Glutaminase 1 inhibition reduces thymidine synthesis in NSCLC

AbstractWe found that non-small cell lung cancer (NSCLC) is remarkably sensitive to the regulation of glutamine supply by testing the metabolic dependency of 11 cancer cell lines against regulation of glycolysis, autophagy, fatty acid synthesis, and glutamine supply. Glutamine is known as a key supplement of cancer cell growth that is converted to α-ketoglutarate for anabolic biogenesis via glutamate by glutaminase 1 (GLS1). GLS1 inhibition using 10 μM of bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) showed about 50% cell growth arrest by SRB assay. By testing the synergistic effects of conventional therapeutics, BPTES combined with 5-fluorouracil (5-FU), an irreversible inhibitor of thymidylate synthase, significant effects were observed on cell growth arrest in NSCLC. We found that GLS1 inhibition using BPTES reduced metabolic intermediates including thymidine and carbamoyl phosphate. Reduction of thymidine and carbamoyl-phosphate synthesis by BPTES treatment exacerbated pyrimidine supply by combination with 5-FU, which induced cell death synergistically in NSCLC

Learning lives with/in digital media: Emergence of online economy disputants in the midst of economic crisis in South Korea

This study aims to understand adult online informal learning illuminating a way of becoming an influential social figure. We interviewed five famous online economy disputants whose postings were very popular in Korea during the global financial crisis in 2008-2009. We explored how they learned and found that their self-directedness interplayed with the context of other- directedness, a sense of being stimulated and indebted enhanced their learning process, and dynamics of anonymity and social recognition were keys to their emergence

Laminaria japonica Extract Enhances Intestinal Barrier Function by Altering Inflammatory Response and Tight Junction-Related Protein in Lipopolysaccharide-Stimulated Caco-2 Cells.

In the normal physiological state, intestinal epithelial cells act as a defensive frontline of host mucosal immunity to tolerate constant exposure to external stimuli. In this study, we investigated the potential anti-inflammatory and gut permeability protective effects of Laminaria japonica (LJ) water extract (LJE) and three types of fermented Laminaria japonica water extracts (LJE-F1, LJE-F2, and LJE-F3) in lipopolysaccharide (LPS)-stimulated Caco-2, human intestinal epithelial cells. All four extracts significantly decreased the production of nitric oxide and interleukin-6 induced by LPS stimulus. In addition, LJE and the three types of LJE-Fs also inhibited LPS-induced loss of monolayer permeability, as assessed by changes in transepithelial electrical resistance. All four LJ extracts significantly prevented the inhibition of the protein levels of occludin, whereas LJE, LJE-F1, and LJE-F3 significantly attenuated the reduction in phosphorylation of adenosine monophosphate-activated protein kinase compared with the LPS-treated group in Caco-2 cells. In conclusion, LJE and its fermented water extracts appear to have potential gut health-promoting effects by reducing inflammation and partially regulating the tight junction-related proteins in human intestinal epithelial cells. Thus, additional studies are warranted to evaluate Laminaria japonica as a therapeutic agent for inflammatory bowel diseases

Visible-ultraviolet spectroscopic ellipsometry of lead zirconate titanate thin films

We measured pseudodielectric functions in the visible-ultraviolet spectral range of Pb(ZrxTi1−x)O3 (x=0.2, 0.56, 0.82) (PZT)grown on platinized silicon substrate using the sol-gel method and also on (0001) sapphire using radio frequency sputtering method. Using a parametric optical constant model, we estimated the dielectric functions of the PZTthin films. Taking the second derivative of the fitted layer dielectric functions and using the standard critical point model, we determined the parameters of the critical points. In the second derivative spectra, the lowest bandgap energy peak near 4eV is fitted as a double peak for annealedPZTs associated with the perovskite phase. As-grown PZTs have mainly pyrochlore phase and the lowest bandgap is fitted as a single peak. We compared the bandgap energies with literature values

