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11,611 results on '"Owen, J. A."'

1. HD152843 b & c: the masses and orbital periods of a sub-Neptune and a super-puff Neptune

Author

Nicholson, B. A., Aigrain, S., Eisner, N. L., Cretignier, M., Barragán, O., Kaye, L., Taylor, J., Owen, J., Mortier, A., Affer, L., Boschin, W., Cameron, A. Collier, Damasso, M., Di Fabrizio, L., DiTomasso, V., Dumusque, X., Gehdina, A., Harutyunyan, A., Latham, D. W., Lopez-Morales, M., Lorenzi, V., Fiorenzano, A. F. Martínez, Molinari, E., Pedani, M., Pinamonti, M., Sozzetti, A., and Rice, K.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

We present the characterisation of the two transiting planets around HD 152843 (TOI 2319, TIC 349488688) using an intensive campaign of HARPS-N radial velocities, and two sectors of TESS data. These data reveal a unique and fascinating system: HD 152843 b and c have near equal masses of around 9 M$_\oplus$ but differing radii of $3.05 \pm 0.11$ R$_\oplus$ and $5.94^{+0.18}_{-0.16}$ R$_\oplus$ , respectively, and orbital periods of $11.62071^{+9.6e-05}_{-0.000106}$ days and $19.502104^{+7.4e-05}_{-8.5e-05}$ days. This indicates that HD 152843 c is in the lowest fifth percentile in density of the known exoplanet population, and has the longest orbital period among these low density planets. Further, HD 152843 c's radius places it in the Saturn valley, the observed lack of planets larger than Neptune, but smaller than Saturn. The orbital periods of these planets indicate they are near a 5:3 mean motion resonance, indicating the possibility of transit timing variations, and hints at the possibility of interaction with a third planet at some point in the evolution of this system. Further, the brightness of the host star and the low density of HD 152843 c make it a key target for atmospheric characterisation., Comment: Submitted for review to the Monthly Notices of the Royal Astronomical Society. 13 pages, 16 figures

Published
2023

2. High-resolution [OI] line spectral mapping of TW Hya consistent with X-ray driven photoevaporation

Author

Rab, Ch., Weber, M., Picogna, G., Ercolano, B., and Owen, J.

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Solar and Stellar Astrophysics
Abstract

Theoretical models indicate that photoevaporative and magnetothermal winds play a crucial role in the evolution and dispersal of protoplanetary disks and affect the formation of planetary systems. However, it is still unclear what wind-driving mechanism is dominant or if both are at work, perhaps at different stages of disk evolution. Recent spatially resolved observations by Fang et al. (2023) of the [OI] 6300 Angstrom spectral line, a common disk wind tracer, in TW Hya revealed that about 80% of the emission is confined to the inner few au of the disk. In this work, we show that state-of-the-art X-ray driven photoevaporation models can reproduce the compact emission and the line profile of the [OI] 6300 Angstrom line. Furthermore, we show that the models also simultaneously reproduce the observed line luminosities and detailed spectral profiles of both the [OI] 6300 Angstrom and the [NeII] 12.8 micron lines. While MHD wind models can also reproduce the compact radial emission of the [OI] 6300 Angstrom line, they fail to match the observed spectral profile of the [OI] 6300 Angstrom line and underestimate the luminosity of the [NeII] 12.8 micron line by a factor of three. We conclude that, while we cannot exclude the presence of an MHD wind component, the bulk of the wind structure of TW Hya is predominantly shaped by a photoevaporative flow., Comment: 7 pages, 4 figures, accepted for publication in Astrophysical Journal Letters

Published
2023
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7. Longitudinal Study of Georgia's Pre-K Program: Pre-K through 4th Grade

Author

University of North Carolina at Chapel Hill, FPG Child Development Institute, Soliday Hong, S., Zadrozny, S., Walker, J., Love, E. N. G., Osborne, J. D., Owen, J. L., and Peisner-Feinberg, E.

