15,993 results on '"Mignon, A."'
Search Results
2. A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases.
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Kim-McManus, Olivia, Gleeson, Joseph, Mignon, Laurence, Smith Fine, Amena, Yan, Winston, Nolen, Nicole, Demarest, Scott, Berry-Kravis, Elizabeth, Finkel, Richard, Leonard, Stefanie, Finlayson, Samuel, Augustine, Erika, Lyon, Gholson, Schule, Rebecca, and Yu, Timothy
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Humans ,Precision Medicine ,Genetic Therapy ,Clinical Trials as Topic ,Genetic Diseases ,Inborn ,Research Design ,United States ,United States Food and Drug Administration - Abstract
Individualized genetic therapies-medicines that precisely target a genetic variant that may only be found in a small number of individuals, as few as only one-offer promise for addressing unmet needs in genetic disease, but present unique challenges for trial design. By nature these new individualized medicines require testing in individualized N-of-1 trials. Here, we provide a framework for maintaining scientific rigor in N-of-1 trials. Building upon best practices from traditional clinical trial design, recent guidance from the United States Food and Drug Administration, and our own clinical research experience, we suggest key considerations including comprehensive baseline natural history, selection of appropriate clinical outcome assessments (COAs) individualized to the patient genotype-phenotype for safety and efficacy assessment over time, and specific statistical considerations. Standardization of N-of-1 trial designs in this fashion will maximize efficient learning from this next generation of targeted individualized therapeutics.
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- 2024
3. The inflated, eccentric warm Jupiter TOI-4914 b orbiting a metal-poor star, and the hot Jupiters TOI-2714 b and TOI-2981 b
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Mantovan, G., Wilson, T. G., Borsato, L., Zingales, T., Biazzo, K., Nardiello, D., Malavolta, L., Desidera, S., Marzari, F., Cameron, A. Collier, Nascimbeni, V., Majidi, F. Z., Montalto, M., Piotto, G., Stassun, K. G., Winn, J. N., Jenkins, J. M., Mignon, L., Bieryla, A., Latham, D. W., Barkaoui, K., Collins, K. A., Evans, P., Fausnaugh, M. M., Granata, V., Kostov, V., Mann, A. W., Pozuelos, F. J., Radford, D. J., Relles, H. M., Rowden, P., Seager, S., Tan, T. -G., Timmermans, M., and Watkins, C. N.
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Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
Recent observations of giant planets have revealed unexpected bulk densities. Hot Jupiters, in particular, appear larger than expected for their masses compared to planetary evolution models, while warm Jupiters seem denser than expected. These differences are often attributed to the influence of the stellar incident flux, but could they also result from different planet formation processes? Is there a trend linking the planetary density to the chemical composition of the host star? In this work we present the confirmation of three giant planets in orbit around solar analogue stars. TOI-2714 b ($P \simeq 2.5$ d, $R_{\rm p} \simeq 1.22 R_{\rm J}$, $M_{\rm p} = 0.72 M_{\rm J}$) and TOI-2981 b ($P \simeq 3.6$ d, $R_{\rm p} \simeq 1.2 R_{\rm J}$, $M_{\rm p} = 2 M_{\rm J}$) are hot Jupiters on nearly circular orbits, while TOI-4914 b ($P \simeq 10.6$ d, $R_{\rm p} \simeq 1.15 R_{\rm J}$, $M_{\rm p} = 0.72 M_{\rm J}$) is a warm Jupiter with a significant eccentricity ($e = 0.41 \pm 0.02$) that orbits a star more metal-poor ([Fe/H]$~= -0.13$) than most of the stars known to host giant planets. Our radial velocity (RV) follow-up with the HARPS spectrograph allows us to detect their Keplerian signals at high significance (7, 30, and 23$\sigma$, respectively) and to place a strong constraint on the eccentricity of TOI-4914 b (18$\sigma$). TOI-4914 b, with its large radius and low insolation flux ($F_\star < 2 \times 10^8~{\rm erg~s^{-1}~cm^{-2}}$), appears to be more inflated than what is supported by current theoretical models for giant planets. Moreover, it does not conform to the previously noted trend that warm giant planets orbiting metal-poor stars have low eccentricities. This study thus provides insights into the diverse orbital characteristics and formation processes of giant exoplanets, in particular the role of stellar metallicity in the evolution of planetary systems., Comment: Accepted for publication in Astronomy & Astrophysics. 21 pages, 26 figures, and 8 tables. Abstract abridged
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- 2024
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4. The factors that influence protostellar multiplicity I: Gas temperature, density, and mass in Perseus with Nobeyama
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Murillo, N. M., Fuchs, C. M., Harsono, D., Sakai, N., Hacar, A., Johnstone, D., Mignon-Risse, R., Zeng, S., Hsieh, T. -H., Yang, Y. -L., Tobin, J. J., and Persson, M. V.
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Astrophysics - Astrophysics of Galaxies - Abstract
Protostellar multiplicity is common at all stages and mass ranges. However, the factors that determine the multiplicity of protostellar systems have not been systematically characterized through their molecular gas. Nobeyama 45m Radio Observatory OTF maps of HCN, HNC, HCO$^+$, and N$_2$H$^+$ (J = 1--0) toward five subregions in Perseus, complemented with single pointing APEX observations of HNC (J = 4--3) are used to derive physical parameters of the dense gas. Both observations have angular resolutions of $\sim$18", equivalent to $\sim$5000 AU scales at the distance of Perseus. Kinetic gas temperature is derived from the $I$(HCN)/$I$(HNC) J = 1--0 ratio, and H$_2$ density is obtained from the HNC J=4--3/J=1--0 ratio. These parameters are used to obtain the N$_2$H$^+$ and HCO$^+$ gas masses. The inferred and derived parameters are compared to source parameters. Inferred mean kinetic gas temperature ($I$(HCN)/$I$(HNC) J=1--0 ratio; ranging between 15 and 26 K), and H$_2$ volumetric density (HNC J=4--3/J=1--0; 10$^5$ -- 10$^6$ cm$^{-3}$) do not show correlations with multiplicity in Perseus. The derived gas and dust masses, 1.3 to 16 $\times~10^{-9}$ M$_{\odot}$ for the N$_2$H$^+$ gas mass, 0.1 to 25 M$_{\odot}$ for envelope dust masses (850 $\mu$m), and 0.8 to 10 $\times~10^{-10}$ M$_{\odot}$ for the HCO$^+$ gas mass, are correlated to multiplicity and number of protostellar components. The warm gas masses are a factor of 16 lower than the cold gas masses. This work shows that gas and dust mass is correlated to multiplicity at $\sim$5000 AU scales in Perseus. Higher order multiples tend to have higher gas and dust masses in general, while close binaries (separations $\leq$7") and single protostars have similar gas and dust mass distributions. On the other hand, H$_2$ density and kinetic gas temperature do not show any correlation with multiplicity., Comment: 25 pages, 12 figures, 3 appendices. Accepted for publication in A&A. The abstract has been modified to comply with arXiv's character limit
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- 2024
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5. LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia
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Wintering, Astrid, Hecht, Anna, Meyer, Julia, Wong, Eric B, Hübner, Juwita, Abelson, Sydney, Feldman, Kira, Kennedy, Vanessa E, Peretz, Cheryl AC, French, Deborah L, Maguire, Jean Ann, Jobaliya, Chintan, Vasquez, Marta Rojas, Desai, Sunil, Dulman, Robin, Nemecek, Eneida, Haines, Hilary, Hammad, Mahmoud, El Haddad, Alaa, Kogan, Scott C, Abdullaev, Zied, Chehab, Farid F, Tasian, Sarah K, Smith, Catherine C, Loh, Mignon L, and Stieglitz, Elliot
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Cancer ,Childhood Leukemia ,Hematology ,Pediatric Cancer ,Stem Cell Research - Nonembryonic - Human ,Stem Cell Research - Nonembryonic - Non-Human ,Genetics ,Pediatric ,Stem Cell Research ,Stem Cell Research - Induced Pluripotent Stem Cell ,Rare Diseases ,2.1 Biological and endogenous factors ,Humans ,Leukemia ,Myelomonocytic ,Juvenile ,Adaptor Proteins ,Signal Transducing ,Male ,Female ,Infant ,Child ,Preschool ,Mutation ,Intracellular Signaling Peptides and Proteins ,Child ,Signal Transduction ,Pyrazoles ,Nitriles ,Pyrimidines ,Immunology - Abstract
Mutations in five canonical Ras pathway genes (NF1, NRAS, KRAS, PTPN11 and CBL) are detected in nearly 90% of patients with juvenile myelomonocytic leukemia (JMML), a frequently fatal malignant neoplasm of early childhood. In this report, we describe seven patients diagnosed with SH2B3-mutated JMML, including five patients who were found to have initiating, loss-of-function mutations in the gene. SH2B3 encodes the adaptor protein LNK, a negative regulator of normal hematopoiesis upstream of the Ras pathway. These mutations were identified to be germline, somatic or a combination of both. Loss of function of LNK, which has been observed in other myeloid malignancies, results in abnormal proliferation of hematopoietic cells due to cytokine hypersensitivity and activation of the JAK/STAT signaling pathway. In vitro studies of induced pluripotent stem cell-derived JMML-like hematopoietic progenitor cells also demonstrated sensitivity of SH2B3-mutated hematopoietic progenitor cells to JAK inhibition. Lastly, we describe two patients with JMML and SH2B3 mutations who were treated with the JAK1/2 inhibitor ruxolitinib. This report expands the spectrum of initiating mutations in JMML and raises the possibility of targeting the JAK/STAT pathway in patients with SH2B3 mutations.
