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Highly efficient non-relativistic Edelstein effect in nodal p-wave magnets
Get PDFThe origin and efficiency of charge-to-spin conversion, known as the Edelstein effect (EE), has been typically linked to spin-orbit coupling mechanisms, which require materials with heavy elements within a non-centrosymmetric environment. Here we demonstrate that the high efficiency of spin-charge conversion can be achieved even without spin-orbit coupling in the recently identified coplanar p-wave magnets. The non-relativistic Edelstein effect (NREE) in these magnets exhibits a distinct phenomenology compared to the relativistic EE, characterized by a strongly anisotropic response and an out-of-plane polarized spin density resulting from the spin symmetries. We illustrate the NREE through minimal tight-binding models, allowing a direct comparison to different systems. Through first-principles calculations, we further identify the nodal p-wave candidate material CeNiAsO as a high-efficiency NREE material, revealing a ~ 25 times larger response than the maximally achieved relativistic EE and other reported NREE in non-collinear magnetic systems with broken time-reversal symmetry. This highlights the potential for efficient spin-charge conversion in p-wave magnetic systems
Dissecting substrate recognition by GID Ubiquitin ligases
Get PDFProtein degradation is an essential process for maintaining the health of the cell, with a variety of different functions in the maintenance of homeostasis, regulation of processes in the cell, the response to environmental stresses, and quality control of the proteome. Perturbation of this system leads to a variety of diseases, including neurodegenerative diseases such as Alzheimer's disease or frontotemporal dementia.
To degrade proteins, the cell uses two main pathways, autophagy and the ubiquitin proteasome system, the latter of which will be the focus of this study. In this pathway, ubiquitin is attached to substrate proteins by the action of E3 ligases. One such E3 ligase of rising importance is the GID/CTLH complex, which was originally found to be involved in the degradation of gluconeogenic enzymes starting with proline via its substrate receptor Gid4. In more recent years, further substrate receptor proteins have been discovered for the GID complex with Gid10 and Gid11, together with the complex’s ability to non-canonically recognize substrates via WDR26 in human cells.
Thus far, Gid11 is relatively poorly understood, besides it seeming to recognize N-terminal threonine residues. One of the aims of this study is to better characterize Gid11, analyze its substrate specificities, and identify residues or regions within Gid11 important for substrate recognition. For this purpose, this study the tandem-fluorescent timer approach was used. This study highlights the importance of the third intrinsically disordered region of Gid11, as well as a variety of residues within its binding pocket. Furthermore, it shows that N-termini recognized by Gid11 are usually non-acetylated. Additionally, the Gid11-dependent turnover of two proteins without threonine N-degrons was investigated, leading to the hypothesis that Blm10 is potentially recognized via the fifth intrinsically disordered region of Gid11. A potential example of trans-ubiquitination of Cpa1 via recognition of its complex partner Cpa2 was investigated and disproven.
There are several more proteins such as Hsm3 whose turnover depends on the GID complex, but which do currently not possess a known substrate receptor. Using overexpression of potential substrate receptors to compete for the binding of Gid5, it could be shown that this approach is a viable strategy to find additional, currently unknown Gid5-dependent substrate receptor proteins of the GID complex.
Additional experiments were conducted to investigate the functional conservation of various GID components, both in different yeast species in case of Gid11, and in human cells in the case of core GID components, showing that most human homologs of GID components are non-functional in yeast.
As a side project, the specificity of human ATE1, NTAN1, and NTAQ1 was investigated, highlighting differences between these enzymes and their human counterparts.
Overall, this study provides a characterization of Gid11, its substrate specificities, and identifies several key features necessary for its function. Furthermore, it highlights potential ways to identify further, currently unknown substrate receptors of the GID complex.Proteinabbau ist ein essenzieller Prozess zur Aufrechterhaltung der Zellgesundheit und erfüllt eine Vielzahl von Funktionen wie die Aufrechterhaltung der Homöostase, die Regulation zellulärer Prozesse, die Antwort auf Umweltstress und die Qualitätskontrolle des Proteoms. Eine Störung dieses Systems führt zu einer Vielzahl von Krankheiten, darunter neurodegenerative Erkrankungen wie Alzheimer oder frontotemporale Demenz.
