9 results on '"Pfeiffer, A T"'
Search Results
2. Phosphorylation patterns in the AT1R C-terminal tail specify distinct downstream signaling pathways.
- Author
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Gareri, Clarice, Pfeiffer, Conrad T., Jiang, Xue, Paulo, Joao A., Gygi, Steven P., Pham, Uyen, Chundi, Anand, Wingler, Laura M., Staus, Dean P., Stepniewski, Tomasz Maciej, Selent, Jana, Lucero, Emilio Y., Grogan, Alyssa, Rajagopal, Sudarshan, and Rockman, Howard A.
- Subjects
G proteins ,ANGIOTENSIN II ,MOLECULAR dynamics ,LIGANDS (Biochemistry) ,G protein coupled receptors ,PHOSPHORYLATION - Abstract
Different ligands stabilize specific conformations of the angiotensin II type 1 receptor (AT1R) that direct distinct signaling cascades mediated by heterotrimeric G proteins or β-arrestin. These different active conformations are thought to engage distinct intracellular transducers because of differential phosphorylation patterns in the receptor C-terminal tail (the "barcode" hypothesis). Here, we identified the AT1R barcodes for the endogenous agonist AngII, which stimulates both G protein activation and β-arrestin recruitment, and for a synthetic biased agonist that only stimulates β-arrestin recruitment. The endogenous and β-arrestin–biased agonists induced two different ensembles of phosphorylation sites along the C-terminal tail. The phosphorylation of eight serine and threonine residues in the proximal and middle portions of the tail was required for full β-arrestin functionality, whereas phosphorylation of the serine and threonine residues in the distal portion of the tail had little influence on β-arrestin function. Similarly, molecular dynamics simulations showed that the proximal and middle clusters of phosphorylated residues were critical for stable β-arrestin–receptor interactions. These findings demonstrate that ligands that stabilize different receptor conformations induce different phosphorylation clusters in the C-terminal tail as barcodes to evoke distinct receptor-transducer engagement, receptor trafficking, and signaling. Editor's summary: The specific patterns of phosphorylation in the intracellular tail of a G protein–coupled receptor (GPCR) are thought to act as a barcode that determines whether G proteins are stimulated or β-arrestins are recruited. Gareri et al. investigated the role of phosphorylation barcodes in signaling by the angiotensin II type 1 receptor (AT1R). AT1R elicits both G protein activation and β-arrestin recruitment in response to the endogenous agonist AngII but stimulates only β-arrestin recruitment in response to a synthetic biased agonist. The authors identified patterns of serine and threonine phosphorylation that stabilized specific conformations of β-arrestin and were necessary for β-arrestin function. These findings demonstrate the importance of phosphorylation barcodes in determining the consequences of AT1R activation. —Annalisa M. VanHook [ABSTRACT FROM AUTHOR]
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- 2024
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3. Proximity labeling for investigating protein-protein interactions
- Author
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Pfeiffer, Conrad T., primary, Paulo, Joao A., additional, Gygi, Steven P., additional, and Rockman, Howard A., additional
- Published
- 2022
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4. Preventing Health Disparities during COVID through Perinatal Home Screening as Black Authoritative Knowledge
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Chapman, Rachel R., primary, Mohamed, Sumaya B., additional, Rage, Hodan, additional, Abdulahi, Ayan, additional, Jimenez, Jan, additional, Gavin, Amelia R., additional, Zetell, Jasmine, additional, Chatterjee, Kavya N., additional, Valderrábano, Susie, additional, Sundar, Savita, additional, Madey, Halima, additional, and Pfeiffer, James T., additional
- Published
- 2023
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5. Spiroligomer‐Based Macrocycles for Atomically Precise Membranes
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Xie, Yihui, primary, Luo, Danni, additional, Wiener, Jesse A., additional, Koval, Alexander B., additional, Pfeiffer, Conrad T., additional, and Schafmeister, Christian E., additional
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- 2023
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6. Risk factors, management, and outcomes in isolated parafalcine or tentorial subdural hematomas
