61 research outputs found
Making Optimal Decisions of Assembly Products in Supply Chain
The strategic pricing decisions of assembly products in assembly products supply chain are studied in this paper. Firstly, a two-stage assembly products supply chain model is developed. By building Nash game model, the Nash equilibrium solution of pricing strategy of supplier and assemblers is obtained. Next, a union decision model is built to analyze the optimal combination pricing strategy of assembly products, and the relationship between the optimal strategies is established. The law of the changing in combination pricing strategy, assemblers’ profits and supplier’s profit along with the variety of some characteristics has been investigated by using numerical simulation. The results are consistent with economics principles.</p
Learning from evolved next release problem instances
International audienceTaking the Next Release Problem (NRP) as a case study, we intend to analyze the relationship between heuristics and the software engineering problem instances. We adopt an evolutionary algorithm to evolve NRP instances that are either hard or easy for the target heuristic (GRASP in this study), to investigate where a heuristic works well and where it does not, when facing a software engineering problem. Thereafter, we use a feature-based approach to predict the hardness of the evolved instances, with respect to the target heuristic. Experimental results reveal that, the proposed algorithm is able to evolve NRP instances with different hardness. Furthermore, the problem-specific features enables the prediction of the target heuristic's performance
LIP5, a MVB biogenesis regulator, is required for rice growth
LYST-INTERACTING PROTEIN5 (LIP5) is a conserved regulator of multivesicular body (MVB) biogenesis in eukaryotes. In Arabidopsis, AtLIP5 is a target of stress-responsive MITOGEN-ACTIVATED PROTEIN KINASE3 and 6 and mediates stress-induced MVB biogenesis to promote stress responses. However, Arabidopsis atlip5 knockout mutants are normal in growth and development. Here we report that rice OsLIP5 gene could fully restore both the disease resistance and salt tolerance of the Arabidopsis oslip5 mutant plants to the wild-type levels. Unlike Arabidopsis atlip5 mutants, rice oslip5 mutants were severely stunted, developed necrotic lesions and all died before flowering. Unlike in Arabidopsis, LIP5 regulated endocytosis under both stress and normal conditions in rice. These findings indicate that there is strong evolutionary divergence among different plants in the role of the conserved LIP5-regulated MVB pathway in normal plant growth
Elevated CO negates O impacts on terrestrial carbon and nitrogen cycles
Increasing tropospheric concentrations of ozone (e[O]) and carbon dioxide (e[CO]) profoundly perturb terrestrial ecosystem functions through carbon and nitrogen cycles, affecting beneficial services such as their capacity to combat climate change and provide food. However, the interactive effects of e[O] and e[CO] on these functions and services remain unclear. Here, we synthesize the results of 810 studies (9,109 observations), spanning boreal to tropical regions around the world, and show that e[O] significantly decreases global net primary productivity and food production as well as the capacity of ecosystems to store carbon and nitrogen, which are stimulated by e[CO]. More importantly, simultaneous increases in [CO] and [O] negate or even overcompensate the negative effects of e[O3] on ecosystem functions and carbon and nitrogen cycles. Therefore, the negative effects of e[O] on terrestrial ecosystems would be overestimated if e[CO] impacts are not considered, stressing the need for evaluating terrestrial carbon and nitrogen feedbacks to concurrent changes in global atmospheric composition
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The association of serum total bile acid with non-alcoholic fatty liver disease in Chinese adults: a cross sectional study
Background
Non-alcoholic fatty liver disease (NAFLD) is currently the major cause of chronic liver disease globally. Bile acids (BAs) have emerged as relevant signaling molecules that are associated with NAFLD development. This study was aimed to examine the association of serum total bile acids (TBAs) with NAFLD in a large population of Chinese subjects.
Methods
This cross sectional study recruited 152,336 participants from the Second Xiangya Hospital, China. NAFLD was diagnosed based on the presence of hepatic steatosis on ultrasonography, without significant alcohol consumption and other known causes for chronic liver disease. A multivariate logistic regression model was used to test for the association of serum TBAs with NAFLD, adjusting for conventional risk factors of NAFLD.
Results
A total of 27.4% of the participants had NAFLD. Patients with NAFLD had slightly higher TBA levels than those without, 3.4 vs. 3.0 μmol/L (p < 0.001). However, TBA levels were not associated with NAFLD in the multivariate logistic regression model, which adjusted for age, gender and other acknowledged risk factors for NAFLD (OR = 1.00. 95% CI: 1.00–1.00, p = 0.797).