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- 2024
6. NIRPS first light and early science: breaking the 1 m/s RV precision barrier at infrared wavelengths
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Artigau, Étienne, Bouchy, François, Doyon, René, Baron, Frédérique, Malo, Lison, Wildi, François, Pepe, Franceso, Cook, Neil J., Thibault, Simon, Reshetov, Vladimir, Dumusque, Xavier, Lovis, Christophe, Sosnowska, Danuta, Martins, Bruno L. Canto, De Medeiros, Jose Renan, Delfosse, Xavier, Santos, Nuno, Rebolo, Rafael, Abreu, Manuel, Allain, Guillaume, Allart, Romain, Auger, Hugues, Barros, Susana, Bazinet, Luc, Blind, Nicolas, Boisse, Isabelle, Bonfils, Xavier, Bourrier, Vincent, Bovay, Sébastien, Broeg, Christopher, Brousseau, Denis, Bruniquel, Vincent, Cabral, Alexandre, Cadieux, Charles, Carmona, Andres, Carteret, Yann, Challita, Zalpha, Chazelas, Bruno, Cloutier, Ryan, Coelho, João, Cointepas, Marion, Conod, Uriel, Cowan, Nicolas, Cristo, Eduardo, da Silva, João Gomes, Dauplaise, Laurie, Gomes, Roseane de Lima, Delgado-Mena, Elisa, Ehrenreich, David, Faria, João, Figueira, Pedro, Forveille, Thierry, Frensch, Yolanda, Gagné, Jonathan, Genest, Frédéric, Genolet, Ludovic, Hernández, Jonay I. González, Témich, Félix Gracia, Grieves, Nolan, Hernandez, Olivier, Hobson, Melissa J., Hoeijmakers, Jens, Kerley, Dan, Krishnamurthy, Vigneshwaran, Lafrenière, David, Lamontagne, Pierrot, Larue, Pierre, Leaf, Henry, Leão, Izan C., Lim, Olivia, Curto, Gaspare Lo, Martins, Allan M., Melo, Claudio, Messias, Yuri S., Mignon, Lucile, Moranta, Leslie, Mordasini, Christoph, Moulla, Khaled Al, Mounzer, Dany, L'Heureux, Alexandrine, Nari, Nicola, Nielsen, Louise, Osborn, Ares, Parc, Léna, Pasquini, Luca, Passegger, Vera M., Pelletier, Stefan, Peroux, Céline, Piaulet, Caroline, Plotnykov, Mykhaylo, Poulin-Girard, Anne-Sophie, Rasilla, José Luis, Saint-Antoine, Jonathan, Sarajlic, Mirsad, Segovia, Alex, Seidel, Julia, Ségransan, Damien, Silva, Ana Rita Costa, Srivastava, Avidaan, Stefanov, Atanas K., Mascareño, Alejandro Suárez, Sordet, Michael, Teixeira, Márcio A., Udry, Stéphane, Valencia, Diana, Vallée, Philippe, Vandal, Thomas, Vaulato, Valentina, Wade, Gregg, Wardenier, Joost P., Wehbé, Bachar, Weisserman, Drew, Wevers, Ivan, and Zins, Gérard
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Earth and Planetary Astrophysics - Abstract
The Near-InfraRed Planet Searcher or NIRPS is a precision radial velocity spectrograph developed through collaborative efforts among laboratories in Switzerland, Canada, Brazil, France, Portugal and Spain. NIRPS extends to the 0.98-1.8 $\mu$m domain of the pioneering HARPS instrument at the La Silla 3.6-m telescope in Chile and it has achieved unparalleled precision, measuring stellar radial velocities in the infrared with accuracy better than 1 m/s. NIRPS can be used either stand-alone or simultaneously with HARPS. Commissioned in late 2022 and early 2023, NIRPS embarked on a 5-year Guaranteed Time Observation (GTO) program in April 2023, spanning 720 observing nights. This program focuses on planetary systems around M dwarfs, encompassing both the immediate solar vicinity and transit follow-ups, alongside transit and emission spectroscopy observations. We highlight NIRPS's current performances and the insights gained during its deployment at the telescope. The lessons learned and successes achieved contribute to the ongoing advancement of precision radial velocity measurements and high spectral fidelity, further solidifying NIRPS' role in the forefront of the field of exoplanets., Comment: Proceeding at the SPIE Astronomical Telescopes + Instrumentation conference [Yokohama,Japan; June 2024]
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- 2024
7. A multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia
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Xu, Jason, Chen, Changya, Sussman, Jonathan H., Yoshimura, Satoshi, Vincent, Tiffaney, Pölönen, Petri, Hu, Jianzhong, Bandyopadhyay, Shovik, Elghawy, Omar, Yu, Wenbao, Tumulty, Joseph, Chen, Chia-hui, Li, Elizabeth Y., Diorio, Caroline, Shraim, Rawan, Newman, Haley, Uppuluri, Lahari, Li, Alexander, Chen, Gregory M., Wu, David W., Ding, Yang-yang, Xu, Jessica A., Karanfilovski, Damjan, Lim, Tristan, Hsu, Miles, Thadi, Anusha, Ahn, Kyung Jin, Wu, Chi-Yun, Peng, Jacqueline, Sun, Yusha, Wang, Alice, Mehta, Rushabh, Frank, David, Meyer, Lauren, Loh, Mignon L., Raetz, Elizabeth A., Chen, Zhiguo, Wood, Brent L., Devidas, Meenakshi, Dunsmore, Kimberly P., Winter, Stuart S., Chang, Ti-Cheng, Wu, Gang, Pounds, Stanley B., Zhang, Nancy R., Carroll, William, Hunger, Stephen P., Bernt, Kathrin, Yang, Jun J., Mullighan, Charles G., Tan, Kai, and Teachey, David T.
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- 2024
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8. Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study
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Rheingold, Susan R., Bhojwani, Deepa, Ji, Lingyun, Xu, Xinxin, Devidas, Meenakshi, Kairalla, John A., Shago, Mary, Heerema, Nyla A., Carroll, Andrew J., Breidenbach, Heather, Borowitz, Michael, Wood, Brent L., Angiolillo, Anne L., Asselin, Barbara L., Bowman, W. Paul, Brown, Patrick, Dreyer, ZoAnn E., Dunsmore, Kimberly P., Hilden, Joanne M., Larsen, Eric, Maloney, Kelly, Matloub, Yousif, Mattano, Leonard A., Winter, Stuart S., Gore, Lia, Winick, Naomi J., Carroll, William L., Hunger, Stephen P., Raetz, Elizabeth A., and Loh, Mignon L.
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- 2024
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9. Prevention values for copper (low tier approach) in subtropical acidic soils
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de Oliveira, Daniela Aparecida, Freitas, Thiago Ramos, Rosa, Vanessa Mignon Dalla, Oliveira Filho, Luís Carlos Iuñes, da Veiga, Milton, Campos, Mari Lucia, Miquelluti, David José, and Klauberg-Filho, Osmar
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- 2024
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10. Antisense oligonucleotide therapy in an individual with KIF1A-associated neurological disorder
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Ziegler, Alban, Carroll, Joanne, Bain, Jennifer M., Sands, Tristan T., Fee, Robert J., Uher, David, Kanner, Cara H., Montes, Jacqueline, Glass, Sarah, Douville, Julie, Mignon, Laurence, Gleeson, Joseph G., Crooke, Stanley T., and Chung, Wendy K.
