s notorious perception of history as a “long defeat” (Letters 195) and to that “heart-racking sense of the vanished past” which pervades Tolkien’s works – the emotion which, in his words, moved him “supremely” and which he found “small difficulty in evoking” (Letters 91). The paper analyses the reception of narratives of decline in Tolkien’s legendarium, pointing out similarities but also contrasts and differences, with the aim to discuss some key patterns of (classical) reception in Tolkien’s theory and practice (‘renewal’, ‘accommodation’, ‘focalization’).
Im Sinne einer „Meta-Reflexivität“ zielt dieser Beitrag darauf ab, den strukturtheoretischen und kompetenzorientierten Professionalisierungsansatz im Konstrukt der adaptiven Lehrkompetenz zusammenzuführen, was vor allem für inklusionsorientierte Ansätze vielversprechend erscheint: Anhand der Konstruktfacetten adaptiver diagnostischer, didaktischer sowie Sach- und Klassenführungskompetenz werden mögliche Herangehensweisen für eine inklusionsorientierte Lehrkräftebildung formuliert, die sowohl konkrete Kompetenzbereiche benennen als auch die Reflexion entsprechender Spannungsverhältnisse im strukturtheoretischen Sinne voraussetzen. So soll der Beitrag einen knappen theoretischen Aufriss zur Zusammenführung der unterschiedlichen Professionalisierungsansätze unter der Prämisse (mehr) Reflexion für (mehr) Inklusion leisten.
(Moralisch) guter Sex
(2023)
In einem kürzlich erschienenen Artikel argumentiert Almut v. Wedelstaedt überzeugend, warum Zustimmung zwar „die Bedingung für die Legitimation von Sex“ ist (2020, 127), dass die moralische Güte von Sex aber nur dann einzuschätzen ist, wenn wir darauf achten, ob die Beteiligten der Handlung sich auf Augenhöhe begegnen. Die Idee ist: Es gibt legitime sexuelle Handlungen, die moralisch gut sind, und es gibt legitime sexuelle Handlungen, die moralisch besser sind. Hier möchte ich die Idee des besseren Sexes genauer ausloten. Während v. Wedelstaedt von moralisch gelungenem Sex spricht und somit auf der Ebene der moralischen Bewertung von Sex bleibt, möchte ich die Frage danach stellen, was Sex qualitativ gut macht. Tatsächlich wird in der Zustimmungsdebatte meist davon ausgegangen, dass diese zwei Fragen wenig gemeinsam haben; ob eine sexuelle Handlung legitim ist, hat zunächst nichts damit zu tun, ob diese auch gut ist. Ich werde drei Argumente liefern, warum wir legitimen Sex und qualitativ guten Sex zusammen betrachten sollten – und es wird sich zeigen, dass die gegenwärtige philosophische und rechtstheoretische Debatte Zustimmung verkürzt diskutiert und daher alleingenommen wenig hilfreich ist, stattdessen benötigt die Zustimmungsdebatte auch eine Untersuchung von qualitativ gutem Sex.
We present novel experimental evidence on the availability and the status of exhaustivity inferences with focus partitioning in German, English, and Hungarian. Results suggest that German and English focus-background clefts and Hungarian focus share important properties, (É. Kiss 1998, 1999; Szabolcsi 1994; Percus 1997; Onea & Beaver 2009). Those constructions are anaphoric devices triggering an existence presupposition. EXH-inferences are not obligatory in such constructions in English, German, or Hungarian, against some previous literature (Percus 1997; Büring & Križ 2013; É. Kiss 1998), but in line with pragmatic analyses of EXH-inferences in clefts (Horn 1981, 2016; Pollard & Yasavul 2016). The cross-linguistic differences in the distribution of EXH-inferences are attributed to properties of the Hungarian number marking system.
Monolithic perovskite silicon tandem solar cells can overcome the theoretical efficiency limit of silicon solar cells. This requires an optimum bandgap, high quantum efficiency, and high stability of the perovskite. Herein, a silicon heterojunction bottom cell is combined with a perovskite top cell, with an optimum bandgap of 1.68 eV in planar p-i-n tandem configuration. A methylammonium-free FA(0.75)Cs(0.25)Pb(I0.8Br0.2)(3) perovskite with high Cs content is investigated for improved stability. A 10% molarity increase to 1.1 m of the perovskite precursor solution results in approximate to 75 nm thicker absorber layers and 0.7 mA cm(-2) higher short-circuit current density. With the optimized absorber, tandem devices reach a high fill factor of 80% and up to 25.1% certified efficiency. The unencapsulated tandem device shows an efficiency improvement of 2.3% (absolute) over 5 months, showing the robustness of the absorber against degradation. Moreover, a photoluminescence quantum yield analysis reveals that with adapted charge transport materials and surface passivation, along with improved antireflection measures, the high bandgap perovskite absorber has the potential for 30% tandem efficiency in the near future.