FDI and Its Impact on Trade in the East Asian Transition Economies

As globalization and trade liberalization have increased integration of the world economy through financial and trade flows, the role of FDI and trade on economic growth is becoming more influential. This paper investigates the impact of FDI on trade of the East Asian economic transition countries, namely the China, Cambodia, Lao PDR, and Vietnam, employing FDI flow and FDI stock data separately. The data from these four countries during the period 1990–2019 have been collected, and OLS and panel within fixed effect estimators are utilized. The main findings show that, first, when estimated using FDI flow as independent variable, there exists complementary effect between FDI and trade, and the coefficients are significant except for Cambodia. Second, when estimated using FDI stock as independent variable, the impact of FDI decreases and even substitutability effect is found in China at significant level. Third, in both cases, the coefficient of FDI is shown positive and significant in Vietnam. In addition, the paper finds the effects of human capital, GDP, and WTO accession on trade are positive, while the effects of exchange rate, financial development, and tariff rate vary among the East Asian economic transition countries

Temperature-scaling behavior of the Hall conductivity for Hg-based superconducting thin films

The Hall conductivities of HgBa_{2}CaCu_{2}O_{6+\delta}and HgBa_{2}Ca_{2}Cu_{3}O_{8+\delta} thin films are investigated for a magnetic field parallel to the c axis. The mixed-state Hall conductivity for these compounds is well described by \sigma_{xy}=C_{1}/H+C_{2}+C_{3}H. The prefactor C_1 shows a temperature dependence of the form C_1 = A(1-t)^n near T_c, where t=T/T_c is the reduced temperature. Contrary to the previous results, C_2 also follows a temperature-scaling behavior similar to that of the coefficient C_1. The observed value of n = 1.8 - 2.3 is comparable to the previously observed values for YBa_{2}Cu_{3}O_{7-\delta} and La_{2-x}Sr_{x}CuO_{4}.Comment: 5 pages, 4 eps figure

Leveraging Image Augmentation for Object Manipulation: Towards Interpretable Controllability in Object-Centric Learning

The binding problem in artificial neural networks is actively explored with the goal of achieving human-level recognition skills through the comprehension of the world in terms of symbol-like entities. Especially in the field of computer vision, object-centric learning (OCL) is extensively researched to better understand complex scenes by acquiring object representations or slots. While recent studies in OCL have made strides with complex images or videos, the interpretability and interactivity over object representation remain largely uncharted, still holding promise in the field of OCL. In this paper, we introduce a novel method, Slot Attention with Image Augmentation (SlotAug), to explore the possibility of learning interpretable controllability over slots in a self-supervised manner by utilizing an image augmentation strategy. We also devise the concept of sustainability in controllable slots by introducing iterative and reversible controls over slots with two proposed submethods: Auxiliary Identity Manipulation and Slot Consistency Loss. Extensive empirical studies and theoretical validation confirm the effectiveness of our approach, offering a novel capability for interpretable and sustainable control of object representations

Comparison of Two Mice Strains, A/J and C57BL/6, in Caspase-1 Activity and IL-1β Secretion of Macrophage to Mycobacterium leprae Infection

A/J mice were found to have amino acid differences in Naip5, one of the NOD-like receptors (NLRs) involved in the cytosolic recognition of pathogen-associated molecular patterns and one of the adaptor proteins for caspase-1 activation. This defect was associated with a susceptibility to Legionella infection, suggesting an important role for Naip5 in the immune response also to other intracellular pathogens, such as Mycobacterium leprae. In this study, the immune responses of macrophages from A/J mice against M. leprae were compared to those of macrophages from C57BL/6 mice. Infection with M. leprae induced high levels of TNF-α production and NF-κB activation in A/J and C57BL/6 macrophages. Caspase-1 activation and IL-1β secretion were also induced in both macrophages. However, macrophages from A/J mice exhibited reduced caspase-1 activation and IL-1β secretion compared to C57BL/6 macrophages. These results suggest that NLR family proteins may have a role in the innate immune response to M. leprae

Orthogonal Stability of an Additive-quartic Functional Equation in Non-Archimedean Spaces

Using fixed point method, we prove the Hyers-Ulam stability of the orthogonally additive-quartic functional equation f(2x+y)+ f(2x-y)=4 f(x+y)+ 4 f(x-y) + 10 f(x) + 14f(-x) - 3 f(y)-3f(-y) for all $x, y$ with $xperp y$, in non-Archimedean Banach spaces. Here $perp$ is the orthogonality in the sense of Rätz