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Juhasz, Kristin A., primary, Iszkula, Erik R., additional, English, Gregory R., additional, Desiderio, Daniel B., additional, Estrada, Carmen Y., additional, Leshikar, David E., additional, Pfeiffer, Benjamin T., additional, Roesel, Emily H., additional, Wagle, Ashley E., additional, and Holmes, James F., additional
- Published
- 2023
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7. The SPARC Toroidal Field Model Coil Program
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Hartwig, Zachary S., Vieira, Rui F., Dunn, Darby, Golfinopoulos, Theodore, LaBombard, Brian, Lammi, Christopher J., Michael, Philip C., Agabian, Susan, Arsenault, David, Barnett, Raheem, Barry, Mike, Bartoszek, Larry, Beck, William K., Bellofatto, David, Brunner, Daniel, Burke, William, Burrows, Jason, Byford, William, Cauley, Charles, Chamberlain, Sarah, Chavarria, David, Cheng, JL, Chicarello, James, Diep, Van, Dombrowski, Eric, Doody, Jeffrey, Doos, Raouf, Eberlin, Brian, Estrada, Jose, Fry, Vincent, Fulton, Matthew, Garberg, Sarah, Granetz, Robert, Greenberg, Aliya, Greenwald, Martin, Heller, Samuel, Hubbard, Amanda E., Ihloff, Ernest, Irby, James H., Iverson, Mark, Jardin, Peter, Korsun, Daniel, Kuznetsov, Sergey, Lane-Walsh, Stephen, Landry, Richard, Lations, Richard, Leccacorvi, Rick, Levine, Matthew, Mackay, George, Metcalfe, Kristen, Moazeni, Kevin, Mota, John, Mouratidis, Theodore, Mumgaard, Robert, Muncks, JP, Murray, Richard A., Nash, Daniel, Nottingham, Ben, O'Shea, Colin, Pfeiffer, Andrew T., Pierson, Samuel Z., Purdy, Clayton, Radovinsky, Alexi, Ravikumar, Dhananjay K., Reyes, Veronica, Riva, Nicolo, Rosati, Ron, Rowell, Michael, Salazar, Erica E., Santoro, Fernando, Sattarov, Akhdiyor, Saunders, Wayne, Schweiger, Patrick, Schweiger, Shane, Shepard, Maise, Shiraiwa, Syun'ichi, Silveira, Maria, Snowman, FT, Sorbom, Brandon N., Stahle, Peter, Stevens, Ken, Stillerman, Joshua, Tammana, Deepthi, Toland, Thomas L., Tracey, David, Turcotte, Ronnie, Uppalapati, Kiran, Vernacchia, Matthew, Vidal, Christopher, Voirin, Erik, Warner, Alex, Watterson, Amy, Whyte, Dennis G., Wilcox, Sidney, Wolf, Michael, Wood, Bruce, Zhou, Lihua, and Zhukovsky, Alex
- Abstract
The SPARC Toroidal Field Model Coil (TFMC) Program was a three-year effort between 2018 and 2021 that developed novel rare earth barium copper oxide (REBCO) superconductor technologies and then successfully utilized these technologies to design, build, and test a first-in-class, high-field (∼20 T), representative-scale (∼3 m) superconducting toroidal field (TF) coil. The program was executed jointly by the MIT Plasma Science and Fusion Center (PSFC) and Commonwealth Fusion Systems (CFS) as a technology enabler of the superconducting high-field pathway to fusion energy, and, in particular, as a risk retirement program for the no insulation (NI) TF magnet in the SPARC net-energy fusion tokamak. The TFMC achieved its programmatic goal of experimentally demonstrating a large-scale high-field REBCO magnet, achieving 20.1 T peak field-on-conductor with 40.5 kA of terminal current, 815 kN/m of Lorentz loading on the REBCO stacks, and almost 1 GPa of mechanical stress accommodated by the structural case. Fifteen internal demountable pancake-to-pancake joints operated in the 0.5 to 2.0 nΩ range at 20 K and in magnetic fields up to 12 T. The dc and ac electromagnetic performance of the magnet predicted by new advances in high-fidelity computational models was confirmed in two test campaigns while the parallel, single-pass, pressure-vessel style coolant scheme capable of large heat removal was validated. In the test facility, a feeder system composed of REBCO current leads and cables was experimentally qualified up to 50 kA, and a liquid-free cryocooler-based helium cryogenic system provided 600 W of cooling power at 20 K with mass flow rates up to 70 g/s at a maximum design pressure of 2 MPa for the test campaigns. Finally, the feasibility of using passive, self-protection against a quench in a fusion-scale NI TF coil was experimentally assessed. While the TFMC was intentionally not optimized for quench resiliency—and suffered localized thermal damage in response to an intentional open-circuit quench at 31.5 kA terminal current—the extensive data and validated models that it produced represent a critical step towards this important objective.
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- 2024
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8. Development of the first non-planar REBCO stellarator coil using VIPER cable.