Abstract

Georgia's Pre-K Longitudinal Study followed a statewide sample of 1,169 children who attended Georgia's Pre-K Program in 2013-14 through their 4th grade year in 2018-19. The study was conducted by researchers at the Frank Porter Graham (FPG) Child Development Institute at the University of North Carolina at Chapel Hill. The following summary describes the design and results of the full study. [For the full report, see ED630837.]

Published
2023

8. Longitudinal Study of Georgia's Pre-K Program. Final Report: Pre-K through 4th Grade

Author

University of North Carolina at Chapel Hill, FPG Child Development Institute, Soliday Hong, S., Zadrozny, S., Walker, J., Love, E. N. G., Osborne, J. D., Owen, J. L., and Peinser-Feinberg, E.

Abstract

The purpose of this evaluation study was to examine children's longitudinal academic and social outcomes associated with attendance in Georgia's Pre-K Program and to examine the quality of the classrooms attended. This report covers pre-k to 4th grade outcomes collected between the 2013-2014 and 2018-2019 school years as well as a sub-study comparing 3rd and 4th grade outcomes of children who attended Georgia's Pre-K Program with children who did not attend any pre-k program. The primary evaluation questions include: (1) What are the longitudinal outcomes through 4th grade for children who attended Georgia's Pre-K Program?; (2) What factors predict better longitudinal outcomes for children?; (3) What is the quality of children's instructional experiences from pre-k through 4th grade?; and (4) Are there differential long-term outcomes for children with and without Georgia's Pre-K experience? [For the summary report, see ED630838.]

Published
2023

9. A compact multi-planet system transiting HIP 29442 (TOI-469) discovered by TESS and ESPRESSO. Radial velocities lead to the detection of transits with low signal-to-noise ratio

Author

Damasso, M., Rodrigues, J., Castro-González, A., Lavie, B., Davoult, J., Osorio, M. R. Zapatero, Dou, J., Sousa, S. G., Owen, J. E., Sossi, P., Adibekyan, V., Osborn, H., Leinhardt, Z., Alibert, Y., Lovis, C., Mena, E. Delgado, Sozzetti, A., Barros, S. C. C., Bossini, D., Ziegler, C., Ciardi, D. R., Matthews, E. C., Carter, P. J., Lillo-Box, J., Mascareño, A. Suárez, Cristiani, S., Pepe, F., Rebolo, R., Santos, N. C., Prieto, C. Allende, Benatti, S., Bouchy, F., Briceño, C., Di Marcantonio, P., D'Odorico, V., Dumusque, X., Egger, J. A., Ehrenreich, D., Faria, J., Figueira, P., Santos, R. Génova, Gonzales, E. J., Hernández, J. I. González, Law, N., Curto, G. Lo, Mann, A. W., Martins, C. J. A. P., Mehner, A., Micela, G., Molaro, P., Nunes, N. J., Palle, E., Poretti, E., Schlieder, J. E., and Udry, S.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