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- 2024
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11. Characterisation of the stellar activity of M dwarfs. II. Relationship between Ca, H$\alpha$, and Na chromospheric emissions
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Meunier, Nadège, Mignon, Lucile, Kretzschmar, Matthieu, and Delfosse, Xavier
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Earth and Planetary Astrophysics - Abstract
The chromospheric emission estimated in the core of different lines, such as Ca II H & K, Na D1 and D2, and Halpha, is not always correlated between lines, as the Ca II H & K and Halpha emission time series are anti-correlated for a few percent of the stars, contrary to what is observed on the Sun. This puzzling result has been observed for both solar-type and M stars. Our objective is to characterise these relationships in more detail using complementary criteria, based on a set of spectra obtained with HARPS for a large sample of M dwarfs, to evaluate whether or not additional processes are required to explain the observations. We analysed the time average and variability of the Ca, Na, and Halpha emissions for 177 M0-M8 stars. We computed synthetic Halpha time series based on different assumptions of plage properties. The statistical properties of our sample, in terms of correlations and slopes between indices at different timescales, differ from what we previously obtained for FGK stars, with fewer stars with a null correlation, and a weaker dependence of the correlations on timescale. However, there can be a large dispersion from one season to another for stars. We find a clear indication of a change in the slope sign from the relation between averaged Ca (or Na) and Halpha for the most massive M dwarfs, as well as a change in slope in the Na-Ca relation. At this stage, we are not able to find simple plage properties that, alone, are sufficient to reproduce the observations. Simulations shows that it is not straightforward to compare the temporal variability correlation and the integrated indices and demonstrate the need for complex activity patterns to explain some of the observations. We conclude that the relation between these indices exhibits a large diversity in behaviour. More detailed simulations with complex activity patterns are necessary to understand these observations., Comment: Paper accepted in Astronomy and Astrophysics 15 January 2024
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- 2024
12. Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children's Oncology Group.
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Stieglitz, Elliot, Lee, Alex G, Angus, Steven P, Davis, Christopher, Barkauskas, Donald A, Hall, David, Kogan, Scott C, Meyer, Julia, Rhodes, Steven D, Tasian, Sarah K, Xuei, Xiaoling, Shannon, Kevin, Loh, Mignon L, Fox, Elizabeth, and Weigel, Brenda J
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Oncology and Carcinogenesis ,Clinical Research ,Hematology ,Cancer ,Clinical Trials and Supportive Activities ,Regenerative Medicine ,Transplantation ,Pediatric ,Pediatric Cancer ,Childhood Leukemia ,Rare Diseases ,Stem Cell Research ,Evaluation of treatments and therapeutic interventions ,6.2 Cellular and gene therapies ,6.1 Pharmaceuticals ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Juvenile myelomonocytic leukemia (JMML) is a hematologic malignancy of young children caused by mutations that increase Ras signaling output. Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment, but patients with relapsed or refractory (advanced) disease have dismal outcomes. This phase II trial evaluated the safety and efficacy of trametinib, an oral MEK1/2 inhibitor, in patients with advanced JMML. Ten infants and children were enrolled, and the objective response rate was 50%. Four patients with refractory disease proceeded to HSCT after receiving trametinib. Three additional patients completed all 12 cycles permitted on study and continue to receive off-protocol trametinib without HSCT. The remaining three patients had progressive disease with two demonstrating molecular evolution by the end of cycle 2. Transcriptomic and proteomic analyses provided novel insights into the mechanisms of response and resistance to trametinib in JMML. ClinicalTrials.gov Identifier: NCT03190915. Significance: Trametinib was safe and effective in young children with relapsed or refractory JMML, a lethal disease with poor survival rates. Seven of 10 patients completed the maximum 12 cycles of therapy or used trametinib as a bridge to HSCT and are alive with a median follow-up of 24 months.
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- 2024
13. A Case Study from the Overexpression of OsTZF5, Encoding a CCCH Tandem Zinc Finger Protein, in Rice Plants Across Nineteen Yield Trials.
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Grondin, Alexandre, Natividad, Mignon, Ogata, Takuya, Jan, Asad, Gaudin, Amélie, Trijatmiko, Kurniawan, Liwanag, Evelyn, Maruyama, Kyonoshin, Fujita, Yasunari, Yamaguchi-Shinozaki, Kazuko, Nakashima, Kazuo, Slamet-Loedin, Inez, and Henry, Amelia
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Drought ,Rice ,Transgene expression ,Transgenic ,Yield - Abstract
BACKGROUND: Development of transgenic rice overexpressing transcription factors involved in drought response has been previously reported to confer drought tolerance and therefore represents a means of crop improvement. We transformed lowland rice IR64 with OsTZF5, encoding a CCCH-tandem zinc finger protein, under the control of the rice LIP9 stress-inducible promoter and compared the drought response of transgenic lines and nulls to IR64 in successive screenhouse paddy and field trials up to the T6 generation. RESULTS: Compared to the well-watered conditions, the level of drought stress across experiments varied from a minimum of - 25 to - 75 kPa at a soil depth of 30 cm which reduced biomass by 30-55% and grain yield by 1-92%, presenting a range of drought severities. OsTZF5 transgenic lines showed high yield advantage under drought over IR64 in early generations, which was related to shorter time to flowering, lower shoot biomass and higher harvest index. However, the increases in values for yield and related traits in the transgenics became smaller over successive generations despite continued detection of drought-induced transgene expression as conferred by the LIP9 promoter. The decreased advantage of the transgenics over generations tended to coincide with increased levels of homozygosity. Background cleaning of the transgenic lines as well as introgression of the transgene into an IR64 line containing major-effect drought yield QTLs, which were evaluated starting at the BC3F1 and BC2F3 generation, respectively, did not result in consistently increased yield under drought as compared to the respective checks. CONCLUSIONS: Although we cannot conclusively explain the genetic factors behind the loss of yield advantage of the transgenics under drought across generations, our results help in distinguishing among potential drought tolerance mechanisms related to effectiveness of the transgenics, since early flowering and harvest index most closely reflected the levels of yield advantage in the transgenics across generations while reduced biomass did not.
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- 2024
14. Dialysis for paediatric acute kidney injury in Cape Town, South Africa
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McCulloch, Mignon I., Luyckx, Valerie A., Morrow, Brenda, Nourse, Peter, Coetzee, Ashton, Reddy, Deveshni, Du Buisson, Christel, Buckley, Jonathan, Webber, Ilana, Numanoglu, Alp, Sinclair, Gina, Nelson, Candice, Salie, Shamiel, Reichmuth, Kirsten, and Argent, Andrew C.
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- 2024
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15. The genomic basis of childhood T-lineage acute lymphoblastic leukaemia
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Pölönen, Petri, Di Giacomo, Danika, Seffernick, Anna Eames, Elsayed, Abdelrahman, Kimura, Shunsuke, Benini, Francesca, Montefiori, Lindsey E., Wood, Brent L., Xu, Jason, Chen, Changya, Cheng, Zhongshan, Newman, Haley, Myers, Jason, Iacobucci, Ilaria, Li, Elizabeth, Sussman, Jonathan, Hedges, Dale, Hui, Yawei, Diorio, Caroline, Uppuluri, Lahari, Frank, David, Fan, Yiping, Chang, Yunchao, Meshinchi, Soheil, Ries, Rhonda, Shraim, Rawan, Li, Alexander, Bernt, Kathrin M., Devidas, Meenakshi, Winter, Stuart S., Dunsmore, Kimberly P., Inaba, Hiroto, Carroll, William L., Ramirez, Nilsa C., Phillips, Aaron H., Kriwacki, Richard W., Yang, Jun J., Vincent, Tiffaney L., Zhao, Yaqi, Ghate, Pankaj S., Wang, Jian, Reilly, Colleen, Zhou, Xin, Sanders, Mathijs A., Takita, Junko, Kato, Motohiro, Takasugi, Nao, Chang, Bill H., Press, Richard D., Loh, Mignon, Rampersaud, Evadnie, Raetz, Elizabeth, Hunger, Stephen P., Tan, Kai, Chang, Ti-Cheng, Wu, Gang, Pounds, Stanley B., Mullighan, Charles G., and Teachey, David T.
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- 2024
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16. Geographical migration and fitness dynamics of Streptococcus pneumoniae
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Belman, Sophie, Lefrancq, Noémie, Nzenze, Susan, Downs, Sarah, du Plessis, Mignon, Lo, Stephanie W., McGee, Lesley, Madhi, Shabir A., von Gottberg, Anne, Bentley, Stephen D., and Salje, Henrik
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- 2024
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17. The SOPHIE search for northern extrasolar planets-XIX. A system including a cold sub-Neptune potentially transiting a V = 6.5 star HD88986
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Heidari, N., Boisse, I., Hara, N. C., Wilson, T. G., Kiefer, F., Hébrard, G., Philipot, F., Hoyer, S., Stassun, K. G., Henry, G. W., Santos, N. C., Acuña, L., Almasian, D., Arnold, L., Astudillo-Defru, N., Attia, O., Bonfils, X., Bouchy, F., Bourrier, V., Collet, B., Cortés-Zuleta, P., Carmona, A., Delfosse, X., Dalal, S., Deleuil, M., Demangeon, O. D. S., Díaz, R. F., Dumusque, X., Ehrenreich, D., Forveille, T., Hobson, M. J., Jenkins, J. S., Jenkins, J. M., Lagrange, A. M., Latham, D. W., Larue, P., Liu, J., Moutou, C., Mignon, L., Osborn, H. P., Pepe, F., Rapetti, D., Rodrigues, J., Santerne, A., Segransan, D., Shporer, A., Sulis, S., Torres, G., Udry, S., Vakili, F., Vanderburg, A., Venot, O., Vivien, H. G., and Vines, J. I.
