12762 research outputs found
Sort by
Controlling few-body reaction pathways using a Feshbach resonance
Gaining control over chemical reactions at the quantum level is a central goal of cold and ultracold chemistry. Here we demonstrate a method for coherently steering the reaction flux across different product spin channels for a three-body recombination process in a cloud of trapped cold atoms. We use a magnetically tunable Feshbach resonance to admix, in a controlled way, a specific spin state to the reacting collision complex. This allows us to control the reaction flux into the admixed spin channel, which can be used to alter the reaction products. We also investigate the influence of an Efimov resonance on the reaction dynamics, observing a global enhancement of three-body recombination without favouring particular reaction channels. Our control scheme can be extended to other reaction processes and could be combined with other methods, such as quantum interference of reaction paths, to achieve further tuning capabilities of few-body reactions
Einseitige Abszesstonsillektomie gemäß Leitlinienempfehlung - Langzeitergebnisse
Durch die 2015 veröffentlichte Sk2-Leitlinie der AWMF „Therapie entzündlicher Erkrankungen der Gaumenmandeln – Tonsillitis“ wurde das Operationsverfahren von einer Abszesstonsillektomie und gleichzeitiger Tonsillektomie der Gegenseite zu einer einseitigen Abszesstonsillektomie umgestellt.
Durch diese Arbeit sollte anhand einer retrospektiven Befragung von Patienten, welche eine einseitige Abszesstonsillektomie im Zeitraum 2015 bis 2020 an der Hals-Nasen-Ohren-Uniklinik Ulm erhielten, erörtert werden, ob ein Langzeitergebnis und Langzeiterfolg im Sinne der Vermeidung einer weiteren Operation auf der gleichen oder anderen Seite nach einer einseitigen Abszesstonsillektomie zu erfassen ist.
Die durch die Leitlinie festgelegten Entscheidungsgrundlagen zur einseitigen Peritonsillarabszess berücksichtigen keine Risikofaktoren. Somit stellt sich die Frage, ob bei Vorliegen bestimmter Risikofaktoren nicht ohnehin verstärkt mit einer späteren Entfernung der Gegenseite zu rechnen ist und man aufgrund dessen gleichzeitig eine beidseitige Entfernung vornehmen sollte. Als Langzeitergebnis durch Auswertung der Befragung konnte festgestellt werden, dass insbesondere männliche Personen, junges Alter und Nikotinkonsum als Risikofaktoren für eine erneute Operation festzulegen sind. Dies ist auch durch aktuellen Stand der Literatur belegbar.
Somit ist die einseitige Abszesstonsillektomie ohne Tonsillektomie der Gegenseite als Langzeiterfolg im Sinne der Vermeidung einer weiteren Operation auf der gleichen oder anderen Seite zu sehen und wird unter Berücksichtigung bestimmter Risikofaktoren als geeignetes Operationsverfahren empfohlen. Zudem ist das postoperative Nachblutungsrisiko bei nur einseitiger Abszesstonsillektomie deutlich reduziert.The Sk2 guideline published in 2015 by AWMF „Therapie entzündlicher Erkrankungen der Gaumenmandeln – Tonsillitis“ changed the surgical procedure from abscess tonsillectomy and simultaneous tonsillectomy of the opposite side to unilateral abscess tonsillectomy.
The aim of this study was to use a retrospective survey of patients who underwent unilateral abscess tonsillectomy at the Hals-Nasen-Ohren-Uniklinik Ulm between 2015 and 2020 to determine whether a long-term outcome and long-term success in terms of avoiding further surgery on the same or opposite side after unilateral abscess tonsillectomy can be recorded.