We followed-up with ESPRESSO the K0V star HIP 29442 (TOI-469), already known to host a validated sub-Neptune companion TOI-469.01. We aim to verify the planetary nature of TOI-469.01. We modelled radial velocity and photometric time series to measure the dynamical mass, radius, and ephemeris, and to characterise the internal structure and composition of TOI-469.01. We confirmed the planetary nature of TOI-469.01. Thanks to ESPRESSO we discovered two additional close-in companions. We also detected their low signal-to-noise transit signals in the TESS light curve. HIP 29442 is a compact multi-planet system, and the three planets have orbital periods $P_{\rm orb, b}=13.63083\pm0.00003$, $P_{\rm orb, c}=3.53796\pm0.00003$, and $P_{\rm orb, d}=6.42975^{+0.00009}_{-0.00010}$ days, and we measured their masses with high precision: $m_{\rm p, b}=9.6\pm0.8~M_{\oplus}$, $m_{\rm p, c}=4.5\pm0.3~M_{\oplus}$, and $m_{\rm p, d}=5.1\pm0.4~M_{\oplus}$. We measured radii and bulk densities of all the planets (the 3$\sigma$ confidence intervals are shown in parenthesis): $R_{\rm p, b}=3.48^{+0.07 (+0.19)}_{-0.08 (-0.28)} ~R_{\oplus}$ and $\rho_{\rm p, b}=1.3\pm0.2 (0.3) g~cm^{-3}$; $R_{\rm p, c}=1.58^{+0.10 (+0.30)}_{-0.11 (-0.34)}~R_{\oplus}$ and $\rho_{\rm p, c}=6.3^{+1.7 (+6.0)}_{-1.3 (-2.7)} g~cm^{-3}$; $R_{\rm p, d}=1.37\pm0.11^{(+0.32)}_{(-0.43)}~R_{\oplus}$ and $\rho_{\rm p, d}=11.0^{+3.4 (+21.0)}_{-2.4 (-6.3)} g~cm^{-3}$. We used the more conservative 3$\sigma$ confidence intervals for the radii as input to the interior structure modelling. We find that HIP 29442 $b$ appears as a typical sub-Neptune, likely surrounded by a gas layer of pure H-He with a mass of $0.27^{+0.24}_{-0.17} M_{\oplus}$ and a thickness of $1.4\pm0.5 R_{\oplus}$. For the innermost companions HIP 29442 $c$ HIP 29442 $d$, the model supports an Earth-like composition., Comment: Accepted for publication on A&A

Published
2023

10. An M dwarf accompanied by a close-in giant orbiter with SPECULOOS

Author

Triaud, Amaury H. M. J., Dransfield, Georgina, Kagetani, Taiki, Timmermans, Mathilde, Narita, Norio, Barkaoui, Khalid, Hirano, Teruyuki, Rackham, Benjamin V., Mori, Mayuko, Baycroft, Thomas, Benkhaldoun, Zouhair, Burgasser, Adam J., Caldwell, Douglas A., Collins, Karen A., Davis, Yasmin T., Delrez, Laetitia, Demory, Brice-Oliver, Ducrot, Elsa, Fukui, Akihiko, Muñoz, Clàudia Jano, Jehin, Emmanuël, García, Lionel J., Ghachoui, Mourad, Gillon, Michaël, Chew, Yilen Gómez Maqueo, Hooton, Matthew J., Ikoma, Masahiro, Kawauchi, Kiyoe, Kotani, Takayuki, Levine, Alan M., Pallé, Enric, Pedersen, Peter P., Pozuelos, Francisco J., Queloz, Didier, Scutt, Owen J., Seager, Sara, Sebastian, Daniel, Tamura, Motohide, Thompson, Samantha, Watanabe, Noriharu, de Wit, Julien, Winn, Joshua N., and Zúñiga-Fernández, Sebastián

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Solar and Stellar Astrophysics
Abstract

In the last decade, a dozen close-in giant planets have been discovered orbiting stars with spectral types ranging from M0 to M4, a mystery since known formation pathways do not predict the existence of such systems. Here, we confirm TOI-4860 b, a Jupiter-sized planet orbiting an M4.5 host, a star at the transition between fully and partially convective interiors. First identified with TESS data, we validate the transiting companion's planetary nature through multicolour photometry from the TRAPPIST-South/North, SPECULOOS, and MuSCAT3 facilities. Our analysis yields a radius of $0.76 \pm 0.02~ \rm R_{Jup}$ for the planet, a mass of $0.34~\rm M_\odot$ for the star, and an orbital period of 1.52 d. Using the newly commissioned SPIRIT InGaAs camera at the SPECULOOS-South Observatory, we collect infrared photometry in zYJ that spans the time of secondary eclipse. These observations do not detect a secondary eclipse, placing an upper limit on the brightness of the companion. The planetary nature of the companion is further confirmed through high-resolution spectroscopy obtained with the IRD spectrograph at Subaru Telescope, from which we measure a mass of $0.67 \pm 0.14~\rm M_{Jup}$ . Based on its overall density, TOI-4860 b appears to be rich in heavy elements, like its host star., Comment: Accepted for publication in MNRAS Letters

