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1,076 results on '"Hall, Benjamin A"'

156. Relating evolutionary selection and mutant clonal dynamics in normal epithelia

Author

Hall, Michael, Jones, Philip, Hall, Benjamin, Jones, Philip [0000-0002-5904-795X], Hall, Benjamin [0000-0003-0355-2946], and Apollo - University of Cambridge Repository

Subjects
oesophagus, Models, Genetic, stem cells, Mutation, cancer, Eyelids, Humans, Epithelial Cells, DNA sequencing, Epidermis, Selection, Genetic, Clone Cells
Abstract

Cancer develops from mutated cells in normal tissues. Whether somatic mutations alter normal cell dynamics is key to understanding cancer risk and guiding interventions to reduce it. An analysis of the first incomplete moment of size distributions of clones carrying cancer-associated mutations in normal human eyelid skin gives a good fit with neutral drift, arguing mutations do not affect cell fate. However, this suggestion conflicts with genetic evidence in the same dataset that argues for strong positive selection of a subset of mutations. This implies cells carrying these mutations have a competitive advantage over normal cells, leading to large clonal expansions within the tissue. In normal epithelium, clone growth is constrained by the limited size of the proliferating compartment and competition with surrounding cells. We show that if these factors are taken into account, the first incomplete moment of the clone size distribution is unable to exclude non-neutral behaviour. Furthermore, experimental factors can make a non-neutral clone size distribution appear neutral. We validate these principles with a new experimental data set showing that when experiments are appropriately designed, the first incomplete moment can be a useful indicator of non-neutral competition. Finally, we discuss the complex relationship between mutant clone sizes and genetic selection.

Published
2019

164. Vibratory parameters of blades from coordinate measurement machine data

Author

Sinha, Alok, Hall, Benjamin, Cassenti, Brice, and Hilbert, Gary

Subjects
Blades -- Mechanical properties, Turbomachines -- Research, Finite element method -- Models, Science and technology
Abstract

This paper deals with the development of a procedure to model geometric variations of blades. Specifically, vibratory parameters of blades are extracted from coordinate measurement machine (CMM) data on an integrally bladed rotor (IBR). The method is based on a proper orthogonal decomposition of CMM data, solid modeling, and finite element techniques. In addition to obtaining natural frequencies and mode shapes of each blade on an IBR, statistics of these modal parameters are also computed and characterized. Numerical results are validated by comparison with experimental results. [DOI: 10.1115/1.2749293]

Published
2008

166. The Roland von Glasow Air-Sea-Ice Chamber (RvG-ASIC): an experimental facility for studying ocean–sea-ice–atmosphere interactions

Author

Thomas, Max, France, James, Crabeck, Odile, Hall, Benjamin, Hof, Verena, Notz, Dirk, Rampai, Tokoloho, Riemenschneider, Leif, Tooth, Oliver, Tranter, Mathilde, Kaiser, Jan, Thomas, Max, France, James, Crabeck, Odile, Hall, Benjamin, Hof, Verena, Notz, Dirk, Rampai, Tokoloho, Riemenschneider, Leif, Tooth, Oliver, Tranter, Mathilde, and Kaiser, Jan

Abstract

Sea ice is difficult, expensive, and potentially dangerous to observe in nature. The remoteness of the Arctic and Southern Oceans complicates sampling logistics, while the heterogeneous nature of sea ice and rapidly changing environmental conditions present challenges for conducting process studies. Here, we describe the Roland von Glasow Air-Sea-Ice Chamber (RvG-ASIC), a laboratory facility designed to reproduce polar processes and overcome some of these challenges. The RvG-ASIC is an open-topped 3.5 m3 glass tank housed in a coldroom (temperature range: −55 to +30 °C). The RvG-ASIC is equipped with a wide suite of instruments for ocean, sea ice, and atmospheric measurements, as well as visible and UV lighting. The infrastructure, available instruments, and typical experimental protocols are described.

Published
2021

179. Notch1mutations drive clonal expansion in normal esophageal epithelium but impair tumor growth

Author

Abby, Emilie, Dentro, Stefan C., Hall, Michael W. J., Fowler, Joanna C., Ong, Swee Hoe, Sood, Roshan, Herms, Albert, Piedrafita, Gabriel, Abnizova, Irina, Siebel, Christian W., Gerstung, Moritz, Hall, Benjamin A., and Jones, Philip H.

