SEMPAI: a Self‐Enhancing Multi‐Photon Artificial Intelligence for Prior‐Informed Assessment of Muscle Function and Pathology

Deep learning (DL) shows notable success in biomedical studies. However, most DL algorithms work as black boxes, exclude biomedical experts, and need extensive data. This is especially problematic for fundamental research in the laboratory, where often only small and sparse data are available and the objective is knowledge discovery rather than automation. Furthermore, basic research is usually hypothesis‐driven and extensive prior knowledge (priors) exists. To address this, the Self‐Enhancing Multi‐Photon Artificial Intelligence (SEMPAI) that is designed for multiphoton microscopy (MPM)‐based laboratory research is presented. It utilizes meta‐learning to optimize prior (and hypothesis) integration, data representation, and neural network architecture simultaneously. By this, the method allows hypothesis testing with DL and provides interpretable feedback about the origin of biological information in 3D images. SEMPAI performs multi‐task learning of several related tasks to enable prediction for small datasets. SEMPAI is applied on an extensive MPM database of single muscle fibers from a decade of experiments, resulting in the largest joint analysis of pathologies and function for single muscle fibers to date. It outperforms state‐of‐the‐art biomarkers in six of seven prediction tasks, including those with scarce data. SEMPAI's DL models with integrated priors are superior to those without priors and to prior‐only approaches.The Self‐Enhancing Multi‐Photon AI (SEMPAI) that is designed specifically for basic laboratory research with microscopy is presented. It allows to integrate hypotheses and uses meta‐learning in a biologically interpretable configuration space for knowledge discovery. SEMPAI is applied to a large database of multi‐photon microscopy images of single muscle fibers to gain a deeper understanding of structure–function relationships and pathologies. image European Union's Horizon Marie Skłodowska‐Curie2021 Emerging Talents Initiative of the Friedrich‐Alexander UniversityGerman Research Foundation http://dx.doi.org/10.13039/50110000165

Symbolic Object Code Analysis

Current software model checkers quickly reach their limit when being applied to verifying pointer safety properties in source code that includes function pointers and inlined assembly. This paper introduces an alternative technique for checking pointer safety violations, called Symbolic Object Code Analysis (SOCA), which is based on bounded symbolic execution, incorporates path-sensitive slicing, and employs the SMT solver Yices as its execution and verification engine. Extensive experimental results of a prototypic SOCA Verifier, using the Verisec suite and almost 10,000 Linux device driver functions as benchmarks, show that SOCA performs competitively to current source-code model checkers and that it also scales well when applied to real operating systems code and pointer safety issues. SOCA effectively explores semantic niches of software that current software verifiers do not reach

Myocardial Infarction after Long-Term Treatment with a Tyrosine Kinase Inhibitor (TKI) with Anti-VEGF Receptor Activity

TKIs including anti-VEGF receptor activity have been approved for the treatment of patients with radioiodine resistant thyroid carcinomas. For lenvatinib arterial thromboembolic events are listed as adverse events of special interest with lenvatinib. In the phase III study, arterial thromboembolic events were reported in 3% of lenvatinib-treated patients and 1% in the placebo group. Most of the patients had predisposing factors. Only one myocardial infarct was reported in the lenvatinib phase III study. We report a 73-year-old female patient with metastatic thyroid papillary carcinoma who was treated with total thyroidectomy. The operation was followed by four radioiodine therapies over a period of 6 years. At 6 years she developed lung metastasis without radioiodine uptake, one solitary liver metastasis and one solitary right renal metastasis. One year after the first diagnosis of radioiodine resistant lung metastasis the lung metastasis showed progression according to RECIST criteria. This treatment was resulting in prolonged partial response with disappearance of a hepatic and renal metastasis. A myocardial infarction occurred after 39 months of lenvatinib treatment resulting in implantation of 3 stents and a two chamber pacemaker. The treatment was discontinued. Except for well controlled hypertension there were neither predisposing diseases like diabetes nor symptoms of cardiac ischemia on exertion. However, the family history for cardiovascular diseases was positive for cardiac infarction reported for one brother. Another brother was treated for hypertension and the patient’s mother suffered from a cerebral infarction at the age of 60. While only one myocardial infarct was reported in the lenvatinib phase III study with 392 patients this case suggests that long-term treatment with lenvatinib may be associated with an increased risk for myocardial infarct also in patients with no predisposing diseases except well controlled hypertension and positive family history for cardiovascular diseases.Peer Reviewe

Tailoring the orientations of complex niobate films on perovskite substrates

Ferroelectric complex niobates with tetragonal tungsten bronze (TTB) structure are of significant interest for a variety of device applications. For many of these applications thin films are required whose properties, due to the particular structure, are sensitively dependent on the film structure and orientation. Based on the system of the relaxor CaxBa1-xNb2O6 (CBN) and the perovskite substrate SrTiO3 (STO) the crystal orientation relationships between film and substrate are determined as (001)(CBN)//{001}(STO),[100](CBN)//(STO), and [010](CBN)//(STO). Employing an advanced imaging technique in an aberration-corrected transmission electron microscope we reveal the atomic configuration of both the cation and oxygen columns at the heterointerface. The interface structure as well as the orientation relations can be understood in terms of lowest-energy considerations based on a near-coincidence site lattice model. These results reveal a pathway for tailoring the film orientation of TTB niobates on perovskites for optimizing the film properties for device applications. (c) 2006 Acta Materialia, Inc. Published by Elsevier Ltd. All rights reserved