The decision-making basis for unilateral peritonsillar abscesses defined by the guideline does not take risk factors into account. This raises the question of whether, in the presence of certain risk factors, a later removal of the opposite side is not to be expected anyway and whether a bilateral removal should be carried out at the same time due to this. As a long-term result of analysing the survey, it was found that males, young age and nicotine consumption in particular are risk factors for a repeat operation. This can also be confirmed by the current state of the literature. This means that unilateral abscess tonsillectomy without tonsillectomy of the opposite side can be seen as a long-term success in terms of avoiding further surgery on the same or other side and is recommended as a suitable surgical procedure, taking certain risk factors into account. In addition, the postoperative risk of post-operative haemorrhage is significantly reduced with only unilateral abscess tonsillectomy
Statistical Computing 2025 : Abstracts der 55. Arbeitstagung
Statistical Computing 2025. Abstracts der 55. Arbeitstagung Statistical Computing (GMDS/IBS-DR), Klassifikation und Datenanalyse in den Biowissenschaften (GfKl), 2025-07-27 - 2022-07-30, Schloss Reisensburg, Günzburg
Battery properties elucidated by quantum chemical calculations
The rechargeable alkali-ion battery has emerged as a transformative technology, revolutionizing portable energy storage in a wide range of applications, from small electronic devices to large electric vehicles. In this review, we combine modern theoretical and computational methods with an examination of electrochemical properties for lithium and post lithium-ion batteries. From fundamental thermodynamics and kinetics to computational techniques for materials design, we examine frameworks for deriving relationships for key battery properties such as voltage and capacity. We also explore the complexities of ion migration processes, including hopping mechanisms between lattice sites, and extend our focus to the broader field of electrochemical properties, including conductivity, redox potentials and interfacial properties. Finally, we outline perspectives on the outstanding challenges and promising opportunities in the theory and computation of rechargeable battery materials, paving the way for future advances in energy storage technology
Adaptive caching for operation-based versioning of models : Adaptive caching for operation-based...
Abstract
In a collaborative multi-user model-driven engineering context, it becomes important to track who changed what model part how and why. Operation-based versioning addresses this need by persisting a meaningful edit history which enables a single user to navigate through a model’s evolution over time, to analyze arbitrary previous model versions, or to trace the impact of an operation. However, to load a distinct prior version, it must be restored by reapplying all previous operations, which is time-consuming and, thus, interrupts a user’s workflow. Caching with a fixed distance between caches helps to overcome this problem to the cost of increasing memory requirements. Further, there is no caching approach supporting branches, merges, and possibly resolved conflicts. We propose two advanced caching strategies for operation-based versioning capable of the previously mentioned features: zonal and adaptive caching. Both strategies reduce the memory in use by not applying the same static distance between two caches across the whole edit history. Instead, the distance increases depending on a version’s age and its distance to a branch’s head. Both strategies aim to reduce the restoration time of arbitrary prior versions below a threshold to not interrupt a user’s flow of thought. Zonal caching employs predefined distances compatible with a broad range of model sizes. In contrast, adaptive caching derives the distances individually depending on the initial time to load the model on a user’s computer and the model’s size.We conducted controlled experiments with models of varying sizes and compared the time to restore model versions and the memory in use for no caching, caching with static distances, zonal, and adaptive strategies on different computers. The developed strategies decrease the time to restore a version remarkably while using less memory than static caching. Our results show that for all considered systems and models individual adaptive caching reduces memory usage even further compared to zone-based caching while still satisfying application responsiveness requirements
Barriers and Facilitators of Sleep Restriction Therapy in Internet-Delivered CBT-I : A Qualitative Content Analysis and the Development of a Treatment Path Model
