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5,030 results on '"Williams, L"'

1. Mass & Light in Galaxy Clusters: The case of Abell 370

Author

Limousin, M., Niemiec, A., Beauchesne, B., Diego, J., Jauzac, M., Koekemoer, A., Sharon, K., Acebron, A., Lagattuta, D., Mahler, G., Williams, L., Richard, J., Jullo, E., Furtak, L., Faisst, A., Frye, B., Hibon, P., Natarajan, P., and Rich, M.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

Parametric strong lensing studies of galaxy clusters often display "misleading features". This is the case in the galaxy cluster Abell 370. Using strong lensing techniques, it has been described parametrically by a four dark matter clumps model and galaxy scale perturbers, as well as a significant external shear component, which physical origin remains a challenge. The dark matter distribution features a mass clump with no stellar counterpart and a significant offset between one of the dark matter clumps and its associated stellar counterpart. In this paper, based on BUFFALO data, we begin by revisiting this mass model. We find a four dark matter clumps solution which does not require any external shear and provides a slightly better RMS compared to previous models. Investigating further this new solution, we present a class of models which can accurately reproduce the strong lensing data, but whose parameters for the dark matter component are poorly constrained. We then develop a model where each large scale dark matter component must be associated with a stellar counterpart. This model is unable to reproduce the observational constraints with an RMS smaller than 2.3", and the parameters describing this dark matter component remain poorly constrained. Examining the total projected mass maps, we find a good agreement between the total mass and the stellar distribution, both being bimodal. We interpret the "misleading features" of the four dark matter clumps mass model and the failure of the three dark matter clumps mass model as being symptomatic of the lack of realism of a parametric description of the dark matter distribution, and encourage caution and criticism on the outputs of parametric strong lensing modelling. We briefly discuss the implications of our results for using Abell 370 as a gravitational telescope., Comment: Abstract largely abridged - A&A accepted on 25/10/2024

Published
2024

2. Benchmarking the design of the cryogenics system for the underground argon in DarkSide-20k

Author

Collaboration, DarkSide-20k, Acerbi, F., Adhikari, P., Agnes, P., Ahmad, I., Albergo, S., Albuquerque, I. F. M., Alexander, T., Alton, A. K., Amaudruz, P., Angiolilli, M., Aprile, E., Ardito, R., Corona, M. Atzori, Auty, D. J., Ave, M., Avetisov, I. C., Azzolini, O., Back, H. O., Balmforth, Z., Olmedo, A. Barrado, Barrillon, P., Batignani, G., Bhowmick, P., Blua, S., Bocci, V., Bonivento, W., Bottino, B., Boulay, M. G., Buchowicz, A., Bussino, S., Busto, J., Cadeddu, M., Cadoni, M., Calabrese, R., Camillo, V., Caminata, A., Canci, N., Capra, A., Caravati, M., Cárdenas-Montes, M., Cargioli, N., Carlini, M., Castellani, A., Castello, P., Cavalcante, P., Cebrian, S., Ruiz, J. Cela, Chashin, S., Chepurnov, A., Cifarelli, L., Cintas, D., Citterio, M., Cleveland, B., Coadou, Y., Cocco, V., Colaiuda, D., Vilda, E. Conde, Consiglio, L., Costa, B. S., Czubak, M., D'Aniello, M., D'Auria, S., Rolo, M. D. Da Rocha, Darbo, G., Davini, S., De Cecco, S., De Guido, G., Dellacasa, G., Derbin, A. V., Devoto, A., Di Capua, F., Di Ludovico, A., Di Noto, L., Di Stefano, P., Dias, L. K., Mairena, D. Díaz, Ding, X., Dionisi, C., Dolganov, G., Dordei, F., Dronik, V., Elersich, A., Ellingwood, E., Erjavec, T., Diaz, M. Fernandez, Ficorella, A., Fiorillo, G., Franchini, P., Franco, D., Gatti, H. Frandini, Frolov, E., Gabriele, F., Gahan, D., Galbiati, C., Galiński, G., Gallina, G., Gallus, G., Garbini, M., Abia, P. Garcia, Gawdzik, A., Gendotti, A., Ghisi, A., Giovanetti, G. K., Casanueva, V. Goicoechea, Gola, A., Grandi, L., Grauso, G., di Cortona, G. Grilli, Grobov, A., Gromov, M., Guerzoni, M., Gulino, M., Guo, C., Hackett, B. R., Hallin, A., Hamer, A., Haranczyk, M., Harrop, B., Hessel, T., Hill, S., Horikawa, S., Hu, J., Hubaut, F., Hucker, J., Hugues, T., Hungerford, E. V., Ianni, A., Ippolito, V., Jamil, A., Jillings, C., Jois, S., Kachru, P., Keloth, R., Kemmerich, N., Kemp, A., Kendziora, C. L., Kimura, M., Kish, A., Kondo, K., Korga, G., Kotsiopoulou, L., Koulosousas, S., Kubankin, A., Kunzé, P., Kuss, M., Kuźniak, M., Kuzwa, M., La Commara, M., Lai, M., Guirriec, E. Le, Leason, E., Leoni, A., Lidey, L., Lissia, M., Luzzi, L., Lychagina, O., Macfadyen, O., Machulin, I. N., Manecki, S., Manthos, I., Mapelli, L., Marasciulli, A., Mari, S. M., Mariani, C., Maricic, J., Martinez, M., Martoff, C. J., Matteucci, G., Mavrokoridis, K., McDonald, A. B., Mclaughlin, J., Merzi, S., Messina, A., Milincic, R., Minutoli, S., Mitra, A., Moharana, A., Moioli, S., Monroe, J., Moretti, E., Morrocchi, M., Mroz, T., Muratova, V. N., Murphy, M., Murra, M., Muscas, C., Musico, P., Nania, R., Nessi, M., Nieradka, G., Nikolopoulos, K., Nikoloudaki, E., Nowak, J., Olchanski, K., Oleinik, A., Oleynikov, V., Organtini, P., de Solórzano, A. Ortiz, Pallavicini, M., Pandola, L., Pantic, E., Paoloni, E., Papi, D., Pastuszak, G., Paternoster, G., Peck, A., Pegoraro, P. A., Pelczar, K., Pellegrini, L. A., Perez, R., Perotti, F., Pesudo, V., Piacentini, S. I., Pino, N., Plante, G., Pocar, A., Poehlmann, M., Pordes, S., Pralavorio, P., Price, D., Puglia, S., Bazetto, M. Queiroga, Ragusa, F., Ramachers, Y., Ramirez, A., Ravinthiran, S., Razeti, M., Renshaw, A. L., Rescigno, M., Retiere, F., Rignanese, L. P., Rivetti, A., Roberts, A., Roberts, C., Rogers, G., Romero, L., Rossi, M., Rubbia, A., Rudik, D., Sabia, M., Salomone, P., Samoylov, O., Sandford, E., Sanfilippo, S., Santone, D., Santorelli, R., Santos, E. M., Savarese, C., Scapparone, E., Schillaci, G., Schuckman II, F. G., Scioli, G., Semenov, D. A., Shalamova, V., Sheshukov, A., Simeone, M., Skensved, P., Skorokhvatov, M. D., Smirnov, O., Smirnova, T., Smith, B., Sotnikov, A., Spadoni, F., Spangenberg, M., Stefanizzi, R., Steri, A., Stornelli, V., Stracka, S., Sulis, S., Sung, A., Sunny, C., Suvorov, Y., Szelc, A. M., Taborda, O., Tartaglia, R., Taylor, A., Taylor, J., Tedesco, S., Testera, G., Thieme, K., Thompson, A., Thorpe, T. N., Tonazzo, A., Torres-Lara, S., Tricomi, A., Unzhakov, E. V., Vallivilayil, T. J., Van Uffelen, M., Velazquez-Fernandez, L., Viant, T., Viel, S., Vishneva, A., Vogelaar, R. B., Vossebeld, J., Vyas, B., Wada, M., Walczak, M. B., Wang, H., Wang, Y., Westerdale, S., Williams, L., Wojaczyński, R., Wojcik, M., Wojcik, M. M., Wright, T., Xiao, X., Xie, Y., Yang, C., Yin, J., Zabihi, A., Zakhary, P., Zani, A., Zhang, Y., Zhu, T., Zichichi, A., Zuzel, G., and Zykova, M. P.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

DarkSide-20k (DS-20k) is a dark matter detection experiment under construction at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy. It utilises ~100 t of low radioactivity argon from an underground source (UAr) in its inner detector, with half serving as target in a dual-phase time projection chamber (TPC). The UAr cryogenics system must maintain stable thermodynamic conditions throughout the experiment's lifetime of >10 years. Continuous removal of impurities and radon from the UAr is essential for maximising signal yield and mitigating background. We are developing an efficient and powerful cryogenics system with a gas purification loop with a target circulation rate of 1000 slpm. Central to its design is a condenser operated with liquid nitrogen which is paired with a gas heat exchanger cascade, delivering a combined cooling power of >8 kW. Here we present the design choices in view of the DS-20k requirements, in particular the condenser's working principle and the cooling control, and we show test results obtained with a dedicated benchmarking platform at CERN and LNGS. We find that the thermal efficiency of the recirculation loop, defined in terms of nitrogen consumption per argon flow rate, is 95 % and the pressure in the test cryostat can be maintained within $\pm$(0.1-0.2) mbar. We further detail a 5-day cool-down procedure of the test cryostat, maintaining a cooling rate typically within -2 K/h, as required for the DS-20k inner detector. Additionally, we assess the circuit's flow resistance, and the heat transfer capabilities of two heat exchanger geometries for argon phase change, used to provide gas for recirculation. We conclude by discussing how our findings influence the finalisation of the system design, including necessary modifications to meet requirements and ongoing testing activities., Comment: 45 pages, 24 figures

Published
2024

3. DarkSide-20k sensitivity to light dark matter particles

Author

Collaboration, DarkSide-20k, Acerbi, F., Adhikari, P., Agnes, P., Ahmad, I., Albergo, S., Albuquerque, I. F. M., Alexander, T., Alton, A. K., Amaudruz, P., Angiolilli, M., Aprile, E., Ardito, R., Corona, M. Atzori, Auty, D. J., Ave, M., Avetisov, I. C., Azzolini, O., Back, H. O., Balmforth, Z., Olmedo, A. Barrado, Barrillon, P., Batignani, G., Bhowmick, P., Blua, S., Bocci, V., Bonivento, W., Bottino, B., Boulay, M. G., Buchowicz, A., Bussino, S., Busto, J., Cadeddu, M., Cadoni, M., Calabrese, R., Camillo, V., Caminata, A., Canci, N., Capra, A., Caravati, M., Cárdenas-Montes, M., Cargioli, N., Carlini, M., Castellani, A., Castello, P., Cavalcante, P., Cebrian, S., Ruiz, J. M. Cela, Chashin, S., Chepurnov, A., Cifarelli, L., Cintas, D., Citterio, M., Cleveland, B., Coadou, Y., Cocco, V., Colaiuda, D., Vilda, E. Conde, Consiglio, L., Costa, B. S., Czubak, M., D'Aniello, M., D'Auria, S., Rolo, M. D. Da Rocha, Darbo, G., Davini, S., De Cecco, S., De Guido, G., Dellacasa, G., Derbin, A. V., Devoto, A., Di Capua, F., Di Ludovico, A., Di Noto, L., Di Stefano, P., Dias, L. K., Mairena, D. Díaz, Ding, X., Dionisi, C., Dolganov, G., Dordei, F., Dronik, V., Elersich, A., Ellingwood, E., Erjavec, T., Diaz, M. Fernandez, Ficorella, A., Fiorillo, G., Franchini, P., Franco, D., Gatti, H. Frandini, Frolov, E., Gabriele, F., Gahan, D., Galbiati, C., Galiński, G., Gallina, G., Gallus, G., Garbini, M., Abia, P. Garcia, Gawdzik, A., Gendotti, A., Ghisi, A., Giovanetti, G. K., Casanueva, V. Goicoechea, Gola, A., Grandi, L., Grauso, G., di Cortona, G. Grilli, Grobov, A., Gromov, M., Guerzoni, M., Gulino, M., Guo, C., Hackett, B. R., Hallin, A., Hamer, A., Haranczyk, M., Harrop, B., Hessel, T., Hill, S., Horikawa, S., Hu, J., Hubaut, F., Hucker, J., Hugues, T., Hungerford, E. V., Ianni, A., Ippolito, V., Jamil, A., Jillings, C., Jois, S., Kachru, P., Keloth, R., Kemmerich, N., Kemp, A., Kendziora, C. L., Kimura, M., Kondo, K., Korga, G., Kotsiopoulou, L., Koulosousas, S., Kubankin, A., Kunzé, P., Kuss, M., Kuźniak, M., Kuzwa, M., La Commara, M., Lai, M., Guirriec, E. Le, Leason, E., Leoni, A., Lidey, L., Lissia, M., Luzzi, L., Lychagina, O., Macfadyen, O., Machulin, I. N., Manecki, S., Manthos, I., Mapelli, L., Marasciulli, A., Mari, S. M., Mariani, C., Maricic, J., Martinez, M., Martoff, C. J., Matteucci, G., Mavrokoridis, K., McDonald, A. B., Mclaughlin, J., Merzi, S., Messina, A., Milincic, R., Minutoli, S., Mitra, A., Moioli, S., Monroe, J., Moretti, E., Morrocchi, M., Mroz, T., Muratova, V. N., Murphy, M., Murra, M., Muscas, C., Musico, P., Nania, R., Nessi, M., Nieradka, G., Nikolopoulos, K., Nikoloudaki, E., Nowak, J., Olchanski, K., Oleinik, A., Oleynikov, V., Organtini, P., de Solórzano, A. Ortiz, Pallavicini, M., Pandola, L., Pantic, E., Paoloni, E., Papi, D., Pastuszak, G., Paternoster, G., Peck, A., Pegoraro, P. A., Pelczar, K., Pellegrini, L. A., Perez, R., Perotti, F., Pesudo, V., Piacentini, S. I., Pino, N., Plante, G., Pocar, A., Poehlmann, M., Pordes, S., Pralavorio, P., Price, D., Puglia, S., Bazetto, M. Queiroga, Ragusa, F., Ramachers, Y., Ramirez, A., Ravinthiran, S., Razeti, M., Renshaw, A. L., Rescigno, M., Retiere, F., Rignanese, L. P., Rivetti, A., Roberts, A., Roberts, C., Rogers, G., Romero, L., Rossi, M., Rubbia, A., Rudik, D., Sabia, M., Salomone, P., Samoylov, O., Sandford, E., Sanfilippo, S., Santone, D., Santorelli, R., Santos, E. M., Savarese, C., Scapparone, E., Schillaci, G., Schuckman II, F. G., Scioli, G., Semenov, D. A., Shalamova, V., Sheshukov, A., Simeone, M., Skensved, P., Skorokhvatov, M. D., Smirnov, O., Smirnova, T., Smith, B., Sotnikov, A., Spadoni, F., Spangenberg, M., Stefanizzi, R., Steri, A., Stornelli, V., Stracka, S., Sulis, S., Sung, A., Sunny, C., Suvorov, Y., Szelc, A. M., Taborda, O., Tartaglia, R., Taylor, A., Taylor, J., Tedesco, S., Testera, G., Thieme, K., Thompson, A., Tonazzo, A., Torres-Lara, S., Tricomi, A., Unzhakov, E. V., Vallivilayil, T. J., Van Uffelen, M., Velazquez-Fernandez, L., Viant, T., Viel, S., Vishneva, A., Vogelaar, R. B., Vossebeld, J., Vyas, B., Walczak, M. B., Wang, Y., Wang, H., Westerdale, S., Williams, L., Wojaczyński, R., Wojcik, M., Wojcik, M. M., Wright, T., Xie, Y., Yang, C., Yin, J., Zabihi, A., Zakhary, P., Zani, A., Zhang, Y., Zhu, T., Zichichi, A., Zuzel, G., and Zykova, M. P.