Zum Proteinabbau nutzt die Zelle zwei Hauptwege: Autophagie und das Ubiquitin-Proteasom-System, wobei Letzteres im Fokus dieser Arbeit steht. In diesem Weg werden Zielproteine durch E3-Ligasen mit Ubiquitin markiert. Eine zunehmend bedeutsame E3-Ligase ist der GID/CTLH-Komplex, der ursprünglich für den Abbau von Glukoneogenese-Enzymen mit N-terminalem Prolin durch den Substratrezeptor Gid4 beschrieben wurde. In den letzten Jahren wurden mit Gid10 und Gid11 weitere Substratrezeptoren entdeckt sowie eine nicht-kanonische Substraterkennung über WDR26 in menschlichen Zellen beschrieben.
Gid11 ist bislang nur unzureichend charakterisiert, abgesehen davon, dass es N-terminale Threoninreste erkennt. Ein Ziel dieser Arbeit ist es, Gid11 näher zu charakterisieren, dessen Substratspezifitäten zu analysieren und wichtige Bereiche oder Aminosäuren für die Substraterkennung zu identifizieren. Hierfür wurde die Tandem-Fluoreszenz-Timer-Methode verwendet. Die Ergebnisse zeigen die Bedeutung der dritten intrinsisch ungeordneten Region von Gid11 sowie diverser Reste in der Bindungstasche. Zudem wird gezeigt, dass N-Termini, die durch Gid11 erkannt werden, in der Regel nicht acetyliert sind. Darüber hinaus wurde der Gid11-abhängige Abbau zweier Proteine ohne Threonin-N-degron untersucht, was zur Hypothese führte, dass Blm10 möglicherweise über die fünfte ungeordnete Region von Gid11 erkannt wird. Ein mögliches Beispiel für trans-Ubiquitinierung von Cpa1 über dessen Komplexpartner Cpa2 konnte widerlegt werden.
Es existieren weitere Proteine, wie Hsm3, deren Abbau vom GID-Komplex abhängt, für die jedoch bisher kein Substratrezeptor bekannt ist. Durch Überexpression potenzieller Substratrezeptoren konnte gezeigt werden, dass diese Methode geeignet ist, bisher unbekannte Gid5-abhängige Substratrezeptoren des GID-Komplexes zu identifizieren.
Weitere Experimente untersuchten die funktionelle Konservierung verschiedener GID-Komponenten sowohl zwischen unterschiedlichen Hefespezies im Fall von Gid11 als auch in menschlichen Zellen bei Kernkomponenten des GID-Komplexes. Dabei zeigte sich, dass die meisten humanen Homologe in Hefe nicht funktional sind.
In einem Nebenprojekt wurde zudem die Spezifität von humanem ATE1, NTAN1 und NTAQ1 untersucht, wobei Unterschiede zwischen diesen Enzymen und ihren Hefehomologen festgestellt wurden.
Insgesamt liefert diese Arbeit eine Charakterisierung von Gid11, seiner Substratspezifität sowie Schlüsselfaktoren, die für seine Funktion notwendig sind. Außerdem werden mögliche Ansätze zur Identifizierung weiterer, bislang unbekannter Substratrezeptoren des GID-Komplexes aufgezeigt.V, 131 Seiten ; Illustrationen, Diagramm
Drops on lubricated polymer brushes and gels
Get PDFIn this thesis, we engage with the physics of drops deposited on polymer brushes and gels that can also be swollen by a lubricant. We discuss results from simulation, theory, and experiment at three different levels: equilibrium, approach towards equilibrium, and steady state dynamics.
At the level of equilibrium, we use Molecular Dynamics (MD) simulations using the Many-body Dissipative Particle Dynamics (MDPD) model. We tune our model to emulate a water drop on a PDMS substrate. To characterize the brush, we find the point where it is saturated with lubricant and the corresponding brush height. In addition, we calculate the surface tension for different lubricant fractions. We show that the contact angle should theoretically be independent of the swelling of the brush. Afterwards, we show that drops deposited on lubricated polymer brushes undergo a cloaking transition, where the drop becomes covered by a film of lubricant. The transition sets in after a particular amount of lubricant is infused in the brush, a result which is supported by a theoretical thermodynamic analysis of the system. For spherical drops on dry brushes we reveal the presence in MDPD of a line tension that promotes the spreading of the drop. On lubricated brushes, the relation is not as transparent, though we do see a dependence of contact angles on the size of the drop. We also find that the brush in the area of the wetting ridge is swollen to a height that is close to the height at saturation, especially after the cloaking transition sets it. We complement our results for spherical drops with an analysis of cylindrical drops to eliminate the effect of line tension. In terms of the cloaking transition the results for both spherical and cylindrical drops are consistent. However, we see opposite behavior for the contact angle as a function of the lubricant fraction in the brush, which is indicative of a possible dependence of line tension on the swelling of the brush.
