Extending the scope of microscopic solvability: Combination of the Kruskal-Segur method with Zauderer decomposition

Successful applications of the Kruskal-Segur approach to interfacial pattern formation have remained limited due to the necessity of an integral formulation of the problem. This excludes nonlinear bulk equations, rendering convection intractable. Combining the method with Zauderer's asymptotic decomposition scheme, we are able to strongly extend its scope of applicability and solve selection problems based on free boundary formulations in terms of partial differential equations alone. To demonstrate the technique, we give the first analytic solution of the problem of velocity selection for dendritic growth in a forced potential flow.Comment: Submitted to Europhys. Letters, No figures, 5 page

Statins aggravate the risk of insulin resistance in human muscle

Beside their beneficial effects on cardiovascular events, statins are thought to contribute to insulin resistance and type-2 diabetes. It is not known whether these effects are long-term events from statin-treatment or already triggered with the first statin-intake. Skeletal muscle is considered the main site for insulin-stimulated glucose uptake and therefore, a primary target for insulin resistance in the human body. We analyzed localization and expression of proteins related to GLUT4 mediated glucose uptake via AMPKα or AKT in human skeletal muscle tissue from patients with statin-intake >6 months and in primary human myotubes after 96 h statin treatment. The ratio for AMPKα activity significantly increased in human skeletal muscle cells treated with statins for long- and short-term. Furthermore, the insulin-stimulated counterpart, AKT, significantly decreased in activity and protein level, while GSK3ß and mTOR protein expression reduced in statin-treated primary human myotubes, only. However, GLUT4 was normally distributed whereas CAV3 was internalized from plasma membrane around the nucleus in statin-treated primary human myotubes. Statin-treatment activates AMPKα-dependent glucose uptake and remains active after long-term statin treatment. Permanent blocking of its insulin-dependent counterpart AKT activation may lead to metabolic inflexibility and insulin resistance in the long run and may be a direct consequence of statin-treatment

Immunoadsorption of agonistic autoantibodies against α1-adrenergic receptors in patients with mild to moderate dementia

Dementia has been shown to be associated with agonistic autoantibodies. The deleterious action of autoantibodies on the {alpha}1-adrenergic receptor for brain vasculature has been demonstrated in animal studies. In the current study, 169 patients with dementia were screened for the presence of agonistic autoantibodies. 47% of patients suffering from mild to moderate Alzheimer's disease and/or vascular dementia carried these autoantibodies. Eight patients positive for autoantibodies underwent immunoadsorption. Patients treated on four consecutive days were subsequently negative for autoantibodies and displayed stabilization of cognitive and mental condition during 12-18 months' follow-up. In patients treated for 2-3 days, autoantibodies were reduced by only 78%. They suffered a rebound of autoantibodies during follow-up, benefited from immunoadsorption too, but their mental parameters worsened. We provide first data on the clinical relevance of agonistic autoantibodies in dementia and show that immunoadsorption is safe and efficient in removing autoantibodies with overall benefits for patients

Quantum phase transition of Ising-coupled Kondo impurities

We investigate a model of two Kondo impurities coupled via an Ising interaction. Exploiting the mapping to a generalized single-impurity Anderson model, we establish that the model has a singlet and a (pseudospin) doublet phase separated by a Kosterlitz-Thouless quantum phase transition. Based on a strong-coupling analysis and renormalization group arguments, we show that at this transition the conductance G through the system either displays a zero-bias anomaly, G ~ |V|^{-2(\sqrt{2}-1)}, or takes a universal value, G = e^2/(\pi\hbar) cos^2[\pi/(2\sqrt{2})], depending on the experimental setup. Close to the Toulouse point of the individual Kondo impurities, the strong-coupling analysis allows to obtain the location of the phase boundary analytically. For general model parameters, we determine the phase diagram and investigate the thermodynamics using numerical renormalization group calculations. In the singlet phase close to the quantum phase transtion, the entropy is quenched in two steps: first the two Ising-coupled spins form a magnetic mini-domain which is, in a second step, screened by a Kondoesque collective resonance in an effective solitonic Fermi sea. In addition, we present a flow equation analysis which provides a different mapping of the two-impurity model to a generalized single-impurity Anderson model in terms of fully renormalized couplings, which is applicable for the whole range of model parameters.Comment: 24 pages, 12 figs; (v2) minor changes, flow equation section extende

Dislocation Creep of Olivine: Backstress Evolution Controls Transient Creep at High Temperatures

Transient creep occurs during geodynamic processes that impose stress changes on rocks at high temperatures. The transient is manifested as evolution in the viscosity of the rocks until steady-state flow is achieved. Although several phenomenological models of transient creep in rocks have been proposed, the dominant microphysical processes that control such behavior remain poorly constrained. To identify the intragranular processes that contribute to transient creep of olivine, we performed stress-reduction tests on single crystals of olivine at temperatures of 1250–1300°C. In these experiments, samples undergo time‐dependent reverse strain after the stress reduction. The magnitude of reverse strain is ~10-3 and increases with increasing magnitude of the stress reduction. High-angular resolution electron backscatter diffraction analyses of deformed material reveal lattice curvature and heterogeneous stresses associated with the dominant slip system. The mechanical and microstructural data are consistent with transient creep of the single crystals arising from accumulation and release of backstresses among dislocations. These results allow the dislocation‐glide component of creep at high temperatures to be isolated, and we use these data to calibrate a flow law for olivine to describe the glide component of creep over a wide temperature range. We argue that this flow law can be used to estimate both transient creep and steady‐state viscosities of olivine, with the transient evolution controlled by the evolution of the backstress. This model is able to predict variability in the style of transient (normal versus inverse) and the load-relaxation response observed in previous work.LH and DW acknowledge support from the Natural Environment Research Council, grant NE/M000966/1, LH and CT acknowledge support from the Natural Environment Research Council, grant 1710DG008/JC4, and DW acknowledges support from the Netherlands Organisation for Scientific Research, User Support Programme Space Research, grant ALWGO.2018.038, and startup funds from Utrecht University. LH recognizes funds used to develop the uniaxial apparatus from the John Fell Fund at the University of Oxford

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License