Subjects
High Energy Physics - Experiment, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The dual-phase liquid argon time projection chamber is presently one of the leading technologies to search for dark matter particles with masses below 10 GeV/c$^2$. This was demonstrated by the DarkSide-50 experiment with approximately 50 kg of low-radioactivity liquid argon as target material. The next generation experiment DarkSide-20k, currently under construction, will use 1,000 times more argon and is expected to start operation in 2027. Based on the DarkSide-50 experience, here we assess the DarkSide-20k sensitivity to models predicting light dark matter particles, including Weakly Interacting Massive Particles (WIMPs) and sub-GeV/c$^2$ particles interacting with electrons in argon atoms. With one year of data, a sensitivity improvement to dark matter interaction cross-sections by at least one order of magnitude with respect to DarkSide-50 is expected for all these models. A sensitivity to WIMP--nucleon interaction cross-sections below $1\times10^{-42}$ cm$^2$ is achievable for WIMP masses above 800 MeV/c$^2$. With 10 years exposure, the neutrino fog can be reached for WIMP masses around 5 GeV/c$^2$., Comment: submitted to Nature Communications

Published
2024

4. A new hybrid gadolinium nanoparticles-loaded polymeric material for neutron detection in rare event searches

Author

Collaboration, DarkSide-20k, Acerbi, F., Adhikari, P., Agnes, P., Ahmad, I., Albergo, S., Albuquerque, I. F., Alexander, T., Alton, A. K., Amaudruz, P., Angiolilli, M., Aprile, E., Ardito, R., Corona, M. Atzori, Auty, D. J., Ave, M., Avetisov, I. C., Azzolini, O., Back, H. O., Balmforth, Z., Olmedo, A. Barrado, Barrillon, P., Batignani, G., Bhowmick, P., Bocci, V., Bonivento, W., Bottino, B., Boulay, M. G., Buchowicz, A., Bussino, S., Busto, J., Cadeddu, M., Cadoni, M., Calabrese, R., Camillo, V., Caminata, A., Canci, N., Capra, A., Caravati, M., Cárdenas-Montes, M., Cargioli, N., Carlini, M., Castellani, A., Castello, P., Cavalcante, P., Cavallo, D., Cebrian, S., Ruiz, J. Cela, Chashin, S., Chepurnov, A., Cifarelli, L., Cintas, D., Citterio, M., Cleveland, B., Coadou, Y., Cocco, V., Colaiuda, D., Vilda, E. Conde, Consiglio, L., Costa, B. S., Czubak, M., D'Auria, S., Rolo, M. D. Da Rocha, Darbo, G., Davini, S., De Cecco, S., De Guido, G., Dellacasa, G., Derbin, A. V., Devoto, A., Di Capua, F., Di Ludovico, A., Di Noto, L., Di Stefano, P., Dias, L. K., Mairena, D. Díaz, Ding, X., Dionisi, C., Dolganov, G., Dordei, F., Dronik, V., Elersich, A., Ellingwood, E., Erjavec, T., Diaz, M. Fernandez, Ficorella, A., Fiorillo, G., Franchini, P., Franco, D., Gatti, H. Frandini, Frolov, E., Gabriele, F., Gahan, D., Galbiati, C., Galinski, G., Gallina, G., Garbini, M., Abia, P. Garcia, Gawdzik, A., Gendotti, A., Ghisi, A., Giovanetti, G. K., Casanueva, V. Goicoechea, Gola, A., Grandi, L., Grauso, G., di Cortona, G. Grilli, Grobov, A., Gromov, M., Guerzoni, M., Gulino, M., Guo, C., Hackett, B. R., Hallin, A., Hamer, A., Haranczyk, M., Harrop, B., Hessel, T., Hill, S., Horikawa, S., Hu, J., Hubaut, F., Hucker, J., Hugues, T., Hungerford, E. V., Ianni, A., Ippolito, V., Jamil, A., Jillings, C., Keloth, R., Kemmerich, N., Kemp, A., Kendziora, C. L., Kimura, M., Kondo, K., Korga, G., Kotsiopoulou, L., Koulosousas, S., Kubankin, A., Kuss, M., Kuzniak, M., Kuzwa, M., La Commara, M., Lai, M., Guirriec, E. Le, Leason, E., Leoni, A., Lidey, L., Lissia, M., Luzzi, L., Lychagina, O., Macfadyen, O., Machulin, I. N., Manecki, S., Manthos, I., Mapelli, L., Marasciulli, A., Mari, S. M., Mariani, C., Maricic, J., Marini, A., Martinez, M., Martoff, C. J., Matteucci, G., Mavrokoridis, K., McDonald, A. B., Mclaughlin, J., Merzi, S., Messina, A., Milincic, R., Minutoli, S., Mitra, A., Moharana, A., Moioli, S., Monroe, J., Moretti, E., Morrocchi, M., Mroz, T., Muratova, V. N., Murphy, M., Murra, M., Muscas, C., Musico, P., Nania, R., Nessi, M., Nieradka, G., Nikolopoulos, K., Nikoloudaki, E., Nowak, J., Olchanski, K., Oleinik, A., Oleynikov, V., Organtini, P., de Solórzano, A. Ortiz, Pallavicini, M., Pandola, L., Pantic, E., Paoloni, E., Papi, D., Pastuszak, G., Paternoster, G., Peddis, D., Pegoraro, P. A., Pelczar, K., Pellegrini, L. A., Perez, R., Perotti, F., Pesudo, V., Piacentini, S. I., Pino, N., Plante, G., Pocar, A., Poehlmann, M., Pordes, S., Pralavorio, P., Price, D., Puglia, S., Bazetto, M. Queiroga, Ragusa, F., Ramachers, Y., Ramirez, A., Ravinthiran, S., Razeti, M., Renshaw, A. L., Rescigno, M., Retiere, F., Rignanese, L. P., Rivetti, A., Roberts, A., Roberts, C., Rogers, G., Romero, L., Rossi, M., Rubbia, A., Rudik, D., Sabia, M., Sadashivajois, S., Salomone, P., Samoylov, O., Sandford, E., Sanfilippo, S., Santone, D., Santorelli, R., Santos, E. M., Savarese, C., Scapparone, E., Schillaci, G., Schuckman II, F. G., Scioli, G., Semenov, D. A., Sheshukov, A., Simeone, M., Skensved, P., Skorokhvatov, M. D., Slimani, S., Smirnov, O., Smirnova, T., Smith, B., Sotnikov, A., Spadoni, F., Spangenberg, M., Stefanizzi, R., Steri, A., Stornelli, V., Stracka, S., Sulis, S., Sung, A., Sunny, C., Suvorov, Y., Szelc, A. M., Taborda, O., Tartaglia, R., Taylor, A., Taylor, J., Tedesco, S., Testera, G., Thieme, K., Thompson, A., Tonazzo, A., Torres-Lara, S., Tosi, S., Tricomi, A., Unzhakov, E. V., Vallivilayil, T. J., Van Uffelen, M., Velazquez-Fernandez, L., Viant, T., Vicini, S., Viel, S., Vishneva, A., Vogelaar, R. B., Vossebeld, J., Vyas, B., Wada, M., Walczak, M. B., Wang, H., Wang, Y., Westerdale, S., Williams, L., Wojaczynski, R., Wojcik, M. M., Wojcik, M., Wright, T., Xie, Y., Yang, C., Yin, J., Zabihi, A., Zakhary, P., Zani, A., Zhang, Y., Zhu, T., Zichichi, A., Zuzel, G., and Zykova, M. P.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

Experiments aimed at direct searches for WIMP dark matter require highly effective reduction of backgrounds and control of any residual radioactive contamination. In particular, neutrons interacting with atomic nuclei represent an important class of backgrounds due to the expected similarity of a WIMP-nucleon interaction, so that such experiments often feature a dedicated neutron detector surrounding the active target volume. In the context of the development of DarkSide-20k detector at INFN Gran Sasso National Laboratory (LNGS), several R&D projects were conceived and developed for the creation of a new hybrid material rich in both hydrogen and gadolinium nuclei to be employed as an essential element of the neutron detector. Thanks to its very high cross-section for neutron capture, gadolinium is one of the most widely used elements in neutron detectors, while the hydrogen-rich material is instrumental in efficiently moderating the neutrons. In this paper results from one of the R&Ds are presented. In this effort the new hybrid material was obtained as a poly(methyl methacrylate) (PMMA) matrix, loaded with gadolinium oxide in the form of nanoparticles. We describe its realization, including all phases of design, purification, construction, characterization, and determination of mechanical properties of the new material.

Published
2024
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5. A commensal Fast Radio Burst search pipeline for the Murchison Widefield Array

Author

Sokolowski, M., Morrison, I. S., Price, D., Sleap, G., Crosse, B., Williams, A., Williams, L., James, C., Meyers, B. W., McSweeney, S., Bhat, N. D. R., and Anderson, G.

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

We present a demonstration version of a commensal pipeline for Fast Radio Burst (FRB) searches using a real-time incoherent beam from the Murchison Widefield Array (MWA). The main science target of the pipeline are bright nearby FRBs from the local Universe which are the best candidates to probe FRB progenitors and understand physical mechanisms powering these extremely energetic events. The new MWA beamformer, known as the "MWAX multibeam beamformer", can form multiple incoherent and coherent beams commensally to any on-going MWA observations. One of the beams is currently used for FRB searches (tested in 10 kHz frequency resolution and time resolutions between 0.1 and 100 ms). A second beam is used for a Search for Extraterrestrial Intelligence (SETI). This paper focuses on the FRB search pipeline and its verification on selected known bright pulsars. The pipeline uses the FREDDA implementation of the Fast Dispersion Measure Transform algorithm (FDMT) for single pulse searches. Initially, it was tested during standard MWA observations, and more recently using dedicated observations of selected 11 bright pulsars. The pulsar PSR J0835-4510 (aka Vela) has been routinely used as the primary probe of the data quality because its folded profile was always detected in the frequency band 200 - 230 MHz with typical SNR >10. Similarly, the low DM pulsar PSR B0950+08 was always detected in folded profile in the frequency band 140 - 170 MHz, and so far has been the only object for which single pulses were detected. We present the estimated sensitivity of the search in the currently limited observing bandwidth of a single MWA coarse channel (1.28 MHz) and for the upgraded, future system with 12.8 MHz (10 channels) of bandwidth. Based on expected sensitivity and existing FRB rate measurements, we estimate an expected number of FRB detections to be between a few and a few tens per year., Comment: 22 pages, 12 figures, 4 tables. Accepted for publication in PASA

Published
2024

6. The SARAO MeerKAT 1.3 GHz Galactic Plane Survey

Author

Goedhart, S., Cotton, W. D., Camilo, F., Thompson, M. A., Umana, G., Bietenholz, M., Woudt, P. A., Anderson, L. D., Bordiu, C., Buckley, D. A. H., Buemi, C. S., Bufano, F., Cavallaro, F., Chen, H., Chibueze, J. O., Egbo, D., Frank, B. S., Hoare, M. G., Ingallinera, A., Irabor, T., Kraan-Korteweg, R. C., Kurapati, S., Leto, P., Loru, S., Mutale, M., Obonyo, W. O., Plavin, A., Rajohnson, S. H. A., Rigby, A., Riggi, S., Seidu, M., Serra, P., Smart, B. M., Stappers, B. W., Steyn, N., Surnis, M., Trigilio, C., Williams, G. M., Abbott, T. D., Adam, R. M., Asad, K. M. B., Baloyi, T., Bauermeister, E. F., Bennet, T. G. H., Bester, H., Botha, A. G., Brederode, L. R. S., Buchner, S., Burger, J. P., Cheetham, T., Cloete, K., de Villiers, M. S., de Villiers, D. I. L., Toit, L. J. du, Esterhuyse, S. W. P., Fanaroff, B. L., Fourie, D. J., Gamatham, R. R. G., Gatsi, T. G., Geyer, M., Gouws, M., Gumede, S. C., Heywood, I., Hokwana, A., Hoosen, S. W., Horn, D. M., Horrell, L. M. G., Hugo, B. V., Isaacson, A. I., Józsa, G. I. G., Jonas, J. L., Jordaan, J. D. B. L., Joubert, A. F., Julie, R. P. M., Kapp, F. B., Kriek, N., Kriel, H., Krishnan, V. K., Kusel, T. W., Legodi, L. S., Lehmensiek, R., Lord, R. T., Macfarlane, P. S., Magnus, L. G., Magozore, C., Main, J. P. L., Malan, J. A., Manley, J. R., Marais, S. J., Maree, M. D. J., Martens, A., Maruping, P., McAlpine, K., Merry, B. C., Mgodeli, M., Millenaar, R. P., Mokone, O. J., Monama, T. E., New, W. S., Ngcebetsha, B., Ngoasheng, K. J., Nicolson, G. D., Ockards, M. T., Oozeer, N., Passmoor, S. S., Patel, A. A., Peens-Hough, A., Perkins, S. J., Ramaila, A. J. T., Ratcliffe, S. M., Renil, R., Richter, L. L., Salie, S., Sambu, N., Schollar, C. T. G., Schwardt, L. C., Schwartz, R. L., Serylak, M., Siebrits, R., Sirothia, S. K., Slabber, M. J., Smirnov, O. M., Tiplady, A. J., van Balla, T. J., van der Byl, A., Van Tonder, V., Venter, A. J., Venter, M., Welz, M. G., and Williams, L. P.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

We present the SARAO MeerKAT Galactic Plane Survey (SMGPS), a 1.3 GHz continuum survey of almost half of the Galactic Plane (251\deg $\le l \le$ 358\deg and 2\deg $\le l \le$ 61\deg at $|b| \le 1.5\deg $). SMGPS is the largest, most sensitive and highest angular resolution 1 GHz survey of the Plane yet carried out, with an angular resolution of 8" and a broadband RMS sensitivity of $\sim$10--20 $\mu$ Jy/beam. Here we describe the first publicly available data release from SMGPS which comprises data cubes of frequency-resolved images over 908--1656 MHz, power law fits to the images, and broadband zeroth moment integrated intensity images. A thorough assessment of the data quality and guidance for future usage of the data products are given. Finally, we discuss the tremendous potential of SMGPS by showcasing highlights of the Galactic and extragalactic science that it permits. These highlights include the discovery of a new population of non-thermal radio filaments; identification of new candidate supernova remnants, pulsar wind nebulae and planetary nebulae; improved radio/mid-IR classification of rare Luminous Blue Variables and discovery of associated extended radio nebulae; new radio stars identified by Bayesian cross-matching techniques; the realisation that many of the largest radio-quiet WISE HII region candidates are not true HII regions; and a large sample of previously undiscovered background HI galaxies in the Zone of Avoidance., Comment: Accepted for publication in MNRAS. The data release is live and links can be found in the Data Availability Statement in the paper

Published
2023

7. Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes

Author

Keener, Rebecca, Chhetri, Surya B, Connelly, Carla J, Taub, Margaret A, Conomos, Matthew P, Weinstock, Joshua, Ni, Bohan, Strober, Benjamin, Aslibekyan, Stella, Auer, Paul L, Barwick, Lucas, Becker, Lewis C, Blangero, John, Bleecker, Eugene R, Brody, Jennifer A, Cade, Brian E, Celedon, Juan C, Chang, Yi-Cheng, Cupples, L Adrienne, Custer, Brian, Freedman, Barry I, Gladwin, Mark T, Heckbert, Susan R, Hou, Lifang, Irvin, Marguerite R, Isasi, Carmen R, Johnsen, Jill M, Kenny, Eimear E, Kooperberg, Charles, Minster, Ryan L, Naseri, Take, Viali, Satupa’itea, Nekhai, Sergei, Pankratz, Nathan, Peyser, Patricia A, Taylor, Kent D, Telen, Marilyn J, Wu, Baojun, Yanek, Lisa R, Yang, Ivana V, Albert, Christine, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Bis, Joshua C, Blackwell, Thomas W, Boerwinkle, Eric, Burchard, Esteban G, Carson, April P, Chen, Zhanghua, Chen, Yii-Der Ida, Darbar, Dawood, de Andrade, Mariza, Ellinor, Patrick T, Fornage, Myriam, Gelb, Bruce D, Gilliland, Frank D, He, Jiang, Islam, Talat, Kaab, Stefan, Kardia, Sharon LR, Kelly, Shannon, Konkle, Barbara A, Kumar, Rajesh, Loos, Ruth JF, Martinez, Fernando D, McGarvey, Stephen T, Meyers, Deborah A, Mitchell, Braxton D, Montgomery, Courtney G, North, Kari E, Palmer, Nicholette D, Peralta, Juan M, Raby, Benjamin A, Redline, Susan, Rich, Stephen S, Roden, Dan, Rotter, Jerome I, Ruczinski, Ingo, Schwartz, David, Sciurba, Frank, Shoemaker, M Benjamin, Silverman, Edwin K, Sinner, Moritz F, Smith, Nicholas L, Smith, Albert V, Tiwari, Hemant K, Vasan, Ramachandran S, Weiss, Scott T, Williams, L Keoki, Zhang, Yingze, Ziv, Elad, Raffield, Laura M, Reiner, Alexander P, Arvanitis, Marios, Greider, Carol W, Mathias, Rasika A, and Battle, Alexis