To study the approach towards equilibrium, our experimental collaborators ran experiments where a glycerol drop was deposited on PDMS gels swollen with high viscosity silicone oils. There, the lubricant separates from the gel so that the wetting ridge has a liquid component. We show that as the ridge grows, it does so in a geometrically similar fashion, maintaining the same shape. The separation height between the apex of the wetting ridge and the gel is followed through time and shown to depend on both the degree of swelling and the viscosity of the oil. We support the experimental findings with a theoretical model based on diffusion, and find that the results agree very well with the experiments for saturated gels, but not so much for undersaturated ones. To follow the approach towards equilibrium in terms of cloaking, we perform experiments where a drop is pending from a swollen gel, and follow the evolution of the shape with time. Unfortunately, few conclusions could be drawn from the experiments due to a lack of reproducibility. In addition, we perform numerical simulations using the MDPD model to follow the cloaking away from equilibrium. We find that the cloak front progresses on the drop linearly with time, with the rate increasing with the fraction of oil. Additionally, the cloak creeps onto the drop as it thickens simultaneously, and continues to get thicker after it covers the entire drop. We also find that the distribution of lubricant throughout the brush is consistent with our assumption that the time scale is set through the diffusion of lubricant across the brush.
Finally, we address the steady state dynamics of drops moving on lubricated polymer brushes. The results of our experimental collaborators for water drops on PDMS brushes reveal an asymptotic power law relation between the dissipated power and the velocity of the drop. Our numerical simulations also show such a power law, albeit with different exponents. The exponent in the experiments is the same for two preparation methods of the brush. Meanwhile, in simulation, the exponent depends weakly on the swelling of the brush. To understand the discrepancy and the dissipation mechanisms that influence the exponent, we quantify the height of the wetting ridge and the flow field inside the drop. The analysis rules out slip as a major contributor to dissipation, but neither viscous dissipation in the drop nor viscoelastic dissipation in the brush can be ruled out at this stage. Instead, we find that the viscoelastic dissipation can remain relevant even at high velocities since the wetting ridge does not vanish at any velocity; in addition, the flow field inside the drop is complex with the possible presence of multiple vortices, and can possibly explain the observed exponents.viii, 209 seiten ; Illustrationen, Diagramm
G8 geriatrischer Screening Fragebogen als unabhängiger Prognosefaktor für das postoperative progressionsfreie Überleben älterer Patientinnen mit Ovarialkarzinomen – Ergebnisse einer retrospektiven, unizentrischen Kohortenstudie
Get PDFV, 70 Seiten ; Illustrationen, Diagramm
„Non-Surgical Assisted Rapid Maxillary Expansion“ (N-SARME) – Untersuchung eines modifizierten Drehprotokolls zur erfolgreichen Gaumennahterweiterung beim Erwachsenen
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Alveolar ridge augmentation in Oral and Maxillofacial Surgery : a study on current practices, patient management and innovations in Germany
Get PDFIntroduction
This study identifies current practices, patient management concepts and innovations in alveolar ridge augmentation (ARA) in Oral and Maxillofacial Surgery (OMFS) in Germany.
Material and methods
A survey with a dynamic online questionnaire with up to 40 questions was designed to collect general and specific data on ARA, such as case numbers, imaging, surgical techniques, (bio-)materials, and case management in OMFS. After internal and external validation, 1863 OMF surgeons within the German Association for Oral and Maxillofacial Surgery (DGMKG) were invited via email to participate. Data management was anonymized and descriptively.
