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1. RIS-Vis: A Novel Visualization Platform for Seismic, Geodetic, and Weather Data Relevant to Antarctic Cryosphere Science

Author

Chakravarthy, Aishwarya, Mondal, Dhiman, Barrett, John, Ruszczyk, Chet, and Elosegui, Pedro

Subjects
Physics - Atmospheric and Oceanic Physics, Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Antarctic ice shelves play a vital role in preserving the physical conditions of the Antarctic cryosphere and the Southern Ocean, and beyond. By serving as a buttressing force, ice shelves prevent sea-level rise by restraining the flow of continental ice and glaciers to the sea. Sea-level rise impacts the global environment in multiple ways, including flooding habitats, eroding coastlines, and contaminating soil and groundwater. It is therefore essential to monitor the stability of Antarctic ice shelves, for which a variety of complementary data sources is required. We have developed RIS-Vis, a novel data visualization platform to monitor Antarctic ice shelves. Although focused on the Ross Ice Shelf (RIS), RIS-Vis could be readily scaled to monitor other ice shelves around Antarctica, and elsewhere. Currently, RIS-Vis is capable of analyzing and visualizing seismic, geodetic, and weather data to provide meaningful information for Antarctic cryosphere research. RIS-Vis was built using Python libraries including Obspy, APScheduler, and the Plotly Dash framework, and uses SQLite as the backing database. Visualizations developed on RIS-Vis include filtered seismic waveforms, spectrograms, and power spectral densities, geodetic-based ice-shelf flow, and meteorological variables such as atmospheric temperature and pressure. The dashboard visualization platform abstracts away the time-intensive analysis process of raw data and allows scientists to better concentrate on RIS science.

Published
2024

2. Optimizing VGOS observations using an SNR-based scheduling approach

Author

Schartner, Matthias, Petrachenko, Bill, Titus, Mike, Krásná, Hana, Barrett, John, Hoak, Dan, Mondal, Dhiman, Xu, Minghui, and Soja, Benedikt

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The geodetic and astrometric VLBI community is in the process of upgrading its existing infrastructure with VGOS. The primary objective of VGOS is to substantially boost the number of scans per hour for enhanced parameter estimation. However, the current observing strategy results in fewer scans than anticipated. During 2022, six 24-hour VGOS R&D sessions were conducted to demonstrate a proof-of-concept aimed at addressing this shortcoming. The new observation strategy centers around a signal-to-noise (SNR)-based scheduling approach combined with eliminating existing overhead times in existing VGOS sessions. Two SNR-based scheduling approaches were tested during these sessions: one utilizing inter-/extrapolation of existing S/X source flux density models and another based on a newly derived source flux density catalog at VGOS frequencies. Both approaches proved effective, leading to a 2.3-fold increase in the number of scheduled scans per station and a 2.6-fold increase in the number of observations per station, while maintaining a high observation success rate of approximately 90-95%. Consequently, both strategies succeeded in the main objective of these sessions by successfully increasing the number of scans per hour. The strategies described in this work can be easily applied to operational VGOS observations. Besides outlining and discussing the observation strategy, we further provide insight into the resulting signal-to-noise ratios, and discuss the impact on the precision of the estimated geodetic parameters. Monte Carlo simulations predicted a roughly 50% increase in geodetic precision compared to operational VGOS sessions. The analysis confirmed that the formal errors in estimated station coordinates were reduced by 40-50%. Additionally, Earth orientation parameters showed significant improvement, with a 40-50% reduction in formal errors.

Published
2024

3. Commuting Clifford actions

Author

Barrett, John W.

Subjects
Mathematical Physics, High Energy Physics - Theory, Mathematics - Quantum Algebra, 15A66, 58B34
Abstract

It shown that if a vector space carries commuting actions of two Clifford algebras, then the quadratic monomials using generators from either Clifford algebra determine a spinor representation of an orthogonal Lie algebra. Examples of this construction have applications to high energy physics, particularly to the standard model and unification. It is shown how to use Clifford data to construct spectral triples for the Pati-Salam model that admit an action of Spin(10)., Comment: Approx 10 pages

Published
2024

4. Fermion integrals for finite spectral triples

Author

Barrett, John W.

Subjects
Mathematical Physics, High Energy Physics - Lattice, High Energy Physics - Theory, Quantum Physics, 58B34, 81T75
Abstract

Fermion functional integrals are calculated for the Dirac operator of a finite real spectral triple. Complex, real and chiral functional integrals are considered for each KO-dimension where they are non-trivial, and phase ambiguities in the definition are noted., Comment: Approx 9 pages; v2: corrections and improvements, additional references

Published
2024

5. The genomic and evolutionary landscapes of anaplastic thyroid carcinoma

Author

Zeng, Peter YF, Prokopec, Stephenie D, Lai, Stephen Y, Pinto, Nicole, Chan-Seng-Yue, Michelle A, Clifton-Bligh, Roderick, Williams, Michelle D, Howlett, Christopher J, Plantinga, Paul, Cecchini, Matthew J, Lam, Alfred K, Siddiqui, Iram, Wang, Jianxin, Sun, Ren X, Watson, John D, Korah, Reju, Carling, Tobias, Agrawal, Nishant, Cipriani, Nicole, Ball, Douglas, Nelkin, Barry, Rooper, Lisa M, Bishop, Justin A, Garnis, Cathie, Berean, Ken, Nicolson, Norman G, Weinberger, Paul, Henderson, Ying C, Lalansingh, Christopher M, Tian, Mao, Yamaguchi, Takafumi N, Livingstone, Julie, Salcedo, Adriana, Patel, Krupal, Vizeacoumar, Frederick, Datti, Alessandro, Xi, Liu, Nikiforov, Yuri E, Smallridge, Robert, Copland, John A, Marlow, Laura A, Hyrcza, Martin D, Delbridge, Leigh, Sidhu, Stan, Sywak, Mark, Robinson, Bruce, Fung, Kevin, Ghasemi, Farhad, Kwan, Keith, MacNeil, S Danielle, Mendez, Adrian, Palma, David A, Khan, Mohammed I, Shaikh, Mushfiq, Ruicci, Kara M, Wehrli, Bret, Winquist, Eric, Yoo, John, Mymryk, Joe S, Rocco, James W, Wheeler, David, Scherer, Steve, Giordano, Thomas J, Barrett, John W, Faquin, William C, Gill, Anthony J, Clayman, Gary, Boutros, Paul C, and Nichols, Anthony C

Subjects
Biological Sciences, Genetics, Human Genome, Cancer, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Humans, Thyroid Carcinoma, Anaplastic, Thyroid Neoplasms, Mutation, Adenocarcinoma, Genomics, CP: Cancer, CP: Genomics, anaplastic thyroid cancer, cancer progression, genomics, tumour evolution, tumour heterogeneity, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

Published
2024

6. A search for pulsars around Sgr A* in the first Event Horizon Telescope dataset

Author

Torne, Pablo, Liu, Kuo, Eatough, Ralph P., Wongphechauxsorn, Jompoj, Cordes, James M., Desvignes, Gregory, De Laurentis, Mariafelicia, Kramer, Michael, Ransom, Scott M., Chatterjee, Shami, Wharton, Robert, Karuppusamy, Ramesh, Blackburn, Lindy, Janssen, Michael, Chan, Chi-kwan, Crew, Geoffrey B., Matthews, Lynn D., Goddi, Ciriaco, Rottmann, Helge, Wagner, Jan, Sanchez, Salvador, Ruiz, Ignacio, Abbate, Federico, Bower, Geoffrey C., Salamanca, Juan J., Gomez-Ruiz, Arturo I., Herrera-Aguilar, Alfredo, Jiang, Wu, Lu, Ru-Sen, Pen, Ue-Li, Raymond, Alexander W., Shao, Lijing, Shen, Zhiqiang, Paubert, Gabriel, Sanchez-Portal, Miguel, Kramer, Carsten, Castillo, Manuel, Navarro, Santiago, John, David, Schuster, Karl-Friedrich, Johnson, Michael D., Rygl, Kazi L. J., Akiyama, Kazunori, Alberdi, Antxon, Alef, Walter, Algaba, Juan Carlos, Anantua, Richard, Asada, Keiichi, Azulay, Rebecca, Bach, Uwe, Baczko, Anne-Kathrin, Ball, David, Balokovic, Mislav, Barrett, John, Bauboeck, Michi, Benson, Bradford A., Bintley, Dan, Blundell, Raymond, Bouman, Katherine L., Boyce, Hope, Bremer, Michael, Brinkerink, Christiaan D., Brissenden, Roger, Britzen, Silke, Broderick, Avery E., Broguiere, Dominique, Bronzwaer, Thomas, Bustamante, Sandra, Byun, Do-Young, Carlstrom, John E., Ceccobello, Chiara, Chael, Andrew, Chang, Dominic O., Chatterjee, Koushik, Chen, Ming-Tang, Chen, Yongjun, Cheng, Xiaopeng, Cho, Ilje, Christian, Pierre, Conroy, Nicholas S., Conway, John E., Crawford, Thomas M., Cruz-Osorio, Alejandro, Cui, Yuzhu, Dahale, Rohan, Davelaar, Jordy, Deane, Roger, Dempsey, Jessica, Dexter, Jason, Dhruv, Vedant, Doeleman, Sheperd S., Dougal, Sean, Dzib, Sergio A., Emami, Razieh, Falcke, Heino, Farah, Joseph, Fish, Vincent L., Fomalont, Ed, Ford, H. Alyson, Foschi, Marianna, Fraga-Encinas, Raquel, Freeman, William T., Friberg, Per, Fromm, Christian M., Fuentes, Antonio, Galison, Peter, Gammie, Charles F., Garcia, Roberto, Gentaz, Olivier, Georgiev, Boris, Gold, Roman, Gomez, Jose L., Gu, Minfeng, Gurwell, Mark, Hada, Kazuhiro, Haggard, Daryl, Haworth, Kari, Hecht, Michael H., Hesper, Ronald, Heumann, Dirk, Ho, Luis C., Ho, Paul, Honma, Mareki, Huang, Chih-Wei L., Huang, Lei, Hughes, David H., Ikeda, Shiro, Impellizzeri, C. M. Violette, Inoue, Makoto, Issaoun, Sara, James, David J., Jannuzi, Buell T., Jeter, Britton, Jimenez-Rosales, Alejandra, Jorstad, Svetlana, Joshi, Abhishek V., Jung, Taehyun, Karami, Mansour, Kawashima, Tomohisa, Keating, Garrett K., Kettenis, Mark, Kim, Dong-Jin, Kim, Jae-Young, Kim, Jongsoo, Kim, Junhan, Kino, Motoki, Koay, Jun Yi, Kocherlakota, Prashant, Kofuji, Yutaro, Koyama, Shoko, Krichbaum, Thomas P., Kuo, Cheng-Yu, La Bella, Noemi, Lauer, Tod R., Lee, Daeyoung, Lee, Sang-Sung, Leung, Po Kin, Levis, Aviad, Li, Zhiyuan, Lico, Rocco, Lindahl, Greg, Lindqvist, Michael, Lisakov, Mikhail, Liu, Jun, Liuzzo, Elisabetta, Lo, Wen-Ping, Lobanov, Andrei P., Loinard, Laurent, Lonsdale, Colin J., MacDonald, Nicholas R., Mao, Jirong, Marchili, Nicola, Markoff, Sera, Marrone, Daniel P., Marscher, Alan P., Marti-Vidal, Ivan, Matsushita, Satoki, Medeiros, Lia, Menten, Karl M., Michalik, Daniel, Mizuno, Izumi, Mizuno, Yosuke, Moran, James M., Moriyama, Kotaro, Moscibrodzka, Monika, Muller, Cornelia, Muller, Hendrik, Mus, Alejandro, Musoke, Gibwa, Myserlis, Ioannis, Nadolski, Andrew, Nagai, Hiroshi, Nagar, Neil M., Nakamura, Masanori, Narayan, Ramesh, Narayanan, Gopal, Natarajan, Iniyan, Nathanail, Antonios, Neilsen, Joey, Neri, Roberto, Ni, Chunchong, Noutsos, Aristeidis, Nowak, Michael A., Oh, Junghwan, Okino, Hiroki, Olivares, Hector, Ortiz-Leon, Gisela N., Oyama, Tomoaki, Ozel, Feryal, Palumbo, Daniel C. M., Paraschos, Georgios Filippos, Park, Jongho, Parsons, Harriet, Patel, Nimesh, Pesce, Dominic W., Pietu, Vincent, Plambeck, Richard, PopStefanija, Aleksandar, Porth, Oliver, Potzl, Felix M., Prather, Ben, Preciado-Lopez, Jorge A., Psaltis, Dimitrios, Pu, Hung-Yi, Ramakrishnan, Venkatessh, Rao, Ramprasad, Rawlings, Mark G., Rezzolla, Luciano, Ricarte, Angelo, Ripperda, Bart, Roelofs, Freek, Rogers, Alan, Ros, Eduardo, Romero-Cañizales, Cristina, Roshanineshat, Arash, Roy, Alan L., Ruszczyk, Chet, Sanchez-Arguelles, David, Sasada, Mahito, Satapathy, Kaushik, Savolainen, Tuomas, Schloerb, F. Peter, Schonfeld, Jonathan, Small, Des, Sohn, Bong Won, SooHoo, Jason, Souccar, Kamal, Sun, He, Tetarenko, Alexandra J., Tiede, Paul, Tilanus, Remo P. J., Titus, Michael, Toscano, Teresa, Traianou, Efthalia, Trent, Tyler, Trippe, Sascha, Turk, Matthew, van Bemmel, Ilse, van Langevelde, Huib Jan, van Rossum, Daniel R., Vos, Jesse, Ward-Thompson, Derek, Wardle, John, Weintroub, Jonathan, Wex, Norbert, Wielgus, Maciek, Wiik, Kaj, Witzel, Gunther, Wondrak, Michael F., Wong, George N., Wu, Qingwen, Yadlapalli, Nitika, Yamaguchi, Paul, Yfantis, Aristomenis, Yoon, Doosoo, Young, Andre, Young, Ken, Younsi, Ziri, Yu, Wei, Yuan, Feng, Yuan, Ye-Fei, Zensus, J. Anton, Zhang, Shuo, Zhao, Guang-Yao, and Zhao, Shan-Shan