Sleep Restriction Therapy (SRT) is a core component of cognitive behavioural therapy for insomnia (CBT-I). Yet, adherence to SRT can be a major challenge for patients. As this challenge is evident in conventional face-to-face therapy, it raises the question of adherence to SRT in internet-delivered therapy. This qualitative study investigates adherence to SRT in internet-delivered CBT-I and aims to identify candidate variables that can guide treatment decisions. Participants diagnosed with insomnia who participated in an internet-delivered CBT-I as part of a stepped-care model were interviewed. Data from interviews with 23 participants were included in this study. A qualitative content analysis was employed. Hindering and facilitating individual, intervention-related, and e-coaching-related factors were examined. Moreover, the consequences of SRT (e.g., negative effects and attrition) were examined. Eleven participants consistently implemented SRT, two rejected it from the beginning, eight discontinued, and two showed inconsistent adherence. Docility, low levels of frustration tolerance, and previous negative experiences with SRT emerged as hindering individual factors. In contrast, a high level of insomnia-related burden, social support, perceived individual fit with the program, and being satisfied with the therapeutic guidance appeared to foster adherence. Based on the results of this study, a treatment path model is introduced, postulating candidate predictors for the indication for SRT within internet-delivered CBT-I (e.g., docility and previous negative experiences with SRT), candidate predictors for engagement (e.g., level of commitment and social support), and potential variables for process monitoring (e.g., negative effects and satisfaction with and need for therapeutic guidance)
Einfluss der Nachresektion nach brusterhaltender Therapie auf die Häufigkeit lokoregionärer Rezidive und auf das Gesamtüberleben bei Patientinnen mit frühem Mammakarzinom
Ziel dieser Promotionsarbeit ist es, den Einfluss der Nachresektion nach brusterhaltender Therapie auf die Häufigkeit lokoregionärer Rezidive, auf das Gesamtüberleben und das rezidivfreie Überleben bei Patientinnen mit frühem Mammakarzinom zu bewerten. Beim Mammakarzinom wird nach einer brusterhaltenden Therapie mit positiven/ unklaren Schnitträndern entsprechend der Leitlinie eine Nachresektion (NR) empfohlen.
Darüber hinaus haben wir untersucht, ob der Nachweis eines residuellen Tumors in der Nachresektion mit dem Gesamtüberleben und dem rezidivfreie Überleben assoziiert ist
Novel sustainable polymer-materials as electrodes in energy storage devices
As global energy consumption continues to rise each year, so too does the need for sustainability across
all sectors, driven by the accelerating impact of anthropogenic climate change and the progressive
depletion of finite resources. Electrical energy storage is a key enabling technology across a wide range
of applications, from mobility and communication to various portable electronics, and must
simultaneously meet growing demands for energy and power density, safety, sustainable processing, and
environmental compatibility. This thesis explores the use of functional polymers to address these
challenges and contribute to the advancement of next-generation energy storage systems
Short-distance communication between glioblastoma cells and their microenvironment
Although survival rates for most cancers have shown encouraging improvements, Glioblastomas (GBs) remain an exception and still rank among the deadliest and most aggressive tumours, with an overall survival of only 8-15 months after diagnosis. Despite decades of intensive research, no significant breakthrough in GB treatment has been achieved, and patients have received the same treatment regimen since 2005: maximal safe surgery followed by radiotherapy and chemotherapy. The lack of significant progress is partly due to our limited understanding of the disease, including its tumour biology and the mechanisms that drive treatment resistance and lead to tumour recurrence.
To advance our understanding, suitable model systems are needed. Cell culture models provide a valuable opportunity to investigate fundamental disease processes and evaluate therapeutic compounds in an environment of low complexity. While traditional GB or non-tumour cell lines are limited in their ability to represent the characteristics of their primary tissue, patient-derived primary cells have emerged as a more accurate alternative. Over the past few years, our laboratory has established an exclusive repository of primary cells derived from non-tumour or GB tumour tissue, which were characterised in the first part of the present study. Through the analysis of marker expression and preliminary exploration of transcriptomic profiles, this study demonstrated that the primary cells successfully captured key in vivo features. Non-tumour cells were enriched for astrocytic markers, while primary GB cells captured intertumoural heterogeneity and reflected hierarchies along the stem cell-differentiation axis. These findings underscore the utility of our in vitro cell culture model. The transcriptomic data will serve as a tool for further hypothesis generation, which then can be rigorously tested in vitro
Using this primary cell culture model, the second objective of the present study aimed at investigating the role of connexins (Cxs) in GB. By forming intercellular channels known as gap junctions (GJs), Cxs facilitate the formation of extensive communication networks that are crucial for proper brain development and function. These networks support cellular homeostasis and enable coordinated cellular responses. GBs exploit these mechanisms to promote tumour growth, migration and cellular resistance towards therapy. Previous work in our lab using traditional GB cell lines demonstrated that GJ inhibition reduced viable cell numbers and sensitised cells to both spontaneous and therapy-induced cell death. Similar results were obtained in the present study when primary GB cells were treated with GJ inhibitors, further supporting the idea that Cxs and GJs contribute to GB’s aggressiveness, which was explored in greater detail in this study.
