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1. Alveolar repair following LPS-induced injury requires cell-ECM interactions

Author

Jennifer M.S. Sucre, Fabian Bock, Nicholas M. Negretti, John T. Benjamin, Peter M. Gulleman, Xinyu Dong, Kimberly T. Ferguson, Christopher S. Jetter, Wei Han, Yang Liu, Seunghyi Kook, Jason J. Gokey, Susan H. Guttentag, Jonathan A. Kropski, Timothy S. Blackwell, Roy Zent, and Erin J. Plosa

Subjects
Cell biology, Pulmonology, Medicine
Abstract

During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if β1-containing integrins are required during repair following acute injury, we administered E. coli lipopolysaccharide (LPS) by intratracheal injection to mice with a postdevelopmental deletion of β1 integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, β1-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells coexpressing AT2 epithelial, AT1 epithelial, and mixed intermediate cell state markers, with few mature type 1 cells. AT2 cells deficient in β1 showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that β1-deficient AT2 cells failed to differentiate into mature AT1 epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires β1-containing integrins.

Published
2023
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2. Developmental trajectory of extracellular vesicle characteristics from the lungs of preterm infants

Author

Meaghan A. Ransom, Kaitlyn E. Bunn, Nicholas M. Negretti, Christopher S. Jetter, Zachary J. Bressman, Jennifer M. S. Sucre, and Heather H. Pua

Subjects
Pulmonary and Respiratory Medicine, Rapid Report, Physiology, Physiology (medical), Cell Biology
Abstract

Extracellular vesicles (EVs) are secreted lipid-enclosed particles that have emerged as potential biomarkers and therapeutic agents in lung disease, including bronchopulmonary dysplasia (BPD), a leading complication of preterm birth. Many unanswered questions remain about the content and cargo of EVs in premature infants and their role in lung development. To characterize EVs during human lung development, tracheal aspirates were collected from premature neonates between 22 and 35 wk gestational age and analyzed via nanoparticle tracking analysis, electron microscopy, and bead-based flow cytometry. EVs were detectable across late canalicular through saccular stages of lung development, demonstrating larger sizes earlier in gestation. EVs contained an abundance of the EV-enriched tetraspanins CD9, CD63, and CD81, as well as epithelial cell and immune cell markers. Increases in select surface proteins (CD24 and CD14) on EVs were associated with gestational age and with the risk of BPD. Finally, query of expression data obtained from epithelial cells in a single-cell atlas of murine lung development found that epithelial EV marker expression also changes with developmental time. Together, these data demonstrate an association between EV profile and lung development and provide a foundation for future functional classification of EVs, with the goal of determining their role in cell signaling during development and harnessing their potential as a new therapeutic target in BPD.

Published
2023

3. Epithelial Outgrowth Through Mesenchymal Rings Drives Alveologenesis

Author

Nicholas M. Negretti, Yeongseo Son, Philip Crooke, Erin J. Plosa, John T. Benjamin, Christopher S. Jetter, Claire Bunn, Nicholas Mignemi, John Marini, Alice N. Hackett, Meaghan Ransom, David Nichols, Susan H. Guttentag, Heather H. Pua, Timothy S. Blackwell, William Zacharias, David B. Frank, John A. Kozub, Anita Mahadevan-Jansen, Jonathan A. Kropski, Christopher V.E. Wright, Bryan Millis, and Jennifer M. S. Sucre

Abstract

Determining how alveoli are formed and maintained is critical to understanding lung organogenesis and regeneration after injury. While technological barriers have heretofore limited real-time observation of alveologenesis, we have now used scanned oblique plane illumination microscopy of living lung slices to observe specific cellular behaviors at high resolution over several days. Contrary to the prevailing paradigm that alveoli form by airspace subdivision via ingrowing septa, we find that alveoli form by ballooning epithelial outgrowth supported by stable mesenchymal ring structures. Our systematic analysis allowed creation of a computational model of finely-timed cellular structural changes that drive alveologenesis under normal conditions or with perturbed intercellular Wnt signaling. This new paradigm and platform can be leveraged for mechanistic studies and screening for therapies to promote lung regeneration.One-Sentence SummaryLong-term live analysis of neonatal lungs supports a dynamic epithelial outgrowth model for alveologenesis.