Subjects
Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The Event Horizon Telescope (EHT) observed in 2017 the supermassive black hole at the center of the Milky Way, Sagittarius A* (Sgr A*), at a frequency of 228.1 GHz ($\lambda$=1.3 mm). The fundamental physics tests that even a single pulsar orbiting Sgr A* would enable motivate searching for pulsars in EHT datasets. The high observing frequency means that pulsars - which typically exhibit steep emission spectra - are expected to be very faint. However, it also negates pulse scattering, an effect that could hinder pulsar detections in the Galactic Center. Additionally, magnetars or a secondary inverse Compton emission could be stronger at millimeter wavelengths than at lower frequencies. We present a search for pulsars close to Sgr A* using the data from the three most-sensitive stations in the EHT 2017 campaign: the Atacama Large Millimeter/submillimeter Array, the Large Millimeter Telescope and the IRAM 30 m Telescope. We apply three detection methods based on Fourier-domain analysis, the Fast-Folding-Algorithm and single pulse search targeting both pulsars and burst-like transient emission; using the simultaneity of the observations to confirm potential candidates. No new pulsars or significant bursts were found. Being the first pulsar search ever carried out at such high radio frequencies, we detail our analysis methods and give a detailed estimation of the sensitivity of the search. We conclude that the EHT 2017 observations are only sensitive to a small fraction ($\lesssim$2.2%) of the pulsars that may exist close to Sgr A*, motivating further searches for fainter pulsars in the region., Comment: 33 pages, 7 figures, 6 Tables. Accepted for publication in ApJ

Published
2023

7. Reference Array and Design Consideration for the next-generation Event Horizon Telescope

Author

Doeleman, Sheperd S., Barrett, John, Blackburn, Lindy, Bouman, Katherine, Broderick, Avery E., Chaves, Ryan, Fish, Vincent L., Fitzpatrick, Garret, Fuentes, Antonio, Freeman, Mark, Gómez, José L., Haworth, Kari, Houston, Janice, Issaoun, Sara, Johnson, Michael D., Kettenis, Mark, Loinard, Laurent, Nagar, Neil, Narayanan, Gopal, Oppenheimer, Aaron, Palumbo, Daniel C. M., Patel, Nimesh, Pesce, Dominic W., Raymond, Alexander W., Roelofs, Freek, Srinivasan, Ranjani, Tiede, Paul, Weintroub, Jonathan, and Wielgus, Maciek

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

We describe the process to design, architect, and implement a transformative enhancement of the Event Horizon Telescope (ngEHT). This program - the next-generation Event Horizon Telescope (ngEHT) - will form a networked global array of radio dishes capable of making high-fidelity real-time movies of supermassive black holes (SMBH) and their emanating jets. This builds upon the EHT principally by deploying additional modest-diameter dishes to optimized geographic locations to enhance the current global mm/submm wavelength Very Long Baseline Interferometric (VLBI) array, which has, to date, utilized mostly pre-existing radio telescopes. The ngEHT program further focuses on observing at three frequencies simultaneously for increased sensitivity and Fourier spatial frequency coverage. Here, the concept, science goals, design considerations, station siting and instrument prototyping are discussed, and a preliminary reference array to be implemented in phases is described., Comment: Submitted to the journal Galaxies

Published
2023

8. Comparison of Polarized Radiative Transfer Codes used by the EHT Collaboration

Author

Prather, Ben S., Dexter, Jason, Moscibrodzka, Monika, Pu, Hung-Yi, Bronzwaer, Thomas, Davelaar, Jordy, Younsi, Ziri, Gammie, Charles F., Gold, Roman, Wong, George N., Akiyama, Kazunori, Alberdi, Antxon, Alef, Walter, Algaba, Juan Carlos, Anantua, Richard, Asada, Keiichi, Azulay, Rebecca, Bach, Uwe, Baczko, Anne-Kathrin, Ball, David, Baloković, Mislav, Barrett, John, Bauböck, Michi, Benson, Bradford A., Bintley, Dan, Blackburn, Lindy, Blundell, Raymond, Bouman, Katherine L., Bower, Geoffrey C., Boyce, Hope, Bremer, Michael, Brinkerink, Christiaan D., Brissenden, Roger, Britzen, Silke, Broderick, Avery E., Broguiere, Dominique, Bustamante, Sandra, Byun, Do-Young, Carlstrom, John E., Ceccobello, Chiara, Chael, Andrew, Chan, Chi-kwan, Chang, Dominic O., Chatterjee, Koushik, Chatterjee, Shami, Chen, Ming-Tang, Chen, Yongjun, Cheng, Xiaopeng, Cho, Ilje, Christian, Pierre, Conroy, Nicholas S., Conway, John E., Cordes, James M., Crawford, Thomas M., Crew, Geoffrey B., Cruz-Osorio, Alejandro, Cui, Yuzhu, De Laurentis, Mariafelicia, Deane, Roger, Dempsey, Jessica, Desvignes, Gregory, Dhruv, Vedant, Doeleman, Sheperd S., Dougal, Sean, Dzib, Sergio A., Eatough, Ralph P., Emami, Razieh, Falcke, Heino, Farah, Joseph, Fish, Vincent L., Fomalont, Ed, Ford, H. Alyson, Fraga-Encinas, Raquel, Freeman, William T., Friberg, Per, Fromm, Christian M., Fuentes, Antonio, Galison, Peter, García, Roberto, Gentaz, Olivier, Georgiev, Boris, Goddi, Ciriaco, Gómez-Ruiz, Arturo I., Gómez, José L., Gu, Minfeng, Gurwell, Mark, Hada, Kazuhiro, Haggard, Daryl, Haworth, Kari, Hecht, Michael H., Hesper, Ronald, Heumann, Dirk, Ho, Luis C., Ho, Paul, Honma, Mareki, Huang, Chih-Wei L., Huang, Lei, Hughes, David H., Ikeda, Shiro, Impellizzeri, C. M. Violette, Inoue, Makoto, Issaoun, Sara, James, David J., Jannuzi, Buell T., Janssen, Michael, Jeter, Britton, Jiang, Wu, Jiménez-Rosales, Alejandra, Johnson, Michael D., Jorstad, Svetlana, Joshi, Abhishek V., Jung, Taehyun, Karami, Mansour, Karuppusamy, Ramesh, Kawashima, Tomohisa, Keating, Garrett K., Kettenis, Mark, Kim, Dong-Jin, Kim, Jae-Young, Kim, Jongsoo, Kim, Junhan, Kino, Motoki, Koay, Jun Yi, Kocherlakota, Prashant, Kofuji, Yutaro, Koyama, Shoko, Kramer, Carsten, Kramer, Michael, Krichbaum, Thomas P., Kuo, Cheng-Yu, La Bella, Noemi, Lauer, Tod R., Lee, Daeyoung, Lee, Sang-Sung, Leung, Po Kin, Levis, Aviad, Li, Zhiyuan, Lico, Rocco, Lindahl, Greg, Lindqvist, Michael, Lisakov, Mikhail, Liu, Jun, Liu, Kuo, Liuzzo, Elisabetta, Lo, Wen-Ping, Lobanov, Andrei P., Loinard, Laurent, Lonsdale, Colin J., Lu, Ru-Sen, MacDonald, Nicholas R., Mao, Jirong, Marchili, Nicola, Markoff, Sera, Marrone, Daniel P., Marscher, Alan P., Martí-Vidal, Iván, Matsushita, Satoki, Matthews, Lynn D., Medeiros, Lia, Menten, Karl M., Michalik, Daniel, Mizuno, Izumi, Mizuno, Yosuke, Moran, James M., Moriyama, Kotaro, Müller, Cornelia, Mus, Alejandro, Musoke, Gibwa, Myserlis, Ioannis, Nadolski, Andrew, Nagai, Hiroshi, Nagar, Neil M., Nakamura, Masanori, Narayan, Ramesh, Narayanan, Gopal, Natarajan, Iniyan, Nathanail, Antonios, Fuentes, Santiago Navarro, Neilsen, Joey, Neri, Roberto, Ni, Chunchong, Noutsos, Aristeidis, Nowak, Michael A., Oh, Junghwan, Okino, Hiroki, Olivares, Héctor, Ortiz-León, Gisela N., Oyama, Tomoaki, Özel, Feryal, Palumbo, Daniel C. M., Paraschos, Georgios Filippos, Park, Jongho, Parsons, Harriet, Patel, Nimesh, Pen, Ue-Li, Pesce, Dominic W., Piétu, Vincent, Plambeck, Richard, PopStefanija, Aleksandar, Porth, Oliver, Pötzl, Felix M., Preciado-López, Jorge A., Psaltis, Dimitrios, Ramakrishnan, Venkatessh, Rao, Ramprasad, Rawlings, Mark G., Raymond, Alexander W., Rezzolla, Luciano, Ricarte, Angelo, Ripperda, Bart, Roelofs, Freek, Rogers, Alan, Ros, Eduardo, Romero-Cañizales, Cristina, Roshanineshat, Arash, Rottmann, Helge, Roy, Alan L., Ruiz, Ignacio, Ruszczyk, Chet, Rygl, Kazi L. J., Sánchez, Salvador, Sánchez-Argüelles, David, Sánchez-Portal, Miguel, Sasada, Mahito, Satapathy, Kaushik, Savolainen, Tuomas, Schloerb, F. Peter, Schonfeld, Jonathan, Schuster, Karl-Friedrich, Shao, Lijing, Shen, Zhiqiang, Small, Des, Sohn, Bong Won, SooHoo, Jason, Souccar, Kamal, Sun, He, Tazaki, Fumie, Tetarenko, Alexandra J., Tiede, Paul, Tilanus, Remo P. J., Titus, Michael, Torne, Pablo, Traianou, Efthalia, Trent, Tyler, Trippe, Sascha, Turk, Matthew, van Bemmel, Ilse, van Langevelde, Huib Jan, van Rossum, Daniel R., Vos, Jesse, Wagner, Jan, Ward-Thompson, Derek, Wardle, John, Weintroub, Jonathan, Wex, Norbert, Wharton, Robert, Wielgus, Maciek, Wiik, Kaj, Witzel, Gunther, Wondrak, Michael F., Wu, Qingwen, Yamaguchi, Paul, Yfantis, Aristomenis, Yoon, Doosoo, Young, André, Young, Ken, Yu, Wei, Yuan, Feng, Yuan, Ye-Fei, Zensus, J. Anton, Zhang, Shuo, Zhao, Guang-Yao, and Zhao, Shan-Shan

Subjects
Astrophysics - High Energy Astrophysical Phenomena
Abstract

Interpretation of resolved polarized images of black holes by the Event Horizon Telescope (EHT) requires predictions of the polarized emission observable by an Earth-based instrument for a particular model of the black hole accretion system. Such predictions are generated by general relativistic radiative transfer (GRRT) codes, which integrate the equations of polarized radiative transfer in curved spacetime. A selection of ray-tracing GRRT codes used within the EHT collaboration is evaluated for accuracy and consistency in producing a selection of test images, demonstrating that the various methods and implementations of radiative transfer calculations are highly consistent. When imaging an analytic accretion model, we find that all codes produce images similar within a pixel-wise normalized mean squared error (NMSE) of 0.012 in the worst case. When imaging a snapshot from a cell-based magnetohydrodynamic simulation, we find all test images to be similar within NMSEs of 0.02, 0.04, 0.04, and 0.12 in Stokes I, Q, U , and V respectively. We additionally find the values of several image metrics relevant to published EHT results to be in agreement to much better precision than measurement uncertainties., Comment: Accepted for publication in ApJ

Published
2023
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9. Analytic approximations of scattering effects on beam chromaticity in 21-cm global experiments

Author

Rogers, Alan E. E., Barrett, John P., Bowman, Judd D., Cappallo, Rigel, Lonsdale, Colin J., Mahesh, Nivedita, Monsalve, Raul A., Murray, Steven G., and Sims, Peter H.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

Scattering from objects near an antenna produce correlated signals from strong compact radio sources in a manner similar to those used by the Sea Interferometer to measure the radio source positions using the fine frequency structure in the total power spectrum of a single antenna. These fringes or ripples due to correlated signal interference are present at a low level in the spectrum of any single antenna and are a major source of systematics in systems used to measure the global redshifted 21-cm signal from the early universe. In the Sea Interferometer a single antenna on a cliff above the sea is used to add the signal from the direct path to the signal from the path reflected from the sea thereby forming an interferometer. This was used for mapping radio sources with a single antenna by Bolton and Slee in the 1950s. In this paper we derive analytic expressions to determine the level of these ripples and compare these results in a few simple cases with electromagnetic modeling software to verify that the analytic calculations are sufficient to obtain the magnitude of the scattering effects on the measurements of the global 21-cm signal. These analytic calculations are needed to evaluate the magnitude of the effects in cases that are either too complex or take too much time to be modeled using software.

