150 research outputs found
Analysis of tangential contact damping mechanism by direct observation using X-ray computed tomography
The damping of metal contact surfaces considerably influences the dynamic characteristics of machines. However, the contact damping mechanism has not yet been sufficiently clarified because it is difficult to directly observe metal–metal contact surfaces. In this study, the deformation of the metal surface asperity caused by a tangential load was analyzed using a combination of X-ray computed tomography and finite element method (FEM) simulations. The FEM simulation considering the elastic–plastic deformation and slip reproduced the experimental results well. The contribution of the elastic–plastic deformation and slip of asperities to contact damping was discussed using the developed simulation
Optimal Location-dependent Pricing Policies on Railways and Roads in a Continuous City
This paper explores optimal location-dependent but time-invariant peak-load charges on a road and a train in a continuous closed city with bottleneck road congestion and rail overcrowding. In our model, rail and car commuters both choose their departure times, considering their schedule delay costs and dynamically changing transportation costs, and their residential locations. Our theoretical results show that when the bottleneck is located at the fringe of the CBD area (Situation 1), the optimal uniform toll and fares are determined by the difference in price distortions between the train and cars. When the bottleneck on the road is located some distance from the CBD (Situation 2), the optimal uniform toll and fares are represented by price distortions of the cars and train, respectively. Our quantitative results show that, in Situation 1, our toll and fares can achieve 25% of the first-best welfare gains, whereas, in Situation 2, our toll and fares can achieve approximately 30% of the first-best welfare gains
Synthesis and biological properties of two dimeric forms of human α-atrial natriuretic peptide
AbstractTwo dimeric forms of human α-atrial natriuretic peptide (α-ANP) were synthesized by solution methods and compared with monomeric α-ANP in terms of some biological and immunochemical properties. The parallel form (β'-ANP) and the antiparallel form (β-ANP) were equipotent in smooth muscle relaxant activity in isolated rat aorta and their ED50 values were estimated to be 1.7 × 10−8 M and 1.6 × 10−8 M, respectively. Diuretic and natriuretic responses induced by β-ANP and β'-ANP in anesthetized rats were equally less potent but exhibited a significantly longer duration than those induced by α-ANP. β-ANP and β'-ANP possessed immunoreactivities of 60–100% and 50–90% (α-ANP, 100% on a molar basis), respectively, with three different antisera raised against α-ANP-related peptides
Novel Oral Derivative UD-017, a Highly Selective CDK7 Inhibitor, Exhibits Anticancer Activity by Inducing Cell-Cycle Arrest and Apoptosis in Human Colorectal Cancer
Objective: This study aimed to investigate the anticancer profile of a new cyclin-dependent kinase 7 (CDK7) inhibitor, UD-017, by examining its mechanism of action using HCT-116 colorectal cancer cells.
Methods: The anticancer properties of UD-017 were assessed using several assays, including in vitro kinase, proliferation, and apoptosis assays, western blot analysis, and an in vivo xenograft mouse model.
Results: UD-017 significantly inhibited CDK7 activity (IC50 = 16 nM) with high selectivity in an in vitro kinase assay testing a panel of over 300 proteins and lipid kinases. UD-017 also inhibited the growth of HCT-116 cells (GI50 = 19 nM) and inhibited the phosphorylation of various downstream mediators of CDK7 signaling. In cell cycle and apoptosis assays using HCT-116 cells, UD-017 increased the number of cells in both G1 and G2/M phases and induced apoptosis. In vivo, UD-017 inhibited tumor growth in an HCT-116 xenograft mouse model by 33%, 64%, and 88% at doses of 25, 50, and 100 mg/kg, respectively, with clear dose-dependency. Co-administration of 5-FU and 50 mg/kg UD-017 had a strong synergistic effect, as reflected in the complete inhibition of tumor growth.
Conclusion: CDK7 may play a major role in colorectal cancer growth by regulating the cell cycle and apoptosis. UD-017 is a promising candidate therapeutic agent for the treatment of cancer involving CDK7 signaling
High-density Integrated Linkage Map Based on SSR Markers in Soybean
A well-saturated molecular linkage map is a prerequisite for modern plant breeding. Several genetic maps have been developed for soybean with various types of molecular markers. Simple sequence repeats (SSRs) are single-locus markers with high allelic variation and are widely applicable to different genotypes. We have now mapped 1810 SSR or sequence-tagged site markers in one or more of three recombinant inbred populations of soybean (the US cultivar ‘Jack’ × the Japanese cultivar ‘Fukuyutaka’, the Chinese cultivar ‘Peking’ × the Japanese cultivar ‘Akita’, and the Japanese cultivar ‘Misuzudaizu’ × the Chinese breeding line ‘Moshidou Gong 503’) and have aligned these markers with the 20 consensus linkage groups (LGs). The total length of the integrated linkage map was 2442.9 cM, and the average number of molecular markers was 90.5 (range of 70–114) for the 20 LGs. We examined allelic diversity for 1238 of the SSR markers among 23 soybean cultivars or lines and a wild accession. The number of alleles per locus ranged from 2 to 7, with an average of 2.8. Our high-density linkage map should facilitate ongoing and future genomic research such as analysis of quantitative trait loci and positional cloning in addition to marker-assisted selection in soybean breeding
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