Subjects
Biological Sciences, Genetics, Human Genome, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Generic health relevance, Humans, Genome-Wide Association Study, Telomere, K562 Cells, Telomere Homeostasis, Polymorphism, Single Nucleotide, Gene Expression Regulation, CRISPR-Cas Systems, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed Structural Variation Working Group
Abstract

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

Published
2024

8. Directionality of nuclear recoils in a liquid argon time projection chamber

Author

Collaboration, The DarkSide-20k, Agnes, P., Ahmad, I., Albergo, S., Albuquerque, I. F. M., Alexander, T., Alton, A. K., Amaudruz, P., Corona, M. Atzori, Ave, M., Avetisov, I. Ch., Azzolini, O., Back, H. O., Balmforth, Z., Barrado-Olmedo, A., Barrillon, P., Basco, A., Batignani, G., Bocci, V., Bonivento, W. M., Bottino, B., Boulay, M. G., Busto, J., Cadeddu, M., Caminata, A., Canci, N., Cappello, G., Capra, A., Caprioli, S., Caravati, M., Cargioli, N., Carlini, M., Castello, P., Cataudella, V., Cavalcante, P., Cavuoti, S., Cebrian, S., Ruiz, J. M. Cela, Chashin, S., Chepurnov, A., Chyhyrynets, E., Cifarelli, L., Cintas, D., Citterio, M., Cleveland, B., Cocco, V., Vilda, E. Conde, Consiglio, L., Copello, S., Covone, G., Czubak, M., D'Aniello, M., D'Auria, S., Rolo, M. D. Da Rocha, Davini, S., de Candia, A., De Cecco, S., De Gruttola, D., De Filippis, G., Dell'Aquila, D., De Pasquale, S., De Rosa, G., Dellacasa, G., Derbin, A. V., Devoto, A., Di Capua, F., Di Noto, L., Dionisi, C., Di Stefano, P., Dolganov, G., Dordei, F., Elersich, A., Ellingwood, E., Erjavec, T., Diaz, M. Fernandez, Fiorillo, G., Franchini, P., Franco, D., Funicello, N., Gabriele, F., Gahan, D., Galbiati, C., Gallina, G., Gallus, G., Garbini, M., Abia, P. Garcia, Gendotti, A., Ghiano, C., Giganti, C., Giovanetti, G. K., Casanueva, V. Goicoechea, Gola, A., Grauso, G., di Cortona, G. Grilli, Grobov, A., Gromov, M., Guan, M., Guerzoni, M., Gulino, M., Guo, C., Hackett, B. R., Hallin, A. L., Hamer, A., Haranczyk, M., Hessel, T., Hill, S., Horikawa, S., Hubaut, F., Hucker, J., Hugues, T., Ianni, An., Ippolito, V., Jillings, C., Jois, S., Kachru, P., Kemmerich, N., Kemp, A. A., Kendziora, C. L., Kimura, M., Kochanek, I., Kondo, K., Korga, G., Koulosousas, S., Kubankin, A., Kuss, M., Kuzniak, M., La Commara, M., Lai, M., Guirriec, E. Le, Leason, E., Leoni, A., Li, X., Lidey, L., Lissia, M., Luzzi, L., Lychagina, O., Macfadyen, O., Machulin, I. N., Manecki, S., Manthos, I., Mapelli, L., Margotti, A., Marik, S. M., Mariani, C., Maricic, J., Marini, A., Martínez, M., Martoff, C. J., Matteucci, G., Mavrokoridis, K., McDonald, A. B., Messina, A., Milincic, R., Mitra, A., Moharana, A., Monroe, J., Moretti, E., Morrocchi, M., Mróz, T., Muratova, V. N., Muscas, C., Musico, P., Nania, R., Nessi, M., Nieradka, G., Nikolopoulos, K., Nowak, J., Olchansky, K., Oleinik, A., Oleynikov, V., Organtini, P., de Solórzano, A. Ortiz, Pagani, L., Pallavicini, M., Pandola, L., Pantic, E., Paoloni, E., Paternoster, G., Pegoraro, P. A., Pelczar, K., Pesudo, V., Piacentini, S., Pino, N., Pocar, A., Poehlmann, D. M., Pordes, S., Pralavorio, P., Price, D., Ragusa, F., Ramachers, Y., Razeti, M., Renshaw, A. L., Rescigno, M., Retiere, F., Rignanese, L. P., Ripoli, C., Rivetti, A., Roberts, A., Roberts, C., Rode, J., Rogers, G., Romero, L., Rossi, M., Rubbia, A., Sabia, M. A., Salomone, P., Sandford, E., Sanfilippo, S., Santone, D., Santorelli, R., Savarese, C., Scapparone, E., Schillaci, G., Schuckman II, F. G., Scioli, G., Simeone, M., Skensved, P., Skorokhvatov, M. D., Smirnov, O., Smirnova, T., Smith, B., Sosa, A., Spadoni, F., Spangenberg, M., Stefanizzi, R., Steri, A., Stornelli, V., Stracka, S., Stringer, M., Sulis, S., Sung, A., Suvorov, Y., Szelc, A. M., Tartaglia, R., Taylor, A., Taylor, J., Tedesco, S., Testera, G., Thieme, K., Thorpe, T. N., Tonazzo, A., Tricomi, A., Unzhakov, E. V., John, T. Vallivilayil, Van Uffelen, M., Viant, T., Viel, S., Vogelaar, R. B., Vossebeld, J., Wada, M., Walczak, M. B., Wang, H., Wang, Y., Westerdale, S., Williams, L., Wingerter-Seez, I., Wojaczynski, R., Wojcik, Ma. M., Wright, T., Xie, Y., Yang, C., Zabihi, A., Zakhary, P., Zani, A., Zichichi, A., Zuzel, G., and Zykova, M. P.

Subjects
Physics - Instrumentation and Detectors
Abstract

The direct search for dark matter in the form of weakly interacting massive particles (WIMP) is performed by detecting nuclear recoils (NR) produced in a target material from the WIMP elastic scattering. A promising experimental strategy for direct dark matter search employs argon dual-phase time projection chambers (TPC). One of the advantages of the TPC is the capability to detect both the scintillation and charge signals produced by NRs. Furthermore, the existence of a drift electric field in the TPC breaks the rotational symmetry: the angle between the drift field and the momentum of the recoiling nucleus can potentially affect the charge recombination probability in liquid argon and then the relative balance between the two signal channels. This fact could make the detector sensitive to the directionality of the WIMP-induced signal, enabling unmistakable annual and daily modulation signatures for future searches aiming for discovery. The Recoil Directionality (ReD) experiment was designed to probe for such directional sensitivity. The TPC of ReD was irradiated with neutrons at the INFN Laboratori Nazionali del Sud, and data were taken with 72 keV NRs of known recoil directions. The direction-dependent liquid argon charge recombination model by Cataudella et al. was adopted and a likelihood statistical analysis was performed, which gave no indications of significant dependence of the detector response to the recoil direction. The aspect ratio R of the initial ionization cloud is estimated to be 1.037 +/- 0.027 and the upper limit is R < 1.072 with 90% confidence level, Comment: 20 pages, 10 figures, submitted to Eur. Phys. J. C

Published
2023

10. MWAX: A New Correlator for the Murchison Widefield Array

Author

Morrison, I. S., Crosse, B., Sleap, G., Wayth, R. B., Williams, A., Johnston-Hollitt, M., Jones, J., Tingay, S. J., Walker, M., and Williams, L.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

We describe the design, validation, and commissioning of a new correlator termed "MWAX" for the Murchison Widefield Array (MWA) low-frequency radio telescope. MWAX replaces an earlier generation MWA correlator, extending correlation capabilities and providing greater flexibility, scalability, and maintainability. MWAX is designed to exploit current and future Phase II/III upgrades to MWA infrastructure, most notably the simultaneous correlation of all 256 of the MWA's antenna tiles (and potentially more in future). MWAX is a fully software-programmable correlator based around an ethernet multicast architecture. At its core is a cluster of 24 high-performance GPU-enabled commercial-off-the-shelf compute servers that together process in real-time up to 24 coarse channels of 1.28 MHz bandwidth each. The system is highly flexible and scalable in terms of the number of antenna tiles and number of coarse channels to be correlated, and it offers a wide range of frequency / time resolution combinations to users. We conclude with a roadmap of future enhancements and extensions that we anticipate will be progressively rolled out over time., Comment: Accepted for publication in PASA. 22 pages, 14 figures, 2 tables

Published
2023
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11. Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP).

Author

Li, Josephine, Perry, James, Jablonski, Kathleen, Srinivasan, Shylaja, Chen, Ling, Todd, Jennifer, Harden, Maegan, Mercader, Josep, Pan, Qing, Dawed, Adem, Yee, Sook Wah, Pearson, Ewan, Giacomini, Kathleen, Giri, Ayush, Hung, Adriana, Xiao, Shujie, Williams, L, Franks, Paul, Hanson, Robert, Kahn, Steven, Knowler, William, Pollin, Toni, and Florez, Jose

Subjects
Humans, Metformin, Diabetes Mellitus, Type 2, Genome-Wide Association Study, Prediabetic State, Genetic Variation, Polymorphism, Single Nucleotide
Abstract

Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 10-9). In the MET arm, rs144322333 near ENOSF1 (minor allele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, β = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10-12). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, β = -7.55 [95% CI -9.88, -5.22]; P = 3.2 × 10-10) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 10-4]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.

Published
2023

12. The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Author

Weinstock, Joshua S, Laurie, Cecelia A, Broome, Jai G, Taylor, Kent D, Guo, Xiuqing, Shuldiner, Alan R, O’Connell, Jeffrey R, Lewis, Joshua P, Boerwinkle, Eric, Barnes, Kathleen C, Chami, Nathalie, Kenny, Eimear E, Loos, Ruth JF, Fornage, Myriam, Redline, Susan, Cade, Brian E, Gilliland, Frank D, Chen, Zhanghua, Gauderman, W James, Kumar, Rajesh, Grammer, Leslie, Schleimer, Robert P, Psaty, Bruce M, Bis, Joshua C, Brody, Jennifer A, Silverman, Edwin K, Yun, Jeong H, Qiao, Dandi, Weiss, Scott T, Lasky-Su, Jessica, DeMeo, Dawn L, Palmer, Nicholette D, Freedman, Barry I, Bowden, Donald W, Cho, Michael H, Vasan, Ramachandran S, Johnson, Andrew D, Yanek, Lisa R, Becker, Lewis C, Kardia, Sharon, He, Jiang, Kaplan, Robert, Heckbert, Susan R, Smith, Nicholas L, Wiggins, Kerri L, Arnett, Donna K, Irvin, Marguerite R, Tiwari, Hemant, Correa, Adolfo, Raffield, Laura M, Gao, Yan, de Andrade, Mariza, Rotter, Jerome I, Rich, Stephen S, Manichaikul, Ani W, Konkle, Barbara A, Johnsen, Jill M, Wheeler, Marsha M, Custer, Brian S, Duggirala, Ravindranath, Curran, Joanne E, Blangero, John, Gui, Hongsheng, Xiao, Shujie, Williams, L Keoki, Meyers, Deborah A, Li, Xingnan, Ortega, Victor, McGarvey, Stephen, Gu, C Charles, Chen, Yii-Der Ida, Lee, Wen-Jane, Shoemaker, M Benjamin, Darbar, Dawood, Roden, Dan, Albert, Christine, Kooperberg, Charles, Desai, Pinkal, Blackwell, Thomas W, Abecasis, Goncalo R, Smith, Albert V, Kang, Hyun M, Mathias, Rasika, Natarajan, Pradeep, Jaiswal, Siddhartha, Reiner, Alexander P, Bick, Alexander G, and Consortium, NHLBI Trans-Omics for Precision Medicine

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Lung, Genetic Testing, Clinical Research, Biotechnology, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Humans, Middle Aged, Hematopoiesis, Mutation, Germ-Line Mutation, Mutation, Missense, Phenotype, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Abstract

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.

Published
2023

13. Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.

Author

Weinstock, Joshua, Gopakumar, Jayakrishnan, Burugula, Bala, Uddin, Md, Jahn, Nikolaus, Belk, Julia, Bouzid, Hind, Daniel, Bence, Miao, Zhuang, Ly, Nghi, Mack, Taralynn, Luna, Sofia, Prothro, Katherine, Mitchell, Shaneice, Laurie, Cecelia, Broome, Jai, Taylor, Kent, Guo, Xiuqing, Sinner, Moritz, von Falkenhausen, Aenne, Kääb, Stefan, Shuldiner, Alan, OConnell, Jeffrey, Lewis, Joshua, Boerwinkle, Eric, Barnes, Kathleen, Chami, Nathalie, Kenny, Eimear, Loos, Ruth, Fornage, Myriam, Hou, Lifang, Lloyd-Jones, Donald, Redline, Susan, Cade, Brian, Psaty, Bruce, Bis, Joshua, Brody, Jennifer, Silverman, Edwin, Yun, Jeong, Qiao, Dandi, Palmer, Nicholette, Freedman, Barry, Bowden, Donald, Cho, Michael, DeMeo, Dawn, Vasan, Ramachandran, Yanek, Lisa, Becker, Lewis, Kardia, Sharon, Peyser, Patricia, He, Jiang, Rienstra, Michiel, Van der Harst, Pim, Kaplan, Robert, Heckbert, Susan, Smith, Nicholas, Wiggins, Kerri, Arnett, Donna, Irvin, Marguerite, Tiwari, Hemant, Cutler, Michael, Knight, Stacey, Muhlestein, J, Correa, Adolfo, Raffield, Laura, Gao, Yan, de Andrade, Mariza, Rotter, Jerome, Rich, Stephen, Tracy, Russell, Konkle, Barbara, Johnsen, Jill, Wheeler, Marsha, Smith, J, Melander, Olle, Nilsson, Peter, Custer, Brian, Duggirala, Ravindranath, Curran, Joanne, Blangero, John, McGarvey, Stephen, Williams, L, Xiao, Shujie, Yang, Mao, Gu, C, Chen, Yii-Der, Lee, Wen-Jane, Kane, John, Pullinger, Clive, Shoemaker, M, Darbar, Dawood, Roden, Dan, Albert, Christine, Kooperberg, Charles, Zhou, Ying, Manson, JoAnn, Desai, Pinkal, Johnson, Andrew, Mathias, Rasika, and Blackwell, Thomas

Subjects
Animals, Humans, Mice, Alleles, Clonal Hematopoiesis, Genome-Wide Association Study, Hematopoiesis, Hematopoietic Stem Cells, Mutation, Promoter Regions, Genetic
Abstract

Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, but this effect was not seen in clones with driver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimental knockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.

