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Investigation of the kinematics involved in compton scattering and hard X-ray photoabsorption
(2023)
The present work investigates the kinematics of Compton scattering at gaseous, internally-cool helium and molecular nitrogen targets in the high- and the low-energy regime. Additionally, photoionization at molecular nitrogen with high-energy photons is investigated. These exeprimental regimes were previously inaccessible due to the extremely small cross sections involved. Nowadays, the third- and fourth-generation synchrotron machines produce sufficient photon flux, enabling the investiagtion of the above processes. The utilized cold-target recoil-ion momentum spectroscopy (COLTRIMS) technique further increases the detection efficiency of the observed processes, since it enables full-solid-angle detection by exploiting momentum conservation.
Compton scattering is investigated at both high (helium and N2) and low (helium) photon energies. In the high-energy regime, the impulse approximation is mostly valid, which is not the case for the low-energy regime. The impulse approximation assumes that the Compton-scattering process takes place at a free electron with a momentum distribution as if it was bound, thus ignoring the binding energy of the system. In the low-energy regime, the impulse approximation is not valid.
Photoionization is investigated at high photon energies, where the linear momentum of the photon cannot be neglected, as is the fashion of the commonly used dipole approximation.
N6-methyladenosine (m6A) is the most abundant and well understood modification in eukaryotic mRNA and was first identified in polyadenylated parts of the mRNA.The distinct distribution of m6A in the transcriptome with special enrichment in long internal exons, 39UTRs and around stop codons was uncovered by early biochemical work and later on antibody based sequencing techniques. The so called m6A writer, reader and eraser machinery is responsible for the dynamic and with that regulatory nature of the m6A modification. As m6A writer, the human N6-methyltransferase complex (MTC) cotranscriptionally methylates the central adenine within a RRACH (preferably GGACU) sequence context to form m6A in the nascent RNA chain.9–15 The catalytic core of the complex is formed by the two proteins METTL3 and METTL14, with the active site located in the methyltransferase domain (MTD) of METTL3.16–18 The DPPW motif near the methyl donor S-adenosylmethionine (SAM) binding site in this MTD was postulated to bind the target adenine during catalysis. Moreover, a positively charged groove in the METTL3-METTL14 interface, the C-terminal RGG domain in METTL14 and the zinc finger motifs in METTL3 were identified as important domains for RNA binding. However, to date there are no full-length or substrate-RNA-bound structures of the catalytic METTL3-METTL14 complex.
In addition, a set of accessory proteins assembles to the METTL3-METTL14 heterodimer to form the full MTC, mediated by WTAP that firmly binds to the N-terminal leader helix in METTL3.20 WTAP was shown to locate the whole complex to the nuclear speckles and can modulate m6A deposition to specific sites in the RNA. Moreover, WTAP acts as binding platform for other accessory proteins including VIRMA, RBM15, ZC3H13 and HAKAI that are mostly identified to mediate position specific methylation. For example, RBM15 was shown to mediates region-selective methylation in a WTAP dependent manner, directing specificity towards U-rich sequences.
The observed specificity of the methyltransferase complex to methylate only site specific DRACH sequenced is still poorly understood. Some possible modulators like the role of the accessory proteins are under investigation, however, the structural context of the RNA methylation sites or a structural preference of the complex have been mainly neglected so far. Moreover, the structural dynamics of this methylation process still remain elusive. This thesis contributes to the afore-mentioned aspects by analysis of the methylation process regarding RNA structure sensitivity with enzymatic activity assays and its dynamic nature by implementing a smFRET approach.
We hypothesized the target RNA secondary structure to be an additional important modulator of methylation efficiency, based on the RNA binding elements of the complex (positively charged binding groove, zinc finger domain, RGG domain) and the supposed target adenine binding in the active site. Here, we postulated the possibility for a flipped-out adenine to be of special relevance, which is closely related to the local stability of the target adenine containing structure. Moreover, efficient binding of the protein complex to the RNA should require the ability to anchor the RNA on both sides of the target sequence.
Parallel global edge switching for the uniform sampling of simple graphs with prescribed degrees
(2023)
The uniform sampling of simple graphs matching a prescribed degree sequence is an important tool in network science, e.g. to construct graph generators or null-models. Here, the Edge Switching Markov Chain (ES-MC) is a common choice. Given an arbitrary simple graph with the required degree sequence, ES-MC carries out a large number of small changes, called edge switches, to eventually obtain a uniform sample. In practice, reasonably short runs efficiently yield approximate uniform samples.
In this work, we study the problem of executing edge switches in parallel. We discuss parallelizations of ES-MC, but find that this approach suffers from complex dependencies between edge switches. For this reason, we propose the Global Edge Switching Markov Chain (G-ES-MC), an ES-MC variant with simpler dependencies. We show that G-ES-MC converges to the uniform distribution and design shared-memory parallel algorithms for ES-MC and G-ES-MC. In an empirical evaluation, we provide evidence that G-ES-MC requires not more switches than ES-MC (and often fewer), and demonstrate the efficiency and scalability of our parallel G-ES-MC implementation.
Party auf dem Campus Westend
(2023)
This thesis deals with several aspects of non-perturbative calculations in low-dimensional quantum field theories. It is split into two main parts:
The first part focuses on method development and testing. Using exactly integrable QFTs in zero spacetime dimensions as toy models, the need for non-perturbative methods in QFT is demonstrated. In particular, we focus on the functional renormalization group (FRG) as a non-perturbative exact method and present a novel fluid-dynamic reformulation of certain FRG flow equations. This framework and the application of numerical schemes from the field of computational fluid dynamics (CFD) to the FRG is tested and benchmarked against exact results for correlation functions. We also draw several conclusions for the qualitative understanding and interpretation of renormalization group (RG) flows from this fluid-dynamic reformulation and discuss the generalization of our findings to realistic higher-dimensional QFTs.
The topics discussed in the second part are also manifold. In general, the second part of this thesis deals with the Gross-Neveu (GN) model, which is a prototype of a relativistic QFT. Even though being a model in two spacetime dimensions, it shares many features of realistic models and theories for high-energy particle physics, but also emerges as a limiting case from systems in solid state physics. Especially, it is interesting to study the model at non-vanishing temperatures and densities, thus, its thermodynamic properties and phase structure.
First, we use this model to test and apply our findings of the first part of this thesis in a realistic environment. We analyze how the fluid-dynamic aspects of the FRG realize themselves in the RG flow of a full-fledged QFT and how we profit from this numeric framework in actual calculations. Thereby, however, we also aim at answering a long-standing question: Is there still symmetry breaking and condensation at non-zero temperatures in the GN model, if one relaxes the commonly used approximation of an infinite number of fermion species and works with a finite number of fermions? In short: Is matter (in the GN model) in a single spatial dimension at non-zero temperature always gas-like?
In general, we also use the GN model to learn about the correct description of QFTs at non-zero temperatures and densities. This is of utmost relevance for model calculations in low-energy quan- tum chromodynamics (QCD) or other QFTs in medium and we draw several conclusions for the requirements for stable calculations at non-zero chemical potential.
Künstliche Intelligenz mit Vorurteilen oder falsch zugeordnete Gräber von Wikingerinnen – Geschlecht und Vielfalt können ganz unterschiedliche und mitunter unerwartete Bedeutung für die Forschung entfalten. Um dem gerecht zu werden, will die Goethe-Universität die Reflexion von Geschlecht und Vielfalt noch stärker als bisher in ihren Forschungsaktivitäten verankern. Dafür wurde ein Zehn-Punkte-Papier erarbeitet, das universitätsintern mit externen Fachleuten diskutiert wurde.
Das Verständnis von Tumorerkrankungen wurde durch neue technologische und ökonomische Verbesserungen für die Next-Generation-Sequencing Analyse (NGS) gefördert. Die Komplexität der Interpretation genomischer Daten erschwert jedoch die Anwendung von NGS-Analysen im klinischen Kontext. Die Herausforderung besteht darin bei stetig wachsendem medizinischem Wissen dieses im klinischen Kontext zu interpretieren und eine personalisierte Therapieempfehlung abzugeben. Einen ressourcensparenden Ansatz können KI-unterstützende Software-Programme bieten, welche die genomischen Varianten mit der aktuellen Literatur vergleichen, eine Bewertung der Therapieoptionen geben und klinische Studien empfehlen können. In dieser retrospektiven Arbeit wurden Patient:innen mit metastasiertem Brustkrebs (n=77) mittels gezielter NGS-Analyse anhand von sogenannten Genpanels mit 126 bzw. 540 krebsrelevanten Genen im Zeitraum von 01/2019-02/2022 untersucht. Mit Hilfe von bioinformatischen Methoden wurden patientenspezifische genomische Veränderungen mit Behandlungsoptionen abgeglichen. Diese Methoden stützen sich vollständig auf öffentliche Datenbanken über somatische Varianten mit prädiktiver Evidenz für das Ansprechen auf bestimmte Medikamente. Diese Versorgungsforschung einer repräsentativen Kohorte des Universitätsklinikums Frankfurt in Kooperation mit Regionalverbund OncoNet Rhein-Main wurden systematisch ausgewertet inklusive der Bedeutung genomischer Varianten. Das OncoNet Rhein-Main ist eine Kooperation aus führenden onkologischen Zentren und Praxen im Rhein-Main-Gebiet, welche sich als Netzwerk der Aufgabe angenommen haben Patient:innen optimal therapeutisch zu versorgen. Für 51% (39/77) der Patient:innen konnte mindestens eine gezielte Therapieoption mit einem effektivem Biomarker im gleichen Tumortyp gemäß Zulassung der Europäischen Arzneimittelbehörde (EMA) gefunden werden.
