PI3-K/Akt pathway contributes to IL-6-dependent growth of 7TD1 cells

BACKGROUND: Recently, growing evidence suggests the involvement of PI 3-K/Akt in IL-6-dependent survival and proliferative responses in several types of cells. However, whether PI 3-K/Akt plays the same role in IL-6-dependent growth of 7TD1 mouse-mouse B cell hybridoma is not known. METHODS: We investigated the activation status of Akt in 7TD1 cells induced by IL-6. With PI 3-K specific inhibitor wortmannin, we also investigated the biological roles of Akt activation in 7TD1 cells. RESULTS: IL-6 stimulated phosphorylation of Akt in a dose- and time-dependent manner in 7TD1 cells. Wortmannin significantly reduced IL-6-induced phosphorylation of Akt and IL-6-dependent growth of 7TD1 cells. Furthermore, wortmannin blocked IL-6-induced up-regulation of XIAP, but not Bcl-2 in 7TD1 cells. CONCLUSION: The data suggest that IL-6-induced PI 3-K/Akt activation is essential for the optimal growth of 7TD1 cells through up-regulation of anti-apoptosis proteins such as XIAP

Coordination in functional traits of Populus euphratica leaves under salt stress

Leaf functional traits allow plant survival and maintain their ecosystem function. Salinity affects leaf functional traits, but coordination among leaf functional traits is poorly known and may depend on salt severity. To increase our understanding of the coordination of leaf functional traits under salt stress, we determined hydraulic, gas exchange, and physiological and biochemical parameters in Populus euphratica Oliv. (P. euphratica) grown under salinity treatments, as well as gas exchange parameters under different CO2 concentrations. We found that P. euphratica can reinforce its hydraulic capacity by increasing the water transfer efficiency of both its leaves and stems when a salinity threat occurs for a specific duration of stress. Its stems were more adaptable than leaves. The economic and hydraulic traits of P. euphratica leaves were consistent during the middle stages of salt stress, but inconsistent during the onset and late stages of salt stress. There was almost no biochemical limitation under severe salinity conditions, and CO2 enrichment of P. euphratica had a greater effect on leaf economic traits. The mechanism of toxic ion exclusion based on water availability and intracellular mechanisms in leaves contributed to salt tolerance when P. euphratica was exposed to salinity stress. There was also a coordination mechanism for the plants during increasing salt stress. The leaf intracellular traits of P. euphratica can coordinate with the leaf economic and hydraulic traits and form a defense mechanism to reduce salt damage and guarantee growth under saline conditions. In conclusion, P. euphratica, the main constructional species of riparian forests, adapts to saline environments by adjustment and coordination of leaf functional traits, ensuring survival. These results provide a scientific basis for riparian forest restoration

De novo SNP discovery and genetic linkage mapping in poplar using restriction site associated DNA and whole-genome sequencing technologies

Detailed information on genetic distance and linkage phase between adjacent SNP markers on the genetic linkage map of the female P. deltoides ‘I-69’. The corresponding identical SNPs identified based on the P. trichocarpa reference genome are also included. (XLS 452 kb

AdaTT: Adaptive Task-to-Task Fusion Network for Multitask Learning in Recommendations

Multi-task learning (MTL) aims at enhancing the performance and efficiency of machine learning models by training them on multiple tasks simultaneously. However, MTL research faces two challenges: 1) modeling the relationships between tasks to effectively share knowledge between them, and 2) jointly learning task-specific and shared knowledge. In this paper, we present a novel model Adaptive Task-to-Task Fusion Network (AdaTT) to address both challenges. AdaTT is a deep fusion network built with task specific and optional shared fusion units at multiple levels. By leveraging a residual mechanism and gating mechanism for task-to-task fusion, these units adaptively learn shared knowledge and task specific knowledge. To evaluate the performance of AdaTT, we conduct experiments on a public benchmark and an industrial recommendation dataset using various task groups. Results demonstrate AdaTT can significantly outperform existing state-of-the-art baselines

