A Survey on Modelling of Automotive Radar Sensors for Virtual Test and Validation of Automated Driving.

Radar sensors were among the first perceptual sensors used for automated driving. Although several other technologies such as lidar, camera, and ultrasonic sensors are available, radar sensors have maintained and will continue to maintain their importance due to their reliability in adverse weather conditions. Virtual methods are being developed for verification and validation of automated driving functions to reduce the time and cost of testing. Due to the complexity of modelling high-frequency wave propagation and signal processing and perception algorithms, sensor models that seek a high degree of accuracy are challenging to simulate. Therefore, a variety of different modelling approaches have been presented in the last two decades. This paper comprehensively summarises the heterogeneous state of the art in radar sensor modelling. Instead of a technology-oriented classification as introduced in previous review articles, we present a classification of how these models can be used in vehicle development by using the V-model originating from software development. Sensor models are divided into operational, functional, technical, and individual models. The application and usability of these models along the development process are summarised in a comprehensive tabular overview, which is intended to support future research and development at the vehicle level and will be continuously updated.

Gossypol, a novel modulator of VCP, induces autophagic degradation of mutant huntingtin by promoting the formation of VCP/p97-LC3-mHTT complex.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by toxic aggregates of mutant huntingtin protein (mHTT) in the brain. Decreasing mHTT is a potential strategy for therapeutic purpose of HD. Valosin-containing protein (VCP/p97) is a crucial regulator of proteostasis, which regulates the degradation of damaged protein through proteasome and autophagy pathway. Since VCP has been implicated in pathogenesis of HD as well as other neurodegenerative diseases, small molecules that specifically regulate the activity of VCP may be of therapeutic benefits for HD patients. In this study we established a high-throughput screening biochemical assay for VCP ATPase activity measurement and identified gossypol, a clinical approved drug in China, as a novel modulator of VCP. Gossypol acetate dose-dependently inhibited the enzymatic activity of VCP in vitro with IC50 of 6.53±0.6 µM. We further demonstrated that gossypol directly bound to the interface between the N and D1 domains of VCP. Gossypol acetate treatment not only lowered mHTT levels and rescued HD-relevant phenotypes in HD patient iPS-derived Q47 striatal neurons and HD knock-in mouse striatal cells, but also improved motor function deficits in both Drosophila and mouse HD models. Taken together, gossypol acetate acted through a gain-of-function way to induce the formation of VCP-LC3-mHTT ternary complex, triggering autophagic degradation of mHTT. This study reveals a new strategy for treatment of HD and raises the possibility that an existing drug can be repurposed as a new treatment of neurodegenerative diseases.

Targeting Gpr52 lowers mutant HTT levels and rescues Huntington's disease-associated phenotypes.

See Huang and Gitler (doi:10.1093/brain/awy112) for a scientific commentary on this article.Lowering the levels of disease-causing proteins is an attractive treatment strategy for neurodegenerative disorders, among which Huntington's disease is an appealing disease for testing this strategy because of its monogenetic nature. Huntington's disease is mainly caused by cytotoxicity of the mutant HTT protein with an expanded polyglutamine repeat tract. Lowering the soluble mutant HTT may reduce its downstream toxicity and provide potential treatment for Huntington's disease. This is hard to achieve by small-molecule compound drugs because of a lack of effective targets. Here we demonstrate Gpr52, an orphan G protein-coupled receptor, as a potential Huntington's disease drug target. Knocking-out Gpr52 significantly reduces mutant HTT levels in the striatum and rescues Huntington's disease-associated behavioural phenotypes in a knock-in Huntington's disease mouse model expressing endogenous mutant Htt. Importantly, a novel Gpr52 antagonist E7 reduces mutant HTT levels and rescues Huntington's disease-associated phenotypes in cellular and mouse models. Our study provides an entry point for Huntington's disease drug discovery by targeting Gpr52.

Tau Accumulation via Reduced Autophagy Mediates GGGGCC Repeat Expansion-Induced Neurodegeneration in Drosophila Model of ALS.

Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome-lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.

Magnetism and Optical Anisotropy in van der Waals Antiferromagnetic Insulator CrOCl.

van der Waals (vdW) magnetic insulators are of significance in both fundamental research and technological application, but most two-dimensional (2D) vdW magnetic systems are unstable and of high lattice symmetry. Stable 2D vdW magnetic insulators with anisotropic structure are needed to modulate the properties and unlock potential applications. Here we present a stable vdW antiferromagnetic material, CrOCl, with low-symmetry orthorhombic structure, and investigate systematically its magnetism, phase transition behavior, and optical anisotropy. Spin-phonon coupling effects are uncovered by the abnormal frequency shifts of Raman-active modes, suggesting the formation of a magnetic superstructure. The sizable abnormal change of interplanar spacing indicates the presence of a structural transition at around 27 K. Further in-plane vibrational, reflectional, and absorptional anisotropic properties are explored both experimentally and theoretically, revealing a highly polarization sensitive characteristic and linear dichroism in 2D CrOCl. Meanwhile, the particularly high polarization dependency of the second-harmonic generation and the nonlinear susceptibility of ∼2.24 × 10-11 m/V make it suitable in the field of polarization-dependent nonlinear optics. The findings on the intricate properties of 2D CrOCl lay foundations for future applications of low-symmetry vdW magnets in spin-dependent electronic and optoelectronic devices.

Competing spin fluctuations and trace of vortex dynamics in the two-dimensional triangular-lattice antiferromagnet AgCrS2.

The spin dynamics of the two-dimensional triangular-lattice antiferromagnet AgCrS2 is investigated by electron spin resonance (ESR) spectroscopy. The g-factor is found to show an unusual non-monotonously temperature dependent behavior, which, along with the super-Curie behavior observed in the ESR intensity data, provides clear evidence for the competition between ferromagnetic and antiferromagnetic fluctuations at temperatures well above T N. On approaching the Néel temperature T N from above, the linewidth is found to diverge. Such a divergent behavior could be well described by the Kawamura-Miyashita model due to Z2 type magnetic vortex-antivortex pairing, which is consistent with the expectation for a 2D Heisenberg magnetic system.

Critical behavior of the van der Waals bonded high T C ferromagnet Fe3GeTe2.

Fe3GeTe2 is a promising candidate for van der Waals bonded ferromagnet because of its high Curie temperature and the prediction that its ferromagnetism can maintain upon exfoliating down to single layer. Here, we have reported the critical behavior to understand its ferromagnetic exchange. Based on various techniques including modified Arrott plot, Kouvel-Fisher plot, and critical isotherm analysis, a set of reliable critical exponents (ß = 0.327 ± 0.003, γ = 1.079 ± 0.005, and δ = 4.261 ± 0.009) has been obtained. The critical behavior suggests a three-dimensional long-range magnetic coupling with the exchange distance decaying as J(r) ≈ r -4.6 in Fe3GeTe2. The possible origin of three-dimensional magnetic characteristics in van der Waals bonded magnets is discussed.