3-Hydr­oxy-3-nitro­methyl­indolin-2-one

In the title compound, C9H8N2O4, the indolin-2-one ring system is substanti­ally planar [maximum deviation = 0.0353 (15) Å]. In the crystal structure, inter­molecular N—H⋯O and O—H⋯O hydrogen bonds are responsible for the formation of a three-dimensional network

Tempo determination as a key to understanding and performing Mozart’s operas and symphonies, with reference to the ideas of Nikolaus Harnoncourt

How to convey the desired tempo is a problem that every composer had to face before the invention of the metronome. In Mozart’s time, the players could only rely on the information provided by the tempo marks, as well as the implications provided by articulation, drama, rhythm and even common sense. According to Nikolaus Harnoncourt’s observations as express in his book The Musical Dialogue: Thoughts on Monteverdi, Bach and Mozart, Mozart has his own tempo system, and uses his tempo marks in a characteristic way. By exploring the usage of tempo marks in Mozart’s operas The Marriage of Figaro and Don Giovanni, and linking these discoveries to his last three symphonies, this dissertation aims to uncover the meaning of Mozart’s tempo marks, and in this way to establish guidance for the performance of his music

Gallus Heat shock cognate protein 70, a novel binding partner of Apoptin

<p>Abstract</p> <p>Background</p> <p>Chicken anemia virus (CAV) infection of newly hatched chickens induces generalized lymphoid atrophy and causes immunosuppressive. VP3, also known as Apoptin, is non-structural protein of CAV. Apoptin specifically induces apoptosis in transformed or tumor cells but not in normal cells. In particular, there are no known cellular homologues of Apoptin hindering genetic approaches to elucidate its cellular function. Although a number of Apoptin-interacting molecules have been identified, the molecular mechanism underlying Apoptin's action is still poorly understood. To learn more about the molecular mechanism of Apoptin's action, we searched for Apoptin associated proteins.</p> <p>Results</p> <p>Using yeast two-hybrid and colony-life filter approaches we got five positive yeast clones. Through sequencing and BLASTed against NCBI, one of the clones was confirmed containing Gallus heat shock cognate protein 70 (Hsc70). Hsc70 gene was clone into pRK5-Flag plasmid, coimmunoprecipitation assay show both exogenous Hsc70 and endogenous Hsc70 can interact with Apoptin. Truncated Apoptin expression plasmids were made and coimmunoprecipitation were performed, the results show the binding domain of Apoptin with Hsc70 is located between amino acids 30-60. Truncated expression plasmids of Hsc70 were also constructed and coimmunoprecipitation were performed, the results show the peptide-binding and variable domains of Hsc70 are responsible for the binding to Apoptin. Confocal assays were performed and results show that under physiological condition Hsc70 is predominantly distributed in cytoplasm, whereas Hsc70 is translocated into the nuclei and colocalized with Apoptin in the presence of Apoptin in DF-1 cell. Functional studies show that Apoptin markedly down-regulate the mRNA level of RelA/p65 in DF-1 cell. To explore the effect of Hsc70 on Apoptin-mediated RelA/p65 gene expression, we have searched two Hsc70 RNAi sequences, and found that all of them dramatically inhibited the expression of endogenous Hsc70, with the #2 Hsc70 RNAi sequence being the most effective. Knockdown of Hsc70 show Apoptin-inhibited RelA/p65 expression was abolished. Our data demonstrate that Hsc70 is responsible for the down-regulation of Apoptin induced RelA/p65 gene expression.</p> <p>Conclusion</p> <p>We identified Gallus Hsc70 as an Apoptin binding protein and showed the translocation of Hsc70 into the nuclei of DF-1 cells treated with Apoptin. Hsc70 regulates RelA/p65 gene expression induced by Apoptin.</p

Dynamic Demand Forecast and Assignment Model for Bike-and-Ride System

Bike-and-Ride (B&R) has long been considered as an effective way to deal with urbanization-related issues such as traffic congestion, emissions, equality, etc. Although there are some studies focused on the B&R demand forecast, the influencing factors from previous studies have been excluded from those forecasting methods. To fill this gap, this paper proposes a new B&R demand forecast model considering the influencing factors as dynamic rather than fixed ones to reach higher forecasting accuracy. This model is tested in a theoretical network to validate the feasibility and effectiveness and the results show that the generalised cost does have an effect on the demand for the B&R system.</p

MiR-155 protects against sepsis-induced cardiomyocyte apoptosis via activation of NO/cGMP signaling pathway by eNOS