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Astrophysics - Earth and Planetary Astrophysics - Abstract
Transiting planets with orbital periods longer than 40 d are extremely rare among the 5000+ planets discovered so far. The lack of discoveries of this population poses a challenge to research into planetary demographics, formation, and evolution. Here, we present the detection and characterization of HD88986b, a potentially transiting sub-Neptune, possessing the longest orbital period among known transiting small planets (< 4 R$_{\oplus}$) with a precise mass measurement ($\sigma_M/M$ > 25%). Additionally, we identified the presence of a massive companion in a wider orbit around HD88986. Our analysis reveals that HD88986b, based on two potential single transits on sector 21 and sector 48 which are both consistent with the predicted transit time from the RV model, is potentially transiting. The joint analysis of RV and photometric data show that HD88986b has a radius of 2.49$\pm$0.18 R$_{\oplus}$, a mass of 17.2$^{+4.0}_{-3.8}$ M$_{\oplus}$, and it orbits every 146.05$^{+0.43}_{-0.40}$ d around a subgiant HD88986 which is one of the closest and brightest exoplanet host stars (G2V type, R=1.543 $\pm$0.065 R$_{\odot}$, V=$6.47\pm 0.01$ mag, distance=33.37$\pm$0.04 pc). The nature of the outer, massive companion is still to be confirmed; a joint analysis of RVs, Hipparcos, and Gaia astrometric data shows that with a 3$\sigma$ confidence interval, its semi-major axis is between 16.7 and 38.8 au and its mass is between 68 and 284 M$_{Jup}$. HD88986b's wide orbit suggests the planet did not undergo significant mass loss due to extreme-ultraviolet radiation from its host star. Therefore, it probably maintained its primordial composition, allowing us to probe its formation scenario. Furthermore, the cold nature of HD88986b (460$\pm$8 K), thanks to its long orbital period, will open up exciting opportunities for future studies of cold atmosphere composition characterization., Comment: 37 pages, accepted to be published in A&A
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- 2023
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18. New Mass and Radius Constraints on the LHS 1140 Planets -- LHS 1140 b is Either a Temperate Mini-Neptune or a Water World
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Cadieux, Charles, Plotnykov, Mykhaylo, Doyon, René, Valencia, Diana, Jahandar, Farbod, Dang, Lisa, Turbet, Martin, Fauchez, Thomas J., Cloutier, Ryan, Cherubim, Collin, Artigau, Étienne, Cook, Neil J., Edwards, Billy, Hallatt, Tim, Charnay, Benjamin, Bouchy, François, Allart, Romain, Mignon, Lucile, Baron, Frédérique, Barros, Susana C. C., Benneke, Björn, Martins, B. L. Canto, Cowan, Nicolas B., De Medeiros, J. R., Delfosse, Xavier, Delgado-Mena, Elisa, Dumusque, Xavier, Ehrenreich, David, Hara, Nathan C., Lafrenière, David, Frensch, Yolanda G. C., Hernández, J. I. González, Curto, Gaspare Lo, Malo, Lison, Melo, Claudio, Mounzer, Dany, Passeger, Vera Maria, Pepe, Francesco, Poulin-Girard, Anne-Sophie, Santos, Nuno C., Sosnowska, Danuta, Mascareño, Alejandro Suárez, Thibault, Simon, Vaulato, Valentina, Wade, Gregg A., and Wildi, François
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Astrophysics - Earth and Planetary Astrophysics - Abstract
The two-planet transiting system LHS 1140 has been extensively observed since its discovery in 2017, notably with $Spitzer$, HST, TESS, and ESPRESSO, placing strong constraints on the parameters of the M4.5 host star and its small temperate exoplanets, LHS 1140 b and c. Here, we reanalyse the ESPRESSO observations of LHS 1140 with the novel line-by-line framework designed to fully exploit the radial velocity content of a stellar spectrum while being resilient to outlier measurements. The improved radial velocities, combined with updated stellar parameters, consolidate our knowledge on the mass of LHS 1140 b (5.60$\pm$0.19 M$_{\oplus}$) and LHS 1140 c (1.91$\pm$0.06 M$_{\oplus}$) with unprecedented precision of 3%. Transits from $Spitzer$, HST, and TESS are jointly analysed for the first time, allowing us to refine the planetary radii of b (1.730$\pm$0.025 R$_{\oplus}$) and c (1.272$\pm$0.026 R$_{\oplus}$). Stellar abundance measurements of refractory elements (Fe, Mg and Si) obtained with NIRPS are used to constrain the internal structure of LHS 1140 b. This planet is unlikely to be a rocky super-Earth as previously reported, but rather a mini-Neptune with a $\sim$0.1% H/He envelope by mass or a water world with a water-mass fraction between 9 and 19% depending on the atmospheric composition and relative abundance of Fe and Mg. While the mini-Neptune case would not be habitable, a water-abundant LHS 1140 b potentially has habitable surface conditions according to 3D global climate models, suggesting liquid water at the substellar point for atmospheres with relatively low CO$_2$ concentration, from Earth-like to a few bars., Comment: 31 pages, 18 figures, accepted for publication in ApJL
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- 2023
19. Neural network approach for a rapid prediction of metal-supported borophene properties
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Mignon, Pierre, Allouche, Abdul-Rahman, Innis, Neil Richard, and Bousige, Colin
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Condensed Matter - Materials Science ,Physics - Chemical Physics ,Physics - Computational Physics - Abstract
We develop a high-dimensional neural network potential (NNP) to describe the structural and energetic properties of borophene deposited on silver. This NNP has the accuracy of DFT calculations while achieving computational speedups of several orders of magnitude, allowing the study of extensive structures that may reveal intriguing moir\'e patterns or surface corrugations. We describe an efficient approach to constructing the training data set using an iterative technique known as the "adaptive learning approach". The developed NNP potential is able to produce, with an excellent agreement, the structure, energy and forces of DFT. Finally, the calculated stability of various borophene polymorphs, including those not initially included in the training dataset, shows better stabilization for $\nu\sim0.1$ hole density, and in particular for the allotrope $\alpha$ ($\nu=\frac{1}{9}$). The stability of borophene on the metal surface is shown to depend on its orientation, implying structural corrugation patterns that can only be observed from long time simulations on extended systems. The NNP also demonstrates its ability to simulate vibrational densities of states and produce realistic structures, with simulated STM images closely matching the experimental ones.
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- 2023
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20. Impact of pneumococcal conjugate vaccines on invasive pneumococcal disease-causing lineages among South African children
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Lekhuleni, Cebile, Ndlangisa, Kedibone, Gladstone, Rebecca A., Chochua, Sopio, Metcalf, Benjamin J., Li, Yuan, Kleynhans, Jackie, de Gouveia, Linda, Hazelhurst, Scott, Ferreira, Ana D. S., Skosana, Happy, Walaza, Sibongile, Quan, Vanessa, Meiring, Susan, Hawkins, Paulina A., McGee, Lesley, Bentley, Stephen D., Cohen, Cheryl, Lo, Stephanie W., von Gottberg, Anne, and du Plessis, Mignon
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- 2024
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21. Characteristics of infections with ancestral, Beta and Delta variants of SARS-CoV-2 in the PHIRST-C community cohort study, South Africa, 2020-2021
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Cohen, Cheryl, Kleynhans, Jackie, von Gottberg, Anne, McMorrow, Meredith L., Wolter, Nicole, Bhiman, Jinal N., Moyes, Jocelyn, du Plessis, Mignon, Carrim, Maimuna, Buys, Amelia, Martinson, Neil A., Kahn, Kathleen, Tollman, Stephen, Lebina, Limakatso, Wafawanaka, Floidy, du Toit, Jacques, Gómez-Olivé, Francesc Xavier, Dawood, Fatimah S., Mkhencele, Thulisa, and Tempia, Stefano
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- 2024
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22. A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases
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Olivia Kim-McManus, Joseph G. Gleeson, Laurence Mignon, Amena Smith Fine, Winston Yan, Nicole Nolen, Scott Demarest, Elizabeth Berry-Kravis, Richard Finkel, Stefanie Leonard, Samuel Finlayson, Erika Augustine, Gholson J. Lyon, Rebecca Schule, and Timothy Yu
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Science - Abstract
Abstract Individualized genetic therapies—medicines that precisely target a genetic variant that may only be found in a small number of individuals, as few as only one—offer promise for addressing unmet needs in genetic disease, but present unique challenges for trial design. By nature these new individualized medicines require testing in individualized N-of-1 trials. Here, we provide a framework for maintaining scientific rigor in N-of-1 trials. Building upon best practices from traditional clinical trial design, recent guidance from the United States Food and Drug Administration, and our own clinical research experience, we suggest key considerations including comprehensive baseline natural history, selection of appropriate clinical outcome assessments (COAs) individualized to the patient genotype-phenotype for safety and efficacy assessment over time, and specific statistical considerations. Standardization of N-of-1 trial designs in this fashion will maximize efficient learning from this next generation of targeted individualized therapeutics.