Bei 12/77 (16%) wurde mindestens eine Alteration mit einem effektivem Biomarker und einer OFF-Label Therapieoption gefunden. Bei 30% der Patient:innen wurden Veränderungen in optionalen Biomarkern gefunden, welche Resistenzmechanismen erklären. Die umfassende molekulare Analyse von Patient:innen mit fortgeschrittenem Brustkrebs erlaubt die Behandlungsoption zu verbessern und ermöglicht durch die Analyse von bekannten Resistenzmarkern auch den klinischen Verlauf besser zu verstehen. Die interdisziplinäre Besprechung der Befunde im molekularem Tumorboard ist im Hinblick auf kontinuierliches Lernen aller Beteiligten sowie zur Qualitätssicherung eine entscheidende obligate Maßnahme.
Gastroschisis und Omphalozele zählen zu den häufigsten angeborenen Bauchwanddefekten. Dabei wird zwischen einfacher (ohne sekundäre Darmveränderungen) und komplexer (mit sekundären Darmveränderungen) Gastroschisis unterschieden. Bei der Omphalozele ist es wichtig, ob eine Protrusion der Leber vorliegt. Die Therapie beider Fehlbildungen besteht aus der Reposition der Bauchorgane in den Bauchraum und einem operativen Bauchdeckenverschluss in den ersten Lebenstagen.
Daten zu Langzeitverläufen nach dem operativen Bauchdeckenverschluss, insbesondere in Hinblick auf gastrointestinale Komplikationen mit erneutem chirurgischen Interventionsbedarf, sind in der Literatur rar.
Ziel dieser Studie ist es daher, die Inzidenz und die Art von operativen Eingriffen nach dem Bauchdeckenverschluss bei Patienten mit einer Gastroschisis und einer Omphalozele nach einem Bauchdeckenverschluss am eigenen Patientenkollektiv zu untersuchen. Hierzu wurden die Akten aller Patienten mit Gastroschisis und Omphalozele, die in der Klinik für Kinderchirurgie und Kinderurologie des Universitätsklinikums Frankfurt von 2010 bis 2019 behandelt wurden, retrospektiv ausgewertet. Die Inzidenz von Operationen nach Bauchdeckenverschluss wurde anhand der mittleren kumulativen Ein-Jahres-Anzahl an Operationen pro Patienten und der kumulativen Ein-Jahres-Inzidenz der Operationen ermittelt.
Insgesamt wurden 61 Patienten identifiziert. Nach Ausschluss von vier Patienten (Krankenhausverlegung (ein Patient) und Versterben (drei Patienten)) konnten die Verläufe von 33 Patienten mit Gastroschisis (18 mit einfacher und 15 mit komplexer Gastroschisis) und 24 Patienten mit Omphalozele (je zwölf mit und ohne Leberprotrusion) ausgewertet werden.
Bei 23 Patienten mit Gastroschisis und bei 20 Patienten mit Omphalozele kam es innerhalb des ersten Jahres nach Bauchdeckenverschluss zu erneuten Operationen. Das Risiko sich einer erneuten Operation unterziehen zu müssen, war bei Patienten mit komplexer Gastroschisis signifikant höher als bei Patienten mit einfacher Gastroschisis (kumulative Ein-Jahres-Inzidenz: 64,3% vs. 24,4%; p= 0,05). Zwischen den beiden 6 Formen der Omphalozele bestand kein Unterschied in der Inzidenz chirurgischer Eingriffe. Im Median kam es bei Patienten mit Gastroschisis nach 84 Tagen und bei Patienten mit Omphalozele nach 114,5 Tagen zu einer erneuten Operation.
74% der Patienten mit Gastroschisis und 30% der Patienten mit Omphalozele wurden aufgrund einer gastrointestinalen Komplikation operiert. Die Patienten mit komplexer Gastroschisis hatten im Vergleich zu Patienten mit einfacher Gastroschisis ein signifikant erhöhtes Risiko für eine Operation zur Behandlung einer gastrointestinalen Komplikation (kumulative Ein-Jahres-Inzidenz 64,3% vs. 11,1%; p= 0,015). In Bezug auf die Anzahl der Operationen pro Patienten und Jahr hatten die Patienten mit komplexer Gastroschisis und Patienten mit Omphalozele und Leberprotrusion die meisten operativen Eingriffe (kumulative Ein-Jahres-Anzahl 1,664 und 1,417 vs. einfache Gastroschisis (0,326) und Omphalozele ohne Leberprotrusion (0,333)). Dieses Verhältnis spiegelt sich auch in der kumulativen Ein-Jahres-Anzahl an Operationen mit gastrointestinalen Indikationen wider (komplexe Gastroschisis: 1,462 Operationen; Omphalozele mit Leberprotrusion: 0,500 Operationen; einfache Gastroschisis: 0,111 Operationen; Omphalozele ohne Leberprotrusion: keine Operation)
Nach dem Bauchdeckenverschluss kam es zu zwei Todesfällen bei Patienten mit komplexer Gastroschisis und zu drei Todesfällen bei den Patienten mit Omphalozele und Leberprotrusion. Bei den beiden Patienten mit komplexer Gastroschisis lag eine gastrointestinale Ursache vor (Leberversagen, Dünndarmvolvulus). Die Patienten mit der Omphalozele verstarben aufgrund assoziierter kardialer und pulmonaler Erkrankungen. Die Daten zeigen, dass Patienten mit Gastroschisis und Omphalozele im ersten Lebensjahr nach dem Bauchdeckenverschluss ein hohes Risiko für weitere Operationen haben. Patienten mit komplexer Gastroschisis und mit einer Omphalozele und Leberprotrusion haben das größte Risiko für eine erneute Operation nach Bauchdeckenverschluss. Bei Patienten mit einfacher Gastroschisis und Omphalozele ohne Leberprotrusion ist dieses Risiko gering. Die Mehrzahl der Operationen erfolgt aufgrund von gastrointestinalen Ursachen. Nur bei Patienten mit komplexer Gastroschisis tragen gastrointestinale Komplikationen zu einer erhöhten Mortalitätsrate bei. Die Ergebnisse dieser Arbeit können für Aufklärungs- und Beratungsgespräche von Eltern von Kindern mit Gastroschisis und Omphalozele herangezogen werden.
The Compressed Baryonic Matter (CBM) is one of the core experiments at the future Facility for Anti-proton and Ion Research (FAIR), Darmstadt, Germany. Its goal is to investigate nuclear matter characteristics at high net-baryon densities and moderate temperatures. The Silicon Tracking System (STS) is a central detector system of CBM.
It is placed inside a 1Tm magnet and operated at a temperature of about −10 °C to keep radiation-induced bulk current in the 300μm double-sided microstrip silicon sensors low. The design of the STS aims to minimize the material budget in the detector acceptance (2.5° < θ < 25°). In order to do so, the readout electronics is placed outside the active area, and the analog signals are transported via ultra-thin micro-cables. The STS comprises eight tracking stations with 876 modules. Each module is assembled on a carbon fiber ladder, which is subsequently mounted in the C-shaped aluminum frame.
The scope of the thesis focused on developing a modular control system framework that can be implemented for different sizes of experimental setups. The developed framework was used for setups that required a remote operation, like the irradiation of the powering modules for the front-end electronics (FEE), but also in laboratory-based setups where the automation and archiving were needed (thermal cycling of the STS electronics).
The low voltage powering modules will be placed in the vicinity of the experiment, therefore they will experience a total dose of up to 40mGy over the 10 years of STS lifetime.
To estimate the effects of the radiation on the low-voltage module performance, a dedicated irradiation campaign took place. It aimed at estimating the rate of radiation induced soft errors, that lead to the switch off of the FEE.
Regular power cycles of multiple front-end boards (FEBs) pose a risk to the experiment operation. Firstly, such behavior could negatively influence the physics performance but also have deteriorating effects on the hardware. It was further assessed what are the limitations of the FEBs with respect to the thermal cycling and the mechanical stress. The results served as an indication of possible failure modes of the FEB at the end of STS lifetime. Failure modes after repeated cycles and potential reasons were determined (e.g., Coefficient of Thermal Expansion (CTE) difference between the materials).
