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The Chinese Altai is characterized by abundant granitoids, which not only are indicators of the interaction between crust and mantle but also provide critical constraints on the tectonic evolution of the orogen. This study presents zircon U‒Pb‒O isotopes, whole-rock major and trace element and Nd‒Hf‒Pb isotopes data for granite porphyries from the Keziergayin region in the Kelan Basin. The granite porphyries intrude in the Kangbutiebao Formation with zircon U‒Pb dating of 394 ± 3 Ma. They have the characteristics of subalkaline and metaluminous to weakly peraluminous and show geochemical affinity with I-type granite. The granite porphyry samples display negative εNd(t) (−1.9 to −1.4), positive εHf(t) (+4.3 to +11.4) values, with Nd–Hf decoupling; low Pb isotope compositions; δ18OV-SMOW (6.38‰–8.45‰) is less than 10‰, within the range of O isotopes of medium-basic igneous rocks. These geochemical signatures indicate that the granite porphyries originated from lower crust medium−basic igneous rocks extracted from the lithospheric mantle metasomatized by subducted melt. They are characterized by high SiO2 contents and Rb/Sr ratios; low CaO contents and K/Rb ratios, hinting that they were formed by highly evolved magmas, with fractionation crystallization of feldspar, apatite, garnet, allanite and/or monazite. The granite porphyries possess positive Rb, Th, U, Nd, Zr, Pb and light rare Earth elements (LREEs) anomalies with strong negative Ba, Nb, Ta, Sr, P, Ti and Eu anomalies, implying that their formation were related to an island arc. Combined with previous studies, it is suggested that the existence of the Early Devonian arc-basin system associated with subducting slab rollback in the Chinese Altai, which belongs to the Siberian active continental margin system.

This paper theoretically studies the interaction between an informed borrower and an uninformed lender facing possible default of a loan application. The lender is motivated to invest cognitive resources before making a lending decision. If the regulatory fine is weak, it is impossible for a bad-debt borrower to fully disclose his situation in the application. In this case, when the likelihood of a bad debt is low, the borrower always claims that nothing in the application is wrong. Otherwise, the borrower randomizes between full disclosure and information suppression. The transaction cost of the lender’s pre-lending cognition increases with the default probability, as the default probability is small and decreases thereafter. Evidence from a peer-to-peer lending platform with 816,274 observations between 2012 and 2015 in the United States is largely consistent with our model implications.

Summary: Mechanisms coordinating pancreatic β cell metabolism with insulin secretion are essential for glucose homeostasis. One key mechanism of β cell nutrient sensing uses the mitochondrial GTP (mtGTP) cycle. In this cycle, mtGTP synthesized by succinyl-CoA synthetase (SCS) is hydrolyzed via mitochondrial PEPCK (PEPCK-M) to make phosphoenolpyruvate, a high-energy metabolite that integrates TCA cycling and anaplerosis with glucose-stimulated insulin secretion (GSIS). Several strategies, including xenotopic overexpression of yeast mitochondrial GTP/GDP exchanger (GGC1) and human ATP and GTP-specific SCS isoforms, demonstrated the importance of the mtGTP cycle. These studies confirmed that mtGTP triggers and amplifies normal GSIS and rescues defects in GSIS both in vitro and in vivo. Increased mtGTP synthesis enhanced calcium oscillations during GSIS. mtGTP also augmented mitochondrial mass, increased insulin granule number, and membrane proximity without triggering de-differentiation or metabolic fragility. These data highlight the importance of the mtGTP signal in nutrient sensing, insulin secretion, mitochondrial maintenance, and β cell health. : Jesinkey et al. report that mitochondrial GTP (mtGTP) is an integrative nutrient sentinel regulating β cell function. Signaling from mtGTP raises calcium independent of oxidative phosphorylation to promote insulin secretion. Without overworking the β cell, mtGTP cycling potentiates insulin secretion, nutrient sensing, and mitochondrial expansion alongside promoting health and increasing insulin reserves. Keywords: mitochondrial GTP, PEPCK-M, insulin secretion, oxidative phosphorylation, phosphoenolpyruvate, anaplerosis, succinyl-CoA synthetase, stable isotope, metabolic flux, MIMOSA