Published
2023

14. Strong Lensing by Galaxies

Author

Shajib, A. J., Vernardos, G., Collett, T. E., Motta, V., Sluse, D., Williams, L. L. R., Saha, P., Birrer, S., Spiniello, C., and Treu, T.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

Strong gravitational lensing at the galaxy scale is a valuable tool for various applications in astrophysics and cosmology. The primary uses of galaxy-scale lensing are to study elliptical galaxies' mass structure and evolution, constrain the stellar initial mass function, and measure cosmological parameters. Since the discovery of the first galaxy-scale lens in the 1980s, this field has made significant advancements in data quality and modeling techniques. In this review, we describe the most common methods for modeling lensing observables, especially imaging data, as they are the most accessible and informative source of lensing observables. We then summarize the primary findings from the literature on the astrophysical and cosmological applications of galaxy-scale lenses. We also discuss the current limitations of the data and methodologies and provide an outlook on the expected improvements in both areas in the near future., Comment: Submitted to Space Science Reviews, Topical Collection "Strong Gravitational Lensing", eds. J. Wambsganss et al. This version: updated after peer review

Published
2022

15. Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel

Author

Agnes, P., Ahmad, I., Albergo, S., Albuquerque, I. F. M., Alexander, T., Alton, A. K., Amaudruz, P., Corona, M. Atzori, Auty, D. J., Ave, M., Avetisov, I. Ch., Avetisov, R. I., Azzolini, O., Back, H. O., Balmforth, Z., Barbarian, V., Olmedo, A. Barrado, Barrillon, P., Basco, A., Batignani, G., Berzin, E., Bondar, A., Bonivento, W. M., Borisova, E., Bottino, B., Boulay, M. G., Buccino, G., Bussino, S., Busto, J., Buzulutskov, A., Cadeddu, M., Cadoni, M., Caminata, A., Canci, N., Capra, A., Caprioli, S., Caravati, M., Cárdenas-Montes, M., Cargioli, N., Carlini, M., Castello, P., Cataudella, V., Cavalcante, P., Cavuoti, S., Cebrian, S., Ruiz, J. M. Cela, Chashin, S., Chepurnov, A., Chyhyrynets, E, Cicalò, C., Cifarelli, L., Cintas, D., Cocco, V., Vilda, E. Conde, Consiglio, L., Copello, S., Covone, G., Cross, S., Czudak, P., D'Aniello, M., D'Auria, S., Rolo, M. D. Da Rocha, Dadoun, O., Daniel, M., Davini, S., De Candia, A., De Cecco, S., De Falco, A., De Filippis, G., De Gruttola, D., De Pasquale, S., De Rosa, G., Dellacasa, G., Derbin, A. V., Devoto, A., Di Capua, F., Di Noto, L., Di Stefano, P., Dionisi, C., Dolganov, G., Dordei, F., Doria, L., Erjavec, T., Diaz, M. Fernandez, Fiorillo, G., Franceschi, A., Franchini, P., Franco, D., Frolov, E., Funicello, N., Gabriele, F., Gahan, D., Galbiati, C., Gallina, G., Gallus, G., Garbini, M., Abia, P. Garcia, Gendotti, A., Ghiano, C., Giampaolo, R. A., Giganti, C., Giorgi, M. A., Giovanetti, G. K., Casanueva, V. Goicoechea, Gola, A., Gorman, D., Diaz, R. Graciani, Grauso, G., di Cortona, G. Grilli, Grobov, A., Gromov, M., Guan, M., Guerzoni, M., Gulino, M., Guo, C., Hackett, B. R., Hall, J. B., Hallin, A. L., Hamer, A., Helton, H., Haranczyk, M., Hessel, T., Hill, S., Horikawa, S., Hubaut, F., Hugues, T., Hungerford, E. V., Ianni, An., Ippolito, V., Jillings, C., Kachru, P., Kemp, A. A., Kendziora, C. L., Keppel, G., Khomyakov, A. V., Kimura, M., Kochanek, I., Kondo, K., Korga, G., Koulosousas, S., Kubankin, A., Kuss, M., Kuźniak, M., La Commara, M., Lai, M., Guirriec, E. Le, Leason, E., Li, X., Lidey, L., Lipp, J., Lissia, M., Longo, G., Luzzi, L., Macfadyen, O., Machulin, I. N., Manthos, I., Mapelli, L., Margotti, A., Mari, S. M., Mariani, C., Maricic, J., Marini, A., Martínez, M., Martoff, C. J., Masoni, A., Mavrokoridis, K., Mazzi, A., McDonald, A. B., Messina, A., Milincic, R., Moggi, A., Moharana, A., Monroe, J., Morrocchi, M., Mozhevitina, E. N., Mróz, T., Muratova, V. N., Muscas, C., Musico, P., Nania, R., Napolitano, T., Nessi, M., Nieradka, G., Nikolopoulos, K., Nikulin, I., Nowak, J., Olchansky, K., Oleinik, A., Oleynikov, V., Organtini, P., de Solórzano, A. Ortiz, Pagani, L., Pallavicini, M., Pandola, L., Pantic, E., Paoloni, E., Paternoster, G., Pegoraro, P. A., Pelczar, K., Pellegrino, C., Perotti, F., Pesudo, V., Piacentini, S., Pietropaolo, F., Pino, N., Pira, C., Pocar, A., Poehlmann, D. M., Pordes, S., Pralavorio, P., Price, D., Raffaelli, F., Ragusa, F., Ramachers, Y., Ramirez, A., Razeti, M., Razeto, A., Renshaw, A. L., Rescigno, M., Resnati, F., Retiere, F., Rignanese, L. P., Ripoli, C., Rivetti, A., Roberts, A., Roberts, C., Rode, J., Rogers, G., Romero, L., Rossi, M., Rubbia, A., Sadashivajois, S., Saffold, T. R., Samoylov, O., Sandford, E., Sanfilippo, S., Santone, D., Santorelli, R., Savarese, C., Scapparone, E., Scioli, G., Semenov, D. A., Shchagin, A., Sheshukov, A., Simeone, M., Skensved, P., Skorokhvatov, M. D., Smirnov, O., Smirnova, T., Smith, B., Sokolov, A., Spangenberg, M., Stefanizzi, R., Steri, A., Stracka, S., Strickland, V., Stringer, M., Sulis, S., Sung, A., Suvorov, Y., Szelc, A. M., Türkoğ, C., Tartaglia, R., Taylor, A., Taylor, J., Tedesco, S., Testera, G., Thieme, K., Thorpe, T. N., Tonazzo, A., Torres-Lara, S., Tricomi, A., Unzhakov, E. V., John, T. Vallivilayil, Van Uffelen, M., Viant, T., Viel, S., Vishneva, A., Vogelaar, R. B., Vossebeld, J., Wada, M., Walczak, M. B., Wang, Y., Westerdale, S., Wheadon, R. J., Williams, L., Wingerter-Seez, I., Wojaczyński, R., Wojcik, Ma. M., Wojcik, Ma., Wright, T., Xie, Y., Yang, C., Zabihi, A., Zakhary, P., Zani, A., Zichichi, A., Zuzel, G., and Zykova, M. P.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

Dark matter lighter than 10 GeV/c$^2$ encompasses a promising range of candidates. A conceptual design for a new detector, DarkSide-LowMass, is presented, based on the DarkSide-50 detector and progress toward DarkSide-20k, optimized for a low-threshold electron-counting measurement. Sensitivity to light dark matter is explored for various potential energy thresholds and background rates. These studies show that DarkSide-LowMass can achieve sensitivity to light dark matter down to the solar neutrino floor for GeV-scale masses and significant sensitivity down to 10 MeV/c$^2$ considering the Migdal effect or interactions with electrons. Requirements for optimizing the detector's sensitivity are explored, as are potential sensitivity gains from modeling and mitigating spurious electron backgrounds that may dominate the signal at the lowest energies.

Published
2022
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16. The 1.28 GHz MeerKAT Galactic Center Mosaic

Author

Heywood, I., Rammala, I., Camilo, F., Cotton, W. D., Yusef-Zadeh, F., Abbott, T. D., Adam, R. M., Adams, G., Aldera, M. A., Asad, K. M. B., Bauermeister, E. F., Bennett, T. G. H., Bester, H. L., Bode, W. A., Botha, D. H., Botha, A. G., Brederode, L. R. S., Buchner, S., Burger, J. P., Cheetham, T., de Villiers, D. I. L., Dikgale-Mahlakoana, M. A., Toit, L. J. du, Esterhuyse, S. W. P., Fanaroff, B. L., February, S., Fourie, D. J., Frank, B. S., Gamatham, R. R. G., Geyer, M., Goedhart, S., Gouws, M., Gumede, S. C., Hlakola, M. J., Hokwana, A., Hoosen, S. W., Horrell, J. M. G., Hugo, B., Isaacson, A. I., Józsa, G. I. G., Jonas, J. L., Joubert, A. F., Julie, R. P. M., Kapp, F. B., Kenyon, J. S., Kotzé, P. P. A., Kriek, N., Kriel, H., Krishnan, V. K., Lehmensiek, R., Liebenberg, D., Lord, R. T., Lunsky, B. M., Madisa, K., Magnus, L. G., Mahgoub, O., Makhaba, A., Makhathini, S., Malan, J. A., Manley, J. R., Marais, S. J., Martens, A., Mauch, T., Merry, B. C., Millenaar, R. P., Mnyandu, N., Mokone, O. J., Monama, T. E., Mphego, M. C., New, W. S., Ngcebetsha, B., Ngoasheng, K. J., Ockards, M. T., Oozeer, N., Otto, A. J., Passmoor, S. S., Patel, A. A., Peens-Hough, A., Perkins, S. J., Ramaila, A. J. T., Ramanujam, N. M. R., Ramudzuli, Z. R., Ratcliffe, S. M., Robyntjies, A., Salie, S., Sambu, N., Schollar, C. T. G., Schwardt, L. C., Schwartz, R. L., Serylak, M., Siebrits, R., Sirothia, S. K., Slabber, M., Smirnov, O. M., Sofeya, L., Taljaard, B., Tasse, C., Tiplady, A. J., Toruvanda, O., Twum, S. N., van Balla, T. J., van der Byl, A., van der Merwe, C., Van Tonder, V., Van Wyk, R., Venter, A. J., Venter, M., Wallace, B. H., Welz, M. G., Williams, L. P., and Xaia, B.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The inner $\sim$200 pc region of the Galaxy contains a 4 million M$_{\odot}$ supermassive black hole (SMBH), significant quantities of molecular gas, and star formation and cosmic ray energy densities that are roughly two orders of magnitude higher than the corresponding levels in the Galactic disk. At a distance of only 8.2 kpc, the region presents astronomers with a unique opportunity to study a diverse range of energetic astrophysical phenomena, from stellar objects in extreme environments, to the SMBH and star-formation driven feedback processes that are known to influence the evolution of galaxies as a whole. We present a new survey of the Galactic center conducted with the South African MeerKAT radio telescope. Radio imaging offers a view that is unaffected by the large quantities of dust that obscure the region at other wavelengths, and a scene of striking complexity is revealed. We produce total intensity and spectral index mosaics of the region from 20 pointings (144 hours on-target in total), covering 6.5 square degrees with an angular resolution of 4$"$,at a central frequency of 1.28 GHz. Many new features are revealed for the first time due to a combination of MeerKAT's high sensitivity, exceptional $u,v$-plane coverage, and geographical vantage point. We highlight some initial survey results, including new supernova remnant candidates, many new non-thermal filament complexes, and enhanced views of the Radio Arc Bubble, Sgr A and Sgr B regions. This project is a SARAO public legacy survey, and the image products are made available with this article., Comment: 29 pages, 15 figures, 3 tables, accepted for publication in the The Astrophysical Journal. Replacement arXiv version with higher quality figures

Published
2022
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17. The MeerKAT Galaxy Cluster Legacy Survey I. Survey Overview and Highlights

Author

Knowles, K., Cotton, W. D., Rudnick, L., Camilo, F., Goedhart, S., Deane, R., Ramatsoku, M., Bietenholz, M. F., Brüggen, M., Button, C., Chen, H., Chibueze, J. O., Clarke, T. E., de Gasperin, F., Ianjamasimanana, R., Józsa, G. I. G., Hilton, M., Kesebonye, K. C., Kolokythas, K., Kraan-Korteweg, R. C., Lawrie, G., Lochner, M., Loubser, S. I., Marchegiani, P., Mhlahlo, N., Moodley, K., Murphy, E., Namumba, B., Oozeer, N., Parekh, V., Pillay, D. S., Passmoor, S. S., Ramaila, A. J. T., Ranchod, S., Retana-Montenegro, E., Sebokolodi, L., Sikhosana, S. P., Smirnov, O., Thorat, K., Venturi, T., Abbott, T. D., Adam, R. M., Adams, G., Aldera, M. A., Bauermeister, E. F., Bennett, T. G. H., Bode, W. A., Botha, D. H., Botha, A. G., Brederode, L. R. S., Buchner, S., Burger, J. P., Cheetham, T., de Villiers, D. I. L., Dikgale-Mahlakoana, M. A., Toit, L. J. du, Esterhuyse, S. W. P., Fadana, G., Fanaroff, B. L., Fataar, S., Foley, A. R., Fourie, D. J., Frank, B. S., Gamatham, R. R. G., Gatsi, T. G., Geyer, M., Gouws, M., Gumede, S. C., Heywood, I., Hlakola, M. J., Hokwana, A., Hoosen, S. W., Horn, D. M., Horrell, J. M. G., Hugo, B. V., Isaacson, A. R., Jonas, J. L., Jordaan, J. D. B., Joubert, A. F., Julie, R. P. M., Kapp, F. B., Kasper, V. A., Kenyon, J. S., Kotzé, P. P. A., Kotze, A. G., Kriek, N., Kriel, H., Krishnan, V. K., Kusel, T. W., Legodi, L. S., Lehmensiek, R., Liebenberg, D., Lord, R. T., Lunsky, B. M., Madisa, K., Magnus, L. G., Main, J. P. L., Makhaba, A., Makhathini, S., Malan, J. A., Manley, J. R., Marais, S. J., Maree, M. D. J., Martens, A., Mauch, T., McAlpine, K., Merry, B. C., Millenaar, R. P., Mokone, O. J., Monama, T. E., Mphego, M. C., New, W. S., Ngcebetsha, B., Ngoasheng, K. J., Ockards, M. T., Otto, A. J., Patel, A. A., Peens-Hough, A., Perkins, S. J., Ramanujam, N. M., Ramudzuli, Z. R., Ratcliffe, S. M., Renil, R., Robyntjies, A., Rust, A. N., Salie, S., Sambu, N., Schollar, C. T. G., Schwardt, L. C., Schwartz, R. L., Serylak, M., Siebrits, R., Sirothia, S. K., Slabber, M., Sofeya, L., Taljaard, B., Tasse, C., Tiplady, A. J., Toruvanda, O., Twum, S. N., van Balla, T. J., van der Byl, A., van der Merwe, C., van Dyk, C. L., Van Tonder, V., Van Wyk, R., Venter, A. J., Venter, M., Welz, M. G., Williams, L. P., and Xaia, B.

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

MeerKAT's large number of antennas, spanning 8 km with a densely packed 1 km core, create a powerful instrument for wide-area surveys, with high sensitivity over a wide range of angular scales. The MeerKAT Galaxy Cluster Legacy Survey (MGCLS) is a programme of long-track MeerKAT L-band (900-1670 MHz) observations of 115 galaxy clusters, observed for $\sim$6-10 hours each in full polarisation. The first legacy product data release (DR1), made available with this paper, includes the MeerKAT visibilities, basic image cubes at $\sim$8" resolution, and enhanced spectral and polarisation image cubes at $\sim$8" and 15" resolutions. Typical sensitivities for the full-resolution MGCLS image products are $\sim$3-5 {\mu}Jy/beam. The basic cubes are full-field and span 4 deg^2. The enhanced products consist of the inner 1.44 deg^2 field of view, corrected for the primary beam. The survey is fully sensitive to structures up to $\sim$10' scales and the wide bandwidth allows spectral and Faraday rotation mapping. HI mapping at 209 kHz resolution can be done at $0

Published
2021
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18. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Author

Budu-Aggrey, Ashley, Kilanowski, Anna, Sobczyk, Maria K., Shringarpure, Suyash S., Mitchell, Ruth, Reis, Kadri, Reigo, Anu, Mägi, Reedik, Nelis, Mari, Tanaka, Nao, Brumpton, Ben M., Thomas, Laurent F., Sole-Navais, Pol, Flatley, Christopher, Espuela-Ortiz, Antonio, Herrera-Luis, Esther, Lominchar, Jesus V. T., Bork-Jensen, Jette, Marenholz, Ingo, Arnau-Soler, Aleix, Jeong, Ayoung, Fawcett, Katherine A., Baurecht, Hansjorg, Rodriguez, Elke, Alves, Alexessander Couto, Kumar, Ashish, Sleiman, Patrick M., Chang, Xiao, Medina-Gomez, Carolina, Hu, Chen, Xu, Cheng-jian, Qi, Cancan, El-Heis, Sarah, Titcombe, Philip, Antoun, Elie, Fadista, João, Wang, Carol A., Thiering, Elisabeth, Wu, Baojun, Kress, Sara, Kothalawala, Dilini M., Kadalayil, Latha, Duan, Jiasong, Zhang, Hongmei, Hadebe, Sabelo, Hoffmann, Thomas, Jorgenson, Eric, Choquet, Hélène, Risch, Neil, Njølstad, Pål, Andreassen, Ole A., Johansson, Stefan, Almqvist, Catarina, Gong, Tong, Ullemar, Vilhelmina, Karlsson, Robert, Magnusson, Patrik K. E., Szwajda, Agnieszka, Burchard, Esteban G., Thyssen, Jacob P., Hansen, Torben, Kårhus, Line L., Dantoft, Thomas M., Jeanrenaud, Alexander C.S.N., Ghauri, Ahla, Arnold, Andreas, Homuth, Georg, Lau, Susanne, Nöthen, Markus M., Hübner, Norbert, Imboden, Medea, Visconti, Alessia, Falchi, Mario, Bataille, Veronique, Hysi, Pirro, Ballardini, Natalia, Boomsma, Dorret I., Hottenga, Jouke J., Müller-Nurasyid, Martina, Ahluwalia, Tarunveer S., Stokholm, Jakob, Chawes, Bo, Schoos, Ann-Marie M., Esplugues, Ana, Bustamante, Mariona, Raby, Benjamin, Arshad, Syed, German, Chris, Esko, Tõnu, Milani, Lili A., Metspalu, Andres, Terao, Chikashi, Abuabara, Katrina, Løset, Mari, Hveem, Kristian, Jacobsson, Bo, Pino-Yanes, Maria, Strachan, David P., Grarup, Niels, Linneberg, Allan, Lee, Young-Ae, Probst-Hensch, Nicole, Weidinger, Stephan, Jarvelin, Marjo-Riitta, Melén, Erik, Hakonarson, Hakon, Irvine, Alan D., Jarvis, Deborah, Nijsten, Tamar, Duijts, Liesbeth, Vonk, Judith M., Koppelmann, Gerard H., Godfrey, Keith M., Barton, Sheila J., Feenstra, Bjarke, Pennell, Craig E., Sly, Peter D., Holt, Patrick G., Williams, L. Keoki, Bisgaard, Hans, Bønnelykke, Klaus, Curtin, John, Simpson, Angela, Murray, Clare, Schikowski, Tamara, Bunyavanich, Supinda, Weiss, Scott T., Holloway, John W., Min, Josine L., Brown, Sara J., Standl, Marie, and Paternoster, Lavinia

Published
2023
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19. A new class of monopole solutions in five-dimensional general relativity and the role of negative scalar field energy in vacuum solutions

Author

Balytskyi, Y., Hoyer, D., Pinchuk, A. O., and Williams, L. L.