Due to the conditions inside the STS efficient temperature and humidity monitoring and control are required to avoid icing or water condensation on the electronics or silicon sensors. The most important properties of a suitable sensor candidate are resilience to the magnetic field, ionizing radiation tolerance, and fairly small size.
A general strategy for ambient parameters monitoring inside the STS was developed, and potential sensor candidates were chosen. To characterize the chosen relative humidity sensors the developed control framework was introduced. A sampling system with a ceramic sensor and Fiber Optic Sensors (FOS) were identified as reliable solutions for the distributed sensing system. Additionally, the industrial capacitive sensors will be used as a reference during the commissioning.
Two different designs of FOS were tested: a hygrometer and 5 sensors multiplexed in an array. The FOS hygrometer turned out to be a more reliable solution. One of the possible reasons for a worse performance is a relatively low distance between the subsequent sensors (15 cm) and a thicker coating. The results obtained from the time response study pointed out that the thinner coating of about 15μm should be a good compromise between the humidity sensitivity and the time response.
The implementation of the containerized-based control system framework for the mSTS is described in detail. The deployed EPICS-based framework proved to be a reliable solution and ensured the safety of the detector for almost 1.5 years. Moreover, the data related to the performance of the detector modules were analyzed and significant progress in the quality of modules was noted. Obtained data was also used to estimate the total fluence, which was based on the leakage current changes.
The developed framework provided a unique opportunity to automate and control different experimental setups which provided crucial data for the STS. Furthermore, the work underlines the importance of such a system and outlines the next steps toward the realization of a reliable Detector Control System for STS.
Metabolism has long served as a broad organizing concept in Russian and Soviet culture for the exchange of material and energy between organisms and their environment. The Russian term 'obmen veshchestv', literally meaning "exchange of substances", semantically ranges beyond the Latinate 'metabolizm' (metabolism) and provides a framework for reflecting on bodies and material objects as open systems engaged in a constant process of transformation. 'Obmen veshchestv' appears in public discourse in mid-19th century Russia as a calque from the German term 'Stoffwechsel' (or 'Wechsel der Materie'). Its usage in Russia reflects the enduring influence of German science. In this entry, I will explore the development and expansion of this concept of material and energy exchange between organisms and their environment in Russia and the Soviet Union. In the course of a century, metabolism migrated from discussions of plant nutrition into physiology, thermodynamics, and ultimately into the Soviet practice of state economic planning. This entry will therefore pay particular attention to the early Soviet period when existing debates on metabolism took on new urgency as tools for praxis on every scale, from the body of the individual worker to humanity's future collective management of planetary material and energy flows.
Deviance detection describes an increase of neural response strength caused by a stimulus with a low probability of occurrence. This ubiquitous phenomenon has been reported for multiple species, from subthalamic areas to auditory cortex. While cortical deviance detection has been well characterised by a range of studies covering neural activity at population level (mismatch negativity, MMN) as well as at cellular level (stimulus-specific adaptation, SSA), subcortical deviance detection has been studied mainly on cellular level in the form of SSA. Here, we aim to bridge this gap by using noninvasively recorded auditory brainstem responses (ABRs) to investigate deviance detection at population level in the lower stations of the auditory system of a hearing specialist: the bat Carollia perspicillata. Our present approach uses behaviourally relevant vocalisation stimuli that are closer to the animals' natural soundscape than artificial stimuli used in previous studies that focussed on subcortical areas. We show that deviance detection in ABRs is significantly stronger for echolocation pulses than for social communication calls or artificial sounds, indicating that subthalamic deviance detection depends on the behavioural meaning of a stimulus. Additionally, complex physical sound features like frequency- and amplitude-modulation affected the strength of deviance detection in the ABR. In summary, our results suggest that at population level, the bat brain can detect different types of deviants already in the brainstem. This shows that subthalamic brain structures exhibit more advanced forms of deviance detection than previously known.
»Just Computing?« – der Titel des Auftakts war bewusst doppeldeutig gewählt. Bedeutet die digitale Transformation »nur«, dass rechnergestützte Methoden Prozesse allerorten optimieren? Oder ist damit auch ein Wandel gemeint, der »gerecht« gestaltet werden kann? Antworten auf solch grundlegende Fragen – so viel stellte Uni-Präsident Enrico Schleiff bei der Eröffnung klar – können nur gemeinsam erarbeitet werden mit einem neuen, Fachgrenzen überschreitenden Denken. »Eine Mammutaufgabe und nicht ohne Risiko«, so Schleiff, aber notwendig, weshalb er das Zentrum in seiner Präsidentschaftsbewerbung auch »versprochen« habe. Nun ist es da, und zwölf neue »ausfinanzierte« Professuren sollen in den kommenden zwei Jahren dorthin berufen werden, gab der Sprecher des Gründungsvorstands Christoph Burchard bekannt. Neben dem Juristen Burchard gehören diesem Gründungsvorstand die Bioinformatikerin Franziska Matthäus an, der Informatiker Ulrich Meyer und die Erziehungswissenschaftlerin Juliane Engel – die angestrebte Perspektivenvielfalt ist auf dieser Ebene also schon einmal vorhanden.
Für die anstehende Runde der Exzellenzstrategie des Bundes und der Länder bewirbt sich die Goethe-Universität Frankfurt mit vier neuen Clustern zu den Forschungsthemen Vertrauen im Konflikt (CONTRUST), Infektion und Entzündung (EMTHERA), Ursprung der schweren Elemente (ELEMENTS) und zelluläre Architekturen (SCALE). Die Anträge vereinen die Kompetenzen und zukunftsweisenden Ideen der Goethe-Universität mit denen der Kolleg*innen des Verbunds der Rhein-Main-Universitäten (RMU) und weiterer Partner der vier großen Organisationen der außeruniversitären Forschung. Der seit 2019 bestehende Exzellenzcluster Cardiopulmonary Institute (CPI) wird im kommenden Jahr direkt einen Vollantrag einreichen.
Einleitung: Allergisches Asthma bronchiale ist eine chronische Atemwegserkrankung, deren Prävalenz zunimmt. Angesichts der immensen gesellschaftlichen und individuellen Belastung durch Asthma ist es dringend erforderlich, neue Strategien zur Behandlung der Krankheit zu entwickeln. Immunologisch ist allergisches Asthma durch ein Ungleichgewicht zwischen TH2-Zellen und TH1-Zellen gekennzeichnet, das durch regulatorische T-Zellen (Tregs) reguliert wird. Tregalizumab ist ein monoklonaler IgG-Antikörper, der Tregs selektiv aktiviert. Ziel der vorliegenden Arbeit war es daher, die Wirkung von Tregalizumab auf die allergeninduzierte allergische Entzündung bei Patienten mit Hausstaubmilbenallergie anhand eines bronchialen Provokationsmodells zu untersuchen.
Methoden: In einer prospektiven, randomisierten, doppelblinden und placebokontrollierten Studie wurden 42 Probanden mit allergischem Asthma und Hausstaubmilbenallergie zwölf Wochen lang mit Tregalizumab 100 mg oder Placebo behandelt. Bronchiale Provokation mit HSM wurde vor (V4) und nach (V17) Tregalizumab-Gabe durchgeführt. Induziertes Sputum (Visite V5, V16, V18) und peripheres Blut (Visite V4, V5, V18) wurden entnommen und Zelldifferenzierung, Zytokine und Transkriptionsfaktoren wurden durch Mikroskopie, Durchflusszytometrie bzw. RT-PCR bewertet.
Ergebnisse: Sowohl in der Verum- als auch in der Placebogruppe zeigte sich zwischen Visite V5 (24 Stunden nach Provokation) und vier Wochen nach Provokation bei Visite V16 (p<0,05) ein signifikanter Rückgang des Anteils eosinophiler Granulozyten (wie auch des ECP-Levels). Interessanterweise konnte bei V18 (24 Stunden nach Provokation) nur in der Placebogruppe ein signifikanter Anstieg beobachtet werden (p<0,01). Die Konzentration des TH-2-Zytokins IL-5 nahm zwischen V5 und V16 in der Verumgruppe signifikant ab (p<0,05). Zwischen V16 und V18 konnte wiederum nur in der Placebogruppe ein signifikanter Anstieg festgestellt werden (p<0,01). Dieser spätere Effekt wurde auch auf Protein- und Transkriptionsebene und im peripheren Blut sowie bei der Expression des Transkriptionsfaktors FoxP3 gefunden. Auf der Ebene der TH-1-Zytokine konnten keine signifikanten Veränderungen festgestellt werden.