Published
2022

4. Alveolar Repair Following Lipopolysaccharide-induced Injury Requires Cell-Extracellular Matrix Interactions

Author

Jennifer M.S. Sucre, Fabian Bock, Nicholas M. Negretti, John T. Benjamin, Peter M. Gulleman, Xinyu Dong, Kimberly T. Ferguson, Christopher S. Jetter, Wei Han, Yang Liu, Seunghyi Kook, Jason J. Gokey, Susan H. Guttentag, Jonathan A. Kropski, Timothy S. Blackwell, Roy Zent, and Erin J. Plosa

Abstract

During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat type 1 alveolar epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if β1-containing integrins are required during repair following acute injury, we administeredE. colilipopolysaccharide (LPS) by intratracheal injection to mice with a post-developmental deletion of β1 integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, β1-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells co-expressing type 2, type 1, and mixed intermediate cell state markers, with few mature type 1 cells. β1-deficient AT2 cells showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that β1-deficient AT2 cells failed to differentiate into mature type 1 alveolar epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires β1-containing integrins.

Published
2022

6. Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters

Author

Ran eYe, Meagan A. Quinlan, Hideki eIwamoto, Hsiao-Huei eWu, Noah H. Green, Christopher S. Jetter, Douglas G. McMahon, Jeremy eVeenstra-VanderWeele, Pat R. Levitt, and Randy D. Blakely

Subjects
Raphe Nuclei, Protein complex, serotonin transporter, neurexin, neuroligin, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) modulates many key brain functions including those subserving sensation, emotion, reward and cognition. Efficient clearance of 5-HT after release is achieved by the antidepressant-sensitive 5-HT transporter (SERT, SLC6A4). To identify novel SERT regulators, we pursued a proteomic analysis of mouse midbrain SERT complexes, evaluating findings in the context of prior studies that established a SERT-linked transcriptome. Remarkably, both efforts converged on a relationship of SERT with the synaptic adhesion protein neuroligin 2 (NLGN2), a postsynaptic partner for presynaptic neurexins, and a protein well known to organize inhibitory GABAergic synapses. Western blots of midbrain reciprocal immunoprecipitations confirmed SERT/NLGN2 associations, and also extended to other NLGN2 associated proteins (e.g. -neurexin (NRXN), gephyrin). Midbrain SERT/NLGN2 interactions were found to be Ca2+-independent, supporting cis versus trans-synaptic interactions, and were absent in hippocampal preparations, consistent with interactions arising in somatodendritic compartments. Dual color in situ hybridization confirmed co-expression of Tph2 and Nlgn2 mRNA in the dorsal raphe, with immunocytochemical studies confirming SERT:NLGN2 co-localization in raphe cell bodies but not axons. Consistent with correlative mRNA expression studies, loss of NLGN2 expression in Nlgn2 null mice produced significant reductions in midbrain and hippocampal SERT expression and function. Additionally, dorsal raphe 5-HT neurons from Nlgn2 null mice exhibit reduced excitability, a loss of GABAA receptor-mediated IPSCs, and increased 5-HT1A autoreceptor sensitivity. Finally, Nlgn2 null mice display significant changes in behaviors known to be responsive to SERT and/or 5-HT receptor manipulations. We discuss our findings in relation to the possible coordination of intrinsic and extrinsic regulation afforded by somatodendritic SERT:NLGN2 complexes.

Published
2016
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7. Hyperoxia Injury in the Developing Lung Is Mediated by Mesenchymal Expression of Wnt5A

Author

John T. Benjamin, Alissa Cutrone, Meaghan Ransom, Jennifer M.S. Sucre, Erin J. Plosa, Zachary Anderson, Namasivayam Ambalavanan, Christopher S. Jetter, Timothy S. Blackwell, Kasey C. Vickers, Ethan Lee, Susan H. Guttentag, Andries Zijlstra, Melanie Königshoff, Bryan A. Millis, Quanhu Sheng, and Benjamin A. Fensterheim

Subjects
Pulmonary and Respiratory Medicine, In situ hybridization, Hyperoxia, Lung injury, Critical Care and Intensive Care Medicine, Wnt-5a Protein, Andrology, In vivo, Humans, Medicine, Lung, Wnt Signaling Pathway, Bronchopulmonary Dysplasia, business.industry, Mesenchymal stem cell, Infant, Newborn, Wnt signaling pathway, Original Articles, respiratory system, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, Bronchopulmonary dysplasia, cardiovascular system, medicine.symptom, business
Abstract

Rationale: Bronchopulmonary dysplasia (BPD) is a leading complication of preterm birth that affects infants born in the saccular stage of lung development at