Subjects
General Relativity and Quantum Cosmology
Abstract

Using numerical algebra tools, new classes of monopole solutions are obtained to the static, spherically-symmetric vacuum field equations of five-dimensional general relativity. First proposed by Kaluza, 5D general relativity unites gravity and classical electromagnetism with a scalar field. These monopoles correspond to bodies carrying mass, electric charge, and scalar charge. The Reissner-Nordstr\"om limit allows us to constrain the signature of the fifth component to be spacelike, but valid solutions are obtained for either sign of the scalar field. We find that Kaluza vacuum solutions imply the scalar field energy density is the negative of the electric field energy density, so the total electric and scalar field energy of the monopole is zero. Yet the new solutions provide reasonable Reissner-Nordstr\"om and Coulomb limits in mathematical form, with varying possibilities for the scalar field. The vanishing of the total electric and scalar field energy density for vacuum solutions seems to imply the scalar field can be understood as a negative-energy foundation on which the electric field is built., Comment: 12 pages, 1 table, no figures

Published
2021

20. Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Author

Taub, Margaret A, Conomos, Matthew P, Keener, Rebecca, Iyer, Kruthika R, Weinstock, Joshua S, Yanek, Lisa R, Lane, John, Miller-Fleming, Tyne W, Brody, Jennifer A, Raffield, Laura M, McHugh, Caitlin P, Jain, Deepti, Gogarten, Stephanie M, Laurie, Cecelia A, Keramati, Ali, Arvanitis, Marios, Smith, Albert V, Heavner, Benjamin, Barwick, Lucas, Becker, Lewis C, Bis, Joshua C, Blangero, John, Bleecker, Eugene R, Burchard, Esteban G, Celedón, Juan C, Chang, Yen Pei C, Custer, Brian, Darbar, Dawood, de las Fuentes, Lisa, DeMeo, Dawn L, Freedman, Barry I, Garrett, Melanie E, Gladwin, Mark T, Heckbert, Susan R, Hidalgo, Bertha A, Irvin, Marguerite R, Islam, Talat, Johnson, W Craig, Kaab, Stefan, Launer, Lenore, Lee, Jiwon, Liu, Simin, Moscati, Arden, North, Kari E, Peyser, Patricia A, Rafaels, Nicholas, Seidman, Christine, Weeks, Daniel E, Wen, Fayun, Wheeler, Marsha M, Williams, L Keoki, Yang, Ivana V, Zhao, Wei, Aslibekyan, Stella, Auer, Paul L, Bowden, Donald W, Cade, Brian E, Chen, Zhanghua, Cho, Michael H, Cupples, L Adrienne, Curran, Joanne E, Daya, Michelle, Deka, Ranjan, Eng, Celeste, Fingerlin, Tasha E, Guo, Xiuqing, Hou, Lifang, Hwang, Shih-Jen, Johnsen, Jill M, Kenny, Eimear E, Levin, Albert M, Liu, Chunyu, Minster, Ryan L, Naseri, Take, Nouraie, Mehdi, Reupena, Muagututi A Sefuiva, Sabino, Ester C, Smith, Jennifer A, Smith, Nicholas L, Lasky-Su, Jessica, Taylor, James G, Telen, Marilyn J, Tiwari, Hemant K, Tracy, Russell P, White, Marquitta J, Zhang, Yingze, Wiggins, Kerri L, Weiss, Scott T, Vasan, Ramachandran S, Taylor, Kent D, Sinner, Moritz F, Silverman, Edwin K, Shoemaker, M Benjamin, Sheu, Wayne H-H, Sciurba, Frank, Schwartz, David A, Rotter, Jerome I, Roden, Daniel, Redline, Susan, and Raby, Benjamin A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Good Health and Well Being, NHLBI CARE Network, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed Structural Variation Working Group
Abstract

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value

Published
2022

21. Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness

Author

Joo, Jaehyun, Mak, Angel CY, Xiao, Shujie, Sleiman, Patrick M, Hu, Donglei, Huntsman, Scott, Eng, Celeste, Kan, Mengyuan, Diwakar, Avantika R, Lasky-Su, Jessica A, Weiss, Scott T, Sordillo, Joanne E, Wu, Ann C, Cloutier, Michelle, Canino, Glorisa, Forno, Erick, Celedón, Juan C, Seibold, Max A, Hakonarson, Hakon, Williams, L Keoki, Burchard, Esteban G, and Himes, Blanca E

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Pharmacology and Pharmaceutical Sciences, Minority Health, Health Disparities, Precision Medicine, Pediatric, Prevention, Asthma, Human Genome, Lung, Clinical Research, Biotechnology, 2.1 Biological and endogenous factors, Respiratory, Good Health and Well Being, Axonemal Dyneins, Bronchodilator Agents, Child, Ethnicity, Genome-Wide Association Study, Hispanic or Latino, Humans, Mexican Americans, Minority Groups, Polymorphism, Single Nucleotide
Abstract

Variability in response to short-acting β2-agonists (e.g., albuterol) among patients with asthma from diverse racial/ethnic groups may contribute to asthma disparities. We sought to identify genetic variants associated with bronchodilator response (BDR) to identify potential mechanisms of drug response and risk factors for worse asthma outcomes. Genome-wide association studies of bronchodilator response (BDR) were performed using TOPMed Whole Genome Sequencing data of the Asthma Translational Genomic Collaboration (ATGC), which corresponded to 1136 Puerto Rican, 656 Mexican and 4337 African American patients with asthma. With the population-specific GWAS results, a trans-ethnic meta-analysis was performed to identify BDR-associated variants shared across the three populations. Replication analysis was carried out in three pediatric asthma cohorts, including CAMP (Childhood Asthma Management Program; n = 560), GACRS (Genetics of Asthma in Costa Rica Study; n = 967) and HPR (Hartford-Puerto Rico; n = 417). A genome-wide significant locus (rs35661809; P = 3.61 × 10-8) in LINC02220, a non-coding RNA gene, was identified in Puerto Ricans. While this region was devoid of protein-coding genes, capture Hi-C data showed a distal interaction with the promoter of the DNAH5 gene in lung tissue. In replication analysis, the GACRS cohort yielded a nominal association (1-tailed P

Published
2022

22. Inductive rectilinear frame dragging and local coupling to the gravitational field of the universe

Author

Williams, L. L. and Inan, N.

Subjects
General Relativity and Quantum Cosmology
Abstract

There is a drag force on objects moving in the background cosmological metric, known from galaxy cluster dynamics. The force is quite small over laboratory timescales, yet it applies in principle to all moving bodies in the universe. It means it is possible for matter to exchange momentum and energy with the gravitational field of the universe, and that the cosmological metric can be determined in principle from local measurements on moving bodies. The drag force can be understood as inductive rectilinear frame dragging. This dragging force exists in the rest frame of a moving object, and arises from the off-diagonal components induced in the boosted-frame metric. Unlike the Kerr metric or other typical frame-dragging geometries, cosmological inductive dragging occurs at uniform velocity, along the direction of motion, and dissipates energy. Proposed gravito-magnetic invariants formed from contractions of the Riemann tensor do not appear to capture inductive dragging effects, and this might be the first identification of inductive rectilinear dragging., Comment: 13 pages, 1 figure

Published
2021
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23. Exotic Image Formation in Strong Gravitational Lensing by Clusters of Galaxies -- II: Uncertainties

Author

Meena, Ashish Kumar, Ghosh, Agniva, Bagla, J. S., and Williams, L. L. R.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

Due to the finite amount of observational data, the best-fit parameters corresponding to the reconstructed cluster mass have uncertainties. In turn, these uncertainties affect the inferences made from these mass models. Following our earlier work, we have studied the effect of such uncertainties on the singularity maps in simulated and actual galaxy clusters. The mass models for both simulated and real clusters have been constructed using grale. The final best-fit mass models created using grale give the simplest singularity maps and a lower limit on the number of point singularities that a lens has to offer. The simple nature of these singularity maps also puts a lower limit on the number of three image (tangential and radial) arcs that a cluster lens has. Hence, we estimate the number of galaxy sources giving rise to the three image arcs, which can be observed with the James Webb Space Telescope (JWST). We find that we expect to observe at least 20-30 tangential and 5-10 radial three-image arcs in the Hubble Frontier Fields cluster lenses with the JWST., Comment: 15 pages, 7 figures. Accepted in MNRAS

Published
2021
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25. Null-result test for effect on weight from large electrostatic charge

Author

Hathaway, G. and Williams, L. L.

Subjects
General Relativity and Quantum Cosmology, Physics - Classical Physics
Abstract

We report test results searching for an effect of electrostatic charge on weight. For conducting test objects of mass of order 1 kilogram, we found no effect on weight, for potentials ranging from 10 V to 200 kV, corresponding to charge states ranging from $10^{-9}$ to over $10^{-5}$ coulombs, and for both polarities, to within a measurement precision of 2 grams. While such a result may not be unexpected, this is the first unipolar, high-voltage, meter-scale, static test for electro-gravitic effects reported in the literature. Our investigation was motivated by the search for possible coupling to a long-range scalar field that could surround the planet, yet go otherwise undetected. The large buoyancy force predicted within the classical Kaluza theory involving a long-range scalar field is falsified by our results, and this appears to be the first such experimental test of the classical Kaluza theory in the weak field regime where it was otherwise thought identical with known physics. A parameterization is suggested to organize the variety of electro-gravitic experiment designs.

Published
2021

26. Separating $^{39}$Ar from $^{40}$Ar by cryogenic distillation with Aria for dark matter searches

Author

DarkSide Collaboration, Agnes, P., Albergo, S., Albuquerque, I. F. M., Alexander, T., Alici, A., Alton, A. K., Amaudruz, P., Arba, M., Arpaia, P., Arcelli, S., Ave, M., Avetissov, I. Ch., Avetisov, R. I., Azzolini, O., Back, H. O., Balmforth, Z., Barbarian, V., Olmedo, A. Barrado, Barrillon, P., Basco, A., Batignani, G., Bondar, A., Bonivento, W. M., Borisova, E., Bottino, B., Boulay, M. G., Buccino, G., Bussino, S., Busto, J., Buzulutskov, A., Cadeddu, M., Cadoni, M., Caminata, A., Canesi, E. V., Canci, N., Cappello, G., Caravati, M., C, M., Cargioli, N., Carlini, M., Carnesecchi, F., Castello, P., Castellani, A., Catalanotti, S., Cataudella, V., Cavalcante, P., Cavuoti, S., Cebrian, S., Ruiz, J. M. Cela, Celano, B., Chashin, S., Chepurnov, A., Cical, C., Cifarelli, L., Cintas, D., Coccetti, F., Cocco, V., Colocci, M., Vilda, E. Conde, Consiglio, L., Copello, S., Corning, J., Covone, G., Czudak, P., D'Aniello, M., D'Auria, S., Rolo, M. D. Da Rocha, Dadoun, O., Daniel, M., Davini, S., De Candia, A., De Cecco, S., De Falco, A., De Filippis, G., De Gruttola, D., De Guido, G., De Rosa, G., Della Valle, M., Dellacasa, G., De Pasquale, S., Derbin, A. V., Devoto, A., Di Noto, L., Di Eusanio, F., Dionisi, C., Di Stefano, P., Dolganov, G., Dongiovanni, D., Dordei, F., Downing, M., Erjavec, T., Falciano, S., Farenzena, S., Diaz, M. Fernandez, Filip, C., Fiorillo, G., Franceschi, A., Franco, D., Frolov, E., Funicello, N., Gabriele, F., Galbiati, C., Garbini, M., Abia, P. Garcia, Gendotti, A., Ghiano, C., Giampaolo, R. A., Giganti, C., Giorgi, M. A., Giovanetti, G. K., Gligan, M. L., Casanueva, V. Goicoechea, Gola, A., Goretti, A. M., Diaz, R. Graciani, Grigoriev, G. Y., Grobov, A., Gromov, M., Guan, M., Guerzoni, M., Guetti, M., Gulino, M., Guo, C., Hackett, B. R., Hallin, A., Haranczyk, M., Hill, S., Horikawa, S., Hubaut, F., Hugues, T., Hungerford, E. V., Ianni, An., Ippolito, V., James, C. C., Jillings, C., Kachru, P., Kemp, A. A., Kendziora, C. L., Keppel, G., Khomyakov, A. V., Kim, S., Kish, A., Kochanek, I., Kondo, K., Korga, G., Kubankin, A., Kugathasan, R., Kuss, M., Kuźniak, M., La Commara, M., La Delfa, L., La Grasta, D., Lai, M., Lami, N., Langrock, S., Leyton, M., Li, X., Lidey, L., Lippi, F., Lissia, M., Longo, G., Maccioni, N., Machulin, I. N., Mapelli, L., Marasciulli, A., Margotti, A., Mari, S. M., Maricic, J., Marinelli, M., Mart, M., Rojas, A. D. Martinez, Martini, A., Martoff, C. J., Mascia, M., Masetto, M., Masoni, A., Mazzi, A., McDonald, A. B., Mclaughlin, J., Messina, A., Meyers, P. D., Miletic, T., Milincic, R., Miola, R., Moggi, A., Moharana, A., Moioli, S., Monroe, J., Morisi, S., Morrocchi, M., Mozhevitina, E. N., Mr, T., Muratova, V. N., Murenu, A., Muscas, C., Musenich, L., Musico, P., Nania, R., Napolitano, T., Agasson, A. Navrer, Nessi, M., Nikulin, I., Nowak, J., Oleinik, A., Oleynikov, V., Pagani, L., Pallavicini, M., Palmas, S., Pandola, L., Pantic, E., Paoloni, E., Paternoster, G., Pegoraro, P. A., Pellegrini, L. A., Pellegrino, C., Pelczar, K., Perotti, F., Pesudo, V., Picciau, E., Pietropaolo, F., Pinna, T., Pocar, A., Podda, P., Poehlmann, D. M., Pordes, S., Poudel, S. S., Pralavorio, P., Price, D., Raffaelli, F., Ragusa, F., Ramirez, A., Razeti, M., Razeto, A., Renshaw, A. L., Rescia, S., Rescigno, M., Resnati, F., Retiere, F., Rignanese, L. P., Ripoli, C., Rivetti, A., Rode, J., Romero, L., Rossi, M., Rubbia, A., Rucaj, M., Sabiu, G. M., Salatino, P., Samoylov, O., S, E., Sandford, E., Sanfilippo, S., Sangiorgio, V. A., Santacroce, V., Santone, D., Santorelli, R., Santucci, A., Savarese, C., Scapparone, E., Schlitzer, B., Scioli, G., Semenov, D. A., Shaw, B., Shchagin, A., Sheshukov, A., Simeone, M., Skensved, P., Skorokhvatov, M. D., Smirnov, O., Smith, B., Sokolov, A., Stefanizzi, R., Steri, A., Stracka, S., Strickland, V., Stringer, M., Sulis, S., Suvorov, Y., Szelc, A. M., Zsücs-Balázs, J. Z., Tartaglia, R., Testera, G., Thorpe, T. N., Tonazzo, A., Torres-Lara, S., Tosti, S., Tricomi, A., Tuveri, M., Unzhakov, E. V., Usai, G., John, T. Vallivilayil, Vescovi, S., Viant, T., Viel, S., Vishneva, A., Vogelaar, R. B., Wada, M., Wang, H., Wang, Y., Westerdale, S., Wheadon, R. J., Williams, L., Wojcik, Ma. M., Wojcik, Ma., Xiao, X., Yang, C., Zani, A., Zenobio, F., Zichichi, A., Zuzel, G., and Zykova, M. P.