Diskussion: Der Anteil eosinophiler Granulozyten, die Konzentration von IL-5 in Blut und Sputum sowie die Konzentration von ECP im Sputum haben sich als gute Parameter zur Beurteilung der Entzündungsreaktion bei unseren Studienteilnehmern erwiesen. Wir haben gezeigt, dass allergische Entzündungen, die durch das Provokationsmodell verursacht wurden, durch die analysierten Parameter im Sputum, aber auch im Blut gut überwacht werden konnten. Ein klinischer Effekt von Tregalizumab konnte in dieser Studie jedoch nicht festgestellt werden und dieses Ergebnis stimmt gut mit der Analyse der Entzündungsparameter im induzierten Sputum überein.
Märzgefallene : Anmerkungen zum publizistischen Gebrauch einer politischen Bezeichnung 1848–1898
(2023)
Das Wort 'Märzgefallene' ist eine Bezeichnung, die in der wissenschaftlichen wie populären Literatur vor allem über die Geschichte der Berliner Märzrevolution von 1848 auftaucht. Die vorliegende Analyse untersucht die Verwendung der Bezeichnung in der Tagespresse in den 50 Jahren nach der Revolution von 1848/49 bis zum 50. Jubiläum im Jahr 1898. [...] Die Analyse erfolgt in temporaler, quantitativer und qualitativer Hinsicht. Untersucht werden das erste Auftreten, die Häufigkeiten im Wandel der Jahrzehnte, Synonyme des Wortes sowie seine metaphorische Verwendung. Dadurch werden implizit auch eine Geschichte der Rezeption der Revolution von 1848/49 skizziert und die unterschiedlichen semantischen Varianten uneigentlichen Sprechens der Bezeichnung 'Märzgefallene' aufgezeigt.
Vladimir Vernadsky's concept of living matter is central to his biogeochemistry, the science he founded. For several reasons, his original understanding of living matter is one of the most complex notions in the history of the life sciences. First, biogeochemistry is by definition an interdisciplinary enterprise that embraces biology, including evolutionary theory, geology, and chemistry, and combines them into a unique research program. Second, if understood in the original sense as used by Vernadsky, living matter is a concept built into idiosyncratic metaphysics constructed around the so-called principle of life's eternity. Third, the concept of living matter reflects the specificity of Vernadsky's sophisticated philosophy of science as he insisted that 'scientific thought' is a planetary phenomenon as well as a geological force. In our contribution, we will introduce Vernadsky's concept of living matter in its historical context. Accordingly, we will also give some chronology of Vernadsky's work related to the growth of his biosphere concept highlighting the 'Ukrainian' period as it is in this period that he intensively elaborated on the notion of living matter. This will be followed by his theory of living matter as it was formulated in his major works of the later period. We are going to locate the notion of living matter within Vernadsky's theoretical system and demonstrate that he regarded his theory of the living as an evolutionary theory complementary to that of Charles Darwin from the very beginning. Additionally, we will briefly present Vladimir Beklemishev's concept of 'geomerida' which he developed at approximately the same time as Vernadsky was elaborating on his 'living matter' to highlight the specificity of the latter's methodology.
The essay will focus on three of the "many faces of irreversibility", sketching a history of irreversibility in 20th-century Russian thought: The abstract irreversibility of time in physics, the 'embodied' irreversibility of biological evolution and, finally, the irreversibility of cultural processes. The first part will trace the history of irreversibility in 19th-century physics and biology. The second part will discuss Vladimir Vernadsky's theory of biological time as an attempt to synthesize physical and biological irreversible processes ('neobratimye protsessy') as phenomena of asymmetry in space-time. The third part will look at the migration of scientific ideas of irreversibility into the theory of culture, i.e., Juri Lotman's semiotic theory of irreversibility as unpredictable and unrepeatable processes of culture. In this three-step sketch, the history of irreversibility will be outlined as one of spatialization (from an abstract law to the image of 'time's arrow') and of specialization (from the law of entropy to the case of the generation of meaning).
Editorial
(2023)
Das Forum Interdisziplinäre Begriffsgeschichte hat in seiner zwölfjährigen Geschichte immer wieder Begriffe an der Schnittstelle von Biologie sowie Gesellschaft und Kultur, insbesondere aber solche des ökologischen Diskurses thematisiert. [...] Das vorliegende, von der Slawistin Tatjana Petzer (Universität Graz) als Gastherausgeberin gestaltete Schwerpunktthema "Ecology in Eastern European Terminology" lässt sich als Fortsetzung dieser Thematiken verstehen. Die Beiträge verdeutlichen, wie Wissenschaftlerinnen und Wissenschaftler osteuropäischer Länder und der Sowjetunion, die oftmals zunächst im engen Kontakt mit westeuropäischen Wissenschaftsentwicklungen standen, aufgrund der späteren, vor allem im Kalten Krieg forcierten Abkoppelung eigenständige Terminologien und Konzepte entwickelten, deren Zusammenhang mit westlichen Ideen dadurch verdeckt waren, und doch mitunter auch wieder auf sie zurückwirkten. Viele der behandelten interdisziplinären Begriffe (Biogeochemie, Biogeozönose, Metabolismus, Regulation oder Geocryologie) thematisieren den heute so intensiv diskutierten Zusammenhang zwischen Ökologie und Geologie.
Der Humboldt-Forschungspreis wird an Wissenschaftlerinnen und Wissenschaftler aus dem Ausland verliehen in Anerkennung ihres bisherigen Gesamtschaffens. Einer der aktuellen Preisträger ist Alexander Fidora. Für den Mittelalterphilosophen aus Barcelona bedeutet der Preis eine Rückkehr an seine frühere Wirkungsstätte.
We compute the critical exponents of the O(N) model within the Functional Renormalization Group (FRG) approach. We use recent advances which are based on the observation that the FRG flow equation can be put into the form of an advection-diffusion equation. This allows to employ well-tested hydrodynamical algorithms for its solution. In this study we work in the local potential approximation (LPA) for the effective average action and put special emphasis on estimating the various sources of errors. Our results complement previous results for the critical exponents obtained within the FRG approach in LPA. Despite the limitations imposed by restricting the discussion to the LPA, the results compare favorably with those obtained via other methods.
Improved measurement of the branching fractions of the inclusive decays D⁺ → Kₛ⁰X and D⁰ → Kₛ⁰X
(2023)
By analyzing 2.93 fb−1 of 𝑒+𝑒− collision data taken at the center-of-mass energy of 3.773 GeV with the BESIII detector, the branching fractions of the inclusive decays 𝐷+→𝐾0 𝑆𝑋 and 𝐷0→𝐾0 𝑆𝑋 are measured to be (33.11±0.13±0.36)% and (20.75±0.12±0.20)%, respectively, where the first uncertainties are statistical and the second are systematic. These results are consistent with the world averages of previous measurements, but with much improved precision.
Der Beitrag widmet sich der Figurenanalyse als Bestandteil der Texterschließung im intersektional ausgerichteten Deutschunterricht und konzipiert ein konkretes methodisches Analyseverfahren, das intersektionale Fragestellungen bei der Figurenanalyse zu erarbeiten und darzustellen vermag. Über eine erste literaturdidaktische Fundierung der Figurenanalyse als Texterschließungsverfahren werden Anknüpfungspunkte zum Intersektionalitätsparadigma aufgezeigt Der Beitrag versteht sich als Vorschlag für eine mögliche kulturtheoretische Fundierung der Figurenanalyse durch das Intersektionalitätsparadigma, welches mit dem Kollektivansatz von Klaus P. Hansen und dessen Fortführung durch Jürgen Bolten zum fuzzy culture-Ansatz in Bezug gesetzt wird. Aus dieser theoretischen Verbindung wird ein konkretes Instrumentarium zur intersektional orientierten Figurenanalyse in literaturdidaktischen Settings entwickelt, das sich durch eine strukturierte visuelle Aufarbeitung intersektionaler Fragestellungen in Bezug auf literarische Figuren auszeichnet. Die folgenden Ausführungen bieten zunächst einen kurzen Überblick über die literarische Figur allgemein und ihre Merkmale sowie die Bedeutung der Figurenanalyse im Deutschunterricht, bevor letztere unter intersektionalen Gesichtspunkten beleuchtet und in ein konkretes Analyseinstrumentarium überführt wird. Dieses wird abschließend an Eleonora Hummels Roman "Die Fische von Berlin" beispielhaft erprobt.
Im Netzwerk „Breiter Kanon“, gegründet 2021 in Frankfurt, arbeiten rund 60 Personen aus Wissenschaft, Schule, Buchbranche und Journalismus daran,vergessene und marginalisierte Texte sichtbarzu machen. Ein Projekt ist die „Lückenliste“, durchsuchbar und verschlagwortetzu finden unter lueckenliste.de
Die Ausstellung „Von Listen und Lücken – Lektüren und Empfehlungen“ ist noch bis 22. Oktober im Schopenhauer-Studio der Uni-Bibliothek Frankfurt zu sehen sowie virtuell unter https://breiterkanon.hypotheses.org. Dort ist auch das Vademecum für Lehrende online und als PDF zu bekommen.
