16 results on '"M. WEIL"'
Search Results
2. Persistence of Gamma-H2AX Foci in Bronchial Cells Correlates with Susceptibility to Radiation Associated Lung Cancer in Mice
- Author
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Peter Demant, Takamitsu A. Kato, Donasian O. Ochola, Christina M. Fallgren, Sylvain V. Costes, Thomas J. Keefe, Michael M. Weil, Joel S. Bedford, and Rabab Sharif
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0301 basic medicine ,Male ,Lung Neoplasms ,Neoplasms, Radiation-Induced ,Biophysics ,Bronchi ,Biology ,Persistence (computer science) ,Histones ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,DNA Breaks, Double-Stranded ,Genetic Predisposition to Disease ,Lung cancer ,Mice, Inbred BALB C ,Radiation ,Strain (chemistry) ,Epithelial Cells ,medicine.disease ,030104 developmental biology ,Gamma h2ax ,030220 oncology & carcinogenesis ,Dna breaks ,Radiation associated ,Cancer research ,Female ,Double stranded - Abstract
The risk of developing radiation-induced lung cancer differs between different strains of mice, but the underlying cause of the strain differences is unknown. Strains of mice also differ in how quickly they repair radiation-induced DNA double-strand breaks (DSBs). We assayed mouse strains from the CcS/Dem recombinant congenic strain set for their efficacy in repairing DNA DSBs during protracted irradiation. We measured unrepaired γ-H2AX radiation-induced foci (RIF), which persisted after chronic 24-h gamma irradiation, as a surrogate marker for repair efficiency in bronchial epithelial cells for 17 of the CcS/Dem strains and the BALB/c founder strain. We observed a very strong correlation (R
- Published
- 2018
3. Raymond E. Meyn, Jr., Ph.D.1942–2017
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Michael M. Weil and Michael D. Story
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Radiation ,media_common.quotation_subject ,Radiation Oncologists ,Biophysics ,Art history ,Historical Article ,Biography ,Art ,History, 20th Century ,History, 21st Century ,United States ,Portrait ,Radiology, Nuclear Medicine and imaging ,media_common - Published
- 2018
4. Incidence of Acute Myeloid Leukemia and Hepatocellular Carcinoma in Mice Irradiated with 1 GeV/nucleon56Fe Ions
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Paula C. Genik, Robert L. Ullrich, E. J. Ehrhart, Michael M. Weil, Joel S. Bedford, Helle Bielefeldt-Ohmann, Christine L. R. Battaglia, F. Andrew Ray, Christina M. Fallgren, Brad Charles, Matthew A. Callan, and Fitsum Hailu
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Male ,Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Neoplasms, Radiation-Induced ,Iron ,Biophysics ,Radiation Dosage ,medicine.disease_cause ,Risk Assessment ,Leukemogenic ,Mice ,Risk Factors ,medicine ,Animals ,Heavy Ions ,Radiology, Nuclear Medicine and imaging ,Irradiation ,Radiation ,Chemistry ,Incidence ,Liver Neoplasms ,Myeloid leukemia ,Cancer ,Dose-Response Relationship, Radiation ,medicine.disease ,Leukemia ,Dose–response relationship ,Leukemia, Myeloid ,Hepatocellular carcinoma ,Cancer research ,Carcinogenesis ,Cosmic Radiation ,Whole-Body Irradiation - Abstract
Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the leukemogenic efficacy of one such HZE species, 1 GeV (56)Fe ions, a component of space radiation, in a mouse model for radiation-induced acute myeloid leukemia. CBA/CaJ mice were irradiated with 1 GeV/nucleon (56)Fe ions or (137)Cs gamma rays and followed until they were moribund or to 800 days of age. We found that 1 GeV/nucleon (56)Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia (AML). However, (56)Fe-ion-irradiated mice had a much higher incidence of hepatocellular carcinoma (HCC) than gamma-irradiated mice, with an estimated RBE of approximately 50. These data suggest a difference in the effects of HZE iron ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis.