Published
2022
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10. A Bayesian approach to modelling spectrometer data chromaticity corrected using beam factors -- I. Mathematical formalism

Author

Sims, Peter H., Bowman, Judd D., Mahesh, Nivedita, Murray, Steven G., Barrett, John P., Cappallo, Rigel, Monsalve, Raul A., Rogers, Alan E. E., Samson, Titu, and Vydula, Akshatha K.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Accurately accounting for spectral structure in spectrometer data induced by instrumental chromaticity on scales relevant for detection of the 21-cm signal is among the most significant challenges in global 21-cm signal analysis. In the publicly available EDGES low-band data set, this complicating structure is suppressed using beam-factor based chromaticity correction (BFCC), which works by dividing the data by a sky-map-weighted model of the spectral structure of the instrument beam. Several analyses of this data have employed models that start with the assumption that this correction is complete. However, while BFCC mitigates the impact of instrumental chromaticity on the data, given realistic assumptions regarding the spectral structure of the foregrounds, the correction is only partial. This complicates the interpretation of fits to the data with intrinsic sky models (models that assume no instrumental contribution to the spectral structure of the data). In this paper, we derive a BFCC data model from an analytic treatment of BFCC and demonstrate using simulated observations that, in contrast to using an intrinsic sky model for the data, the BFCC data model enables unbiased recovery of a simulated global 21-cm signal from beam-factor chromaticity corrected data in the limit that the data is corrected with an error-free beam-factor model., Comment: 26 pages, 8 figures; accepted for publication in MNRAS

Published
2022
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11. Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification

Author

Zeng, Peter YF, Cecchini, Matthew J, Barrett, John W, Shammas-Toma, Matthew, De Cecco, Loris, Serafini, Mara S, Cavalieri, Stefano, Licitra, Lisa, Hoebers, Frank, Brakenhoff, Ruud H, Leemans, C René, Scheckenbach, Kathrin, Poli, Tito, Wang, Xiaowei, Liu, Xinyi, Laxague, Francisco, Prisman, Eitan, Poh, Catherine, Bose, Pinaki, Dort, Joseph C, Shaikh, Mushfiq H, Ryan, Sarah EB, Dawson, Alice, Khan, Mohammed I, Howlett, Christopher J, Stecho, William, Plantinga, Paul, da Silva, Sabrina Daniela, Hier, Michael, Khan, Halema, MacNeil, Danielle, Mendez, Adrian, Yoo, John, Fung, Kevin, Lang, Pencilla, Winquist, Eric, Palma, David A, Ziai, Hedyeh, Amelio, Antonio L, Li, Shawn S-C, Boutros, Paul C, Mymryk, Joe S, and Nichols, Anthony C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Prevention, Infectious Diseases, Precision Medicine, Radiation Oncology, Digestive Diseases, Sexually Transmitted Infections, Dental/Oral and Craniofacial Disease, Good Health and Well Being, Humans, Papillomavirus Infections, Retrospective Studies, Neoplasm Recurrence, Local, Oropharyngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Prognosis, Biomarkers, Human Papillomavirus Viruses, Head and Neck Neoplasms, Papillomaviridae, Head and neck squamous cell carcinoma, Transcriptomics, Cancer immunology, HPV, De-escalation, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundThere is significant interest in treatment de-escalation for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV+ OPSCC patients.MethodsWe created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes.FindingsA three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2-25.5, P = 3.6 × 10-5) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation.InterpretationWith additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned.FundingCIHR, European Union, and the NIH.

Published
2022

12. Introduction and expression of PIK3CAE545K in a papillary thyroid cancer BRAFV600E cell line leads to a dedifferentiated aggressive phenotype

Author

Pinto, Nicole, Ruicci, Kara M, Khan, Mohammed Imran, Shaikh, Mushfiq Hassan, Zeng, Yu Fan Peter, Yoo, John, Fung, Kevin, MacNeil, S Danielle, Mendez, Adrian, Mymryk, Joe S, Barrett, John W, Boutros, Paul C, and Nichols, Anthony C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Aetiology, 2.1 Biological and endogenous factors, Animals, Cell Line, Cell Line, Tumor, Class I Phosphatidylinositol 3-Kinases, Humans, Mice, Mice, Nude, Mutation, Phenotype, Proto-Oncogene Proteins B-raf, Thyroid Cancer, Papillary, Thyroid Neoplasms, Papillary thyroid cancer, Anaplastic thyroid cancer, Disease progression, Dedifferentiation, Otorhinolaryngology, Clinical sciences
Abstract

Anaplastic thyroid cancer (ATC) is a rare, aggressive form of undifferentiated thyroid cancer, which exhibits rapid progression and is almost universally fatal. At least a subset of ATC is thought to arise from pre-existing well-differentiated thyroid cancer, most frequently papillary thyroid cancer (PTC). While PIK3CA mutations are rare in PTC, they are common in ATC and tend to co-occur with BRAF mutations. This provided the rationale for our study to identify the potential role of PIK3CA mutations in the progression from well-differentiated to undifferentiated thyroid cancer. We introduced PIK3CAE545K into the LAM1 PTC cell line, which carries a BRAFV600E mutation. In culture, the engineered cell line (LAM1:PIK3CAE545K) proliferated faster and demonstrated increased clonogenic potential relative to the parental line carrying an empty vector (LAM1EV). Both the LAM1EV and LAM1:PIK3CAE545K edited lines were implanted into hind flanks of athymic nude mice for in vivo determination of disease progression. While tumour weights and volumes were not significantly higher in LAM1:PIK3CAE545K mice, there was a decrease in expression of thyroid differentiation markers TTF-1, thyroglobulin, PAX8 and B-catenin, suggesting that introduction of PIK3CAE545K led to dedifferentiation in vivo. Collectively, this study provides evidence of a role for PIK3CAE545K in driving disease progression from a well-differentiated to an undifferentiated thyroid cancer; however, over-expression was not a determinant of an accelerated growth phenotype in ATC.

Published
2022

13. Event Horizon Telescope observations of the jet launching and collimation in Centaurus A

Author

Janssen, Michael, Falcke, Heino, Kadler, Matthias, Ros, Eduardo, Wielgus, Maciek, Akiyama, Kazunori, Baloković, Mislav, Blackburn, Lindy, Bouman, Katherine L., Chael, Andrew, Chan, Chi-kwan, Chatterjee, Koushik, Davelaar, Jordy, Edwards, Philip G., Fromm, Christian M., Gómez, José L., Goddi, Ciriaco, Issaoun, Sara, Johnson, Michael D., Kim, Junhan, Koay, Jun Yi, Krichbaum, Thomas P., Liu, Jun, Liuzzo, Elisabetta, Markoff, Sera, Markowitz, Alex, Marrone, Daniel P., Mizuno, Yosuke, Müller, Cornelia, Ni, Chunchong, Pesce, Dominic W., Ramakrishnan, Venkatessh, Roelofs, Freek, Rygl, Kazi L. J., van Bemmel, Ilse, Alberdi, Antxon, Alef, Walter, Algaba, Juan Carlos, Anantua, Richard, Asada, Keiichi, Azulay, Rebecca, Baczko, Anne-Kathrin, Ball, David, Barrett, John, Benson, Bradford A., Bintley, Dan, Blundell, Raymond, Boland, Wilfred, Bower, Geoffrey C., Boyce, Hope, Bremer, Michael, Brinkerink, Christiaan D., Brissenden, Roger, Britzen, Silke, Broderick, Avery E., Broguiere, Dominique, Bronzwaer, Thomas, Byun, Do-Young, Carlstrom, John E., Chatterjee, Shami, Chen, Ming-Tang, Chen, Yongjun, Chesler, Paul M., Cho, Ilje, Christian, Pierre, Conway, John E., Cordes, James M., Crawford, Thomas M., Crew, Geoffrey B., Cruz-Osorio, Alejandro, Cui, Yuzhu, De Laurentis, Mariafelicia, Deane, Roger, Dempsey, Jessica, Desvignes, Gregory, Dexter, Jason, Doeleman, Sheperd S., Eatough, Ralph P., Farah, Joseph, Fish, Vincent L., Fomalont, Ed, Ford, H. Alyson, Fraga-Encinas, Raquel, Friberg, Per, Fuentes, Antonio, Galison, Peter, Gammie, Charles F., García, Roberto, Gelles, Zachary, Gentaz, Olivier, Georgiev, Boris, Gold, Roman, Gómez-Ruiz, Arturo I., Gu, Minfeng, Gurwell, Mark, Hada, Kazuhiro, Haggard, Daryl, Hecht, Michael H., Hesper, Ronald, Himwich, Elizabeth, Ho, Luis C., Ho, Paul, Honma, Mareki, Huang, Chih-Wei L., Huang, Lei, Hughes, David H., Ikeda, Shiro, Inoue, Makoto, James, David J., Jannuzi, Buell T., Jeter, Britton, Jiang, Wu, Jimenez-Rosales, Alejandra, Jorstad, Svetlana, Jung, Taehyun, Karami, Mansour, Karuppusamy, Ramesh, Kawashima, Tomohisa, Keating, Garrett K., Kettenis, Mark, Kim, Dong-Jin, Kim, Jae-Young, Kim, Jongsoo, Kino, Motoki, Kofuji, Yutaro, Koyama, Shoko, Kramer, Michael, Kramer, Carsten, Kuo, Cheng-Yu, Lauer, Tod R., Lee, Sang-Sung, Levis, Aviad, Li, Yan-Rong, Li, Zhiyuan, Lindqvist, Michael, Lico, Rocco, Lindahl, Greg, Liu, Kuo, Lo, Wen-Ping, Lobanov, Andrei P., Loinard, Laurent, Lonsdale, Colin, Lu, Ru-Sen, MacDonald, Nicholas R., Mao, Jirong, Marchili, Nicola, Marscher, Alan P., Martí-Vidal, Iván, Matsushita, Satoki, Matthews, Lynn D., Medeiros, Lia, Menten, Karl M., Mizuno, Izumi, Moran, James M., Moriyama, Kotaro, Moscibrodzka, Monika, Musoke, Gibwa, Mejías, Alejandro Mus, Nagai, Hiroshi, Nagar, Neil M., Nakamura, Masanori, Narayan, Ramesh, Narayanan, Gopal, Natarajan, Iniyan, Nathanail, Antonios, Neilsen, Joey, Neri, Roberto, Noutsos, Aristeidis, Nowak, Michael A., Okino, Hiroki, Olivares, Héctor, Ortiz-León, Gisela N., Oyama, Tomoaki, Özel, Feryal, Palumbo, Daniel C. M., Park, Jongho, Patel, Nimesh, Pen, Ue-Li, Piétu, Vincent, Plambeck, Richard, PopStefanija, Aleksandar, Porth, Oliver, Pötzl, Felix M., Prather, Ben, Preciado-López, Jorge A., Psaltis, Dimitrios, Pu, Hung-Yi, Rao, Ramprasad, Rawlings, Mark G., Raymond, Alexander W., Rezzolla, Luciano, Ricarte, Angelo, Ripperda, Bart, Rogers, Alan, Rose, Mel, Roshanineshat, Arash, Rottmann, Helge, Roy, Alan L., Ruszczyk, Chet, Sánchez, Salvador, Sánchez-Arguelles, David, Sasada, Mahito, Savolainen, Tuomas, Schloerb, F. Peter, Schuster, Karl-Friedrich, Shao, Lijing, Shen, Zhiqiang, Small, Des, Sohn, Bong Won, SooHoo, Jason, Sun, He, Tazaki, Fumie, Tetarenko, Alexandra J., Tiede, Paul, Tilanus, Remo P. J., Titus, Michael, Torne, Pablo, Trent, Tyler, Traianou, Efthalia, Trippe, Sascha, van Langevelde, Huib Jan, van Rossum, Daniel R., Wagner, Jan, Ward-Thompson, Derek, Wardle, John, Weintroub, Jonathan, Wex, Norbert, Wharton, Robert, Wong, George N., Wu, Qingwen, Yoon, Doosoo, Young, André, Young, Ken, Younsi, Ziri, Yuan, Feng, Yuan, Ye-Fei, Zensus, J. Anton, Zhao, Guang-Yao, and Zhao, Shan-Shan

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics, Astrophysics - High Energy Astrophysical Phenomena
Abstract

Very-long-baseline interferometry (VLBI) observations of active galactic nuclei at millimeter wavelengths have the power to reveal the launching and initial collimation region of extragalactic radio jets, down to $10-100$ gravitational radii ($r_g=GM/c^2$) scales in nearby sources. Centaurus A is the closest radio-loud source to Earth. It bridges the gap in mass and accretion rate between the supermassive black holes (SMBHs) in Messier 87 and our galactic center. A large southern declination of $-43^{\circ}$ has however prevented VLBI imaging of Centaurus A below ${\lambda}1$cm thus far. Here, we show the millimeter VLBI image of the source, which we obtained with the Event Horizon Telescope at $228$GHz. Compared to previous observations, we image Centaurus A's jet at a tenfold higher frequency and sixteen times sharper resolution and thereby probe sub-lightday structures. We reveal a highly-collimated, asymmetrically edge-brightened jet as well as the fainter counterjet. We find that Centaurus A's source structure resembles the jet in Messier 87 on ${\sim}500r_g$ scales remarkably well. Furthermore, we identify the location of Centaurus A's SMBH with respect to its resolved jet core at ${\lambda}1.3$mm and conclude that the source's event horizon shadow should be visible at THz frequencies. This location further supports the universal scale invariance of black holes over a wide range of masses., Comment: 27 pages, 9 figures. This is a post-peer-review, pre-copyedit version of an article published in Nature Astronomy. The final authenticated version is available online at: https://doi.org/10.1038/s41550-021-01417-w

Published
2021
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14. The Variability of the Black-Hole Image in M87 at the Dynamical Time Scale