Published
2023
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12. Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer

Author

Malla, Sudhir B., Byrne, Ryan M., Lafarge, Maxime W., Corry, Shania M., Fisher, Natalie C., Tsantoulis, Petros K., Mills, Megan L., Ridgway, Rachel A., Lannagan, Tamsin R. M., Najumudeen, Arafath K., Gilroy, Kathryn L., Amirkhah, Raheleh, Maguire, Sarah L., Mulholland, Eoghan J., Belnoue-Davis, Hayley L., Grassi, Elena, Viviani, Marco, Rogan, Emily, Redmond, Keara L., Sakhnevych, Svetlana, McCooey, Aoife J., Bull, Courtney, Hoey, Emily, Sinevici, Nicoleta, Hall, Holly, Ahmaderaghi, Baharak, Domingo, Enric, Blake, Andrew, Richman, Susan D., Isella, Claudio, Miller, Crispin, Bertotti, Andrea, Trusolino, Livio, Loughrey, Maurice B., Kerr, Emma M., Tejpar, Sabine, Maughan, Timothy S., Lawler, Mark, Campbell, Andrew D., Leedham, Simon J., Koelzer, Viktor H., Sansom, Owen J., and Dunne, Philip D.

Published
2024
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16. Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes

Author

Wieder, Nechama, primary, D’Souza, Elston N., additional, Martin-Geary, Alexandra C., additional, Lassen, Frederik H., additional, Talbot-Martin, Jonathan, additional, Fernandes, Maria, additional, Chothani, Sonia P., additional, Rackham, Owen J. L., additional, Schafer, Sebastian, additional, Aspden, Julie L., additional, MacArthur, Daniel G., additional, Davies, Robert W., additional, and Whiffin, Nicola, additional

Published
2024
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17. Figure 3 from Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., primary, Johnson, Emma, primary, Mackintosh, Agata, primary, Bielik, Robert, primary, Peters, Adam, primary, Soloviev, Dmitry, primary, Brown, Gavin, primary, Jackstadt, Rene, primary, Nixon, Colin, primary, Gilroy, Kathryn, primary, Campbell, Andrew, primary, Sansom, Owen J., primary, and Lewis, David Y., primary

Published
2024
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18. Figure 2 from Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., primary, Johnson, Emma, primary, Mackintosh, Agata, primary, Bielik, Robert, primary, Peters, Adam, primary, Soloviev, Dmitry, primary, Brown, Gavin, primary, Jackstadt, Rene, primary, Nixon, Colin, primary, Gilroy, Kathryn, primary, Campbell, Andrew, primary, Sansom, Owen J., primary, and Lewis, David Y., primary

Published
2024
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19. Figure 5 from Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., primary, Johnson, Emma, primary, Mackintosh, Agata, primary, Bielik, Robert, primary, Peters, Adam, primary, Soloviev, Dmitry, primary, Brown, Gavin, primary, Jackstadt, Rene, primary, Nixon, Colin, primary, Gilroy, Kathryn, primary, Campbell, Andrew, primary, Sansom, Owen J., primary, and Lewis, David Y., primary

Published
2024
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20. Supplementary Data 1 from Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., primary, Johnson, Emma, primary, Mackintosh, Agata, primary, Bielik, Robert, primary, Peters, Adam, primary, Soloviev, Dmitry, primary, Brown, Gavin, primary, Jackstadt, Rene, primary, Nixon, Colin, primary, Gilroy, Kathryn, primary, Campbell, Andrew, primary, Sansom, Owen J., primary, and Lewis, David Y., primary

Published
2024
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21. Figure 1 from Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., primary, Johnson, Emma, primary, Mackintosh, Agata, primary, Bielik, Robert, primary, Peters, Adam, primary, Soloviev, Dmitry, primary, Brown, Gavin, primary, Jackstadt, Rene, primary, Nixon, Colin, primary, Gilroy, Kathryn, primary, Campbell, Andrew, primary, Sansom, Owen J., primary, and Lewis, David Y., primary

