606 results on '"Walker, Christopher P."'
Search Results
2. Semiparametric Bayesian Inference for a Conditional Moment Equality Model
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Walker, Christopher D.
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Economics - Econometrics - Abstract
Conditional moment equality models are regularly encountered in empirical economics, yet they are difficult to estimate. These models map a conditional distribution of data to a structural parameter via the restriction that a conditional mean equals zero. Using this observation, I introduce a Bayesian inference framework in which an unknown conditional distribution is replaced with a nonparametric posterior, and structural parameter inference is then performed using an implied posterior. The method has the same flexibility as frequentist semiparametric estimators and does not require converting conditional moments to unconditional moments. Importantly, I prove a semiparametric Bernstein-von Mises theorem, providing conditions under which, in large samples, the posterior for the structural parameter is approximately normal, centered at an efficient estimator, and has variance equal to the Chamberlain (1987) semiparametric efficiency bound. As byproducts, I show that Bayesian uncertainty quantification methods are asymptotically optimal frequentist confidence sets and derive low-level sufficient conditions for Gaussian process priors. The latter sheds light on a key prior stability condition and relates to the numerical aspects of the paper in which these priors are used to predict the welfare effects of price changes.
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- 2024
3. Star and Planet Formation with the Single Aperture Large Telescope for Universe Studies (SALTUS) Space Observatory
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Schwarz, Kamber, Tielens, Alexander, Najita, Joan, Bergner, Jennifer, Kral, Quentin, Anderson, Carrie, Chin, Gordon, Leisawitz, David, Wilner, David, Roelfsema, Peter, van der Tak, Floris, Young, Erick, and Walker, Christopher
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
The Single Aperture Large Telescope for Universe Studies (SALTUS) is a far-infrared space mission concept with unprecedented spatial and spectral resolution. Saltus consists of a 14-m inflatable primary, providing 16 times the sensitivity and 4 times the angular resolution of Herschel, and two cryogenic detectors spanning a wavelength range of 34-660 microns and spectral resolving power of 300 - 1e7. Spectroscopic observations in the far-infrared offer many unique windows into the processes of star and planet formation. These include observations of low energy water transitions, the H2 mass tracer HD, many CHONS constraining molecules such as NH3 and H2S, and emission lines from the phonon modes of molecular ices. Observing these species will allow us to build a statistical sample of protoplanetary disk masses, characterize the water snowline, identify Kuiper Belt like debris rings around other stars, and trace the evolution CHONS from prestellar cores, through to protoplanetary disks and debris disks. This paper details details several key star and planet formation science goals achievable with SALTUS., Comment: 48 pages, 8 figures, submitted to SPIE JATIS
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- 2024
4. 14-m aperture deployable off-axis far-IR space telescope design for SALTUS observatory
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Kim, Daewook, Kim, Youngsik, Choi, Heejoo, Esparza, Marcos, Wu, Oliver, Takashima, Yuzuru, Palisoc, Art, and Walker, Christopher
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
The Single Aperture Large Telescope for Universe Studies (SALTUS) is a deployable space telescope designed to provide the astrophysics community with an extremely large far-infrared (far-IR) space observatory to explore our cosmic origins. The SALTUS observatory can observe thousands of faint astrophysical targets, including the first galaxies, protoplanetary disks in various evolutionary states, and a wide variety of solar system objects. The SALTUS design architecture utilizes radiatively cooled, 14-m diameter unobscured aperture, and cryogenic instruments to enable both high spectral and spatial resolution at unprecedented sensitivity over a wavelength range largely unavailable to any existing ground or space observatories. The unique SALTUS optical design, utilizing a large inflatable off-axis primary mirror, provides superb sensitivity, angular resolution, and imaging performance at far-IR wavelengths over a wide +/-0.02 x 0.02 degree Field of View. SALTUS design, with its highly compact form factor, allows it to be readily stowed in available launch fairings and subsequently deployed in orbit.
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- 2024
5. Design, Implementation, and Performance of the Primary Reflector for SALTUS
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Arenberg, Jonathan W., Harding, Leon K., Chang, Bob, Kuehn, Steve, Oberg, Dave, Villarreal, Michaela N., Palisoc, Arthur L., Walker, Christopher, Kim, Daewook, Lung, Zach, and Lung, Dave
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
The Single Aperture Large Telescope for Universe Studies (SALTUS) is a mission concept for a far-infrared observatory developed under the recent Astrophysics Probe Explorer opportunity from NASA. The enabling element of the program is a 14 m diameter inflatable primary mirror, M1. Due to its importance to SALTUS and potentially other space observatories, this paper focuses entirely on M1. We present a historical overview of inflatable systems, illustrating that M1 is the logical next step in the evolution of such systems. The process of design and manufacture is addressed. We examine how M1 performs in its environment in terms of operating temperature, interaction with the solar wind, and shape change due to non-penetrating particles. We investigate the longevity of the inflatant in detail and show it meets mission lifetime requirements with ample margin and discuss the development and testing to realize the flight M1., Comment: Submitted to the J. Astron. Telesc. Instrum. Syst. (JATIS), 87 pages, 36 figures, 4 tables
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- 2024
6. Single Aperture Large Telescope for Universe Studies (SALTUS): Science Overview
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Chin, Gordon, Anderson, Carrie M., Bergner, Jennifer, Biver, Nicolas, Bjoraker, Gordon L., Cavalie, Thibault, DiSanti, Michael, Gao, Jian-Rong, Hartogh, Paul, Harding, Leon K., Hu, Qing, Kim, Daewook, Kulesa, Craig, de Lange, Gert, Leisawitz, David T., Levy, Rebecca C., Lichtenberger, Arthur, Marronh, Daniel P., Najita, Joan, Newswander, Trent, Rieke, George H., Rigopoulou, Dimitra, Roefsema, Peter, Roth, Nathan X., Schwarz, Kamber, Shirley, Yancy, Spilker, Justin, Stark, Antony A., van der Tak, Floris, Takashima, Yuzuru, Tielens, Alexander, Willner, David J., Wollack, Edward J., Yates, Stephen, Young, Erick, and Walker, Christopher K.
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
The SALTUS Probe mission will provide a powerful far-infrared (far-IR) pointed space observatory to explore our cosmic origins and the possibility of life elsewhere. The observatory employs an innovative deployable 14-m aperture, with a sunshield that will radiatively cool the off-axis primary to <45K. This cooled primary reflector works in tandem with cryogenic coherent and incoherent instruments that span the 34 to 660 micron far-IR range at both high and moderate spectral resolutions., Comment: 49 pages, 10 figures, 3 tables, submitted to SPIE JATIS
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- 2024
7. SALTUS Probe Class Space Mission: Observatory Architecture and Mission Design
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Harding, Leon K., Arenberg, Jonathan W., Donovan, Benjamin, Oberg, Dave, Goold, Ryan, Chang, Bob, Walker, Christopher, Turse, Dana, Moore, Jim, Pearson Jr, Jim C., Kidd Jr, John N., Lung, Zach, and Lung, Dave
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
We describe the space observatory architecture and mission design of the SALTUS mission, a NASA Astrophysics Probe Explorer concept. SALTUS will address key far-infrared science using a 14-m diameter <45 K primary reflector (M1) and will provide unprecedented levels of spectral sensitivity for planet, solar system, and galactic evolution studies, and cosmic origins. Drawing from Northrop Grumman's extensive NASA mission heritage, the observatory flight system is based on the LEOStar-3 spacecraft platform to carry the SALTUS Payload. The Payload is comprised of the inflation control system (ICS), Sunshield Module (SM), Cold Corrector Module (CCM), Warm Instrument Electronics Module, and Primary Reflector Module (PRM). The 14-m M1 is an off-axis inflatable membrane radiatively cooled by a two-layer sunshield (~1,000 m2 per layer). The CCM corrects for residual aberration from M1 and delivers a focused beam to two instruments - High Resolution Receiver (HiRX) and SAFARI-Lite. The CCM and PRM reside atop a truss-based composite deck which also provides a platform for the attitude control system. The 5-year mission lifetime is driven by a two-consumable architecture: the propellant system and the ICS. The Core Interface Module (CIM), a multi-faceted composite truss structure, provides a load path with high stiffness, mechanical attachment, and thermal separation between the Payload and spacecraft. The SM attaches outside the CIM with its aft end integrating directly to the bus. The spacecraft maintains an attitude off M1's boresight with respect to the Sun line to facilitate the <45 K thermal environment. SALTUS will reside in a Sun-Earth halo L2 orbit with a maximum Earth slant range of 1.8 million km thereby reducing orbit transfer delta-v. The instantaneous field of regard provides two continuous 20-deg viewing zones around the ecliptic poles resulting in full sky coverage in six months., Comment: Submitted to the J. Astron. Telesc. Instrum. Syst. (JATIS), 67 pages, 16 figures, 12 tables
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- 2024
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8. Milky Way and Nearby Galaxies Science with the Single Aperture Large Telescope for Universe Studies (SALTUS) Space Observatory
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Levy, Rebecca C., Tielens, Alexander, Spilker, Justin, Marrone, Daniel P., Narayanan, Desika, and Walker, Christopher K.