Author

Satapathy, Kaushik, Psaltis, Dimitrios, Ozel, Feryal, Medeiros, Lia, Dougall, Sean T., Chan, Chi-kwan, Wielgus, Maciek, Prather, Ben S., Wong, George N., Gammie, Charles F., Akiyama, Kazunori, Alberdi, Antxon, Alef, Walter, Algaba, Juan Carlos, Anantua, Richard, Asada, Keiichi, Azulay, Rebecca, Baczko, Anne-Kathrin, Ball, David R., Baloković, Mislav, Barrett, John, Benson, Bradford A., Bintley, Dan, Blackburn, Lindy, Blundell, Raymond, Boland, Wilfred, Bouman, Katherine L., Bower, Geoffrey C., Boyce, Hope A., Bremer, Michael, Brinkerink, Christiaan D., Brissenden, Roger, Britzen, Silke, Broderick, Avery E., Broguiere, Dominique, Bronzwaer, Thomas, Bustamente, Sandra, Byun, Do-Young, Carlstrom, John E., Chael, Andrew, Chatterjee, Koushik, Chatterjee, Shami, Chen, Ming-Tang, Chen, Yongjun, Cho, Ilje, Christian, Pierre, Conway, John E., Cordes, James M., Crawford, Thomas, Crew, Geoffrey B., Osorio, Alejandro Cruz, Cui, Yuzhu, Davelaar, Jordy, De Laurentis, Mariafelicia, Deane, Roger, Dempsey, Jessica T., Desvignes, Gregory, Dexter, Jason, Doeleman, Sheperd S., Eatough, Ralph, Falcke, Heino, Farah, Joseph R., Fish, Vincent, Fomalont, Edward B., Ford, H. Alyson, Fraga-Encinas, Raquel, Friberg, Per, Fromm, Christian M., Fuentes, Antonio, Galison, Peter, García, Roberto, Gentaz, Olivier, Georgiev, Boris, Goddi, Ciriaco, Gold, Roman, Gomez-Ruiz, Arturo I., Gómez, Jose L., Gu, Minfeng, Gurwell, Mark A., Hada, Kazuhiro, Haggard, Daryl, Hecht, Michael, Hesper, Ronald, Ho, Luis C., Ho, Paul T., Honma, Mareki, Huang, Chih-Wei L., Huang, Lei, Hughes, David H., Ikeda, Shiro, Inoue, Makoto, Issaoun, Sara, James, David J., Jannuzi, Buell T., Janssen, Michael, Jeter, Britton, Jiang, Wu, Rosales, Alejandra Jimenez, Johnson, Michael D., Jorstad, Svetlana G., Jung, Taehyun, Karami, Mansour, Karuppusamy, Ramesh, Kawashima, Tomohisa, Keating, Garrett K., Kettenis, Mark, Kim, Dong-Jin, Kim, Jae-Young, Kim, Jongsoo, Kim, Junhan, Kino, Motoki, Koay, Jun Yi, Kofuji, Yutaro, Koch, Patrick M., Koyama, Shoko, Kramer, Carsten, Kramer, Michael, Krichbaum, Thomas P., Kuo, Cheng-Yu, Lauer, Tod R., Lee, Sang-Sung, Levis, Aviad, Li, Yan-Rong, Li, Zhiyuan, Lindqvist, Michael, Lico, Rocco, Lindahl, Greg, Liu, Jun, Liu, Kuo, Liuzzo, Miss Elisabetta, Lo, Wen-Ping, Lobanov, Andrei, Loinard, Laurent, Lonsdale, Colin J., Lu, Rusen, MacDonald, Nicholas R., Mao, Jirong, Marchili, Nicola, Markoff, Sera, Marrone, Daniel, Marscher, Alan P., Marti-Vidal, Ivan, Matsushita, Satoki, Matthews, Lynn, Menten, Karl M., Mizuno, Izumi, Mizuno, Yosuke, Moran, James, Moriyama, Kotaro, Moscibrodzka, Monika, Muller, Cornelia, Mejias, Alejandro M., Musoke, Gibwa, Nagai, Hiroshi, Nagar, Neil M., Nakamura, Masanori, Narayan, Ramesh, Narayanan, Gopal, Natarajan, Iniyan, Nathanail, Antonios, Neilsen, Joey, Neri, Roberto, Ni, Chunchong, Noutsos, Aristeidis, Nowak, Michael A., Okino, Hiroki, Olivares, Hector, Ortiz-Leon, Gisela N., Oyama, Tomoaki, Palumbo, Daniel C., Park, Jongho, Patel, Nimesh A., Pen, Ue-Li, Pesce, Dominic W., Pietu, Vincent, Plambeck, Richard L., PopStefanija, Aleksandar, Porth, Oliver, Potzl, Felix, Preciado-López, Jorge A., Pu, Hung-Yi, Ramakrishnan, Venkatessh, Rao, Ramprasad, Rawlings, Mark, Raymond, Alexander W., Rezzolla, Luciano, Ripperda, Bart, Roelofs, Freek, Rogers, Alan E. E., Ros, Eduardo, Rose, Mel, Roshanineshat, Arash, Rottmann, Helge, Roy, Alan L., Ruszczyk, Chet, Rygl, Kazi, Sanchez, Salvador, Sanchez-Arguelles, David, Sasada, Mahito, Savolainen, Tuomas, Schloerb, F Peter, Schuster, Karl-Friedrich, Shao, Lijing, Shen, Zhi-Qiang, Small, Des, Sohn, Bong Won, SooHoo, Jason, Sun, He, Tazaki, Fumie, Tetarenko, Alexandra J., Tiede, Paul, Tilanus, Remo, Titus, Michael, Toma, Kenji, Torne, Pablo, Traianou, E., Trent, Tyler, Trippe, Sascha, van Bemmel, Ilse, van Langevelde, Huib Jan, van Rossum, Daniel R., Wagner, Jan, Ward-Thompson, Derek, Wardle, John F., Weintroub, Jonathan, Wex, Norbert, Wharton, Robert, Wiik, Kaj, Wu, Qingwen, Yoon, DooSoo, Young, Andre, Young, Ken H., Younsi, Ziri, Yuan, Feng, Yuan, Ye-Fei, Zensus, J. Anton, Zhao, Guang-Yao, and Zhao, Shan-Shan

Subjects
Astrophysics - High Energy Astrophysical Phenomena
Abstract

The black-hole images obtained with the Event Horizon Telescope (EHT) are expected to be variable at the dynamical timescale near their horizons. For the black hole at the center of the M87 galaxy, this timescale (5-61 days) is comparable to the 6-day extent of the 2017 EHT observations. Closure phases along baseline triangles are robust interferometric observables that are sensitive to the expected structural changes of the images but are free of station-based atmospheric and instrumental errors. We explored the day-to-day variability in closure phase measurements on all six linearly independent non-trivial baseline triangles that can be formed from the 2017 observations. We showed that three triangles exhibit very low day-to-day variability, with a dispersion of $\sim3-5^\circ$. The only triangles that exhibit substantially higher variability ($\sim90-180^\circ$) are the ones with baselines that cross visibility amplitude minima on the $u-v$ plane, as expected from theoretical modeling. We used two sets of General Relativistic magnetohydrodynamic simulations to explore the dependence of the predicted variability on various black-hole and accretion-flow parameters. We found that changing the magnetic field configuration, electron temperature model, or black-hole spin has a marginal effect on the model consistency with the observed level of variability. On the other hand, the most discriminating image characteristic of models is the fractional width of the bright ring of emission. Models that best reproduce the observed small level of variability are characterized by thin ring-like images with structures dominated by gravitational lensing effects and thus least affected by turbulence in the accreting plasmas., Comment: Accepted for Publication in ApJ

Published
2021
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15. Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer

Author

Kim, Hugh AJ, Zeng, Peter YF, Sorgini, Alana, Shaikh, Mushfiq H, Khan, Halema, MacNeil, Danielle, Khan, Mohammed I, Mendez, Adrian, Yoo, John, Fung, Kevin, Lang, Pencilla, Palma, David A, Mymryk, Joe S, Barrett, John W, Patel, Krupal B, Boutros, Paul C, and Nichols, Anthony C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Dental/Oral and Craniofacial Disease, Rare Diseases, Cancer, Clinical Research, Genetics, Black People, Head and Neck Neoplasms, Health Status Disparities, Humans, Squamous Cell Carcinoma of Head and Neck, Survival Rate, White People, genomics, HNSCC, HPV-negative, mutational status, racio-ethnic group, Clinical Sciences, Dentistry, Otorhinolaryngology, Clinical sciences
Abstract

BackgroundNumerous studies of head and neck squamous cell carcinoma (HNSCC) have demonstrated disparate outcomes by race and ethnicity. Beyond known associations with socioeconomic variables, whether these are also associated with differences in tumor molecular composition has thus far been poorly explored.MethodsWe downloaded clinical and multiplatform molecular data from The Cancer Genome Atlas and other published studies. These were compared between non-Hispanic Black (n = 43) and White (n = 354) patients with non-HPV-related tumors, using multivariable models. Publicly available validation cohorts were used.ResultsBlack patients had poorer progression-free survival than White patients. Tumors of Black patients had greater copy number aberrations, and increased SFRP1 methylation and miRNA-mediated PRG4 silencing associated with poor survival. PI3K/AkT/mTOR pathway proteins were differentially expressed.ConclusionsThere are molecular differences between tumors of Black and White patients that may partially account for differences in survival. These may inform targeted treatment decisions to achieve equitable outcomes.

Published
2022

17. Constraints on black-hole charges with the 2017 EHT observations of M87*

Author

Kocherlakota, Prashant, Rezzolla, Luciano, Falcke, Heino, Fromm, Christian M., Kramer, Michael, Mizuno, Yosuke, Nathanail, Antonios, Olivares, Hector, Younsi, Ziri, Akiyama, Kazunori, Alberdi, Antxon, Alef, Walter, Algaba, Juan Carlos, Anantua, Richard, Asada, Keiichi, Azulay, Rebecca, Baczko, Anne-Kathrin, Ball, David, Balokovic, Mislav, Barrett, John, Benson, Bradford A., Bintley, Dan, Blackburn, Lindy, Blundell, Raymond, Boland, Wilfred, Bouman, Katherine L., Bower, Geoffrey C., Boyce, Hope, Bremer, Michael, Brinkerink, Christiaan D., Brissenden, Roger, Britzen, Silke, Broderick, Avery E., Broguiere, Dominique, Bronzwaer, Thomas, Byun, Do-Young, Carlstrom, John E., Chael, Andrew, Chan, Chi-kwan, Chatterjee, Shami, Chatterjee, Koushik, Chen, Ming-Tang, Chen, Yongjun, Chesler, Paul M., Cho, Ilje, Christian, Pierre, Conway, John E., Cordes, James M., Crawford, Thomas M., Crew, Geoffrey B., Cruz-Osorio, Alejandro, Cui, Yuzhu, Davelaar, Jordy, De Laurentis, Mariafelicia, Deane, Roger, Dempsey, Jessica, Desvignes, Gregory, Doeleman, Sheperd S., Eatough, Ralph P., Farah, Joseph, Fish, Vincent L., Fomalont, Ed, Fraga-Encinas, Raquel, Friberg, Per, Ford, H. Alyson, Fuentes, Antonio, Galison, Peter, Gammie, Charles F., Garcia, Roberto, Gentaz, Olivier, Georgiev, Boris, Goddi, Ciriaco, Gold, Roman, Gomez, Jose L., Gomez-Ruiz, Arturo I., Gu, Minfeng, Gurwell, Mark, Hada, Kazuhiro, Haggard, Daryl, Hecht, Michael H., Hesper, Ronald, Ho, Luis C., Ho, Paul, Honma, Mareki, Huang, Chih-Wei L., Huang, Lei, Hughes, David H., Ikeda, Shiro, Inoue, Makoto, Issaoun, Sara, James, David J., Jannuzi, Buell T., Janssen, Michael, Jeter, Britton, Jiang, Wu, Jimenez-Rosales, Alejandra, Johnson, Michael D., Jorstad, Svetlana, Jung, Taehyun, Karami, Mansour, Karuppusamy, Ramesh, Kawashima, Tomohisa, Keating, Garrett K., Kettenis, Mark, Kim, Dong-Jin, Kim, Jae-Young, Kim, Jongsoo, Kim, Junhan, Kino, Motoki, Koay, Jun Yi, Kofuji, Yutaro, Koch, Patrick M., Koyama, Shoko, Kramer, Carsten, Krichbaum, Thomas P., Kuo, Cheng-Yu, Lauer, Tod R., Lee, Sang-Sung, Levis, Aviad, Li, Yan-Rong, Li, Zhiyuan, Lindqvist, Michael, Lico, Rocco, Lindahl, Greg, Liu, Jun, Liu, Kuo, Liuzzo, Elisabetta, Lo, Wen-Ping, Lobanov, Andrei P., Loinard, Laurent, Lonsdale, Colin, Lu, Ru-Sen, MacDonald, Nicholas R., Mao, Jirong, Marchili, Nicola, Markoff, Sera, Marrone, Daniel P., Marscher, Alan P., Marti-Vidal, Ivan, Matsushita, Satoki, Matthews, Lynn D., Medeiros, Lia, Menten, Karl M., Mizuno, Izumi, Moran, James M., Moriyama, Kotaro, Moscibrodzka, Monika, Muller, Cornelia, Musoke, Gibwa, Mejias, Alejandro Mus, Nagai, Hiroshi, Nagar, Neil M., Nakamura, Masanori, Narayan, Ramesh, Narayanan, Gopal, Natarajan, Iniyan, Neilsen, Joseph, Neri, Roberto, Ni, Chunchong, Noutsos, Aristeidis, Nowak, Michael A., Okino, Hiroki, Ortiz-Leon, Gisela N., Oyama, Tomoaki, Ozel, Feryal, Palumbo, Daniel C. M., Park, Jongho, Patel, Nimesh, Pen, Ue-Li, Pesce, Dominic W., Pietu, Vincent, Plambeck, Richard, PopStefanija, Aleksandar, Porth, Oliver, Potzl, Felix M., Prather, Ben, Preciado-Lopez, Jorge A., Psaltis, Dimitrios, Pu, Hung-Yi, Ramakrishnan, Venkatessh, Rao, Ramprasad, Rawlings, Mark G., Raymond, Alexander W., Ricarte, Angelo, Ripperda, Bart, Roelofs, Freek, Rogers, Alan, Ros, Eduardo, Rose, Mel, Roshanineshat, Arash, Rottmann, Helge, Roy, Alan L., Ruszczyk, Chet, Rygl, Kazi L. J., Sanchez, Salvador, Sanchez-Arguelles, David, Sasada, Mahito, Savolainen, Tuomas, Schloerb, F. Peter, Schuster, Karl-Friedrich, Shao, Lijing, Shen, Zhiqiang, Small, Des, Sohn, Bong Won, SooHoo, Jason, Sun, He, Tazaki, Fumie, Tetarenko, Alexandra J., Tiede, Paul, Tilanus, Remo P. J., Titus, Michael, Toma, Kenji, Torne, Pablo, Trent, Tyler, Traianou, Efthalia, Trippe, Sascha, van Bemmel, Ilse, van Langevelde, Huib Jan, van Rossum, Daniel R., Wagner, Jan, Ward-Thompson, Derek, Wardle, John, Weintroub, Jonathan, Wex, Norbert, Wharton, Robert, Wielgus, Maciek, Wong, George N., Wu, Qingwen, Yoon, Doosoo, Young, Andre, Young, Ken, Yuan, Feng, Yuan, Ye-Fei, Zensus, J. Anton, Zhao, Guang-Yao, Zhao, Shan-Shan, and Collaboration, The EHT