Standard applications of the consumption-based asset pricing model assume that goods and services within the nondurable consumption bundle are substitutes. We estimate substitution elasticities between different consumption bundles and show that households cannot substitute energy consumption by consumption of other nondurables. As a consequence, energy consumption affects the pricing function as a separate factor. Variation in energy consumption betas explains a large part of the premia related to value, investment, and operating profitability. For example, value stocks are typically more energy-intensive than growth stocks and thus riskier, since they suffer more from the oil supply shocks that also affect households.
Can consumption-based mechanisms generate positive and time-varying real term premia as we see in the data? I show that only models with time-varying risk aversion or models with high consumption risk can independently produce these patterns. The latter explanation has not been analysed before with respect to real term premia, and it relies on a small group of investors exposed to high consumption risk. Additionally, it can give rise to a “consumption-based arbitrageur” story of term premia. In relation to preferences, I consider models with both time-separable and recursive utility functions. Specifically for recursive utility, I introduce a novel perturbation solution method in terms of the intertemporal elasticity of substitution. This approach has not been used before in such models, it is easy to implement, and it allows a wide range of values for the parameter of intertemporal elasticity of substitution.
We propose a model with mean-variance foreign investors who exhibit a convex disutility associated to brown bond holdings. The model predicts that bond green premia should be smaller in economies with a closer financial account and highly volatile exchange rates. This happens because foreign intermediaries invest relatively less in such economies, and this lowers the marginal disutility of investing in polluting activities. We find strong empirical evidence in favor of this hypothesis using a global bond market dataset. Exchange rate volatility and financial account openness are thus able to explain the higher financing costs of green projects in emerging markets relative to advanced economies, especially when green bonds are denominated in local currency: a disadvantage that we can call the "green sin" of emerging economies.
The European bison was saved from the brink of extinction due to considerable conservation efforts since the early 20th century. The current global population of > 9,500 individuals is the result of successful ex situ breeding based on a stock of only 12 founders, resulting in an extremely low level of genetic variability. Due to the low allelic diversity, traditional molecular tools, such as microsatellites, fail to provide sufficient resolution for accurate genetic assessments in European bison, let alone from non-invasive samples. Here, we present a SNP panel for accurate high-resolution genotyping of European bison, which is suitable for a wide variety of sample types. The panel accommodates 96 markers allowing for individual and parental assignment, sex determination, breeding line discrimination, and cross-species detection. Two applications were shown to be utilisable in further Bos species with potential conservation significance. The new SNP panel will allow to tackle crucial tasks in European bison conservation, including the genetic monitoring of reintroduced populations, and a molecular assessment of pedigree data documented in the world’s first studbook of a threatened species.
ISOE-Newsletter Nr. 4/2023
(2023)
„Ein verregneter Sommer bringt uns das verlorene Grundwasser nicht zurück“ +++ Klimawandel und Gleichstellungspolitik – Session mit ISOE-Forscher bei der LABOR.A 2023 +++ Zukunft aus dem Reallabor? Was die Forschungsmethode für die Nachhaltigkeitsforschung bringt und wie das geplante „Reallabor-Gesetz“ zu bewerten ist +++ ISOE-Wissenschaftler*innen stellen sozial-ökologische Forschungsarbeiten beim „DKG’23“ vor +++ Wie steht es um die kommunale Klimaanpassung in Deutschland? +++ „Das Experiment hat uns überrascht“ – wie nachhaltiges Pendeln durch einen Reallabor-Versuch gelingen kann +++ Wie Chemikalieneinsatz und der Verlust der Artenvielfalt zusammenhängen +++ Das ISOE in den Medien +++ Aktuelle Beiträge im ISOE-Blog +++ Termine +++ Publikationen
ISOE-Newsletter Nr. 2/2023
(2023)
Flurina Schneider in den Klimabeirat der Hessischen Landesregierung berufen +++ Reallaborprojekt „transform-R“ für kommunalen Klimaschutz und interkommunale Zusammenarbeit gestartet +++ Verlust der Insektenvielfalt in Naturschutzgebieten – wie Handlungsbereitschaft für Insektenschutz entstehen kann +++ Soziale Ökologie und Transdisziplinarität in der Lehre +++ So lassen sich Herausforderungen transdisziplinärer Forschung angehen +++ Insektenvielfalt in der Stadt: Frankfurter Forschungsprojekt ruft Bürger*innen zum Mitmachen auf +++ Rückblick auf das Forschungsjahr 2022 +++ Gesellschaft für transdisziplinäre und partizipative Forschung gegründet +++ Bundesministerin Paus beruft ISOE-Forscher in Kommission für Gleichstellungsbericht +++ Interessenkonflikte um den Wald der Zukunft +++ Aktuelle Beiträge im ISOE-Blog +++ Aus dem ISOE +++ Termine +++ Publikationen
ISOE-Newsletter Nr. 5/2023
(2023)
Bundesweite Befragung zur Klimaanpassung in Deutschland erfolgreich abgeschlossen +++ Wasserknappheit – eine unterschätzte Gefahr? +++ Lehrveranstaltungen des ISOE zur Sozialen Ökologie +++ Wie eine Trendwende beim Biodiversitätsschutz gelingen kann +++ Transferprogramm „GeisTreich“ für zukunftsfähigen Weinbau gestartet +++ Sonderausstellung „Stadtinsekten – Frankfurts kleine Helfer“ +++ Reallabore-Gesetz: Experimentierräume nachhaltig und partizipativ gestalten +++ Aktuelle Beiträge im ISOE-Blog +++ Aus dem ISOE +++ Das ISOE in den Medien +++ Termine +++ Publikationen
ISOE-Newsletter Nr. 3/2023
(2023)
Alternativen zum privaten Auto – wie ein Umstieg gelingt +++ Insect Embassy – eine diplomatische Vertretung für Insekten in der Stadt +++ Dokuabend Rhein-Main: Frankfurt – eine Stadt für Insekten? +++ Wie die Grundwasserqualität geschützt werden kann +++ tdAcademy startet in die zweite Forschungsphase +++ Mit RNAi gegen gefährliche Stechmücken – neue technologische Entwicklung aus Hessen kann vor der Verbreitung tropischer Krankheiten schützen +++ Gründungsfeier in Berlin der Fachgesellschaft für transdisziplinäre und partizipative Forschung +++ „Das ist für mich so Pendelfreizeit“ – Interviewstudie im Forschungsprojekt PendelLabor erschienen +++ Das ISOE in den Medien +++ Aktuelle Beiträge im ISOE-Blog +++ Termine +++ Publikationen
This thesis comprises the usage of two commonly known hinge-binding moieties in drug discovery. First, the quinazoline scaffold of gefitinib (5) was utilized in a macrocyclization strategy to introduce selectivity. In general, the quinazoline hinge-binding moiety is a commonly used scaffold which can be found in 14% of approved kinase inhibitors. The most familiar applications are EGFR inhibitors such as gefitinib (5), erlotinib (6), afatinib, or dacomitinib for the treatment of NSCLC. But other kinases like CDK2, CDK4, or p38 are reported targets as well.
The N-phenylquinazolin-4-amine moiety of gefitinib (5) was conserved however, the residues at the aromatic ring in the linker were modified, the residue targeting the solvent-exposed region was varied, and the linker at the C6 position of the quinazoline was adjusted to enable the macrocyclization. An overview of the structural modifications is shown in Figure 35A.
Kinome-wide screening of gefitinib (5) revealed several off-targets besides EGFR (Figure 35B), making it an excellent starting point for a macrocyclization strategy. Introducing a linker to the N phenylquinazoline-4-amine scaffold and retaining the residues on the aromatic ring as well as the methoxy group targeting the solvent-exposed region improved the selectivity profile and the efficacy towards EGFR WT and its mutants. Truncation of the linker moiety led to the mutant selective macrocycle 26f with an excellent kinome-wide selectivity profile (Figure 35B). An inhibitor that is effective on EGFR mutations while ineffective on the EGFR WT could represent an enhancement of patient treatment, as it potentially causes less side effects. Further studies could determine the effect of the most promising macrocycles in lung cancer cell lines. Additionally, the pharmacokinetic properties could be optimized, e.g. by introducing solubilizing groups, targeting the solvent-exposed region.
The second scaffold comprises the 3-aminopyrazole-based hinge-binding moiety. It is a privileged scaffold in medicinal chemistry for the development of kinase inhibitors. Previous publications report the anti-proliferative and anti-cancer potential of pyrazole-based molecules. They play a crucial role in the treatment of various diseases and cancer types like inflammation disorders, lymphoma, or breast cancer. This scaffold can be found e.g. in the aurora kinase inhibitor tozasertib or in the promiscuous kinase inhibitor 23, published by Statsuk et. al. Rescreening compound 23 in a comprehensive kinase panel against 468 human protein kinases confirmed the unselective behavior with a selectivity score of S35 = 0.56 (Figure 36B), making it a great starting point for further optimizations. The N-(1H-pyrazol-3-yl)pyrimidin-4-amine scaffold was conserved however, the residues targeting the solvent-exposed region were varied and different linkers were attached.