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Astrophysics of Galaxies - Abstract
This paper presents an overview of the Milky Way and nearby galaxies science case for the \textit{Single Aperture Large Telescope for Universe Studies} (SALTUS) far-infrared NASA probe-class mission concept. SALTUS offers enormous gains in spatial resolution and spectral sensitivity over previous far-IR missions, thanks to its cold ($<$40~K) 14-m primary mirror. Key Milky Way and nearby galaxies science goals for SALTUS focus on understanding the role of star formation in feedback in the Local Universe. In addition to this science case, SALTUS would open a new window to to of Galactic and extragalactic communities in the 2030s, enable fundamentally new questions to be answered, and be a far-IR analog to the near- and mid-IR capabilities of JWST. This paper summarizes the Milky Way and nearby galaxies science case and plans for notional observing programs in both guaranteed and guest (open) time., Comment: Resubmitted to JATIS as part of a special issue on SALTUS
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- 2024
9. High-Redshift Extragalactic Science with the Single Aperture Large Telescope for Universe Studies (SALTUS) Space Observatory
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Spilker, Justin, Levy, Rebecca C., Marrone, Daniel, Alberts, Stacey, Chapman, Scott C., Dickinson, Mark, Egami, Eiichi, Endsley, Ryan, Narayanan, Desika, Rieke, George, Stark, Antony A., Tielens, Alexander, and Walker, Christopher K.
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
This paper presents an overview of the high-redshift extragalactic science case for the Single Aperture Large Telescope for Universe Studies (SALTUS) far-infrared NASA probe-class mission concept. Enabled by its 14m primary reflector, SALTUS offers enormous gains in spatial resolution and spectral sensitivity over previous far-IR missions. SALTUS would be a versatile observatory capable of responding to the scientific needs of the extragalactic community in the 2030s, and a natural follow-on to the near- and mid-IR capabilities of JWST. Key early-universe science goals for SALTUS focus on understanding the role of galactic feedback processes in regulating galaxy growth across cosmic time, and charting the rise of metals and dust from the early universe to the present. This paper summarizes these science cases and the performance metrics most relevant for high-redshift observations., Comment: Submitted to JATIS as part of a special issue on SALTUS. Key performance metrics in Figs. 1 and 2
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- 2024
10. The Use of Quantitative Metrics and Machine Learning to Predict Radiologist Interpretations of MRI Image Quality and Artifacts
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McCullum, Lucas, Wood, John, Gule-Monroe, Maria, Liu, Ho-Ling Anthony, Chen, Melissa, Shah, Komal, Chasen, Noah Nathan, Kumar, Vinodh, Hou, Ping, Stafford, Jason, Chung, Caroline, Ahmad, Moiz, Walker, Christopher, and Yung, Joshua
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Physics - Medical Physics - Abstract
A dataset of 3D-GRE and 3D-TSE brain 3T post contrast T1-weighted images as part of a quality improvement project were collected and shown to five neuro-radiologists who evaluated each sequence for both image quality and imaging artifacts. The same scans were processed using the MRQy tool for objective, quantitative image quality metrics. Using the combined radiologist and quantitative metrics dataset, a decision tree classifier with a bagging ensemble approach was trained to predict radiologist assessment using the quantitative metrics. A machine learning model was developed for the following three tasks: (1) determine the best model / performance for each MRI sequence and evaluation metric, (2) determine the best model / performance across all MRI sequences for each evaluation metric, and (3) determine the best general model / performance across all MRI sequences and evaluations. Model performance for imaging artifact was slightly higher than image quality, for example, the final generalized model AUROC for image quality was 0.77 (0.41 - 0.84, 95% CI) while imaging artifact was 0.78 (0.60 - 0.93, 95% CI). Further, it was noted that the generalized model performed slightly better than the individual models (AUROC 0.69 for 3D-GRE image quality, for example), indicating the value in comprehensive training data for these applications. These models could be deployed in the clinic as automatic checks for real-time image acquisition to prevent patient re-scanning requiring another appointment after retrospective radiologist analysis or improve reader confidence in the study. Further work needs to be done to validate the model described here on an external dataset. The results presented here suggest that MRQy could be used as a foundation for quantitative metrics as a surrogate for radiologist assessment.
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- 2023
11. 4x2 Hot electron bolometer mixer arrays for detection at 1.46, 1.9 and 4.7 THz for a balloon borne terahertz observatory
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Silva, José R. G., Laauwen, Wouter M., Mirzaei, Behnam, Vercruyssen, Nathan, Finkel, Matvey, Westerveld, Menno, More, Nikhil, Silva, Vitor, Young, Abram, Kulesa, Craig, Walker, Christopher, van der Tak, Floris, and Gao, Jian Rong
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Physics - Instrumentation and Detectors - Abstract
We have demonstrated three 4x2 hot electron bolometer (HEB) mixer arrays for operation at local oscillator (LO) frequencies of 1.46, 1.9 and 4.7 THz, respectively. They consist of spiral antenna coupled NbN HEB mixers combined with elliptical lenses. These are to date the highest pixel count arrays using a quasi-optical coupling scheme at supra-THz frequencies. At 1.4 THz, we measured an average double sideband mixer noise temperature of 330 K, a mixer conversion loss of 5.7 dB, and an optimum LO power of 210 nW. The array at 1.9 THz has an average mixer noise temperature of 420K, a conversion loss of 6.9 dB, and an optimum LO power of 190 nW. For the array at 4.7 THz, we obtained an average mixer noise temperature of 700 K, a conversion loss of 9.7 dB, and an optimum LO power of 240 nW. We found the arrays to be uniform regarding the mixer noise temperature with a standard deviation of 3-4%, the conversion loss with a standard deviation of 7-10%, and optimum LO power with a standard deviation of 5-6%. The noise bandwidth was also measured, being 3.5 GHz for the three arrays. These performances are comparable to previously reported values in the literature for single pixels and also other detector arrays. Our arrays meet the requirements of the Galactic/Extra-Galactic ULDB Spectroscopic Terahertz Observatory (GUSTO), a NASA balloon borne observatory, and are therefore scheduled to fly as part of the payload, which is expected to be launched in December 2023.
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- 2023
12. Rapid Quantification of Dynamic and Spall Strength of Metals Across Strain Rates
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Prameela, Suhas Eswarappa, Walker, Christopher C., DiMarco, Christopher S., Mallick, Debjoy D., Sun, Xingsheng, Hernandez, Stephanie, Sasaki, Taisuke, Wilkerson, Justin W., Ramesh, K. T., Pharr, George M., and Weihs, Timothy P.
