Prediction of histone deacetylase inhibition by triazole compounds based on artificial intelligence

A quantitative structure-activity relationship (QSAR) study was conducted to predict the anti-colon cancer and HDAC inhibition of triazole-containing compounds. Four descriptors were selected from 579 descriptors which have the most obvious effect on the inhibition of histone deacetylase (HDAC). Four QSAR models were constructed using heuristic algorithm (HM), random forest (RF), radial basis kernel function support vector machine (RBF-SVM) and support vector machine optimized by particle swarm optimization (PSO-SVM). Furthermore, the robustness of four QSAR models were verified by K-fold cross-validation method, which was described by Q2. In addition, the R2 of the four models are greater than 0.8, which indicates that the four descriptors selected are reasonable. Among the four models, model based on PSO-SVM method has the best prediction ability and robustness with R2 of 0.954, root mean squared error (RMSE) of 0.019 and Q2 of 0.916 for the training set and R2 of 0.965, RMSE of 0.017 and Q2 of 0.907 for the test set. In this study, four key descriptors were discovered, which will help to screen effective new anti-colon cancer drugs in the future

Quantifying the Effect of Mobile Channel Visits on Firm Revenue

The explosive penetration of mobile devices is one of the most prominent trends in e-business. Although the importance of mobile channel has prompted growing literature, little is known about the revenue implications of customer visit toward mobile channel. This study examines (1) the differential effect of mobile visits in affecting firm revenue (i.e. mobile vs. desktop visits), and (2) which type of mobile visits are more effective (i.e., direct vs. search engine and referral traffic; visits for high vs. low involvement products). We collect an unique objective daily data from a leading online travel agency in China. With a vector autoregressive (VAR) method, we find that, compared with desktop channel, mobile channel visits have shorter carryover effect, but larger short-term effect on firm revenues. Further, mobile channel has larger short-term effect on firm revenues for search engine traffic and lower involvement products. Our findings provide important theoretical contributions and notable implications for mobile commerce strategy

The Impact of Digital Platform Rapid Release Strategy on App Update Behavior: An Empirical Study of Firefox

The success of platform-based software ecosystems depends on the crucial coordination between the platform and third-party applications during co-evolution. Leveraging the change of platform release governance of Firefox, this paper examines the impact of the rapid release process on app update behavior (app responsiveness and app size change). Drawing on boundary resource perspective, we theorize how rapid release process as a social boundary resource affects app update behavior, and how app developers’ usage of technical boundary resource (i.e. platform API) affects this impact. Using a unique longitudinal dataset in Firefox, we conduct empirical analyses and conclude that the rapid release process decreases size change of app updates while platform API usage enhances app responsiveness. Moreover, platform API usage strengthens the effects of the rapid release process on app update behavior. This research enhances our understanding of the impact of platform governance practices on platform-third party coordination and provides practical guidance. Keywords: Platform-based software ecosystem, platform governance, app update, Rapid Release, boundary resourc

Dnmt3b ablation impairs fracture repair through upregulation of Notch pathway

We previously established that DNA methyltransferase 3b (Dnmt3b) is the sole Dnmt responsive to fracture repair and that Dnmt3b expression is induced in progenitor cells during fracture repair. In the current study, we confirmed that Dnmt3b ablation in mesenchymal progenitor cells (MPCs) resulted in impaired endochondral ossification, delayed fracture repair, and reduced mechanical strength of the newly formed bone in Prx1-Cre;Dnmt3bf/f (Dnmt3bPrx1) mice. Mechanistically, deletion of Dnmt3b in MPCs led to reduced chondrogenic and osteogenic differentiation in vitro. We further identified Rbpjκ as a downstream target of Dnmt3b in MPCs. In fact, we located 2 Dnmt3b binding sites in the murine proximal Rbpjκ promoter and gene body and confirmed Dnmt3b interaction with the 2 binding sites by ChIP assays. Luciferase assays showed functional utilization of the Dnmt3b binding sites in murine C3H10T1/2 cells. Importantly, we showed that the MPC differentiation defect observed in Dnmt3b deficiency cells was due to the upregulation of Rbpjκ, evident by restored MPC differentiation upon Rbpjκ inhibition. Consistent with in vitro findings, Rbpjκ blockage via dual antiplatelet therapy reversed the differentiation defect and accelerated fracture repair in Dnmt3bPrx1 mice. Collectively, our data suggest that Dnmt3b suppresses Notch signaling during MPC differentiation and is necessary for normal fracture repair