Results
324 OMF surgeons participated in the study (response rate 17.39%). Most participants (60.8%) work in private practices without inpatient care. 62.03% of participants insert > 200 implants, and 28.70% perform > 200 ARA annually. About 30.86% also provide implant-based prosthetic restorations. Cone-beam computed tomography (CBCT) is the imaging method most preferred by 87.74% of participants. The most common ARA techniques are external and internal sinus lift (SL) and bone block augmentation (97.31%, 90.57%, and 73.4%, respectively). Intraoral harvested autogenous bone grafts (ABG) are most commonly used for ARA (96.63%). The oblique line is the participants’ preferred donor site for ABG (93.27%). ABG and xenogeneic bone substitutes are the most frequently used graft combinations (72.73%). Platelet-rich fibrin (PRF) is used by 58.59% of participants for ARA, mostly in SL procedures (76.44%). PRF is the most common substitute used to biofunctionalize biomaterials (48.16%). Oral antibiotics are used by 86.40% pre-/intraoperatively and by 88.97% postoperatively for ARA. Most participants believe the surgical technique (94.49%) and the surgeon's experience (92.28%) are the most critical factors for ARA success. 46.32% of participants aim to perform ARA within the skeletal envelope.
Conclusion
The findings highlight current practices, patient management, and innovations in ARA in OMFS in Germany. They show standard practices and numerous variations in several aspects.
Clinical relevance
Surgical technique, experience, patient health and compliance are relevant ARA success factors. This underlies the importance of extended surgical training and careful patient selection
Die Antwortqualität von künstlicher Intelligenz und Zahnärzten/-innen im Vergleich - Kommunikation in der Zahnmedizin
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Quality assessment of a training program for undergraduate sonography peer tutors : paving the future way for peer-assisted learning in medical ultrasound education
Get PDFIntroduction: Peer tutoring has been increasingly used to support university sonography teaching, necessitating well-qualified tutors. This study aims to evaluate the quality of a training program for sonography peer tutors developed and implemented at a university hospital.
Materials and methods: A training program consisting of 11 modules was developed and subsequently evaluated for success with two subjective and two objective assessments of peer-tutoring quality. The two subjective assessments measured subjective scores of the peer tutors’ specialist and didactic skills using a Likert scale (1 = very low; 7 = very high) from the perspective of the individuals the peer tutor taught (assessment 1) and from the peer tutors themselves (assessment 2). The peer tutors also rated the training concept itself. The objective assessments evaluated the peer tutors’ specialist skills with a theoretical test (assessment 3) and a practical examination (assessment 4). Data collection for assessment 1 began in 2017, while data for assessments 2 to 4 were collected from 2021 to 2024.
Results: A total of 2,980 data sets for assessment 1, 92 data sets for 2, 44 data sets for assessment 3, and 147 data sets for assessment 4 were included in the analysis. Peer tutors scored highly positively on assessments 1 [6.6 ± 0.63 scale points (SP)] and 2 (5.53 ± 0.63 SP), and these results remained consistently high throughout the semesters. Assessments 3 (74.7 ± 7.9%) and 4 (85.6 ± 10.5%) also showed strongly positive values that remained constant over time. Assessment 1 results were significantly higher than the others (p < 0.01.), while no significant differences were found between assessments 2, 3, and 4.
Conclusion: The data indicate that the training concept developed established and maintained high-quality peer-tutor training throughout the reviewed semesters. Future efforts should promote the development of national and international standards for peer-tutor training and provide certification opportunities for peer tutors
Durchführung, Komplikationen und Entwöhnungsergebnisse nach Punktionstracheotomie bei Patienten nach Herz-Operationen Retrospektive Auswertung aus der Klinik für Herz-, Lungen- und Gefäßchirurgie des Westpfalz-Klinikums Kaiserslautern
Get PDFHintergrund:
Patienten nach Herzoperationen weisen häufig ein erhöhtes Risiko für eine prolongierte Beatmung auf. Die perkutane dilatative Tracheotomie (PDT) hat sich als standardisiertes, sicheres und effizientes Verfahren etabliert, um die Atemwegssicherung und das Weaning zu erleichtern. Dennoch fehlen spezifische Daten zu Ergebnissen und Prädiktoren des Entwöhnungserfolgs bei herzchirurgischen Patienten.
