The Impact of Metal Ion Exposure on the Cellular Behavior of Human Osteoblasts and PBMCs: In Vitro Analyses of Osteolytic Processes

Osteolysis in the periprosthetic tissue can be caused by metallic wear particles and ions that can originate from implant surface corrosion. These products influence cellular behavior and stimulate the expression of proinflammatory cytokines. The purpose of this study was to evaluate the impact of CoCr29Mo6 ions on cell survival, differentiation, and cytokine expression in human osteoblasts and peripheral blood mononuclear cells (PBMCs). Thus, we exposed cells with a mixture of 200 mu g/L ion solution and determined cell viability and apoptosis/necrosis. Gene expression analyses of osteoblastic and osteoclastic differentiation markers as well as pro-osteolytic mediators (IL-6, IL-8, TNF-alpha, MCP-1, MMP1, TIMP1) were performed. These markers were also investigated in mixed cultures of adherent and non-adherent PBMCs as well as in co-cultures of human osteoblasts and PBMCs. The ion solution induced necrosis in osteoblasts and PBMCs in single cultures. All examined mediators were highly expressed in the co-culture of osteoblasts and PBMCs whereas in the single cell cultures only IL-6, IL-8, and MMP1 were found to be stimulated. While the applied concentration of the CoCr29Mo6 ion solutions had only marginal effects on human osteoblasts and PBMCs alone, the co-culture may provide a comprehensive model to study osteolytic processes in response to Co and Cr ions

Selection criteria for early breast cancer patients in the DBCG proton trial – The randomised phase III trial strategy

Background and purpose Adjuvant radiotherapy of internal mammary nodes (IMN) improves survival in high-risk early breast cancer patients but inevitably leads to more dose to heart and lung. Target coverage is often compromised to meet heart/lung dose constraints. We estimate heart and lung dose when target coverage is not compromised in consecutive patients. These estimates are used to guide the choice of selection criteria for the randomised Danish Breast Cancer Group (DBCG) Proton Trial.Materials and methods 179 breast cancer patients already treated with loco-regional IMN radiotherapy from 18 European departments were included. If the clinically delivered treatment plan did not comply with defined target coverage requirements, the plan was modified retrospectively until sufficient coverage was reached. The choice of selection criteria was based on the estimated number of eligible patients for different heart and lung dose thresholds in combination with proton therapy capacity limitations and dose-response relationships for heart and lung.Results Median mean heart dose was 3.0 Gy (range, 1.1-8.2 Gy) for left-sided and 1.4 Gy (0.4-11.5 Gy) for right-sided treatment plans. Median V17Gy/V20Gy (hypofractionated/normofractionated plans) for ipsilateral lung was 31% (9-57%). The DBCG Radiotherapy Committee chose mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37% as thresholds for inclusion in the randomised trial. Using these thresholds, we estimate that 22% of patients requiring loco-regional IMN radiotherapy will be eligible for the trial.Conclusion The patient selection criteria for the DBCG Proton Trial are mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37%

Exposure to the Amino Acids Histidine, Lysine, and Threonine Reduces mTOR Activity and Affects Neurodevelopment in a Human Cerebral Organoid Model

Evidence of the impact of nutrition on human brain development is compelling. Previous in vitro and in vivo results show that three specific amino acids, histidine, lysine, and threonine, synergistically inhibit mTOR activity and behavior. Therefore, the prenatal availability of these amino acids could be important for human neurodevelopment. However, methods to study the underlying mechanisms in a human model of neurodevelopment are limited. Here, we pioneer the use of human cerebral organoids to investigate the impact of amino acid supplementation on neurodevelopment. In this study, cerebral organoids were exposed to 10 mM and 50 mM of the amino acids threonine, histidine, and lysine. The impact was determined by measuring mTOR activity using Western blots, general cerebral organoid size, and gene expression by RNA sequencing. Exposure to threonine, histidine, and lysine led to decreased mTOR activity and markedly reduced organoid size, supporting findings in rodent studies. RNA sequencing identified comprehensive changes in gene expression, with enrichment in genes related to specific biological processes (among which are mTOR signaling and immune function) and to specific cell types, including proliferative precursor cells, microglia, and astrocytes. Altogether, cerebral organoids are responsive to nutritional exposure by increasing specific amino acid concentrations and reflect findings from previous rodent studies. Threonine, histidine, and lysine exposure impacts the early development of human cerebral organoids, illustrated by the inhibition of mTOR activity, reduced size, and altered gene expression