Subjects
Physics - Instrumentation and Detectors, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The Aria project consists of a plant, hosting a 350 m cryogenic isotopic distillation column, the tallest ever built, which is currently in the installation phase in a mine shaft at Carbosulcis S.p.A., Nuraxi-Figus (SU), Italy. Aria is one of the pillars of the argon dark-matter search experimental program, lead by the Global Argon Dark Matter Collaboration. Aria was designed to reduce the isotopic abundance of $^{39}$Ar, a $\beta$-emitter of cosmogenic origin, whose activity poses background and pile-up concerns in the detectors, in the argon used for the dark-matter searches, the so-called Underground Argon (UAr). In this paper, we discuss the requirements, design, construction, tests, and projected performance of the plant for the isotopic cryogenic distillation of argon. We also present the successful results of isotopic cryogenic distillation of nitrogen with a prototype plant, operating the column at total reflux.

Published
2021
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27. Maxwellian mirages in general relativity

Author

Williams, L. L. and Inan, N.

Subjects
General Relativity and Quantum Cosmology
Abstract

Maxwellian approximations to linear general relativity are revisited in light of relatively recent results on the degrees of freedom in the linear gravitational field. The well-known Maxwellian formalism obtained in harmonic coordinates is compared with a Maxwellian formalism obtained under a coordinate choice where each of the metric components corresponds to each of the coordinate-invariant degrees of freedom of the linear gravitational field. The coordinate freedom of general relativity can be exploited to cast the field equations into Maxwellian form, but such forms can be mere mirages of the coordinate choice -- mirages such as vector gravitational waves. A coordinate choice that yields perfectly-Maxwellian field equations, will yield a force equation that is not Lorentzian. If field definitions are chosen to obtain Lorentz-like terms in the force equation, then Maxwellian forms are compromised in the field equations. Many treatments of gravito-electromagnetism will make inconsistent ordering choices between the field equations and force equations, or else truncate terms of relevant order from the force equation. Often such mistakes reflect an attempt to force exact Maxwellian analogs simultaneously in both the field equations and the force equation, with the result that terms dropped are as large as those kept.

Published
2020
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28. Sensitivity of future liquid argon dark matter search experiments to core-collapse supernova neutrinos

Author

Agnes, P., Albergo, S., Albuquerque, I. F. M., Alexander, T., Alici, A., Alton, A. K., Amaudruz, P., Arcelli, S., Ave, M., Avetissov, I. Ch., Avetisov, R. I., Azzolini, O., Back, H. O., Balmforth, Z., Barbarian, V., Olmedo, A. Barrado, Barrillon, P., Basco, A., Batignani, G., Bondar, A., Bonivento, W. M., Borisova, E., Bottino, B., Boulay, M. G., Buccino, G., Bussino, S., Busto, J., Buzulutskov, A., Cadeddu, M., Cadoni, M., Caminata, A., Canci, N., Cappello, G., Caravati, M., Cárdenas-Montes, M., Carlini, M., Carnesecchi, F., Castello, P., Catalanotti, S., Cataudella, V., Cavalcante, P., Cavuoti, S., Cebrian, S., Ruiz, J. M. Cela, Celano, B., Chashin, S., Chepurnov, A., Chyhyrynets, E, Cicalò, C., Cifarelli, L., Cintas, D., Coccetti, F., Cocco, V., Colocci, M., Vilda, E. Conde, Consiglio, L., Copello, S., Corning, J., Covone, G., Czudak, P., D'Auria, S., Rolo, M. D. Da Rocha, Dadoun, O., Daniel, M., Davini, S., De Candia, A., De Cecco, S., De Falco, A., De Filippis, G., De Gruttola, D., De Guido, G., De Rosa, G., Della Valle, M., Dellacasa, G., De Pasquale, S., Derbin, A. V., Devoto, A., Di Noto, L., Dionisi, C., Di Stefano, P., Dolganov, G., Dordei, F., Doria, L., Downing, M., Erjavec, T., Diaz, M. Fernandez, Fiorillo, G., Franceschi, A., Franco, D., Frolov, E., Funicello, N., Gabriele, F., Galbiati, C., Garbini, M., Abia, P. Garcia, Gendotti, A., Ghiano, C., Giampaolo, R. A., Giganti, C., Giorgi, M. A., Giovanetti, G. K., Casanueva, V. Goicoechea, Gola, A., Diaz, R. Graciani, Grigoriev, G. Y., Grobov, A., Gromov, M., Guan, M., Guerzoni, M., Gulino, M., Guo, C., Hackett, B. R., Hallin, A., Haranczyk, M., Hill, S., Horikawa, S., Hubaut, F., Hugues, T., Hungerford, E. V., Ianni, An., Ippolito, V., James, C. C., Jillings, C., Kachru, P., Kemp, A. A., Kendziora, C. L., Keppel, G., Khomyakov, A. V., Kim, S., Kish, A., Kochanek, I., Kondo, K., Korga, G., Kubankin, A., Kugathasan, R., Kuss, M., Kuźniak, M., La Commara, M., Lai, M., Langrock, S., Leyton, M., Li, X., Lidey, L., Lissia, M., Longo, G., Machulin, I. N., Mapelli, L., Marasciulli, A., Margotti, A., Mari, S. M., Maricic, J., Martínez, M., Rojas, A. D. Martinez, Martoff, C. J., Masoni, A., Mazzi, A., McDonald, A. B., Mclaughlin, J., Messina, A., Meyers, P. D., Miletic, T., Milincic, R., Moggi, A., Moharana, A., Moioli, S., Monroe, J., Morisi, S., Morrocchi, M., Mozhevitina, E. N., Mróz, T., Muratova, V. N., Muscas, C., Musenich, L., Musico, P., Nania, R., Napolitano, T., Agasson, A. Navrer, Nessi, M., Nikulin, I., Nowak, J., Oleinik, A., Oleynikov, V., Pagani, L., Pallavicini, M., Pandola, L., Pantic, E., Paoloni, E., Paternoster, G., Pegoraro, P. A., Pelczar, K., Pellegrini, L. A., Pellegrino, C., Perotti, F., Pesudo, V., Picciau, E., Pietropaolo, F., Pira, C., Pocar, A., Poehlmann, D. M., Pordes, S., Poudel, S. S., Pralavorio, P., Price, D., Raffaelli, F., Ragusa, F., Ramirez, A., Razeti, M., Razeto, A., Renshaw, A. L., Rescia, S., Rescigno, M., Resnati, F., Retiere, F., Rignanese, L. P., Ripoli, C., Rivetti, A., Rode, J., Romero, L., Rossi, M., Rubbia, A., Salatino, P., Samoylov, O., García, E. Sánchez, Sandford, E., Sanfilippo, S., Santone, D., Santorelli, R., Savarese, C., Scapparone, E., Schlitzer, B., Scioli, G., Semenov, D. A., Shaw, B., Shchagin, A., Sheshukov, A., Simeone, M., Skensved, P., Skorokhvatov, M. D., Smirnov, O., Smith, B., Sokolov, A., Steri, A., Stracka, S., Strickland, V., Stringer, M., Sulis, S., Suvorov, Y., Szelc, A. M., Tartaglia, R., Testera, G., Thorpe, T. N., Tonazzo, A., Torres-Lara, S., Tricomi, A., Unzhakov, E. V., Usai, G., John, T. Vallivilayil, Viant, T., Viel, S., Vishneva, A., Vogelaar, R. B., Wada, M., Wang, H., Wang, Y., Westerdale, S., Wheadon, R. J., Williams, L., Wojcik, Ma. M., Wojcik, Ma., Xiao, X., Yang, C., Ye, Z., Zani, A., Zichichi, A., Zuzel, G., and Zykova, M. P.

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

Future liquid-argon DarkSide-20k and ARGO detectors, designed for direct dark matter search, will be sensitive also to core-collapse supernova neutrinos, via coherent elastic neutrino-nucleus scattering. This interaction channel is flavor-insensitive with a high-cross section, enabling for a high-statistics neutrino detection with target masses of $\sim$50~t and $\sim$360~t for DarkSide-20k and ARGO, respectively. Thanks to the low-energy threshold of $\sim$0.5~keV$_{nr}$ achievable by exploiting the ionization channel, DarkSide-20k and ARGO have the potential to discover supernova bursts throughout our galaxy and up to the Small Magellanic Cloud, respectively, assuming a 11-M$_{\odot}$ progenitor star. We report also on the sensitivity to the neutronization burst, whose electron neutrino flux is suppressed by oscillations when detected via charged current and elastic scattering. Finally, the accuracies in the reconstruction of the average and total neutrino energy in the different phases of the supernova burst, as well as its time profile, are also discussed, taking into account the expected background and the detector response., Comment: 21 pages, 8 figures

Published
2020
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29. Long-range scalar forces in five-dimensional general relativity

Author

Williams, L. L.

Subjects
General Relativity and Quantum Cosmology
Abstract

Kaluza first observed that the vacuum Einstein equations written in 5 dimensions (5D) reproduce exactly 4D general relativity and classical electrodynamics, when derivatives of the 5D metric with respect to the 5th coordinate are set to zero. The 15th component of the 5D metric is a 4D long-range scalar field, and the 4D limit emerges as the scalar field goes to one. Here we report new analysis, results, and force effects from the long-range Kaluza scalar field. These considerations reveal a strong electro-gravitic buoyancy force arising from a gravitational coupling between the electric charge of a body and the scalar field around a planet. A new, third characteristic lengthscale for the electro-gravitic fields of a body of mass $M$ and charge $Q$ is identified, $\mu_0 Q^2/M$, to go along with the Reissner-Nordstrom lengthscales, $GM/c^2$ and $Q\sqrt{G\mu_0 /c^2}$. At atomic scales, 5D covariance of the source terms requires that the electric, scalar, and gravitational forces all become proportional to electric charge. We discuss these results relative to foundational work by Dicke on long range scalar interactions and the Brans-Dicke scalar-tensor theory, including how interaction with the scalar implies a variable rest mass, and the energetics of the joint scalar-gravitational interaction. We discuss the problems of tuning the only available free parameter, the invariant 5D length element of the sources, to neutralize the scalar force and avoid the otherwise-large scalar force predictions. We conclude that large classical forces are a testable prediction of 5D general relativity sufficient to falsify the 5D hypothesis. Yet the emergence of a new physical interaction lengthscale is suggestive of further unexplored physics of the long range scalar field., Comment: text and mathematics, no figures. Table I did not render well

Published
2020
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30. Time Delay Lens Modelling Challenge

Author

Ding, X., Treu, T., Birrer, S., Chen, G. C. -F., Coles, J., Denzel, P., Galan, M. Frigo A., Marshall, P. J., Millon, M., More, A., Shajib, A. J., Sluse, D., Tak, H., Xu, D., Auger, M. W., Bonvin, V., Chand, H., Courbin, F., Despali, G., Fassnacht, C. D., Gilman, D., Hilbert, S., Kumar, S. R., Lin, Y. -Y., Park, J. W., Saha, P., Vegetti, S., Van de Vyvere, L., and Williams, L. L. R.

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

In recent years, breakthroughs in methods and data have enabled gravitational time delays to emerge as a very powerful tool to measure the Hubble constant $H_0$. However, published state-of-the-art analyses require of order 1 year of expert investigator time and up to a million hours of computing time per system. Furthermore, as precision improves, it is crucial to identify and mitigate systematic uncertainties. With this time delay lens modelling challenge we aim to assess the level of precision and accuracy of the modelling techniques that are currently fast enough to handle of order 50 lenses, via the blind analysis of simulated datasets. The results in Rung 1 and Rung 2 show that methods that use only the point source positions tend to have lower precision ($10 - 20\%$) while remaining accurate. In Rung 2, the methods that exploit the full information of the imaging and kinematic datasets can recover $H_0$ within the target accuracy ($ |A| < 2\%$) and precision ($< 6\%$ per system), even in the presence of poorly known point spread function and complex source morphology. A post-unblinding analysis of Rung 3 showed the numerical precision of the ray-traced cosmological simulations to be insufficient to test lens modelling methodology at the percent level, making the results difficult to interpret. A new challenge with improved simulations is needed to make further progress in the investigation of systematic uncertainties. For completeness, we present the Rung 3 results in an appendix, and use them to discuss various approaches to mitigating against similar subtle data generation effects in future blind challenges., Comment: 23 pages, 12 figures, 6 tables, MNRAS accepted

Published
2020
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31. The 1.28 GHz MeerKAT DEEP2 Image

Author

Mauch, T., Cotton, W. D., Condon, J. J., Matthews, A. M., Abbott, T. D., Adam, R. M., Aldera, M. A., Asad, K. M. B., Bauermeister, E. F., Bennett, T. G. H., Bester, H., Botha, D. H., Brederode, L. R. S., Brits, Z. B., Buchner, S. J., Burger, J. P., Camilo, F., Chalmers, J. M., Cheetham, T., de Villiers, D., de Villiers, M. S., Dikgale-Mahlakoana, M. A., Toit, L. J. du, Esterhuyse, S. W. P., Fadana, G., Fanaroff, B. L., Fataar, S., February, S., Frank, B. S., Gamatham, R. R. G., Geyer, M., Goedhart, S., Gounden, S., Gumede, S. C., Heywood, I., Hlakola, M. J., Horrell, J. M. G., Hugo, B., Isaacson, A. R., Józsa, G. I. G., Jonas, J. L., Julie, R. P. M., Kapp, F. B., Kasper, V. A., Kenyon, J. S., Kotzé, P. P. A., Kriek, N., Kriel, H., Kusel, T. W., Lehmensiek, R., Loots, A., Lord, R. T., Lunsky, B. M., Madisa, K., Magnus, L. G., Main, J. P. L., Malan, J. A., Manley, J. R., Marais, S. J., Martens, A., Merry, B., Millenaar, R., Mnyandu, N., Moeng, I. P. T., Mokone, O. J., Monama, T. E., Mphego, M. C., New, W. S., Ngcebetsha, B., Ngoasheng, K. J., Ockards, M. T. O., Oozeer, N., Otto, A. J., Patel, A. A., Peens-Hough, A., Perkins, S. J., Ramaila, A. J. T., Ramudzuli, Z. R., Renil, R., Richter, L. L., Robyntjies, A., Salie, S., Schollar, C. T. G., Schwardt, L. C., Serylak, M., Siebrits, R., Sirothia, S. K., Smirnov, O. M., Sofeya, L., Stone, G., Taljaard, B., Tasse, C., Theron, I. P., Tiplady, A. J., Toruvanda, O., Twum, S. N., van Balla, T. J., van der Byl, A., van der Merwe, C., Van Tonder, V., Wallace, B. H., Welz, M. G., Williams, L. P., and Xaia, B.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

We present the confusion-limited 1.28 GHz MeerKAT DEEP2 image covering one $\approx 68'$ FWHM primary beam area with $7.6''$ FWHM resolution and $0.55 \pm 0.01$ $\mu$Jy/beam rms noise. Its J2000 center position $\alpha=04^h 13^m 26.4^s$, $\delta=-80^\circ 00' 00''$ was selected to minimize artifacts caused by bright sources. We introduce the new 64-element MeerKAT array and describe commissioning observations to measure the primary beam attenuation pattern, estimate telescope pointing errors, and pinpoint $(u,v)$ coordinate errors caused by offsets in frequency or time. We constructed a 1.4 GHz differential source count by combining a power-law count fit to the DEEP2 confusion $P(D)$ distribution from $0.25$ to $10$ $\mu$Jy with counts of individual DEEP2 sources between $10$ $\mu$Jy and $2.5$ mJy. Most sources fainter than $S \sim 100$ $\mu$Jy are distant star-forming galaxies obeying the FIR/radio correlation, and sources stronger than $0.25$ $\mu$Jy account for $\sim93\%$ of the radio background produced by star-forming galaxies. For the first time, the DEEP2 source count has reached the depth needed to reveal the majority of the star formation history of the universe. A pure luminosity evolution of the 1.4 GHz local luminosity function consistent with the Madau & Dickinson (2014) model for the evolution of star-forming galaxies based on UV and infrared data underpredicts our 1.4 GHz source count in the range $-5 \lesssim \log[S(\mathrm{Jy})] \lesssim -4$., Comment: 20 pages, 18 figures. Accepted for publication in ApJ

Published
2019
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32. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma

Author

Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P., Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Daniel, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J.F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A., Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Pleiness, Jacob, Pollin, Toni, Post, Wendy, Powers Becker, Julia, Preethi Boorgula, Meher, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T., Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Williams, Scott, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Baojun, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Recto, Kathryn, Kachroo, Priyadarshini, Huan, Tianxiao, Lee, Gha Young, Bui, Helena, Lee, Dong Heon, Gereige, Jessica, Yao, Chen, Hwang, Shih-Jen, Joehanes, Roby, O’Connor, George T., and DeMeo, Dawn L.