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Condensed Matter - Materials Science - Abstract
The response of metals and their microstructures under extreme dynamic conditions can be markedly different from that under quasistatic conditions. Traditionally, high strain rates and shock stresses are measured using cumbersome and expensive methods such as the Kolsky bar or large spall experiments. These methods are low throughput and do not facilitate high-fidelity microstructure-property linkages. In this work, we combine two powerful small-scale testing methods, custom nanoindentation, and laser-driven micro-flyer shock, to measure the dynamic and spall strength of metals. The nanoindentation system is configured to test samples from quasistatic to dynamic strain rate regimes (10$^{-3}$ s$^{-1}$ to 10$^{+4}$ s$^{-1}$). The laser-driven micro-flyer shock system can test samples through impact loading between 10$^{+5}$ s$^{-1}$ to 10$^{+7}$ s$^{-1}$ strain rates, triggering spall failure. The model material used for testing is Magnesium alloys, which are lightweight, possess high-specific strengths and have historically been challenging to design and strengthen due to their mechanical anisotropy. Here, we modulate their microstructure by adding or removing precipitates to demonstrate interesting upticks in strain rate sensitivity and evolution of dynamic strength. At high shock loading rates, we unravel an interesting paradigm where the spall strength of these materials converges, but the failure mechanisms are markedly different. Peak aging, considered to be a standard method to strengthen metallic alloys, causes catastrophic failure, faring much worse than solutionized alloys. Our high throughput testing framework not only quantifies strength but also teases out unexplored failure mechanisms at extreme strain rates, providing valuable insights for the rapid design and improvement of metals for extreme environments.
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- 2023
13. Parametrization, Prior Independence, and the Semiparametric Bernstein-von Mises Theorem for the Partially Linear Model
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Walker, Christopher D.
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Mathematics - Statistics Theory ,Economics - Econometrics - Abstract
I prove a semiparametric Bernstein-von Mises theorem for a partially linear regression model with independent priors for the low-dimensional parameter of interest and the infinite-dimensional nuisance parameters. My result avoids a prior invariance condition that arises from a loss of information in not knowing the nuisance parameter. The key idea is a feasible reparametrization of the regression function that mimics the Gaussian profile likelihood. This allows a researcher to assume independent priors for the model parameters while automatically accounting for the loss of information associated with not knowing the nuisance parameter. As these prior stability conditions often impose strong restrictions on the underlying data-generating process, my results provide a more robust asymptotic normality theorem than the original parametrization of the partially linear model.
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- 2023
14. New fungal primers reveal the diversity of Mucoromycotinian arbuscular mycorrhizal fungi and their response to nitrogen application
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Seeliger, Mirjam, Hilton, Sally, Muscatt, George, Walker, Christopher, Bass, David, Albornoz, Felipe, Standish, Rachel J., Gray, Neil D., Mercy, Louis, Rempelos, Leonidas, Schneider, Carolin, Ryan, Megan H., Bilsborrow, Paul E., and Bending, Gary D.
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- 2024
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15. Germline genetic regulation of the colorectal tumor immune microenvironment
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Schmit, Stephanie L., Tsai, Ya-Yu, Bonner, Joseph D., Sanz-Pamplona, Rebeca, Joshi, Amit D., Ugai, Tomotaka, Lindsey, Sidney S., Melas, Marilena, McDonnell, Kevin J., Idos, Gregory E., Walker, Christopher P., Qu, Chenxu, Kast, W. Martin, Da Silva, Diane M., Glickman, Jonathan N., Chan, Andrew T., Giannakis, Marios, Nowak, Jonathan A., Rennert, Hedy S., Robins, Harlan S., Ogino, Shuji, Greenson, Joel K., Moreno, Victor, Rennert, Gad, and Gruber, Stephen B.
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- 2024
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16. Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia
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Rees, Tayla A., Tasma, Zoe, Garelja, Michael L., O’Carroll, Simon J., Walker, Christopher S., and Hay, Debbie L.
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- 2024
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17. British societies guideline on the management of emergencies in implantable left ventricular assist device recipients in transplant centres
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Akhtar, Waqas, Baston, Veronica Rial, Berman, Marius, Bhagra, Sai, Chue, Colin, Deakin, Charles D., Dalzell, Jonathan R., Dunning, Joel, Dunning, John, Gardner, Roy S., Kiff, Kristine, Kore, Shishir, Lim, Sern, MacGowan, Guy, Naldrett, Ian, Ostermann, Marlies, Pinto, Sofia, Pettit, Stephen, Gil, Fernando Riesgo, Rosenberg, Alex, Rubino, Antonio, Sayeed, Rana, Sequeira, Joao, Swanson, Neil, Tsui, Steven, Walker, Christopher, Webb, Stephen, Woods, Andrew, Ventkateswaran, Rajamiyer, and Bowles, Christopher T.
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- 2024
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18. Protoplanetary Disk Science with the Orbiting Astronomical Satellite Investigating Stellar Systems (OASIS) Observatory
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Schwarz, Kamber, Najita, Joan, Bergner, Jennifer, Carr, John, Tielens, Alexander, Bergin, Edwin, Wilner, David, Leisawitz, David, and Walker, Christopher
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Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
The Orbiting Astronomical Satellite for Investigating Stellar Systems (OASIS) is a NASA Astrophysics MIDEX-class mission concept, with the stated goal of following water from galaxies, through protostellar systems, to Earth's oceans. This paper details the protoplanetary disk science achievable with OASIS. OASIS's suite of heterodyne receivers allow for simultaneous, high spectral resolution observations of water emission lines spanning a large range of physical conditions within protoplanetary disks. These observations will allow us to map the spatial distribution of water vapor in disks across evolutionary stages and assess the importance of water, particularly the location of the midplane water snowline, to planet formation. OASIS will also detect the H2 isotopologue HD in 100+ disks, allowing for the most accurate determination of total protoplanetary disk gas mass to date. When combined with the contemporaneous water observations, the HD detection will also allow us to trace the evolution of water vapor across evolutionary stages. These observations will enable OASIS to characterize the time development of the water distribution and the role water plays in the process of planetary system formation., Comment: 19 pages, 5 figures, published in Space Science Reviews
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- 2023
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19. A tabletop x-ray tomography instrument for nanometer-scale imaging: demonstration of the 1,000-element transition-edge sensor subarray
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Szypryt, Paul, Nakamura, Nathan, Becker, Daniel T., Bennett, Douglas A., Dagel, Amber L., Doriese, W. Bertrand, Fowler, Joseph W., Gard, Johnathon D., Harris, J. Zachariah, Hilton, Gene C., Imrek, Jozsef, Jimenez, Edward S., Larson, Kurt W., Levine, Zachary H., Mates, John A. B., McArthur, D., Miaja-Avila, Luis, Morgan, Kelsey M., O'Neil, Galen C., Ortiz, Nathan J., Pappas, Christine G., Schmidt, Daniel R., Thompson, Kyle R., Ullom, Joel N., Vale, Leila, Vissers, Michael R., Walker, Christopher, Weber, Joel C., Wessels, Abigail L., Wheeler, Jason W., and Swetz, Daniel S.
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Physics - Instrumentation and Detectors - Abstract
We report on the 1,000-element transition-edge sensor (TES) x-ray spectrometer implementation of the TOMographic Circuit Analysis Tool (TOMCAT). TOMCAT combines a high spatial resolution scanning electron microscope (SEM) with a highly efficient and pixelated TES spectrometer to reconstruct three-dimensional maps of nanoscale integrated circuits (ICs). A 240-pixel prototype spectrometer was recently used to reconstruct ICs at the 130 nm technology node, but to increase imaging speed to more practical levels, the detector efficiency needs to be improved. For this reason, we are building a spectrometer that will eventually contain 3,000 TES microcalorimeters read out with microwave superconducting quantum interference device (SQUID) multiplexing, and we currently have commissioned a 1,000 TES subarray. This still represents a significant improvement from the 240-pixel system and allows us to begin characterizing the full spectrometer performance. Of the 992 maximimum available readout channels, we have yielded 818 devices, representing the largest number of TES x-ray microcalorimeters simultaneously read out to date. These microcalorimeters have been optimized for pulse speed rather than purely energy resolution, and we measure a FWHM energy resolution of 14 eV at the 8.0 keV Cu K$\alpha$ line., Comment: 5 pages, 4 figures, submitted to IEEE Transactions on Applied Superconductivity
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- 2022
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20. Nanoscale Three-Dimensional Imaging of Integrated Circuits using a Scanning Electron Microscope and Transition-Edge Sensor Spectrometer
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Nakamura, Nathan, Szypryt, Paul, Dagel, Amber L., Alpert, Bradley K., Bennett, Douglas A., Doriese, W. Bertrand, Durkin, Malcolm, Fowler, Joseph W., Fox, Dylan T., Gard, Johnathon D., Goodner, Ryan N., Harris, J. Zachariah, Hilton, Gene C., Jimenez, Edward S., Kernen, Burke L., Larson, Kurt W., Levine, Zachary H., McArthur, Daniel, Morgan, Kelsey M., O'Neil, Galen C., Ortiz, Nathan J., Pappas, Christine G., Reintsema, Carl D., Schmidt, Daniel R., Schultz, Peter A., Thompson, Kyle R., Ullom, Joel N., Vale, Leila, Vaughan, Courtenay T., Walker, Christopher, Weber, Joel C., Wheeler, Jason W., and Swetz, Daniel S.
