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The RMaP challenge of predicting RNA modifications by nanopore sequencing
Get PDFThe field of epitranscriptomics is undergoing a technology-driven revolution. During past decades, RNA modifications like N6-methyladenosine (m6A), pseudouridine (ψ), and 5-methylcytosine (m5C) became acknowledged for playing critical roles in cellular processes. Direct RNA sequencing by Oxford Nanopore Technologies (ONT) enabled the detection of modifications in native RNA, by detecting noncanonical RNA nucleosides properties in raw data. Consequently, the field’s cutting edge has a heavy component in computer science, opening new avenues of cooperation across the community, as exchanging data is as impactful as exchanging samples. Therefore, we seize the occasion to bring scientists together within the RNA Modification and Processing (RMaP) challenge to advance solutions for RNA modification detection and discuss ideas, problems and approaches. We show several computational methods to detect the most researched mRNA modifications (m6A, ψ, and m5C). Results demonstrate that a low prediction error and a high prediction accuracy can be achieved on these modifications across different approaches and algorithms. The RMaP challenge marks a substantial step towards improving algorithms’ comparability, reliability, and consistency in RNA modification prediction. It points out the deficits in this young field that need to be addressed in further challenges
Die Untersuchung der lokalen Hautverfärbungen nach Injektion von eisenhaltigen Nanopartikeln zur Sentinellymphknotenbiopsie beim Mammakarzinom
Get PDFIII, 64 Seiten ; Illustrationen, Diagramm
tert-Butyl 5-{2-[2-(N-ethynyl-4-methylbenzenesulfonamido)phenyl]ethynyl}furan-2-carboxylate
Get PDFThe crystal structure of an o,N-dialkynyltosylaniline, C26H23NO5S, is presented. Two essentially planar and nearly parallel branches are connected to the aniline unit and the angle between the alkynes amounts to 26 (4)°. Weak intramolecular aromatic π–π stacking occurs
Biomechanical and cellular assessment of novel partially demineralized allogeneic bone plates: an ex-vivo and in-vitro study
Get PDFPurpose
This study aimed to compare commercial allogeneic cortical bone plates (cCP) with innovative, differently demineralized CP (dCP) in biomechanics and human osteoblast (HOB) viability ex-vivo and in-vitro.
Methods
Breaking strength (BS; in N) and flexibility (F; in mm) of cCP and dCP were assessed and compared using four groups ((1) non-hydrated, (2) hydrated for 10, (3) 30, and (4) 60 min in saline), respectively. Cell viability of HOB was evaluated by resazurin reduction on non-hydrated cCP and dCP after 3, 7, and 10 days. Scanning electron microscopy (SEM) visualized CP breaking edges, internal structures, HOB cell morphology, and growth patterns.
Results
BS of hydrated dCP (d10: 15.45 ± 7.01 N, d30: 19.40 ± 3.78 N, d60: 20.31 ± 4.90 N) was significantly lower than that of non-hydrated dCP (d0: 74.70 ± 29.48 N) and native and hydrated cCP (c0: 75.00 ± 19.27 N, c10: 83.73 ± 10.92 N, c30: 83.80 ± 22.63 N, c60: 75.58 ± 14.25 N, p < 0.001 each). Next, dCP groups (d0: 2.64 ± 0.78 mm, d10: 2.14 ± 1.15 mm, d30: 2.76 ± 3.78 mm, d60: 2.86 ± 0.89 mm) exhibited significantly higher F than cCP groups (c0: 0.49 ± 0.14 mm, c10: 0.66 ± 0.10 mm, c30: 0.67 ± 0.16 mm, c60: 0.59 ± 0.12 mm, p < 0.05 each). No significant differences in F were observed among the different dCP groups. HOB cell viability was significantly increased on cCP compared to dCP after 7 (97.64 ± 2.11% vs. 76.88 ± 4.82%) and 10 days (96.14 ± 4.13% vs. 76.45 ± 4.64%; p < 0.001 each). SEM revealed well-defined breaking edges in cCP, whereas dCP displayed tear-off edges with shearing extensions. SEM showed disordered growth patterns and a physiological HOB cell morphology on dCP, contrasting with a parallel growth of fibroblast-like-looking HOB on cCP.