Published
2023
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33. Mapping the 17q12-21.1 Locus for Variants Associated with Early-Onset Asthma in African Americans.

Author

Gui, Hongsheng, Levin, Albert M, Hu, Donglei, Sleiman, Patrick, Xiao, Shujie, Mak, Angel CY, Yang, Mao, Barczak, Andrea J, Huntsman, Scott, Eng, Celeste, Hochstadt, Samantha, Zhang, Ellen, Whitehouse, Kyle, Simons, Samantha, Cabral, Whitney, Takriti, Sami, Abecasis, Gonçalo, Blackwell, Thomas W, Kang, Hyun Min, Nickerson, Deborah A, Germer, Soren, Lanfear, David E, Gilliland, Frank, Gauderman, W James, Kumar, Rajesh, Erle, David J, Martinez, Fernando D, Hakonarson, Hakon, Burchard, Esteban G, and Williams, L Keoki

Subjects
Lung, Asthma, Genetics, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Black or African American, Age of Onset, Child, Child, Preschool, Chromosome Mapping, Chromosomes, Human, Pair 17, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Humans, Infant, Infant, Newborn, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, United States, White People, Young Adult, asthma, African Americans, chromosome 17, GSDMB, ORMDL3, Medical and Health Sciences, Respiratory System
Abstract

Rationale: The 17q12-21.1 locus is one of the most highly replicated genetic associations with asthma. Individuals of African descent have lower linkage disequilibrium in this region, which could facilitate identifying causal variants.Objectives: To identify functional variants at 17q12-21.1 associated with early-onset asthma among African American individuals.Methods: We evaluated African American participants from SAPPHIRE (Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity) (n = 1,940), SAGE II (Study of African Americans, Asthma, Genes and Environment) (n = 885), and GCPD-A (Study of the Genetic Causes of Complex Pediatric Disorders-Asthma) (n = 2,805). Associations with asthma onset at ages under 5 years were meta-analyzed across cohorts. The lead signal was reevaluated considering haplotypes informed by genetic ancestry (i.e., African vs. European). Both an expression-quantitative trait locus analysis and a phenome-wide association study were performed on the lead variant.Measurements and Main Results: The meta-analyzed results from SAPPHIRE, SAGE II, and the GCPD-A identified rs11078928 as the top association for early-onset asthma. A haplotype analysis suggested that the asthma association partitioned most closely with the rs11078928 genotype. Genetic ancestry did not appear to influence the effect of this variant. In the expression-quantitative trait locus analysis, rs11078928 was related to alternative splicing of GSDMB (gasdermin-B) transcripts. The phenome-wide association study of rs11078928 suggested that this variant was predominantly associated with asthma and asthma-associated symptoms.Conclusions: A splice-acceptor polymorphism appears to be a causal variant for asthma at the 17q12-21.1 locus. This variant appears to have the same magnitude of effect in individuals of African and European descent.

Published
2021

34. Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event

Author

Heywood, I., Camilo, F., Cotton, W. D., Yusef-Zadeh, F., Abbott, T. D., Adam, R. M., Aldera, M. A., Bauermeister, E. F., Booth, R. S., Botha, A. G., Botha, D. H., Brederode, L. R. S., Brits, Z. B., Buchner, S. J., Burger, J. P., Chalmers, J. M., Cheetham, T., de Villiers, D., Dikgale-Mahlakoana, M. A., Toit, L. J. du, Esterhuyse, S. W. P., Fanaroff, B. L., Foley, A. R., Fourie, D. J., Gamatham, R. R. G., Goedhart, S., Gounden, S., Hlakola, M. J., Hoek, C. J., Hokwana, A., Horn, D. M., Horrell, J. M. G., Hugo, B., Isaacson, A. R., Jonas, J. L., Jordaan, J. D. B. L., Joubert, A. F., Józsa, G. I. G., Julie, R. P. M., Kapp, F. B., Kenyon, J. S., Kotzé, P. P. A., Kriel, H., Kusel, T. W., Lehmensiek, R., Liebenberg, D., Loots, A., Lord, R. T., Lunsky, B. M., Macfarlane, P. S., Magnus, L. G., Magozore, C. M., Mahgoub, O., Main, J. P. L., Malan, J. A., Malgas, R. D., Manley, J. R., Maree, M. D. J., Merry, B., Millenaar, R., Mnyandu, N., Moeng, I. P. T., Monama, T. E., Mphego, M. C., New, W. S., Ngcebetsha, B., Oozeer, N., Otto, A. J., Passmoor, S. S., Pate, A. A., Peens-Hough, A., Perkins, S. J., Ratcliffe, S. M., Renil, R., Rust, A., Salie, S., Schwardt, L. C., Serylak, M., Siebrits, R., Sirothia, S. K., Smirnov, O. M., Sofeya, L., Swart, P. S., Tasse, C., Taylor, D. T., Theron, I. P., Thorat, K., Tiplad, A. J., Tshongweni, S., van Balla, T. J., van der Byl, A., van der Merwe, C., van Dyk, C. L., Van Rooyen, R., Van Tonder, V., Van Wyk, R., Wallace, B. H., Welz, M. G., and Williams, L. P.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The Galactic Centre contains a supermassive black hole with a mass of 4 million suns within an environment that differs markedly from that of the Galactic disk. While the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings. Also, while the levels of star formation in the Galactic Centre have been approximately constant over the last few hundred Myr, there is evidence of elevated short-duration bursts, strongly influenced by interaction of the black hole with the enhanced gas density present within the ring-like Central Molecular Zone at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200 pc region is characterized by large amounts of warm molecular gas, a high cosmic ray ionization rate, unusual gas chemistry, enhanced synchrotron emission, and a multitude of radio-emitting magnetised filaments, the origin of which has not been established. Here we report radio imaging that reveals bipolar bubbles spanning 1 degree x 3 degrees (140 parsecs x 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 x 10^52 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities., Comment: 25 pages, 3 figures, 3 tables, authors' version of a Letter published in Nature on 11 September 2019

Published
2019
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36. Cluster structures in Schubert varieties in the Grassmannian

Author

Serhiyenko, K., Sherman-Bennett, M., and Williams, L.

Subjects
Mathematics - Combinatorics, Mathematics - Rings and Algebras, Mathematics - Representation Theory
Abstract

In this article we explain how the coordinate ring of each (open) Schubert variety in the Grassmannian can be identified with a cluster algebra, whose combinatorial structure is encoded using (target labelings of) Postnikov's plabic graphs. This result generalizes a theorem of Scott (Scott 2006) for the Grassmannian, and proves a folklore conjecture for Schubert varieties that has been believed by experts since (Scott 2006), though the statement was not formally written down until M\"uller-Speyer explicitly conjectured it (M\"uller-Speyer 2016). To prove this conjecture we use a result of Leclerc (Leclerc 2016), who used the module category of the preprojective algebra to prove that coordinate rings of many Richardson varieties in the complete flag variety can be identified with cluster algebras. Our proof also uses a construction of Karpman (Karpman 2016) to build plabic graphs associated to reduced expressions. We additionally generalize our result to the setting of skew Schubert varieties; the latter result uses generalized plabic graphs, i.e. plabic graphs whose boundary vertices need not be labeled in cyclic order., Comment: 44 pages, 27 figures. Version 2: Simplified Section 6, expanded Remark 2.9

Published
2019
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37. Lung Function in African American Children with Asthma Is Associated with Novel Regulatory Variants of the KIT Ligand KITLG/SCF and Gene-By-Air-Pollution Interaction

Author

Mak, Angel CY, Sajuthi, Satria, Joo, Jaehyun, Xiao, Shujie, Sleiman, Patrick M, White, Marquitta J, Lee, Eunice Y, Saef, Benjamin, Hu, Donglei, Gui, Hongsheng, Keys, Kevin L, Lurmann, Fred, Jain, Deepti, Abecasis, Gonçalo, Kang, Hyun Min, Nickerson, Deborah A, Germer, Soren, Zody, Michael C, Winterkorn, Lara, Reeves, Catherine, Huntsman, Scott, Eng, Celeste, Salazar, Sandra, Oh, Sam S, Gilliland, Frank D, Chen, Zhanghua, Kumar, Rajesh, Martínez, Fernando D, Wu, Ann Chen, Ziv, Elad, Hakonarson, Hakon, Himes, Blanca E, Williams, L Keoki, Seibold, Max A, and Burchard, Esteban G

Subjects
Biological Sciences, Genetics, Biotechnology, Asthma, Precision Medicine, Lung, Pediatric, Human Genome, 2.1 Biological and endogenous factors, Respiratory, Good Health and Well Being, Adolescent, Black or African American, Air Pollution, Child, Chromosomes, Human, Pair 12, Female, Forced Expiratory Volume, Gene-Environment Interaction, Humans, Linkage Disequilibrium, Male, Nasal Mucosa, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Stem Cell Factor, Young Adult, GWAS, African American, FEV(1)gene-by-environment interaction, GxE, air pollution, KITLG, SCF, FEV1 gene-by-environment interaction, Developmental Biology, Biochemistry and cell biology
Abstract

Baseline lung function, quantified as forced expiratory volume in the first second of exhalation (FEV1), is a standard diagnostic criterion used by clinicians to identify and classify lung diseases. Using whole-genome sequencing data from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine project, we identified a novel genetic association with FEV1 on chromosome 12 in 867 African American children with asthma (P = 1.26 × 10-8, β = 0.302). Conditional analysis within 1 Mb of the tag signal (rs73429450) yielded one major and two other weaker independent signals within this peak. We explored statistical and functional evidence for all variants in linkage disequilibrium with the three independent signals and yielded nine variants as the most likely candidates responsible for the association with FEV1 Hi-C data and expression QTL analysis demonstrated that these variants physically interacted with KITLG (KIT ligand, also known as SCF), and their minor alleles were associated with increased expression of the KITLG gene in nasal epithelial cells. Gene-by-air-pollution interaction analysis found that the candidate variant rs58475486 interacted with past-year ambient sulfur dioxide exposure (P = 0.003, β = 0.32). This study identified a novel protective genetic association with FEV1, possibly mediated through KITLG, in African American children with asthma. This is the first study that has identified a genetic association between lung function and KITLG, which has established a role in orchestrating allergic inflammation in asthma.

Published
2020

38. Asthma and its relationship to mitochondrial copy number: Results from the Asthma Translational Genomics Collaborative (ATGC) of the Trans-Omics for Precision Medicine (TOPMed) program.

Author

Cocco, Maxwell P, White, Evan, Xiao, Shujie, Hu, Donglei, Mak, Angel, Sleiman, Patrick, Yang, Mao, Bobbitt, Kevin R, Gui, Hongsheng, Levin, Albert M, Hochstadt, Samantha, Whitehouse, Kyle, Rynkowski, Dean, Barczak, Andrea J, Abecasis, Gonçalo, Blackwell, Thomas W, Kang, Hyun Min, Nickerson, Deborah A, Germer, Soren, Ding, Jun, Lanfear, David E, Gilliland, Frank, Gauderman, W James, Kumar, Rajesh, Erle, David J, Martinez, Fernando, Hakonarson, Hakon, Burchard, Esteban G, and Williams, L Keoki

Subjects
Leukocytes, Humans, Asthma, Electron Transport Chain Complex Proteins, DNA, Mitochondrial, RNA, Flow Cytometry, Logistic Models, Proportional Hazards Models, Sensitivity and Specificity, Cohort Studies, Base Sequence, Adult, Middle Aged, African Americans, Female, Male, Young Adult, DNA Copy Number Variations, Translational Medical Research, Whole Genome Sequencing, Human Genome, Biotechnology, Lung, Clinical Research, Genetics, Respiratory, General Science & Technology
Abstract

BackgroundMitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis.ObjectiveGiven the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma.MethodsWhole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing.ResultsAverage mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P

Published
2020

39. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L, Ahluwalia, Tarunveer S, Cho, Michael H, Qiao, Dandi, Kelly, Rachel S, Chu, Su H, Virkud, Yamini V, Huang, Mengna, Barnes, Kathleen C, Burchard, Esteban G, Eng, Celeste, Hu, Donglei, Celedón, Juan C, Daya, Michelle, Levin, Albert M, Gui, Hongsheng, Williams, L Keoki, Forno, Erick, Mak, Angel CY, Avila, Lydiana, Soto-Quiros, Manuel E, Cloutier, Michelle M, Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A, Lange, Christoph, Weiss, Scott T, Lasky-Su, Jessica A, National Heart, Lung, Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette Palmer, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, and Das, Sayantan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Asthma, Genetics, Pediatric, Biotechnology, Human Genome, Lung, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Cell Adhesion Molecules, Child, Child, Preschool, Costa Rica, Female, Forced Expiratory Volume, Humans, Interferon Regulatory Factors, Male, Middle Aged, Respiratory Physiological Phenomena, Vital Capacity, Whole Genome Sequencing, Young Adult, airway hyperresponsiveness, asthma, lung function, whole genome sequencing, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAsthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.MethodsWGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes.ResultsA genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR.ConclusionsThese findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Published
2019

43. Measurement of isotopic separation of argon with the prototype of the cryogenic distillation plant Aria for dark matter searches

Author

Aaron, E., Agnes, P., Ahmad, I., Albergo, S., Albuquerque, I. F. M., Alexander, T., Alton, A. K., Amaudruz, P., Atzori Corona, M., Ave, M., Avetisov, I. Ch., Azzolini, O., Back, H. O., Balmforth, Z., Barrado, A., Barrillon, P., Basco, A., Batignani, G., Bocci, V., Bonivento, W. M., Bottino, B., Boulay, M. G., Busto, J., Cadeddu, M., Caminata, A., Canci, N., Capra, A., Caprioli, S., Caravati, M., Cargioli, N., Carlini, M., Castello, P., Cavalcante, P., Cavuoti, S., Cebrian, S., Cela Ruiz, J. M., Chashin, S., Chepurnov, A., Chyhyrynets, E., Cifarelli, L., Cintas, D., Citterio, M., Cleveland, B., Cocco, V., Conde Vilda, E., Consiglio, L., Copello, S., Covone, G., Czubak, M., D’Aniello, M., D’Auria, S., Da Rocha Rolo, M. D., Davini, S., De Cecco, S., De Guido, G., De Gruttola, D., De Pasquale, S., De Rosa, G., Dellacasa, G., Derbin, A. V., Devoto, A., Di Capua, F., Di Noto, L., Di Stefano, P., Dolganov, G., Dordei, F., Ellingwood, E., Erjavec, T., Farenzena, S., Fernandez Diaz, M., Fiorillo, G., Franchini, P., Franco, D., Funicello, N., Gabriele, F., Gahan, D., Galbiati, C., Gallina, G., Gallus, G., Garbini, M., Garcia Abia, P., Gendotti, A., Ghiano, C., Giganti, C., Giovanetti, G. K., Goicoechea Casanueva, V., Gola, A., Grauso, G., Grilli di Cortona, G., Grobov, A., Gromov, M., Guan, M., Guerzoni, M., Gulino, M., Guo, C., Hackett, B. R., Hallin, A. L., Hamer, A., Haranczyk, M., Hessel, T., Hill, S., Horikawa, S., Hubaut, F., Hucker, J., Hugues, T., Ianni, An., Ippolito, V., Jillings, C., Jois, S., Kachru, P., Kemp, A. A., Kendziora, C. L., Kimura, M., Kochanek, I., Kondo, K., Korga, G., Koulosousas, S., Kubankin, A., Kuss, M., Kuźniak, M., La Commara, M., Lai, M., Lami, N., Le Guirriec, E., Leason, E., Leoni, A., Lidey, L., Lippi, F., Lissia, M., Luzzi, L., Lychagina, O., Maccioni, N., Macfadyen, O., Machulin, I. N., Manecki, S., Manthos, I., Mapelli, L., Margotti, A., Mari, S. M., Mariani, C., Maricic, J., Marini, A., Martínez, M., Martoff, C. J., Mascia, M., Masoni, A., Matteucci, G., Mavrokoridis, K., Maxia, C., McDonald, A. B., Messina, A., Milincic, R., Mitra, A., Moharana, A., Moioli, S., Monroe, J., Moretti, E., Morrocchi, M., Mróz, T., Muratova, V. N., Muscas, C., Musico, P., Nania, R., Nessi, M., Nikolopoulos, K., Nowak, J., Olchansky, K., Oleinik, A., Oleynikov, V., Organtini, P., de Solórzano, A. Ortiz, Pagani, L., Pallavicini, M., Pandola, L., Pantic, E., Paoloni, E., Paternoster, G., Pegoraro, P. A., Pelczar, K., Pellegrini, L. A., Pellegrino, C., Pesudo, V., Piacentini, S., Pietrofaccia, L., Pino, N., Pocar, A., Poehlmann, D. M., Pordes, S., Pralavorio, P., Price, D., Ragusa, F., Ramachers, Y., Razeti, M., Renshaw, A. L., Rescigno, M., Retiere, F., Rignanese, L. P., Ripoli, C., Rivetti, A., Roberts, A., Roberts, C., Rode, J., Rogers, G., Romero, L., Rossi, M., Rubbia, A., Sabia, M. A., Sabiu, G. M., Salomone, P., Sandford, E., Sanfilippo, S., Santone, D., Santorelli, R., Savarese, C., Scapparone, E., Schillaci, G., Schukman, F., Scioli, G., Simeone, M., Skensved, P., Skorokhvatov, M. D., Smirnov, O., Smirnova, T., Smith, B., Spadoni, F., Spangenberg, M., Stefanizzi, R., Steri, A., Stornelli, V., Stracka, S., Stringer, M., Sulis, S., Sung, A., Suvorov, Y., Szelc, A. M., Tartaglia, R., Taylor, A., Taylor, J., Tedesco, S., Testera, G., Thieme, K., Thorpe, T. N., Tonazzo, A., Tricomi, A., Unzhakov, E. V., Vallivilayil John, T., Van Uffelen, M., Viant, T., Viel, S., Vogelaar, R. B., Vossebeld, J., Wada, M., Walczak, M. B., Wang, H., Wang, Y., Westerdale, S., Williams, L., Wingerter-Seez, I., Wojaczyński, R., Wojcik, Ma. M., Wright, T., Xie, Y., Yang, C., Zabihi, A., Zakhary, P., Zani, A., Zichichi, A., Zuzel, G., and Zykova, M. P.