Multi-scale friction modeling for sheet metal forming

Finite element (FE) formability analyses are everyday practice in the metal-forming industry to reduce costs and lead time of new metal products. Although the predictive capabilities of FE software codes have improved significantly over the years, unfortunately, the experimental trial-and-error process can still not be entirely replaced by virtual design. The simplistic handling of friction in FE software is one of the main reasons for this. \ud \ud In this thesis, friction mechanisms in metal forming are addressed and a physical based friction model is proposed to improve the description of friction in metal forming processes. As an input, the model requires the properties of the metal-lubricant combination used and the surface characteristics of the tooling and the workpiece material. As an output, the friction conditions are predicted in both the boundary and mixed lubrication regime, including the effect of surface changes due to normal loading, sliding and straining the underlying bulk material. Adhesion and ploughing effects are accounted for to characterize friction conditions on the micro scale. To account for lubrication effects, special hydrodynamic contact elements have been developed. The boundary friction model and the hydrodynamic friction model have been coupled to describe friction in the mixed lubrication regime. The friction model has been implemented in an FE software code to model boundary and mixed lubrication friction in metal forming simulations, while minimally influencing the computation time. \ud \ud FE simulations have been carried out using the advanced friction model for 2 sheet metal forming processes, i.e. the forming of a top hat section and a cross-die product. In addition, experimental validation of the numerical results was performed. The computed local friction coefficients show a dependency on the punch stroke, punch speed and location in the product. A comparison between numerically and experimentally obtained results demonstrated a good correspondence. Also for varying process settings, the advanced friction model enables the accurate prediction of experimental results

Design and optimization of a magnetic gravity compensator

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Positioning and Control of an Unmanned Aerial Vehicle

In the CDIO-project course in Automatic Control, an Autonomous Unmanned Aerial vehicle (UAV) is constructed, utilizing an existing radio controlled model aircraft. By adding an inertial sensor measuring acceleration and rotation, together with a Global Positioning System (GPS) sensor, the aim is to construct an accurate positioning system. This is used by an on board computer to calculate rudder control signals to a set of DC-servos in order to follow a predefined way-point trajectory. The project involves 17 students, which is roughly three times as big as previous projects, and it comprises both positioning, control, and hardware design. Since the project is still ongoing some preliminary results and conclusions are presented

Low immediate postoperative serum-cortisol nadir predicts the short-term, but not long-term, remission after pituitary surgery for Cushing’s disease

Background Cushing’s disease is an ACTH-producing pituitary adenoma, and the primary treatment is microscopic or endoscopic transsphenoidal selective adenectomy. The aims of the present study were to evaluate whether the early postoperative S-cortisol level can serve as a prognostic marker for short- and long-term remission, and retrospectively review our own short and long term results after surgery for Cushing’s disease. Methods This single centre, retrospective study consists of 19 consecutive patients with Cushing’s disease who underwent transsphenoidal surgery. S-cortisol was measured every 6 h after the operation without any glucocorticoid replacement. We have follow-up on all patients, with a mean follow-up of 68 months. Results At the three-month follow-up, 16 patients (84 %) were in remission; at 12 months, 18 (95 %) were in remission and at the final follow-up (mean 68 months), 13 (68 %) were in remission. Five-years recurrence rate was 26 %. The mean postoperative S-cortisol nadir was significantly lower in the group of patients in remission than in the non-remission group at 3 months, but there was no difference between those in long-term remission compared to those in long-term non-remission. The optimal cut-off value for classifying 3-month remission was 74 nmol/l. Conclusion We achieved a 95 % 1-year remission rate with transsphenoidal surgery for Cushing’s disease in this series of consecutive patients. However, the 5-year recurrence rate was 26 %, showing the need for regular clinical and biochemical controls in this patient group. The mean postoperative serum-cortisol nadir was significantly lower in patients in remission at 3 months compared to patients not in remission at 3 months, but a low postoperative S-cortisol did not predict long-term remission

Temperature Dependent Friction Modelling: The Influence of Temperature on Product Quality

In the stamping of industrial parts, friction and lubrication play a key role in achieving high quality products and reducing scrap. Especially in the start-up phase of new production runs, transient effects can have a significant impact on the product quality. Before a steady-state production run is established, heating up of tools influence tribological conditions. This influences the performance of the forming operation and, consequently, the quality of the formed product. In the development process of new industrial parts, it is therefore crucial to accurately account for these transient effects in sheet metal forming simulations. This paper presents the modeling of the frictional behavior of two tribological systems as developed within the ASPECT project. The first tribology systems consist of a stainless steel with corresponding drawing oil and tool material. The sheet material of the second tribology system is a hot dip galvanized bake hardened steel. Subsequently, it is shown how temperature affects the frictional behavior of these tribology systems. Finally, generated friction models have been applied to a spare wheel well of Opel. The spare wheel well is modelled using a generally applicable approach to account for transient effects under industrial sheet metal forming process conditions. For varying temperature and tribological conditions, the spare wheel well can show cracks and differences in thinning and draw-in. This emphasizes the strong influence of transient effects on both part quality and the overall production stability