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- 2024
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23. A community-based treatment and rehabilitation pathway for people with mental disorders recently convicted of an offence
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Lara Arsuffi, Kerry Ozcelik, Clare Bingham, Pamela J. Taylor, and Mignon French
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Mental health treatment requirements ,community sentences ,mentally disordered offenders ,probation ,community mental health teams ,Psychiatry ,RC435-571 - Abstract
People with mental disorders can receive treatment in the community. Some, however, fall out of services and into the criminal justice system, running the risk of imprisonment and a deteriorating mental health cycle. This editorial describes Mental Health Treatment Requirements (MHTRs), that is court-imposed sentences that enable people in the UK to access treatment in the community and divert them from short custodial sentences. MHTRs have proven successful for people with primary care mental health needs. It remains difficult to secure these sentences for people with secondary care mental health needs. Three new ‘proof of concept’ sites for secondary care MHTRs may help understand barriers and find solutions.
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- 2024
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24. Voice of a caregiver: call for action for multidisciplinary teams in the care for children with atypical hemolytic uremic syndrome
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Burke, Linda, Sethi, Sidharth Kumar, Boyer, Olivia, Licht, Christoph, McCulloch, Mignon, Shah, Raghav, Luyckx, Valerie A., and Raina, Rupesh
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- 2024
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25. Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: A Report from the Children's Oncology Group
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Stieglitz, Elliot, Lee, Alex, Angus, Steven P, Davis, Christopher, Barkauskas, Donald, Hall, David, Kogan, Scott C, Meyer, Julia, Rhodes, Steven D, Xuei, Xiaoling, Shannon, Kevin, Loh, Mignon L, Fox, Elizabeth, and Weigel, Brenda J
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Oncology and Carcinogenesis ,Stem Cell Research - Nonembryonic - Non-Human ,Minority Health ,Hematology ,Stem Cell Research ,Genetics ,Rare Diseases ,Pediatric Cancer ,Childhood Leukemia ,Cancer ,Pediatric ,Clinical Trials and Supportive Activities ,Transplantation ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Inflammatory and immune system ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Paediatrics and Reproductive Medicine ,Immunology ,Biochemistry and cell biology ,Cardiovascular medicine and haematology ,Paediatrics - Abstract
Background: Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of infants and toddlers. Upfront therapies typically include high-dose cytarabine or azacitidine, but the only definitive treatment is hematopoietic stem cell transplantation (HSCT). While HSCT cures ~50% of patients, the prognosis is dismal for those who relapse. In the absence of a second HSCT, patients who relapse have a 2-year overall survival of ~10%. JMML is initiated by germline and somatic driver mutations in NF1, KRAS, NRAS, PTPN11, and CBL. These mutations converge on Ras signaling, leading to elevated levels of active Ras-GTP in specific cell lineages. Genetically engineered mouse (GEM) models accurately model key molecular, biologic, and biochemical features of JMML. Preclinical trials of the allosteric MEK inhibitors in Kras and Nf1 mutant mice demonstrated dramatic phenotypic responses with reduction in white blood cell counts, resolution of splenomegaly, and reversion to normal erythropoiesis. Based on the promising efficacy signal in GEM models, we evaluated trametinib, an orally bioavailable allosteric inhibitor of MEK1/2, in a prospective clinical trial in children with relapsed or refractory JMML to determine the overall response rate to trametinib. Results: Ten infants and children with JMML (median age 23.6 months) were enrolled and all were evaluable for safety and efficacy. Patients received age-adjusted dosing of trametinib for 28-day cycles and could remain on study for up to 12 cycles in the absence of disease progression or toxicity. A clonal Ras pathway mutation was confirmed in the blood and/or bone marrow of all patients. The objective response rate was 50% (two complete and three partial clinical responses). Four patients proceeded to HSCT after receiving protocol therapy and remain alive in complete remission with undetectable levels of the Ras pathway mutation identified at enrollment. Three additional patients completed 12 cycles of trametinib and continue to receive off-protocol therapy 6-24 months later with no change in the variant allele frequency of the underlying Ras pathway mutation. The remaining three patients had progressive disease with two demonstrating molecular evolution by the end of cycle 2. Paired pre- and post-trametinib RNASeq and proteomic analyses confirmed on-target biochemical effects of trametinib with down-regulation of both Ras/MAPK pathway related gene expression and MEK1/2 kinase activity, respectively. To gain deeper insight into how trametinib might affect distinct populations of hematopoietic cells, we generated single cell RNASeq data before and after treatment. The most prominent finding was a reduction in the proportions of classical and non-classical monocytes and broad downregulation of immune-related pathways in all cell populations. However, the downregulation of MAPK signaling genes was confined to specific cell types including, macrophages, classical monocytes, and granulocyte-monocyte progenitors, which uniquely displayed downregulated KRAS-related signatures following treatment. High DNA methylation and the presence of >1 mutation at enrollment correlated with lack of response to trametinib. Conclusions: We conducted an open label, phase 2 trial of trametinib in children with relapsed or refractory JMML. This is the first completed study of a MEK inhibitor in any hematologic malignancy in children. The trial met its primary objective and demonstrated a 50% objective response rate with 70% of patients bridging to a successful HSCT or completing the maximum 12 cycles permitted on study. The three patients who completed 12 cycles continue to receive trametinib off study for as long as 2 years. Although limited by a small number of patients, the long-term survival, and correlative molecular analyses from this trial raise provocative questions about whether certain patients with JMML might be spared the long-term adverse health risks of genotoxic HSCT conditioning regimens based on favorable molecular characteristics at diagnosis. This hypothesis will now be tested in a national, risk-stratified therapeutic trial (NCT05849662) of trametinib in combination with azacitidine in newly diagnosed patients. The authors would like to acknowledge funding and support from: NCTN Operations Center Grant (U10CA180886), NCTN Statistics & Data Center Grant (U10CA180899), and the St. Baldrick's Foundation.
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- 2023
26. A 6-year review of acute post-streptococcal glomerulonephritis at a public children’s hospital in Cape Town, South Africa
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Abugrain, Khadija, McCulloch, Mignon I, Muloiwa, Rudzani, Luyckx, Valerie A, and Buys, Heloise
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- 2024
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27. Evaluation of the prognostic potential of histopathological subtyping in high-grade serous ovarian carcinoma
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Zelisse, Hein S., Hwan, Robin A., van de Vijver, Marc J., Dijk, Frederike, Mom, Constantijne H., Hooijer, Gerrit K. J., van Gent, Mignon D. J. M., and Snijders, Malou L. H.
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- 2024
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28. Impact of pneumococcal conjugate vaccines on invasive pneumococcal disease-causing lineages among South African children
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Cebile Lekhuleni, Kedibone Ndlangisa, Rebecca A. Gladstone, Sopio Chochua, Benjamin J. Metcalf, Yuan Li, Jackie Kleynhans, Linda de Gouveia, Scott Hazelhurst, Ana D. S. Ferreira, Happy Skosana, Sibongile Walaza, Vanessa Quan, Susan Meiring, Paulina A. Hawkins, Lesley McGee, Stephen D. Bentley, Cheryl Cohen, Stephanie W. Lo, Anne von Gottberg, and Mignon du Plessis
- Subjects
Science - Abstract
Abstract Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged
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- 2024
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29. South African urban youth responses to living in a world with covid: Lessons from #Slam4urLife
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Mazetti, Cara, Schmidt, Sophie, Hardie, Mignon, Boulle, Jacqueline, and Parnell, Susan
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- 2022
30. Tretinoin Enhances the Effects of Chemotherapy in Juvenile Myelomonocytic Leukemia Using an Ex Vivo Drug Sensitivity Assay.
