Development of innovative automated solutions for the assembly of multifunctional thermoplastic composite fuselage

In this study, the development of innovative tooling and end-effector systems for the assembly of a multifunctional thermoplastic fuselage is presented. The increasing demand for cleaner and new aircraft requires utilising novel materials and technologies. Advanced thermoplastic composites provide an excellent material option thanks to their weldability, low density, low overall production cost, improved fracture toughness and recyclability. However, to fully appreciate their potentials, new manufacturing approaches and techniques are needed. Hence, this project develops three end-effector solutions to demonstrate the feasibility of assembling a full-scale multifunctional-integrated thermoplastic lower fuselage shell, including the integration of a fully equipped floor and cargo structure. The developed assembly solution comprises three individual yet well-integrated tooling systems that allow housing the skin and assembly; picking, placing and welding of the assembly parts, i.e. clips and stringers; and welding of frames and floor beam sub-assemblies. The process of developing these systems including the end-user requirements, technical challenges, tooling and end-effectors design and manufacturing process are detailed in this paper.This study is part of the TCTool project, which has received funding from the Clean Sky 2 Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 865131. Project partners: GKN-Fokker Aerospace (Topic Manager), TWI Ltd., Andalusian Foundation for Aerospace Development – Advanced Center for Aerospace Technologies, Brunel University London (Brunel Composites Centre), London South Bank University, Acroflight Ltd., and Smart Advanced Manufacturing XL (SAM|XL)

Lysozyme M deficiency leads to an increased susceptibility to Streptococcus pneumoniae-induced otitis media

<p>Abstract</p> <p>Background</p> <p>Lysozyme is an antimicrobial innate immune molecule degrading peptidoglycan of the bacterial cell wall. Lysozyme shows the ubiquitous expression in wide varieties of species and tissues including the tubotympanum of mammals. We aim to investigate the effects of lysozyme depletion on pneumococcal clearance from the middle ear cavity.</p> <p>Methods</p> <p>Immunohistochemistry was performed to localize lysozyme in the Eustachian tube. Lysozyme expression was compared between the wild type and the lysozyme M^-/-mice using real time quantitative RT-PCR and western blotting. Muramidase activity and bactericidal activity of lysozyme was measured using a lysoplate radial diffusion assay and a liquid broth assay, respectively. To determine if depletion of lysozyme M increases a susceptibility to pneumococal otitis media, 50 CFU of <it>S. pneumoniae </it>6B were transtympanically inoculated to the middle ear and viable bacteria were counted at day 3 and 7 with clinical grading of middle ear inflammation.</p> <p>Results</p> <p>Immunolabeling revealed that localization of lysozyme M and lysozyme P is specific to some/particular cell types of the Eustachian tube. Lysozyme P of lysozyme M^-/-mice was mainly expressed in the submucosal gland but not in the tubal epithelium. Although lysozyme M^-/-mice showed compensatory up-regulation of lysozyme P, lysozyme M depletion resulted in a decrease in both muramidase and antimicrobial activities. Deficiency in lysozyme M led to an increased susceptibility to middle ear infection with <it>S. pneumoniae </it>6B and resulted in severe middle ear inflammation, compared to wild type mice.</p> <p>Conclusion</p> <p>The results suggest that lysozyme M plays an important role in protecting the middle ear from invading pathogens, particularly in the early phase. We suggest a possibility of the exogenous lysozyme as an adjuvant therapeutic agent for otitis media, but further studies are necessary.</p

T cells fail to develop in the human skin-cell explants system; an inconvenient truth

BACKGROUND: Haplo-identical hematopoietic stem cell (HSC) transplantation is very successful in eradicating haematological tumours, but the long post-transplant T-lymphopenic phase is responsible for high morbidity and mortality rates. Clark et al. have described a skin-explant system capable of producing host-tolerant donor-HSC derived T-cells. Because this T-cell production platform has the potential to replenish the T-cell levels following transplantation, we set out to validate the skin-explant system. RESULTS: Following the published procedures, while using the same commercial components, it was impossible to reproduce the skin-explant conditions required for HSC differentiation towards mature T-cells. The keratinocyte maturation procedure resulted in fragile cells with minimum expression of delta-like ligand (DLL). In most experiments the generated cells failed to adhere to carriers or were quickly outcompeted by fibroblasts. Consequently it was not possible to reproduce cell-culture conditions required for HSC differentiation into functional T-cells. Using cell-lines over-expressing DLL, we showed that the antibodies used by Clark et al. were unable to detect native DLL, but instead stained 7AAD+ cells. Therefore, it is unlikely that the observed T-lineage commitment from HSC is mediated by DLL expressed on keratinocytes. In addition, we did confirm expression of the Notch-ligand Jagged-1 by keratinocytes. CONCLUSIONS: Currently, and unfortunately, it remains difficult to explain the development or growth of T-cells described by Clark et al., but for the fate of patients suffering from lymphopenia it is essential to both reproduce and understand how these co-cultures really &quot;work&quot;. Fortunately, alternative procedures to speed-up T-cell reconstitution are being established and validated and may become available for patients in the near future

Glycosaminoglycan Binding Facilitates Entry of a Bacterial Pathogen into Central Nervous Systems

Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications

The story of Wanderwolf: A contested tale on the re-emergence of 'new wilderness' in the Netherlands

In this chapter, the author studies what the particular wolf has come to signify culturally in the contemporary public imagination and understanding of the Dutch landscape. It suggests that the Wanderwolf 'wandered' into the production of a new landscape ideology, i.e., another genesis of the Dutch landscape, in which it fulfils a different kind, yet equally controversial, iconic role compared to those we know from West-European ethnological and folkloric traditions. The media commotion surrounding the sightings of the Wanderwolf should be seen in the context of a much larger interest and effort to 'rewild' Europe. The visions expressed by the enthusiasts on the apparent return of the wolf reflect strongly those which Cronon has critically analysed in his influential essay on the notion of wilderness. The wolf's adversaries spoke out equally during the Wanderwolf's appearance. As media announced during the Wanderwolf incident, the comeback of the wolf is no longer a fairy tale