40Ar/39Ar dating of a hydrothermal pegmatitic buddingtonite–muscovite assemblage from Volyn, Ukraine
(2022)
We determined Ar-40/Ar-39 ages of buddingtonite, occurring together with muscovite, with the laser-ablation method. This is the first attempt to date the NH4-feldspar buddingtonite, which is typical for sedimentary-diagenetic environments of sediments, rich in organic matter, or in hydrothermal environments, associated with volcanic geyser systems. The sample is a hydrothermal breccia, coming from the Paleoproterozoic pegmatite field of the Korosten Plutonic Complex, Volyn, Ukraine. A detailed characterization by optical methods, electron microprobe analyses, backscattered electron imaging, and IR analyses showed that the buddingtonite consists of euhedral-appearing platy crystals of tens of micrometers wide, 100 or more micrometers in length, which consist of fine-grained fibers of <= 1 mu m thickness. The crystals are sector and growth zoned in terms of K-NH4-H3O content. The content of K allows for an age determination with the Ar-40/Ar-39 method, as well as in the accompanying muscovite, intimately intergrown with the buddingtonite. The determinations on muscovite yielded an age of 1491 +/- 9 Ma, interpreted as the hydrothermal event forming the breccia. However, buddingtonite apparent ages yielded a range of 563 +/- 14 Ma down to 383 +/- 12 Ma, which are interpreted as reset ages due to Ar loss of the fibrous buddingtonite crystals during later heating. We conclude that buddingtonite is suited for Ar-40/Ar-39 age determinations as a supplementary method, together with other methods and minerals; however, it requires a detailed mineralogical characterization, and the ages will likely represent minimum ages.
(40)A/Ar-39 step-heating of mica and amphibole megacrysts from hauyne-bearing olivine melilitite scoria/tephra from the Zelezna hurka yielded a 435 +/- 108 ka isotope correlation age for phlogopite and a more imprecise 1.55 Ma total gas age of the kaersutite megacryst. The amphibole megacrysts may constitute the first, and the younger phlogopite megacrysts the later phase of mafic, hydrous melilitic magma crystallization. It cannot be ruled out that the amphibole megacrysts are petrogenetically unrelated to tephra and phlogopite megacrysts and were derived from mantle xenoliths or disaggregated older, deep crustal pegmatites. This is in line both with the rarity of amphibole at Zelezna hurka and with the observed signs of magmatic resorption at the edges of amphibole crystals.
Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
A Cell-free Expression Pipeline for the Generation and Functional Characterization of Nanobodies
(2022)
Cell-free systems are well-established platforms for the rapid synthesis, screening, engineering and modification of all kinds of recombinant proteins ranging from membrane proteins to soluble proteins, enzymes and even toxins. Also within the antibody field the cell-free technology has gained considerable attention with respect to the clinical research pipeline including antibody discovery and production. Besides the classical full-length monoclonal antibodies (mAbs), so-called "nanobodies" (Nbs) have come into focus. A Nb is the smallest naturally-derived functional antibody fragment known and represents the variable domain (VHH, similar to 15 kDa) of a camelid heavy-chain-only antibody (HCAb). Based on their nanoscale and their special structure, Nbs display striking advantages concerning their production, but also their characteristics as binders, such as high stability, diversity, improved tissue penetration and reaching of cavity-like epitopes. The classical way to produce Nbs depends on the use of living cells as production host. Though cell-based production is well-established, it is still time-consuming, laborious and hardly amenable for high-throughput applications. Here, we present for the first time to our knowledge the synthesis of functional Nbs in a standardized mammalian cell-free system based on Chinese hamster ovary (CHO) cell lysates. Cell-free reactions were shown to be time-efficient and easy-to-handle allowing for the "on demand" synthesis of Nbs. Taken together, we complement available methods and demonstrate a promising new system for Nb selection and validation.
Incorporation of noncanonical amino acids (ncAAs) with bioorthogonal reactive groups by amber suppression allows the generation of synthetic proteins with desired novel properties. Such modified molecules are in high demand for basic research and therapeutic applications such as cancer treatment and in vivo imaging. The positioning of the ncAA-responsive codon within the protein's coding sequence is critical in order to maintain protein function, achieve high yields of ncAA-containing protein, and allow effective conjugation. Cell-free ncAA incorporation is of particular interest due to the open nature of cell-free systems and their concurrent ease of manipulation. In this study, we report a straightforward workflow to inquire ncAA positions in regard to incorporation efficiency and protein functionality in a Chinese hamster ovary (CHO) cell-free system. As a model, the well-established orthogonal translation components Escherichia coli tyrosyl-tRNA synthetase (TyrRS) and tRNATyr(CUA) were used to site-specifically incorporate the ncAA p-azido-l-phenylalanine (AzF) in response to UAG codons. A total of seven ncAA sites within an anti-epidermal growth factor receptor (EGFR) single-chain variable fragment (scFv) N-terminally fused to the red fluorescent protein mRFP1 and C-terminally fused to the green fluorescent protein sfGFP were investigated for ncAA incorporation efficiency and impact on antigen binding. The characterized cell-free dual fluorescence reporter system allows screening for ncAA incorporation sites with high incorporation efficiency that maintain protein activity. It is parallelizable, scalable, and easy to operate. We propose that the established CHO-based cell-free dual fluorescence reporter system can be of particular interest for the development of antibody-drug conjugates (ADCs).
