Tumor-Infiltrating Mast Cells Confer Resistance to Immunotherapy in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) exhibits an immunosuppressive tumor microenvironment (TME) contributing to its therapeutic resistance. Following our previous studies, we report that mast cells infiltrating the PDAC TME foster this immunosuppression and desmoplasia. Mast cell infiltration correlated with human PDAC progression, and genetic or pharmacological mast cell depletion reduced tumor growth and desmoplasia while enhancing survival in mouse PDAC models. Mechanistically, mast cell-derived IL-10 promoted PDAC progression. Strikingly, combining an agonistic anti-OX40 immunotherapy with mast cell blockade synergistically elicited durable anti-tumor immunity, marked by increased infiltration of CD

Deglacial biogenic opal peaks revealing enhanced Southern Ocean upwelling during the last 513 ka

Strength of Southern Ocean upwelling controls the exchange of carbon dioxide (CO2) between deep ocean reservoirs and atmosphere, as well as the communication of dissolved silicon with the euphotic zone of the Southern Ocean. The silicon supply could limit diatom opal productivity in the high-latitudes of Southern Ocean and the subsequent burial of biogenic opal in underlying sediments. Here we report a record of biogenic opal export off the Prydz Bay south of the polar front of the Southern Ocean, indicating strengthened upwelling during the past five glacial terminations. In all five terminations (Isingle bondV), opal peaks occur in line with Northern Hemisphere summer insolation intensity as well as the existing IRDs, indicating that freshwater injection associated with retreat of the Northern Hemisphere ice sheets could be the cause of enhanced upwelling in the Southern Ocean during terminations. This could in turn promote CO2 outgassing, finally accelerating the completion of the terminations. In addition, the enhanced upwelling could export the Si-rich deep water to low latitudes via Antarctic Intermediate Water (AAIW) and Subantarctic Mode Water (SAMW), potentially leading to deglacial opal peaks in subtropical North Atlantic

Electrochemical generation of silver nanowires

1016-1018Novel silver nanowires about 30-40 nm in diameter have been successfully fabricated by electrochemical reduction in aqueous solution of poly(methacrylic acid) at room temperature. Different morphologic silver products have been obtained by adjusting the polymer concentration. Field emission scanning electron microscopy and X-ray photoelectron spectro scopy have been used to characterize the obtained silver products. The possible formation mechanism is discussed. The synthesis process provides a facile method for low temperature solution growth of metal nanowires

Non-Probabilistic Time-Varying Reliability-Based Analysis of Corroded Pipelines Considering the Interaction of Multiple Uncertainty Variables

Reliability analysis of corroded pipelines is critical to the integrity and safe working of pipeline infrastructure. Aiming at less probability information is obtained for corrosion pipeline engineering, and the mechanical properties of pipeline with corrosion defects deteriorate caused by the accumulative effect of corrosion growth. Based on the quasi-static analysis method and non-probability theory, this paper presents a reliability model for assessing corroded pipelines with corrosion growth. In fact, reliability analysis of corroded pipelines needs to consider the interaction of multiple uncertainty variables. By introducing interaction theory, a mathematical model of corrosion defects considering the interaction of variables is put forward. Moreover, this paper develops a non-probabilistic time-varying reliability method for pipeline systems with multiple defects. Thus, several numerical examples are investigated to discuss the effectiveness of the proposed methodology. The results show that a two-dimensional or even three-dimensional ellipsoid model with correlation has more accurate results to evaluate corroded pipelines under the interaction of multiple corroded defects with poor information. Furthermore, a non-probabilistic time-varying reliability model is established according to the time-varying characteristics of the corroded pipeline under the influence of multiple factors. An effective complement to the theory of non-probabilistic reliability analysis of system is investigated. The analysis of the results suggests that interaction of corroded pipeline has a negligible impact on reliability. It also provides a theoretical basis for maintenance and is of great significance for risk- and reliability-informed decisions regarding buried oil and gas pipelines