- Published
- 2009
5. Levels of γ-H2AX Foci after Low-Dose-Rate Irradiation Reveal a DNA DSB Rejoining Defect in Cells from HumanATMHeterozygotes in Two AT Families and in Another Apparently Normal Individual
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J. B. Little, Michael M. Weil, Joel S. Bedford, Takamitsu A. Kato, and Hatsumi Nagasawa
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Male ,Proband ,DNA Repair ,γ h2ax foci ,Biophysics ,Loss of Heterozygosity ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,Protein Serine-Threonine Kinases ,Biology ,Ionizing radiation ,Histones ,Ataxia Telangiectasia ,chemistry.chemical_compound ,Humans ,Radiology, Nuclear Medicine and imaging ,A-DNA ,Irradiation ,Chromosome Aberrations ,Genetics ,Radiation ,Dose-Response Relationship, Drug ,Tumor Suppressor Proteins ,Heterozygote advantage ,DNA ,Fibroblasts ,Low dose rate irradiation ,Molecular biology ,DNA-Binding Proteins ,chemistry ,Gamma Rays ,Cytogenetic Analysis ,Female ,DNA Damage - Abstract
We have investigated the use of the gamma-H2AX assay, reflecting the presence of DNA double-strand breaks, as a possible means for identifying individuals who are mildly hypersensitive to ionizing radiation, such as some ATM heterozygotes. We compared levels of gamma-H2AX foci after irradiation in cells from six apparently normal individuals as well as from individuals from two separate AT families including the proband, mother, father and three unaffected siblings in each family. After a 1-Gy single acute (high-dose-rate) gamma-ray dose delivered to noncycling contact-inhibited monolayers of cells, clear differences were seen between samples from normal individuals (ATM(+/+)) and probands (ATM(-/-)) at nearly all sampling times after irradiation, but no clear distinctions were seen for cells from normal compared to obligate heterozygotes (ATM(+/-)). In contrast, after 24 h of continuous irradiation at a dose rate of 10 cGy/h, appreciable differences in numbers of foci per cell were observed for cells from individuals for all the known ATM genotypes compared with controls. Four unaffected siblings had mean numbers of foci per cell similar to that for the obligate heterozygotes, whereas the other two had mean values similar to that for normal controls. We determined independently that those siblings with mean numbers of foci per cell in the range of ATM heterozygotes carried the mutant allele, while both siblings with a normal number of foci per cell after irradiation had normal alleles. A more limited set of experiments using lymphoblastoid cell strains in the low-dose-rate assay also revealed distinct differences for normal compared to ATM heterozygotes from the same families and opens the possibility of using peripheral blood lymphocytes as a more suitable material for an assay to detect mild hypersensitivities to radiation among individuals.
- Published
- 2006
6. Leukemogenesis in heterozygous PU.1 knockout mice
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Helle Bielefeldt-Ohmann, Scott R. McKercher, Paula C. Genik, Michael M. Weil, Jeffery W. Bacher, Irina Vyazunova, F. Andrew Ray, Christina M. Fallgren, Robert L. Ullrich, and Leta S. Steffen
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Male ,Heterozygote ,Myeloid ,Biophysics ,Biology ,medicine.disease_cause ,Mice ,Proto-Oncogene Proteins ,Conditional gene knockout ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Allele ,Codon ,Leukemia, Radiation-Induced ,Mice, Knockout ,Gene knockdown ,Mutation ,Radiation ,Heterozygote advantage ,medicine.disease ,Molecular biology ,Mice, Inbred C57BL ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,fms-Like Tyrosine Kinase 3 ,Knockout mouse ,Mice, Inbred CBA ,Trans-Activators ,Microsatellite Instability ,Chromosome Deletion - Abstract
Most murine radiation-induced acute myeloid leukemias involve biallelic inactivation of the PU.1 gene, with one allele being lost through a radiation-induced chromosomal deletion and the other allele affected by a recurrent point mutation in codon 235 that is likely to be spontaneous. The short latencies of acute myeloid leukemias occurring in nonirradiated mice engineered with PU.1 conditional knockout or knockdown alleles suggest that once both copies of PU.1 have been lost any other steps involved in leukemogenesis occur rapidly. Yet, spontaneous acute myeloid leukemias have not been reported in mice heterozygous for a PU.1 knockout allele, an observation that conflicts with the understanding that the PU.1 codon 235 mutation is spontaneous. Here we describe experiments that show that the lack of spontaneous leukemia in PU.1 heterozygous knockout mice is not due to insufficient monitoring times or mouse numbers or the genetic background of the knockout mice. The results reveal that spontaneous leukemias that develop in mice of the mixed 129S2/SvPas and C57BL/6 background of knockout mice arise by a pathway that does not involve biallelic PU.1 mutation. In addition, the latency of radiation-induced leukemia in PU.1 heterozygous mice on a genetic background susceptible to radiation-induced leukemia indicates that the codon 235 mutation is not a rate-limiting step in radiation leukemogenesis driven by PU.1 loss.