A circulatory loop
(2023)
In the digitalization debate, gender biases in digital technologies play a significant role because of their potential for social exclusion and inequality. It is therefore remarkable that organizations as drivers of digitalization and as places for social integration have been widely overlooked so far. Simultaneously, gender biases and digitalization have structurally immanent connections to organizations. Therefore, a look at the reciprocal relationship between organizations, digitalization, and gender is needed. The article provides answers to the question of whether and how organizations (re)produce, reinforce, or diminish gender‐specific inequalities during their digital transformations. On the one hand, gender inequalities emerge when organizations use post‐bureaucratic concepts through digitalization. On the other hand, gender inequalities are reproduced when organizations either program or implement digital technologies and fail to establish control structures that prevent gender biases. This article shows that digitalization can act as a catalyst for inequality‐producing mechanisms, but also has the potential to mitigate inequalities. We argue that organizations must be considered when discussing the potential of exclusion through digitalization.
Genomic prediction has revolutionized crop breeding despite remaining issues of transferability of models to unseen environmental conditions and environments. Usage of endophenotypes rather than genomic markers leads to the possibility of building phenomic prediction models that can account, in part, for this challenge. Here, we compare and contrast genomic prediction and phenomic prediction models for 3 growth-related traits, namely, leaf count, tree height, and trunk diameter, from 2 coffee 3-way hybrid populations exposed to a series of treatment-inducing environmental conditions. The models are based on 7 different statistical methods built with genomic markers and ChlF data used as predictors. This comparative analysis demonstrates that the best-performing phenomic prediction models show higher predictability than the best genomic prediction models for the considered traits and environments in the vast majority of comparisons within 3-way hybrid populations. In addition, we show that phenomic prediction models are transferrable between conditions but to a lower extent between populations and we conclude that chlorophyll a fluorescence data can serve as alternative predictors in statistical models of coffee hybrid performance. Future directions will explore their combination with other endophenotypes to further improve the prediction of growth-related traits for crops.
A comparative whole-genome approach identifies bacterial traits for marine microbial interactions
(2022)
Luca Zoccarato, Daniel Sher et al. leverage publicly available bacterial genomes from marine and other environments to examine traits underlying microbial interactions.
Their results provide a valuable resource to investigate clusters of functional and linked traits to better understand marine bacteria community assembly and dynamics.
Microbial interactions shape the structure and function of microbial communities with profound consequences for biogeochemical cycles and ecosystem health. Yet, most interaction mechanisms are studied only in model systems and their prevalence is unknown. To systematically explore the functional and interaction potential of sequenced marine bacteria, we developed a trait-based approach, and applied it to 473 complete genomes (248 genera), representing a substantial fraction of marine microbial communities.
We identified genome functional clusters (GFCs) which group bacterial taxa with common ecology and life history. Most GFCs revealed unique combinations of interaction traits, including the production of siderophores (10% of genomes), phytohormones (3-8%) and different B vitamins (57-70%). Specific GFCs, comprising Alpha- and Gammaproteobacteria, displayed more interaction traits than expected by chance, and are thus predicted to preferentially interact synergistically and/or antagonistically with bacteria and phytoplankton. Linked trait clusters (LTCs) identify traits that may have evolved to act together (e.g., secretion systems, nitrogen metabolism regulation and B vitamin transporters), providing testable hypotheses for complex mechanisms of microbial interactions.
Our approach translates multidimensional genomic information into an atlas of marine bacteria and their putative functions, relevant for understanding the fundamental rules that govern community assembly and dynamics.
Air pollution is a pressing issue that is associated with adverse effects on human health, ecosystems, and climate. Despite many years of effort to improve air quality, nitrogen dioxide (NO2) limit values are still regularly exceeded in Europe, particularly in cities and along streets. This study explores how concentrations of nitrogen oxides (NOx = NO + NO2) in European urban areas have changed over the last decades and how this relates to changes in emissions. To do so, the incremental approach was used, comparing urban increments (i.e. urban background minus rural concentrations) to total emissions, and roadside increments (i.e. urban roadside concentrations minus urban background concentrations) to traffic emissions. In total, nine European cities were assessed. The study revealed that potentially confounding factors like the impact of urban pollution at rural monitoring sites through atmospheric transport are generally negligible for NOx. The approach proves therefore particularly useful for this pollutant. The estimated urban increments all showed downward trends, and for the majority of the cities the trends aligned well with the total emissions. However, it was found that factors like a very densely populated surrounding or local emission sources in the rural area such as shipping traffic on inland waterways restrict the application of the approach for some cities. The roadside increments showed an overall very diverse picture in their absolute values and trends and also in their relation to traffic emissions. This variability and the discrepancies between roadside increments and emissions could be attributed to a combination of local influencing factors at the street level and different aspects introducing inaccuracies to the trends of the emis-sion inventories used, including deficient emission factors. Applying the incremental approach was evaluated as useful for long-term pan-European studies, but at the same time it was found to be restricted to certain regions and cities due to data availability issues. The results also highlight that using emission inventories for the prediction of future health impacts and compliance with limit values needs to consider the distinct variability in the concentrations not only across but also within cities.