The introduction of different residues at the pyrazole dramatically influenced the selectivity profile of the desired kinases. Ester moieties caused to a favorable combination of selectivity and potency towards the kinase of interest CDK16. The removal of additional residues at the pyrimidine, targeting the solvent-exposed region, increased the efficiency towards CDK16. Further optimization led to the highly potent and selective CDK16 inhibitor 98d (IC50 = 33 nM). NanoBRETTM screening against the complete CDK family revealed a preferred inhibition of the PCTAIRE and PFTAIRE subfamily with cellular IC50 values of 20 nM – 120 nM and 50 nM – 180 nM, respectively. A FUCCI cell cycle assay and viability assessment of 98d confirmed previously published results, reporting a G2/M cell cycle arrest followed by apoptosis and accumulation of p27 through knockout of CDK16 in SCC cells. Consequently, further studies could evaluate the anti-tumor activity of 98d in SCC and NSCLC or elucidate the effect of 98d in AMPK-related macroautophagy. 98d represents a novel tool compound to investigate the understudied kinases of the PCTAIRE family and enable to enlighten the biological role of those kinases.
Macrocyclization of the N-(1H-pyrazol-3-yl)pyrimidin-4-amine core resulted in the selective BMPR2 inhibitor 110a. It showed a good binding affinity towards BMPR2 with a KD value of 205 nM as well as a good potency with an IC50 value of 506 nM. A comprehensive selectivity screen against 468 kinases revealed an excellent selectivity profile with S35 = 0.01. As no BMPR2 inhibitors have been published so far, 110a represents a novel compound that may provide further insights into the canonical BMP pathway, noncanonical signaling, or its impact on BMPR2-associated diseases like PAH.
The introduction of additional residues targeting the solvent-exposed region shifted the selectivity towards the MST kinases. The exchange from the pyrimidine to a quinazoline moiety resulted in the highly potent and selective macrocyclic MST3 inhibitor 113c. NanoBRETTM measurements demonstrated the preferred inhibition of MST3 with IC50 values of 210 nM and 30 nM for intact and lysed cells, respectively. A weaker activity could be seen for MST4 with 1.8 µM and 510 nM, while MST1 and MST2 were not affected. To date, no selective MST3 inhibitors have been published, making 113c a valuable tool compound for further functional studies. As MST3 is influencing the cell cycle progression, 113c could be tested in a further cell cycle assay to elucidate the inhibitory effect of 113c on MST3 and consequently on the cell cycle. Furthermore, the anti-tumor activity of 113c in breast cancer could be determined, as Madsen et. al. reported a high MST3 and MST4 activity triggered by FAM40B mutations.
My aim in this paper is to make the debates about epistemic injustice fruitful for an analysis of trust in the knowledge of others. Epistemic trust is understood here in a broad sense: not only as trust in scientific knowledge or expert knowledge, but also as trust in implicit, positioned and experience-based knowledge. Using insights from discussions of epistemic injustice, I argue for three interrelated theses:
1. Questions of epistemic trust and trustworthiness cannot be answered with reference to individual virtue alone; rather, they have a structural component.
2. The rationality of epistemic trust must be analyzed against the background of social structures and social relations of domination.
3. Epistemic trust is (also) a political phenomenon and epistemically just relations depend on political transformation processes that promote equality.
Dieser Arbeit lag die Fragestellung zugrunde, welchen Einfluss die jeweilige Transfusionsstrategie auf AML-Patienten unter intensiver Induktionschemotherapie hat.
Dafür wurde ein am Universitätsklinikum Frankfurt zwischen 2007 und 2018 behandeltes Kollektiv von 352 Patienten untersucht. So erfolgte hier bis ins Jahr 2015 hinein die Transfusion eines EK ab einem Hb-Wert <8g/dl und nach Änderung des Transfusionstriggers ab einem Hb <7g/dl. AML-Patienten aus dem Jahr 2015 – dem Jahr der Änderung der Transfusionsregel – wurden von weiterer Untersuchung ausgeschlossen, um zwei klar abgrenzbare Kohorten erhalten zu können.
Es zeigte sich, dass die weniger restriktive Transfusionskohorte unter Induktionschemotherapie einen durchschnittlich um 1g/dl höheren Hb-Wert aufwies und früher als die restriktive Kohorte transfundiert wurde. Die Anzahl an Fiebertagen, CRP-Werte, Aufenthalte auf Intensivstation sowie die Dauer des Krankenhausaufenthaltes betrachtend, zeigte sich hingegen kein signifikanter Unterscheid zwischen beiden Kohorten.
Basierend auf unserer Arbeit ergeben sich keine Hinweise dafür, dass die restriktive Transfusionspraxis einer weniger restriktiven für AML-Patienten unterlegen ist. Limitierend auf die Aussagekraft der Ergebnisse wirken sich dabei die retrospektive Natur der Arbeit sowie die zeitliche Verschiebung der Behandlungszeiträume beider Kohorten aus.
Ergebnisse der bislang ausstehenden randomisierten Studien, die den Einfluss unterschiedlicher Transfusionsregimes auf Patienten mit hämatologischen Krankheiten untersuchen, sind in Bälde zu erwarten. Die bereits vorliegenden Pilotstudien und Ergebnisse der TRIST-Studie decken sich mit der von uns beobachteten Nicht-Unterlegenheit der restriktiven Transfusionspraxis für ein hämatoonkologisches Patientenkollektiv, sodass es abzuwarten gilt, ob sich dies auch in weiteren größeren randomisierten und kontrollierten Studien beweisen kann.
A taxonomic study on twenty-nine species of jumping spiders from South China is presented. Twenty new species are diagnosed and described: Heliophanoides proszynskii Wang, Mi & Peng sp. nov. (♂♀), Myrmage lii Wang, Mi & Peng sp. nov. (♂♀), Myrmarachne hamata Wang, Mi & Peng sp. nov. (♂), M. xingrenensis Wang, Mi & Peng sp. nov. (♂♀), M. yinae Wang, Mi & Peng sp. nov. (♂♀), Phintella fodingensis Wang, Mi & Peng sp. nov. (♂♀), P. jiugongensis Wang, Mi & Peng sp. nov. (♂♀), P. liae Wang, Mi & Peng sp. nov. (♂), P. liui Wang, Mi & Peng sp. nov. (♂♀), P. subpanda Wang, Mi & Peng sp. nov. (♂♀), P. wandae Wang, Mi & Peng sp. nov. (♂♀), Ptocasius dian Wang, Mi & Peng sp. nov. (♂♀), P. subhubeiensis Wang, Mi & Peng sp. nov. (♂♀), Rhene elongata Wang, Mi & Peng sp. nov. (♂♀), Stertinius donglinsiensis Wang, Mi & Peng sp. nov. (♂♀), S. logunovi Wang, Mi & Peng sp. nov. (♂), Synagelides fanjingensis Wang, Mi & Peng sp. nov. (♂♀), Thyene xingrenensis Wang, Mi & Peng sp. nov. (♂♀), Toxeus fodingensis Wang, Mi & Peng sp. nov. (♂♀), and Yaginumaella zabkai Wang, Mi & Peng sp. nov. (♂♀). The genus Heliophanoides Prószyński, 1992 is redefined and two new combinations, transferred from the genus Phintella Strand, 1906, are proposed: H. tengchongensis (Lei & Peng 2013) comb. nov., and H. longlingensis (Lei & Peng 2013) comb. nov. The unknown sexes of the following six species are described for the first time: Phintella fanjingshan Li, Wang, Zhang & Chen, 2019, P. panda Huang, Wang & Peng, 2015, P. pygmaea (Wesołowska, 1981), P. sancha Cao & Li, 2016, P. wulingensis Huang, Wang & Peng, 2015, and Rhene yunnanensis (Peng & Xie, 1995). Brettus anchorum Wanless, 1979 and Phintella aequipeiformis Żabka, 1985 are newly recorded from China. Icius indicus (Simon, 1901) comb. nov. (transferred from Phintella) is re-described. Phintella levii Huang, Wang & Peng, 2015 is assigned to be a synonym of P. arcuata Huang, Wang & Peng, 2015. Thyene zhangi (Peng, Yin, Yan & Kim, 1998) comb. nov. is transferred from Plexippoides Prószyński, 1984, and T. bilaguncula (Xie & Peng, 1995) comb. nov. is transferred from Ptocasius Simon, 1885. Diagnostic illustrations of the twenty-nine species and the distributional maps of the studied specimens are provided.