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Physics - Instrumentation and Detectors - Abstract
X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but is difficult to implement due to competing requirements on X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while changing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot in a metal target held micrometers away from the sample of interest, while the TES spectrometer isolates target photons with high signal-to-noise. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enable nanoscale, element-specific X-ray imaging in a compact footprint. The proof-of-concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in 6 layers of a Cu-SiO2 integrated circuit, and a path towards finer resolution and enhanced imaging capabilities is discussed.
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- 2022
21. Design of a 3000-pixel transition-edge sensor x-ray spectrometer for microcircuit tomography
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Szypryt, Paul, Bennett, Douglas A., Boone, William J., Dagel, Amber L., Dalton, Gabriella, Doriese, W. Bertrand, Fowler, Joseph W., Garboczi, Edward J., Gard, Johnathon D., Hilton, Gene C., Imrek, Jozsef, Jimenez, Edward S., Kotsubo, Vincent Y., Larson, Kurt, Levine, Zachary H., Mates, John A. B., McArthur, Daniel, Morgan, Kelsey M., Nakamura, Nathan, O'Neil, Galen C., Ortiz, Nathan J., Pappas, Christine G., Reintsema, Carl D., Schmidt, Daniel R., Swetz, Daniel S., Thompson, Kyle R., Ullom, Joel N., Walker, Christopher, Weber, Joel C., Wessels, Abigail L., and Wheeler, Jason W.
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Physics - Instrumentation and Detectors - Abstract
Feature sizes in integrated circuits have decreased substantially over time, and it has become increasingly difficult to three-dimensionally image these complex circuits after fabrication. This can be important for process development, defect analysis, and detection of unexpected structures in externally sourced chips, among other applications. Here, we report on a non-destructive, tabletop approach that addresses this imaging problem through x-ray tomography, which we uniquely realize with an instrument that combines a scanning electron microscope (SEM) with a transition-edge sensor (TES) x-ray spectrometer. Our approach uses the highly focused SEM electron beam to generate a small x-ray generation region in a carefully designed target layer that is placed over the sample being tested. With the high collection efficiency and resolving power of a TES spectrometer, we can isolate x-rays generated in the target from background and trace their paths through regions of interest in the sample layers, providing information about the various materials along the x-ray paths through their attenuation functions. We have recently demonstrated our approach using a 240 Mo/Cu bilayer TES prototype instrument on a simplified test sample containing features with sizes of $\sim$1 $\mu$m. Currently, we are designing and building a 3000 Mo/Au bilayer TES spectrometer upgrade, which is expected to improve the imaging speed by factor of up to 60 through a combination of increased detector number and detector speed., Comment: 5 pages, 3 figures, published in IEEE Transactions on Applied Superconductivity
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- 2022
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22. Model‐constrained reconstruction accelerated with Fourier‐based undersampling for hyperpolarized [1‐13C] pyruvate imaging
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Xu, Zhan, Michel, Keith A, Walker, Christopher M, Harlan, Collin J, Martinez, Gary V, Gordon, Jeremy W, Chen, Hsin‐Yu, Vigneron, Daniel B, and Bankson, James A
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Engineering ,Biomedical Engineering ,Urologic Diseases ,Cancer ,Prostate Cancer ,Bioengineering ,Biomedical Imaging ,Male ,Humans ,Pyruvic Acid ,Retrospective Studies ,Magnetic Resonance Imaging ,Prostatic Neoplasms ,Phantoms ,Imaging ,Lactates ,constrained reconstruction ,hyperpolarized MR ,pharmacokinetic modeling ,pyruvate ,undersampling ,Nuclear Medicine & Medical Imaging ,Biomedical engineering - Abstract
PurposeModel-constrained reconstruction with Fourier-based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1-13 C]-pyruvate.MethodsThe MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single-channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity of reconstructed metabolite time series.ResultsAll three data sets showed successful reconstruction using MoReFUn. In simulation and retrospective phantom data, the restored time series of pyruvate and lactate maintained the image details, and the mean square residual error of the accelerated reconstruction increased only slightly (
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- 2023
23. A Roadmap For Scientific Ballooning 2020-2030
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Gorham, Peter, Anderson, James, Bernasconi, Pietro, Chakrabarti, Supriya, Guzik, T. Gregory, Jones, William, Kierans, Carolyn, Millan, Robyn, Vieregg, Abigail, Walker, Christopher, and Young, Eliot
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
From 2018 to 2020, the Scientific Balloon Roadmap Program Analysis Group (Balloon Roadmap PAG) served as an community-based, interdisciplinary forum for soliciting and coordinating community analysis and input in support of the NASA Scientific Balloon Program. The Balloon Roadmap PAG was tasked with articulating and prioritizing the key science drivers and needed capabilities of the Balloon Program for the next decade. Additionally, the Balloon Roadmap PAG was asked to evaluate the potential for achieving science goals and maturing technologies of the Science Mission Directorate, evaluate the Balloon Program goals towards community outreach, and asses commercial balloon launch opportunities. The culmination of this work has been a written report submitted to the NASA Astrophysics Division Director., Comment: 95 pages, 69 figures, prepared by the NASA Balloon Program Analysis Group for the NASA Astrophysics Division Director and the 2020 Astrophysics Decadal Survey
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- 2022
24. Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG)
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Ozga, Michael, Nicolet, Deedra, Mrózek, Krzysztof, Yilmaz, Ayse S., Kohlschmidt, Jessica, Larkin, Karilyn T., Blachly, James S., Oakes, Christopher C., Buss, Jill, Walker, Christopher J., Orwick, Shelley, Jurinovic, Vindi, Rothenberg-Thurley, Maja, Dufour, Annika, Schneider, Stephanie, Sauerland, Maria Cristina, Görlich, Dennis, Krug, Utz, Berdel, Wolfgang E., Woermann, Bernhard J., Hiddemann, Wolfgang, Braess, Jan, Subklewe, Marion, Spiekermann, Karsten, Carroll, Andrew J., Blum, William G., Powell, Bayard L., Kolitz, Jonathan E., Moore, Joseph O., Mayer, Robert J., Larson, Richard A., Uy, Geoffrey L., Stock, Wendy, Metzeler, Klaus H., Grimes, H. Leighton, Byrd, John C., Salomonis, Nathan, Herold, Tobias, Mims, Alice S., and Eisfeld, Ann-Kathrin
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- 2024
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25. Mutual-Information Based Optimal Experimental Design for Hyperpolarized $^{13}$C-Pyruvate MRI
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Jha, Prashant K., Walker, Christopher, Mitchell, Drew, Oden, J. Tinsley, Schellingerhout, Dawid, Bankson, James A., and Fuentes, David T.