Historically, most research on Cxs/GJs in GB has focused on GJA1/Cx43, the prototypical astrocytic Cxs. However, given the diversity of Cxs and their distinct functional roles, this study aimed for a more comprehensive approach by first mapping the Cx expression pattern in GBs. We screened our exclusive repository of primary brain tumour-derived cells (n = 26) for the expression of all 21 human Cxs. Remarkably, two distinct Cx expression patterns were identified, which were associated with the morphological appearance of cultured neurospheres, suggesting that Cxs shape cellular interactions. Primary non-tumour cells (n = 2) displayed a distinct Cx expression pattern. When comparing brain tumours, particularly GBs, to non-tumour brains, most Cxs were found to be dysregulated, offering valuable insights warranting further investigations.
Among all Cxs, GJB2/Cx26 stood out due to its significantly increased expression levels in GBs. This overexpression was notable not only in comparison to other Cxs but also from a broader perspective. GJB2/Cx26 consistently showed prognostic significance, with high expression levels associated with shorter overall survival across all analysed cohorts. In the healthy brain, GJB2/Cx26 is expressed in various cell types and plays an important role in regulating proliferation, migration, and cellular communication networks during brain development. In GBs, GJB2/Cx26 expression was modulated by the TGF-β1 signalling axis and strongly associated with the mesenchymal subtype. Within the tumour, GJB2/Cx26 expression was highest in the core and correlated with the recently described connectivity signature, suggesting its potential involvement in tumour networks. When cultured in the presence of an extracellular matrix substrate, the CRISPR-Cas9-mediated knockout of GJB2/Cx26 in primary GB cells significantly impaired the cell´s ability to form morphological networks and disrupted cell-to-cell connectivity, emphasising the critical role of GJB2/Cx26 as a mediator of cellular connectivity in GB.
In summary, this study confirmed that primary tumour and non-tumour cells can recapitulate critical in vivo characteristics, emphasising their value as cell culture models. Additionally, it provided novel insights into the Cx biology of brain tumours, underscoring the pivotal role of GJB2/Cx26 in GBs and highlighting the intricate relationship between neurodevelopmental mechanisms and GB biology
Immune modulatory effects of head and neck cancer patient-derived sEVs through the NF-κB signaling pathway
Head and neck squamous cell carcinoma (HNSCC) is a highly immunosuppressive malignancy, which is often diagnosed at advanced stage and has not significantly improved therapy response of patients in recent years. Major risk factors for HNSCC are exposure to carcinogens, such as alcohol and tobacco, or infection with human papilloma virus (HPV), causing two distinct subtypes of HNSCC with differences in gene expression, mutational and immunological characteristics. HPV(+) HNSCC patients generally have better response to anti-tumor therapy, highlighting the need to develop new therapeutic strategies, which decrease therapy-associated toxicity and improve quality of life in HPV(+) HNSCC patients. Circulating small extracellular vesicles (sEVs) contribute to systemic immunosuppression and promote tumorigenesis in HNSCC patients. Furthermore, immune cells in the tumor microenvironment (TME), especially tumor-associated macrophages (TAM), were shown to actively contribute to tumor progression and modulate the TME of the primary tumor as well as the pre-metastatic niche. In this work, the effect of circulating sEVs on macrophage functions was investigated and their capability to transform them into pro-tumorigenic TAMs.
