Role of Pirh2 in Mediating the Regulation of p53 and c-Myc

Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in response to DNA damage. We also demonstrate that c-Myc is a novel interacting protein for Pirh2 and that Pirh2 mediates its polyubiquitylation and proteolysis. Pirh2 mutant mice display elevated levels of c-Myc and are predisposed for plasma cell hyperplasia and tumorigenesis. Consistent with the role p53 plays in suppressing c-Myc-induced oncogenesis, its deficiency exacerbates tumorigenesis of Pirh2−/− mice. We also report that low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival. Collectively, our data reveal the in vivo roles of Pirh2 in the regulation of p53 and c-Myc stability and support its role as a tumor suppressor

Planning for automated vehicles with human trust

Recent work has considered personalized route planning based on user profiles, but none of it accounts for human trust. We argue that human trust is an important factor to consider when planning routes for automated vehicles. This paper presents a trust-based route planning approach for automated vehicles. We formalize the human-vehicle interaction as a partially observable Markov decision process (POMDP) and model trust as a partially observable state variable of the POMDP, representing the human’s hidden mental state. We build data-driven models of human trust dynamics and takeover decisions, which are incorporated in the POMDP framework, using data collected from an online user study with 100 participants on the Amazon Mechanical Turk platform. We compute optimal routes for automated vehicles by solving optimal policies in the POMDP planning, and evaluate the resulting routes via human subject experiments with 22 participants on a driving simulator. The experimental results show that participants taking the trust-based route generally reported more positive responses in the after-driving survey than those taking the baseline (trust-free) route. In addition, we analyze the trade-offs between multiple planning objectives (e.g., trust, distance, energy consumption) via multi-objective optimization of the POMDP. We also identify a set of open issues and implications for real-world deployment of the proposed approach in automated vehicles

Metallogenic Material Source and Genesis of the Jilinbaolige Pb-Zn-Ag Deposit, the Great Xing’an Range, China: Constraints from Mineralogical, S Isotopic, and Pb Isotopic Studies of Sulfide Ores

The Jilinbaolige Pb-Zn-Ag polymetallic deposit is located in the eastern part of Inner Mongolia and in the central-southern part of the Great Xing’an Range, in which several large-sized Pb-Zn-Ag deposits have been found. The Jilinbaolige deposit, which occurs mainly at the contact zone between Yanshanian granite intrusion and sedimentary strata, shows strong NE-to-NNE structural control. The deposit includes three ore-forming stages: (1) the arsenopyrite–pyrite–chalcopyrite–sphalerite stage, (2) the galena–sphalerite–quartz stage, and (3) the pyrite–calcite–quartz stage. In this study, we present a systematic study on the mineralogical and geochemical characteristics (including major elements, S isotopes, and Pb isotopes) of the main sulfide ore minerals in the Jilinbaolige Pb-Zn-Ag deposit in order to evaluate the metallogenic environment, ore-forming material source, and genesis of this polymetallic deposit. The sulfide typomorphic characteristics, ore fabric, and thermometry suggest that the genesis of sulfides in the deposit is closely related to magmatic-hydrothermal activity. The early stage of mineralization might have evolved from a high-temperature hydrothermal environment. The sulfur isotopic results show that the δ34S values in the Jilinbaolige deposit range from 2.3‰ to 6.1‰, with an average value of 3.98‰, indicating that the sulfur originated from magmas with both mantle and crustal components. The Pb isotopic compositions (206Pb/204Pb = 18.214–18.330, 207Pb/204Pb = 15.478–15.615, 208Pb/204Pb = 37.957–38.292, μ = 9.24–9.50, ω = 34.49–36.49) of the sulfide ores suggest that that the lead is of crust-mantle mixed origin. The comparison between the S and Pb isotopic compositions of the Jilinbaolige deposit and the polymetallic deposits from the central-southern parts of the Great Xing’an Range suggests that these deposits have a similar metallogenic source, which is closely related to the Yanshanian granite and medium-temperature hydrothermal fluids. These ore-bearing hydrothermal fluids that evolved from deep magmatic sources migrated along the contact and fracture zones and during the subsequent gradual decrease in temperature, and the metallogenic components were deposited in the relatively open fracture and fissure space. Our results provide insights for further mineral prospecting in the south-central part of the Great Xing’an Range

Metallogenic Material Source and Genesis of the Jilinbaolige Pb-Zn-Ag Deposit, the Great Xing’an Range, China: Constraints from Mineralogical, S Isotopic, and Pb Isotopic Studies of Sulfide Ores

The Jilinbaolige Pb-Zn-Ag polymetallic deposit is located in the eastern part of Inner Mongolia and in the central-southern part of the Great Xing’an Range, in which several large-sized Pb-Zn-Ag deposits have been found. The Jilinbaolige deposit, which occurs mainly at the contact zone between Yanshanian granite intrusion and sedimentary strata, shows strong NE-to-NNE structural control. The deposit includes three ore-forming stages: (1) the arsenopyrite–pyrite–chalcopyrite–sphalerite stage, (2) the galena–sphalerite–quartz stage, and (3) the pyrite–calcite–quartz stage. In this study, we present a systematic study on the mineralogical and geochemical characteristics (including major elements, S isotopes, and Pb isotopes) of the main sulfide ore minerals in the Jilinbaolige Pb-Zn-Ag deposit in order to evaluate the metallogenic environment, ore-forming material source, and genesis of this polymetallic deposit. The sulfide typomorphic characteristics, ore fabric, and thermometry suggest that the genesis of sulfides in the deposit is closely related to magmatic-hydrothermal activity. The early stage of mineralization might have evolved from a high-temperature hydrothermal environment. The sulfur isotopic results show that the δ34S values in the Jilinbaolige deposit range from 2.3‰ to 6.1‰, with an average value of 3.98‰, indicating that the sulfur originated from magmas with both mantle and crustal components. The Pb isotopic compositions (206Pb/204Pb = 18.214–18.330, 207Pb/204Pb = 15.478–15.615, 208Pb/204Pb = 37.957–38.292, μ = 9.24–9.50, ω = 34.49–36.49) of the sulfide ores suggest that that the lead is of crust-mantle mixed origin. The comparison between the S and Pb isotopic compositions of the Jilinbaolige deposit and the polymetallic deposits from the central-southern parts of the Great Xing’an Range suggests that these deposits have a similar metallogenic source, which is closely related to the Yanshanian granite and medium-temperature hydrothermal fluids. These ore-bearing hydrothermal fluids that evolved from deep magmatic sources migrated along the contact and fracture zones and during the subsequent gradual decrease in temperature, and the metallogenic components were deposited in the relatively open fracture and fissure space. Our results provide insights for further mineral prospecting in the south-central part of the Great Xing’an Range