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Computer Science - Information Theory ,Physics - Biological Physics ,62B10, 92B05, 62P10 - Abstract
A key parameter of interest recovered from hyperpolarized (HP) MRI measurements is the apparent pyruvate-to-lactate exchange rate, $k_{PL}$, for measuring tumor metabolism. This manuscript presents an information-theory-based optimal experimental design (OED) approach that minimizes the uncertainty in the rate parameter, $k_{PL}$, recovered from HP-MRI measurements. Mutual information (MI) is employed to measure the information content of the HP measurements with respect to the first-order exchange kinetics of the pyruvate conversion to lactate. Flip angles of the pulse sequence acquisition are optimized with respect to the mutual information. Further, a spatially varying model (high-fidelity) based on the Block-Torrey equations is proposed and utilized as a control. A time-varying flip angle scheme leads to a higher parameter optimization that can further improve the quantitative value of mutual information over a constant flip angle scheme. However, the constant flip angle scheme leads to the best accuracy and precision when considering inference from noise-corrupted data. For the particular MRI data examined here, pyruvate and lactate flip angles of 35 and 28 degrees, respectively, were the best choice in terms of accuracy and precision of the parameter recovery. Moreover, the recovery of rate parameter $k_{PL}$ from the data generated from the high-fidelity model highlights the influence of diffusion and strength of vascular source on the recovered rate parameter. Since the existing pharmacokinetic models for HP-MRI do not account for spatial variation, the optimized design parameters may not be fully optimal in a more general 3D setting., Comment: 20 pages, 8 figures
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- 2022
26. How cooperatively folding are homopolymer molecular knots?
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Walker, Christopher C., Fobe, Theodore L., and Shirts, Michael R.
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Condensed Matter - Statistical Mechanics ,Condensed Matter - Soft Condensed Matter - Abstract
Detailed thermodynamic analysis of complex systems with multiple stable configurational states allows for insight into the cooperativity of each individual transition. In this work we derive a heat capacity decomposition comprising contributions from each individual configurational state, which together sum to a baseline heat capacity, and contributions from each state-to-state transition. We apply this analysis framework to a series of replica exchange molecular dynamics simulations of linear and 1-1 coarse-grained homo-oligomer models which fold into stable, configurationally well-defined molecular knots, in order to better understand the parameters leading to stable and cooperative folding of these knots. We find that a stiff harmonic backbone bending angle potential is key to achieving knots with specific 3D structures. Tuning the backbone equilibrium angle in small increments yields a variety of knot topologies, including $3_1$, $5_1$, $7_1$, and $8_{19}$ types. Populations of different knotted states as functions of temperature can also be manipulated by tuning backbone torsion stiffness or by adding side chain beads. We find that sharp total heat capacity peaks for the homo-oligomer knots are largely due to a coil-to-globule transition, rather than a cooperative knotting step. However, in some cases the cooperativity of globule-to-knot and coil-to-globule transitions are comparable, suggesting that highly cooperative folding to knotted structures can be achieved by refining the model parameters or adding sequence specificity., Comment: 39 pages, 14 figures + supporting information
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- 2022
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27. XPO1 inhibition sensitises CLL cells to NK cell mediated cytotoxicity and overcomes HLA-E expression
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Fisher, Jack G., Doyle, Amber D. P., Graham, Lara V., Sonar, Shreyanshi, Sale, Ben, Henderson, Isla, Del Rio, Luis, Johnson, Peter W. M., Landesman, Yosef, Cragg, Mark S., Forconi, Francesco, Walker, Christopher J., Khakoo, Salim. I., and Blunt, Matthew D.
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- 2023
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28. Cell entry and release of quasi-enveloped human hepatitis viruses
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Das, Anshuman, Rivera-Serrano, Efraín E., Yin, Xin, Walker, Christopher M., Feng, Zongdi, and Lemon, Stanley M.
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- 2023
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29. Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial
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Gounder, Mrinal M, Razak, Albiruni Abdul, Somaiah, Neeta, Chawla, Sant, Martin-Broto, Javier, Grignani, Giovanni, Schuetze, Scott M, Vincenzi, Bruno, Wagner, Andrew J, Chmielowski, Bartosz, Jones, Robin L, Riedel, Richard F, Stacchiotti, Silvia, Loggers, Elizabeth T, Ganjoo, Kristen N, Le Cesne, Axel, Italiano, Antoine, del Muro, Xavier Garcia, Burgess, Melissa, Piperno-Neumann, Sophie, Ryan, Christopher, Mulcahy, Mary F, Forscher, Charles, Penel, Nicolas, Okuno, Scott, Elias, Anthony, Hartner, Lee, Philip, Tony, Alcindor, Thierry, Kasper, Bernd, Reichardt, Peter, Lapeire, Lore, Blay, Jean-Yves, Chevreau, Christine, Morales, Claudia Maria Valverde, Schwartz, Gary K, Chen, James L, Deshpande, Hari, Davis, Elizabeth J, Nicholas, Garth, Gröschel, Stefan, Hatcher, Helen, Duffaud, Florence, Herráez, Antonio Casado, Beveridge, Roberto Diaz, Badalamenti, Giuseppe, Eriksson, Mikael, Meyer, Christian, von Mehren, Margaret, Van Tine, Brian A, Götze, Katharina, Mazzeo, Filomena, Yakobson, Alexander, Zick, Aviad, Lee, Alexander, Gonzalez, Anna Estival, Napolitano, Andrea, Dickson, Mark A, Michel, Dayana, Meng, Changting, Li, Lingling, Liu, Jianjun, Ben-Shahar, Osnat, Van Domelen, Dane R, Walker, Christopher J, Chang, Hua, Landesman, Yosef, Shah, Jatin J, Shacham, Sharon, Kauffman, Michael G, and Attia, Steven
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Genetics ,Clinical Trials and Supportive Activities ,Patient Safety ,6.1 Pharmaceuticals ,Cancer ,Child ,Double-Blind Method ,Humans ,Hydrazines ,Liposarcoma ,Triazoles ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
PurposeAntitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.MethodsSEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: NCT02606461).ResultsTwo hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001).ConclusionPatients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.
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- 2022
30. A Three-Gene Signature Predicts Response to Selinexor in Multiple Myeloma.
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Restrepo, Paula, Bhalla, Sherry, Ghodke-Puranik, Yogita, Aleman, Adolfo, Leshchenko, Violetta, Melnekoff, David, Agte, Sarita, Jiang, Joy, Madduri, Deepu, Richter, Joshua, Richard, Shambavi, Chari, Ajai, Cho, Hearn, Jagannath, Sundar, Walker, Christopher, Landesman, Yosef, Laganà, Alessandro, and Parekh, Samir
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Antineoplastic Combined Chemotherapy Protocols ,Humans ,Hydrazines ,Multiple Myeloma ,Neoplasm Recurrence ,Local ,Triazoles - Abstract
PURPOSE: Selinexor is the first selective inhibitor of nuclear export to be approved for the treatment of relapsed or refractory multiple myeloma (MM). Currently, there are no known genomic biomarkers or assays to help select MM patients at higher likelihood of response to selinexor. Here, we aimed to characterize the transcriptomic correlates of response to selinexor-based therapy. METHODS: We performed RNA sequencing on CD138+ cells from the bone marrow of 100 patients with MM who participated in the BOSTON study, followed by differential gene expression and pathway analysis. Using the differentially expressed genes, we used cox proportional hazard models to identify a gene signature predictive of response to selinexor, followed by validation in external cohorts. RESULTS: The three-gene signature predicts response to selinexor-based therapy in patients with MM in the BOSTON cohort. Then, we validated this gene signature in 64 patients from the STORM cohort of triple-class refractory MM and additionally in an external cohort of 35 patients treated in a real-world setting outside of clinical trials. We found that the signature tracks with both depth and duration of response, and it also validates in a different tumor type using a cohort of pretreatment tumors from patients with recurrent glioblastoma. Furthermore, the genes involved in the signature, WNT10A, DUSP1, and ETV7, reveal a potential mechanism through upregulated interferon-mediated apoptotic signaling that may prime tumors to respond to selinexor-based therapy. CONCLUSION: In this study, we present a present a novel, three-gene expression signature that predicts selinexor response in MM. This signature has important clinical relevance as it could identify patients with cancer who are most likely to benefit from treatment with selinexor-based therapy.
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- 2022
31. Astrochemistry with the Orbiting Astronomical Satellite for Investigating Stellar Systems (OASIS)
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Bergner, Jennifer B., Shirley, Yancy L., Jorgensen, Jes K., McGuire, Brett, Aalto, Susanne, Anderson, Carrie M., Chin, Gordon, Gerin, Maryvonne, Hartogh, Paul, Kim, Daewook, Leisawitz, David, Najita, Joan, Schwarz, Kamber R., Tielens, Alexander G. G. M., Walker, Christopher K., Wilner, David J., and Wollack, Edward J.