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Riva, N, Granetz, R S, Vieira, R, Hubbard, A, Pfeiffer, A T, Harris, P, Chamberlain, C, Hartwig, Z S, Watterson, A, Anderson, D, and Volberg, R
- Subjects
STELLARATORS ,HIGH temperature superconductors ,SUPERCONDUCTING magnets ,VIPERIDAE ,CRITICAL currents ,COPPER oxide ,MAGNETIC fields - Abstract
The benefits of operating fusion devices, such as tokamaks and stellarators, at high fields make high-temperature superconducting magnets necessary to realize a compact fusion power system. Superconducting stellarators, such as W7-X, have used standard low-temperature superconductor technology niobium-titanium. ARPA-E has recently funded a two-year project led by the startup Type One Energy and involving the Fusion Technology Institute at the University of Wisconsin-Madison, the Plasma Science to design and fabricate the first non-planar high-temperature superconductor (HTS) rare-earth barium copper oxide (REBCO) coil for a high-field stellarator based on the SPARC tokamak's VIPER cable concept. The design consists of a 1.5-turn non-planar REBCO coil supported by a pair of 3D printed stainless steel radial plates. The ultimate goals of the project are to determine if commercial REBCO tapes and additive manufacturing can be used to fabricate high field ( ⩾ 10 T ) non-planar coils with tight bending radii ( ≃ 100 m m ) and with a degradation of the critical current smaller than 20% with respect to the expected performance. In this work we present numerical analysis for non-planar coils (critical current, magnetic field map, Lorentz forces and quench aspects) at the operating conditions of 77 K and 20 K and the fabrication and testing in liquid nitrogen (77 K) of the first two non-planar demonstrators for stellarators based on a VIPER cable. The first demonstrator is a short NO n-planar V IP E R cab L e (cable demonstrator at which we will refer to as NOVEL) equipped with 100 HTS REBCO tapes and with a critical current of 5700 A at 77 K (self-field); the second is a M ult I ple turns (1.5-turns) NO n-pl AN ar coil (coil demonstrator at which we will refer to as MINOAN) equipped with 30 HTS tapes and with a critical current of 2100 A at 77 K (self-field). Both demonstrators were tested at 77 K (liquid nitrogen bath) and the results showed that—even after being bent into non-planar shapes with bend radii ≃ 100 m m —the degradation of the critical current I c was within 15%, meeting the expected goals of the project. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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9. The SPARC Toroidal Field Model Coil Program
- Author
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Hartwig, Zachary S., primary, Vieira, Rui F., additional, Dunn, Darby, additional, Golfinopoulos, Theodore, additional, LaBombard, Brian, additional, Lammi, Christopher J., additional, Michael, Philip C., additional, Agabian, Susan, additional, Arsenault, David, additional, Barnett, Raheem, additional, Barry, Mike, additional, Bartoszek, Larry, additional, Beck, William K., additional, Bellofatto, David, additional, Brunner, Daniel, additional, Burke, William, additional, Burrows, Jason, additional, Byford, William, additional, Cauley, Charles, additional, Chamberlain, Sarah, additional, Chavarria, David, additional, Cheng, JL, additional, Chicarello, James, additional, Diep, Van, additional, Dombrowski, Eric, additional, Doody, Jeffrey, additional, Doos, Raouf, additional, Eberlin, Brian, additional, Estrada, Jose, additional, Fry, Vincent, additional, Fulton, Matthew, additional, Garberg, Sarah, additional, Granetz, Robert, additional, Greenberg, Aliya, additional, Greenwald, Martin, additional, Heller, Samuel, additional, Hubbard, Amanda E., additional, Ihloff, Ernest, additional, Irby, James H., additional, Iverson, Mark, additional, Jardin, Peter, additional, Korsun, Daniel, additional, Kuznetsov, Sergey, additional, Lane-Walsh, Stephen, additional, Landry, Richard, additional, Lations, Richard, additional, Leccacorvi, Rick, additional, Levine, Matthew, additional, Mackay, George, additional, Metcalfe, Kristen, additional, Moazeni, Kevin, additional, Mota, John, additional, Mouratidis, Theodore, additional, Mumgaard, Robert, additional, Muncks, JP, additional, Murray, Richard A., additional, Nash, Daniel, additional, Nottingham, Ben, additional, O'Shea, Colin, additional, Pfeiffer, Andrew T., additional, Pierson, Samuel Z., additional, Purdy, Clayton, additional, Radovinsky, Alexi, additional, Ravikumar, Dhananjay K., additional, Reyes, Veronica, additional, Riva, Nicolo, additional, Rosati, Ron, additional, Rowell, Michael, additional, Salazar, Erica E., additional, Santoro, Fernando, additional, Sattarov, Akhdiyor, additional, Saunders, Wayne, additional, Schweiger, Patrick, additional, Schweiger, Shane, additional, Shepard, Maise, additional, Shiraiwa, Syun'ichi, additional, Silveira, Maria, additional, Snowman, FT, additional, Sorbom, Brandon N., additional, Stahle, Peter, additional, Stevens, Ken, additional, Stillerman, Joshua, additional, Tammana, Deepthi, additional, Toland, Thomas L., additional, Tracey, David, additional, Turcotte, Ronnie, additional, Uppalapati, Kiran, additional, Vernacchia, Matthew, additional, Vidal, Christopher, additional, Voirin, Erik, additional, Warner, Alex, additional, Watterson, Amy, additional, Whyte, Dennis G., additional, Wilcox, Sidney, additional, Wolf, Michael, additional, Wood, Bruce, additional, Zhou, Lihua, additional, and Zhukovsky, Alex, additional
- Published
- 2023
- Full Text
- View/download PDF
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