Conclusions
Compared to cCP, dCP showed increased flexibility but lower breaking strength and reduced HOB vitality. The increased flexibility and a decrease in breaking strength are likely due to differences in elasticity between dCP and cCP. The use of dCP may improve clinical handling efficiency
Approaching “the expert” in times of (digital) disruptions : towards a geography of expertise
Get PDFThe demand for “experts” and “expertise” has never been higher than in the present time, characterized by complexities, uncertainties and (digital) disruptions. At the same time, expertise has never been more contested and attacked, particularly due to social media. In this paper, we delve into the social-scientific literature on expert(ise) and argue for a strong differentiation between knowledge and expertise. We outline a geography of expertise, to be developed at the intersection of the three relational categories “authority,” “trust,” and “coalitions” and pay particular attention to digital media as the key driver for the re-configuration of expertise and expert roles
A reduced perception of sensory information is linked with elevated boredom in people with and without attention-deficit hyperactivity disorder
Get PDFOur brains have evolved to represent and process sensory information from our environment and use it to guide behavior. The perception of sensory information and subsequent responses, such as boredom, however, vary across situations and individuals, impressively depicted by patients with attentional disorders who show extensive boredom across many situations. Despite these implications, it remains unclear how environmental features and individual traits act together to allow effective transmission of sensory information, and how both factors relate to boredom experience. We present a framework to address this issue, exposing human participants to text stimuli with defined objective information content, while assessing perceived information, boredom and text sentiment. Using information theory to formalize external and internal factors of information transmission, we find that lower information transmission predicts higher boredom. Moreover, individuals with attention deficit hyperactivity disorder show lower information transmission, compared to a control sample. Together, delineating the interaction of sensory information content with individual traits, boredom emerges as a situational consequence of reduced information-decoding, heightened in ADHD
Human models for White Sutton syndrome: POGZ mutations change the transcriptome and induce defects in neural progenitor cell biology
Get PDFIntellectual disability (ID) and autism spectrum disorders (ASD) are complex neurodevelopmental conditions with high genetic heterogeneity. Studies indicate that 10%-40% of individuals with ID also have ASD, suggesting shared molecular mechanisms between these disorders. Recent next-generation sequencing studies have highlighted a significant role of de novo mutations in ASD, particularly those with large effects. Among these, POGZ (Pogo Transposable Element with zinc finger “ZNF” domain) has emerged as a frequently mutated gene with potential loss-of-function effects in ASD patients. However, the underlying molecular mechanisms and the pathogenic impact of POGZ mutations are not fully understood.
POGZ encodes a protein that is mainly binds to heterochromatin protein 1α and contributes to gene regulatory functions. Functionally, POGZ is critical for kinetochore assembly, sister chromatid cohesion, and mitotic chromosome segregation. POGZ deficiency can lead to premature mitotic exit, polyploidy, and potential cell death or genomic instability, which may disrupt neural development and brain function. POGZ thought to act as a transcriptional regulator, potentially influencing molecular networks that are critical for neuronal function.
This PhD study investigated the cellular and molecular mechanisms by which POGZ mutations contribute to neurodevelopmental disorders (NDDs) using human induced pluripotent stem cells (iPSCs) derived from patient and CRISPR/Cas9-mediated gene editing to introduce heterozygous POGZ mutations. These mutant iPSCs were differentiated into neural progenitor cells (NPCs) and neurons under both two-dimensional (2D) and three-dimensional (3D) culture conditions to analyze the effects of POGZ mutations on neural development.
Key findings of the study indicated that frameshift mutations in the N-terminus or the HP1-binding zinc finger-like (HPZ) domain of POGZ led to decreased POGZ protein expression without disrupting its nuclear localization. Using 3D neurospheres and brain organoids, it was found that POGZ-deficient cells exhibited impaired self-renewal of NPCs, alongside enhanced differentiation and increased neuronal migration. Additionally, analysis of the transcriptome via RNA sequencing revealed widespread changes in gene expression in NPCs carrying POGZ mutations. These alterations were significantly enriched for genes involved in mitotic chromatid segregation, DNA repair, nonsense-mediated decay, and alternative splicing. Notably, the data revealed a transcriptomic signature characterized by the elevated expression of neuron-specific genes, suggesting an "accelerated differentiation" phenotype in mutant NPCs, mirroring the behavior observed in the 3D neurosphere models.
Furthermore, CUT&Tag sequencing was employed to identify direct targets of POGZ, providing evidence that POGZ directly regulated genes linked to synaptic function, chromosome segregation, and Wnt signaling. The overrepresentation of autism-associated risk genes among POGZ-regulated targets further suggested a potential link between POGZ dysfunction and the etiology of NDDs, including ASD.
This analysis emphasized the critical role of POGZ in regulating neural development at both the cellular and molecular levels. Understanding how POGZ mutations drive alterations in NPC behavior and gene regulation, is crucial for developing targeted therapeutic strategies for conditions associated with POGZ dysfunction. Ultimately, this study aimed to bridge the gap between genetic findings and pathophysiological mechanisms in NDDs, providing deeper insights into the developmental disruptions caused by POGZ mutations.197 Seiten ; Illustrationen, Diagramm
Monte Carlo Lagrangian modeling of ice microphysical process in wintertime clouds
Get PDFThis study explores the intricate processes governing ice microphysics, particularly the evolution of ice habits and their consequential impact on cloud microphysics and precipitation patterns.