Narcissists are assumed to lack the motivation and ability to share and understand the mental states of others. Prior empirical research, however, has yielded inconclusive findings and has differed with respect to the specific aspects of narcissism and socioemotional cognition that have been examined. Here, we propose a differentiated facet approach that can be applied across research traditions and that distinguishes between facets of narcissism (agentic vs. antagonistic) on the one hand, and facets of socioemotional cognition ability (SECA; self-perceived vs. actual) on the other. Using five nonclinical samples in two studies (total N = 602), we investigated the effect of facets of grandiose narcissism on aspects of socioemotional cognition across measures of affective and cognitive empathy, Theory of Mind, and emotional intelligence, while also controlling for general reasoning ability. Across both studies, agentic facets of narcissism were found to be positively related to perceived SECA, whereas antagonistic facets of narcissism were found to be negatively related to perceived SECA. However, both narcissism facets were negatively related to actual SECA. Exploratory condition-based regression analyses further showed that agentic narcissists had a higher directed discrepancy between perceived and actual SECA: They self-enhanced their socio-emotional capacities. Implications of these results for the multifaceted theoretical understanding of the narcissism-SECA link are discussed.
The past three decades of policy process studies have seen the emergence of a clear intellectual lineage with regard to complexity. Implicitly or explicitly, scholars have employed complexity theory to examine the intricate dynamics of collective action in political contexts. However, the methodological counterparts to complexity theory, such as computational methods, are rarely used and, even if they are, they are often detached from established policy process theory. Building on a critical review of the application of complexity theory to policy process studies, we present and implement a baseline model of policy processes using the logic of coevolving networks. Our model suggests that an actor's influence depends on their environment and on exogenous events facilitating dialogue and consensus-building. Our results validate previous opinion dynamics models and generate novel patterns. Our discussion provides ground for further research and outlines the path for the field to achieve a computational turn.
Apoptotic death of cells damaged by genotoxic stress requires regulatory input from surrounding tissues. The C. elegans scaffold protein KRI-1, ortholog of mammalian KRIT1/CCM1, permits DNA damage-induced apoptosis of cells in the germline by an unknown cell non-autonomous mechanism. We reveal that KRI-1 exists in a complex with CCM-2 in the intestine to negatively regulate the ERK-5/MAPK pathway. This allows the KLF-3 transcription factor to facilitate expression of the SLC39 zinc transporter gene zipt-2.3, which functions to sequester zinc in the intestine. Ablation of KRI-1 results in reduced zinc sequestration in the intestine, inhibition of IR-induced MPK-1/ERK1 activation, and apoptosis in the germline. Zinc localization is also perturbed in the vasculature of krit1(-/-) zebrafish, and SLC39 zinc transporters are mis-expressed in Cerebral Cavernous Malformations (CCM) patient tissues. This study provides new insights into the regulation of apoptosis by cross-tissue communication, and suggests a link between zinc localization and CCM disease.
Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers.
Model-informed precision dosing (MIPD) is a quantitative dosing framework that combines prior knowledge on the drug-disease-patient system with patient data from therapeutic drug/ biomarker monitoring (TDM) to support individualized dosing in ongoing treatment. Structural models and prior parameter distributions used in MIPD approaches typically build on prior clinical trials that involve only a limited number of patients selected according to some exclusion/inclusion criteria. Compared to the prior clinical trial population, the patient population in clinical practice can be expected to also include altered behavior and/or increased interindividual variability, the extent of which, however, is typically unknown. Here, we address the question of how to adapt and refine models on the level of the model parameters to better reflect this real-world diversity. We propose an approach for continued learning across patients during MIPD using a sequential hierarchical Bayesian framework. The approach builds on two stages to separate the update of the individual patient parameters from updating the population parameters. Consequently, it enables continued learning across hospitals or study centers, because only summary patient data (on the level of model parameters) need to be shared, but no individual TDM data. We illustrate this continued learning approach with neutrophil-guided dosing of paclitaxel. The present study constitutes an important step toward building confidence in MIPD and eventually establishing MIPD increasingly in everyday therapeutic use.