Published
2023
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44. Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

Author

Camilo, F., Scholz, P., Serylak, M., Buchner, S., Merryfield, M., Kaspi, V. M., Archibald, R. F., Bailes, M., Jameson, A., van Straten, W., Sarkissian, J., Reynolds, J. E., Johnston, S., Hobbs, G., Abbott, T. D., Adam, R. M., Adams, G. B., Alberts, T., Andreas, R., Asad, K. M. B., Baker, D. E., Baloyi, T., Bauermeister, E. F., Baxana, T., Bennett, T. G. H., Bernardi, G., Booisen, D., Booth, R. S., Botha, D. H., Boyana, L., Brederode, L. R. S., Burger, J. P., Cheetham, T., Conradie, J., Conradie, J. P., Davidson, D. B., de Bruin, G., de Swardt, B., de Villiers, C., de Villiers, D. I. L., de Villiers, M. S., de Villiers, W., de Waal, C., Dikgale, M. A., Toit, G. du, Toit, L. J. du, Esterhuyse, S. W. P., Fanaroff, B., Fataar, S., Foley, A. R., Foster, G., Fourie, D., Gamatham, R., Gatsi, T., Geschke, R., Goedhart, S., Grobler, T. L., Gumede, S. C., Hlakola, M. J., Hokwana, A., Hoorn, D. H., Horn, D., Horrell, J., Hugo, B., Isaacson, A., Jacobs, O., van Rensburg, J. P. Jansen, Jonas, J. L., Jordaan, B., Joubert, A., Joubert, F., Jozsa, G. I. G., Julie, R., Julius, C. C., Kapp, F., Karastergiou, A., Karels, F., Kariseb, M., Karuppusamy, R., Kasper, V., Knox-Davies, E. C., Koch, D., Kotze, P. P. A., Krebs, A., Kriek, N., Kriel, H., Kusel, T., Lamoor, S., Lehmensiek, R., Liebenberg, D., Liebenberg, I., Lord, R. T., Lunsky, B., Mabombo, N., Macdonald, T., Macfarlane, P., Madisa, K., Mafhungo, L., Magnus, L. G., Magozore, C., Mahgoub, O., Main, J. P. L., Makhathini, S., Malan, J. A., Malgas, P., Manley, J. R., Manzini, M., Marais, L., Marais, N., Marais, S. J., Maree, M., Martens, A., Matshawule, S. D., Matthysen, N., Mauch, T., Nally, L. D. Mc, Merry, B., Millenaar, R. P., Mjikelo, C., Mkhabela, N., Mnyandu, N., Moeng, I. T., Mokone, O. J., Monama, T. E., Montshiwa, K., Moss, V., Mphego, M., New, W., Ngcebetsha, B., Ngoasheng, K., Niehaus, H., Ntuli, P., Nzama, A., Obies, F., Obrocka, M., Ockards, M. T., Olyn, C., Oozeer, N., Otto, A. J., Padayachee, Y., Passmoor, S., Patel, A. A., Paula, S., Peens-Hough, A., Pholoholo, B., Prozesky, P., Rakoma, S., Ramaila, A. J. T., Rammala, I., Ramudzuli, Z. R., Rasivhaga, M., Ratcliffe, S., Reader, H. C., Renil, R., Richter, L., Robyntjies, A., Rosekrans, D., Rust, A., Salie, S., Sambu, N., Schollar, C. T. G., Schwardt, L., Seranyane, S., Sethosa, G., Sharpe, C., Siebrits, R., Sirothia, S. K., Slabber, M. J., Smirnov, O., Smith, S., Sofeya, L., Songqumase, N., Spann, R., Stappers, B., Steyn, D., Steyn, T. J., Strong, R., Struthers, A., Stuart, C., Sunnylall, P., Swart, P. S., Taljaard, B., Tasse, C., Taylor, G., Theron, I. P., Thondikulam, V., Thorat, K., Tiplady, A., Toruvanda, O., van Aardt, J., van Balla, T., Heever, L. van den, van der Byl, A., van der Merwe, C., van der Merwe, P., van Niekerk, P. C., van Rooyen, R., van Staden, J. P., van Tonder, V., van Wyk, R., Wait, I., Walker, A. L., Wallace, B., Welz, M., Williams, L. P., Xaia, B., Young, N., and Zitha, S.

Subjects
Astrophysics - High Energy Astrophysical Phenomena
Abstract

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation., Comment: Published in ApJ (2018 April 5); 13 pages, 4 figures

Published
2018
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45. Author Correction: Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Author

Daya, Michelle, Rafaels, Nicholas, Brunetti, Tonya M, Chavan, Sameer, Levin, Albert M, Shetty, Aniket, Gignoux, Christopher R, Boorgula, Meher Preethi, Wojcik, Genevieve, Campbell, Monica, Vergara, Candelaria, Torgerson, Dara G, Ortega, Victor E, Doumatey, Ayo, Johnston, Henry Richard, Acevedo, Nathalie, Araujo, Maria Ilma, Avila, Pedro C, Belbin, Gillian, Bleecker, Eugene, Bustamante, Carlos, Caraballo, Luis, Cruz, Alvaro, Dunston, Georgia M, Eng, Celeste, Faruque, Mezbah U, Ferguson, Trevor S, Figueiredo, Camila, Ford, Jean G, Gan, Weiniu, Gourraud, Pierre-Antoine, Hansel, Nadia N, Hernandez, Ryan D, Herrera-Paz, Edwin Francisco, Jiménez, Silvia, Kenny, Eimear E, Knight-Madden, Jennifer, Kumar, Rajesh, Lange, Leslie A, Lange, Ethan M, Lizee, Antoine, Maul, Pissamai, Maul, Trevor, Mayorga, Alvaro, Meyers, Deborah, Nicolae, Dan L, O'Connor, Timothy D, Oliveira, Ricardo Riccio, Olopade, Christopher O, Olopade, Olufunmilayo, Qin, Zhaohui S, Rotimi, Charles, Vince, Nicolas, Watson, Harold, Wilks, Rainford J, Wilson, James G, Salzberg, Steven, Ober, Carole, Burchard, Esteban G, Williams, L Keoki, Beaty, Terri H, Taub, Margaret A, Ruczinski, Ingo, Mathias, Rasika A, Barnes, Kathleen C, and CAAPA

Subjects
CAAPA
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

46. A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma

Author

Spear, Melissa L, Hu, Donglei, Pino-Yanes, Maria, Huntsman, Scott, Eng, Celeste, Levin, Albert M, Ortega, Victor E, White, Marquitta J, McGarry, Meghan E, Thakur, Neeta, Galanter, Joshua, Mak, Angel CY, Oh, Sam S, Ampleford, Elizabeth, Peters, Stephen P, Davis, Adam, Kumar, Rajesh, Farber, Harold J, Meade, Kelley, Avila, Pedro C, Serebrisky, Denise, Lenoir, Michael A, Brigino-Buenaventura, Emerita, Cintron, William Rodriguez, Thyne, Shannon M, Rodriguez-Santana, Jose R, Ford, Jean G, Chapela, Rocio, Estrada, Andrés Moreno, Sandoval, Karla, Seibold, Max A, Winkler, Cheryl A, Bleecker, Eugene R, Myers, Deborah A, Williams, L Keoki, Hernandez, Ryan D, Torgerson, Dara G, and Burchard, Esteban G

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Lung, Genetics, Asthma, Human Genome, Respiratory, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Short-acting β2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10-8). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.

Published
2019

47. Integrative approach identifies corticosteroid response variant in diverse populations with asthma

Author

Levin, Albert M, Gui, Hongsheng, Hernandez-Pacheco, Natalia, Yang, Mao, Xiao, Shujie, Yang, James J, Hochstadt, Samantha, Barczak, Andrea J, Eckalbar, Walter L, Rynkowski, Dean, Samedy, Lesly-Anne, Kwok, Pui-Yan, Pino-Yanes, Maria, Erle, David J, Lanfear, David E, Burchard, Esteban G, and Williams, L Keoki

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Lung, Genetics, Patient Safety, Human Genome, Clinical Trials and Supportive Activities, Clinical Research, Asthma, Respiratory, Adolescent, Adrenal Cortex Hormones, Adult, Black or African American, Child, Cohort Studies, Disease Progression, Eosinophil-Derived Neurotoxin, Eosinophils, Genome-Wide Association Study, Genotype, Hispanic or Latino, Humans, Leukocyte Count, Male, Metered Dose Inhalers, Middle Aged, Pharmacogenomic Variants, Phenotype, Polymorphism, Single Nucleotide, Treatment Outcome, United States, Young Adult, Pharmacogenetics, EDDM3B, RNASE2, eosinophil-derived neurotoxin, transcriptome, eosinophils, Immunology, Allergy
Abstract

BackgroundAlthough inhaled corticosteroid (ICS) medication is considered the cornerstone treatment for patients with persistent asthma, few ICS pharmacogenomic studies have involved nonwhite populations.ObjectiveWe sought to identify genetic predictors of ICS response in multiple population groups with asthma.MethodsThe discovery group comprised African American participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE) who underwent 6 weeks of monitored ICS therapy (n = 244). A genome-wide scan was performed to identify single nucleotide polymorphism (SNP) variants jointly associated (ie, the combined effect of the SNP and SNP × ICS treatment interaction) with changes in asthma control. Top associations were validated by assessing the joint association with asthma exacerbations in 3 additional groups: African Americans (n = 803 and n = 563) and Latinos (n = 1461). RNA sequencing data from 408 asthmatic patients and 405 control subjects were used to examine whether genotype was associated with gene expression.ResultsOne variant, rs3827907, was significantly associated with ICS-mediated changes in asthma control in the discovery set (P = 7.79 × 10-8) and was jointly associated with asthma exacerbations in 3 validation cohorts (P = .023, P = .029, and P = .041). RNA sequencing analysis found the rs3827907 C-allele to be associated with lower RNASE2 expression (P = 6.10 × 10-4). RNASE2 encodes eosinophil-derived neurotoxin, and the rs3827907 C-allele appeared to particularly influence ICS treatment response in the presence of eosinophilic inflammation (ie, high pretreatment eosinophil-derived neurotoxin levels or blood eosinophil counts).ConclusionWe identified a variant, rs3827907, that appears to influence response to ICS treatment in multiple population groups and likely mediates its effect through eosinophils.

Published
2019

48. An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos

Author

Gignoux, Christopher R, Torgerson, Dara G, Pino-Yanes, Maria, Uricchio, Lawrence H, Galanter, Joshua, Roth, Lindsey A, Eng, Celeste, Hu, Donglei, Nguyen, Elizabeth A, Huntsman, Scott, Mathias, Rasika A, Kumar, Rajesh, Rodriguez-Santana, Jose, Thakur, Neeta, Oh, Sam S, McGarry, Meghan, Moreno-Estrada, Andres, Sandoval, Karla, Winkler, Cheryl A, Seibold, Max A, Padhukasahasram, Badri, Conti, David V, Farber, Harold J, Avila, Pedro, Brigino-Buenaventura, Emerita, Lenoir, Michael, Meade, Kelley, Serebrisky, Denise, Borrell, Luisa N, Rodriguez-Cintron, William, Thyne, Shannon, Joubert, Bonnie R, Romieu, Isabelle, Levin, Albert M, Sienra-Monge, Juan-Jose, Del Rio-Navarro, Blanca Estela, Gan, Weiniu, Raby, Benjamin A, Weiss, Scott T, Bleecker, Eugene, Meyers, Deborah A, Martinez, Fernando J, Gauderman, W James, Gilliland, Frank, London, Stephanie J, Bustamante, Carlos D, Nicolae, Dan L, Ober, Carole, Sen, Saunak, Barnes, Kathleen, Williams, L Keoki, Hernandez, Ryan D, and Burchard, Esteban G

Subjects
Biomedical and Clinical Sciences, Immunology, Human Genome, Clinical Research, Lung, Asthma, Genetics, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Chromosome Mapping, Chromosomes, Human, Pair 18, Genetic Predisposition to Disease, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Smad2 Protein, asthma exacerbations, admixture mapping, meta-analysis, Latinos, SMAD2, gene expression, targeted sequencing, rare variation, Allergy
Abstract

BackgroundAsthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.ObjectiveWe sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.MethodsWe leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.ResultsWe identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10-6), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10-3, combined P = 2.6 × 10-7). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P

Published
2019

49. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Author

Daya, Michelle, Rafaels, Nicholas, Brunetti, Tonya M, Chavan, Sameer, Levin, Albert M, Shetty, Aniket, Gignoux, Christopher R, Boorgula, Meher Preethi, Wojcik, Genevieve, Campbell, Monica, Vergara, Candelaria, Torgerson, Dara G, Ortega, Victor E, Doumatey, Ayo, Johnston, Henry Richard, Acevedo, Nathalie, Araujo, Maria Ilma, Avila, Pedro C, Belbin, Gillian, Bleecker, Eugene, Bustamante, Carlos, Caraballo, Luis, Cruz, Alvaro, Dunston, Georgia M, Eng, Celeste, Faruque, Mezbah U, Ferguson, Trevor S, Figueiredo, Camila, Ford, Jean G, Gan, Weiniu, Gourraud, Pierre-Antoine, Hansel, Nadia N, Hernandez, Ryan D, Herrera-Paz, Edwin Francisco, Jiménez, Silvia, Kenny, Eimear E, Knight-Madden, Jennifer, Kumar, Rajesh, Lange, Leslie A, Lange, Ethan M, Lizee, Antoine, Maul, Pissamai, Maul, Trevor, Mayorga, Alvaro, Meyers, Deborah, Nicolae, Dan L, O'Connor, Timothy D, Oliveira, Ricardo Riccio, Olopade, Christopher O, Olopade, Olufunmilayo, Qin, Zhaohui S, Rotimi, Charles, Vince, Nicolas, Watson, Harold, Wilks, Rainford J, Wilson, James G, Salzberg, Steven, Ober, Carole, Burchard, Esteban G, Williams, L Keoki, Beaty, Terri H, Taub, Margaret A, Ruczinski, Ingo, Mathias, Rasika A, Barnes, Kathleen C, and CAAPA

Subjects
CAAPA, Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 17, Humans, Asthma, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, African Americans, Hispanic Americans, United States, Genome-Wide Association Study, Genetic Loci, Chromosomes, Human, Pair 12, Pair 17, Pair 8, Polymorphism, Single Nucleotide
Abstract

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.

Published
2019

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