Published
2024
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22. Table S1 from Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., primary, Johnson, Emma, primary, Mackintosh, Agata, primary, Bielik, Robert, primary, Peters, Adam, primary, Soloviev, Dmitry, primary, Brown, Gavin, primary, Jackstadt, Rene, primary, Nixon, Colin, primary, Gilroy, Kathryn, primary, Campbell, Andrew, primary, Sansom, Owen J., primary, and Lewis, David Y., primary

Published
2024
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23. Data from Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., primary, Johnson, Emma, primary, Mackintosh, Agata, primary, Bielik, Robert, primary, Peters, Adam, primary, Soloviev, Dmitry, primary, Brown, Gavin, primary, Jackstadt, Rene, primary, Nixon, Colin, primary, Gilroy, Kathryn, primary, Campbell, Andrew, primary, Sansom, Owen J., primary, and Lewis, David Y., primary

Published
2024
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24. Figure 4 from Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., primary, Johnson, Emma, primary, Mackintosh, Agata, primary, Bielik, Robert, primary, Peters, Adam, primary, Soloviev, Dmitry, primary, Brown, Gavin, primary, Jackstadt, Rene, primary, Nixon, Colin, primary, Gilroy, Kathryn, primary, Campbell, Andrew, primary, Sansom, Owen J., primary, and Lewis, David Y., primary

Published
2024
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27. Feline cardiomyopathy-driven thrombogenesis: imaging and computational fluid dynamics for the study of left atrial morphology and haemodynamics

Author

Pons, Maria Isabel, primary, Olivares, Andy L., additional, Mill, Jordi, additional, Matos, Jose Novo, additional, Garcia-Canadilla, Patricia, additional, Cerrada, Inma, additional, Guy, Anna, additional, Morales, Xabier, additional, Hutchinson, J. Ciaran, additional, Simcock, Ian C., additional, Arthurs, Owen J., additional, Cook, Andrew C., additional, Fuentes, Virginia Luis, additional, and Camara, Oscar, additional

Published
2024
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28. Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author

Malviya, Gaurav, primary, Lannagan, Tamsin R.M., additional, Johnson, Emma, additional, Mackintosh, Agata, additional, Bielik, Robert, additional, Peters, Adam, additional, Soloviev, Dmitry, additional, Brown, Gavin, additional, Jackstadt, Rene, additional, Nixon, Colin, additional, Gilroy, Kathryn, additional, Campbell, Andrew, additional, Sansom, Owen J., additional, and Lewis, David Y., additional

Published
2024
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29. JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors

Author

Pennel, Kathryn A. F., primary, Hatthakarnkul, Phimmada, additional, Wood, Colin S., additional, Lian, Guang-Yu, additional, Al-Badran, Sara S. F., additional, Quinn, Jean A., additional, Legrini, Assya, additional, Inthagard, Jitwadee, additional, Alexander, Peter G., additional, van Wyk, Hester, additional, Kurniawan, Ahmad, additional, Hashmi, Umar, additional, Gillespie, Michael A., additional, Mills, Megan, additional, Ammar, Aula, additional, Hay, Jennifer, additional, Andersen, Ditte, additional, Nixon, Colin, additional, Rebus, Selma, additional, Chang, David K., additional, Kelly, Caroline, additional, Harkin, Andrea, additional, Graham, Janet, additional, Church, David, additional, Tomlinson, Ian, additional, Saunders, Mark, additional, Iveson, Tim, additional, Lannagan, Tamsin R. M., additional, Jackstadt, Rene, additional, Maka, Noori, additional, Horgan, Paul G., additional, Roxburgh, Campbell S. D., additional, Sansom, Owen J., additional, McMillan, Donald C., additional, Steele, Colin W., additional, Jamieson, Nigel B., additional, Park, James H., additional, Roseweir, Antonia K., additional, and Edwards, Joanne, additional

Published
2024
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32. Removal of endothelial surface-associated von villebrand factor suppresses accelerate datherosclerosis after myocardial infarction

