Search

A misconception lingers in the minds of some wine consumers that Champagne wines should not age much after the minimum period of 15 months in contact with dead yeasts, known as maturation on lees. It is certainly a myth, as far as the best cuvees are concerned. Dissolved CO2 being responsible for bubble formation in sparkling wines, keeping it as efficiently as possible in the sealed bottles during aging is therefore a challenge of importance for old vintages likely to mature on lees for several decades. Measurements of dissolved CO2 were done on an outstanding vertical collection of successive vintages from a prestige cuvee, showing maturation on lees ranging from several months up to 35 years at a constant temperature of 12 °C. Progressive losses of dissolved CO2 during aging on lees were evidenced and discussed on the basis of a previously developed exponential-decay type model taking into account the main geometrical parameters of both the cork and bottle. The prestige cuvee (with a narrow bottleneck, and sealed with premium natural cork stoppers) was found to hold much more efficiently dissolved CO2 during aging than a batch of standard Champagne and sparkling wines bottles showing 3 mm wider bottlenecks. By fitting our data with the exponential-decay model, the diffusion coefficient of gas-phase CO2 through the cork stoppers used to seal this prestige cuvee was found to range between about 5 × 10 − 11 and 9 × 10 − 11 m 2 s − 1 . Moreover, by extrapolating the data well beyond the measurement range, it was suggested that very long maturation on lees of the order of 76 ± 19 years should be needed to decrease the level of dissolved CO2 in the prestige cuvee below the critical concentration required for bubbling.

Recent strategies targeting the interaction of the programmed cell death ligand-1 (PD-L1, B7-H1, CD274) with its receptor, PD-1, resulted in promising activity in early phase clinical trials. In this study, we used various antibodies and in situ mRNA hybridization to measure PD-L1 in non-small cell lung cancer (NSCLC) using a quantitative fluorescence (QIF) approach to determine the frequency of expression and prognostic value in two independent populations. A control tissue microarray (TMA) was constructed using PD-L1-transfected cells, normal human placenta and known PD-L1-positive NSCLC cases. Only one of four antibodies against PD-L1 (5H1) validated for specificity on this TMA. In situ PD-L1 mRNA using the RNAscope method was similarly validated. Two cohorts of NSCLC cases in TMAs including 340 cases from hospitals in Greece and 204 cases from Yale University were assessed. Tumors showed PD-L1 protein expression in 36% (Greek) and 25% (Yale) of the cases. PD-L1 expression was significantly associated with tumor-infiltrating lymphocytes in both cohorts. Patients with PD-L1 (both protein and mRNA) expression above the detection threshold showed statistically significant better outcome in both series (log-rank P=0.036 and P=0.027). Multivariate analysis showed that PD-L1 expression was significantly associated with better outcome independent of histology. Measurement of PD-L1 requires specific conditions and some commercial antibodies show lack of specificity. Expression of PD-L1 protein or mRNA is associated with better outcome. Further studies are required to determine the value of this marker in prognosis and prediction of response to treatments targeting this pathway.

We report here on the formation of a bioactive hierarchically structured membrane by self-assembly. The membrane is formed with hyaluronic acid and peptide amphiphiles with binding affinity for heparin, and its hierarchical structure contains both an amorphous zone and a layer of fibrils oriented perpendicular to the membrane plane. The design of bioactivity is based on the potential ability to bind and slowly release heparin-binding growth factors. Human mesenchymal stem cells seeded on these membranes attached and remained viable. Basic fibroblast growth factor (FGF2) and vascular endothelial growth factor (VEGF) were incorporated within the membrane structure prior to self-assembly and released into media over a prolonged period of time (14 days). Using the chicken chorioallantoic membrane (CAM) assay, we also found that these membranes induced a significant and rapid enhancement of angiogenesis relative to controls.