Browsing by Author "Wang, M"

Now showing 1 - 6 of 6
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    A constitutively active mutant beta 2-adrenergic receptor is constitutively desensitized and phosphorylated.
    (Proc Natl Acad Sci U S A, 1994-03-29) Pei, G; Samama, P; Lohse, M; Wang, M; Codina, J; Lefkowitz, RJ
    The beta 2-adrenergic receptor (beta 2AR) can be constitutively activated by mutations in the third intracellular loop. Whereas the wild-type receptor exists predominantly in an inactive conformation (R) in the absence of agonist, the mutant receptor appears to spontaneously adopt an active conformation (R*). We now demonstrate that not only is the mutant beta 2AR constitutively active, it is also constitutively desensitized and down-regulated. To assess whether the mutant receptor can constitutively engage a known element of the cellular desensitization machinery, the receptor was purified and reconstituted into phospholipid vesicles. These preparations retained the essential properties of the constitutively active mutant receptor: agonist-independent activity [to stimulate guanine nucleotide-binding protein (Gs)-GTPase] and agonist-specific increase in binding affinity. Moreover, the purified mutant receptor, in the absence of agonist, was phosphorylated by recombinant beta AR-specific kinase (beta ARK) in a fashion comparable to the agonist-occupied wild-type receptor. Thus, the conformation of the mutated receptor is equivalent to the active conformation (R*), which stimulates Gs protein and is identical to the beta ARK substrate.
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    Deep multiscale model learning
    (Journal of Computational Physics, 2019-11) Wang, Y; Cheung, SW; Chung, ET; Efendiev, Y; Wang, M
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    Genetic variants in the TEP1 gene are associated with prostate cancer risk and recurrence.
    (Prostate Cancer Prostatic Dis, 2015-12) Gu, C; Li, Q; Zhu, Y; Qu, Y; Zhang, G; Wang, M; Yang, Y; Wang, J; Jin, L; Wei, Q; Ye, D
    BACKGROUND: Telomere-related genes play an important role in carcinogenesis and progression of prostate cancer (PCa). It is not fully understood whether genetic variations in telomere-related genes are associated with development and progression in PCa patients. METHODS: Six potentially functional single-nucleotide polymorphisms (SNPs) of three key telomere-related genes were evaluated in 1015 PCa cases and 1052 cancer-free controls, to test their associations with risk of PCa. Among 426 PCa patients who underwent radical prostatectomy (RP), the prognostic significance of the studied SNPs on biochemical recurrence (BCR) was also assessed using the Kaplan-Meier analysis and Cox proportional hazards regression model. The relative telomere lengths (RTLs) were measured in peripheral blood leukocytes using real-time PCR in the RP patients. RESULTS: TEP1 rs1760904 AG/AA genotypes were significantly associated with a decreased risk of PCa (odds ratio (OR): 0.77, 95% confidence interval (CI): 0.64-0.93, P=0.005) compared with the GG genotype. By using median RTL as a cutoff level, RP patients with TEP1 rs1760904 AG/AA genotypes tended to have a longer RTL than those with the GG genotype (OR: 1.55, 95% CI: 1.04-2.30, P=0.031). A significant interaction between TEP1 rs1713418 and age in modifying PCa risk was observed (P=0.005). After adjustment for clinicopathologic risk factors, the presence of heterozygotes or rare homozygotes of TEP1 rs1760904 and TNKS2 rs1539042 were associated with BCR in the RP cohorts (hazard ratio: 0.53, 95% CI: 0.36-0.79, P=0.002 and hazard ratio: 1.67, 95% CI: 1.07-2.48, P=0.017, respectively). CONCLUSIONS: These data suggest that genetic variations in the TEP1 gene may be biomarkers for risk of PCa and BCR after RP.
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    Guest Editors’ Introduction: The Urban In-Between
    (Positions, 2022-08-01) Chu, N; Litzinger, R; Wang, M; Zhu, Q
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    Introduction: Video Illustrations of Techniques and Strategies for Adult and Pediatric Spinal Deformity Surgery
    (Neurosurgical Focus: Video, 2020-01-01) Smith, JS; Shaffrey, CI; Wang, M; Bydon, M; Lenke, L
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    The effect of lead time and demand uncertainties in (r, q) inventory systems
    (Operations Research, 2010-01-01) Song, JS; Zhang, H; Hou, Y; Wang, M
    We study a single-item (r, q) inventory system, where r is the reorder point and q is the order quantity. The demand is a compound-Poisson process. We investigate the behavior of the optimal policy parameters and the long-run average cost of the system in response to stochastically shorter or less-variable lead times. We show that although some of the properties of the base-stock system can be extended to this more general model, some cannot. The same findings also apply when the comparison is conducted on the lead-time demand distributions. © 2010 INFORMS.