National Action Plans (NAPs) have been increas-ingly adopted world-wide after the Vienna Dec-laration in 1993, where it was urged to consider the improvement and promotion of Human Rights. In this paper, we discuss their usefulness and success by analysing the challenges present-ed during NAP processes as well as the benefits this set of actions entails: The challenges for their implementation outweigh its actual benefits. Nevertheless, NAPs have great potential. Based on new research, we elaborate a set of recom-mendations for improving the design and imple-mentation of national action planning. In order to effectively bring NAP into practice, we consider it crucial to plan and analyse every state local circumstances in detail. The latter is important, since the implementation of a concrete set of actions is intended to directly transform and improve the local living conditions of the people. In a long-term perspective, we defend the benefit of NAP’s implementation for complying obliga-tions set up by HR treaties.
The last years have been affected by Covid-19 and the international emergency mecha-nism to deal with health-related threats. The effects of this period manifested differ-ently worldwide, depending on matters such as international relations, national policies, power dynamics etc. Additionally, the impact of this time will likely have long-term effects which are yet to be known. This paper gives a critical overview of the Public Health Emergency of International Concern (PHEIC) mechanism in the context of Covid-19. It does so by explaining the legal framework for states of emergency, specifically in the context of a PHEIC, while considering its restrictions and limitations on human rights. It further outlines issues in the manifestation of global protections and limitations on human rights during Covid-19. Lastly, considering the likelihood of future PHEICs and the known systemic obstructions, this paper offers ways to im-prove this mechanism from a holistic, non-zero-sum perspective.
Compound natural hazards likeEl Ninoevents cause high damage to society, which to manage requires reliable risk assessments. Damage modelling is a prerequisite for quantitative risk estimations, yet many procedures still rely on expert knowledge, and empirical studies investigating damage from compound natural hazards hardly exist. A nationwide building survey in Peru after theEl Ninoevent 2017 - which caused intense rainfall, ponding water, flash floods and landslides - enables us to apply data-mining methods for statistical groundwork, using explanatory features generated from remote sensing products and open data. We separate regions of different dominant characteristics through unsupervised clustering, and investigate feature importance rankings for classifying damage via supervised machine learning. Besides the expected effect of precipitation, the classification algorithms select the topographic wetness index as most important feature, especially in low elevation areas. The slope length and steepness factor ranks high for mountains and canyons. Partial dependence plots further hint at amplified vulnerability in rural areas. An example of an empirical damage probability map, developed with a random forest model, is provided to demonstrate the technical feasibility.
A expulsão do Éden
(2021)
A temática da migração está intimamente vinculada à história humana, desde a narrativa bíblica da expulsão do paraíso. O ser humano não apenas empregou técnicas cada vez mais sofisticadas para a violência, como também transmitiu, através dos séculos, técnicas de conservação e uso de seu saberconviver. Nesse sentido móvel da história, e em consonância com as literaturas do mundo, a partir de suas diversas origens, é possível dizer que existe um “Homo migrans” desde que existe o “Homo sapiens”. Assim, é possível afirmar que as ideias territoriais ou territorializantes com proveniência histórico-espacial permitem, vez ou outra, reconhecer seus esforços para filtrar e isolar a dimensão histórico-móvel e vetorial da história como narrativa, para tentar construir, com a ajuda de ideias estáticas, novos lugares da promessa ou da perda, da abundância ou da queda.
A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A
(2019)
The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein’s anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex genetic patterns in cardiovascular disease aetiology.
Biogenic greenhouse gas emissions, e.g., of methane (CH4) and carbon dioxide (CO2) from inland waters, contribute substantially to global warming. In aquatic systems, dissolved greenhouse gases are highly heterogeneous in both space and time. To better understand the biological and physical processes that affect sources and sinks of both CH4 and CO2, their dissolved concentrations need to be measured with high spatial and temporal resolution. To achieve this goal, we developed the Fast-Response Automated Gas Equilibrator (FaRAGE) for real-time in situ measurement of dissolved CH4 and CO2 concentrations at the water surface and in the water column. FaRAGE can achieve an exceptionally short response time (t(95%) = 12 s when including the response time of the gas analyzer) while retaining an equilibration ratio of 62.6% and a measurement accuracy of 0.5% for CH4. A similar performance was observed for dissolved CO2 (t(95%) = 10 s, equilibration ratio 67.1 %). An equilibration ratio as high as 91.8% can be reached at the cost of a slightly increased response time (16 s). The FaRAGE is capable of continuously measuring dissolved CO2 and CH4 concentrations in the nM-to-submM (10(-9)-10(-3) mol L-1) range with a detection limit of subnM (10(-10) mol L-1), when coupling with a cavity ring-down greenhouse gas analyzer (Picarro GasScouter). FaRAGE allows for the possibility of mapping dissolved concentration in a "quasi" three-dimensional manner in lakes and provides an inexpensive alternative to other commercial gas equilibrators. It is simple to operate and suitable for continuous monitoring with a strong tolerance for suspended particles. While the FaRAGE is developed for inland waters, it can be also applied to ocean waters by tuning the gas-water mixing ratio. The FaRAGE is easily adapted to suit other gas analyzers expanding the range of potential applications, including nitrous oxide and isotopic composition of the gases.
