An efficient and robust simulator for wear of total knee replacements

Wear on total knee replacements is an important criterion for their performance characteristics. Numerical simulations of such wear have seen increasing attention over the last years. They have the potential to be much faster and less expensive than the in vitro tests in use today. While it is unlikely that in silico tests will replace actual physical tests in the foreseeable future, a judicious combination of both approaches can help making both implant design and pre-clinical testing quicker and more cost-effective. The challenge today for the design of simulation methods is to obtain results that convey quantitative information and to do so quickly and reliably. This involves the choice of mathematical models as well as the numerical tools used to solve them. The correctness of the choice can only be validated by comparing with experimental results. In this article, we present finite element simulations of the wear in total knee replacements during the gait cycle standardized in the ISO 14243-1 document, used for compliance testing in several countries. As the ISO 14243-1 standard is precisely defined and publicly available, it can serve as an excellent benchmark for comparison of wear simulation methods. We use comparatively simple wear and material models, but we solve them using a new wear algorithm that combines extrapolation of the geometry changes with a contact algorithm based on nonsmooth multigrid ideas. The contact algorithm works without Lagrange multipliers and penalty parameters, achieving unparalleled stability and efficiency. We compare our simulation results with the experimental data from physical tests using two different actual total knee replacements. Even though the model is simple, we can predict the total mass loss due to wear after 5-million gait cycles, and we observe a good match between the wear patterns seen in experiments and our simulation results. When compared with a state-of-the-art penalty-based solver for the same model, we measure a roughly fivefold increase of execution speed

Activation of Rac-1 and RhoA contributes to podocyte injury in chronic kidney disease

Rho-family GTPases like RhoA and Rac-1 are potent regulators of cellular signaling that control gene expression, migration and inflammation. Activation of Rho-GTPases has been linked to podocyte dysfunction, a feature of chronic kidney diseases (CKD). We investigated the effect of Rac-1 and Rho kinase (ROCK) inhibition on progressive renal failure in mice and studied the underlying mechanisms in podocytes. SV129 mice were subjected to 5/6-nephrectomy which resulted in arterial hypertension and albuminuria. Subgroups of animals were treated with the Rac-1 inhibitor EHT1846, the ROCK inhibitor SAR407899 and the ACE inhibitor Ramipril. Only Ramipril reduced hypertension. In contrast, all inhibitors markedly attenuated albumin excretion as well as glomerular and tubulo-interstitial damage. The combination of SAR407899 and Ramipril was more effective in preventing albuminuria than Ramipril alone. To study the involved mechanisms, podocytes were cultured from SV129 mice and exposed to static stretch in the Flexcell device. This activated RhoA and Rac-1 and led via TGFβ to apoptosis and a switch of the cells into a more mesenchymal phenotype, as evident from loss of WT-1 and nephrin and induction of α-SMA and fibronectin expression. Rac-1 and ROCK inhibition as well as blockade of TGFβ dramatically attenuated all these responses. This suggests that Rac-1 and RhoA are mediators of podocyte dysfunction in CKD. Inhibition of Rho-GTPases may be a novel approach for the treatment of CKD

Antimicrobial effects of microwave-induced plasma torch (MiniMIP) treatment on Candida albicans biofilms

The susceptibility of Candida albicans biofilms to a non-thermal plasma treatment has been investigated in terms of growth, survival and cell viability by a series of in vitro experiments. For different time periods, the C. albicans strain SC5314 was treated with a microwave-induced plasma torch (MiniMIP). The MiniMIP treatment had a strong effect (reduction factor (RF) = 2.97 after 50 s treatment) at a distance of 3 cm between the nozzle and the superior regions of the biofilms. In addition, a viability reduction of 77% after a 20 s plasma treatment and a metabolism reduction of 90% after a 40 s plasma treatment time were observed for C. albicans. After such a treatment, the biofilms revealed an altered morphology of their cells by atomic force microscopy (AFM). Additionally, fluorescence microscopy and confocal laser scanning microscopy (CLSM) analyses of plasma-treated biofilms showed that an inactivation of cells mainly appeared on the bottom side of the biofilms. Thus, the plasma inactivation of the overgrown surface reveals a new possibility to combat biofilms. © 2019 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology

