A new model to determine the dispersion of fatigue damage evaluations

Reliable predictions of remaining lives of civil or mechanical structures subjected to fatigue damage are very difficult to be made. In general, fatigue damage is extremely sensitive to the random variations of material mechanical properties, environment and loading. These variations may induce large dispersions when the structural fatigue life has to be predicted. Wirsching (1970) mentions dispersions of the order of 30 to 70 % of the mean calculated life. The presented paper introduces a model to estimate the fatigue damage dispersion based on known statistical distributions of the fatigue parameters (material properties and loading). The model is developed by expanding into Taylor series the set of equations that describe fatigue damage for crack initiation

Entrepreneurial universities and the third mission paradigm shift from economic performance to impact entrepreneurship: Germany's EXIST program and ESG orientation

The proliferation and intensity of modern grand challenges, and the current broad public awareness of them, has resulted in a demand for entrepreneurship with an eye toward environmental, social and governance (ESG) matters, not just profits and economic gain. When it comes to economic applications, this realigned focus on impact-oriented entrepreneurship has significantly altered the way in which entrepreneurial universities address their third mission of service to society. The overall paradigm shift toward an ESG orientation drives these entrepreneurial universities to structure their efforts in technology transfer and creating academic spinoffs to produce startups which heavily employ impact entrepreneurship and ESG principles. This paper finds that governments can assist with this transition by creating funding programs, or updating existing funding programs, which favor the selection of impact entrepreneurship focused spinoffs that make use of ideas and knowledge from the university sphere. The EXIST program from the German government serves as a prime example of just such a financial mechanism that has evolved across multiple decades to more heavily incentivize academic spinoffs that place ESG at the core of what they do, in addition to the original goals of producing economic and technological development and increasing local, regional and national competitiveness. These findings bear implications for government and university leaders in regard to technology transfer policy and academic spinoffs at entrepreneurial universities

OVA-PEG-R848 nanocapsules stimulate neonatal conventional and plasmacytoid dendritic cells

Childhood mortality represents a major issue with 5. 3 million worldwide deaths of children under 5 years of age in 2019. Approximately half of those deaths can be attributed to easily preventable, infectious diseases. Currently approved neonatal vaccines are typically effective only after multiple doses leaving infants especially vulnerable during the first 6 months of life. Survival rates could be improved significantly by developing new and more potent vaccines that are capable of overcoming inherently tolerogenic neonatal immune systems. TLR agonists have garnered a great deal of attention in recent years due to their extensive capacities to activate innate immunity. Herein, the superior capacity of the TLR7/8 agonist, resiquimod (R848), to activate adult and neonatal primary peripheral blood dendritic cells is demonstrated. Moreover, R848 can be conjugated to polyethylene glycol and encapsulated in ovalbumin nanocapsules to efficiently co-deliver antigen and adjuvant in vitro. This study is among the first to demonstrate the capacity of encapsulated R848 to activate neonatal dendritic cells. These findings support the potential incorporation of R848 as adjuvant in neonatal vaccines, making them more effective in eliciting a robust immune response

A-405 - The basal cell carcinoma-one-stop-shop-study [Abstract]

Background: The treatment of basal cell carcinomas (BCCs) poses significant challenges due to the invasive, time-intensive and costly nature of margin mapping techniques such as Mohs micrographic surgery.[1][2] To address these limitations, we developed the "BCC-One-Stop-Shop-Method", integrating in-vivo and ex-vivo margin mapping using Line-field Confocal Optical Coherence Tomography (LC-OCT). This method aims to streamline diagnosis, surgery and margin control process, allowing for completion within one patient visit. This study outlines the process, the results compared to histology and highlights its advantages in clinical practice. Methods: BCC lesions were marked using color-coded tattoo pens to delineate margins in four quadrants. Dermoscopic mosaic images were captured for AI-assisted colocalization, ensuring precise margin mapping. LC-OCT was used in-vivo to record videos along the marked margins with an integrated AI providing real-time BCC probability scores. Images of the center were taken by LC-OCT to assess depth and subtype. After excision, the tissue was placed in an ex-vivo setup, with the LC-OCT handheld adapted to a movable sample holder for imaging of the specimen. Videos and 3D stacks were recorded to confirm margin clearance. Then the tissue undergoes conventional histological processing for correlation with LC-OCT findings. Results: 50 BCCs of 43 patients were examined, 32 lesions also with ex-vivo LC-OCT. 195 tissue quarters were evaluated and compared. 38 lesions were located on the head (76 %), 7 on the trunk (14 %), 5 on the extremities (10 %). 6 BCCs were superficial, 26 nodular, 14 infiltrative, 4 mixed subtypes and 1 was undefined. For in-vivo LC-OCT vs. histology sensitivity was 81.8 % (86.4 %), specificity 94.8 % (96.5 %) for the lesion (quarter) level. For ex-vivo LC-OCT vs. histology sensitivity was 71.4 % (86.6 %), specificity 96.0 % (96.4 %) for the lesion (quarter) level. Accuracy of overall performances for in-vivo for the lesion (quarter) level was 92 % (95.4 %), for ex-vivo 90.6 % (81.1 %). Conclusions: Our study presents a new approach for integrating advanced imaging technologies into BCC management, offering a comprehensive solution for preoperative margin mapping and intraoperative evaluation. Initial findings suggest this method is efficient, easy to implement, and well-accepted by patients. Further studies will confirm its efficacy and potential in BCC treatment, potentially reducing the psychological and economic burden associated with traditional methods