Subjects
General Relativity and Quantum Cosmology
Abstract

Our understanding of strong gravity near supermassive compact objects has recently improved thanks to the measurements made by the Event Horizon Telescope (EHT). We use here the M87* shadow size to infer constraints on the physical charges of a large variety of nonrotating or rotating black holes. For example, we show that the quality of the measurements is already sufficient to rule out that M87* is a highly charged dilaton black hole. Similarly, when considering black holes with two physical and independent charges, we are able to exclude considerable regions of the space of parameters for the doubly-charged dilaton and the Sen black holes., Comment: 15 pages, 4 figures, published in PRD on May 19

Published
2021
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18. The Polarized Image of a Synchrotron Emitting Ring of Gas Orbiting a Black Hole

Author

Narayan, Ramesh, Palumbo, Daniel C. M., Johnson, Michael D., Gelles, Zachary, Himwich, Elizabeth, Chang, Dominic O., Ricarte, Angelo, Dexter, Jason, Gammie, Charles F., Chael, Andrew A., Collaboration, The Event Horizon Telescope, Akiyama, Kazunori, Alberdi, Antxon, Alef, Walter, Algaba, Juan Carlos, Anantua, Richard, Asada, Keiichi, Azulay, Rebecca, Baczko, Anne-Kathrin, Ball, David, Balokovic, Mislav, Barrett, John, Benson, Bradford A., Bintley, Dan, Blackburn, Lindy, Blundell, Raymond, Boland, Wilfred, Bouman, Katherine L., Bower, Geoffrey C., Boyce, Hope, Bremer, Michael, Brinkerink, Christiaan D., Brissenden, Roger, Britzen, Silke, Broderick, Avery E., Broguiere, Dominique, Bronzwaer, Thomas, Byun, Do-Young, Carlstrom, John E., Chan, Chi-kwan, Chatterjee, Shami, Chatterjee, Koushik, Chen, Ming-Tang, Chen, Yongjun, Chesler, Paul M., Cho, Ilje, Christian, Pierre, Conway, John E., Cordes, James M., Crawford, Thomas M., Crew, Geoffrey B., Cruz-Osorio, Alejandro, Cui, Yuzhu, Davelaar, Jordy, DeLaurentis, Mariafelicia, Deane, Roger, Dempsey, Jessica, Desvignes, Gregory, Doeleman, Sheperd S., Eatough, Ralph P., Falcke, Heino, Farah, Joseph, Fish, Vincent L., Fomalont, Ed, Ford, H. Alyson, Fraga-Encinas, Raquel, Friberg, Per, Fromm, Christian M., Fuentes, Antonio, Galison, Peter, Garcıa, Roberto, Gentaz, Olivier, Georgiev, Boris, Goddi, Ciriaco, Gold, Roman, Gomez, Jose L., Gomez-Ruiz, Arturo I., Gu, Minfeng, Gurwell, Mark, Hada, Kazuhiro, Haggard, Daryl, Hecht, Michael H., Hesper, Ronald, Ho, Luis C., Ho, Paul, Honma, Mareki, Huang, Chih-Wei L., Huang, Lei, Hughes, David H., Ikeda, Shiro, Inoue, Makoto, Issaoun, Sara, James, David J., Jannuzi, Buell T., Janssen, Michael, Jeter, Britton, Jiang, Wu, Jimenez-Rosales, Alejandra, Jorstad, Svetlana, Jung, Taehyun, Karami, Mansour, Karuppusamy, Ramesh, Kawashima, Tomohisa, Keating, Garrett K., Kettenis, Mark, Kim, Dong-Jin, Kim, Jae-Young, Kim, Jongsoo, Kim, Junhan, Kino, Motoki, Koay, Jun Yi, Kofuji, Yutaro, Koch, Patrick M., Koyama, Shoko, Kramer, Michael, Kramer, Carsten, Krichbaum, Thomas P., Kuo, Cheng-Yu, Lauer, Tod R., Lee, Sang-Sung, Levis, Aviad, Li, Yan-Rong, Li, Zhiyuan, Lindqvist, Michael, Lico, Rocco, Lindahl, Greg, Liu, Jun, Liu, Kuo, Liuzzo, Elisabetta, Lo, Wen-Pin, Lobanov, Andrei P., Loinard, Laurent, Lonsdale, Colin, Lu, Ru-Sen, MacDonald, Nicholas R., Mao, Jirong, Marchili, Nicola, Markoff, Sera, Marrone, Daniel P., Martı-Vidal, Alan P. Marscher Ivan, Matsushita, Satoki, Matthews, Lynn D., Medeiros, Lia, Menten, Karl M., Mizuno, Izumi, Mizuno, Yosuke, Moran, James M., Moriyama, Kotaro, Moscibrodzka, Monika, Muller, Cornelia, Musoke, Gibwa, Mejıas, Alejandro Mus, Nagai, Hiroshi, Nagar, Neil M., Nakamura, Masanori, Narayanan, Gopal, Natarajan, Iniyan, Nathanail, Antonios, Neilsen, Joey, Neri, Roberto, Ni, Chunchong, Noutsos, Aristeidis, Nowak, Michael A., Okino, Hiroki, Olivares, Hector, Ortiz-Leon, Gisela N., Oyama, Tomoaki, Ozel, Feryal, Park, Jongho, Patel, Nimesh, Pen, Ue-Li, Pesce, Dominic W., Pietu, Vincent, Plambeck, Richard, PopStefanija, Aleksandar, Porth, Oliver, Potzl, Felix M., Prather, Ben, Preciado-Lopez, Jorge A., Psaltis, Dimitrios, Pu, Hung-Yi, Ramakrishnan, Venkatessh, Rao, Ramprasad, Rawlings, Mark G., Raymond, Alexander W., Rezzolla, Luciano, Ripperda, Bart, Roelofs, Freek, Rogers, Alan, Ros, Eduardo, Rose, Mel, Roshanineshat, Arash, Rottmann, Helge, Roy, Alan L., Ruszczyk, Chet, Rygl, Kazi L. J., Sanchez, Salvador, Sanchez-Arguelles, David, Sasada, Mahito, Savolainen, Tuomas, Schloerb, F. Peter, Schuster, Karl-Friedrich, Shao, Lijing, Shen, Zhiqiang, Small, Des, Sohn, Bong Won, SooHoo, Jason, Sun, He, Tazaki, Fumie, Tetarenko, Alexandra J., Tiede, Paul, Tilanus, Remo P. J., Titus, Michael, Toma, Kenji, Torne, Pablo, Trent, Tyler, Traianou, Efthalia, Trippe, Sascha, van Bemmel, Ilse, van Langevelde, Huib Jan, van Rossum, Daniel R., Wagner, Jan, Ward-Thompson, Derek, Wardle, John, Weintroub, Jonathan, Wex, Norbert, Wharton, Robert, Wielgus, Maciek, Wong, George N., Wu, Qingwen, Yoon, Doosoo, Young, Andre, Young, Ken, Younsi, Ziri, Yuan, Feng, Yuan, Ye-Fei, Zensus, J. Anton, Zhao, Guang-Yao, and Zhao, Shan-Shan

Subjects
Astrophysics - High Energy Astrophysical Phenomena
Abstract

Synchrotron radiation from hot gas near a black hole results in a polarized image. The image polarization is determined by effects including the orientation of the magnetic field in the emitting region, relativistic motion of the gas, strong gravitational lensing by the black hole, and parallel transport in the curved spacetime. We explore these effects using a simple model of an axisymmetric, equatorial accretion disk around a Schwarzschild black hole. By using an approximate expression for the null geodesics derived by Beloborodov (2002) and conservation of the Walker-Penrose constant, we provide analytic estimates for the image polarization. We test this model using currently favored general relativistic magnetohydrodynamic simulations of M87*, using ring parameters given by the simulations. For a subset of these with modest Faraday effects, we show that the ring model broadly reproduces the polarimetric image morphology. Our model also predicts the polarization evolution for compact flaring regions, such as those observed from Sgr A* with GRAVITY. With suitably chosen parameters, our simple model can reproduce the EVPA pattern and relative polarized intensity in Event Horizon Telescope images of M87*. Under the physically motivated assumption that the magnetic field trails the fluid velocity, this comparison is consistent with the clockwise rotation inferred from total intensity images., Comment: 29 pages, 11 figures, published in ApJ on May 3

Published
2021
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19. Absolute Calibration of Diffuse Radio Surveys at 45 and 150 MHz

Author

Monsalve, Raul A., Rogers, Alan E. E., Bowman, Judd D., Mahesh, Nivedita, Murray, Steven G., Mozdzen, Thomas J., Johnson, Leroy, Barrett, John, Samson, Titu, and Lewis, David

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We use EDGES measurements to determine scale and zero-level corrections to the diffuse radio surveys by Guzm\'an et al. at $45$ MHz and Landecker & Wielebinski at $150$ MHz. We find that the Guzm\'an et al. map requires a scale correction of $1.076 \pm 0.034$ ($2\sigma$) and a zero-level correction of $-160 \pm 78$ K ($2\sigma$) to best-fit the EDGES data. For the Landecker & Wielebinski map, the scale correction is $1.112 \pm 0.023$ ($2\sigma$) and the zero-level correction is $0.7 \pm 6.0$ K ($2\sigma$). The correction uncertainties are dominated by systematic effects, of which the most significant are uncertainty in the calibration of the EDGES receivers, antenna pointing, and tropospheric and ionospheric effects. We propagate the correction uncertainties to estimate the uncertainties in the corrected maps themselves and find that the $2\sigma$ uncertainty in the map brightness temperature is in the range $3.2-7.5\%$ for the Guzm\'an et al. map and $2.1-9.0\%$ for the Landecker & Wielebinski map, with the largest percent uncertainties occurring at high Galactic latitudes. The corrected maps could be used to improve existing diffuse low-frequency radio sky models, which are essential tools in analyses of cosmological $21$ cm observations, as well as to investigate the existence of a radio monopole excess above the cosmic microwave background and known Galactic and extragalactic contributions., Comment: Accepted for publication in ApJ

Published
2020
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20. Gravitational Test Beyond the First Post-Newtonian Order with the Shadow of the M87 Black Hole

Author

Psaltis, Dimitrios, Medeiros, Lia, Christian, Pierre, Ozel, Feryal, Akiyama, Kazunori, Alberdi, Antxon, Alef, Walter, Asada, Keiichi, Azulay, Rebecca, Ball, David, Balokovic, Mislav, Barrett, John, Bintley, Dan, Blackburn, Lindy, Boland, Wilfred, Bower, Geoffrey C., Bremer, Michael, Brinkerink, Christiaan D., Brissenden, Roger, Britzen, Silke, Broguiere, Dominique, Bronzwaer, Thomas, Byun, Do-Young, Carlstrom, John E., Chael, Andrew, Chan, Chi-kwan, Chatterjee, Shami, Chatterjee, Koushik, Chen, Ming-Tang, Chen, Yongjun, Cho, Ilje, Conway, John E., Cordes, James M., Crew, Geoffrey B., Cui, Yuzhu, Davelaar, Jordy, De Laurentis, Mariafelicia, Deane, Roger, Dempsey, Jessica, Desvignes, Gregory, Dexter, Jason, Eatough, Ralph P., Falcke, Heino, Fish, Vincent L., Fomalont, Ed, Fraga-Encinas, Raquel, Friberg, Per, Fromm, Christian M., Gammie, Charles F., García, Roberto, Gentaz, Olivier, Goddi, Ciriaco, Gomez, Jose L., Gu, Minfeng, Gurwell, Mark, Hada, Kazuhiro, Hesper, Ronald, Ho, Luis C., Ho, Paul, Honma, Mareki, Huang, Chih-Wei L., Huang, Lei, Hughes, David H., Inoue, Makoto, Issaoun, Sara, James, David J., Jannuzi, Buell T., Janssen, Michael, Jiang, Wu, Jimenez-Rosales, Alejandra, Johnson, Michael D., Jorstad, Svetlana, Jung, Taehyun, Karami, Mansour, Karuppusamy, Ramesh, Kawashima, Tomohisa, Keating, Garrett K., Kettenis, Mark, Kim, Jae-Young, Kim, Junhan, Kim, Jongsoo, Kino, Motoki, Koay, Jun Yi, Koch, Patrick M., Koyama, Shoko, Kramer, Michael, Kramer, Carsten, Krichbaum, Thomas P., Kuo, Cheng-Yu, Lauer, Tod R., Lee, Sang-Sung, Li, Yan-Rong, Li, Zhiyuan, Lindqvist, Michael, Lico, Rocco, Liu, Jun, Liu, Kuo, Liuzzo, Elisabetta, Lo, Wen-Ping, Lobanov, Andrei P., Lonsdale, Colin, Lu, Ru-Sen, Mao, Jirong, Markoff, Sera, Marrone, Daniel P., Marscher, Alan P., Martí-Vidal, Ivan, Matsushita, Satoki, Mizuno, Yosuke, Mizuno, Izumi, Moran, James M., Moriyama, Kotaro, Moscibrodzka, Monika, Muller, Cornelia, Musoke, Gibwa, Mejías, Alejandro Mus, Nagai, Hiroshi, Nagar, Neil M., Narayan, Ramesh, Narayanan, Gopal, Natarajan, Iniyan, Neri, Roberto, Noutsos, Aristeidis, Okino, Hiroki, Olivares, Hector, Oyama, Tomoaki, Palumbo, Daniel C. M., Park, Jongho, Patel, Nimesh, Pen, Ue-Li, Pietu, Vincent, Plambeck, Richard, PopStefanija, Aleksandar, Prather, Ben, Preciado-Lopez, Jorge A., Ramakrishnan, Venkatessh, Rao, Ramprasad, Rawlings, Mark G., Raymond, Alexander W., Ripperda, Bart, Roelofs, Freek, Rogers, Alan, Ros, Eduardo, Rose, Mel, Roshanineshat, Arash, Rottmann, Helge, Roy, Alan L., Ruszczyk, Chet, Ryan, Benjamin R., Rygl, Kazi L. J., Sanchez, Salvador, Sanchez-Arguelles, David, Sasada, Mahito, Savolainen, Tuomas, Schloerb, F. Peter, Schuster, Karl-Friedrich, Shao, Lijing, Shen, Zhiqiang, Small, Des, Sohn, Bong Won, SooHoo, Jason, Tazaki, Fumie, Tilanus, Remo P. J., Titus, Michael, Torne, Pablo, Trent, Tyler, Traianou, Efthalia, Trippe, Sascha, van Bemmel, Ilse, van Langevelde, Huib Jan, van Rossum, Daniel R., Wagner, Jan, Wardle, John, Ward-Thompson, Derek, Weintroub, Jonathan, Wex, Norbert, Wharton, Robert, Wielgus, Maciek, Wong, George N., Wu, Qingwen, Yoon, Doosoo, Young, Andre, Young, Ken, Younsi, Ziri, Yuan, Feng, Yuan, Ye-Fei, Zhao, Shan-Shan, and Collaboration, the EHT