Author

Koya Ozawa, William Packwood, Matthew A Muller, Yue Qi, Aris Xie, Oleg Varlamov, Owen J. McCarty, Dominic Chung, José A. López, and Jonathan R. Lindner

Subjects
Atherosclerosis, Molecular imaging, Platelets, Von Willebrand factor, Medicine
Abstract

Abstract Background Thromboinflammation involving platelet adhesion to endothelial surface-associated von Willebrand factor (VWF) has been implicated in the accelerated progression of non-culprit plaques after MI. The aim of this study was to use arterial endothelial molecular imaging to mechanistically evaluate endothelial-associated VWF as a therapeutic target for reducing remote plaque activation after myocardial infarction (MI). Methods Hyperlipidemic mice deficient for the low-density lipoprotein receptor and Apobec-1 underwent closed-chest MI and were treated chronically with either: (i) recombinant ADAMTS13 which is responsible for proteolytic removal of VWF from the endothelial surface, (ii) N-acetylcysteine (NAC) which removes VWF by disulfide bond reduction, (iii) function-blocking anti-factor XI (FXI) antibody, or (iv) no therapy. Non-ischemic controls were also studied. At day 3 and 21, ultrasound molecular imaging was performed with probes targeted to endothelial-associated VWF A1-domain, platelet GPIbα, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) at lesion-prone sites of the aorta. Histology was performed at day 21. Results Aortic signal for P-selectin, VCAM-1, VWF, and platelet-GPIbα were all increased several-fold (p 50% (p

Published
2024
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33. Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes

Author

Nechama Wieder, Elston N. D’Souza, Alexandra C. Martin-Geary, Frederik H. Lassen, Jonathan Talbot-Martin, Maria Fernandes, Sonia P. Chothani, Owen J. L. Rackham, Sebastian Schafer, Julie L. Aspden, Daniel G. MacArthur, Robert W. Davies, and Nicola Whiffin

Subjects
5’ untranslated regions, 5’UTR, Translational regulation, Upstream open reading frame, uORF, Dosage sensitivity, Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5’UTRs, correlates with gene dosage sensitivity. Results We investigate 5’UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5’UTRs to form secondary structures. We explore how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5’UTR length and complexity. Genes that are most intolerant to LoF have longer 5’UTRs, greater TSS diversity, and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated. Conclusions Our results confirm the importance of post-transcriptional regulation through 5'UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR, that supports exploration of the composition of individual 5'UTRs and the impact of genetic variation within them.

Published
2024
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34. JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors

Author

Kathryn A. F. Pennel, Phimmada Hatthakarnkul, Colin S. Wood, Guang-Yu Lian, Sara S. F. Al-Badran, Jean A. Quinn, Assya Legrini, Jitwadee Inthagard, Peter G. Alexander, Hester van Wyk, Ahmad Kurniawan, Umar Hashmi, Michael A. Gillespie, Megan Mills, Aula Ammar, Jennifer Hay, Ditte Andersen, Colin Nixon, Selma Rebus, David K. Chang, Caroline Kelly, Andrea Harkin, Janet Graham, David Church, Ian Tomlinson, Mark Saunders, Tim Iveson, Tamsin R. M. Lannagan, Rene Jackstadt, Noori Maka, Paul G. Horgan, Campbell S. D. Roxburgh, Owen J. Sansom, Donald C. McMillan, Colin W. Steele, Nigel B. Jamieson, James H. Park, Antonia K. Roseweir, and Joanne Edwards