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- 2014
7. Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6 mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma rays. Part I. Experimental observations
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Xianan Liu, Joel S. Bedford, Paula C. Genik, F. Andrew Ray, Robert L. Ullrich, Michael M. Weil, Christy Warner, Christophe Badie, Natalie Brown, Simon Bouffler, Matthew A. Callan, Rosemary Finnon, Yuanlin Peng, and Thomas B. Borak
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C57BL/6 ,Male ,Chromosomes, Artificial, Bacterial ,Neoplasms, Radiation-Induced ,Iron ,Biophysics ,Leukemogenic ,Chromosomes ,Ionizing radiation ,Mice ,Proto-Oncogene Proteins ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Irradiation ,Physics ,Radiation ,Leukemia ,biology ,Gene Expression Regulation, Leukemic ,X-Rays ,Radiochemistry ,Myeloid leukemia ,Chromosome ,Dose-Response Relationship, Radiation ,medicine.disease ,biology.organism_classification ,Molecular biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Gamma Rays ,Mice, Inbred CBA ,Trans-Activators ,Bone marrow - Abstract
Since deletion of the PU.1 gene on chromosome 2 is a crucial acute myeloid leukemia (AML) initiating step in the mouse model, we quantified PU.1 deleted cells in the bone marrow of gamma-, X- and 56Fe-ion-irradiated mice at various times postirradiation. Although 56Fe ions were initially some two to three times more effective than X or gamma rays in inducing PU.1 deletions, by 1 month postirradiation, the proportions of cells with PU.1 deletions were similar for the HZE particles and the sparsely ionizing radiations. These results indicate that while 56Fe ions are more effective in inducing PU.1 deletions, they are also more effective in causing collateral damage that removes hit cells from the bone marrow. After X, gamma or 56Fe-ion irradiation, AML-resistant C57BL/6 mice have fewer cells with PU.1 deletions than CBA mice, and those cells do not persist in the bone marrow of the C57B6/6 mice. Our findings suggest that quantification of PU.1 deleted bone marrow cells 1 month postirradiation can be used as surrogate for the incidence of radiation-induced AML measured in large-scale mouse studies. If so, PU.1 loss could be used to systematically assess the potential leukemogenic effects of other ions and energies in the space radiation environment.
- Published
- 2009
8. gamma-H2AX foci after low-dose-rate irradiation reveal atm haploinsufficiency in mice
- Author
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Paula C. Genik, Michael M. Weil, Hatsumi Nagasawa, Joel S. Bedford, Takamitsu A. Kato, and J. B. Little
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DNA damage ,γ h2ax foci ,Biophysics ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,Biology ,Protein Serine-Threonine Kinases ,Radiation Dosage ,Radiation Tolerance ,Histones ,Mice ,Animals ,Radiology, Nuclear Medicine and imaging ,Irradiation ,Cells, Cultured ,Genetics ,Radiation ,Truncating mutation ,Tumor Suppressor Proteins ,Dose-Response Relationship, Radiation ,Ear ,DNA ,Low dose rate irradiation ,Molecular biology ,DNA-Binding Proteins ,Dose–response relationship ,Atm gene ,Haplotypes ,Haploinsufficiency ,DNA Damage - Abstract
We have investigated the use of the gamma-H2AX assay, reflecting the presence of DNA double-strand breaks (DSBs), as a possible means for identifying individuals who may be intermediate with respect to the extremes of hyper-radiosensitivity phenotypes. In this case, cells were studied from mice that were normal (Atm+/+), heterozygous (Atm+/-), or homozygous recessive (Atm-/-) for a truncating mutation in the Atm gene. After single acute (high-dose-rate) exposures, differences in mean numbers of gamma-H2AX foci per cell between samples from Atm+/+ and Atm-/- mice were clear at nearly all sampling times, but at no sampling time was there a clear distinction for cells from Atm+/+ and Atm+/- mice. In contrast, under conditions of low-dose-rate irradiation at 10 cGy/h, appreciable differences in the levels of gamma-H2AX foci per cell were observed in synchronized G1 cells derived from Atm+/- mice relative to cells from Atm+/+ mice. The levels were intermediate between those for cells from Atm+/+ and Atm-/- mice. After 24 h exposure at this dose rate, measurements in cells from four different mice for each genotype yielded mean frequencies of foci per cell of 1.77 +/- 0.13 (SEM) for Atm+/+ cells, 4.75 +/- 0.20 for the Atm+/- cells, and 11.10 +/- 0.33 for the Atm-/-cells. The distributions of foci per G1 cell were not significantly different from Poisson. To the extent that variations in sensitivity with respect to gamma-H2AX focus formation reflect variations in radiosensitivity for biological effects of concern, such as carcinogenesis, and that similar differences are seen for other genetic DNA DSB processing defects in general, this assay may provide a relatively straightforward means for distinguishing individuals who may be mildly hypersensitive to radiation such as we observed for Atm heterozygous mice.