Purpose: To examine the impact of miR-155 on sepsis-induced myocardial apoptosis and heart failure, and to explore its molecular mechanism. Methods: Mice were divided into four groups and septic myocardial dysfunction was induced by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). The LPS stimulation expression of miR-155 levels was determined by real time-polymerase chain reaction (RT-PCR). In vivo, echocardiography and TUNEL staining were used to investigate the effects of miR-155 in inhibiting cardiac function and myocardial apoptosis. Changes in the expression of eNOS when miR-155 was overexpressed or inhibited were determined by RT-PCR, while double luciferase gene assay assessed the relationship between eNOS and miR-155, eNOS, expression of iNOS, SGC alpha 1, and PKG protein. Results: MiR-155 was significantly increased after LPS stimulation (p &lt; 0.01). In vitro, the inhibition of miR-155 by antagomiR significantly down-regulated the apoptosis of cardiomyocytes (p &lt; 0.05), while overexpression of miR-155 by agomiR significantly up-regulated the apoptosis of cardiomyocytes (p &lt; 0.05). In vivo, ejection fraction, fractional shortening and heart weight were significantly increased (p &lt; 0.05), while apoptosis was significantly decreased (p &lt; 0.05). MiR-155 negatively regulated the expression of eNOS (p &lt; 0.01), and targeted the expression of eNOS mRNA (p &lt; 0.001). In addition, the expression of eNOS, sGCα1 and PKA were significantly up-regulated (p &lt; 0.05), while the expression of iNOS was significantly down-regulated (p &lt; 0.05) after the inhibition of miR-155 in LPS mouse model. Conclusion: MiR-155 regulates sepsis-induced cardiomyocyte apoptosis and heart failure through eNOS /NO/cGMP signaling pathway. Thus, these findings can potentially facilitate the development of an effective strategy for management of heart failure

Unsteady aerodynamic model of flexible flapping wing

Bio-inspired flapping wing has potential application to micro air vehicles (MAV). Due to the nature of lightweight and flexibility of micro flapping wing structures, elastic deformation as a result of aeroelastic coupling is inevitable in flapping motion. This effect can be significant and beneficial to the aerodynamic performance as revealed in the present investigation for a flexible flapping wing of variable camber versus a rigid one. Firstly a two dimensional (2D) unsteady aerodynamic model (UAM) based on potential flow theory has been extended from previous study. Both leading and trailing edge discrete vortices are included in the model with unsteady Kutta condition satisfied to fully characterize the unsteady flow around a flapping wing. A wall function is created to modify the induced velocity of the vortices in the UAM to solve the vortices penetration problem. The modified UAM is then validated by comparing with CFD results of a typical insect-like flapping motion from previous research. Secondly the UAM is further extended for a flexible flapping wing of camber variation. Comparing with a rigid wing in a prescribed plunging and pitching motion, the results show lift increase with positive camber in upstroke by mitigating negative lift. The results also agree well with CFD simulation. Thirdly the 2D UAM is extended to calculate the aerodynamic forces of a 3D wing with camber variation, and validated by CFD results. Finally the model is applied to aerodynamic analysis of a 3D flexible flapping wing with aeroelastic coupling effect. Significant increase of lift coefficient can be achieved for a flexible flapping wing of positive camber and twist in upstroke produced by the structure elastic deformation

Development of a fatty liver model using oleic acid in primary liver cells isolated from Atlantic salmon and the prevention of lipid accumulation using metformin

The following study aimed to develop a fatty liver model in primary hepatocytes isolated from Atlantic salmon. In order to induce the fatty liver, oleic acid (OA) at 0.2 or 0.4 mM was used. Metformin, known to prevent and cure fatty liver in mammalian cells, was used at 1 or 10 mM for 24 hr before addition of OA to test possible prevention effect of metformin on the OA‐induced fatty liver phenotype. Cells grown in 0.2 mM OA did not increase the mean number of lipid droplets, while cells grown in 0.4 mM OA increased the number of lipid droplets within the liver cells (p < 0.0001). Metformin pretreatment prior to OA supplementation reduced the mean number of lipid droplets. Gene expression of ApoB100, CD36 and PPARa increased in cells treated with metformin and most so at 10 mM. On the other hand, gene expression of LXR, SREBP2 and CPT‐1 decreased at both concentrations of metformin, while OA treatment did not affect these genes. Gene expression of IL‐8 increased by 0.4 mM OA (p = 0.002). Metformin reduced the gene expression of IL‐8. Thus, metformin efficiently enhanced the expression of genes related to transport and oxidation of lipids in hepatic cells of salmon, but required higher concentrations of OA and metformin than those required in rodent models to increase and prevent lipid accumulation, respectively.publishedVersio

Investigation on the Rock-Fragmentation Process of Conical-Shaped TBM Cutterhead in Extremely Hard Rock Ground

Conical-shaped cutterhead is one type of tunnel boring machine (TBM) cutterhead which may have advantage of high rock-breaking efficiency in extremely hard rock ground. This study investigated the rock-fragmentation process of disc cutters on the conical-shaped cutterhead via a series of numerical simulations that had been verified by laboratory rock-fragmentation tests. Firstly, the rock-fragmentation numerical model of the six cutters in the 'flat-cone' contiguous part was built based on cutting mode analysis of the conical-shape cutterhead. The rock sample in the numerical model was synthesized using a grain-based discrete element method (GB-DEM) and the reliability of this approach was verified via scaled rock-fragmentation tests conducted on a self-developed linear cutting machine (LCM). Then, a series of numerical simulations were conducted to study the influence of cutterhead cone angle, cutter spacing, and cutter installation angle on the rock-fragmentation performance. The results were as follows: 1) the nature of rock fragmentation in the cone area is the rock fragmentation under side free-face condition; 2) the penetration specific energy can be reduced and thus the rock-fragmentation efficiency can be improved by appropriately increasing the conical angle, reducing the cutter spacing, and increasing the cutter installation angle; 3) for the studied granite, the optimal conical angle is 25°, the cutter spacing is suggested to be no more than 70 mm, and the cutter tilt angle is suggested to be no more than 3°. The results obtained in this paper can be used as guidance for the design of the conical-shaped cutterhead