Efficient estimation of smoothing spline with exact shape constraints

Smoothing spline is a popular method in non-parametric function estimation. For the analysis of data from real applications, specific shapes on the estimated function are often required to ensure the estimated function undeviating from the domain knowledge. In this work, we focus on constructing the exact shape constrained smoothing spline with efficient estimation. The ‘exact’ here is referred as to impose the shape constraint on an infinite set such as an interval in one-dimensional case. Thus the estimation becomes a so-called semi-infinite optimisation problem with an infinite number of constraints. The proposed method is able to establish a sufficient and necessary condition for transforming the exact shape constraints to a finite number of constraints, leading to efficient estimation of the shape constrained functions. The performance of the proposed methods is evaluated by both simulation and real case studies

Responses of water quality and phytoplankton assemblages to remediation projects in two hypereutrophic tributaries of Chaohu Lake

Water shortages and the presence of point and diffuse source pollution have caused a serious deterioration in water quality in two tributaries (the Tangxi River and Shiwuli River) of Chaohu Lake, China. To reduce nutrient pollution and suppress harmful algal blooms (HABs), hard engineering and ecological remediation projects were implemented. A post-project investigation from 2013 to 2016 was carried out to evaluate the outcome of the remediation projects by monitoring the seasonal and spatial variations in water quality and the phytoplankton community. In the Tangxi River, the average total phosphorus (TP) concentrations in the four seasons were below 0.5 mg L-1, with the lowest concentration (0.29 +/- 0.12 mg L-1) found in autumn. Remediation measures including sediment dredging, riparian buffer zone creation, downstream wetland park construction, and water augmentation using reclaimed water and filtered lake water might combine to promote P source mitigation. Moreover, the percentage of bloom-forming cyanobacteria (i.e., Microcystis, Aphanizomenon, Anabaena, Osanatoria, Phormidium and Planktothrix) in the phytoplankton assemblage and the biomass of the dominant species indicated successful HAB control. In the Shiwuli River, water quality improvements and phytoplankton responses have been observed since 2015 after the upgrading of a local wastewater treatment plant (WWTP) with effluent that was used for flow augmentation. Nevertheless, there is still room for improvement via increasing the river self-purification ability (e.g., the creation of downstream wetlands and riparian buffer zones) and promoting water augmentation according to the experience gained in the remediation projects of the Tangxi River.</p

SPOP point mutations regulate substrate preference and affect its function

Abstract The adaptor SPOP recruits substrates to CUL3 E3 ligase for ubiquitination and degradation. Structurally, SPOP harbors a MATH domain for substrate recognition, and a BTB domain responsible for binding CUL3. Reported point mutations always occur in SPOP’s MATH domain and are through to disrupt affinities of SPOP to substrates, thereby leading to tumorigenesis. In this study, we identify the tumor suppressor IRF2BP2 as a novel substrate of SPOP. SPOP enables to attenuate IRF2BP2-inhibited cell proliferation and metastasis in HCC cells. However, overexpression of wild-type SPOP alone suppresses HCC cell proliferation and metastasis. In addition, a HCC-derived mutant, SPOP-M35L, shows an increased affinity to IRF2BP2 in comparison with wild-type SPOP. SPOP-M35L promotes HCC cell proliferation and metastasis, suggesting that M35L mutation possibly reprograms SPOP from a tumor suppressor to an oncoprotein. Taken together, this study uncovers mutations in SPOP’s MATH lead to distinct functional consequences in context-dependent manners, rather than simply disrupting its interactions with substrates, raising a noteworthy concern that we should be prudent to select SPOP as therapeutic target for cancers

Role of the ER/NO/cGMP Signaling Pathway in the Promotion of Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Actaea racemosa Extract

Purpose/Objective. To investigate the effect of Actaea racemosa (AR) extract on in vitro osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) via the ER/NO/cGMP signaling pathway. Methods/Materials. Rat BMSCs were treated with osteogenic differentiation-inducing medium containing AR; estrogen receptor antagonist, ICI 182,780 (10−6 mol/L); and nitric oxide synthase inhibitor, L-nitro arginine methyl ester (L-NAME, 6 × 10−3 mol/L). Markers of osteogenic differentiation (alkaline phosphatase [ALP] activity, osteocalcin secretion, and calcium ion deposit levels) and the levels of key signaling molecules (nitric oxide synthase [NOS], nitric oxide [NO], and cyclic guanosine monophosphate [cGMP]) were assessed. Results. AR (10−1–10−6 g/L) increased ALP activity in a dose-dependent manner, and the highest ALP, osteocalcin, and osteoprotegerin activities were achieved at an AR concentration of 10−4 g/L. Therefore, the concentration of 10−4 g/L was used for promoting osteogenic differentiation of BMSCs in subsequent analyses. At this concentration, AR increased the levels of NO and cGMP, and such effects could be blocked by the estrogen receptor antagonist (ICI 182,780) and nitric oxide synthase inhibitor (L-NAME). Conclusion. AR induced osteogenic differentiation of rat BMSCs through the ER/NO/cGMP signaling pathway. This finding provides the theoretical foundation for the mechanism of AR in the treatment of postmenopausal osteoporosis

Elucidation of piericidin A1 biosynthetic locus revealed a thioesterase-dependent mechanism of a-pyridone ring formation

Piericidins are a class of α-pyridone antibiotics that inhibit mitochondrial respiratory chain and exhibit antimicrobial, antifungal, and antitumor activities. Sequential analysis of Streptomyces piomogeues var. Hangzhouwanensis genome revealed six modu