- Published
- 2006
9. Diurnal variations in the expression of radiation-induced apoptosis
- Author
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A C, Ruifrok, M M, Weil, H D, Thames, and K A, Mason
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Mice ,Mice, Inbred C3H ,Jejunum ,Time Factors ,Gamma Rays ,Animals ,Mitosis ,Apoptosis ,Female ,Circadian Rhythm - Abstract
Experiments were performed to determine whether diurnal variations in apoptosis in the mouse small intestine after irradiation with 2.5 Gy gamma rays depended on the time of day that the mice were irradiated, the time of day that the mice were sacrificed or the interval between irradiation and sacrifice. Experiments were performed with a 12-h light:dark regimen with the light period from 6:00 to 18:00 h. With fixed intervals of 6 h and 24 h between irradiation and sacrifice, a peak in induced apoptosis (16%) was observed in mice sacrificed at 8:00 h, two times higher than the nadir of response at 23:00 h (8%). When variable intervals were used between irradiation and measurement of apoptosis, i.e. sacrifice, at 8:00 h or 23:00 h, the induced apoptosis was dependent on the interval, with a peak for 18-h intervals. However, the level of apoptosis was always about twofold higher when measured at 8:00 h than at 23:00 h. No correlation was observed between diurnal variations in apoptosis and survival of mouse intestinal crypts. The diurnal variations in apoptosis after irradiation can be interpreted either in terms of expression of apoptosis during the G2/M phase of the cell cycle in partially synchronized cells, or in terms of a systemic mechanism such as diurnal variation in the neurohormone melatonin.
- Published
- 1998
10. Genetic basis of strain variation in levels of radiation-induced apoptosis of thymocytes
- Author
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M M, Weil, C I, Amos, K A, Mason, and L C, Stephens
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Male ,Mice, Inbred C57BL ,Mice ,Mice, Inbred C3H ,Species Specificity ,T-Lymphocytes ,Animals ,Apoptosis ,Dose-Response Relationship, Radiation ,Female - Abstract
Levels of radiation-induced apoptosis of thymocytes were compared in C57BL/6J and C3Hf/Kam mice. For up to 8 h after irradiation, levels of apoptosis were higher in the C57BL/6J strain for all doses assayed. The heritability of the strain difference in the extent of apoptosis resulting from irradiation was investigated using a breeding study. Analysis of the F1 and F2 intercross progeny of these two strains provided strong evidence for a maternal effect but little evidence of sex linkage. The results indicate that in this strain combination the level of apoptosis of thymocytes after irradiation is a heritable trait that is likely to be controlled by few genes. These genes should be detectable in a mapping study.