Conclusions
We found that the serum TBA levels were not associated with NAFLD. Future studies in a large population, focusing on serum BA composition may improve the understating of the role of BAs in NAFLD
In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors
Fructose 1,6-bisphosphatase (FBPase) has been identified as a drug discovery target for lowering glucose in type 2 diabetes mellitus. In this study, a large series of 105 FBPase inhibitors were studied using a combinational method by 3D-QSAR, molecular docking and molecular dynamics simulations for a further improvement in potency. The optimal 3D models exhibit high statistical significance of the results, especially for the CoMFA results with rncv2, q2 values of 0.986, 0.514 for internal validation, and rpred2, rm2 statistics of 0.902, 0.828 statistics for external validation. Graphic representation of the results, as contoured 3D coefficient plots, also provides a clue to the reasonable modification of molecules. (1) Substituents with a proper length and size at the C5 position of the thiazole core are required to enhance the potency; (2) A small and electron-withdrawing group at the C2 position linked to the thiazole core is likely to help increase the FBPase inhibition; (3) Substituent groups as hydrogen bond acceptors at the C2 position of the furan ring are favored. In addition, the agreement between 3D-QSAR, molecular docking and molecular dynamics simulation proves the rationality of the developed models. These results, we hope, may be helpful in designing novel and potential FBPase inhibitors
MyoPS A Benchmark of Myocardial Pathology Segmentation Combining Three-Sequence Cardiac Magnetic Resonance Images
Assessment of myocardial viability is essential in diagnosis and treatment
management of patients suffering from myocardial infarction, and classification
of pathology on myocardium is the key to this assessment. This work defines a
new task of medical image analysis, i.e., to perform myocardial pathology
segmentation (MyoPS) combining three-sequence cardiac magnetic resonance (CMR)
images, which was first proposed in the MyoPS challenge, in conjunction with
MICCAI 2020. The challenge provided 45 paired and pre-aligned CMR images,
allowing algorithms to combine the complementary information from the three CMR
sequences for pathology segmentation. In this article, we provide details of
the challenge, survey the works from fifteen participants and interpret their
methods according to five aspects, i.e., preprocessing, data augmentation,
learning strategy, model architecture and post-processing. In addition, we
analyze the results with respect to different factors, in order to examine the
key obstacles and explore potential of solutions, as well as to provide a
benchmark for future research. We conclude that while promising results have
been reported, the research is still in the early stage, and more in-depth
exploration is needed before a successful application to the clinics. Note that
MyoPS data and evaluation tool continue to be publicly available upon
registration via its homepage
(www.sdspeople.fudan.edu.cn/zhuangxiahai/0/myops20/)
Structural Requirements of N-Substituted Spiropiperidine Analogues as Agonists of Nociceptin/Orphanin FQ Receptor
The nociceptin/orphanin FQ (NOP) receptor is involved in a wide range of biological functions, including pain, anxiety, depression and drug abuse. Especially, its agonists have great potential to be developed into anxiolytics. In this work, both the ligand- and receptor-based three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were carried out using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques on 103 N-substituted spiropiperidine analogues as NOP agonists. The resultant optimal ligand-based CoMSIA model exhibited Q2 of 0.501, R2ncv of 0.912 and its predictive ability was validated by using an independent test set of 26 compounds which gave R2pred value of 0.818. In addition, docking analysis and molecular dynamics simulation (MD) were also applied to elucidate the probable binding modes of these agonists. Interpretation of the 3D contour maps, in the context of the topology of the active site of NOP, provided insight into the NOP-agonist interactions. The information obtained from this work can be used to accurately predict the binding affinity of related agonists and also facilitate the future rational design of novel agonists with improved activity
The aging lung: microenvironment, mechanisms, and diseases
With the development of global social economy and the deepening of the aging population, diseases related to aging have received increasing attention. The pathogenesis of many respiratory diseases remains unclear, and lung aging is an independent risk factor for respiratory diseases. The aging mechanism of the lung may be involved in the occurrence and development of respiratory diseases. Aging-induced immune, oxidative stress, inflammation, and telomere changes can directly induce and promote the occurrence and development of lung aging. Meanwhile, the occurrence of lung aging also further aggravates the immune stress and inflammatory response of respiratory diseases; the two mutually affect each other and promote the development of respiratory diseases. Explaining the mechanism and treatment direction of these respiratory diseases from the perspective of lung aging will be a new idea and research field. This review summarizes the changes in pulmonary microenvironment, metabolic mechanisms, and the progression of respiratory diseases associated with aging
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