The investigation of metabolic fluxes and metabolite distributions within cells by means of tracer molecules is a valuable tool to unravel the complexity of biological systems. Technological advances in mass spectrometry (MS) technology such as atmospheric pressure chemical ionization (APCI) coupled with high resolution (HR), not only allows for highly sensitive analyses but also broadens the usefulness of tracer-based experiments, as interesting signals can be annotated de novo when not yet present in a compound library. However, several effects in the APCI ion source, i.e., fragmentation and rearrangement, lead to superimposed mass isotopologue distributions (MID) within the mass spectra, which need to be corrected during data evaluation as they will impair enrichment calculation otherwise. Here, we present and evaluate a novel software tool to automatically perform such corrections. We discuss the different effects, explain the implemented algorithm, and show its application on several experimental datasets. This adjustable tool is available as an R package from CRAN.
This work reviews the literature on an alleged global warming 'pause' in global mean surface temperature (GMST) to determine how it has been defined, what time intervals are used to characterise it, what data are used to measure it, and what methods used to assess it. We test for 'pauses', both in the normally understood meaning of the term to mean no warming trend, as well as for a 'pause' defined as a substantially slower trend in GMST. The tests are carried out with the historical versions of GMST that existed for each pause-interval tested, and with current versions of each of the GMST datasets. The tests are conducted following the common (but questionable) practice of breaking the linear fit at the start of the trend interval ('broken' trends), and also with trends that are continuous with the data bordering the trend interval. We also compare results when appropriate allowance is made for the selection bias problem. The results show that there is little or no statistical evidence for a lack of trend or slower trend in GMST using either the historical data or the current data. The perception that there was a 'pause' in GMST was bolstered by earlier biases in the data in combination with incomplete statistical testing.
Although the use of stable transformation technology has led to great insight into gene function, its application in high-throughput studies remains arduous. Agro-infiltration have been widely used in species such as Nicotiana benthamiana for the rapid detection of gene expression and protein interaction analysis, but this technique does not work efficiently in other plant species, including Arabidopsis thaliana. As an efficient high-throughput transient expression system is currently lacking in the model plant species A. thaliana, we developed a method that is characterized by high efficiency, reproducibility, and suitability for transient expression of a variety of functional proteins in A. thaliana and 7 other plant species, including Brassica oleracea, Capsella rubella, Thellungiella salsuginea, Thellungiella halophila, Solanum tuberosum, Capsicum annuum, and N. benthamiana. Efficiency of this method was independently verified in three independent research facilities, pointing to the robustness of this technique. Furthermore, in addition to demonstrating the utility of this technique in a range of species, we also present a case study employing this method to assess protein-protein interactions in the sucrose biosynthesis pathway in Arabidopsis.
A few months before his death, A. v. Humboldt attended the celebration in honor of the 127th birthday of George Washington at the US legation in Berlin. A letter to the American Envoy, Joseph A. Wright (1810 – 1867), underlines Humboldt’s admiration for the fi rst president of the United States. At the same time Humboldt asked the diplomat to mail a letter to the German-American Bernard Moses (1832 – 1897) in Clinton, Louisiana, who had named his son Alexander Humboldt Moses (grave on the Hebrew Rest Cemetery #2 in New Orleans, burial plot A, 12, 5). It appears to be possible that the Moses family still owns Humboldt’s letter.
Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption.
Aging in speech production is a multidimensional process. Biological, cognitive, social, and communicative factors can change over time, stay relatively stable, or may even compensate for each other. In this longitudinal work, we focus on stability and change at the laryngeal and supralaryngeal levels in the discourse particle euh produced by 10 older French-speaking females at two times, 10 years apart. Recognizing the multiple discourse roles of euh, we divided out occurrences according to utterance position. We quantified the frequency of euh, and evaluated acoustic changes in formants, fundamental frequency, and voice quality across time and utterance position. Results showed that euh frequency was stable with age. The only acoustic measure that revealed an age effect was harmonics-to-noise ratio, showing less noise at older ages. Other measures mostly varied with utterance position, sometimes in interaction with age. Some voice quality changes could reflect laryngeal adjustments that provide for airflow conservation utterance-finally. The data suggest that aging effects may be evident in some prosodic positions (e.g., utterance-final position), but not others (utterance-initial position). Thus, it is essential to consider the interactions among these factors in future work and not assume that vocal aging is evident throughout the signal.