Leveraging the Lagrangian Monte-Carlo ice microphysics model McSnow, several methodological advancements are introduced to refine the representation of ice habits.
McSnow is extended by an explicit habit prediction scheme, combined with the hydrodynamic theory of Böhm.
Böhm's original cylindrical shape assumption for prolates is compared against recent lab results, showing that interpolation between cylinder and prolate yields the best agreement.
For constant temperature and supersaturation, the predicted mass, size, and density agree well with the laboratory results, and a comparison with real clouds using the polarizability ratio shows regimes capable of improvement.
An updated form of the inherent growth function to describe the primary habit growth tendencies is proposed and combined with a habit-dependent ventilation coefficient.
The modifications contrast the results from general mass size relations and significantly impact the main ice microphysical processes. Depending on the thermodynamic regime, ice habits significantly alter depositional growth and affect aggregation and riming.
The findings underscore the critical importance of explicit ice habit prediction in accurately capturing the variability inherent in ice microphysics.
Through comprehensive simulations, the research demonstrates that these detailed representations are essential for modeling the complex feedback mechanisms that occur between microphysical processes and large-scale cloud dynamics.
This is especially pertinent in mixed-phase clouds, where the interaction of liquid and ice phases exerts a substantial influence on cloud longevity, precipitation efficiency, and radiative properties.
A key aspect of the research involves synthesizing model simulations with observational data to enhance the realism of the simulations.
By incorporating polarimetric radar observations, the study evaluates microphysical processes within more realistic atmospheric scenarios.
Although constrained to one-dimensional simulations, these efforts yield significant insights into the feedback loops between cloud microphysics and cloud dynamics, with a particular focus on mixed-phase cloud conditions.
The study thereby highlights the necessity of observational data in both validating and refining model outputs.
In addition to the advancements in microphysical modeling, the research addresses the phenomenon of SIP, with particular emphasis on ice-ice collisions and fragmentation processes.
A revised fragmentation model is proposed, which incorporates an approach for the fragmentation potential based on fragility of particles.
This development is essential for elucidating the rapid increases in ice particle concentrations observed in certain cloud regimes, which hold profound implications for cloud evolution and precipitation development.
The implications of these findings are far-reaching, particularly in the context of atmospheric modeling, where they contribute to enhancing the accuracy of weather forecasting and climate models. The study concludes by identifying several avenues for future research, including the need for further laboratory experiments aimed at refining our understanding of ice habits and their role in cloud microphysical processes.
Higher-dimensional simulations, coupled with the integration of advanced observational techniques, can serve as a crucial step forward in advancing the field of cloud microphysics.
Ultimately, this research contributes to the ongoing efforts to improve the fidelity of atmospheric models, thereby supporting the broader objectives of advancing weather prediction, cloud process understanding, and climate modeling.ix, 168 Seiten ; Illustrationen, Diagramm
Rassegna media dell'Istituto Storico Germanico di Roma : 2002-2011
Get PDFDer Medienspiegel des Deutschen Historischen Instituts (DHI) in Rom dokumentiert von 2002 bis 2011 die mediale Wahrnehmung seiner Aktivitäten während der Leitung von Michael Matheus. Er umfasst Berichte in Printmedien, digitalen Medien, Fernsehen und Radio, wobei insbesondere die wissenschaftlichen Tagungen, Kooperationen, Publikationen sowie spezielle Projekte wie die Rückgabe mittelalterlicher Urkunden und Ausstellungen hervorgehoben werden. Zudem werden Medienresonanzen zu Stellungnahmen einzelner Institutsmitarbeiter zu bedeutenden historischen und aktuellen Ereignissen in Deutschland und Italien sowie interne Entwicklungen, wie Jubiläen und Einweihungen, erfasst. Der Medienspiegel zeigt, wie das Institut durch vielfältige Öffentlichkeitsarbeit sowohl in wissenschaftlichen Kreisen als auch in der breiten Öffentlichkeit präsent ist und wie es als Förderer transnationaler wissenschaftlicher Netzwerke wahrgenommen wird.126 Seite
Scientific translation bibliographies and the construction of a translation knowledge infrastructure after World War II
Get PDFBased on original archival research, this paper observes the sudden emergence of a large number of periodically published scientific and technical translation bibliographies in various Western countries. It proposes that these bibliographies should not (only) be regarded as a resource for research into the history of (scientific) translation, but that they themselves can be conceptualized as a new type of object of such research: translation bibliographies are a form of explicit translation knowledge that can and should be investigated with regard to the historical conditions of their production as well as their functions. This paper claims that these translation bibliographies form the core of a ‘translation knowledge infrastructure’ that was successively built up from 1945 onwards in the wake of the internationalization of the academic field in order to control the massive increase in translation production and to organize it rationally