Subjects
General Relativity and Quantum Cosmology, Astrophysics - High Energy Astrophysical Phenomena
Abstract

The 2017 Event Horizon Telescope (EHT) observations of the central source in M87 have led to the first measurement of the size of a black-hole shadow. This observation offers a new and clean gravitational test of the black-hole metric in the strong-field regime. We show analytically that spacetimes that deviate from the Kerr metric but satisfy weak-field tests can lead to large deviations in the predicted black-hole shadows that are inconsistent with even the current EHT measurements. We use numerical calculations of regular, parametric, non-Kerr metrics to identify the common characteristic among these different parametrizations that control the predicted shadow size. We show that the shadow-size measurements place significant constraints on deviation parameters that control the second post-Newtonian and higher orders of each metric and are, therefore, inaccessible to weak-field tests. The new constraints are complementary to those imposed by observations of gravitational waves from stellar-mass sources., Comment: Physical Review Letters

Published
2020
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21. A Practical Phase Field Method for an Elliptic Surface PDE

Author

Barrett, John W., Deckelnick, Klaus, and Styles, Vanessa

Subjects
Mathematics - Numerical Analysis
Abstract

We consider a diffuse interface approach for solving an elliptic PDE on a given closed hypersurface. The method is based on a (bulk) finite element scheme employing numerical quadrature for the phase field function and hence is very easy to implement compared to other approaches. We estimate the error in natural norms in terms of the spatial grid size, the interface width and the order of the underlying quadrature rule. Numerical test calculations are presented which confirm the form of the error bounds.

Published
2020

22. Connectivity: insights from the U.S. Long Term Ecological Research Network

Author

Iwaniec, David M, Gooseff, Michael, Suding, Katharine N, Johnson, David Samuel, Reed, Daniel C, Peters, Debra PC, Adams, Byron, Barrett, John E, Bestelmeyer, Brandon T, Castorani, Max CN, Cook, Elizabeth M, Davidson, Melissa J, Groffman, Peter M, Hanan, Niall P, Huenneke, Laura F, Johnson, Pieter TJ, McKnight, Diane M, Miller, Robert J, Okin, Gregory S, Preston, Daniel L, Rassweiler, Andrew, Ray, Chris, Sala, Osvaldo E, Schooley, Robert L, Seastedt, Timothy, Spasojevic, Marko J, and Vivoni, Enrique R

Subjects
Life on Land, alpine tundra, Antarctic polar desert, arid grassland, arid shrubland, coastal, estuary, salt marsh, Special Feature: Forecasting Earth's Ecosystems with Long-Term Ecological Research, urban ecosystem, Ecological Applications, Ecology, Zoology
Published
2021

23. A finite element error analysis for axisymmetric mean curvature flow

Author

Barrett, John W., Deckelnick, Klaus, and Nürnberg, Robert

Subjects
Mathematics - Numerical Analysis, 65M60, 65M12, 65M15, 53C44, 35K55
Abstract

We consider the numerical approximation of axisymmetric mean curvature flow with the help of linear finite elements. In the case of a closed genus-1 surface, we derive optimal error bounds with respect to the $L^2$-- and $H^1$--norms for a fully discrete approximation. We perform convergence experiments to confirm the theoretical results, and also present numerical simulations for some genus-0 and genus-1 surfaces, including for the Angenent torus., Comment: 24 pages, 10 figures

Published
2019
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24. A generalization of a result of Hille on analytic implicit functions

Author

Barrett, John F.

Subjects
Mathematics - Functional Analysis
Abstract

Hille in 1959 gave a stronger form for the classical implicit function theorem of Cauchy for equations of the type $y = \psi(x,y)$, $x,y$ real or complex, $\psi$ analytic with a condition which determines a radius of convergence of the resulting series solution. Based on a geometrical interpretation of Hille's condition, this report generalizes his result to the case when x and y are elements of lattice-normed linear spaces in the sense of Kantorovich. This formulation includes the special cases when x and y belong to Banach or Riesz spaces., Comment: 39 pages

Published
2019

25. Stable approximations for axisymmetric Willmore flow for closed and open surfaces

Author

Barrett, John W., Garcke, Harald, and Nürnberg, Robert

Subjects
Mathematics - Numerical Analysis, 65M60, 65M12, 35K55, 53C44
Abstract

For a hypersurface in ${\mathbb R}^3$, Willmore flow is defined as the $L^2$--gradient flow of the classical Willmore energy: the integral of the squared mean curvature. This geometric evolution law is of interest in differential geometry, image reconstruction and mathematical biology. In this paper, we propose novel numerical approximations for the Willmore flow of axisymmetric hypersurfaces. For the semidiscrete continuous-in-time variants we prove a stability result. We consider both closed surfaces, and surfaces with a boundary. In the latter case, we carefully derive weak formulations of suitable boundary conditions. Furthermore, we consider many generalizations of the classical Willmore energy, particularly those that play a role in the study of biomembranes. In the generalized models we include spontaneous curvature and area difference elasticity (ADE) effects, Gaussian curvature and line energy contributions. Several numerical experiments demonstrate the efficiency and robustness of our developed numerical methods., Comment: 52 pages, 19 figures

Published
2019
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26. Analysis of the TCGA Dataset Reveals that Subsites of Laryngeal Squamous Cell Carcinoma Are Molecularly Distinct

Author

Sorgini, Alana, Kim, Hugh Andrew Jinwook, Zeng, Peter YF, Shaikh, Mushfiq Hassan, Mundi, Neil, Ghasemi, Farhad, Di Gravio, Eric, Khan, Halema, MacNeil, Danielle, Khan, Mohammed Imran, Mendez, Adrian, Yoo, John, Fung, Kevin, Lang, Pencilla, Palma, David A, Mymryk, Joe S, Barrett, John W, Patel, Krupal B, Boutros, Paul C, and Nichols, Anthony C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Cancer, Biotechnology, Genetics, Human Genome, Good Health and Well Being, genomics, mutational status, larynx cancer, HNSCC, HPV-negative, Oncology and carcinogenesis
Abstract

Laryngeal squamous cell carcinoma (LSCC) from different subsites have distinct presentations and prognosis. In this study, we carried out a multiomic comparison of LSCC subsites. The Cancer Genome Atlas (TCGA) LSCC cohort was analyzed in the R statistical environment for differences between supraglottic and glottic cancers in single nucleotide variations (SNVs), copy number alterations (CNAs), mRNA abundance, protein abundance, pathway overrepresentation, tumor microenvironment (TME), hypoxia status, and patient outcome. Supraglottic cancers had significantly higher overall and smoking-associated SNV mutational load. Pathway analysis revealed upregulation of muscle related pathways in glottic cancer and neural pathways in supraglottic cancer. Proteins involved in cancer relevant signaling pathways including PI3K/Akt/mTOR, the cell cycle, and PDL1 were differentially abundant between subsites. Glottic and supraglottic tumors have different molecular profiles, which may partially account for differences in presentation and response to therapy.

Published
2021

27. 3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset

Author

Kim, Hugh Andrew Jinwook, Shaikh, Mushfiq Hassan, Lee, Mark, Zeng, Peter YF, Sorgini, Alana, Akintola, Temitope, Deng, Xiaoxiao, Jarycki, Laura, Khan, Halema, MacNeil, Danielle, Khan, Mohammed Imran, Mendez, Adrian, Yoo, John, Fung, Kevin, Lang, Pencilla, Palma, David A, Patel, Krupal, Mymryk, Joe S, Barrett, John W, Boutros, Paul C, Morris, Luc GT, and Nichols, Anthony C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Infectious Diseases, Genetics, Sexually Transmitted Infections, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, head and neck cancer, chromosome loss, copy number alterations, genomics, mutational status, Oncology and carcinogenesis
Abstract

Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had 97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival (p > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (p < 0.05). They were enriched for SNVs in TP53, and depleted for point mutations in CASP8, HRAS, HLA-A, HUWE1, HLA-B, and COL22A1 (false discovery rate, FDR < 0.05). 3p arm loss was associated with CNAs across the whole genome (FDR < 0.1), and pathway analysis revealed low lymphoid-non-lymphoid cell interactions and cytokine signaling (FDR < 0.1). In the tumor microenvironment, 3p arm lost tumors had low immune cell infiltration (FDR < 0.1) and elevated hypoxia (FDR < 0.1). 3p arm lost tumors had lower abundance of proteins phospho-HER3 and ANXA1, and higher abundance of miRNAs hsa-miR-548k and hsa-miR-421, which were all associated with survival. There were no molecular differences by 3p arm status in HPV-positive patients, at least at our statistical power level. 3p arm loss is largely an all or none phenomenon in HPV-negative disease and does not predict poorer survival from the time of diagnosis in TCGA cohort. However, it produces tumors with distinct molecular characteristics and may represent a clinically useful biomarker to guide treatment decisions for HPV-negative patients.

Published
2021

28. Analysis of the TCGA Dataset Reveals that Subsites of Laryngeal Squamous Cell Carcinoma are Molecularly Distinct.

Author

Sorgini, Alana, Kim, Hugh Andrew Jinwook, Zeng, Peter YF, Shaikh, Mushfiq Hassan, Mundi, Neil, Ghasemi, Farhad, Di Gravio, Eric, Khan, Halema, MacNeil, Danielle, Khan, Mohammed Imran, Mendez, Adrian, Yoo, John, Fung, Kevin, Lang, Pencilla, Palma, David A, Mymryk, Joe S, Barrett, John W, Patel, Krupal B, Boutros, Paul C, and Nichols, Anthony C

Subjects
HNSCC, HPV-negative, genomics, larynx cancer, mutational status, Clinical Research, Cancer, Human Genome, Genetics, Biotechnology, Oncology and Carcinogenesis
Abstract

Laryngeal squamous cell carcinoma (LSCC) from different subsites have distinct presentations and prognosis. In this study, we carried out a multiomic comparison of LSCC subsites. The Cancer Genome Atlas (TCGA) LSCC cohort was analyzed in the R statistical environment for differences between supraglottic and glottic cancers in single nucleotide variations (SNVs), copy number alterations (CNAs), mRNA abundance, protein abundance, pathway overrepresentation, tumor microenvironment (TME), hypoxia status, and patient outcome. Supraglottic cancers had significantly higher overall and smoking-associated SNV mutational load. Pathway analysis revealed upregulation of muscle related pathways in glottic cancer and neural pathways in supraglottic cancer. Proteins involved in cancer relevant signaling pathways including PI3K/Akt/mTOR, the cell cycle, and PDL1 were differentially abundant between subsites. Glottic and supraglottic tumors have different molecular profiles, which may partially account for differences in presentation and response to therapy.

Published
2020

29. TAM family receptors in conjunction with MAPK signalling are involved in acquired resistance to PI3Kα inhibition in head and neck squamous cell carcinoma

Author

Ruicci, Kara M, Meens, Jalna, Plantinga, Paul, Stecho, William, Pinto, Nicole, Yoo, John, Fung, Kevin, MacNeil, Danielle, Mymryk, Joe S, Barrett, John W, Howlett, Christopher J, Boutros, Paul C, Ailles, Laurie, and Nichols, Anthony C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Rare Diseases, Dental/Oral and Craniofacial Disease, Biotechnology, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Animals, Apoptosis, Biomarkers, Tumor, Cell Movement, Cell Proliferation, Class I Phosphatidylinositol 3-Kinases, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, Humans, MAP Kinase Signaling System, Mice, Prognosis, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Squamous Cell Carcinoma of Head and Neck, Survival Rate, Thiazoles, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Axl Receptor Tyrosine Kinase, Alpelisib, BYL719, PI3-kinase, PI3K, Head and neck cancer, HNSCC, AXL, TYRO3, Oncology and carcinogenesis
Abstract

BackgroundAberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway is common in many malignancies, including head and neck squamous cell carcinoma (HNSCC). Despite pre-clinical and clinical studies, outcomes from targeting the PI3K pathway have been underwhelming and the development of drug resistance poses a significant barrier to patient treatment. In the present study, we examined mechanisms of acquired resistance to the PI3Kα inhibitor alpelisib (formerly BYL719) in HNSCC cell lines and patient-derived xenografts (PDXs).MethodsFive unique PDX mouse models and three HNSCC cell lines were used. All cell lines and xenografts underwent genomic characterization prior to study. Serial drug treatment was conducted in vitro and in vivo to develop multiple, clinically-significant models of resistance to alpelisib. We then used reverse phase protein arrays (RPPAs) to profile the expression of proteins in parental and drug-resistant models. Top hits were validated by immunoblotting and immunohistochemistry. Flow cytometric analysis and RNA interference studies were then used to interrogate the molecular mechanisms underlying acquired drug resistance.ResultsProlonged treatment with alpelisib led to upregulation of TAM family receptor tyrosine kinases TYRO3 and AXL. Importantly, a significant shift in expression of both TYRO3 and AXL to the cell surface was detected in drug-resistant cells. Targeted knockdown of TYRO3 and AXL effectively re-sensitized resistant cells to PI3Kα inhibition. In vivo, resistance to alpelisib emerged following 20-35 days of treatment in all five PDX models. Elevated TYRO3 expression was detected in drug-resistant PDX tissues. Downstream of TYRO3 and AXL, we identified activation of intracellular MAPK signalling. Inhibition of MAPK signalling also re-sensitized drug-resistant cells to alpelisib.ConclusionsWe have identified TYRO3 and AXL receptors to be key mediators of resistance to alpelisib, both in vitro and in vivo. Our findings suggest that pan-TAM inhibition is a promising avenue for combinatorial or second-line therapy alongside PI3Kα inhibition. These findings advance our understanding of the role TAM receptors play in modulating the response of HNSCC to PI3Kα inhibition and suggest a means to prevent, or at least delay, resistance to PI3Kα inhibition in order to improve outcomes for HNSCC patients.