Supramolecular Toxin Complexes for Targeted Pharmacological Modulation of Polymorphonuclear Leukocyte Functions

The targeted pharmacological modulation of polymorphonuclear leukocytes (PMNs) is of major medical interest. These innate immune cells play a central role in the defense against pathogenic microorganisms. However, their excessive chemotactic recruitment into tissues after traumatic injury is detrimental due to local and systemic inflammation. Rho-GTPases, being the master regulators of the actin cytoskeleton, regulate migration and chemotaxis of PMNs, are attractive pharmacological targets. Herein, supramolecular protein complexes are assembled in a “mix-and-match” approach containing the specific Rho-inhibiting clostridial C3 enzyme and three PMN-binding peptides using an avidin platform. Selective delivery of the C3 Rho-inhibitor with these complexes into the cytosol of human neutrophil-like NB-4 cells and primary human PMNs ex vivo is demonstrated, where they catalyze the adenosine diphosphate (ADP) ribosylation of Rho and induce a characteristic change in cell morphology. Notably, the complexes do not deliver C3 enzyme into human lung epithelial cells, A549 lung cancer cells, and immortalized human alveolar epithelial cells (hAELVi), demonstrating their cell type-selectivity. The supramolecular complexes represent attractive molecular tools to decipher the role of PMNs in infection and inflammation or for the development of novel therapeutic approaches for diseases that are associated with hyperactivity and reactivity of PMNs such as post-traumatic injury

Controlling protein interactions in blood for effective liver immunosuppressive therapy by silica nanocapsules

Immunosuppression with glucocorticoids is a common treatment for autoimmune liver diseases and after liver transplant, which is however associated with severe side-effects. Targeted delivery of glucocorticoids to inflammatory cells, e.g. liver macrophages and Kupffer cells, is a promising approach for minimizing side effects. Herein, we prepare core–shell silica nanocapsules (SiO2 NCs) via a sol–gel process confined in nanodroplets for targeted delivery of dexamethasone (DXM) for liver immunosuppressive therapy. DXM with concentrations up to 100 mg mL−1 in olive oil are encapsulated while encapsulation efficiency remains over 95% after 15 days. Internalization of NCs by non-parenchymal murine liver cells significantly reduces the release of inflammatory cytokines, indicating an effective suppression of inflammatory response of liver macrophages. Fluorescent and magnetic labeling of the NCs allows for monitoring their intracellular trafficking and biodegradation. Controlled interaction with blood proteins and good colloidal stability in blood plasma are achieved via PEGylation of the NCs. Specific proteins responsible for stealth effect, such as apolipoprotein A-I, apolipoprotein A-IV, and clusterin, are present in large amounts on the PEGylated NCs. In vivo biodistribution investigations prove an efficient accumulation of NCs in the liver, underlining the suitability of the SiO2 NCs as a dexamethasone carrier for treating inflammatory liver diseases.Fil: Jiang, Shuai. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Prozeller, Domenik. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Pereira, Jorge. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Simon, Johanna. Max-Planck-Institut für Polymerforschung; Alemania. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Han, Shen. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Wirsching, Sebastian. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Fichter, Michael. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Mottola, Milagro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Lieberwirth, Ingo. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Morsbach, Svenja. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Mailänder, Volker. Max-Planck-Institut für Polymerforschung; Alemania. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Gehring, Stephan. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Crespy, Daniel. Max-Planck-Institut für Polymerforschung; Alemania. Vidyasirimedhi Institute of Science and Technology; TailandiaFil: Landfester, Katharina. Max-Planck-Institut für Polymerforschung; Alemani