The species of Rhyacobates Esaki, 1923 are reviewed. Three new species, R. bui sp. nov. from Guangxi, China and Lạng Sơn, Vietnam, R. elongatus sp. nov. from Hà Tĩnh, Vietnam and R. turgidus sp. nov. from Sichuan and Chongqing, China are described. Supplemental descriptions, diagnoses and new distribution records are provided for the fourteen previously known species, i.e., R. abdominalis Andersen & Chen, 1995, R. anderseni Tran & Yang, 2006, R. angustus Tran & Nguyen, 2016, R. chinensis Hungerford & Matsuda, 1959, R. constrictus Tran & Nguyen, 2016, R. edentatus Andersen & Chen, 1995, R. gongvo Tran & Yang, 2006, R. lundbladi (Hungerford, 1957), R. malaisei Andersen & Chen, 1995, R. recurvus Andersen & Chen, 1995, R. scorpio Andersen & Chen, 1995, R. svenhedini (Lundblad, 1934), R. takahashii Esaki, 1923, and R. zetteli Tran & Nguyen, 2016. Photographs and line drawings of the habitus, diagnostic characteristics of both sexes, the habitat and in-situ photographs are presented. A revised key to the species of Rhyacobates is also provided.
Electrospinning is a versatile and promising drug delivery technology for the development of tailor-made drug delivery systems for various clinical applications. By applying high voltages to drug-loaded polymer solutions, solid polymeric nanofibers can be generated, which encapsulate active pharmaceutical ingredients (APIs) into their polymer matrix. During the electrospinning process, the fibers are deposited on a collector and form a nonwoven network of drug-loaded polymer fibers. These fibers are spatially distributed in aligned or random orientation, providing the opportunity to design highly tunable structural and mechanical properties, which can be adapted to the biological requirements of the intended application site. The mechanically flexible fiber networks can therapeutically be administered to a multitude of pharmaceutical application sites. Their highly porous fiber structure exhibits a large surface-to-volume ratio, which is ideal for controlled drug release kinetics from the polymer matrix upon contact with biological fluids, such as tear fluid, saliva, mucus, wound exudate or gastro-intestinal fluid. For application at the target site, fiber mats are cut into patches. As the patch size determines the quantity of applied API, the electrospinning process must ensure homogeneous distribution of the API throughout the entire fiber mat area.
In this thesis, electrospinning was established as a formulation technology for the rational fabrication of tailor-made multifunctional drug carrier systems for local and site-specific drug delivery to the epithelial interfaces skin, oral mucosa as well as cornea. For adequate characterization and analysis of the drug delivery systems, a broad panel of robust and predictive analytical tools, based of novel investigation techniques for physicochemical characterization of electrospun fibers, was developed.
The initial part of the thesis thematically focuses on the development of predictive analytical techniques, to determine fiber morphology and physicochemical properties, as well as fiber composition and drug release. By designing two model formulations with contrasting properties, and subsequent analysis and characterization with a set of newly developed techniques and state-of-the-art methods, a comprehensive toolset has been made available and evaluated, aiming at advancing and standardizing respective techniques in the scientific field of electrospun drug delivery systems.
Starting with the initiation of the electrospinning formulation process, which often relies on empirical data rather than analytical methods to predict successful processability, analysis of rheological properties of electrospinning solutions was used to rationally detect the minimum polymer concentration required for electrospinning.
For analysis of fiber morphology, scanning electron microscopy is a common technique. However, little attention is given to underlying readout parameters. By analyzing the fiber orientation and diameter of the respective fibers, predictive results regarding mechanical properties could be obtained, which were subsequently confirmed by measuring elongation force with tensile testing. Confocal Raman microscopy, a label-free method for chemically- selective imaging of the fiber samples, was introduced as a complementary visualization technique, enabling the detection of fiber composition and drug distribution.
A novel technique for investigation of water contact angles on the fiber surface of highly hydrophilic polymers was introduced, which provides predictive data regarding interaction with body fluids and the resulting drug release kinetics. Subsequent release testing in a newly developed setup for analyzing drug release from electrospun fibers in low-volume body compartments, confirmed the anticipated drug release kinetics from measurement of the surface hydrophilicity.
By combining complementary analytical methods, including spectral composition analysis, morphology visualization, characterization of physico-chemical properties and drug release kinetics, as well as the application of multivariate data analysis, a robust and predictive toolset has been established, which can support comparability of future electrospinning studies and the translation from the lab bench into clinics.
Based on the analytical toolset, the main part of the thesis focuses on the development and preparation of electrospun platform drug delivery systems for application on epithelial barriers. Electrospun fiber mats are thin, flat, and mechanically flexible, which allows close adherence to epithelial surfaces and reduction of diffusion paths, which enables efficient drug delivery to the skin, oral mucosa, as well as the cornea.
Electrospun fibers bear a high potential for application as wound dressings, while simultaneously controlling the local delivery of APIs to the wound area. Their close resemblance to the extracellular matrix of human skin provides a suitable microenvironment for cellular proliferation and migration for wound closure. In this work, insulin, a fragile proteohormone with growth factor characteristics, was successfully encapsulated into the core of coaxially electrospun fibers, thus maintaining bioactivity throughout and after the electrospinning process. The shell has been designed from biocompatible polymers, which, upon contact with aqueous wound exudate, partially dissolve and form pores through which bioactive insulin is released in a controlled manner. The shell layer provides a hydrophilic surface for interaction with body fluids and skin cells, and possesses substantial mechanical strength, flexibility, and high tensile elongation required for application on wounds. The biocompatibility of the wound dressing was investigated by interaction with primary human dermal fibroblasts and keratinocytes, which displayed healthy cell morphologies without indicating any elevated levels of cytotoxicity markers.
To investigate the effect of insulin on cell migration, in vitro scratch assays on human skin cells were performed. Increased cellular migration speed and wound closure could be observed, indicating improved wound healing. Bio relevance of in vitro wound healing potential results was advanced by development of 3D ex vivo human epidermal skin wound models from reduction surgery donor material. These complex wound models were treated with electrospun insulin fibers and analyzed by proteome analysis to reveal significant increases in wound healing-associated signaling pathways, which could be attributed to a material-driven remarkably positive impact on wound healing of the electrospun fibers...
Anarchival practises : the Clanwilliam Arts Project as re-imagining custodianship of the past
(2023)
Where is the past? It is not really behind us, but with us, constantly imagined and re-imagined in public discourse through historical narrations. Using the Clanwilliam Arts Project as a case study, this volume is founded on the 'anarchive', a conceptual constellation that positions the past in relation to the present, bringing into view strategies to facilitate remembering beyond the colonial archive.
MoSyD Jahresbericht 2022 : Drogentrends in Frankfurt am Main ; Monitoring-System Drogentrends
(2023)
Forschung Frankfurt : das Wissenschaftsmagazin der Goethe-Universität. 1.2023 ; Fremde Welten
(2023)
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
t. This paper presents a taxonomic review of the genus Melanocanthon Halffter, a group of ball-rolling (telocoprid) dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) endemic to eastern North America. The genus comprises five species, each keyed, diagnosed, illustrated and presented with information on distribution, relationships, and biology: Melanocanthon punctaticollis (Schaeffer), M. granulifer (Schmidt), M. nigricornis (Say), M. bispinatus (Robinson) and Melanocanthon vulturnus Edmonds, new species.
ZooBank registration. urn:lsid:zoobank.org:pub:FA7D5D5E-CEB8-48ED-A442-74C315FCF5E4
A faunal study for the order Phasmatodea of the Chicaque Natural Park is presented, including a list of species found, descriptions, redescriptions, and biological notes. A total of nine species were found and studied; two new genera: Ramandeun new genus, Nubilophasma new genus, and four new species: Atratomorpha jorgei new species, Isagoras franciscoverai new species, Nubilophasma chicaquensis new genus and new species, and Ramandeum coronatum new genus and new species are described. The description of the eggs of the new taxa, of the previously unknown eggs of Paraceroys quadrispinosus (Redtenbacher, 1906), and the redescription of the eggs of Libethra rabdota Stål, 1875, and Libethra inchoata Brunner von Wattenwyl, 1907 are provided. Additional comments on the ecology and morphological variation of the reviewed taxa are included. Finally, further studies on the stick insect fauna of the Colombian Andes are discussed and recommended to provide more information to broaden the understanding of the species that inhabit this complex mountain system.
ZooBank registration. urn:lsid:zoobank.org:pub:7D34FF9A-CDEE-4DD4-A643-E0F467E00A5B
Shallow meritocracy
(2023)
Meritocracies aspire to reward hard work and promise not to judge individuals by the circumstances into which they were born. However, circumstances often shape the choice to work hard. I show that people's merit judgments are "shallow" and insensitive to this effect. They hold others responsible for their choices, even if these choices have been shaped by unequal circumstances. In an experiment, US participants judge how much money workers deserve for the effort they exert. Unequal circumstances disadvantage some workers and discourage them from working hard. Nonetheless, participants reward the effort of disadvantaged and advantaged workers identically, regardless of the circumstances under which choices are made. For some participants, this reflects their fundamental view regarding fair rewards. For others, the neglect results from the uncertain counterfactual. They understand that circumstances shape choices but do not correct for this because the counterfactual—what would have happened under equal circumstances—remains uncertain.