Marketing Budget Allocation with Offline Constrained Deep Reinforcement Learning

We study the budget allocation problem in online marketing campaigns that utilize previously collected offline data. We first discuss the long-term effect of optimizing marketing budget allocation decisions in the offline setting. To overcome the challenge, we propose a novel game-theoretic offline value-based reinforcement learning method using mixed policies. The proposed method reduces the need to store infinitely many policies in previous methods to only constantly many policies, which achieves nearly optimal policy efficiency, making it practical and favorable for industrial usage. We further show that this method is guaranteed to converge to the optimal policy, which cannot be achieved by previous value-based reinforcement learning methods for marketing budget allocation. Our experiments on a large-scale marketing campaign with tens-of-millions users and more than one billion budget verify the theoretical results and show that the proposed method outperforms various baseline methods. The proposed method has been successfully deployed to serve all the traffic of this marketing campaign.Comment: WSDM 23, Best Paper Candidat

Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging

ObjectiveEndomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provides quantitative information for specific molecules, for acute rejection assessment in a murine cardiac transplantation model.MethodsMicrobubbles bearing anti-GzB antibodies (MBGzb) or isotype antibodies (MBcon) were prepared. Hearts were transplanted from C57BL/6J (allogeneic) or C3H (syngeneic) donors to C3H recipients. Target ultrasound imaging was performed on Days 2 and 5 post-transplantations. A pathologic assessment was performed. The expression of granzyme B and IL-6 in the heart was detected by Western blotting.ResultsAfter MB injection, we observed and collected data at 3 and 6 min before and after the flash pulse. Quantitative analysis revealed that the reduction in peak intensity was significantly higher in the allogeneic MBGzb group than in the allogeneic MBcon group and the isogeneic MBcon group at PODs 2 and 5. In the allogeneic groups, granzyme B and IL-6 expression levels were higher than those in the isogeneic group. In addition, more CD8 T cells and neutrophils were observed in the allogeneic groups.ConclusionUltrasound molecular imaging of granzyme B can be used as a noninvasive method for acute rejection detection after cardiac transplantation

The effect of symmetrically tilt grain boundary of aluminum on hydrogen diffusion

High-strength aluminum alloys are widely used in industry. Hydrogen embrittlement greatly reduces the performance and service safety of aluminum alloys. The hydrogen traps in alumi-num profoundly affect the hydrogen embrittlement of aluminum. Here, we took a coinci-dence-site lattice (CSL) symmetrically tilted grain boundary (STGB) Σ5(120)[001] as an example to carry out molecular dynamics (MD) simulations of hydrogen diffusion in aluminum at dif-ferent temperatures, and to obtain results and rules consistent with the experiment. At 700 K, three groups of MD simulations with concentrations of 0.5, 2.5 and 5 atomic % hydrogen (at. % H) were carried out for STGB models at different angles. By analyzing the simulation results and the MSD curves of hydrogen atoms, we found that, in the low hydrogen concentration of STGB models, the grain boundaries captured hydrogen atoms and hindered their movement. In high-hydrogen-concentration models, the diffusion rate of hydrogen atoms was not affected by the grain boundaries. The analysis of the simulation results showed that the diffusion of hydro-gen atoms at the grain boundary is anisotropic

Studies on Synthesis and Structure-Activity Relationship (SAR) of Derivatives of a New Natural Product from Marine Fungi as Inhibitors of Influenza Virus Neuraminidase

Based on the natural isoprenyl phenyl ether from a mangrove-derived fungus, 32 analogues were synthesized and evaluated for inhibitory activity against influenza H1N1 neuraminidase. Compound 15 (3-(allyloxy)-4-hydroxybenzaldehyde) exhibited the most potent inhibitory activity, with IC50 values of 26.96 μM for A/GuangdongSB/01/2009 (H1N1), 27.73 μM for A/Guangdong/03/2009 (H1N1), and 25.13 μM for A/Guangdong/ 05/2009 (H1N1), respectively, which is stronger than the benzoic acid derivatives (~mM level). These are a new kind of non-nitrogenous aromatic ether Neuraminidase (NA) inhibitors. Their structures are simple and the synthesis routes are not complex. The structure-activity relationship (SAR) analysis revealed that the aryl aldehyde and unsubstituted hydroxyl were important to NA inhibitory activities. Molecular docking studies were carried out to explain the SAR of the compounds, and provided valuable information for further structure modification