N plus 3 Advanced Concept Studies for Supersonic Commercial Transport Aircraft Entering Service in the 2030-2035 Period

Boeing, with Pratt & Whitney, General Electric, Rolls-Royce, M4 Engineering, Wyle Laboratories and Georgia Institute of Technology, conducted a study of supersonic commercial aircraft concepts and enabling technologies for the year 2030-2035 timeframe. The work defined the market and environmental/regulatory conditions that could evolve by the 2030/35 time period, from which vehicle performance goals were derived. Relevant vehicle concepts and technologies are identified that are anticipated to meet these performance and environmental goals. A series of multidisciplinary analyses trade studies considering vehicle sizing, mission performance and environmental conformity determined the appropriate concepts. Combinations of enabling technologies and the required technology performance levels needed to meet the desired goals were identified. Several high priority technologies are described in detail, including roadmaps with risk assessments that outline objectives, key technology challenges, detailed tasks and schedules and demonstrations that need to be performed. A representative configuration is provided for reference purposes, along with associated performance estimates based on these key technologies

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

Moose Use of Aquatic Resources for Cooling and Sodium Needs

University Honors Capstone Project Poster, University of Minnesota Duluth, 2016. This project was supported in part by University of Minnesota Undergraduate Research Opportunities Program (UROP) funding. Natural Resources Research Institute, Department of Biology University of Minnesota Duluth, and Voyageurs National Park

Green Chemistry PAPER Expanding GSK&apos;s solvent selection guide -embedding sustainability into solvent selection starting at medicinal chemistry †

Solvents make a large contribution to the environmental impact of manufacturing processes of active pharmaceutical ingredients (API), as well as playing an important role in other chemical industries, with millions of tons used and disposed of each year. GlaxoSmithKline (GSK) has previously reported on the both the development of a GSK solvent selection guide and the incorporation of solvent life cycle inventory and assessment information. The GSK solvent selection guide has been further enhanced by: ∑ Revising the assessments of factors that impact process safety, separating reactivity from fire and explosion rankings. ∑ More than doubling the number of solvents in the guide, to a total of 110 from the initial 47. ∑ Adding a customised solvent selection guide appropriate for medicinal chemistry and analytical laboratories. The new GSK solvent selection guide enables GSK scientists to objectively assess solvents and determine whether existing or new solvents brought to market as &apos;greener&apos; alternatives truly represent a more sustainable choice or whether they are just addressing a single issue associated with sustainability

Additional file 1 of A systems framework for implementing healthy food retail in grocery settings

Additional file 1: Appendix 1. Summary of methodological approach to developing the START-G map. Figure S1. Summary of coding and validation process to create a systems map to describe the causal determinants of the adoption, implementation and maintenance of a healthy food marketing and promotion intervention in a grocery setting. Table S1. Description of factors included in final abstracted START-G framework of factors affecting successful implementation of healthy food retail initiatives in grocery settings

Investigating Structural Dynamics of KCNE3 in Different Membrane Environments Using Molecular Dynamics Simulations

KCNE3 is a potassium channel accessory transmembrane protein that regulates the function of various voltage-gated potassium channels such as KCNQ1. KCNE3 plays an important role in the recycling of potassium ion by binding with KCNQ1. KCNE3 can be found in the small intestine, colon, and in the human heart. Despite its biological significance, there is little information on the structural dynamics of KCNE3 in native-like membrane environments. Molecular dynamics (MD) simulations are a widely used as a tool to study the conformational dynamics and interactions of proteins with lipid membranes. In this study, we have utilized all-atom molecular dynamics simulations to characterize the molecular motions and the interactions of KCNE3 in a bilayer composed of: a mixture of POPC and POPG lipids (3:1), POPC alone, and DMPC alone. Our MD simulation results suggested that the transmembrane domain (TMD) of KCNE3 is less flexible and more stable when compared to the N- and C-termini of KCNE3 in all three membrane environments. The conformational flexibility of N- and C-termini varies across these three lipid environments. The MD simulation results further suggested that the TMD of KCNE3 spans the membrane width, having residue A69 close to the center of the lipid bilayers and residues S57 and S82 close to the lipid bilayer membrane surfaces. These results are consistent with previous biophysical studies of KCNE3. The outcomes of these MD simulations will help design biophysical experiments and complement the experimental data obtained on KCNE3 to obtain a more detailed understanding of its structural dynamics in the native membrane environment