Preparative isolation, fractionation and chemical characterization of dissolved organics from natural and industrially derived bitumen-influenced groundwaters from the Athabasca River watershed

Recent analytical advances have provided evidence that groundwater affected by oil sands process-affected water (OSPW) is reaching the Athabasca River at one location. To understand and discriminate the toxicological risks posed by OSPW-influenced groundwater relative to groundwaters associated with natural oil sands deposits, these highly complex mixtures of soluble organics were subjected to toxicological characterization through effects directed analysis. A recently-developed preparative fractionation methodology was applied to bitumen-influenced groundwaters and successfully isolated dissolved organics from both industrial and natural sources into three chemically distinct fractions (F1, F2, F3), enabling multiple toxicological assessments. Analytical techniques included electrospray ionization high resolution mass spectrometry (ESI-HRMS), liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF/MS), gas chromatography mass spectrometry (GC–MS), and synchronous fluorescence spectroscopy (SFS) methods, which did not reveal obvious differences between sources. Comparisons between fractions within each source consistently demonstrated that F3 contained compounds with greater polarity than F2, which in turn was more polar than F1. The abundance of O2 species was confined to F1, including naphthenic acids often cited for being the primary toxicants within bitumen-influenced waters. This result is consistent with earlier work on aged OSPW, as well as with other extraction methods, suggesting that additional factors other than molecular weight and the presence of acid functionalities play a prominent role in defining compound polarities and toxicities within complex bitumen-derived organic mixtures. The similarities in organic abundances, chemical speciation, aromaticity, and double bond equivalents, concomitant with inorganic mixture similarities, demonstrate the resemblances of bitumen-influenced groundwaters regardless of the source, and reinforce the need for more advanced targeted analyses for source differentiation.This work was funded under the Oil Sands Monitoring Program, and is a contribution to the Program, but does not necessarily reflect the position of the Program. Internal resources from Environment and Climate Change Canada were also used to fund this research

Scope

Scope, later retitled Centerscope, was published by the Boston University Medical Center to report on events at and around the Center

Tools and techniques for solvent selection: green solvent selection guides

Driven by legislation and evolving attitudes towards environmental issues, establishing green solvents for extractions, separations, formulations and reaction chemistry has become an increasingly important area of research. Several general purpose solvent selection guides have now been published with the aim to reduce use of the most hazardous solvents. This review serves the purpose of explaining the role of these guides, highlighting their similarities and differences. How they can be used most effectively to enhance the greenness of chemical processes, particularly in laboratory organic synthesis and the pharmaceutical industry, is addressed in detail

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