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1. Drug Metabolism

Author

Lock, R., primary, Webborn, P. J. H., additional, Vose, C. W., additional, and Ings, R. M. J., additional

Published
2023
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2. Autophagy restricts proliferation driven by oncogenic phosphatidylinositol 3-kinase in three-dimensional culture.

Author

Chen, N, Eritja, N, Lock, R, and Debnath, Jayanta

Subjects
Adaptor Proteins, Signal Transducing, Apoptosis, Autophagy, Cell Culture Techniques, Cell Line, Cell Proliferation, Cell Transformation, Neoplastic, Humans, Hydroxychloroquine, Lysosomes, Mechanistic Target of Rapamycin Complex 1, Mitogen-Activated Protein Kinases, Multiprotein Complexes, Mutation, Phosphatidylinositol 3-Kinase, Sequestosome-1 Protein, Sirolimus, TOR Serine-Threonine Kinases
Abstract

Autophagy is a tightly regulated lysosomal self-digestion process that can both promote and impede tumorigenesis. Here, we utilize a three-dimensional (3D) culture model to address how interactions between autophagy and the phosphatidylinositol 3-kinase(PI3K)/Akt/mammalian target of rapamycin pathway impact the malignant behavior of cells carrying a tumor-derived, activating mutation in PI3K (PI3K-H1047R). In this model, autophagy simultaneously mediates tumor-suppressive and -promoting functions within individual glandular structures. In 3D culture, constitutive PI3K activation overcomes proliferation arrest and promotes resistance to anoikis in the luminal space, resulting in aberrant structures with filled lumen. Inhibiting autophagy in PI3K-H1047R structures triggers luminal cell apoptosis, resulting in lumen clearance. At the same time, autophagy gene depletion strongly enhances PI3K-H1047R cell proliferation during 3D morphogenesis, revealing an unexpected role for autophagy in restricting proliferation driven by PI3K activation. Intriguingly, overexpression of the autophagy cargo receptor p62/SQSTM1 in PI3K-H1047R cells is sufficient to enhance cell proliferation, activate the extracellular signal-related kinase/mitogen-activated protein kinase pathway and to promote epidermal growth factor-independent proliferation in 3D culture. Overall, these results indicate that autophagy antagonizes specific aspects of oncogenic PI3K transformation, with the loss of autophagy promoting proliferation.

Published
2013

3. No Tow Trucks Beyond Mars

Author

Lock, R, Boykins, K, Kerber, L, Tucker, S, and Rosing, D

Abstract

UNKNOWN

Published
2018

13. Are We Producing Teaching Technicians or Science Educators? The Consequences of Differential Demands on Trainee Science Teachers.

Author

Finlayson, H., Lock, R., Soares, A., and Tebbutt, M.

Abstract

According to a survey of student teachers (39 in science 38 in history or English), 90% of the science student teachers claimed that 50% of their teaching was in topics outside their subject area and that they experience low self-confidence and difficulty. In contrast, 44% of nonscience student teachers never taught outside their subject area. (SK)

Published
1998

26. Mars Next Orbiter Science Analysis Group (NEX-SAG): White Paper Report to the 2023-2032 Planetary Sciences and Astrobiology Decadal Survey

Author

Zurek, Richard, primary, Campbell, Bruce, additional, Byrne, S., additional, Calvin, W., additional, Carter, L. M., additional, Clancy, R. T., additional, Ehlmann, B., additional, Garvin, J. B., additional, Kahre, M., additional, Kerber, L. A., additional, Murchie, S., additional, Putzig, N. E., additional, Salvatore, M. R., additional, Smith, M. D., additional, Tamppari, L., additional, Thomson, B., additional, Diniega, S., additional, Lock, R. E., additional, Bridges, N., additional, Whitley, R., additional, Bussey, B., additional, Meyer, M., additional, and Pratt, L., additional

Published
2021
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36. Return to Europa: Overview of the Jupiter Europa Orbiter Mission

Author

Clark, K, Tan-Wang, G, Boldt, J, Greeley, R, Jun, I, Lock, R, Ludwinski, J, Pappalardo, R, Van Houten, T, and Yan, T

Subjects
Lunar And Planetary Science And Exploration
Abstract

Missions to explore Europa have been imagined ever since the Voyager mission first suggested that Europa was geologically very young. Subsequently, Galileo supplied fascinating new insights into that satellite's secrets. The Jupiter Europa Orbiter (JEO) would be the NASA-led portion of the Europa Jupiter System Mission (EJSM), an international mission with orbiters developed by NASA, ESA and possibly JAXA. JEO would address a very important subset of the complete EJSM science objectives and is designed to function alone or in conjunction with ESA's Jupiter Ganymede Orbiter (JGO).

Published
2009

37. Analysis of architectures for the scientific exploration of Enceladus

Author

Strange, N, Wertz-Chen, J, Elliott, J, Lock, R, Smythe, W, Borden, C, Moeller, R, and Spilker, T

Abstract

In 2007, a JPL Rapid Mission Architecture (RMA) analysis team identified and evaluated a broad set of mission architecture options for a suite of scientific exploration objectives targeting the Saturnian moon Enceladus. Primary science objectives were largely focused on examination of the driving mechanisms and extent of interactions by the plumes of Enceladus recently discovered by Cassini. Investigation of the architectural trade space spanned a wide range of options, from high-energy flybys of Enceladus as a re-instrumented expansion on the Cassini mission, to more complex, multi-element combinations of Enceladus orbiters carrying multiple variants of in-situ deployable systems. Trajectory design emerged as a critical element of the mission concepts, enabling challenging missions on Atlas V and Delta IV-Heavy class launch vehicles. Various Enceladus Flagship-class mission concepts identified were analyzed and compared against several first-order figures of merit, including mass, cost, risk, mission timeline, and associated science value with respect to accomplishment of the full set of science objectives. Results are presented for these comparative analyses and the characterization of the explored trade space.

Published
2009

45. C1 inhibitor deficiency: consensus document

Author

Gompels, M. M., Lock, R. J., Abinun, M., Bethune, C. A., Davies, G., Grattan, C., Fay, A. C., Longhurst, H. J., Morrison, L., Price, A., Price, M., and Watters, D.

Published
2005

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