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Gu, Christine, Richardson, Michelle, Kita, Ryosuke, Santaguida, Marianne, Ali, Kamran, Strachan, Debbie, Dhar, Anukriti, Yam, George, Anderson, Wade, Anderson, Erica, Hübner, Juwita, Tasian, Sarah, Loh, Mignon, Lacher, Markus, and Stieglitz, Elliot
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Child ,Humans ,Leukemia ,Myelomonocytic ,Juvenile ,Tretinoin ,Azacitidine ,Hematopoietic Stem Cell Transplantation - Abstract
PURPOSE: Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric malignancy with myelodysplastic and myeloproliferative features. Curative treatment is restricted to hematopoietic stem-cell transplantation. Fludarabine combined with cytarabine (FLA) and 5-azacitidine (AZA) monotherapy are commonly used pre-transplant therapies. Here, we present a drug screening strategy using a flow cytometry-based precision medicine platform to identify potential additional therapeutic vulnerabilities. METHODS: We screened 120 dual- and 10 triple-drug combinations (DCs) on peripheral blood (n = 21) or bone marrow (n = 6) samples from 27 children with JMML to identify DCs more effectively reducing leukemic cells than the DCs components on their own. If fewer leukemic cells survived a DC ex vivo treatment compared with that DCs most effective component alone, the drug effect was referred to as cooperative. The difference between the two resistant fractions is the effect size. RESULTS: We identified 26 dual- and one triple-DC more effective than their components. The differentiation agent tretinoin (TRET; all-trans retinoic acid) reduced the resistant fraction of FLA in 19/21 (90%) samples (decrease from 15% [2%-61%] to 11% [2%-50%] with a mean effect size of 3.8% [0.5%-11%]), and of AZA in 19/25 (76%) samples (decrease from 69% [34%-100+%] to 47% [17%-83%] with a mean effect size of 16% [0.3%-40%]). Among the resistant fractions, the mean proportion of CD38+ cells increased from 7% (0.03%-25%; FLA) to 17% (0.3%-38%; FLA + TRET) or from 10% (0.2%-31%; AZA) to 51% (0.8%-88%; AZA + TRET). CONCLUSION: TRET enhanced the effects of FLA and AZA in ex vivo assays with primary JMML samples.
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- 2023
31. What Critical Race Theory Is, What It Isn't, and Why It Is Important, You Should Know: A Call to Action
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Reed, Elaine, Figueroa, Elba, and Carpenter, Mignon
- Abstract
Despite emerging from legal scholars in the 1970s, the term Critical Race Theory is currently at the forefront with increased attention focused on its framework and its use to explore and analyze racism in education. While this has led to school districts examining structural racism and making equitable changes, a subsequent backlash has also occurred. Critical Race Theory's use and application have become part of a contentious debate and there is a misunderstanding about what the theory entails and misperceptions to how it is being used. Forty-one states have passed legislation banning the teaching of Critical Race Theory and concepts associated with it while others have created systems to report complaints of the framework's use and penalize educators. The purpose of this call to action is to open lines of communication, create dialogue and break down the truth about Critical Race Theory.
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- 2022
32. Near-IR and optical radial velocities of the active M dwarf star Gl 388 (AD Leo) with SPIRou at CFHT and SOPHIE at OHP: A 2.23 day rotation period and no evidence for a corotating planet
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Carmona, A., Delfosse, X., Bellotti, S., Cortés-Zuleta, P., Ould-Elhkim, M., Heidari, N., Mignon, L., Donati, J. F., Moutou, C., Cook, N., Artigau, E., Fouqué, P., Martioli, E., Cadieux, C., Morin, J., Forveille, T., Boisse, I., Hébrard, G., Díaz, R. F., Lafrenière, D., Kiefer, F., Petit, P., Doyon, R., Acuña, L., Arnold, L., Bonfils, X., Bouchy, F., Bourrier, V., Dalal, S., Deleuil, M., Demangeon, O., Dumusque, X., Hara, N., Hoyer, S., Mousis, O., Santerne, A., Ségrasan, D., Stalport, M., and Udry, S.
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Earth and Planetary Astrophysics - Abstract
Context: The search for extrasolar planets around the nearest M dwarfs is a crucial step towards identifying the nearest Earth-like planets. One of the main challenges in this search is that M dwarfs can be magnetically active and stellar activity can produce radial velocity (RV) signals that could mimic those of a planet. Aims: We aim to investigate whether the 2.2 day period observed in optical RVs of the nearby active M dwarf star Gl 388 (AD Leo) is due to stellar activity or to a planet that corotates with the star as suggested in the past. Methods: We obtained quasi-simultaneous optical RVs of Gl 388 from 2019 to 2021 with SOPHIE (R~75k) at the OHP in France, and near-IR RV and Stokes V measurements with SPIRou at the CFHT (R~70k). Results: The SOPHIE RV time series displays a periodic signal with a 2.23+-0.01 day period and 23.6+-0.5 m/s amplitude, which is consistent with previous HARPS observations obtained in 2005-2006. The SPIRou RV time series is flat at 5 m/s rms and displays no periodic signals. RV signals of amplitude higher than 5.3 m/s at a period of 2.23 days can be excluded with a confidence level higher than 99%. Using the modulation of the longitudinal magnetic field (Bl) measured with SPIRou, we derive a stellar rotation period of 2.2305+-0.0016 days. Conclusions: SPIRou RV measurements provide solid evidence that the periodic variability of the optical RVs of Gl 388 is due to stellar activity rather than to a corotating planet. The magnetic activity nature of the optical RV signal is further confirmed by the modulation of Bl with the same period. The SPIRou campaign on Gl 388 demonstrates the power of near-IR RV to confirm or infirm planet candidates discovered in the optical around active stars. SPIRou observations reiterate how effective spectropolarimetry is at determining the stellar rotation period., Comment: 25 pages, 23 figures, Accepted by Astronomy and Astrophysics; [v2] version implementing A&A language editor suggestions; [v3] improved ascii characters for ADS metadata visualization; [v4] minor corrections added in proof
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- 2023
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33. The role of magnetic fields in the formation of multiple massive stars
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Mignon-Risse, R., González, M., and Commerçon, B.
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Astrophysics of Galaxies - Abstract
(Abridged) Context. Most massive stars are located in multiple stellar systems. Magnetic fields are believed to be essential in the accretion and ejection processes around single massive protostars. Aims. Our aim is to unveil the influence of magnetic fields in the formation of multiple massive stars, in particular on the fragmentation modes and properties of the multiple protostellar system. Methods. Using RAMSES, we follow the collapse of a massive pre-stellar core with (non-ideal) radiation-(magneto-)hydrodynamics. We choose a setup which promotes multiple stellar system formation. Results. In the purely hydrodynamical models, we always obtain (at least) binary systems. When more than two stars are present, their gravitational interaction triggers mergers until there are two stars left. The following gas accretion increases their orbital separation and hierarchical fragmentation occurs so that both stars host a comparable disk and stellar system which then form similar disks as well. We identify several modes of fragmentation: Toomre-unstable disk fragmentation, arm-arm collision and arm-filament collision. Disks grow in size until they fragment and become truncated as the newly-formed companion gains mass. When including magnetic fields, the picture evolves: the primary disk produces less fragments, arm-filament collision is absent. Magnetic fields reduce the initial orbital separation but do not affect its further evolution, which is mainly driven by gas accretion. With magnetic fields, the growth of individual disks is regulated even in the absence of fragmentation or truncation. Conclusions. Hierarchical fragmentation is seen in unmagnetized and magnetized models. Magnetic fields, including non-ideal effects, are important because they remove certain fragmentation modes and limit the growth of disks, which is otherwise only limited through fragmentation., Comment: 16 pages, 11 figures. Accepted for publication in Astronomy & Astrophysics
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- 2023
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34. Characterisation of stellar activity of M dwarfs. I. Long-timescale variability in a large sample and detection of new cycles
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Mignon, L., Meunier, N., Delfosse, X., Bonfils, X., Santos, N. C., Forveille, T., Gaisné, G., Astudillo-Defru, N., Lovis, C., and Udry, S.