Abstract

NOTCH1mutant clones occupy the majority of normal human esophagus by middle age but are comparatively rare in esophageal cancers, suggesting NOTCH1mutations drive clonal expansion but impede carcinogenesis. Here we test this hypothesis. Sequencing NOTCH1mutant clones in aging human esophagus reveals frequent biallelic mutations that block NOTCH1signaling. In mouse esophagus, heterozygous Notch1mutation confers a competitive advantage over wild-type cells, an effect enhanced by loss of the second allele. Widespread Notch1loss alters transcription but has minimal effects on the epithelial structure and cell dynamics. In a carcinogenesis model, Notch1mutations were less prevalent in tumors than normal epithelium. Deletion of Notch1reduced tumor growth, an effect recapitulated by anti-NOTCH1 antibody treatment. Notch1null tumors showed reduced proliferation. We conclude that Notch1mutations in normal epithelium are beneficial as wild-type Notch1favors tumor expansion. NOTCH1 blockade may have therapeutic potential in preventing esophageal squamous cancer.

Published
2023
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187. Dynamics of the Martian bow shock location

Author

Garnier, Philippe, primary, Jacquey, Christian, additional, Génot, Vincent, additional, Sanchez-Cano, Beatriz, additional, Gendre, Xavier, additional, Mazelle, Christian, additional, Fang, Xiaohua, additional, Gruesbeck, Jacob R, additional, Hall, Benjamin, additional, Halekas, Jasper S, additional, and Jakosky, Bruce M, additional

Published
2021
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189. Selection of Oncogenic Mutant Clones in Normal Human Skin Varies with Body Site

Author

Fowler, Joanna C., primary, King, Charlotte, additional, Bryant, Christopher, additional, Hall, Michael W.J., additional, Sood, Roshan, additional, Ong, Swee Hoe, additional, Earp, Eleanor, additional, Fernandez-Antoran, David, additional, Koeppel, Jonas, additional, Dentro, Stefan C., additional, Shorthouse, David, additional, Durrani, Amer, additional, Fife, Kate, additional, Rytina, Edward, additional, Milne, Doreen, additional, Roshan, Amit, additional, Mahububani, Krishnaa, additional, Saeb-Parsy, Kourosh, additional, Hall, Benjamin A., additional, Gerstung, Moritz, additional, and Jones, Philip H., additional

Published
2021
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194. Transcriptomic Analysis of Human Astrocytes In Vitro Reveals Hypoxia-Induced Mitochondrial Dysfunction, Modulation of Metabolism, and Dysregulation of the Immune Response

Author

Allen, Scott P., primary, Seehra, Rajpinder Singh, additional, Heath, Paul R., additional, Hall, Benjamin P. C., additional, Bates, Jessica, additional, Garwood, Claire J., additional, Matuszyk, Martyna M., additional, Wharton, Stephen B., additional, and Simpson, Julie E., additional

Published
2020
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196. The influence of crustal magnetic fields on the Martian bow shock : a statistical analysis of Mars Volatile EvolutioN and Mars Express observations

Author

Garnier, Philippe, primary, Jacquey, Christian, additional, Mazelle, Christian, additional, Fang, Xiaohua, additional, Gruesbeck, Jacob, additional, Hall, Benjamin, additional, Masunaga, Kei, additional, Halekas, Jasper, additional, Espley, Jared, additional, Jakosky, Bruce, additional, Genot, Vincent, additional, and Penou, Emmanuel, additional

Published
2020
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198. Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium

Author

Colom, Bartomeu, primary, Alcolea, Maria P., additional, Piedrafita, Gabriel, additional, Hall, Michael W. J., additional, Wabik, Agnieszka, additional, Dentro, Stefan C., additional, Fowler, Joanna C., additional, Herms, Albert, additional, King, Charlotte, additional, Ong, Swee Hoe, additional, Sood, Roshan K., additional, Gerstung, Moritz, additional, Martincorena, Inigo, additional, Hall, Benjamin A., additional, and Jones, Philip H., additional

Published
2020
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