Gutenberg Open Science (Univ. Mainz)
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Unraveling cooperative and competitive interactions within protein triplets in the human interactome
Get PDFKnowledge of protein–protein interactions (PPIs) is essential for understanding cellular function, yet most network analyses focus on binary interactions. Higher-order motifs such as protein triplets can reveal cooperative or competitive relationships but are difficult to distinguish systematically. We present a computational framework to classify protein triplets in the human protein interaction network (hPIN) as cooperative or competitive. The hPIN was embedded in hyperbolic space using the LaBNE + HM algorithm, and a Random Forest classifier was trained on structurally validated triplets from Interactome3D, achieving high accuracy (AUC = 0.88). Angular and hyperbolic distances were key predictive features. Predicted cooperative triplets were enriched in paralogous partners, indicating that paralogs often bind together to a shared protein using non-overlapping surfaces. The model proved to be effective when tested on a new dataset. AlphaFold 3 modeling supported these predictions, showing that cooperative partners bind at distinct sites, while competitive ones overlap. Our results demonstrate the value of hyperbolic geometry for capturing functional organization in protein complexes
The relationship between hair cortisol and trauma sequelae in motor vehicle crash survivors: the role of childhood trauma experiences
Get PDFPrevious research highlights inconsistent associations between premorbid hair cortisol concentrations (HCC) and posttraumatic stress disorder (PTSD) symptoms, often neglecting the critical role of childhood trauma (CT) in civilian populations. To address this gap, our study investigates the predictive value of HCC for PTSD symptoms following a motor vehicle crash (MVC), extending our prior findings by assessing CT as a moderator within a sample that includes participants with and without CT. We hypothesize that pre-MVC HCC is positively associated with PTSD risk and that this relationship is moderated by early adversity. We examined N = 272 participants with a traumatic brain injury aged 18–65 years who experienced a MVC between 2010 and 2020. Cortisol concentrations were determined in 3 cm scalp-near segments of hair samples that were obtained at the emergency room shortly after the MVC (t1). Participants completed measuring instruments capturing symptoms of posttraumatic stress (Posttraumatic Diagnostic Scale [PDS]; Impact of Event Scale-Revised [IES-R]) and Childhood Trauma Questionnaire (CTQ). PDS and IES-R were re-collected three months post-MVC (t2). Elevated pre-MVC HCC predicted PTSD symptoms (p < 0.05), emphasizing the role of chronic stress and HPA axis dysregulation in PTSD. Contrary to our hypothesis, CT did not moderate this relationship, suggesting that HCC’s impact on PTSD is independent of early adverse experiences. In this context, CT emerged as an independent predictor of PTSD at the 3-month follow-up, underscoring its lasting influence on psychological trauma vulnerability, particular in the face of recent adversity. Our study confirmed that elevated pre-MVC HCC levels predict PTSD symptoms. Although childhood trauma did not moderate this relationship, it independently predicted PTSD at follow-up. These findings underscore the lasting impact of early adversity on mental health, highlighting the importance of considering both HPA axis regulation and trauma history to develop targeted interventions for adults exposed to new stressors
Dramatic effect of alkali metal alkoxides on the anionic copolymerization of styrene and isoprene
Get PDFThe effect of lithium, sodium, and potassium tert-amylates on the kinetics of the statistical anionic copolymerization of styrene and isoprene in cyclohexane was investigated using in situ near-infrared (NIR) spectroscopy. The reactivity ratios and the related comonomer gradients can be adjusted over the entire range resulting in both random and inverted gradient copolymers. Lithium tert-amylate retards the polymerization at overstoichiometric concentrations. In contrast, even at low concentrations, sodium and potassium tert-amylate increase the rate of styrene polymerization due to a counterion exchange. Only 1/30 equiv of potassium tert-amylate relative to butyllithium is necessary to obtain random copolymers, which unexpectedly consist of short blocks. Remarkably, a high content of isoprene 1,4-units is maintained, leading to a low glass transition temperature of −55 °C of random or inversely tapered poly(styrene-co-isoprene). Thus, in contrast to Lewis base modifiers, the diene microstructure can be decoupled from reaction kinetics, when potassium alkoxides are used
Proximalization of the distal anastomosis in frozen elephant trunk surgery
Get PDFBackground:
The frozen elephant trunk (FET) technique is frequently used in aortic arch diseases. Proximalization of the distal anastomosis from zone 3 to zone 2 results in shorter distal ischemia times and improved outcomes. This study assessed the impact of performing distal anastomoses progressively more proximally.
Methods:
A total of 243 patients treated between March 2016 and December 2023 were identified using our institutional database, and relevant data were analyzed retrospectively. The patients were stratified according to the distal anastomosis zone, and perioperative and outcome variables were compared. A subgroup analysis was performed accordingly for patients with acute aortic dissections.
Results:
Most of the 243 included patients (66%) were treated for acute dissection, followed by chronic dissection (24%) and thoracic aortic aneurysms (10%). The patients’ mean age was 62.5 ± 10.8 years, and 175 patients (72%) were male. The distal ischemia time was significantly reduced with the more proximal anastomoses: 24.5 minutes for zone 0 (69 patients), 37.4 minutes for zone 1 (18 patients), 30.4 minutes for zone 2 (145 patients), and 38.7 minutes for zone 3 (11 patients); P < .001. A longer cross-clamping time in zone 0 was explained by the higher number of root procedures, while other outcome parameters showed no significant differences. These same significant differences also were present in the acute dissection subgroup. In a separate analysis, a shorter duration of distal ischemia correlated with improved long-term survival (P = .002).