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Earth and Planetary Astrophysics - Abstract
M dwarfs are active stars that exhibit variability in chromospheric emission and photometry at short and long timescales, including long cycles that are related to dynamo processes. This activity also impacts the search for exoplanets because it affects the radial velocities. We analysed a large sample of 177 M dwarfs observed with HARPS (2003-2020) in order to characterise the long-term variability of these stars. We compared the variability obtained in three chromospheric activity indices (Ca II H & K, the Na D doublet, and Halpha) and with ASAS photometry. We focused on the detailed analysis of the chromospheric emission based on linear, quadratic, and sinusoidal models. We used various tools to estimate the significance of the variability and to quantify the improvement brought by the models. In addition, we analysed complementary photometric time series for the most variable stars to be able to provide a broader view of the long-term variability in M dwarfs. We find that most stars are significantly variable, even the quietest stars. Most stars in our sample (75%) exhibit a long-term variability, which manifests itself mostly through linear or quadratic variability, although the true behaviour may be more complex. We found significant variability with estimated timescales for 24 stars, and estimated the lower limit for a possible cycle period for an additional 9 stars that were not previously published. We found evidence of complex variability because more than one long-term timescale may be present for at least 12 stars, together with significant differences between the behaviour of the three activity indices. This complexity may also be the source of the discrepancies observed between previous publications. We conclude that long-term variability is present for all spectral types and activity level in M dwarfs, without a significant trend with spectral type or mean activity level., Comment: article accepted in Astronomy and Astrophysics, February 2023, 31 pages
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- 2023
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35. Disk fragmentation around a massive protostar: a comparison of two three-dimensional codes
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Mignon-Risse, Raphaël, Oliva, André, González, Matthias, Kuiper, Rolf, and Commerçon, Benoît
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Astrophysics of Galaxies ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
(Abridged) Most massive stars are located in multiple systems. The modeling of disk fragmentation, a possible mechanism leading to stellar multiplicity, relies on parallel 3D simulation codes whose agreement remains to be evaluated. Using the Cartesian AMR code RAMSES, we compare disk fragmentation in a centrally-condensed protostellar system to the study of Oliva & Kuiper (2020) performed on a grid in spherical coordinates using PLUTO. Two RAMSES runs are considered and give qualitatively distinct pictures. When allowing for unlimited sink particle creation, gas fragmentation leads to a multiple stellar system whose multiplicity is affected by the grid when triggering fragmentation and by numerically-assisted mergers. On the other hand, using a unique, central, fixed sink particle, a centrally-condensed system forms, similar to that reported in PLUTO. The RAMSES-PLUTO comparison is performed with the latter: agreement between the two codes is found regarding the first rotationally-supported disk formation, the presence of an accretion shock onto it, the first fragmentation phase. Gaseous fragments form and their properties are in agreement between the two codes. As a minor difference, fragments dynamics causes the disk structure to be sub-Keplerian in RAMSES whereas it is found to be Keplerian and reaches quiescence in PLUTO. We attribute this discrepancy to the central star being twice less massive in RAMSES because of the different stellar accretion subgrid models. In a centrally-condensed system, the agreement between RAMSES and PLUTO regarding many of the collapse properties and fragmentation process is good. Fragmentation occurring in the innermost region and numerical choices (use of sink particles, grid) have a crucial impact when similar but smooth initial conditions are employed - more crucial than the code's choice - on the system's outcome, multiple or centrally-condensed., Comment: 17 pages, 16 figures; accepted for publication in A&A
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- 2023
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36. Gravitational waves or X-ray counterpart? No need to choose
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Mignon-Risse, Raphaël, Varniere, Peggy, and Casse, Fabien
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Astrophysics - High Energy Astrophysical Phenomena ,General Relativity and Quantum Cosmology - Abstract
Binary black holes emit gravitational waves as they inspiral towards coalescence. Searches for electromagnetic counterparts to these gravitational waves rely on looking for common sources producing both signals. In this paper, we take a different approach: we investigate the impact of radiation zone effects, including retardation effects and gravitational wave propagation onto the circumbinary disk around stellar-mass, spinning black holes, using general relativistic hydrodynamical simulations. Then we used a general relativistic ray-tracing code to extract its X-ray spectrum and lightcurve. This allowed us to show that radiation zone effects leave an imprint onto the disk, leading to quasi-periodic patterns in the X-ray lightcurve. The amplitude of the modulation is weak (<1%) but increases with time and is strongly dependent on the inclination angle., Comment: 6 pages, 5 figures. Accepted for publication in AN
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- 2023
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37. On the origin of the lump in circumbinary discs
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Mignon-Risse, Raphaël, Varniere, Peggy, and Casse, Fabien
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Solar and Stellar Astrophysics - Abstract
Accreting binary black holes (BBHs) are multi-messenger sources, emitting copious electromagnetic (EM) and gravitational waves. One of their most promising EM signatures is the lightcurve modulation caused by a strong, unique and extended azimuthal overdensity structure orbiting at the inner edge of the circumbinary disc (CBD), dubbed "lump". In this paper, we investigate the origin of this structure using 2D general-relativistic (GR) hydrodynamical simulations of a CBD in an approximate BBH spacetime. First, we use the symmetric mass-ratio case to study the transition from the natural m = 2 mode to m = 1. The asymmetry with respect to m = 2 grows exponentially, pointing to an instability origin. We indeed find that the CBD edge is prone to a (magneto-)hydrodynamical instability owing to the disc edge density sharpness: the Rossby Wave Instability (RWI). The RWI criterion is naturally fullfilled at the CBD edge and we report the presence of vortices, which are typical structures of the RWI. The RWI is also at work in the asymmetric mass-ratio cases (from 0.1 to 0.5). However, the CBD edge sharpness decreases with a decreasing mass ratio, and so the lump. By proposing a scenario for this lump formation, our work further supports its existence in astrophysical CBDs and potential source for an EM signature of BBHs. Finally, because the RWI is not caused by GR effects, it is also a robust candidate for the lump origin in CBDs around non-compact objects, e.g. binary protostars., Comment: 11 pages, 11 figures. Accepted for publication in MNRAS
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- 2023
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38. Editorial: Advances toward improved understanding and treatment of uncommon ovarian cancer types and subtypes
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Robert L. Hollis and Mignon D. J. M. van Gent
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ovarian cancer ,uncommon tumors ,endometrioid ovarian carcinoma ,low grade serous ovarian carcinoma ,clear cell ovarian carcinoma (CCOC) ,ovarian carcinosarcomas (OCS) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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39. Reimagining Music and Music-Making in Early Learning Spaces
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Van As, Aletta, Van Vreden, Mignon, Fleer, Marilyn, Series Editor, Pramling Samuelsson, Ingrid, Series Editor, Edwards, Anne, Editorial Board Member, Hedegaard, Mariane, Editorial Board Member, Johansson, Eva, Editorial Board Member, Mejía Arauz, Rebeca, Editorial Board Member, Wallerstedt, Cecilia, Editorial Board Member, Li, Liang, Editorial Board Member, Shaik, Naseema, editor, and Moodley, Trevor, editor
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- 2024
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40. Atomkraft und Endlagerung: Von der parallelen Existenz von (Un-)Gewissheiten in Politik und Zivilgesellschaft seit dem Zweiten Weltkrieg
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Kirchhof, Astrid Mignon, Mez, Lutz, Series Editor, Brunnengräber, Achim, Series Editor, Eckhardt, Anne, editor, Becker, Frank, editor, Mintzlaff, Volker, editor, Scheer, Dirk, editor, and Seidl, Roman, editor
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- 2024
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41. Potential clinical use of azacitidine and MEK inhibitor combination therapy in PTPN11-mutated juvenile myelomonocytic leukemia.
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Pasupuleti, Santhosh, Chao, Karen, Ramdas, Baskar, Kanumuri, Rahul, Palam, Lakshmi, Liu, Sheng, Wan, Jun, Annesley, Colleen, Loh, Mignon, Stieglitz, Elliot, Burke, Michael, and Kapur, Reuben
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5-Azacitidine ,JMML ,MEK inhibitor ,PD-901 ,PTPN11 ,Shp2(E76K/+) ,trametinib ,Animals ,Mice ,Azacitidine ,Leukemia ,Myelomonocytic ,Juvenile ,Mitogen-Activated Protein Kinase Kinases ,Mutation ,Protein Kinase Inhibitors ,Protein Tyrosine Phosphatase ,Non-Receptor Type 11 ,Humans - Abstract
Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative neoplasm of childhood. The molecular hallmark of JMML is hyperactivation of the Ras/MAPK pathway with the most common cause being mutations in the gene PTPN11, encoding the protein tyrosine phosphatase SHP2. Current strategies for treating JMML include using the hypomethylating agent, 5-azacitidine (5-Aza) or MEK inhibitors trametinib and PD0325901 (PD-901), but none of these are curative as monotherapy. Utilizing an Shp2E76K/+ murine model of JMML, we show that the combination of 5-Aza and PD-901 modulates several hematologic abnormalities often seen in JMML patients, in part by reducing the burden of leukemic hematopoietic stem and progenitor cells (HSC/Ps). The reduced JMML features in drug-treated mice were associated with a decrease in p-MEK and p-ERK levels in Shp2E76K/+ mice treated with the combination of 5-Aza and PD-901. RNA-sequencing analysis revealed a reduction in several RAS and MAPK signaling-related genes. Additionally, a decrease in the expression of genes associated with inflammation and myeloid leukemia was also observed in Shp2E76K/+ mice treated with the combination of the two drugs. Finally, we report two patients with JMML and PTPN11 mutations treated with 5-Aza, trametinib, and chemotherapy who experienced a clinical response because of the combination treatment.