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- 1996
11. Murine Prkdc Polymorphisms Impact DNA-PKcs Function
- Author
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Robert L. Ullrich, Lila Ramaiah, Michael M. Weil, Kristin M. Fabre, Ryan C. Dregalla, Susan M. Bailey, and Christian Desaintes
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DNA Repair ,DNA repair ,Biophysics ,Congenic ,Mice, Transgenic ,Single-nucleotide polymorphism ,DNA-Activated Protein Kinase ,Biology ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Article ,Mice ,Species Specificity ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Allele ,Gene ,DNA-PKcs ,Genetics ,Mice, Inbred BALB C ,Mutation ,Radiation ,Nuclear Proteins ,DNA ,Molecular biology ,Telomere ,DNA-Binding Proteins ,Mice, Inbred C57BL - Abstract
Polymorphic variants of DNA repair genes can increase the carcinogenic potential of exposure to ionizing radiation. Two single nucleotide polymorphisms (SNPs) in Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), have been identified in BALB/c mice and linked to reduced DNA-PKcs activity and mammary cancer susceptibility. We examined three additional mouse strains to better define the roles of the BALB/c Prkdc SNPs (R2140C and M3844V). One is a congenic strain (C.B6) that has the C57BL/6 Prkdc allele on a BALB/c background, and the other is a congenic strain (B6.C) that has the BALB/c variant Prkdc allele on a C57BL/6 background. We also examined the LEWES mouse strain, which possesses only one of the BALB/c Prkdc SNPs (M3844V). Our results demonstrate that both Prkdc SNPs are responsible for deficient DNA-PKcs protein expression, DNA repair and telomere function, while the LEWES SNP affects only DNA-PKcs expression and repair capacity. These studies provide insight into the separation of function between the two BALB/c SNPs as well as direct evidence that SNPs positioned within Prkdc can significantly influence DNA-PKcs function involving DNA repair capacity, telomere end-capping, and potentially cancer susceptibility.
- Published
- 2011
12. Diurnal Variations in the Expression of Radiation-Induced Apoptosis
- Author
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Howard D. Thames, Arnout C.C. Ruifrok, Kathryn A. Mason, and Michael M. Weil
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medicine.medical_specialty ,Radiation ,Radiation induced apoptosis ,Chemistry ,Ratón ,Diurnal temperature variation ,Biophysics ,Cell cycle ,Molecular biology ,Small intestine ,Surgery ,Time of day ,medicine.anatomical_structure ,Apoptosis ,medicine ,Radiology, Nuclear Medicine and imaging ,Irradiation - Abstract
Experiments were performed to determine whether diurnal variations in apoptosis in the mouse small intestine after irradiation with 2.5 Gy γ rays depended on the time of day that the mice were irra...
- Published
- 1998
13. Genetic Basis of Strain Variation in Levels of Radiation-Induced Apoptosis of Thymocytes
- Author
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Michael M. Weil, Christopher I. Amos, L. Clifton Stephens, and Kathryn A. Mason
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Genetics ,Radiation ,Strain (chemistry) ,Ratón ,Biophysics ,Maternal effect ,Biology ,Heritability ,Molecular biology ,Thymocyte ,Apoptosis ,Radiology, Nuclear Medicine and imaging ,Radiosensitivity ,Sex linkage - Abstract
Levels of radiation-induced apoptosis of thymocytes were compared in C57BL/6J and C3Hf/Kam mice. For up to 8 h after irradiation, levels of apoptosis were higher in the C57BL/6J strain for all doses assayed. The heritability of the strain difference in the extent of apoptosis resulting from irradiation was investigated using a breeding study. Analysis of the F1 and F2 intercross progeny of these two strains provided strong evidence for a maternal effect but little evidence of sex linkage. The results indicate that in this strain combination the level of apoptosis of thymocytes after irradiation is a heritable trait that is likely to be controlled by few genes. These genes should be detectable in a mapping study.
- Published
- 1996
14. Chronic exposure of rats to 100-MHz (CW) radiofrequency radiation: assessment of biological effects
- Author
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R J, Smialowicz, J S, Ali, E, Berman, S J, Bursian, J B, Kinn, C G, Liddle, L W, Reiter, and C M, Weil
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Male ,Radio Waves ,Reproduction ,Body Weight ,Age Factors ,Brain ,Organ Size ,Radiation Dosage ,Blood Cell Count ,Rats ,Fetus ,Animals, Newborn ,Pregnancy ,Animals ,Female ,Lymphocytes ,Mitogens ,Environmental Health ,Locomotion - Published
- 1981
15. A High Energy LifeThomas B. Borak, PhD August 2, 1942 - January 25, 2021.
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Bedford J, Dynlacht J, Heilbronn L, Riedinger L, Weil M, Whicker W, and Zeitlin C
- Subjects
- Faculty, Health Physics education, History, 20th Century, History, 21st Century, Humans, Radiobiology education, Radiometry history, Societies, Scientific history, United States, Health Physics history, Radiobiology history
- Published
- 2021
- Full Text
- View/download PDF
16. Raymond E. Meyn, Jr., Ph.D. 1942-2017.
- Author
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Story M and Weil M
- Subjects
- History, 20th Century, History, 21st Century, United States, Radiation Oncologists history
- Published
- 2018
- Full Text
- View/download PDF
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