Antibacterial hemostatic dressings with nanoporous bioglass containing silver

Nanoporous bioglass containing silver (n-BGS) was fabricated using the sol-gel method, with cetyltrimethyl ammonium bromide as template. The results showed that n-BGS with nanoporous structure had a surface area of 467 m2/g and a pore size of around 6 nm, and exhibited a significantly higher water absorption rate compared with BGS without nanopores. The n-BGS containing small amounts of silver (Ag) had a slight effect on its surface area. The n-BGS containing 0.02 wt% Ag, without cytotoxicity, had a good antibacterial effect on Escherichia coli, and its antibacterial rate reached 99% in 12 hours. The n-BGS’s clotting ability significantly decreased prothrombin time (PT) and activated partial thromboplastin time (APTT), indicating n-BGS with a higher surface area could significantly promote blood clotting (by decreasing clotting time) compared with BGS without nanopores. Effective hemostasis was achieved in skin injury models, and bleeding time was reduced. It is suggested that n-BGS could be a good dressing, with antibacterial and hemostatic properties, which might shorten wound bleeding time and control hemorrhage

Rosiglitazone Restores Endothelial Dysfunction in a Rat Model of Metabolic Syndrome through PPARγ- and PPARδ-Dependent Phosphorylation of Akt and eNOS

Vascular endothelial dysfunction has been demonstrated in metabolic syndrome (MS). Chronic administration of rosiglitazone ameliorates endothelial dysfunction through PPARγ-mediated metabolic improvements. Recently, studies suggested that single dose of rosiglitazone also has direct vascular effects, but the mechanisms remain uncertain. Here we established a diet-induced rat model of MS. The impaired vasorelaxation in MS rats was improved by incubating arteries with rosiglitazone for one hour. Importantly, this effect was blocked by either inhibition of PPARγ or PPARδ. In cultured endothelial cells, acute treatment with rosiglitazone increased the phosphorylation of Akt and eNOS and the production of NO. These effects were also abolished by inhibition of PPARγ, PPARδ, or PI3K. In conclusion, rosiglitazone improved endothelial function through both PPARγ- and PPARδ-mediated phosphorylation of Akt and eNOS, which might help to reconsider the complex effects and clinical applications of rosiglitazone

The Ginger-shaped Asteroid 4179 Toutatis: New Observations from a Successful Flyby of Chang'e-2

On 13 December 2012, Chang'e-2 conducted a successful flyby of the near-Earth asteroid 4179 Toutatis at a closest distance of 770 $\pm$ 120 meters from the asteroid's surface. The highest-resolution image, with a resolution of better than 3 meters, reveals new discoveries on the asteroid, e.g., a giant basin at the big end, a sharply perpendicular silhouette near the neck region, and direct evidence of boulders and regolith, which suggests that Toutatis may bear a rubble-pile structure. Toutatis' maximum physical length and width are (4.75 $\times$ 1.95 km) $\pm$10$\%$, respectively, and the direction of the +$z$ axis is estimated to be (250$\pm$5$^\circ$, 63$\pm$5$^\circ$) with respect to the J2000 ecliptic coordinate system. The bifurcated configuration is indicative of a contact binary origin for Toutatis, which is composed of two lobes (head and body). Chang'e-2 observations have significantly improved our understanding of the characteristics, formation, and evolution of asteroids in general.Comment: 21 pages, 3 figures, 1 tabl

Absolute co-supplement and absolute co-coclosed modules

A module M is called an absolute co-coclosed (absolute co-supplement) module if whenever M ≅ T/X the submodule X of T is a coclosed (supplement) submodule of T. Rings for which all modules are absolute co-coclosed (absolute co-supplement) are precisely determined. We also investigate the rings whose (finitely generated) absolute co-supplement modules are projective. We show that a commutative domain R is a Dedekind domain if and only if every submodule of an absolute co-supplement R-module is absolute co-supplement. We also prove that the class Coclosed of all short exact sequences 0→A→B→C→0 such that A is a coclosed submodule of B is a proper class and every extension of an absolute co-coclosed module by an absolute co-coclosed module is absolute co-coclosed.Scientific and Technical Research Council of Turke