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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Decoupling of the PI3K pathway via mutation necessitates combinatorial treatment in HER2+ breast cancer

We report here on experimental and theoretical efforts to determine how best to combine drugs that inhibit HER2 and AKT in HER2 + breast cancers. We accomplished this by measuring cellular and molecular responses to lapatinib and the AKT inhibitors (AKT i ) GSK690693 and GSK2141795 in a panel of 22 HER2 + breast cancer cell lines carrying wild type or mutant PIK3CA. We observed that combinations of lapatinib plus AKT i were synergistic in HER2 /PIK3CA mut cell lines but not in HER2 + /PIK3CA wt cell lines. We measured changes in phospho-protein levels in 15 cell lines after treatment with lapatinib, AKT i or lapatinib + AKT i to shed light on the underlying signaling dynamics. This revealed that p-S6RP levels were less well attenuated by lapatinib in HER2 + /PIK3CA mut cells compared to HER2 + /PIK3CA wt cells and that lapatinib + AKT i reduced p-S6RP levels to those achieved in HER2 + /PIK3CA wt cells with lapatinib alone. We also found that that compensatory up-regulation of p-HER3 and p-HER2 is blunted in PIK3CA mut cells following lapatinib + AKT i treatment. Responses of HER2 + SKBR3 cells transfected with lentiviruses carrying control or PIK3CA mut sequences were similar to those observed in HER2 + /PIK3CA mut cell lines but not in HER2 + /PIK3CA wt cell lines. We used a nonlinear ordinary differential equation model to support the idea that PIK3CA mutations act as downstream activators of AKT that blunt lapatinib inhibition of downstream AKT signaling and that the effects of PIK3CA mutations can be countered by combining lapatinib with an AKT i . This combination does not confer substantial benefit beyond lapatinib in HER2 + /PIK3CA wt cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Cosmological Constraints on Decoupled Dark Photons and Dark Higgs

Any neutral boson such as a dark photon or dark Higgs that is part of a non-standard sector of particles can mix with its standard model counterpart. When very weakly mixed with the Standard Model, these particles are produced in the early Universe via the freeze-in mechanism and subsequently decay back to standard model particles. In this work, we place constraints on such mediator decays by considering bounds from Big Bang nucleosynthesis and the cosmic microwave background radiation. We find both nucleosynthesis and CMB can constrain dark photons with a kinetic mixing parameter between log ϵ ~ -10 to -17 for masses between 1 MeV and 100 GeV. Similarly, the dark Higgs mixing angle ϵ with the Standard Model Higgs is constrained between log ϵ ~ -6 to -15. Dramatic improvement on the bounds from CMB spectral distortions can be achieved with proposed experiments such as PIXIE.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2017

Decaf: Decoupled Dataflows for In Situ High-Performance Workflows

Decaf is a dataflow system for the parallel communication of coupled tasks in an HPC workflow. The dataflow can perform arbitrary data transformations ranging from simply forwarding data to complex data redistribution. Decaf does this by allowing the user to allocate resources and execute custom code in the dataflow. All communication through the dataflow is efficient parallel message passing over MPI. The runtime for calling tasks is entirely message-driven; Decaf executes a task when all messages for the task have been received. Such a messagedriven runtime allows cyclic task dependencies in the workflow graph, for example, to enact computational steering based on the result of downstream tasks. Decaf includes a simple Python API for describing the workflow graph. This allows Decaf to stand alone as a complete workflow system, but Decaf can also be used as the dataflow layer by one or more other workflow systems to form a heterogeneous task-based computing environment. In one experiment, we couple a molecular dynamics code with a visualization tool using the FlowVR and Damaris workflow systems and Decaf for the dataflow. In another experiment, we test the coupling of a cosmology code with Voronoi tessellation and density estimation codes using MPI for the simulation, the DIY programming model for the two analysis codes, and Decaf for the dataflow. Such workflows consisting of heterogeneous software infrastructures exist because components are developed separately with different programming models and runtimes, and this is the first time that such heterogeneous coupling of diverse components was demonstrated in situ on HPC systems.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2019

Direct Photosynthetic Production of Biodiesel by Growth-Decoupled Cyanobacteria

The ultimate goal of this project was the production and excretion of a lauroyl ester-based drop-in biofuel by building on the development of a cyanobacterial strain derived from Synechocystis sp. PCC 6803 that is efficient in using sunlight to reduce CO 2 from the atmosphere to produce and excrete laurate, a fatty acid (FA) that is easily used as a biofuel precursor. To achieve this goal the project focused on five primary objectives: (1) produce more laurate, (2) convert laurate to a lauroyl ester by introducing additional genetic modifications for the synthesis of fatty acid esters, (3) arrest cell growth but not metabolic activity, to make resources more available for lauroyl ester production, (4) reduce the native production of exopolysaccharides to increase the amount of fixed carbon available for biofuel production and to reduce the carbon nutrients available in the medium for potential invasive microbes, and (5) perform a techno-economic analysis to evaluate the longer-term promise and viability of lauroyl ester production in cyanobacterial systems. A photosynthetically produced lauroyl ester could be used as a diesel replacement without the need for additional and costly downstream processing steps, a development of great importance to the mission of DOE with regard to biofuel production.

09 BIOMASS FUELS↗