Poesie ermöglicht Zugänge : Potenziale deutschsprachig-muslimischer Lyrik für Unterricht und Praxis
(2023)
The genus Parandes Muir, 1925 (Cixiinae, Andini) is recorded from China for the first time with two new species, Parandes circinatus Wang & Chen sp. nov. and Parandes fuscus Wang & Chen sp. nov. Color images for the adults of the two new species and line drawings for the genitalia are provided. A key is presented to separate all species within the genus.
Weniger hilft mehr
(2023)
Das mildere Gift von Wildbienen verspricht ein größeres pharmazeutisches Anwendungspotenzial als das der Honigbiene, zeigt eine Studie von Forschenden aus Frankfurt und Gießen.
Wird in der Öffentlichkeit von Bienen gesprochen, ist häufig die Honigbiene (Apis mellifera) gemeint. Wildbienen hingegen summen sich erst langsam in unser Bewusstsein, obwohl sie bei Weitem die meisten Arten in der Gruppe der Bienen stellen und viele Pflanzenarten ausschließlich auf Wildbienen als Bestäuber angewiesen sind. Forschende der Goethe-Universität und anderer hessischer Institutionen zeigen nun in einer im Fachjournal »Toxins« veröffentlichten Studie eine weitere Facette der Bedeutung von Wildbienen: Ihr Gift wirkt milder als das der Honigbiene und ließe sich daher künftig leichter für die Entwicklung von Medikamenten nutzen.
Übergabe des Staffelstabes: Ulrich Breuer folgt auf Albrecht Fester als neuer Kanzler der Goethe-Universität. Mit dem UniReport sprachen die beiden über ihre beruflichen Werdegänge, über den Mut zum Neustart und die Herausforderung, auch in schwierigen Situationen als Führungskraft Ruhe zu bewahren.
Adenomera is a genus of Neotropical leaf-litter frogs widely distributed in South America and regarded taxonomic-wise challenging. One of these is the open-habitat Adenomera diptyx from Paraguay, which may correspond to a species complex. An integrative analysis of morphological variation, in combination with acoustic and molecular data of several populations from Argentina, Paraguay, and Brazil resulted in the recharacterization of nominal A. diptyx and the description of a new, closely related species. Adenomera diptyx is recognized by its advertisement call given at a high repetition rate (176–299 per minute), and the dorsal color pattern consisting of a light mid-dorsal line and a dark brown interorbital bar with irregular black edges. In comparison with A. diptyx, the new species, Adenomera guarani sp. nov., produces its advertisement call at a lower repetition rate (73–147 per minute), and the dorsal color pattern consists of a light, broad, mid-dorsal stripe and a mask-like patch in the interorbital region. The redefinition of A. diptyx will contribute to future studies focusing on the taxonomic status of other genetic lineages tentatively assigned to this species complex, which could represent additional unnamed species in the open-habitat Adenomera clade.
Few species of Japygidae (Diplura) have been discovered in cave ecosystems despite their importance as large predators. A small collection of rare specimens of this hexapod group has allowed to explore the taxonomy of japygids from caves in New Zealand, Morocco and South Africa, and to describe one new genus: Imazighenjapyx Sendra & Sánchez-García gen. nov., as well as four new species: Austrjapyx wynbergensis Sendra & Sánchez-García sp. nov., Imazighenjapyx marocanus Sendra & Sánchez-García gen. et sp. nov., Opisthjapyx naledi Sendra & Sánchez-García sp. nov. and Teljapyx aotearoa Sendra & Sánchez-García sp. nov. For each of the new taxa we give a comprehensive description of their habitats. These new findings resulted in a revision of the distribution and allowed to re-evaluate the morphological traits of the fifteen cave-adapted japygids species already known worldwide. The functional morphology of the remarkable abdominal pincers of Japygidae and their adaptation to predation are discussed, as well as their potential role in mating behaviour.
HER2 belongs to the ErbB sub-family of receptor tyrosine kinases and regulates cellular proliferation and growth. Different from other ErbB receptors, HER2 has no known ligand. Activation occurs through heterodimerization with other ErbB receptors and their cognate ligands. This suggests several possible activation paths of HER2 with ligand-specific, differential response, which so far remained unexplored. Using single-molecule tracking and the diffusion profile of HER2 as a proxy for activity, we measured the activation strength and temporal profile in live cells. We found that HER2 is strongly activated by EGFR-targeting ligands EGF and TGFα, yet with a distinguishable temporal fingerprint. The HER4-targeting ligands EREG and NRGβ1 showed weaker activation of HER2, a preference for EREG, and a delayed response to NRGβ1. Our results indicate a selective ligand response of HER2 that may serve as a regulatory element. Our experimental approach is easily transferable to other membrane receptors targeted by multiple ligands.
Intermediate Mass Ratio Inspirals (IMRIs) will be observable with space-based gravitational wave detectors such as the Laser Interferometer Space Antenna (LISA). To this end, the environmental effects in such systems have to be modeled and understood. These effects can include (baryonic) accretion disks and dark matter (DM) overdensities, so called spikes. For the first time, we model an IMRI system with both an accretion disk and a DM spike present and compare their effects on the inspiral and the emitted gravitational wave signal. We study the eccentricity evolution, employ the braking index and derive the dephasing index, which turn out to be complementary observational signatures. They allow us to disentangle the accretion disk and DM spike effects in the IMRI system.
Detection of morphologically indistinguishable cryptic species implies using an integrative taxonomic approach with a combination of molecular, contemporary morphological, ecological and other relevant analyses. Within a contemporary morphological analysis, two approaches are commonly used in hoverfly taxonomy: a geometric morphometric analysis of the wing and surstyle shape. Here, the importance of the R4+5 vein shape is tested in cryptic species delimitation within four Merodon species groups using linear and semilandmark geometric morphometric analyses. As expected, geometric morphometrics showed a stronger resolution compared to linear morphometrics. Linear morphometrics failed to detect differences related to sexual dimorphism or differences among the species M. pruni and M. obscurus. However, all cryptic species and sexes were separated with high significance based on the R4+5 vein shape. Moreover, obtained results concurred with the landmark-defined wing shape and molecular results published in previous studies. Additionally, combining two characters, the semilandmark R4+5 vein shape and the landmark-defined wing shape, provided more detailed and precise insights into the shape differences. Our results showed that the R4+5 vein shape stands out as an important character in species delimitation of hoverflies where the sinuation of this vein is present. Therefore, it can be beneficial as a single character or in combination with a landmark-based wing shape analysis.
Dysmicoccus brevipes (Cockerell) and Dysmicoccus neobrevipes Beardsley are major pests of pineapples, ornamentals, and vegetable crops in many countries around the world. The potential distribution of these mealybug pests into South Korea remains a prime concern because of their high incidence in interceptions screened during inspection. Hence, these species prompted a modelling effort to assess their potential risk of introduction. Potential risk maps were developed for these pests with the CLIMEX model based on occurrence records under environmental data. The potential distribution of these pests in South Korea in the 2020s, 2050s and 2090s is projected based on the RCP 8.5 climate change scenario. Results show that D. brevipes and D. neobrevipes have little potential for invasion in the exterior environment of South Korea due to high cold stress. However, for D. brevipes, three locations in Jejudo were predicted to be marginally suitable for this pest under future climate factors. In that respect, the results of these model predictions could be used to prepare a risk-based surveying program that improves the probability of detecting early D. brevipes and D. neobrevipes populations.
ZooBank registration. urn:lsid:zoobank.org:pub:CE2390B2-6C56-45E7-B4A7-BE30FEEB3F34
Beim Clusterprojekt ELEMENTS von Goethe-Universität, TU Darmstadt, Universität Gießen und GSI Helmholtzzentrum für Schwerionenforschung arbeiten Theorie und Experiment Hand in Hand, um die Struktur der Materie unter extremen Bedingungen zu verstehen. So wird ersichtlich, warum etwa Kollisionen von Neutronensternen viele der schweren Elemente auf unserem Planeten geliefert haben.
The planthopper family Caliscelidae (Hemiptera: Auchenorrhyncha: Fulgoromorpha) and the tribe Adenissini are recorded here for the first time from the Socotra Archipelago (Yemen). A new genus, Oceatra gen. nov., is described for two new species from Socotra Island – Oceatra litoralis gen. et sp. nov. (type species) from coastal sand dunes and salt marshes, and O. scandens gen. et sp. nov. from evergreen montane woodland and shrub communities of the Hagher mountains. Oceatra gen. nov. is similar to Perissana Metcalf, 1952 but differs in the structure of the male style and phallobase. A key to distinguish the genera of the subtribe Adenissina is provided.