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
Chemistry along the star- and planet-formation sequence regulates how prebiotic building blocks -- carriers of the elements CHNOPS -- are incorporated into nascent planetesimals and planets. Spectral line observations across the electromagnetic spectrum are needed to fully characterize interstellar CHNOPS chemistry, yet to date there are only limited astrochemical constraints at THz frequencies. Here, we highlight advances to the study of CHNOPS astrochemistry that will be possible with the Orbiting Astronomical Satellite for Investigating Stellar Systems (OASIS). OASIS is a NASA mission concept for a space-based observatory that will utilize an inflatable 14-m reflector along with a heterodyne receiver system to observe at THz frequencies with unprecedented sensitivity and angular resolution. As part of a survey of H2O and HD towards ~100 protostellar and protoplanetary disk systems, OASIS will also obtain statistical constraints on the inventories of light hydrides including NH3 and H2S towards protoplanetary disks, as well as complex organics in protostellar hot corinos and envelopes. Line surveys of additional star-forming regions, including high-mass hot cores, protostellar outflow shocks, and prestellar cores, will also leverage the unique capabilities of OASIS to probe high-excitation organics and small hydrides, as is needed to fully understand the chemistry of these objects., Comment: Accepted to Frontiers in Astronomy and Space Sciences
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- 2021
32. Mutual-information based optimal experimental design for hyperpolarized 13C-pyruvate MRI
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Jha, Prashant K., Walker, Christopher, Mitchell, Drew, Oden, J. Tinsley, Schellingerhout, Dawid, Bankson, James A., and Fuentes, David T.
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- 2023
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33. Preclinical activity of selinexor in combination with eribulin in uterine leiomyosarcoma
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Mittal, Sonam, Kadamberi, Ishaque Pulikkal, Chang, Hua, Wang, Feng, Kumar, Sudhir, Tsaih, Shirng-Wern, Walker, Christopher J., Chaluvally-Raghavan, Pradeep, Charlson, John, Landesman, Yosef, and Pradeep, Sunila
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- 2023
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34. Next-Generation SINE Compound KPT−8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD
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English, Katherine G, Reid, Andrea L, Samani, Adrienne, Coulis, Gerald JF, Villalta, S Armando, Walker, Christopher J, Tamir, Sharon, and Alexander, Matthew S
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Medical Physiology ,Biomedical and Clinical Sciences ,Duchenne/ Becker Muscular Dystrophy ,Genetics ,Rare Diseases ,Pediatric ,Muscular Dystrophy ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,Orphan Drug ,Aetiology ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,2.1 Biological and endogenous factors ,Musculoskeletal ,DMD ,SINE compound ,KPT-8602 ,inflammation ,KPT−8602 ,Biochemistry and cell biology ,Pharmacology and pharmaceutical sciences ,Medicinal and biomolecular chemistry - Abstract
Duchenne muscular dystrophy (DMD) is a progressive, X-linked childhood neuromuscular disorder that results from loss-of-function mutations in the DYSTROPHIN gene. DMD patients exhibit muscle necrosis, cardiomyopathy, respiratory failure, and loss of ambulation. One of the major driving forces of DMD disease pathology is chronic inflammation. The current DMD standard of care is corticosteroids; however, there are serious side effects with long-term use, thus identifying novel anti-inflammatory and anti-fibrotic treatments for DMD is of high priority. We investigated the next-generation SINE compound, KPT-8602 (eltanexor) as an oral therapeutic to alleviate dystrophic symptoms. We performed pre-clinical evaluation of the effects of KPT-8602 in DMD zebrafish (sapje) and mouse (D2-mdx) models. KPT-8602 improved dystrophic skeletal muscle pathologies, muscle architecture and integrity, and overall outcomes in both animal models. KPT-8602 treatment ameliorated DMD pathology in D2-mdx mice, with increased locomotor behavior and improved muscle histology. KPT-8602 altered the immunological profile of the dystrophic mice, and reduced circulating osteopontin serum levels. These findings demonstrate KPT-8602 as an effective therapeutic in DMD through by promotion of an anti-inflammatory environment and overall improvement of DMD pathological outcomes.
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- 2022
35. Applications of Machine Learning Algorithms In Processing Terahertz Spectroscopic Data
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Seo, Young Min, Goldsmith, Paul F., Tolls, Volker, Shipman, Russell, Kulesa, Craig, Peters, William, Walker, Christopher, and Melnick, Gary
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
We present the data reduction software and the distribution of Level 1 and Level 2 products of the Stratospheric Terahertz Observatory 2 (STO2). STO2, a balloon-borne Terahertz telescope, surveyed star-forming regions and the Galactic plane and produced approximately 300,000 spectra. The data are largely similar to spectra typically produced by single-dish radio telescopes. However, a fraction of the data contained rapidly varying fringe/baseline features and drift noise, which could not be adequately corrected using conventional data reduction software. To process the entire science data of the STO2 mission, we have adopted a new method to find proper off-source spectra to reduce large-amplitude fringes and new algorithms including Asymmetric Least Square (ALS), Independent Component Analysis (ICA), and Density-based spatial clustering of applications with noise (DBSCAN). The STO2 data reduction software efficiently reduced the amplitude of fringes from a few hundred to 10 K and resulted in baselines of amplitude down to a few K. The Level 1 products typically have the noise of a few K in [CII] spectra and ~1 K in [NII] spectra. Using a regridding algorithm, we made spectral maps of star-forming regions and the Galactic plane survey using an algorithm employing a Bessel-Gaussian kernel. Level 1 and 2 products are available to the astronomical community through the STO2 data server and the DataVerse. The software is also accessible to the public through Github. The detailed addresses are given in Section 4 of the paper on data distribution., Comment: Accepted to Journal of Astronomical Instrumentation
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- 2020
36. Inference for Moment Inequalities: A Constrained Moment Selection Procedure
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Tabri, Rami V. and Walker, Christopher D.
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Economics - Econometrics - Abstract
Inference in models where the parameter is defined by moment inequalities is of interest in many areas of economics. This paper develops a new method for improving the performance of generalized moment selection (GMS) testing procedures in finite-samples. The method modifies GMS tests by tilting the empirical distribution in its moment selection step by an amount that maximizes the empirical likelihood subject to the restrictions of the null hypothesis. We characterize sets of population distributions on which a modified GMS test is (i) asymptotically equivalent to its non-modified version to first-order, and (ii) superior to its non-modified version according to local power when the sample size is large enough. An important feature of the proposed modification is that it remains computationally feasible even when the number of moment inequalities is large. We report simulation results that show the modified tests control size well, and have markedly improved local power over their non-modified counterparts., Comment: 53 pages, 3 figures; changes in the new version: 1. embedded illustrative example into Monte Carlo section with no changes to results, 2. expanded discussion of RSW procedure, and 3. minor typos fixed
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- 2020
37. An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia
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Lasry, Audrey, Nadorp, Bettina, Fornerod, Maarten, Nicolet, Deedra, Wu, Huiyun, Walker, Christopher J., Sun, Zhengxi, Witkowski, Matthew T., Tikhonova, Anastasia N., Guillamot-Ruano, Maria, Cayanan, Geraldine, Yeaton, Anna, Robbins, Gabriel, Obeng, Esther A., Tsirigos, Aristotelis, Stone, Richard M., Byrd, John C., Pounds, Stanley, Carroll, William L., Gruber, Tanja A., Eisfeld, Ann-Kathrin, and Aifantis, Iannis
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- 2023
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38. Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment
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Chiou, Kenneth L., DeCasien, Alex R., Rees, Katherina P., Testard, Camille, Spurrell, Cailyn H., Gogate, Aishwarya A., Pliner, Hannah A., Tremblay, Sébastien, Mercer, Arianne, Whalen, Connor J., Negrón-Del Valle, Josué E., Janiak, Mareike C., Bauman Surratt, Samuel E., González, Olga, Compo, Nicole R., Stock, Michala K., Ruiz-Lambides, Angelina V., Martínez, Melween I., Wilson, Melissa A., Melin, Amanda D., Antón, Susan C., Walker, Christopher S., Sallet, Jérôme, Newbern, Jason M., Starita, Lea M., Shendure, Jay, Higham, James P., Brent, Lauren J. N., Montague, Michael J., Platt, Michael L., and Snyder-Mackler, Noah
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- 2022
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39. Understanding policy transfer through social network analysis: expanding methodologies with an intensive case study approach
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Walker, Christopher and Moulis, Alex
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- 2022
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40. Transparent Metasurfaces Counteracting Fogging by Harnessing Sunlight
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Walker, Christopher, Mitridis, Efstratios, Kreiner, Thomas, Eghlidi, Hadi, Schutzius, Thomas M., and Poulikakos, Dimos
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Physics - Applied Physics - Abstract
Surface fogging is a common phenomenon that can have significant and detrimental effects on surface transparency and visibility. It affects the performance in a wide range of applications including windows, windshields, electronic displays, cameras, mirrors, and eyewear. A host of ongoing research is aimed at combating this problem by understanding and developing stable and effective anti-fogging coatings that are capable of handling a wide range of environmental challenges "passively" without consumption of electrical energy. Here we introduce an alternative approach employing sunlight to go beyond state-of-the-art techniques---such as superhydrophilic and superhydrophobic coatings---by rationally engineering solar absorbing metasurfaces that maintain transparency, while upon illumination, induce localized heating to significantly delay the onset of surface fogging or decrease defogging time. For the same environmental conditions, we demonstrate that our metasurfaces are able to reduce defogging time by up to four-fold and under supersaturated conditions inhibit the nucleation of condensate outperforming conventional state-of-the-art approaches in terms of visibility retention. Our research illustrates a durable and environmentally sustainable approach to passive anti-fogging and defogging for transparent surfaces. This work opens up the opportunity for large-scale manufacturing that can be applied to a range of materials, including polymers and other flexible substrates.
