A New Dynamic Population Variation in Genetic Programming

A dynamic population variation (DPV) in genetic programming (GP) with four innovations is proposed for reducing computational effort and accelerating convergence during the run of GP. Firstly, we give a new stagnation phase definition and the characteristic measure for it. Secondly, we propose an exponential pivot function (EXP) in conjunction with the new stagnation phase definition. Thirdly, we propose an appropriate population variation formula for EXP. Finally, we introduce a scheme using an instruction matrix for producing new individuals to maintain diversity of the population. The efficacy of these innovations in our DPV is examined using four typical benchmark problems. Comparisons among the different characteristic measures have been conducted for regression problems and the proposed measure performed best in all characteristic measures. It is demonstrated that the proposed population variation scheme is superior to fixed and proportionate population variation schemes for sequence induction. It is proved that the new DPV has the capacity to provide solutions at a lower computational effort compared with previously proposed population variation methods and standard genetic programming in most problems

AGAMOUS Terminates Floral Stem Cell Maintenance in Arabidopsis by Directly Repressing WUSCHEL through Recruitment of Polycomb Group Proteins

Floral stem cells produce a defined number of floral organs before ceasing to be maintained as stem cells. Therefore, floral stem cells offer an ideal model to study the temporal control of stem cell maintenance within a developmental context. AGAMOUS (AG), a MADS domain transcription factor essential for the termination of floral stem cell fate, has long been thought to repress the stem cell maintenance gene WUSCHEL (WUS) indirectly. Here, we uncover a role of Polycomb Group (PcG) genes in the temporally precise repression of WUS expression and termination of floral stem cell fate. We show that AG directly represses WUS expression by binding to the WUS locus and recruiting, directly or indirectly, PcG that methylates histone H3 Lys-27 at WUS. We also show that PcG acts downstream of AG and probably in parallel with the known AG target KNUCKLES to terminate floral stem cell fate. Our studies identify core components of the network governing the temporal program of floral stem cells

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Study on stress relaxation characteristics of FGH95 powder superalloy treated by laser shock peening

Aiming at the phenomenon that the residual stress induced by Laser Shock Peening (LSP) will relax and redistribute under various loads, temperature, cyclic load, and the dual treatment of temperature and cyclic load on the residual stress relaxation of FGH95 powder superalloy after LSP treatment were studied, and the analysis model of relevant residual stress relaxation was constructed. The purpose is to understand the strengthening effect and stability of the alloy under temperature and cyclic load after LSP treatment. With the increase of treatment temperature, the relaxation of residual stress became more and more obvious. Most of the residual stress relaxation occurred in the first 30 min of temperature treatment, then slowed down and stabilized after 1 h. The residual stress was initially relaxed in the first 50 cycles, remained roughly unchanged between 50 and 5000 cycles. The intensify of the cyclic load increasing, adding material yield level, further plastic deformation and residual stress relaxation rate increases. With the increase of load intensify and load ratio, residual stress relaxation was also increased. The residual stress relaxation rate after 600 °C and cyclic load treatment was 56.2%, both greater than that after 600 °C or cyclic treatment of 25 °C, but less than the sum of the two conditions. The results of this paper provide a reference for the LSP of the FGH95 powder superalloy turbine disk and other aero engine parts

Preparation of Gum Arabic–Maltose–Pea Protein Isolate Complexes for 1−Octacosanol Microcapsule: Improved Storage Stability, Sustained Release in the Gastrointestinal Tract, and Its Effect on the Lipid Metabolism of High−Fat−Diet−Induced Obesity Mice

1-Octacosanol (Octa) is a natural compound with several beneficial properties. However, its poor water solubility and metabolism in the digestive tract reduce its efficacy. The Octa-GA-Malt-PPI microcapsule was prepared as follows: gum Arabic (GA):maltose (Malt):pea protein isolate (PPI) = 2:1:2; core:shell = 1:7.5; emulsification temperature 70 °C; pH 9.0. An in vitro simulated gastrointestinal tract was used to analyze the digestion behavior. C57BL/6 mice were selected to establish an obesity model induced by a high-fat diet (HFD) to evaluate the effect of Octa monomer and the microcapsule. The diffusivity in water and storage stability of Octa improved after encapsulation. The microcapsule was ascribed to electrostatic interactions, hydrogen bonding, and hydrophobic interactions. The sustained release of Octa from the microcapsule was observed in a simulated gastrointestinal tract. Compared with Octa monomer, the microcapsule was more effective in alleviating the symptoms of weight gain, hypertension, and hyperlipidemia induced by HFD in mice. In conclusion, the construction of microcapsule structure can improve the dispersibility and stability of Octa in water, achieve sustained release of Octa in the gastrointestinal tract, and improve its efficiency in alleviating the effects of HFD on the body