Published
2020

30. Finite spectral triples for the fuzzy torus

Author

Barrett, John W. and Gaunt, James

Subjects
Mathematics - Quantum Algebra, General Relativity and Quantum Cosmology, High Energy Physics - Theory, Mathematical Physics, 58B34, 81T75
Abstract

Finite real spectral triples are defined to characterise the non-commutative geometry of a fuzzy torus. The geometries are the non-commutative analogues of flat tori with moduli determined by integer parameters. Each of these geometries has four different Dirac operators, corresponding to the four unique spin structures on a torus. The spectrum of the Dirac operator is calculated. It is given by replacing integers with their quantum integer analogues in the spectrum of the corresponding commutative torus., Comment: 54 pages, 8 figures

Published
2019

31. Parametric finite element approximations of curvature driven interface evolutions

Author

Barrett, John W., Garcke, Harald, and Nürnberg, Robert

Subjects
Mathematics - Numerical Analysis
Abstract

Parametric finite elements lead to very efficient numerical methods for surface evolution equations. We introduce several computational techniques for curvature driven evolution equations based on a weak formulation for the mean curvature. The approaches discussed, in contrast to many other methods, have good mesh properties that avoid mesh coalescence and very non-uniform meshes. Mean curvature flow, surface diffusion, anisotropic geometric flows, solidification, two-phase flow, Willmore and Helfrich flow as well as biomembranes are treated. We show stability results as well as results explaining the good mesh properties., Comment: 144 pages, 7 figures. This review article will appear in HNA vol 21

Published
2019
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32. EHT-HOPS pipeline for millimeter VLBI data reduction

Author

Blackburn, Lindy, Chan, Chi-kwan, Crew, Geoffrey B., Fish, Vincent L., Issaoun, Sara, Johnson, Michael D., Wielgus, Maciek, Akiyama, Kazunori, Barrett, John, Bouman, Katherine L., Cappallo, Roger, Chael, Andrew A., Janssen, Michael, Lonsdale, Colin J., and Doeleman, Sheperd S.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - High Energy Astrophysical Phenomena
Abstract

We present the design and implementation of an automated data calibration and reduction pipeline for very-long-baseline interferometric (VLBI) observations taken at millimeter wavelengths. These short radio-wavelengths provide the best imaging resolution available from ground-based VLBI networks such as the Event Horizon Telescope (EHT) and the Global Millimeter VLBI Array (GMVA), but require specialized processing due to the strong effects from atmospheric opacity and turbulence as well as the heterogeneous nature of existing global arrays. The pipeline builds upon a calibration suite (HOPS) originally designed for precision geodetic VLBI. To support the reduction of data for astronomical observations, we have developed an additional framework for global phase and amplitude calibration which provides output in a standard data format for astronomical imaging and analysis. We test the pipeline on observations taken at 3.5 mm (86 GHz) by the GMVA joined by the phased Atacama Large Millimeter/submillimeter Array in April 2017, and demonstrate the benefits from the specialized processing of high frequency VLBI data with respect to classical analysis techniques.

Published
2019
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33. Spectral estimators for finite non-commutative geometries

Author

Barrett, John W., Druce, Paul, and Glaser, Lisa

Subjects
General Relativity and Quantum Cosmology, High Energy Physics - Lattice, High Energy Physics - Theory, 58B34 81T75 83C65
Abstract

A finite non-commutative geometry consists of a fuzzy space together with a Dirac operator satisfying the axioms of a real spectral triple. This paper addreses the question of how to extract information about these geometries from the spectrum of the Dirac operator. Since the Dirac operator is a finite-dimensional matrix, the usual asymptotics of the eigenvalues makes no sense and is replaced by measurements of the spectrum at a finite energy scale. The spectral dimension of the square of the Dirac operator is improved to provide a new spectral measure of the dimension of a space called the spectral variance. Similarly, the volume of a space can be computed from the spectrum once the dimension is known. Two methods of doing this are investigated: the well-known Dixmier trace and a recent improvement due to Abel Stern. Finally, the distance between two geometries is investigated by comparing the spectral zeta functions using the method of Cornelissen and Kontogeorgis. All of these techniques are tested on the explicit examples of the fuzzy spheres and fuzzy tori, which can be regarded as approximations of the usual Riemannian sphere and flat tori. Then they are applied to characterise some random fuzzy spaces using data generated by a Monte Carlo simulation., Comment: 27 pages, final version with typos and references corrected

Published
2019
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34. First operation of the KATRIN experiment with tritium

Author

Aker, Max, Altenmüller, Konrad, Arenz, Marius, Baek, Woo-Jeong, Barrett, John, Beglarian, Armen, Behrens, Jan, Berlev, Anatoly, Besserer, Uwe, Blaum, Klaus, Block, Fabian, Bobien, Steffen, Bornschein, Beate, Bornschein, Lutz, Bouquet, Heiko, Brunst, Tim, Caldwell, Thomas S, Chilingaryan, Suren, Choi, Wonqook, Debowski, Karol, Deffert, Marco, Descher, Martin, Díaz Barrero, Deseada, Doe, Peter J, Dragoun, Otokar, Drexlin, Guido, Dyba, Stephan, Edzards, Frank, Eitel, Klaus, Ellinger, Enrico, Engel, Ralph, Enomoto, Sanshiro, Eversheim, Dieter, Fedkevych, Mariia, Felden, Arne, Formaggio, Joseph A, Fränkle, Florian M, Franklin, Gregg B, Frankrone, Heinz, Friedel, Fabian, Fuchs, Dominik, Fulst, Alexander, Gauda, Kevin, Gil, Woosik, Glück, Ferenc, Grohmann, Steffen, Grössle, Robin, Gumbsheimer, Rainer, Hackenjos, Moritz, Hannen, Volker, Hartmann, Julius, Haußmann, Norman, Ha-Minh, Martin, Heizmann, Florian, Heizmann, Johannes, Helbing, Klaus, Hickford, Stephanie, Hillesheimer, David, Hinz, Dominic, Höhn, Thomas, Holzapfel, Bernhard, Holzmann, Siegfried, Houdy, Thibaut, Howe, Mark A, Huber, Anton, Jansen, Alexander, Karl, Christian, Kellerer, Jonas, Kernert, Norbert, Kippenbrock, Luke, Klein, Manuel, Köhler, Christoph, Köllenberger, Leonard, Kopmann, Andreas, Korzeczek, Marc, Kovalík, Alojz, Krasch, Bennet, Krause, Holger, Kuffner, Benedikt, Kunka, Norbert, Lasserre, Thierry, La Cascio, Luisa, Lebeda, Ondřej, Lebert, Manuel, Lehnert, Björn, Letnev, Johann, Leven, Fabian, Le, Thanh-Long, Lichter, Steffen, Lokhov, Alexey, Machatschek, Moritz, Malcherek, Emma, Mark, Martin, Marsteller, Alexander, Martin, Eric L, Megas, Fotios, Melzer, Christin, Menshikov, Alexander, Mertens, Susanne, and Meier, Matthias

Subjects
Nuclear and Plasma Physics, Particle and High Energy Physics, Physical Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Quantum Physics, Nuclear & Particles Physics, Astronomical sciences, Atomic, molecular and optical physics, Particle and high energy physics
Abstract

The determination of the neutrino mass is one of the major challenges in astroparticle physics today. Direct neutrino mass experiments, based solely on the kinematics of β -decay, provide a largely model-independent probe to the neutrino mass scale. The Karlsruhe Tritium Neutrino (KATRIN) experiment is designed to directly measure the effective electron antineutrino mass with a sensitivity of 0.2eV (90 % CL). In this work we report on the first operation of KATRIN with tritium which took place in 2018. During this commissioning phase of the tritium circulation system, excellent agreement of the theoretical prediction with the recorded spectra was found and stable conditions over a time period of 13 days could be established. These results are an essential prerequisite for the subsequent neutrino mass measurements with KATRIN in 2019.

Published
2020

35. Flavopiridol causes cell cycle inhibition and demonstrates anti-cancer activity in anaplastic thyroid cancer models

Author

Pinto, Nicole, Prokopec, Stephenie D, Ghasemi, Farhad, Meens, Jalna, Ruicci, Kara M, Khan, Imran M, Mundi, Neil, Patel, Krupal, Han, Myung W, Yoo, John, Fung, Kevin, MacNeil, Danielle, Mymryk, Joe S, Datti, Alessandro, Barrett, John W, Boutros, Paul C, Ailles, Laurie, and Nichols, Anthony C

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Animals, Apoptosis, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cyclin-Dependent Kinase 9, Flavonoids, Humans, Male, Mice, Mice, Inbred NOD, Mice, SCID, Piperidines, Protein Kinase Inhibitors, RNA Interference, RNA, Small Interfering, Thyroid Carcinoma, Anaplastic, Thyroid Neoplasms, Transplantation, Heterologous, General Science & Technology
Abstract

Anaplastic thyroid cancer (ATC) is a rare, but nearly uniformly fatal disease that is typically resistant to chemotherapy and radiation. Alternative strategies to target this cancer at a molecular level are necessary in order to improve dismal outcomes for ATC patients. We examined the effects of flavopiridol, a CDK inhibitor, in a panel of ATC cell lines. When cell lines were treated over a ten-point concentration range, CAL62, KMH2 and BHT-101 cell lines had a sub micromolar half-maximal inhibitory concentration, while no effect was seen in the non-cancerous cell line IMR-90. Flavopiridol treatment resulted in decreased levels of the cell cycle proteins CDK9 and MCL1, and induced cell cycle arrest. Flavopiridol also decreased the in vitro ability of ATC cells to form colonies and impeded migration using a transwell migration assay. In vivo, flavopiridol decreased tumor weight and tumor volume over time in a patient-derived xenograft model of ATC. Given the observed in vitro and in vivo activity, flavopiridol warrants further investigation for treatment of ATC.

Published
2020

36. Tullio Regge's legacy: Regge calculus and discrete gravity

Author

Barrett, John W., Oriti, Daniele, and Williams, Ruth M.

Subjects
General Relativity and Quantum Cosmology, High Energy Physics - Theory
Abstract

The review paper "Discrete Structures in Physics", written in 2000, describes how Regge's discretization of Einstein's theory has been applied in classical relativity and quantum gravity. Here, developments since 2000 are reviewed briefly, with particular emphasis on progress in quantum gravity through spin foam models and group field theories., Comment: 15 pages; a contribution to the forthcoming volume "Tullio Regge: an eclectic genius, from quantum gravity to computer play", Eds. L Castellani, A. Ceresole, R. D'Auria and P. Fr\`e (World Scientific); v2: added references to more relevant work, minor changes to the text

Published
2018

37. Stable discretizations of elastic flow in Riemannian manifolds

Author

Barrett, John W., Garcke, Harald, and Nürnberg, Robert

Subjects
Mathematics - Numerical Analysis, Mathematics - Differential Geometry, 65M60, 53C44, 53A30, 35K55
Abstract

The elastic flow, which is the $L^2$-gradient flow of the elastic energy, has several applications in geometry and elasticity theory. We present stable discretizations for the elastic flow in two-dimensional Riemannian manifolds that are conformally flat, i.e.\ conformally equivalent to the Euclidean space. Examples include the hyperbolic plane, the hyperbolic disk, the elliptic plane as well as any conformal parameterization of a two-dimensional manifold in ${\mathbb R}^d$, $d\geq 3$. Numerical results show the robustness of the method, as well as quadratic convergence with respect to the space discretization., Comment: Minor revision. 31 pages, 6 figures. This article is closely related to arXiv:1809.01973

Published
2018
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38. Genomic and human papillomavirus profiling of an oral cancer cohort identifies TP53 as a predictor of overall survival

Author

Mundi, Neil, Prokopec, Stephenie D, Ghasemi, Farhad, Warner, Andrew, Patel, Krupal, MacNeil, Danielle, Howlett, Christopher, Stecho, William, Plantinga, Paul, Pinto, Nicole, Ruicci, Kara M, Khan, Mohammed Imran, Han, Myung Woul, Yoo, John, Fung, Kevin, Sahovaler, Axel, Palma, David A, Winquist, Eric, Mymryk, Joe S, Barrett, John W, Boutros, Paul C, and Nichols, Anthony C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetic Testing, Biotechnology, Sexually Transmitted Infections, Infectious Diseases, Human Genome, Genetics, Prevention, Cervical Cancer, Dental/Oral and Craniofacial Disease, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Genomics, Mutational status, Oral cancer, Survival, tp53, Oncology and carcinogenesis
Abstract

BackgroundThe genomic landscape of head and neck cancer has been reported through The Cancer Genome Atlas project. We attempt to determine if high-risk human papillomavirus (HPV) or frequently mutated genes are correlated with survival in an oral cancer cohort.MethodsPatient demographic data along with data from final pathology was collected. Tumor DNA was analyzed using a custom Illumina targeted sequencing panel. Five high-risk HPV types were tested by qPCR. Statistical analyses were used to identify associations between patient outcome and mutational status.ResultsHigh-risk HPV types were identified in 7% of cases; HPV status was not associated with survival. Mutations were identified in TP53, TERT promoter, & PIK3CA. Mutations in TP53 were significantly associated with poorer overall survival on multi-variate analysis (p = 0.03).ConclusionsMutations in TP53 were associated with poor patient survival. Expanding our sample size may identify further predictors of outcome to direct customized cancer care.