Non–small cell lung cancer accounts for 85% of all types of lung cancer and is the leading cause of worldwide cancer-associated mortalities. MiR-124 is epigenetically silenced in various types of cancer and plays important roles in tumor development and progression. MiR-124 was also significantly downregulated in non–small cell lung cancer patients. Glycolysis has been considered as a feature of cancer cells; hypoxia-inducible factor 1-alpha/beta and Akt are key enzymes in the regulation of glycolysis and energy metabolism in cancer cells. However, the role of miR-124 in non–small cell lung cancer cell proliferation, glycolysis, and energy metabolism remains unknown. In this research, cell proliferation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; furthermore, glucose consumption and lactic acid production were assessed; adenosine triphosphate content and NAD + /NADH were also detected. These tests were conducted using the normal non–small cell lung cancer cell line A549, which was transfected variedly with miR-mimics, miR-124 mimics, miR-124 inhibitor, pc-DNA3.1(+)-AKT1, and pc-DNA3.1(+)-AKT2 plasmid. Here, we show that miR-124 overexpression directly decreased cell growth, glucose consumption, lactate production, and energy metabolism. MiR-124 also negatively regulates glycolysis rate–limiting enzymes, glucose transporter 1 and hexokinase II. Our results also showed that miR-124 negatively regulates AKT1 and AKT2 but no regulatory effect on hypoxia-inducible factor 1-alpha/beta. Overexpression of AKT reverses the inhibitory effect of miR-124 on cell proliferation and glycolytic metabolism in non–small cell lung cancer. AKT inhibition blocks miR-124 silencing–induced AKT1/2, glucose transporter 1, hexokinase II activation, cell proliferation, and glycolytic or energy metabolism changes. In summary, this study demonstrated that miR-124 is able to inhibit proliferation, glycolysis, and energy metabolism, potentially by targeting AKT1/2–glucose transporter 1/hexokinase II in non–small cell lung cancer cells.

The effect of hydrogen peroxide (H2O2) oxidation on the physicochemical, gelation and antimicrobial properties of gellan gum was studied. The oxidized gellan gum (OGG) was characterized by measuring the carboxyl/carbonyl group contents, Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The H2O2 oxidation resulted in a large increase in the carboxyl groups in gellan gum. The OGG lost gelation ability by oxidation even in the presence of metal ions. The antimicrobial activities of the OGG against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli), and fungal (Aspergillus niger) were tested. The OGG could inhibit the growth of both bacteria and fungal, and the activity was improved with an increase in the oxidation level. Finally, the application of the OGG as an active coatings material to extend the storage of apples was tested.

In numerous economic scenarios, contracting parties may not have a clear picture of all the relevant aspects. A contracting party may be unaware of what she and/or others are entitled to determine. Therefore, she may reject a contract that is too good to be true. Further, a contracting party may actively exert cognitive effort before signing a contract, so as to avoid being trapped into the contractual agreement ex post. In this paper, we propose a general framework to investigate these strategic interactions with unawareness, reasoning and cognition and intend to unify the solution concepts in the contracting context with unawareness. We build our conceptual framework upon the classical principal-agent relationship and compare the behaviors under various degrees of the unaware agent’s sophistication.

Single nucleotide polymorphism (SNP) genotyping is playing an increasing role in genome mapping, pharmacogenetic studies, and drug discovery. To date, genome-wide scans and studies involving thousands of SNPs and samples have been hampered by the lack of a system that can perform genotyping with cost-effective throughput, accuracy, and reliability. To address this need, Orchid has developed an automated, ultra-high throughput system, SNPstream® UHT, which uses multiplexed PCR in conjunction with our next generation SNP-IT™ tag array single base extension genotyping technology. The system employs oligonucleotide microarrays manufactured in a 384-well format on a novel glass-bottomed plate. Multiplexed PCR and genotyping are performed in homogeneous reactions, and assay results are read by direct two-color fluorescence on the SNPstream UHT Array Imager. The system’s flexibility enables large projects involving thousands of SNPs and thousands of samples as well as small projects that have hundreds of SNPs and hundreds of samples to be done cost effectively. We have successfully demonstrated this system in greater than 1 000 000 genotyping assays with >96% of samples giving genotypes with >99% accuracy.

In this work, a modal matching approach is developed to investigate the impact of the spatial correlation of wall pressure fluctuations on structural vibration and its role in suppressing flow-induced vibration in aircraft. The modal matching method defines the wavelength ratio between the convection wave and the flexural wave to capture the spatial characteristics of both the flow mode and the structural mode. In comparison to conventional methods such as the finite element method and analytical method, the proposed modal matching approach allows for obtaining the vibration response in the spatial-wavenumber domain. To validate the spatial correlation effect on structural vibrations obtained with the modal matching approach, a wind tunnel test was conducted to measure flow-induced vibrations. The calculated spatial-wavenumber data for flow-induced vibrations reveal that the crests and troughs of the vibration velocity alternate periodically as the wavelength of the wall pressure fluctuations changes. At the resonance frequency, a vibration velocity trough can be observed when the spatial correlation of wall pressure fluctuations aligns with the structural mode. Additionally, the concept of resonance independence of flow-induced vibrations is introduced to describe the phenomenon where the most severe structural vibration, determined by the matching value between the aerodynamic mode and the structural mode, does not always occur at the resonance frequency. The modal matching approach effectively suppresses structural vibration by utilizing the spatial correlation of wall pressure fluctuations, offering a new perspective on controlling flow-induced vibrations. [ABSTRACT FROM AUTHOR]