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- 2019
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41. Slice profile effects on quantitative analysis of hyperpolarized pyruvate
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Walker, Christopher M, Gordon, Jeremy W, Xu, Zhan, Michel, Keith A, Li, Liang, Larson, Peder EZ, Vigneron, Daniel B, and Bankson, James A
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Urologic Diseases ,Bioengineering ,Biomedical Imaging ,Cancer ,Area Under Curve ,Computer Simulation ,Humans ,Lactic Acid ,Magnetic Resonance Imaging ,Male ,Phantoms ,Imaging ,Prostatic Neoplasms ,Pyruvic Acid ,Reproducibility of Results ,hyperpolarized ,pharmacokinetic analysis ,pyruvate ,quantitative imaging ,slice profile ,hyperpolarized ,pharmacokinetic analysis ,pyruvate ,quantitative imaging ,slice profile ,Medicinal and Biomolecular Chemistry ,Biomedical Engineering ,Clinical Sciences ,Nuclear Medicine & Medical Imaging ,Clinical sciences ,Biomedical engineering - Abstract
Magnetic resonance imaging of hyperpolarized pyruvate provides a new imaging biomarker for cancer metabolism, based on the dynamic in vivo conversion of hyperpolarized pyruvate to lactate. Methods for quantification of signal evolution need to be robust and reproducible across a range of experimental conditions. Pharmacokinetic analysis of dynamic spectroscopic imaging data from hyperpolarized pyruvate and its metabolites generally assumes that signal arises from ideal rectangular slice excitation profiles. In this study, we examined whether this assumption could lead to bias in kinetic analysis of hyperpolarized pyruvate and, if so, whether such a bias can be corrected. A Bloch-McConnell simulator was used to generate synthetic data using a known set of "ground truth" pharmacokinetic parameter values. Signal evolution was then analyzed using analysis software that either assumed a uniform slice profile, or incorporated information about the slice profile into the analysis. To correct for slice profile effects, the expected slice profile was subdivided into multiple sub-slices to account for variable excitation angles along the slice dimension. An ensemble of sub-slices was then used to fit the measured signal evolution. A mismatch between slice profiles used for data acquisition and those assumed during kinetic analysis was identified as a source of quantification bias. Results indicate that imperfect slice profiles preferentially increase detected lactate signal, leading to an overestimation of the apparent metabolic exchange rate. The slice profile-correction algorithm was tested in simulation, in phantom measurements, and applied to data acquired from a patient with prostate cancer. The results demonstrated that slice profile-induced biases can be minimized by accounting for the slice profile during pharmacokinetic analysis. This algorithm can be used to correct data from either single or multislice acquisitions.
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- 2020
42. Desublimation Frosting on Nanoengineered Surfaces
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Walker, Christopher, Lerch, Sebastian, Reininger, Matthias, Eghlidi, Hadi, Milionis, Athanasios, Schutzius, Thomas M., and Poulikakos, Dimos
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Physics - Applied Physics ,Condensed Matter - Mesoscale and Nanoscale Physics - Abstract
Ice nucleation from vapor presents a variety of challenges across a wide range of industries and applications including refrigeration, transportation, and energy generation. However, a rational comprehensive approach to fabricating intrinsically icephobic surfaces for frost formation-both from water condensation (followed by freezing) and in particular from desublimation (direct growth of ice crystals from vapor)-remains elusive. Here, guided by nucleation physics, we investigate the effect of material composition and surface texturing (atomically smooth to nanorough) on the nucleation and growth mechanism of frost for a range of conditions within the sublimation domain (0 C to -55C; partial water vapor pressures 6 to 0.02 mbar). Surprisingly, we observe that on silicon at very cold temperatures-below the homogeneous ice solidification nucleation limit (< -46 C)-desublimation does not become the favorable pathway to frosting. Furthermore we show that surface nanoroughness makes frost formation on silicon more probable. We experimentally demonstrate at temperatures between -48 C and -55 C that nanotexture with radii of curvature within one order of magnitude of the critical radius of nucleation favors frost growth, facilitated by capillary condensation, consistent with Kelvin's Equation. Our findings show that such nanoscale surface morphology imposed by design to impart desired functionalities-such as superhydrophobicity-or from defects, can be highly detrimental for frost icephobicity at low temperatures and water vapor partial pressures (< 0.05 mbar). Our work contributes to the fundamental understanding of heterogeneous phase transitions well within the equilibrium sublimation domain and has implications for applications such as travel, power generation, and refrigeration.
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- 2018
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43. The Emergency (Crisis) E-Learning as a Challenge for Teachers in Poland
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Tomczyk, Lukasz and Walker, Christopher
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The article was written as a consequence of the COVID-19 pandemic in Poland, which had an impact not only on public health, but also on the functioning of the educational sector. The text is an attempt to summarize the challenges of crisis e-learning from the perspective of the challenges faced by teachers in Poland in the period of March-December 2020. The article reveals a number of new phenomena not present in the literature in the context of e-learning implemented in an intuitive, non-linear way, without methodological support, and thus referred to as crisis e-learning. The aim of the research was to explore the characteristics of crisis e-learning in Poland from the perspective of teachers' experiences. Due to epidemiological limitations, the research area was narrowed down to cyberspace. This text presents the results of research relating to statements made by teachers posting in the largest Polish discussion group on education. The group currently consists of over four thousand people. The study uses an analysis of several thousand posts and then identifies and categorizes statements related to crisis e-learning along with a phenomenological interpretation. The analyses made it possible to identify seven categories of challenges attributed to crisis e-learning, such as: technical problems, use of non-standard solutions, the search for solutions to increase the effectiveness of e-learning, the transfer of proven applications and programmes, problems with students, problems with parents, and the modernisation of workstations. The data presented show teacher micro-worlds in the time of the pandemic in Poland. The article is a response to the need to understand the processes occurring in the Polish educational system under the influence of crisis events related to the pandemic. The text may prove valuable for educating future generations of teachers in the field of e-learning and increasing the effectiveness of training activities aimed at strengthening the digital competence of current teachers.
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- 2021
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44. Incidental posterior rib hyperostosis on chest CT: incidence and etiology
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Frager, Luke, Heaton, Dennis, Walker, Christopher M., Young, Kate, and Everist, Brian M.
