Model Reduction for Multiscale Lithium-Ion Battery Simulation

In this contribution we are concerned with efficient model reduction for multiscale problems arising in lithium-ion battery modeling with spatially resolved porous electrodes. We present new results on the application of the reduced basis method to the resulting instationary 3D battery model that involves strong non-linearities due to Buttler-Volmer kinetics. Empirical operator interpolation is used to efficiently deal with this issue. Furthermore, we present the localized reduced basis multiscale method for parabolic problems applied to a thermal model of batteries with resolved porous electrodes. Numerical experiments are given that demonstrate the reduction capabilities of the presented approaches for these real world applications

Loss of Nrf2 abrogates the protective effect of Keap1 down regulation in a preclinical model of cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinomas (cSCC) are the most common and highly mutated human malignancies, challenging identification of driver mutations and targeted therapies. Transcription factor NF-E2 p45-related factor 2 (Nrf2) orchestrates a cytoprotective inducible program, which counteracts the damaging effects of solar UV radiation, the main etiological factor in cSCC development. Downregulation of Kelch-like ECH-associated protein 1 (Keap1), a Cullin-3/Rbx1 ubiquitin ligase substrate adaptor protein, which mediates the ubiquitination and proteasomal degradation of Nrf2, has a strong protective effect in a preclinical model of cSCC. However, in addition to Nrf2, Keap1 affects ubiquitination of other proteins in the carcinogenesis process, including proteins involved in inflammation and DNA damage repair. Here, we generated Keap1(flox/flox) SKH-1 hairless mice in which Nrf2 is disrupted (Keap1(flox/flox)/Nrf2(−/−)) and subjected them chronically to solar-simulated UV radiation. We found that the incidence, multiplicity and burden of cSCC that form in Keap1(flox/flox)/Nrf2(−/−) mice are much greater than in their Keap1(flox/flox)/Nrf2(+/+) counterparts, establishing Nrf2 activation as the protection mediator. Our findings further imply that inhibition of Nrf2 globally, a strategy proposed for cancer treatment, is unlikely to be beneficial

Structural basis for the recognition and cleavage of histone H3 by cathepsin L

Proteolysis of eukaryotic histone tails has emerged as an important factor in the modulation of cell-cycle progression and cellular differentiation. The recruitment of lysosomal cathepsin L to the nucleus where it mediates proteolysis of the mouse histone H3 tail has been described recently. Here, we report the three-dimensional crystal structures of a mature, inactive mutant of human cathepsin L alone and in complex with a peptide derived from histone H3. Canonical substrate–cathepsin L interactions are observed in the complex between the protease and the histone H3 peptide. Systematic analysis of the impact of posttranslational modifications at histone H3 on substrate selectivity suggests cathepsin L to be highly accommodating of all modified peptides. This is the first report of cathepsin L–histone H3 interaction and the first structural description of cathepsin L in complex with a substrate

Analog VLSI Implementation of Adaptive Synapses in Pulsed Neural Networks

Kaulmann T, Ferber M, Witkowski U, Rückert U. Analog VLSI Implementation of Adaptive Synapses in Pulsed Neural Networks. In: Cabestany J, Prieto A, Sandoval DF, eds. Proceedings of the 8th International Work-Conference on Artificial Neural Networks (IWANN). Lecture notes in computer science. Vol 3512. Berlin, Heidelberg: Springer Berlin Heidelberg; 2005: 455-462.An analog VLSI implementation of adaptive synapses being part of an associative memory realised with pulsed neurons is presented. VLSI implementations of dynamic synapses and pulsed neurons are expected to provide robustness and low energy consumption like observed in the human brain. We have developed a VLSI implementation of synaptic connections for an associative memory which is used in a biological inspired image processing system using pulse coded neural networks. The system consists of different layers for feature extraction to decompose the image in several features. The pulsed associative memory is used for completing or binding features. In this paper, we focus on the dynamics and the analog implementation of adaptive synapses. The discussed circuits were designed in a 130 nm CMOS process

Reaction modelling and simulation to assess the integrated use of transketolase and omega-transaminase for the synthesis of an aminotriol

The most attractive, as well as challenging, multistep organic syntheses would preferably be carried out in a single reactor, as a one-pot synthesis. For biocatalytic syntheses, multistep reactions in one-pot mode bring a number of advantages, while at the same time raising unique challenges such as the compatibility of different biocatalysts. In this paper, we have developed a transketolase-transaminase (TK-TAm) two-step one-pot aminotriol synthesis reaction model, which integrates reaction kinetic models with process characterization (consisting of component degradation as a function of pH and concentration, aldehyde toxicity towards the enzyme, and ketol donor and acceptor side-reactions with TAm). Based on the analysis of the effect of the TAm/TK activity ratio on product yield, simulations provided guidance for further process and biocatalyst development