64 research outputs found
Inflatable dams - Prospects for the use of flexible gates Advantages and application range - Hydraulic and structural design - Requirements for materials - Initial experience on Federal waterways
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Virtual Testing of Geometrically Imperfect Additively Manufactured Lattice Structures
Additively manufactured lattice structures increase the lightweight potential of components for technical applications. When modelling the mechanical behaviour of those lattice structures, imperfections within the structures need to be considered. In this contribution we investigate the effect of process induced pores of varying size and location inside the lattice structure during pressure tests using a 2D minimal model in two configurations. It shows that the location of pores with respect to the configuration of the model has a strong influence on whether the imperfection decreases the mechanical performance
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Additively manufactured AlSi10Mg lattices â Potential and limits of modelling as-designed structures
Additive manufacturing overcomes the restrictions of classical manufacturing methods and enables the production of near-net-shaped, complex geometries. In that context, lattice structures are of high interest due to their superior weight reduction potential. AlSi10Mg is a well-known alloy for additive manufacturing and well suited for such applications due to its high strength to material density ratio. It has been selected in this study for producing bulk material and complex geometries of a strut-based lattice type (rhombic dodecahedron). A detailed characterisation of as-built and heat-treated specimens has been conducted including microstructural analyses, identification of imperfections and rigorous mechanical testing under different load conditions. An isotropic elasticâplastic material model is deduced on the basis of tension test results of bulk material test specimens. Performed experiments under compression, shear, torsion and tension load are compared to their virtual equivalents. With the help of numerical modelling, the overall structural behaviour was simulated using the detailed lattice geometry and was successfully predicted by the presented numerical models. The discussion of the limits of this approach aims to evaluate the potential of the numerical assessment in the modelling of the properties for novel lightweight structures
BAW-Brief Nr. 2 - Oktober 2002
565-W/B, Bautechnik, Wasserbau, Untersuchungen zum Einsatz von Schlauchwehren an BundeswasserstraĂen564-B, Bautechnik, Regelwerksituation Wasserbaustein
Reinduction of Hedgehog Inhibitors after Checkpoint Inhibition in Advanced Basal Cell Carcinoma : A Series of 12 Patients
For patients with advanced basal cell carcinoma (aBCC) first-line treatment with hedgehog
inhibitors (HHIs) and second-line treatment with PD1 inhibitors (PD1i) is available, offering combination and sequencing options. Here, we focus on the efficacy and safety of HHI reinduction after PD1i
failure. Retrospective data analysis was performed with 12 patients with aBCC (locally advanced
(n = 8)/metastatic (n = 4)). These patients (male:female 6:6, median age 68 years) initially received
HHIs, leading to complete/partial response (66%) or stable disease (33%). Median treatment duration
was 20.8 (2â64.5) months until discontinuation due to progression (n = 8), adverse events (n = 3), or
patient request (n = 1). Subsequent PD1 inhibition (pembrolizumab 42%, cemiplimab 58%) yielded a
partial response (8%), stable disease (33%), or progression (59%). Median treatment duration was 4.1
(0.8â16.3) months until discontinuation due to progression (n = 9), adverse events (n = 1), patient
request (n = 1), or missing drug approval (n = 1). HHI reinduction resulted in complete/partial
response (33%), stable disease (50%), or progression (17%). Median treatment duration was 3.6 (1â29)
months. Response duration in the four responding patients was 2â29+ months. Thus, a subgroup
of patients with aBCC responded to reinduction of HHI following PD1i failure. Therefore, this
sequential treatment represents a feasible treatment option
Myoglobinâmediated lipid shuttling increases adrenergic activation of brown and white adipocyte metabolism and is as a marker of thermogenic adipocytes in humans
Background: Recruitment and activation of brown adipose tissue (BAT) results in increased energy expenditure (EE) via thermogenesis and represents an intriguing therapeutic approach to combat obesity and treat associated diseases. Thermogenesis requires an increased and efficient supply of energy substrates and oxygen to the BAT. The hemoprotein myoglobin (MB) is primarily expressed in heart and skeletal muscle fibres, where it facilitates oxygen storage and flux to the mitochondria during exercise. In the last years, further contributions of MB have been assigned to the scavenging of reactive oxygen species (ROS), the regulation of cellular nitric oxide (NO) levels and also lipid binding. There is a substantial expression of MB in BAT, which is induced during brown adipocyte differentiation and BAT activation. This suggests MB as a previously unrecognized player in BAT contributing to thermogenesis.
Methods and results: This study analyzed the consequences of MB expression in BAT on mitochondrial function and thermogenesis in vitro and in vivo. Using MB overexpressing, knockdown or knockout adipocytes, we show that expression levels of MB control brown adipocyte mitochondrial respiratory capacity and acute response to adrenergic stimulation, signalling and lipolysis. Overexpression in white adipocytes also increases their metabolic activity. Mutation of lipid interacting residues in MB abolished these beneficial effects of MB. In vivo, whole-body MB knockout resulted in impaired thermoregulation and cold- as well as drug-induced BAT activation in mice. In humans, MB is differentially expressed in subcutaneous (SC) and visceral (VIS) adipose tissue (AT) depots, differentially regulated by the state of obesity and higher expressed in AT samples that exhibit higher thermogenic potential.
Conclusions: These data demonstrate for the first time a functional relevance of MBs lipid binding properties and establish MB as an important regulatory element of thermogenic capacity in brown and likely beige adipocytes.
Keywords: energy expenditure; hemoprotein; metabolism; obesity; oxphos; uncoupling protein
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