Methoden:
Es wurde eine retrospektive Analyse aller konsekutiven Patienten durchgeführt, die zwischen Januar 2019 und Dezember 2022 nach Herzoperationen auf der Intensivstation des Westpfalz-Klinikums Kaiserslautern mittels PDT behandelt wurden. Erfasst wurden demografische Daten, perioperative Parameter, Komplikationen sowie Weaning-Ergebnisse. Es erfolgten uni- und multivariate statistische Analysen zur Identifikation relevanter Risikofaktoren.
Ergebnisse:
In die Studie gingen 87 Patienten ein. Die PDT mittels Ciaglia Blue Rhino wurde in allen Fällen erfolgreich durchgeführt. Die durchschnittliche Eingriffsdauer betrug 13,1 ± 8,2 Minuten. Intraoperative Komplikationen waren selten; am häufigsten trat eine Blutung auf (7,9%). Es kam zu keinem Pneumothorax, keiner Hypoxie und keiner akzidentellen Extubation. Postoperativ traten Blutungen (8%), lokale Infektionen (3,4%) und Mediastinitiden (2,3%) auf; 2 Patienten (2,3%) mussten auf eine chirurgische Tracheotomie umgestellt werden.
Die Entwöhnung gelang bei 65,5% der Patienten. Die Mortalität lag bei 27,6%, wobei kein Todesfall durch die Tracheotomie verursacht wurde. In der univariaten Analyse waren ein niedrigeres Alter, niedrigere präoperative CRP-Werte und ein geringerer SOFA-Score mit einer erfolgreichen Entwöhnung assoziiert. In der multivariaten Analyse blieb ein niedriger präoperativer CRP-Wert der einzige unabhängige Prädiktor.
Schlussfolgerung:
Die PDT ist bei herzchirurgischen Patienten mit prolongierter Beatmung ein sicheres Verfahren mit niedriger Komplikationsrate. Ein niedriger präoperativer CRP-Wert erwies sich als unabhängiger Prädiktor für ein erfolgreiches Weaning. Diese Erkenntnisse können helfen, den optimalen Zeitpunkt der Tracheotomie und die Weaningstrategien zu verbessern.Background:
Prolonged mechanical ventilation is common among cardiac surgery patients with complex comorbidities. Percutaneous dilatational tracheotomy (PDT) has become an important technique in modern intensive care, offering advantages such as reduced invasiveness, lower complication rates, and facilitated weaning. However, data on outcomes, complications, and predictors of successful weaning in cardiac surgery patients remain limited.
Methods:
This retrospective study analyzed all consecutive adult patients who underwent PDT in the cardiothoracic ICU of Westpfalz-Klinikum Kaiserslautern between January 2019 and December 2022 following cardiac surgery. Clinical, perioperative, and postoperative data—including demographics, procedural details, complications, oxygenation indices, and weaning outcomes—were collected and evaluated. Univariate and multivariable statistical analyses were performed to identify predictors of mortality and successful weaning.
Results:
A total of 87 patients were included. PDT was successfully performed using the Ciaglia Blue Rhino technique in all cases. The mean procedure time was 13.1 ± 8.2 minutes. Intraoperative complications were low, with bleeding (7.9%) being the most frequent. No cases of pneumothorax, hypoxia, or accidental extubation occurred. Postoperative complications included bleeding (8%), local infection (3.4%), mediastinitis (2.3%), and conversion to surgical tracheotomy (2.3%).
Weaning was successful in 65.5% of patients, while 27.6% died during hospitalization (none procedure-related). Univariate analysis identified younger age, lower SOFA score, and lower preoperative CRP levels as predictors of successful weaning. In multivariable analysis, only preoperative CRP remained an independent predictor (p = 0.044). Increased mortality was independently associated with longer pre-PDT intubation duration and higher preoperative CRP.
Conclusion:
Percutaneous dilatational tracheotomy is a safe and effective procedure for cardiac surgery patients requiring prolonged ventilation, with low complication rates when performed under bronchoscopic guidance. A lower preoperative CRP level was identified as a significant independent predictor of successful weaning, highlighting the importance of inflammatory status in clinical decision-making. Early identification of factors influencing weaning outcomes may improve patient recovery and optimize ICU resource utilization.III, 44 Seiten ; Illustrationen, Diagramm