Conclusions:
The FET technique with distal anastomosis in zone 2 is a reliable technique that produces good results. Proximalization of the distal anastomosis to zone 0 significantly reduces the ischemic burden and simplifies the procedure
Case presentation of a robot-assisted bilateral benign tonsillectomy using the da Vinci SP system
Get PDFSince the first use of a da Vinci system to perform a radical tonsillectomy in 2007, transoral robotic surgery (TORS) has been further developed and finally accepted as a safe surgical method. The recent introduction of the da Vinci Single-Port (SP) system has brought new innovations in the field of ears, nose and throat (ENT) medicine, e.g. to perform minimally invasive head and neck tumor surgery. In Europe, the da Vinci SP system has recently received CE Mark approval for TORS application.We present the first case of a robot-assisted bilateral benign tonsillectomy with the da Vinci SP system in Germany and demonstrate the technical feasibility of this platform
Observation of a non-reciprocal skyrmion Hall effect of hybrid chiral skyrmion tubes in synthetic antiferromagnetic multilayers
Get PDFA hybrid chiral skyrmion tube is a well-known example of a 3D topological spin texture, exhibiting an intriguing chirality transition along the thickness direction. This transition progresses from left-handed to right-handed Néel-type chirality, passing through a Bloch-type intermediate state. Such an exotic spin configuration potentially exhibits distinctly different dynamics from that of the common skyrmion tube that exhibits a homogeneous chirality; yet these dynamics have not been ascertained so far. Here, we reveal the distinct features of current-induced dynamics that result from the hybrid chiral skyrmion tube structure in synthetic antiferromagnetic (SyAFM) multilayers. Strikingly, the SyAFM hybrid chiral skyrmion tubes exhibit a non-reciprocal skyrmion Hall effect in the flow regime. The non-reciprocity can even be tuned by the degree of magnetic compensation in the SyAFM systems. Our theoretical modeling qualitatively corroborates that the non-reciprocity stems from the dynamic oscillation of skyrmion helicity during its current-induced motion. The findings highlight the critical role of the internal degrees of freedom of these complex skyrmion tubes for their current-induced dynamics
Transformer semantic genetic programming for symbolic regression
Get PDFIn standard genetic programming (stdGP), solutions are varied by modifying their syntax, with uncertain effects on their semantics. Geometric-semantic genetic programming (GSGP), a popular variant of GP, effectively searches the semantic solution space using variation operations based on linear combinations, although it results in significantly larger solutions. This paper presents Transformer Semantic Genetic Programming (TSGP), a novel and flexible semantic approach that uses a generative transformer model as search operator. The transformer is trained on synthetic test problems and learns semantic similarities between solutions. Once the model is trained, it can be used to create offspring solutions with high semantic similarity also for unseen and unknown problems. Experiments on several symbolic regression problems show that TSGP generates solutions with comparable or even significantly better prediction quality than stdGP, SLIM_GSGP, DSR, and DAE-GP. Like SLIM_GSGP, TSGP is able to create new solutions that are semantically similar without creating solutions of large size. An analysis of the search dynamic reveals that the solutions generated by TSGP are semantically more similar than the solutions generated by the benchmark approaches allowing a better exploration of the semantic solution space
Phenomenology of leptogenesis: From cosmological phase transitions to new mechanisms and experimental probes
Get PDFThis thesis addresses several aspects of leptogenesis, a theoretical paradigm that attempts to resolve two prominent open questions in high-energy phenomenology: the origin of neutrino masses and the observed baryon asymmetry of the universe (BAU).
The thesis is structured into three parts, with the first part focusing on first-order phase transitions (FOPTs) and cosmic strings (CSs) within the context of gauged extensions of the Standard Model (SM). Initially, we re-examine the FOPT and gravitational-wave (GW) production in the classically conformal model, identifying regions of parameter space that provide optimal conditions for bubble-assisted leptogenesis. Subsequently, we investigate the production of right-handed neutrinos (RHNs) from CSs and assess the magnitude of the asymmetry that they may source.
The second part of this thesis is dedicated to the recently proposed wash-in leptogenesis (WILG) mechanism, which does not require any violation in the RHN sector. Specifically, we derive a lower bound on the mass of the lightest RHN by requiring WILG to successfully account for the observed BAU. Moreover, we introduce a novel ultraviolet mechanism for WILG based on non-minimal gravitational interactions.
In the final part of this thesis, we present novel strategies to search for new physics (NP) in rare Kaon and -meson decays, focusing on the channels K\rightarrow \pi+\slashed{E}, B\rightarrow K(K^*)+\slashed{E}, and B\rightarrow X_s+\slashed{E}. We demonstrate that careful measurements of the kinematic distributions of missing energy can serve as a powerful tool to distinguish between the effective operators contributing to NP. Particular attention is devoted to lepton-number-violating (LNV) NP, and how observing LNV NP in rare meson decays could put leptogenesis under tension.xi, 242 Seiten ; Illustrationen, Diagramm
Polyamines regulate adaptive antitumor immunity by functional specialization of regulatory T cells
Get PDFIn cancer, metabolic changes and uncontrolled tumor growth alter nutrient availability, impacting antitumor immune responses. Regulatory T (Treg) cells are a subset of T cells with immunosuppressive properties that can also influence tissue homeostasis and repair. However, it is not known how these functions are molecularly controlled and whether they are influenced by tumor metabolism. Here, we report that excessive release of polyamines in the tumor microenvironment directs the functional polarization of Treg cells toward immunosuppression in a protein kinase CK2 (CK2)-dependent manner. Polyamine deprivation as well as genetic or pharmacological inhibition of CK2 activity in Treg cells induced tissue reparative properties in Treg cells that orchestrated efficient antitumor type 2 immune responses and coordinated tissue repair mechanisms to support tumor eradication. These findings suggest that targeted modulation of Treg cell functions could be leveraged as a potential avenue for cancer therapy
