Evidence of convective transport in tropical West Pacific region during SHIVA experiment

Air masses in the convective outflows of four large convective systems near Borneo Island in Malaysia were sampled in the height range 11–13 km within the frame of the SHIVA (Stratospheric Ozone: Halogen Impacts in a Varying Atmosphere) FP7 European project in November and December 2011. Correlated enhancements of CO, CH4 and the short-lived halogen species (CH3I and CHBr3) were detected when the aircraft crossed the anvils of the four systems. These enhancements were interpreted as the fingerprint of vertical transport from the boundary layer by the convective updraft and then horizontal advection in the outflow. For the four observations, the fraction f of air from the boundary layer ranged between 15 and 67%, showing the variability in transport efficiency depending on the dynamics of the convective system

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

Effects of foreign language learning on executive functions in healthy older adults: study protocol for a randomised controlled trial

Background!#!With age, most cognitive functions decline. As the number of people aged 60 years and older is expected to rise rapidly within the next decades, identifying interventions that promote healthy cognitive ageing is of utmost importance. Promising research on bilingualism has led to the notion that learning a foreign language could protect against cognitive decline. Foreign language learning likely promotes executive functions, which are higher-order cognitive abilities particularly affected by age-related cognitive decline. However, evidence is still sparse and has produced contradictory results. This study aims to investigate the effects of short and intensive foreign language learning on executive functions in healthy older adults.!##!Methods!#!In a randomised controlled trial, we will assign 60 native German-speaking monolingual healthy older adults, aged 65-80 years, to either a foreign language learning or a waiting list control group. Language learners will attend a face-to-face, group-based Spanish course for beginners for 1.5 h a day, 5 days a week, for a total of 3 weeks. Cognitive performance in executive functions will be assessed before and after the intervention or after a waiting period of 3 weeks (waiting list control group). Participants will be tested again after 3 months to evaluate longitudinal effects of foreign language learning. The waiting list control group will receive Spanish lessons only after the final assessment and will be invited to an additional voluntary evaluation after completion of the course.!##!Discussion!#!To the best of our knowledge, we are conducting the first randomised controlled trial on the effects of short and intensive foreign language learning in older adulthood on executive functions. Enhanced cognitive performance after foreign language learning would indicate that learning a foreign language could enlarge cognitive reserve and thus promote healthy cognitive ageing in older adults.!##!Trial registration!#!German Clinical Trials Register DRKS00016552 . Registered on 11 February 2019

Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins

Protein ADP-ribosylation is a reversible post-translational modification that regulates important cellular functions. The identification of modified proteins has proven challenging and has mainly been achieved via enrichment methodologies. Random mutagenesis was used here to develop an engineered Af1521 ADP-ribose binding macro domain protein with 1000-fold increased affinity towards ADP-ribose. The crystal structure reveals that two point mutations K35E and Y145R form a salt bridge within the ADP-ribose binding domain. This forces the proximal ribose to rotate within the binding pocket and, as a consequence, improves engineered Af1521 ADPr-binding affinity. Its use in our proteomic ADP-ribosylome workflow increases the ADP-ribosylated protein identification rates and yields greater ADP-ribosylome coverage. Furthermore, generation of an engineered Af1521 Fc fusion protein confirms the improved detection of cellular ADP-ribosylation by immunoblot and immunofluorescence. Thus, this engineered isoform of Af1521 can also serve as a valuable tool for the analysis of cellular ADP-ribosylation under in vivo conditions

Goethite Nanorods: Synthesis and Investigation of the Size Effect on Their Orientation within a Magnetic Field by SAXS

Goethite is a naturally anisotropic, antiferromagnetic iron oxide. Following its atomic structure, crystals grow into a fine needle shape that has interesting properties in a magnetic field. The needles align parallel to weak magnetic fields and perpendicular when subjected to high fields. We synthesized goethite nanorods with lengths between 200 nm and 650 nm in a two-step process. In a first step we synthesized precursor particles made of akaganeite (β-FeOOH) rods from iron(III)chloride. The precursors were then treated in a hydrothermal reactor under alkaline conditions with NaOH and polyvinylpyrrolidone (PVP) to form goethite needles. The aspect ratio was tunable between 8 and 15, based on the conditions during hydrothermal treatment. The orientation of these particles in a magnetic field was investigated by small angle X-ray scattering (SAXS). We observed that the field strength required to trigger a reorientation is dependent on the length and aspect ratio of the particles and could be shifted from 85 mT for the small particles to about 147 mT for the large particles. These particles could provide highly interesting magnetic properties to nanocomposites, that could then be used for sensing applications or membranes

Halocarbon sources and emissions over the Western Pacific

Natural, short-lived halocarbons play a role in the tropospheric and stratospheric ozone budget. The tropical oceans are a known source of reactive iodine and bromine to the atmosphere in the form of iodinated and brominated very short lived substances (VSLS), as e.g. methyl iodide (CH3I), bromoform (CHBr3) and dibromomethane (CH2Br2), which contribute to tropospheric and stratospheric halogens. Elevated atmospheric concentrations above the oceans are related to oceanic supersaturations of the compounds, caused by photochemical and biological production. The tropical Western Pacific is of special interest since it is a largely uncharacterized region for the oceanic compounds and in certain regions a projected hot spot for their emissions and transport pathways through the free troposphere into the stratosphere. From 9 to 25 October 2009 the IFM-GEOMAR (Kiel, Germany) conducted a cruise with RV Sonne in the tropical Western Pacific to investigate trace gas emissions on a 4030 nm (7,500 km) and 60 degrees latitude covering transit between Tomakomai (Japan, 42°N/ 141°E) and Townsville (Australia, 19°S/ 146°E). We will present highlights of the oceanic and atmospheric halogen (inorganic and organic compounds) and ozone measurements, as well as transport simulations of the organic compounds with the Lagrangian particle dispersion model FLEXPART, including the photochemical decay and the wash out of the VSLS source and product gases