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- 2023
42. Impact of a binary black hole on its outer circumbinary disc
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Mignon-Risse, Raphaël, Varniere, Peggy, and Casse, Fabien
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
Accreting supermassive binary black holes (SMBBHs) are potential targets for multi-messenger astronomy as they emit gravitational waves (GW) while their environment emits electromagnetic (EM) waves. In order to get the most out of a joint GW-EM detection we first need to obtain theoretically-predicted EM signals unambiguously linked to BBHs. In that respect, this is the first of a series of papers dedicated to accreting pre-merger BBHs and their associated EM observables. Here, we extend our Numerical Observatory of Violent Accreting systems, e-NOVAs, to any spacetime. Unlike previous studies, almost exclusively focused on the inner regions, we investigated the impact of the BBH on its outer circumbinary disc, located in the radiation (or wave) zone, after implementing an approximate analytical spacetime of spinning, inspiralling BBHs in e-NOVAs. We follow the formation of a weak spiral structure in disc density arising from the retardation effects in the radiation zone metric. Simulation data are then post-processed with a general-relativistic ray-tracing code incorporating the same BBH spacetime, assuming SMBBH sources. The density spiral creates a small (<1%) but unambiguous modulation of the lightcurve at the semi-orbital period. This signal, although weak, is fundamentally different from that of an axisymmetric disc around a single BH providing a lower limit on the impact of a BBH on its outer disc. This potential difference being found, we study how binary parameters impact this modulation in order to find the optimal case which is a high source inclination of any binary mass ratio (from 0.1 to 1)., Comment: 14 pages, 11 figures. Accepted for publication in MNRAS
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- 2022
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43. Fast, broad-band magnetic resonance spectroscopy with diamond widefield relaxometry
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Mignon, C., Moreno, A. R. Ortiz, Shirzad, H., Padamati, S. K., Damle, V., Ong, Y., Schirhagl, R., and Chipaux, M.
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Physics - Applied Physics ,Quantum Physics - Abstract
We present an alternative to conventional Electron Paramagnetic Resonance (EPR) spectroscopy equipment. Avoiding the use of bulky magnets and magnetron equipment, we use the photoluminescence of an ensemble of Nitrogen-Vacancy centers at the surface of a diamond. Monitoring their relaxation time (or T1), we detected their cross-relaxation with a compound of interest. In addition, the EPR spectra are encoded through a localized magnetic field gradient. While recording previous data took 12 minutes per data point with individual NV centers, we were able to reconstruct a full spectrum at once in $3\; \textrm{seconds}$, over a range from $3$ to $11\; \textrm{Gauss}$. In terms of sensitivity, only $0.5\; {\mu}\textrm{L}$ of a $1\; {\mu}\textrm{M}$ hexaaquacopper (II) ion solution was necessary., Comment: Main text (16 pages, 6 Figures) + Supplementary (6 Pages, 7 Figures)
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- 2022
44. Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry
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Raina, Rupesh, Sethi, Sidharth Kumar, Agrawal, Gopal, Wazir, Sanjay, Bajaj, Naveen, Gupta, Naveen Parkash, Tibrewal, Abhishek, Vadhera, Ananya, Mirgunde, Shishir, Balachandran, Binesh, Sahoo, Jagdish, Afzal, Kamran, Shrivastava, Anubha, Bagla, Jyoti, Krishnegowda, Sushma, Konapur, Ananth, Soni, Kritika, Alhasan, Khalid, McCulloch, Mignon, and Bunchman, Timothy
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- 2024
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45. Development of osteonecrosis and improved survival in B-ALL: results of Children’s Oncology Group Trial AALL0232
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Mattano, Jr, Leonard A., Devidas, Meenakshi, Loh, Mignon L., Raetz, Elizabeth A., Chen, Zhiguo, Winick, Naomi J., Hunger, Stephen P., Carroll, William L., and Larsen, Eric C.
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- 2024
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46. Effects of aminophylline therapy on urine output and kidney function in children with acute kidney injury
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Nyann, Beatrice I., Nourse, Peter, Masu, Adelaide, Agyabeng, Kofi, and McCulloch, Mignon I.
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- 2024
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47. A Case Study from the Overexpression of OsTZF5, Encoding a CCCH Tandem Zinc Finger Protein, in Rice Plants Across Nineteen Yield Trials
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Alexandre Grondin, Mignon A. Natividad, Takuya Ogata, Asad Jan, Amélie C. M. Gaudin, Kurniawan R. Trijatmiko, Evelyn Liwanag, Kyonoshin Maruyama, Yasunari Fujita, Kazuko Yamaguchi-Shinozaki, Kazuo Nakashima, Inez H. Slamet-Loedin, and Amelia Henry
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Rice ,Transgenic ,Drought ,Yield ,Transgene expression ,Plant culture ,SB1-1110 - Abstract
Abstract Background Development of transgenic rice overexpressing transcription factors involved in drought response has been previously reported to confer drought tolerance and therefore represents a means of crop improvement. We transformed lowland rice IR64 with OsTZF5, encoding a CCCH-tandem zinc finger protein, under the control of the rice LIP9 stress-inducible promoter and compared the drought response of transgenic lines and nulls to IR64 in successive screenhouse paddy and field trials up to the T6 generation. Results Compared to the well-watered conditions, the level of drought stress across experiments varied from a minimum of − 25 to − 75 kPa at a soil depth of 30 cm which reduced biomass by 30–55% and grain yield by 1–92%, presenting a range of drought severities. OsTZF5 transgenic lines showed high yield advantage under drought over IR64 in early generations, which was related to shorter time to flowering, lower shoot biomass and higher harvest index. However, the increases in values for yield and related traits in the transgenics became smaller over successive generations despite continued detection of drought-induced transgene expression as conferred by the LIP9 promoter. The decreased advantage of the transgenics over generations tended to coincide with increased levels of homozygosity. Background cleaning of the transgenic lines as well as introgression of the transgene into an IR64 line containing major-effect drought yield QTLs, which were evaluated starting at the BC3F1 and BC2F3 generation, respectively, did not result in consistently increased yield under drought as compared to the respective checks. Conclusions Although we cannot conclusively explain the genetic factors behind the loss of yield advantage of the transgenics under drought across generations, our results help in distinguishing among potential drought tolerance mechanisms related to effectiveness of the transgenics, since early flowering and harvest index most closely reflected the levels of yield advantage in the transgenics across generations while reduced biomass did not.
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- 2024
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48. From Silvio Pellico to Selahattіn Demirtaş: Prison Literature and Literary Polemics in Turkey
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Mignon, Laurent
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- 2024
49. Line-by-line velocity measurements, an outlier-resistant method for precision velocimetry
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Artigau, Étienne, Cadieux, Charles, Cook, Neil J., Doyon, René, Vandal, Thomas, Donati, Jean-Françcois, Moutou, Claire, Delfosse, Xavier, Fouqué, Pascal, Martioli, Eder, Bouchy, François, Parsons, Jasmine, Carmona, Andres, Dumusque, Xavier, Astudillo-Defru, Nicola, Bonfils, Xavier, and Mignon, Lucille
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
We present a new algorithm for precision radial velocity (pRV) measurements, a line-by-line (LBL) approach designed to handle outlying spectral information in a simple but efficient manner. The effectiveness of the LBL method is demonstrated on two datasets, one obtained with SPIRou on Barnard's star, and the other with HARPS on Proxima Centauri. In the near-infrared, the LBL provides a framework for m/s-level accuracy in pRV measurements despite the challenges associated with telluric absorption and sky emission lines. We confirm with SPIRou measurements spanning 2.7 years that the candidate super-Earth on a 233-day orbit around Barnard's star is an artifact due to a combination of time-sampling and activity. The LBL analysis of the Proxima Centauri HARPS post-upgrade data alone easily recovers the Proxima b signal and also provides a 2-sigma detection of the recently confirmed 5-day Proxima d planet, but argues against the presence of the candidate Proxima c with a period of 1900 days. We provide evidence that the Proxima c signal is associated with small, unaccounted systematic effects affecting the HARPS-TERRA template matching RV extraction method for long-period signals. Finally, the LBL framework provides a very effective activity indicator, akin to the full width at half maximum derived from the cross-correlation function, from which we infer a rotation period of $92.1^{+4.2}_{-3.5}$ days for Proxima., Comment: Accepted for publication in AJ
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- 2022
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50. Treating the Untreatable: Antisense Oligonucleotides as an Individualized Therapy for Rare Genetic Kidney Diseases
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Tekendo-Ngongang, Cedrik, Gleeson, Joseph G., and Mignon, Laurence
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- 2024
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- View/download PDF
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