Automating Vehicles by Deep Reinforcement Learning using Task Separation with Hill Climbing

Within the context of autonomous driving a model-based reinforcement learning algorithm is proposed for the design of neural network-parameterized controllers. Classical model-based control methods, which include sampling- and lattice-based algorithms and model predictive control, suffer from the trade-off between model complexity and computational burden required for the online solution of expensive optimization or search problems at every short sampling time. To circumvent this trade-off, a 2-step procedure is motivated: first learning of a controller during offline training based on an arbitrarily complicated mathematical system model, before online fast feedforward evaluation of the trained controller. The contribution of this paper is the proposition of a simple gradient-free and model-based algorithm for deep reinforcement learning using task separation with hill climbing (TSHC). In particular, (i) simultaneous training on separate deterministic tasks with the purpose of encoding many motion primitives in a neural network, and (ii) the employment of maximally sparse rewards in combination with virtual velocity constraints (VVCs) in setpoint proximity are advocated.Comment: 10 pages, 6 figures, 1 tabl

Earliest tea as evidence for one branch of the Silk Road across the Tibetan Plateau.

Phytoliths and biomolecular components extracted from ancient plant remains from Chang'an (Xi'an, the city where the Silk Road begins) and Ngari (Ali) in western Tibet, China, show that the tea was grown 2100 years ago to cater for the drinking habits of the Western Han Dynasty (207BCE-9CE), and then carried toward central Asia by ca.200CE, several hundred years earlier than previously recorded. The earliest physical evidence of tea from both the Chang'an and Ngari regions suggests that a branch of the Silk Road across the Tibetan Plateau, was established by the second to third century CE

Improved gradient descent algorithms for time-delay rational state-space systems: Intelligent search method and momentum method

This study proposes two improved gradient descent parameter estimation algorithms for rational state-space models with time-delay. These two algorithms, based on intelligent search method and momentum method, can simultaneously estimate the time-delay and parameters without the matrix eigenvalue calculation in each iteration. Compared with the traditional gradient descent algorithm, the improved algorithms come with two advantages: having quicker convergence rates and less computational efforts, particularly meaningful for those large scale systems. A simulated example is selected to illustrate the efficiency of the proposed algorithms

Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates

The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9th day though on the 14th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and duration of anticancer treatments

Combination of photothermal, prodrug and tumor cell camouflage technologies for triple-negative breast cancer treatment

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype. In the presented work, we have combined several emerging technologies to build up a nanoplatform for TNBC treatment: photothermal therapy, prodrug design and tumor cell camouflage formulation. First, we synthesized a paclitaxel (PTX) based prodrug PTX-SS, and then conjugated it to the surface of gold nanorod (Au NR) @ mesoporous silica (MSN) core-shell nanoparticles (Au@MSN-NH2 NPs). Subsequently, doxorubicin (DOX) was loaded into the Au@PTXSS-MSN NPs and further coated with cell membranes isolated from MDA-MB-231 cells to form cell camouflaged Au@PTXSS-MSN/DOX@CM NPs. The Au@PTXSS-MSN/DOX@CM NPs exhibited very good DOX loading capacity and the prodrug strategy enabled the precise adjustability of PTX-SS loading to achieve the optimized ratio between PTX and DOX to maximize the synergistic effect of these two drugs, as well as enabled GSH-responsive intracellular drug release. More interestingly, the cell membrane coating not only protected the drug from premature release, but also significantly improved the targeting ability of NPs to breast cancer MDA-MB-231 cells. The NPs also showed good photothermal responsiveness with clear improvement in inhibiting MDA-MB231 cell proliferation under laser irradiation. The in vivo studies further confirmed the effectiveness of Au@PTXSS-MSN/DOX@CM NPs on TNBC tumor inhibition in 4T1 cell grafted tumor mice model. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Cellular Tropism, Population Dynamics, Host Range and Taxonomic Status of an Aphid Secondary Symbiont, SMLS (Sitobion miscanthi L Type Symbiont)

SMLS (Sitobion miscanthi L type symbiont) is a newly reported aphid secondary symbiont. Phylogenetic evidence from molecular markers indicates that SMLS belongs to the Rickettsiaceae and has a sibling relationship with Orientia tsutsugamushi. A comparative analysis of coxA nucleotide sequences further supports recognition of SMLS as a new genus in the Rickettsiaceae. In situ hybridization reveals that SMLS is housed in both sheath cells and secondary bacteriocytes and it is also detected in aphid hemolymph. The population dynamics of SMLS differ from those of Buchnera aphidicola and titer levels of SMLS increase in older aphids. A survey of 13 other aphids reveals that SMLS only occurs in wheat-associated species

Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells

Ferroptosis, a form of iron-dependent cell death driven by cellular metabolism and iron-dependent lipid peroxidation, has been implicated as a tumor-suppressor function for cancer therapy. Recent advance revealed that the sensitivity to ferroptosis is tightly linked to numerous biological processes, including metabolism of amino acid and the biosynthesis of glutathione. Here, by using a high-throughput CRISPR/Cas9-based genetic screen in HepG2 hepatocellular carcinoma cells to search for metabolic proteins inhibiting ferroptosis, we identified a branched-chain amino acid aminotransferase 2 (BCAT2) as a novel suppressor of ferroptosis. Mechanistically, ferroptosis inducers (erastin, sorafenib, and sulfasalazine) activated AMPK/SREBP1 signaling pathway through iron-dependent ferritinophagy, which in turn inhibited BCAT2 transcription. We further confirmed that BCAT2 as the key enzyme mediating the metabolism of sulfur amino acid, regulated intracellular glutamate level, whose activation by ectopic expression specifically antagonize system Xc(-) inhibition and protected liver and pancreatic cancer cells from ferroptosis in vitro and in vivo. On the contrary, direct inhibition of BCAT2 by RNA interference, or indirect inhibition by blocking system Xc(-) activity, triggers ferroptosis. Finally, our results demonstrate the synergistic effect of sorafenib and sulfasalazine in downregulating BCAT2 expression and dictating ferroptotic death, where BCAT2 can also be used to predict the responsiveness of cancer cells to ferroptosis-inducing therapies. Collectively, these findings identify a novel role of BCAT2 in ferroptosis, suggesting a potential therapeutic strategy for overcoming sorafenib resistance

Synthesis, Magnetic Anisotropy and Optical Properties of Preferred Oriented Zinc Ferrite Nanowire Arrays

Preferred oriented ZnFe2O4 nanowire arrays with an average diameter of 16 nm were fabricated by post-annealing of ZnFe2 nanowires within anodic aluminum oxide templates in atmosphere. Selected area electron diffraction and X-ray diffraction exhibit that the nanowires are in cubic spinel-type structure with a [110] preferred crystallite orientation. Magnetic measurement indicates that the as-prepared ZnFe2O4 nanowire arrays reveal uniaxial magnetic anisotropy, and the easy magnetization direction is parallel to the axis of nanowire. The optical properties show the ZnFe2O4 nanowire arrays give out 370–520 nm blue-violet light, and their UV absorption edge is around 700 nm. The estimated values of direct and indirect band gaps for the nanowires are 2.23 and 1.73 eV, respectively