Published
2019

39. Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)–an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)

Author

Kansagra, Ankit J, Frey, Noelle V, Bar, Merav, Laetsch, Theodore W, Carpenter, Paul A, Savani, Bipin N, Heslop, Helen E, Bollard, Catherine M, Komanduri, Krishna V, Gastineau, Dennis A, Chabannon, Christian, Perales, Miguel A, Hudecek, Michael, Aljurf, Mahmoud, Andritsos, Leslie, Barrett, John A, Bachanova, Veronika, Bonini, Chiara, Ghobadi, Armin, Gill, Saar I, Hill, Joshua A, Kenderian, Saad, Kebriaei, Partow, Nagler, Arnon, Maloney, David, Liu, Hien D, Shah, Nirali N, Kharfan-Dabaja, Mohamed A, Shpall, Elizabeth J, Mufti, Ghulam J, Johnston, Laura, Jacoby, Elad, Bazarbachi, Ali, DiPersio, John F, Pavletic, Steven Z, Porter, David L, Grupp, Stephan A, Sadelain, Michel, Litzow, Mark R, Mohty, Mohamad, and Hashmi, Shahrukh K

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Pediatric, Childhood Leukemia, Immunization, Genetics, Transplantation, Biotechnology, Gene Therapy, Pediatric Cancer, Pediatric Research Initiative, Hematology, Orphan Drug, Rare Diseases, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Good Health and Well Being, Clinical Sciences, Cardiovascular medicine and haematology, Oncology and carcinogenesis
Abstract

On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Published
2019

41. Numerical approximation of curve evolutions in Riemannian manifolds

Author

Barrett, John W., Garcke, Harald, and Nürnberg, Robert

Subjects
Mathematics - Numerical Analysis, Mathematics - Differential Geometry, 65M60, 53C44, 53A30, 35K55
Abstract

We introduce variational approximations for curve evolutions in two-dimensional Riemannian manifolds that are conformally flat, i.e.\ conformally equivalent to the Euclidean space. Examples include the hyperbolic plane, the hyperbolic disk, the elliptic plane as well as any conformal parameterization of a two-dimensional surface in ${\mathbb R}^d$, $d\geq 3$. In these spaces we introduce stable numerical schemes for curvature flow and curve diffusion, and we also formulate a scheme for elastic flow. Variants of the schemes can also be applied to geometric evolution equations for axisymmetric hypersurfaces in ${\mathbb R}^d$. Some of the schemes have very good properties with respect to the distribution of mesh points, which is demonstrated with the help of several numerical computations., Comment: 49 pages, 15 figures

Published
2018
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42. Finite element methods for fourth order axisymmetric geometric evolution equations

Author

Barrett, John W., Garcke, Harald, and Nürnberg, Robert

Subjects
Mathematics - Numerical Analysis, 65M60, 65M12, 35K55, 53C44
Abstract

Fourth order curvature driven interface evolution equations frequently appear in the natural sciences. Often axisymmetric geometries are of interest, and in this situation numerical computations are much more efficient. We will introduce and analyze several new finite element schemes for fourth order geometric evolution equations in an axisymmetric setting, and for selected schemes we will show existence, uniqueness and stability results. The presented schemes have very good mesh and stability properties, as will be demonstrated by several numerical examples., Comment: Revised version. 37 pages, 27 figures. This article is closely related to arXiv:1805.04322

Published
2018
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43. Variational discretization of axisymmetric curvature flows

Author

Barrett, John W., Garcke, Harald, and Nürnberg, Robert

Subjects
Mathematics - Numerical Analysis, 65M60, 65M12, 53C44, 35K55
Abstract

We present natural axisymmetric variants of schemes for curvature flows introduced earlier by the present authors and analyze them in detail. Although numerical methods for geometric flows have been used frequently in axisymmetric settings, numerical analysis results so far are rare. In this paper, we present stability, equidistribution, existence and uniqueness results for the introduced approximations. Numerical computations show that these schemes are very efficient in computing numerical solutions of geometric flows as only a spatially one-dimensional problem has to be solved. The good mesh properties of the schemes also allow them to compute in very complex axisymmetric geometries., Comment: 49 pages, 17 figures

Published
2018
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44. Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Transplantation and Cellular Therapy

Author

Kansagra, Ankit J, Frey, Noelle V, Bar, Merav, Laetsch, Theodore W, Carpenter, Paul A, Savani, Bipin N, Heslop, Helen E, Bollard, Catherine M, Komanduri, Krishna V, Gastineau, Dennis A, Chabannon, Christian, Perales, Miguel A, Hudecek, Michael, Aljurf, Mahmoud, Andritsos, Leslie, Barrett, John A, Bachanova, Veronika, Bonini, Chiara, Ghobadi, Armin, Gill, Saar I, Hill, Joshua, Kenderian, Saad, Kebriaei, Partow, Nagler, Arnon, Maloney, David, Liu, Hien D, Shah, Nirali N, Kharfan-Dabaja, Mohamed A, Shpall, Elizabeth J, Mufti, Ghulam J, Johnston, Laura, Jacoby, Elad, Bazarbachi, Ali, DiPersio, John F, Pavletic, Steven Z, Porter, David L, Grupp, Stephan A, Sadelain, Michel, Litzow, Mark R, Mohty, Mohamad, and Hashmi, Shahrukh K

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Transplantation, Childhood Leukemia, Pediatric Cancer, Pediatric, Biotechnology, Orphan Drug, Genetics, Pediatric Research Initiative, Cancer, Rare Diseases, Gene Therapy, Immunization, Hematology, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Good Health and Well Being, Antigens, CD19, Child, Critical Pathways, Drug Approval, Expert Testimony, Humans, Immunotherapy, Adoptive, Practice Patterns, Physicians', Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Receptors, Antigen, T-Cell, Societies, Medical, United States, Young Adult, Chimeric antigen receptor, Leukemia, T cell, Clinical Sciences, Cardiovascular medicine and haematology
Abstract

On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Published
2019

45. Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status

Author

Ghasemi, Farhad, Prokopec, Stephenie D, MacNeil, Danielle, Mundi, Neil, Gameiro, Steven F, Howlett, Christopher, Stecho, William, Plantinga, Paul, Pinto, Nicole, Ruicci, Kara M, Khan, Mohammed Imran, Yoo, John, Fung, Kevin, Sahovaler, Axel, Palma, David A, Winquist, Eric, Mymryk, Joe S, Barrett, John W, Boutros, Paul C, and Nichols, Anthony C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Tobacco, Dental/Oral and Craniofacial Disease, Tobacco Smoke and Health, Sexually Transmitted Infections, Infectious Diseases, Clinical Research, Cancer, Genetics, Good Health and Well Being, Head & neck cancer, Oncology, Biomedical and clinical sciences, Health sciences
Abstract

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (>20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive tumors. By contrast, in HPV-negative tumors, NSD1 and COL1A11 were found to be more frequently mutated in heavy smokers, while CASP8 was more frequently altered in never smokers. HPV-negative patients with NSD1 mutations experienced significantly improved overall survival compared with NSD1 WT patients. This improved prognosis was validated in an independent cohort of 77 oral cavity cancer patients and a meta-analysis that included 2 additional data sets (688 total patients, hazard ratio for death 0.44, 95% CI, 0.30-0.65). NSD1 mutations are more common in HPV-negative heavy smokers, define a cohort with favorable prognosis, and may represent a clinically useful biomarker to guide treatment deintensification for HPV-negative patients.

Published
2019

46. Antimicrobial Resistance Genes, Cassettes, and Plasmids Present in Salmonella enterica Associated With United States Food Animals

Author

McMillan, Elizabeth A, Gupta, Sushim K, Williams, Laura E, Jové, Thomas, Hiott, Lari M, Woodley, Tiffanie A, Barrett, John B, Jackson, Charlene R, Wasilenko, Jamie L, Simmons, Mustafa, Tillman, Glenn E, McClelland, Michael, and Frye, Jonathan G

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Microbiology, Clinical Sciences, Medical Microbiology, Emerging Infectious Diseases, Antimicrobial Resistance, Biotechnology, Prevention, Infectious Diseases, Foodborne Illness, Genetics, Vaccine Related, Biodefense, Infection, Zero Hunger, Salmonella, plasmids, antimicrobial resistance, agriculture, integrons, Environmental Science and Management, Soil Sciences, Medical microbiology
Abstract

The ability of antimicrobial resistance (AR) to transfer, on mobile genetic elements (MGEs) between bacteria, can cause the rapid establishment of multidrug resistance (MDR) in bacteria from animals, thus creating a foodborne risk to human health. To investigate MDR and its association with plasmids in Salmonella enterica, whole genome sequence (WGS) analysis was performed on 193 S. enterica isolated from sources associated with United States food animals between 1998 and 2011; 119 were resistant to at least one antibiotic tested. Isolates represented 86 serotypes and variants, as well as diverse phenotypic resistance profiles. A total of 923 AR genes and 212 plasmids were identified among the 193 strains. Every isolate contained at least one AR gene. At least one plasmid was detected in 157 isolates. Genes were identified for resistance to aminoglycosides (n = 472), β-lactams (n = 84), tetracyclines (n = 171), sulfonamides (n = 91), phenicols (n = 42), trimethoprim (n = 8), macrolides (n = 5), fosfomycin (n = 48), and rifampicin (n = 2). Plasmid replicon types detected in the isolates were A/C (n = 32), ColE (n = 76), F (n = 43), HI1 (n = 4), HI2 (n = 20), I1 (n = 62), N (n = 4), Q (n = 7), and X (n = 35). Phenotypic resistance correlated with the AR genes identified in 95.4% of cases. Most AR genes were located on plasmids, with many plasmids harboring multiple AR genes. Six antibiotic resistance cassette structures (ARCs) and one pseudo-cassette were identified. ARCs contained between one and five resistance genes (ARC1: sul2, strAB, tetAR; ARC2: aac3-iid; ARC3: aph, sph; ARC4: cmy-2; ARC5: floR; ARC6: tetB; pseudo-ARC: aadA, aac3-VIa, sul1). These ARCs were present in multiple isolates and on plasmids of multiple replicon types. To determine the current distribution and frequency of these ARCs, the public NCBI database was analyzed, including WGS data on isolates collected by the USDA Food Safety and Inspection Service (FSIS) from 2014 to 2018. ARC1, ARC4, and ARC5 were significantly associated with cattle isolates, while ARC6 was significantly associated with chicken isolates. This study revealed that a diverse group of plasmids, carrying AR genes, are responsible for the phenotypic resistance seen in Salmonella isolated from United States food animals. It was also determined that many plasmids carry similar ARCs.

Published
2019

47. Genomic comparison of diverse Salmonella serovars isolated from swine.

Author

Gupta, Sushim K, Sharma, Poonam, McMillan, Elizabeth A, Jackson, Charlene R, Hiott, Lari M, Woodley, Tiffanie, Humayoun, Shaheen B, Barrett, John B, Frye, Jonathan G, and McClelland, Michael

Subjects
Animals, Swine, Salmonella, Salmonella Infections, Animal, Swine Diseases, Microbial Sensitivity Tests, Disease Reservoirs, Drug Resistance, Bacterial, Genes, Bacterial, Whole Genome Sequencing, Salmonella Infections, Animal, Drug Resistance, Bacterial, Genes, General Science & Technology
Abstract

Food animals act as a reservoir for many foodborne pathogens. Salmonella enterica is one of the leading pathogens that cause food borne illness in a broad host range including animals and humans. They can also be associated with a single host species or a subset of hosts, due to genetic factors associated with colonization and infection. Adult swine are often asymptomatic carriers of a broad range of Salmonella servoars and can act as an important reservoir of infections for humans. In order to understand the genetic variations among different Salmonella serovars, Whole Genome Sequences (WGS) of fourteen Salmonella serovars from swine products were analyzed. More than 75% of the genes were part of the core genome in each isolate and the higher fraction of gene assign to different functional categories in dispensable genes indicated that these genes acquired for better adaptability and diversity. High concordance (97%) was detected between phenotypically confirmed antibiotic resistances and identified antibiotic resistance genes from WGS. The resistance determinants were mainly located on mobile genetic elements (MGE) on plasmids or integrated into the chromosome. Most of known and putative virulence genes were part of the core genome, but a small fraction were detected on MGE. Predicted integrated phage were highly diverse and many harbored virulence, metal resistance, or antibiotic resistance genes. CRISPR (Clustered regularly interspaced short palindromic repeats) patterns revealed the common ancestry or infection history among Salmonella serovars. Overall genomic analysis revealed a great deal of diversity among Salmonella serovars due to acquired genes that enable them to thrive and survive during infection.

Published
2019

50. Gradient flow dynamics of two-phase biomembranes: Sharp interface variational formulation and finite element approximation

Author

Barrett, John W., Garcke, Harald, and Nürnberg, Robert

Subjects
Mathematics - Numerical Analysis, Physics - Computational Physics, 35R01, 49Q10, 65M12, 65M60, 82B26, 92C10
Abstract

A finite element method for the evolution of a two-phase membrane in a sharp interface formulation is introduced. The evolution equations are given as an $L^2$--gradient flow of an energy involving an elastic bending energy and a line energy. In the two phases Helfrich-type evolution equations are prescribed, and on the interface, an evolving curve on an evolving surface, highly nonlinear boundary conditions have to hold. Here we consider both $C^0$-- and $C^1$--matching conditions for the surface at the interface. A new weak formulation is introduced, allowing for a stable semidiscrete parametric finite element approximation of the governing equations. In addition, we show existence and uniqueness for a fully discrete version of the scheme. Numerical simulations demonstrate that the approach can deal with a multitude of geometries. In particular, the paper shows the first computations based on a sharp interface description, which are not restricted to the axisymmetric case., Comment: 46 pages, 22 figures

Published
2017
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