| 1. |
- Liu, Meng, 1976, et al.
(författare)
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Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 107:14, s. 6471-6476
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Tidskriftsartikel (refereegranskat)abstract
- RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.
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| 2. |
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| 4. |
- Liu, Yu, et al.
(författare)
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Tree-ring stable carbon isotope-based May-July temperature reconstruction over Nanwutai, China, for the past century and its record of 20th century warming
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 93, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- Growth anomaly of trees in some regions was detected under current episode of rapid warming. This raises a dilemma for temperature reconstructions by using tree-ring width which is believed to be the most important proxy on inter-annual temperature reconstruction during the past millenniums. Here we employed the tree-ring d13C to reconstruct temperature variations for exploring their potential on capturing signals of rapid warming, and to test how its difference with the tree-ring width based reconstruction. In this study the mean MayeJuly temperature (TMeJ) was reconstructed over the past century by tree-ring d13C of Chinese pine trees growing in the Nanwutai region. The explained variance of the reconstruction was 43.3% (42.1% after adjusting the degrees of freedom). Compared to a ring-width temperature reconstruction (MayeJuly) from the same site, the tree-ring d13C-based temperature reconstruction offered two distinct advantages: 1) it captured a wider range of temperature variability, i.e., at least MayeJuly, even over a longer part of the year, JanuaryeSeptember; and 2) the reconstruction preserved more low-frequency climate information than that of ring width did. The 20th century warming was well represented in the Nanwutai tree-ring d13C temperature reconstruction, which implied that stable carbon isotope of tree rings potentially represents temperature variations during historical episodes of rapid warming. A spatial correlation analysis showed that our temperature reconstruction represented climate variations over the entire Loess Plateau in north-central China. Significant positive correlations (p < 0.1) were found between the temperature reconstruction and ENSO, as well as SSTs in the Pacific and Indian Oceans. The reconstruction showed the periodicities of 22.78-, 4.16-, 3.45e3.97- and 2.04e2.83-year quasi-cycles at a 95% confidence level. Our results suggested that temperature variability in the Nanwutai region may be linked to Pacific and Indian Ocean SST variations and solar activity.
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| 5. |
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| 6. |
- Song, Huiming, et al.
(författare)
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Tree-ring derived temperature records in the central Loess Plateau, China
- 2013
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Ingår i: Quaternary International. - : Elsevier BV. - 1040-6182. ; 283, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Using tree-ring widths of Pinus tabulaeformis Carr. trees, mean temperatures from February to September were reconstructed for the Kongtong Mountain during the past 283 years. The reconstruction could explain 43.7% of temperature variance during the calibration period from 1951 to 2004. It displays similar patterns to several temperature reconstructions in the Loess Plateau. It corresponds well with the temperature regimes in Hokkaido, Japan, indicating that both regions have similar warm and cold intervals. The high correlation between the reconstruction and the CRU (Climatic Research Unit of University of East Anglia, UK) TS3 temperature datasets showed that the temperature reconstruction could be representative of large-scale climate change over northern China. In addition, the Pacific Decadal Oscillation (PDO) affected temperature variations of northern China and even Hokkaido to a certain extent.
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| 7. |
- Wang, Ling, et al.
(författare)
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Perfluorooctanesulfonate Induces Hepatomegaly and Lipoatrophy in Mice through Phosphoenolpyruvate Carboxykinase-Mediated Glyceroneogenesis Inhibition
- 2020
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Ingår i: Environmental Science and Technology Letters. - : American Chemical Society (ACS). - 2328-8930. ; 7:3, s. 185-190
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctansulfonate (PFOS) is a persistent organic pollutant that has attracted a great deal of attention due to toxic effects such as its lipid metabolism-disrupting potential. Exposure to PFOS can cause hepatomegaly and lipoatrophy in mice, but the underlying mechanisms are still unknown. Considering that glyceroneogenesis is the essential pathway for balancing the triglyceride (TG) cycle between liver and white adipose tissue (WAT), we speculate that PFOS acts via glyceroneogenesis inhibition to alter TG metabolism in the two tissues. Combining gene expression, protein expression, an enzyme activity assay, and molecular docking analysis, we report here that PFOS can interact with cytosolic phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of glyceroneogenesis. Specifically, by repression of PEPCK, PFOS can inhibit the glyceroneogenesis process and thus decrease the glyceroneogenesis-derived glycerol level, leading to a reduced re-esterified TG level and causing atrophy in WAT. Moreover, in PFOS-exposed liver tissue, despite the fact that free glycerol and fatty acids released from WAT were being used for TG synthesis, the export of TG slowed. This eventually resulted in the continuous lipolysis of WAT and accumulation of lipid in the liver. PEPCK can be used as a key biomarker to assess the lipid metabolism disorders induced by other conventional and emerging per- and polyfluoroalkyl substances.
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| 8. |
- Zhu, Huiming, et al.
(författare)
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Bayesian Analysis of a Stochastic Volatility Model Using Gibbs Sampling
- 2008
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Ingår i: Hunan Daxue Xuebao (Ziran Kexue Ban). - 1674-2974. ; 35:12
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Tidskriftsartikel (refereegranskat)abstract
- After exploring the statistical structure of the stochastic volatility model, its likelihood functions concrete form is derived, and its parameters conjugate priors are constructed. Then, using the Bayesian theorem, the conditional posterior distributions are derived. In order to obtain the Baysian parameters estimators and their intervals, we develop a Markov chain Monte Carlo algorithm procedure with Gibbs sampling. Finally, using the Shanghai stocks comprehensive index and the Shenzhen stocks composition index, we give an empirical example to illustrate how to use the proposed method. This paper provides a new approach to establish Bayesian models for financial stochastic volatilities with random parameters.
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| 9. |
- Zhu, Huiming, et al.
(författare)
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Bayesian multivariate monitoring models for process mean vectors based on multistage predictive distributions
- 2011
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Ingår i: Hunan Daxue Xuebao (Ziran Kexue Ban). - 1674-2974. ; 38:3, s. 82-86
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to utilize sample information in different stages and solve the parameter uncertainty risk in statistical process control. This paper introduces a reference prior distribution for the parameters in quality models, and constructs the warning lines and action lines to monitor the mean vectors change according to the predictive distribution as well as the relationship between the multivariate t distribution and F distribution. When the current stage is under control, the parametric posterior distribution is considered to be their priori distribution in the next stage, in which the sequential Bayesian mean vector control method is established.
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