mars and tousled-like kinase act in parallel to ensure chromosome fidelity in Drosophila

<p>Abstract</p> <p>Background</p> <p>High levels of <it>Hepatoma Up-Regulated Protein </it>(<it>HURP</it>) and <it>Tousled-Like Kinase </it>(<it>TLK</it>) transcripts are found in hepatocellular carcinoma. <it>HURP </it>overexpression induces anchorage-independent growth of 293-T cells and enhances a rough-eye phenotype resulting from <it>tlk </it>overexpression in <it>Drosophila</it>. In addition, both HURP and Mars, a <it>Drosophila </it>HURP sequence homologue, promote polymerization of mitotic spindles. Thus, the genetic interaction of <it>mars </it>with <it>tlk </it>might be required for accurate chromosome segregation.</p> <p>Methods</p> <p>To reveal whether chromosome fidelity was decreased, the frequency of gynandromorphy, an individual with both male and female characteristics, and of non-disjunction were measured in the progeny from parents with reduced <it>mars </it>and/or <it>tlk </it>activities and analyzed by Student's <it>t</it>-test. To show that the genetic interaction between <it>mars </it>and <it>tlk </it>is epistatic or parallel, a cytological analysis of embryos with either reduced or increased activities of <it>mars </it>and/or <it>tlk </it>was used to reveal defects in mitotic-spindle morphology and chromosome segregation.</p> <p>Results</p> <p>A significant but small fraction of the progeny from parents with reduced <it>mars </it>activity showed gynandromorphy and non-disjunction. Results of cytological analysis revealed that the decrease in chromosome fidelity was a result of delayed polymerization of the mitotic spindle, which led to asynchronous chromosome segregation in embryos that had reduced <it>mars </it>activity. By removing one copy of <it>tousled-like kinase </it>(<it>tlk</it>) from flies with reduced <it>mars </it>activity, chromosome fidelity was further reduced. This was indicated by an increased in the non-disjunction rate and more severe asynchrony. However, the morphology of the mitotic spindles in the embryos at metaphase where both gene activities were reduced was similar to that in <it>mars </it>embryos. Furthermore, <it>tlk </it>overexpression did not affect the morphology of the mitotic spindles and the cellular localization of Mars protein.</p> <p>Conclusion</p> <p>Chromosome fidelity in progeny from parents with reduced <it>mars </it>and/or <it>tlk </it>activity was impaired. The results from cytological studies revealed that <it>mars </it>and <it>tlk </it>function in parallel and that a balance between <it>mars </it>activity and <it>tlk </it>activity is required for cells to progress through mitosis correctly, thus ensuring chromosome fidelity.</p

A SEEMINGLY UNRELETED REGRESSION ANALYSIS ON THE TRADING BEHAVIOR OF MUTUAL FUND INVESTORS

This paper provides a comprehensive investigation on the causality relationship between fund performance and trading flows. We analyze if investors behave asymmetrically in fund purchasing and selling by seemingly unrelated regression which comprises several individual relationships that are linked by the fact that their disturbances or the error terms are correlated. The empirical result shows a significantly negative relationship between fund performance and purchase flows for domestic funds. The magnitude of domestic funds redemption negatively affects current return, but not for international funds. As previousfund return positively affects current net flows,the further lagged performances have no significant impact on the trading flows, revealing that fund investors are sensitive only to short-term past performance. Most importantly, while negative fund performance leads to the increases in redemption, positive performance contrarily leads to the decreases in purchase. The evidences strongly indicate an asymmetry behavior of fund investors in the return-purchase causality relations

Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-oxygenase 1 (HO-1). We previously showed that fluid shear stress increases intracellular reactive oxygen species (ROS) in ECs. Moreover, oxidants are known to stimulate Nrf2. We thus examined the regulation of Nrf2 in cultured human ECs by shear stress.</p> <p>Results</p> <p>Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm²) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1.</p> <p>Conclusion</p> <p>Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system.</p

OPTIMAL INBOUND/OUTBOUND PRICING MODEL FOR REMANUFACTURING IN A CLOSED-LOOP SUPPLY CHAIN

The paper presents a model for optimizing inbound and outbound pricing for closed-loop supply chains that remanufacture reusable products. Remanufacturers create reusable products from returned used products and sell the products “as new” to manufacturers or consumers. By implementing a return subsidy, remanufacturers can encourage the consumer to return used products. Demand for the as-new components often depends on the selling price and inventory. The available inventory increases as the subsidy increases and as the price decreases. Our model can determine the optimal subsidy and selling price for used and remanufactured products, respectively. Our model uses the Karush–Kuhn–Tucker conditions to solve its nonlinear problem. Sensitivity analysis reveals how different parameters affect profit under model-optimized conditions

The Design and Analysis of Passive Pitch Control for Horizontal Axis Wind Turbine

AbstractThe purpose of this thesis is to design and analysis of passive pitch control. Design a mechanics to control different revolution of blade's pitch angle. The use of small wind turbines gradually popularization, but how to overcome the low wind speed start-up and the operation under high wind speed, that is the difficult problems encountered by designers. In order to extend the use and the safe of wind speed, this design is required. This paper is focus on the mechanism design of the passive pitch control for the small horizontal axis wind turbine (HAWT). When the wind speed is fast, the rotation speed is also faster and faster. The system uses centrifugal force to make Pulley disk driven the pitch angle of the blade. It can achieve the effect of passive pitch control. The mechanism is our laboratory's patent. Through the experiments in wind tunnel, it can be observed the variation of the performance curve when the pitch rotation. This system not only successfully operates under high wind speed but also has better performance at low wind speed

Sampling Neural Radiance Fields for Refractive Objects

Recently, differentiable volume rendering in neural radiance fields (NeRF) has gained a lot of popularity, and its variants have attained many impressive results. However, existing methods usually assume the scene is a homogeneous volume so that a ray is cast along the straight path. In this work, the scene is instead a heterogeneous volume with a piecewise-constant refractive index, where the path will be curved if it intersects the different refractive indices. For novel view synthesis of refractive objects, our NeRF-based framework aims to optimize the radiance fields of bounded volume and boundary from multi-view posed images with refractive object silhouettes. To tackle this challenging problem, the refractive index of a scene is reconstructed from silhouettes. Given the refractive index, we extend the stratified and hierarchical sampling techniques in NeRF to allow drawing samples along a curved path tracked by the Eikonal equation. The results indicate that our framework outperforms the state-of-the-art method both quantitatively and qualitatively, demonstrating better performance on the perceptual similarity metric and an apparent improvement in the rendering quality on several synthetic and real scenes.Comment: SIGGRAPH Asia 2022 Technical Communications. 4 pages, 4 figures, 1 table. Project: https://alexkeroro86.github.io/SampleNeRFRO/ Code: https://github.com/alexkeroro86/SampleNeRFR

α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.

Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α-GalCer-induced IL-4 and IFN-γ production from iNKT cells. Consequently, α-LacCer also ameliorated both α-GalCer and GSL-1-induced airway hyperreactivity and α-GalCer-induced neutrophilia when co-administered in vivo. Furthermore, we were able to inhibit the increases of ConA-induced AST, ALT and IFN-γ serum levels through α-LacCer pre-treatment, suggesting α-LacCer could protect against ConA-induced liver injury. Mechanistically, we discerned that α-LacCer suppressed α-GalCer-stimulated cytokine production through competing for CD1d binding. Since iNKT cells play a critical role in the development of AHR and liver injury, the inhibition of iNKT cell activation by α-LacCer present a possible new approach in treating iNKT cell-mediated diseases