Subjects
Colorectal cancer, Cellular signaling, JAK/STAT3 signal transduction, Tumor microenvironment, Prognosis, Spatial biology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression of solid tumors. In this study we investigate the effectiveness of inhibiting JAK/STAT3 in diverse CRC models, establish in which contexts high pathway expression is prognostic and perform in depth analysis underlying phenotypes. In this study we investigated the use of JAK inhibitors for anti-cancer activity in CRC cell lines, mouse model organoids and patient-derived organoids. Immunohistochemical staining of the TransSCOT clinical trial cohort, and 2 independent large retrospective CRC patient cohorts was performed to assess the prognostic value of JAK/STAT3 expression. We performed mutational profiling, bulk RNASeq and NanoString GeoMx® spatial transcriptomics to unravel the underlying biology of aberrant signaling. Inhibition of signal transduction with JAK1/2 but not JAK2/3 inhibitors reduced cell viability in CRC cell lines, mouse, and patient derived organoids (PDOs). In PDOs, reduced Ki67 expression was observed post-treatment. A highly significant association between high JAK/STAT3 expression within tumor cells and reduced cancer-specific survival in patients with high stromal invasion (TSPhigh) was identified across 3 independent CRC patient cohorts, including the TrasnSCOT clinical trial cohort. Patients with high phosphorylated STAT3 (pSTAT3) within the TSPhigh group had higher influx of CD66b + cells and higher tumoral expression of PDL1. Bulk RNAseq of full section tumors showed enrichment of NFκB signaling and hypoxia in these cases. Spatial deconvolution through GeoMx® demonstrated higher expression of checkpoint and hypoxia-associated genes in the tumor (pan-cytokeratin positive) regions, and reduced lymphocyte receptor signaling in the TME (pan-cytokeratin- and αSMA-) and αSMA (pan-cytokeratin- and αSMA +) areas. Non-classical fibroblast signatures were detected across αSMA + regions in cases with high pSTAT3. Therefore, in this study we have shown that inhibition of JAK/STAT3 represents a promising therapeutic strategy for patients with stromal-rich CRC tumors. High expression of JAK/STAT3 proteins within both tumor and stromal cells predicts poor outcomes in CRC, and aberrant signaling is associated with distinct spatially-dependant differential gene expression.

Published
2024
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35. Asteroseismology of $\delta$ Scuti stars: emulating model grids using a neural network

Author

Scutt, Owen J., Murphy, Simon J., Nielsen, Martin B., Davies, Guy R., Bedding, Timothy R., and Lyttle, Alexander J.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Young $\delta$ Scuti stars have proven to be valuable asteroseismic targets but obtaining robust uncertainties on their inferred properties is challenging. We aim to quantify the random uncertainties in grid-based modelling of $\delta$ Sct stars. We apply Bayesian inference using nested sampling and a neural network emulator of stellar models, testing our method on both simulated and real stars. Based on results from simulated stars we demonstrate that our method can recover plausible posterior probability density estimates while accounting for both the random uncertainty from the observations and neural network emulation. We find that the posterior distributions of the fundamental parameters can be significantly non-Gaussian, multi-modal, and have strong covariance. We conclude that our method reliably estimates the random uncertainty in the modelling of $\delta$ Sct stars and paves the way for the investigation and quantification of the systematic uncertainty., Comment: 10 pages, 10 figures, 2 tables, published in Monthly Notices of the Royal Astronomical Society 01/09/2023

Published
2023
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38. Data from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

Published
2024
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39. Supplementary Figure S9 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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40. TABLE 1 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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41. TABLE 4 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

Published
2024
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42. Supplementary Tables from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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43. FIGURE 4 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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44. TABLE 3 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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45. FIGURE 3 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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46. FIGURE 5 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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47. TABLE 2 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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49. FIGURE 2 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

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2024
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50. FIGURE 1 from Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils

Author

Fetit, Rana, primary, McLaren, Alistair S., primary, White, Mark, primary, Mills, Megan L., primary, Falconer, John, primary, Cortes-Lavaud, Xabier, primary, Gilroy, Kathryn, primary, Lannagan, Tamsin R.M., primary, Ridgway, Rachel A., primary, Nixon, Colin, primary, Naiker, Varushka, primary, Njunge, Renee, primary, Clarke, Cassie J., primary, Whyte, Declan, primary, Kirschner, Kristina, primary, Jackstadt, Rene, primary, Norman, Jim, primary, Carlin, Leo M., primary, Campbell, Andrew D., primary, Sansom, Owen J., primary, and Steele, Colin W., primary

Published
2024
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