Characterization of the Melt Quality and Impurity Content of an Lm25 Alloy

The melt quality of an LM25 aluminum casting alloy has been examined using reduced pressure test (RPT) measurements, porous disc filtration analysis (PoDFA), and fatigue and tensile tests. The aim of this study was to determine the existing melt quality and thus to evaluate methods used with respect to monitoring and improving melt cleanliness. Special emphasis was given to the influence of oxides. It was found that the melt quality has varying degrees of effect on the tests used. The results indicate in particular that it was necessary to distinguish between “new” oxides (bifilms) and “hard” inclusions in the melt, as new oxides impact on porosity, whereas hard inclusions impact on ductility. Based on the results of this study, suggestions for the measurement of the melt quality have been proposed.     

Microwave joining of two long hollow tubes: an asymptotic theory and numerical simulations

A nonlinear heat equation which models the microwave assisted joining of two large SiC tubes is analyzed. By exploiting the small fineness ratio of the structure and disparate time scales an asymptotic theory for this problem is systematically deduced. Specifically, a one-dimensional nonlinear heat equation is described which governs the temperature in the outer region. This is a numerically well posed problem and it is efficiently solved using standard methods. This solution is not valid in the inner region which includes the microwave source. An inner asymptotic approximation is derived to describe the temperature in this region. This approximation yields two unknown functions which are determined from matching to the outer solution. The results of the asymptotic theory are compared to calculations done on the full problem. Since the full problem is numerically ill conditioned, the asymptotic theory yields enormous savings in computational time and effort.     

Mechanical robustness of Pseudomonas aeruginosa biofilms

Biofilms grow on various surfaces and in many different environments, a phenomenon that constitutes major problems in industry and medicine. Despite their importance little is known about the viscoelastic properties of biofilms and how these depend on the chemical microenvironment. Here, we find that the mechanical properties of Pseudomonas aeruginosa (P.a.) biofilms are highly robust towards chemical perturbations. Specifically, we observe that P.a. biofilms are able to fully regain their initial stiffness after yielding is enforced, even in the presence of chemicals. Moreover, only trivalent ions and citric acid significantly affect the biofilm elasticity, the first of which also alter the texture of the material. Finally, our results indicate that biofilm mechanics and bacteria viability inside the biofilm are not necessarily linked which suggests that targeting bacteria alone might not be sufficient for biofilm removal strategies.     

Using Drosophila melanogaster to Analyse the Human Paralogs of the ESCRT-III Core Component Shrub/CHMP4/Snf7 and Its Interactions with Members of the LGD/CC2D1 Family

The evolutionary conserved ESCRT-III complex is a device for membrane remodelling in various cellular processes, such as the formation of intraluminal vesicles (ILVs), cytokinesis, and membrane repair. The common theme of all these processes is the abscission of membrane away from the cytosol. At its heart in Drosophila is Shrub, CHMP4 in humans, which dynamically polymerises into filaments through electrostatic interactions among the protomers. For the full activity, Shrub/CHMP4 requires physical interaction with members of the Lgd protein family. This interaction is mediated by the odd-numbered DM14 domains of Lgd, which bind to the negative interaction surface of Shrub. While only one Lgd and one Shrub exist in the genome of Drosophila, mammals have two Lgd orthologs, LGD1/CC2D1B and LGD2/CC2D1A, as well as three CHMP4s in their genomes, CHMP4A, CHMP4B, and CHMP4C. The rationale for the diversification of the ESCRT components is not understood. We here use Drosophila as a model system to analyse the activity of the human orthologs of Shrub and Lgd at an organismal level. This enabled us to use the plethora of available techniques available for Drosophila. We present evidence that CHMP4B is the true ortholog of Shrub, while CHMP4A and CHMP4C have diverging activities. Nevertheless, CHMP4A and CHMP4C can enhance the activity of CHMP4B, raising the possibility that they can form heteropolymers in vivo. Our structure-function analysis of the LGD1 and LGD2 indicates that the C2 domain of the LGD proteins has a specific function beyond protein stability and subcellular localisation. Moreover, our data specify that CHMP4B interacts more efficiently with LGD1 than with LGD2.     

The Pro-Inflammatory Deletion Allele of the NF-κB1 Polymorphism Is Characterized by a Depletion of Subunit p50 in Sepsis

The functionally important NF-κB1 promoter polymorphism (−94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both healthy volunteers (n = 20) and septic patients (n = 10). All individuals were genotyped for the −94ins/delATTG NF-κB1 promoter polymorphism. We found a diminished nuclear activity of the NF-κB subunit p50 in ID/DD genotypes after 48 h of lipopolysaccharide stimulation compared to II genotypes (p = 0.025). This was associated with higher TNF-α (p = 0.005) and interleukin 6 concentrations (p = 0.014) and an increased production of mitochondrial radical oxygen species in ID/DD genotypes (p = 0.001). Although ID/DD genotypes showed enhanced activation of mitochondrial biogenesis, they still had a significantly diminished cellular ATP content (p = 0.046) and lower mtDNA copy numbers (p = 0.010) compared to II genotypes. Strikingly, these findings were mirrored in peripheral blood mononuclear cells taken from septic patients. Our results emphasize the crucial aspect of considering NF-κB subunits in sepsis. We showed here that the deletion allele of the NF-κB1 (−94ins/delATTG) polymorphism was associated with the lower nuclear activity of subunit p50, which, in turn, was associated with aggravated inflammation and mitochondrial dysfunction.     

Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.     

Newer Non-ionic A2B2-Type Enzyme-Responsive Amphiphiles for Drug Delivery

A new series of nonionic gemini amphiphiles have been synthesized in a multi-step chemoenzymatic approach by using a novel A₂B₂-type central core consisting of conjugating glycerol and propargyl bromide on 5-hydroxy isophthalic acid. A pair of hydrophilic monomethoxy poly(ethylene glycol) (mPEG) and hydrophobic linear alkyl chains (C₁₂/C₁₅) were then added to the core to obtain amphiphilic architectures. The aggregation tendency in aqueous media was studied by dynamic light scattering, fluorescence spectroscopy and cryogenic transmission electron microscopy. The nanotransport potential of the amphiphiles was studied for model hydrophobic guests, that is, the dye Nile Red and the drug Nimodipine by using UV/Vis and fluorescence spectroscopy. Evaluation of the viability of amphiphile-treated A549 cells showed them to be well tolerated up to the concentrations studied. Being ester based, these amphiphiles exhibit stimuli-responsive sensitivity towards esterases, and a rupture of amphiphilic architecture was observed in the presence of immobilized Candida antarctica lipase (Novozym 435), thus facilitating release of the encapsulated guest from the aggregate.     

Einfluss von Vorschädigung auf das Reibungsverhalten nasslaufender Lamellenkupplungen im Dauerschaltbetrieb

Forschung im Ingenieurwesen - Ausfälle von Lamellenkupplungen müssen aufgrund von sicherheitskritischen Funktionalitäten im Antriebsstrang sicher ausgeschlossen werden. Neben...