55 research outputs found

    High atmospheric demand for water can limit forest carbon uptake and transpiration as severely as dry soil

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    When stressed by low soil water content (SWC) or high vapor pressure deficit (VPD), plants close stomata, reducing transpiration and photosynthesis. However, it has historically been difficult to disentangle the magnitudes of VPD compared to SWC limitations on ecosystem-scale fluxes. We used a 13 year record of eddy covariance measurements from a forest in south central Indiana, USA, to quantify how transpiration and photosynthesis respond to fluctuations in VPD versus SWC. High VPD and low SWC both explained reductions in photosynthesis relative to its long-term mean, as well as reductions in transpiration relative to potential transpiration estimated with the Penman-Monteith equation. Flux responses to typical fluctuations in SWC and VPD had similar magnitudes. Integrated over the year, VPD fluctuations accounted for significant reductions of GPP in both nondrought and drought years. Our results suggest that increasing VPD under climatic warming could reduce forest CO2 uptake regardless of changes in SWC

    Synthetic Cationic Helical Polypeptides for the Stimulation of Antitumour Innate Immune Pathways in Antigen-Presenting Cells

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    Intracellular DNA sensors regulate innate immunity and can provide a bridge to adaptive immunogenicity. However, the activation of the sensors in antigen-presenting cells (APCs) by natural agonists such as double-stranded DNAs or cyclic nucleotides is impeded by poor intracellular delivery, serum stability, enzymatic degradation and rapid systemic clearance. Here we show that the hydrophobicity, electrostatic charge and secondary conformation of helical polypeptides can be optimized to stimulate innate immune pathways via endoplasmic reticulum stress in APCs. One of the three polypeptides that we engineered activated two major intracellular DNA-sensing pathways (cGAS-STING (for cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes) and Toll-like receptor 9) preferentially in APCs by promoting the release of mitochondrial DNA, which led to the efficient priming of effector T cells. In syngeneic mouse models of locally advanced and metastatic breast cancers, the polypeptides led to potent DNA-sensor-mediated antitumour responses when intravenously given as monotherapy or with immune checkpoint inhibitors. The activation of multiple innate immune pathways via engineered cationic polypeptides may offer therapeutic advantages in the generation of antitumour immune responses

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

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    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

    Eye Movement Analysis and Usability Assessment on Affective Computing Combined with Intelligent Tutoring System

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    Education is the key to achieving sustainable development goals in the future, and quality education is the basis for improving the quality of human life and achieving sustainable development. In addition to quality education, emotions are an important factor to knowledge acquisition and skill training. Affective computing makes computers more humane and intelligent, and good emotional performance can create successful learning. In this study, affective computing is combined with an intelligent tutoring system to achieve relevant and effective learning results through affective intelligent learning. The system aims to change negative emotions into positive ones of learning to improve students’ interest in learning. With a total of 30 participants, this study adopts quantitative research design to explore the learning situations. We adopt the System Usability Scale (SUS) to evaluate overall availability of the system and use the Scan Path to explore if the subject stays longer in learning the course. This study found that both availability and satisfaction of affective tutoring system are high. The emotional feedback mechanism of the system can help users in transforming negative emotions into positive ones. In addition, the system is able to increase the learning duration the user spends on learning the course as well

    Impacts of Affective Tutoring System on the Academic Achievement of Primary School Students with Different Cognitive Styles - An Example of Marine Education

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    The study is trying to use ATS (Affective Tutoring System) with emotional calculating technology in the activity of the shell education program. The result is used to study the academic achievement of students with different cognitive styles and system usability. There were 61 fifth-grade children from two different classes participating in this experiment. Every child had to do GEFT (Group Figure-Embedded Test) and academic achievement pre-test before they started the ATS. Then students engaged in ATS learning. Academic achievement post-test was done and the System Usability Scale for Learning Questionnaire after they finished the ATS. The experiment yielded the following results: (1) Learning with ATS not only can give learners an excellent feeling of system usability, but also help learners to promote academic achievement more effectively. (2) According to the system usability and academic achievement, the Field-independent learners were acting better than the Field-dependent learners
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