HNSCC sEVs were internalized by macrophages and tumor cells and accumulated in the cytoplasm around the nucleus in both cell types. Macrophage proteomes were altered after incubation with HNSCC sEVs, with the main underlying mechanism being modulation of protein expression rather than transfer of proteins. Proteomics data also indicated activation of NF-κB signaling by HNSCC sEVs as levels of p65 were increased in sEV-treated macrophages. Measuring nuclear translocation of p65 confirmed transient activation of NF-κB signaling, which could be reversed by NF-κB inhibitors Bay, CAPE and curcumin. Increased NF-κB activation was expected to modulate expression of cytokines, which are among the target genes of NF-κB signaling, but first, no alterations in cytokine levels were observed. However, when separating the sEV samples according to the HPV status, HPV(+) sEVs induced increased levels of CCL22, while HPV(-) sEVs decreased CCL22 production. This differential regulation of CCL22 secretion was the rationale to investigate the effect of HPV status also on NF-κB activation. In line with differences in CCL22 expression, HPV(+) sEVs showed a trend of increased NF-κB activation compared to HPV(-) sEVs. Furthermore, analysis of several NF-κB-related analytes revealed activation of pro-survival and canonical NF-κB signaling by HPV(+) sEVs. Moreover, HPV(+) sEVs were internalized more efficiently than HPV(-) sEVs. Using cell culture-derived sEVs from HPV(+) and HPV(-) HNSCC cells, no differences in the activation of NF-κB signaling were detected, suggesting the effect was not mediated by tumor-derived sEVs, but by the total circulating sEV population. Co-incubation with uptake inhibitors dynasore and genistein revealed decrease of sEV-mediated NF-κB activation, however, NF-κB signaling was also decreased in the absence of sEVs, indicating genistein might be an inhibitor of NF-κB activation. Dynasore did not decrease NF-κB activation in the absence of sEVs. Also, no inhibition of NF-κB activation after co-incubation with HPV(+) sEVs was visible, while NF-κB activation by HPV(-) sEVs was decreased. This indicates that HPV(-) sEVs require internalization to activate NF-κB signaling, while HPV(+) sEVs might interact with cell surface receptors. Further proteomics and transcriptomic analysis did not explore more HPV-related differences in sEV-treated macrophages due to high variability using primary material, but could show that the proteome and transcriptome profile differed between macrophages incubated with sEVs from HNSCC patients or from healthy donors. Macrophage activation markers responded differently to sEVs from HD and HNSCC patients. Moreover, efferocytosis, the process by which macrophages clear dead cells, was reduced in macrophages treated with HNSCC-derived sEVs compared to those exposed to HD sEVs, suggesting that HNSCC sEVs may promote tumor-supporting functions in macrophages. TAMs were reported to modulate other components in the TME and in this study, the effects of sEV-treated macrophages on tumor cell growth and T cell chemotaxis and activation were investigated as well. While conditioned medium of HNSCC-sEV-treated macrophages decreased tumor cell growth slightly, no effects were observed on CD8+ T cell activation. However, chemotaxis of CD8+ T cells was decreased by sEVs from macrophages incubated with HNSCC sEVs. Furthermore, HNSCC sEVs directly added to CD8+ T cells decreased activation and increased apoptosis in these cells.
In conclusion, our data suggest that in HPV-associated HNSCC, circulating sEVs contribute to immune modulation and tumor progression by activating NF-κB signaling in macrophages, causing downstream production of pro-tumorigenic CCL2, while in HPV(-) HNSCC the effect of sEVs is not dependent on NF-κB activation. These results highlight the importance of different treatment options for HPV(+) and HPV(-) HNSCC patients, as HPV(+) HNSCC patients might benefit from therapies targeting sEV-mediated NF-κB activation