Author summary <br /> Switching between local and global attention is a general strategy in human information processing. We investigate whether this strategy is a viable approach to model sequences of fixations generated by a human observer in a free viewing task with natural scenes. Variants of the basic model are used to predict the experimental data based on Bayesian inference. Results indicate a high predictive power for both aggregated data and individual differences across observers. The combination of a novel model with state-of-the-art Bayesian methods lends support to our two-state model using local and global internal attention states for controlling eye movements. <br /> Understanding the decision process underlying gaze control is an important question in cognitive neuroscience with applications in diverse fields ranging from psychology to computer vision. The decision for choosing an upcoming saccade target can be framed as a selection process between two states: Should the observer further inspect the information near the current gaze position (local attention) or continue with exploration of other patches of the given scene (global attention)? Here we propose and investigate a mathematical model motivated by switching between these two attentional states during scene viewing. The model is derived from a minimal set of assumptions that generates realistic eye movement behavior. We implemented a Bayesian approach for model parameter inference based on the model's likelihood function. In order to simplify the inference, we applied data augmentation methods that allowed the use of conjugate priors and the construction of an efficient Gibbs sampler. This approach turned out to be numerically efficient and permitted fitting interindividual differences in saccade statistics. Thus, the main contribution of our modeling approach is two-fold; first, we propose a new model for saccade generation in scene viewing. Second, we demonstrate the use of novel methods from Bayesian inference in the field of scan path modeling.
Author summary <br /> The use of orally inhaled drugs for treating lung diseases is appealing since they have the potential for lung selectivity, i.e. high exposure at the site of action -the lung- without excessive side effects. However, the degree of lung selectivity depends on a large number of factors, including physiochemical properties of drug molecules, patient disease state, and inhalation devices. To predict the impact of these factors on drug exposure and thereby to understand the characteristics of an optimal drug for inhalation, we develop a predictive mathematical framework (a "pharmacokinetic model"). In contrast to previous approaches, our model allows combining knowledge from different sources appropriately and its predictions were able to adequately predict different sets of clinical data. Finally, we compare the impact of different factors and find that the most important factors are the size of the inhaled particles, the affinity of the drug to the lung tissue, as well as the rate of drug dissolution in the lung. In contrast to the common belief, the solubility of a drug in the lining fluids is not found to be relevant. These findings are important to understand how inhaled drugs should be designed to achieve best treatment results in patients. <br /> The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic processes such as particle deposition, pulmonary drug dissolution, and mucociliary clearance. Even though each single process has been systematically investigated, a quantitative understanding on the interaction of processes remains limited and therefore identifying optimal drug and formulation characteristics for orally inhaled drugs is still challenging. To investigate this complex interplay, the pulmonary processes can be integrated into mathematical models. However, existing modeling attempts considerably simplify these processes or are not systematically evaluated against (clinical) data. In this work, we developed a mathematical framework based on physiologically-structured population equations to integrate all relevant pulmonary processes mechanistically. A tailored numerical resolution strategy was chosen and the mechanistic model was evaluated systematically against data from different clinical studies. Without adapting the mechanistic model or estimating kinetic parameters based on individual study data, the developed model was able to predict simultaneously (i) lung retention profiles of inhaled insoluble particles, (ii) particle size-dependent pharmacokinetics of inhaled monodisperse particles, (iii) pharmacokinetic differences between inhaled fluticasone propionate and budesonide, as well as (iv) pharmacokinetic differences between healthy volunteers and asthmatic patients. Finally, to identify the most impactful optimization criteria for orally inhaled drugs, the developed mechanistic model was applied to investigate the impact of input parameters on both the pulmonary and systemic exposure. Interestingly, the solubility of the inhaled drug did not have any relevant impact on the local and systemic pharmacokinetics. Instead, the pulmonary dissolution rate, the particle size, the tissue affinity, and the systemic clearance were the most impactful potential optimization parameters. In the future, the developed prediction framework should be considered a powerful tool for identifying optimal drug and formulation characteristics.
A Metabarcoding Analysis of the Mycobiome of Wheat Ears Across a Topographically Heterogeneous Field
(2019)
The MOOChub is a joined web-based catalog of all relevant German and Austrian MOOC platforms that lists well over 750 Massive Open Online Courses (MOOCs). Automatically building such a catalog requires that all partners describe and publicly offer the metadata of their courses in the same way. The paper at hand presents the genesis of the idea to establish a common metadata standard and the story of its subsequent development. The result of this effort is, first, an open-licensed de-facto-standard, which is based on existing commonly used standards and second, a first prototypical platform that is using this standard: the MOOChub, which lists all courses of the involved partners. This catalog is searchable and provides a more comprehensive overview of basically all MOOCs that are offered by German and Austrian MOOC platforms. Finally, the upcoming developments to further optimize the catalog and the metadata standard are reported.