Flux ramp modulation based MHz frequency-division dc-SQUID multiplexer

We present a MHz frequency-division dc-SQUID multiplexer that is based on flux ramp modulation and a series array of $N$ identical current-sensing dc-SQUIDs with tightly coupled input coil. By running a periodic, sawtooth-shaped current signal through an additional modulation coil being tightly, but non-uniformly coupled to the individual SQUIDs, the voltage drop across the array changes according to the superposition of the flux-to-voltage characteristics of the individual SQUIDs within each cycle of the modulation signal. In this mode of operation, an input signal injected in the input coil of one of the SQUIDs and being quasi-static within a time frame adds a constant flux offset and leads to a phase shift of the associated SQUID characteristics. The latter is inherently proportional to the input signal and can be inferred by channelizing and down-converting the sampled array output voltage. Using a prototype multiplexer as well as a self-developed high-speed readout electronics for real-time phase determination, we demonstrate the simultaneous readout of four signal sources with MHz bandwidth per channel.Comment: The article has been submitted to Applied Physics Letter

Simultaneous MMC readout using a tailored {\mu}MUX based readout system

Magnetic microcalorimeters (MMCs) are cryogenic, energy-dispersive single-particle detectors providing excellent energy resolution, intrinsically fast signal rise time, quantum efficiency close to 100\%, large dynamic range as well as almost ideal linear response. One of the remaining challenges to be overcome to ultimately allow for the utilization of large-scale MMC based detector arrays with thousands to millions of individual pixels is the realization of a SQUID based multiplexing technique particularly tailored for MMC readout. Within this context, we report on the first truly multiplexed readout of an MMC based detector array using a frequency-division multiplexing approach realized by a custom microwave SQUID multiplexer based readout system.Comment: Conference: ASC2022 (accepted for publication in IEEE Transactions on Applied Superconductivity

Differential Role of gp130-Dependent STAT and Ras Signalling for Haematopoiesis Following Bone-Marrow Transplantation

INTRODUCTION: Bone marrow transplantation (BMT) is a complex process regulated by different cytokines and growth factors. The pleiotropic cytokine IL-6 (Interleukin-6) and related cytokines of the same family acting on the common signal transducer gp130 are known to play a key role in bone marrow (BM) engraftment. In contrast, the exact signalling events that control IL-6/gp130-driven haematopoietic stem cell development during BMT remain unresolved. METHODS: Conditional gp130 knockout and knockin mice were used to delete gp130 expression (gp130(ΔMx)), or to selectively disrupt gp130-dependent Ras (gp130(ΔMxRas)) or STAT signalling (gp130(ΔMxSTAT)) in BM cells. BM derived from the respective strains was transplanted into irradiated wildtype hosts and repopulation of various haematopoietic lineages was monitored by flow cytometry. RESULTS: BM derived from gp130 deficient donor mice (gp130(ΔMx)) displayed a delayed engraftment, as evidenced by reduced total white blood cells (WBC), marked thrombocytopenia and anaemia in the early phase after BMT. Lineage analysis unravelled a restricted development of CD4(+) and CD8(+) T-cells, CD19(+) B-cells and CD11b(+) myeloid cells after transplantation of gp130-deficient BM grafts. To further delineate the two major gp130-induced signalling cascades, Ras-MAPK and STAT1/3-signalling respectively, we used gp130(ΔMxRas) and gp130(ΔMxSTAT) donor BM. BMT of gp130(ΔMxSTAT) cells significantly impaired engraftment of CD4(+), CD8(+), CD19(+) and CD11b(+) cells, whereas gp130(ΔMxRas) BM displayed a selective impairment in early thrombopoiesis. Importantly, gp130-STAT1/3 signalling deficiency in BM grafts severely impaired survival of transplanted mice, thus demonstrating a pivotal role for this pathway in BM graft survival and function. CONCLUSION: Our data unravel a vital function of IL-6/gp130-STAT1/3 signals for BM engraftment and haematopoiesis, as well as for host survival after transplantation. STAT1/3 and ras-dependent pathways thereby exert distinct functions on individual bone-marrow-lineages

Adaptive modelling of coupled hydrological processes with application in water management

This paper presents recent results of a network project aiming at the modelling and simulation of coupled surface and subsurface flows. In particular, a discontinuous Galerkin method for the shallow water equations has been developed which includes a special treatment of wetting and drying. A robust solver for saturated-unsaturated groundwater flow in homogeneous soil is at hand, which, by domain decomposition techniques, can be reused as a subdomain solver for flow in heterogeneous soil. Coupling of surface and subsurface processes is implemented based on a heterogeneous nonlinear Dirichlet-Neumann method, using the dune-grid-glue module in the numerics software Dune