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- 2022
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45. Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate
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Walker, Christopher M, Fuentes, David, Larson, Peder EZ, Kundra, Vikas, Vigneron, Daniel B, and Bankson, James A
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Engineering ,Biomedical Engineering ,Carbon Isotopes ,Computer Simulation ,Lactic Acid ,Magnetic Resonance Spectroscopy ,Pyruvic Acid ,Reproducibility of Results ,Signal Processing ,Computer-Assisted ,excitation angle ,hyperpolarized C-13 ,pyruvate ,quantitative modeling ,sequence design ,hyperpolarized13C ,Nuclear Medicine & Medical Imaging ,Biomedical engineering - Abstract
PurposeVarious excitation strategies have been proposed for dynamic imaging of hyperpolarized agents such as [1-13 C]-pyruvate, but the impact of these strategies on quantitative evaluation of signal evolution remains unclear. To better understand their relative performance, we compared the accuracy and repeatability of measurements made using variable excitation angle strategies and conventional constant excitation angle strategies.MethodsSignal evolution for constant and variable excitation angle schedules was simulated using a pharmacokinetic model of hyperpolarized pyruvate with 2 chemical pools and 2 physical compartments. Noisy synthetic data were then fit using the same pharmacokinetic model with the apparent chemical exchange term as an unknown, and fit results were compared with simulation parameters to determine accuracy and reproducibility.ResultsConstant excitations and a variable excitation strategy that maximizes the HP lactate signal yielded data that supported quantitative analyses with similar accuracy and repeatability. Variable excitation angle strategies that were designed to produce a constant signal level resulted in lower signal and worse quantitative accuracy and repeatability, particularly for longer acquisition times.ConclusionsThese results suggest that either constant excitation angle or variable excitation angles that attempt to maximize total signal, as opposed to maintaining a constant signal level, are preferred for metabolic quantification using hyperpolarized pyruvate.
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- 2019
46. Mitochondrial pyruvate import is a metabolic vulnerability in androgen receptor-driven prostate cancer.
- Author
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Bader, David, Hartig, Sean, Putluri, Vasanta, Foley, Christopher, Hamilton, Mark, Smith, Eric, Saha, Pradip, Panigrahi, Anil, Walker, Christopher, Zong, Lin, Martini-Stoica, Heidi, Chen, Rui, Rajapakshe, Kimal, Coarfa, Cristian, Sreekumar, Arun, Mitsiades, Nicholas, Bankson, James, Ittmann, Michael, OMalley, Bert, Putluri, Nagireddy, and McGuire, Sean
- Subjects
Animals ,Biological Transport ,Cell Line ,Tumor ,Disease Models ,Animal ,Gene Expression Regulation ,Neoplastic ,Glutamine ,Humans ,Male ,Metabolic Networks and Pathways ,Mice ,Mice ,Transgenic ,Mitochondria ,Mitochondrial Membrane Transport Proteins ,Monocarboxylic Acid Transporters ,Prostatic Neoplasms ,Prostatic Neoplasms ,Castration-Resistant ,Protein Binding ,Pyruvic Acid ,Receptors ,Androgen ,Signal Transduction - Abstract
Specific metabolic underpinnings of androgen receptor (AR)-driven growth in prostate adenocarcinoma (PCa) are largely undefined, hindering the development of strategies to leverage the metabolic dependencies of this disease when hormonal manipulations fail. Here we show that the mitochondrial pyruvate carrier (MPC), a critical metabolic conduit linking cytosolic and mitochondrial metabolism, is transcriptionally regulated by AR. Experimental MPC inhibition restricts proliferation and metabolic outputs of the citric acid cycle (TCA) including lipogenesis and oxidative phosphorylation in AR-driven PCa models. Mechanistically, metabolic disruption resulting from MPC inhibition activates the eIF2α/ATF4 integrated stress response (ISR). ISR signaling prevents cell cycle progression while coordinating salvage efforts, chiefly enhanced glutamine assimilation into the TCA, to regain metabolic homeostasis. We confirm that MPC function is operant in PCa tumors in-vivo using isotopomeric metabolic flux analysis. In turn, we apply a clinically viable small molecule targeting the MPC, MSDC0160, to pre-clinical PCa models and find that MPC inhibition suppresses tumor growth in hormone-responsive and castrate-resistant conditions. Collectively, our findings characterize the MPC as a tractable therapeutic target in AR-driven prostate tumors.
- Published
- 2019
47. Extragalactic Science with the Orbiting Astronomical Satellite Investigating Stellar Systems (OASIS) Observatory
- Author
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Aalto, Susanne, Battersby, Cara, Chin, Gordon, Hunt, Leslie K., Rigopoulou, Dimitra, Stark, Antony A., Viti, Serena, and Walker, Christopher K.
- Published
- 2023
- Full Text
- View/download PDF
48. Alpha transcranial alternating current stimulation reduces depressive symptoms in people with schizophrenia and auditory hallucinations: a double-blind, randomized pilot clinical trial
- Author
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Zhang, Mengsen, Force, Rachel B., Walker, Christopher, Ahn, Sangtae, Jarskog, L. Fredrik, and Frohlich, Flavio
- Published
- 2022
- Full Text
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49. Detergency and its implications for oil emulsion sieving and separation
- Author
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Schutzius, Thomas M., Walker, Christopher, Maitra, Tanmoy, Schönherr, Romy, Stamatopoulos, Christos, Jung, Stefan, Antonini, Carlo, Eghlidi, Hadi, Fife, Julie L., Patera, Alessandra, Derome, Dominique, and Poulikakos, Dimos
- Subjects
Condensed Matter - Soft Condensed Matter - Abstract
Separating petroleum hydrocarbons from water is an important problem to address in order to mitigate the disastrous effects of hydrocarbons on aquatic ecosystems. A rational approach to address the problem of marine oil water separation is to disperse the oil with the aid of surfactants in order to minimize the formation of large slicks at the water surface and to maximize the oil-water interfacial area. Here we investigate the fundamental wetting and transport behavior of such surfactant-stabilized droplets and the flow conditions necessary to perform sieving and separation of these stabilized emulsions. We show that, for water soluble surfactants, such droplets are completely repelled by a range of materials (intrinsically underwater superoleophobic) due to the detergency effect; therefore, there is no need for surface micro/nanotexturing or chemical treatment to repel the oil and prevent fouling of the filter. We then simulate and experimentally investigate the effect of emulsion flow rate on the transport and impact behavior of such droplets on rigid meshes to identify the minimum pore opening (w) necessary to filter a droplet with a given diameter (d) in order to minimize the pressure drop across the mesh and therefore maximize the filtering efficiency, which is strongly dependent on w. We define a range of flow conditions and droplet sizes where minimum droplet deformation is to be expected and therefore find that the condition of is sufficient for efficient separation. With this new understanding, we demonstrate the use of a commercially available filter--without any additional surface engineering or functionalization--to separate oil droplets from a surfactant stabilized emulsion with a flux of 11,000 L m$^{-2}$ hr$^{-1}$ bar$^{-1}$. We believe these findings can inform the design of future oil separation materials.
- Published
- 2017
- Full Text
- View/download PDF
50. ACR Appropriateness Criteria® Tracheobronchial Disease.
- Author
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Little, Brent P., Walker, Christopher M., Bang, Tami J., Brixey, Anupama G., Christensen, Jared D., De Cardenas, Jose, Hobbs, Stephen B., Klitzke, Alan, Madan, Rachna, Maldonado, Fabien, Marshall, M. Blair, Moore, William H., Rosas, Edwin, and Chung, Jonathan H.
- Abstract
A variety of thoracic imaging modalities and techniques have been used to evaluate diseases of the trachea and central bronchi. This document evaluates evidence for the use of thoracic imaging in the evaluation of tracheobronchial disease, including clinically suspected tracheal or bronchial stenosis, tracheomalacia or bronchomalacia, and bronchiectasis. Appropriateness guidelines for initial imaging evaluation of tracheobronchial disease and for pretreatment planning or posttreatment evaluation are included. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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