Atmospheric water vapour content is a key variable that controls the development of deep convective storms and rainfall extremes over the central Andes. Direct measurements of water vapour are challenging; however, recent developments in microwave processing allow the use of phase delays from L-band radar to measure the water vapour content throughout the atmosphere: Global Navigation Satellite System (GNSS)-based integrated water vapour (IWV) monitoring shows promising results to measure vertically integrated water vapour at high temporal resolutions. Previous works also identified convective available potential energy (CAPE) as a key climatic variable for the formation of deep convective storms and rainfall in the central Andes. Our analysis relies on GNSS data from the Argentine Continuous Satellite Monitoring Network, Red Argentina de Monitoreo Satelital Continuo (RAMSAC) network from 1999 to 2013. CAPE is derived from version 2.0 of the ECMWF’s (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-interim) and rainfall from the TRMM (Tropical Rainfall Measuring Mission) product. In this study, we first analyse the rainfall characteristics of two GNSS-IWV stations by comparing their complementary cumulative distribution function (CCDF). Second, we separately derive the relation between rainfall vs. CAPE and GNSS-IWV. Based on our distribution fitting analysis, we observe an exponential relation of rainfall to GNSS-IWV. In contrast, we report a power-law relationship between the daily mean value of rainfall and CAPE at the GNSS-IWV station locations in the eastern central Andes that is close to the theoretical relationship based on parcel theory. Third, we generate a joint regression model through a multivariable regression analysis using CAPE and GNSS-IWV to explain the contribution of both variables in the presence of each other to extreme rainfall during the austral summer season. We found that rainfall can be characterised with a higher statistical significance for higher rainfall quantiles, e.g., the 0.9 quantile based on goodness-of-fit criterion for quantile regression. We observed different contributions of CAPE and GNSS-IWV to rainfall for each station for the 0.9 quantile. Fourth, we identify the temporal relation between extreme rainfall (the 90th, 95th, and 99th percentiles) and both GNSS-IWV and CAPE at 6 h time steps. We observed an increase before the rainfall event and at the time of peak rainfall—both for GNSS-integrated water vapour and CAPE. We show higher values of CAPE and GNSS-IWV for higher rainfall percentiles (99th and 95th percentiles) compared to the 90th percentile at a 6-h temporal scale. Based on our correlation analyses and the dynamics of the time series, we show that both GNSS-IWV and CAPE had comparable magnitudes, and we argue to consider both climatic variables when investigating their effect on rainfall extremes.
In this study, we model a sequence of a confined and a full eruption, employing the relaxed end state of the confined eruption of a kink-unstable flux rope as the initial condition for the ejective one. The full eruption, a model of a coronal mass ejection, develops as a result of converging motions imposed at the photospheric boundary, which drive flux cancellation. In this process, parts of the positive and negative external flux converge toward the polarity inversion line, reconnect, and cancel each other. Flux of the same amount as the canceled flux transfers to a flux rope, increasing the free magnetic energy of the coronal field. With sustained flux cancellation and the associated progressive weakening of the magnetic tension of the overlying flux, we find that a flux reduction of approximate to 11% initiates the torus instability of the flux rope, which leads to a full eruption. These results demonstrate that a homologous full eruption, following a confined one, can be driven by flux cancellation.
In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
We consider a sequential cascade of molecular first-reaction events towards a terminal reaction centre in which each reaction step is controlled by diffusive motion of the particles. The model studied here represents a typical reaction setting encountered in diverse molecular biology systems, in which, e.g. a signal transduction proceeds via a series of consecutive 'messengers': the first messenger has to find its respective immobile target site triggering a launch of the second messenger, the second messenger seeks its own target site and provokes a launch of the third messenger and so on, resembling a relay race in human competitions. For such a molecular relay race taking place in infinite one-, two- and three-dimensional systems, we find exact expressions for the probability density function of the time instant of the terminal reaction event, conditioned on preceding successful reaction events on an ordered array of target sites. The obtained expressions pertain to the most general conditions: number of intermediate stages and the corresponding diffusion coefficients, the sizes of the target sites, the distances between them, as well as their reactivities are arbitrary.
In an attempt to pave the way for more extensive Computer Science Education (CSE) coverage in K-12, this research developed and made a preliminary evaluation of a blended-learning Introduction to CS program based on an academic MOOC. Using an academic MOOC that is pedagogically effective and engaging, such a program may provide teachers with disciplinary scaffolds and allow them to focus their attention on enhancing students’ learning experience and nurturing critical 21st-century skills such as self-regulated learning. As we demonstrate, this enabled us to introduce an academic level course to middle-school students. In this research, we developed the principals and initial version of such a program, targeting ninth-graders in science-track classes who learn CS as part of their standard curriculum. We found that the middle-schoolers who participated in the program achieved academic results on par with undergraduate students taking this MOOC for academic credit. Participating students also developed a more accurate perception of the essence of CS as a scientific discipline. The unplanned school closure due to the COVID19 pandemic outbreak challenged the research but underlined the advantages of such a MOOCbased blended learning program above classic pedagogy in times of global or local crises that lead to school closure. While most of the science track classes seem to stop learning CS almost entirely, and the end-of-year MoE exam was discarded, the program’s classes smoothly moved to remote learning mode, and students continued to study at a pace similar to that experienced before the school shut down.
Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.