Published
2020

8. A single-cell atlas of mouse lung development

Author

Nicholas M. Negretti, Erin J. Plosa, John T. Benjamin, Bryce A. Schuler, A. Christian Habermann, Christopher S. Jetter, Peter Gulleman, Claire Bunn, Alice N. Hackett, Meaghan Ransom, Chase J. Taylor, David Nichols, Brittany K. Matlock, Susan H. Guttentag, Timothy S. Blackwell, Nicholas E. Banovich, Jonathan A. Kropski, and Jennifer M. S. Sucre

Subjects
Organogenesis, Embryonic Development, Gene Expression Regulation, Developmental, Cell Differentiation, Epithelial Cells, Mesenchymal Stem Cells, Embryo, Mammalian, Mice, Techniques and Resources, Animals, Cell Lineage, RNA-Seq, Single-Cell Analysis, Transcriptome, Molecular Biology, Lung, Developmental Biology
Abstract

Lung organogenesis requires precise timing and coordination to effect spatial organization and function of the parenchymal cells. To provide a systematic broad-based view of the mechanisms governing the dynamic alterations in parenchymal cells over crucial periods of development, we performed a single-cell RNA-sequencing time-series yielding 102,571 epithelial, endothelial and mesenchymal cells across nine time points from embryonic day 12 to postnatal day 14 in mice. Combining computational fate-likelihood prediction with RNA in situ hybridization and immunofluorescence, we explore lineage relationships during the saccular to alveolar stage transition. The utility of this publicly searchable atlas resource (www.sucrelab.org/lungcells) is exemplified by discoveries of the complexity of type 1 pneumocyte function and characterization of mesenchymal Wnt expression patterns during the saccular and alveolar stages – wherein major expansion of the gas-exchange surface occurs. We provide an integrated view of cellular dynamics in epithelial, endothelial and mesenchymal cell populations during lung organogenesis.

Published
2021

9. Single-cell transcriptomic assessment of cellular phenotype stability in human precision-cut lung slices

Author

Austin J. Gutierrez, Jonathan A. Kropski, Jason J. Gokey, Christopher S. Jetter, Chase J. Taylor, Jane E. Camarata, Nicholas E. Banovich, Linh T. Bui, Matthew Bacchetta, Nichelle I. Winters, and Jennifer M.S. Sucre

Subjects
Endothelial stem cell, Transcriptome, Immune system, medicine.anatomical_structure, Lung, Cell, Alveolar epithelial cell, medicine, Biology, Cellular phenotype, Ex vivo, Cell biology
Abstract

Precision-cut lung slices (PCLS) are increasingly utilized for ex vivo disease modeling, but a high-resolution characterization of cellular phenotype stability in PCLS has not been reported. Comparing the single-cell transcriptomic profile of human PCLS after five days of culture to freshly isolated human lung tissue, we found striking changes in endothelial cell and alveolar epithelial cell programs, reflecting both injury and pathways activated in static culture, while immune cell frequencies and programs remained largely intact and similar to the native lung. These cellular dynamics should be considered when utilizing PCLS as a model of the human lung.

Published
2021

10. A high precision calibration of the nonlinear energy response at Daya Bay

Author

X. L. Ji, E. Naumova, D. A. Dwyer, T. J. Langford, L. Mora Lepin, H. M. Steiner, Y. Q. Ma, Xiao-yan Li, J. J. Cherwinka, N. Raper, Rupert Leitner, A. Higuera, Zhi-zhong Xing, Qinglong Wu, Kam Biu Luk, Christopher G. White, M. Qi, Tian Xue, J. L. Sun, S. H. Kettell, Artem Chukanov, X. B. Ma, Y. K. Heng, K. Whisnant, C. Li, Lawrence Pinsky, Jinjuan Ren, J. Park, Q. J. Li, Y. Z. Yang, X.F. Zhang, Tao Hu, N. Y. Wang, B. Viren, Maxim Gonchar, L. H. Wei, R. T. Lei, Qingmin Zhang, F. S. Deng, R. A. Johnson, Jiawen Zhang, J. H. C. Lee, Guanghua Gong, C. C. Zhang, Minfang Yeh, B. Z. Hu, Wei Wang, S. J. Patton, Lei Zhou, B. R. Littlejohn, Jia Xu, Yufeng Li, Y. M. Zhang, Jim Napolitano, Hongzhao Yu, K. L. Jen, Bing-Lin Young, Jianrun Hu, J. P. Cummings, Z. Guo, L. Guo, Y. Chang, Patrick Huber, Hanxiong Huang, L. Kang, Jun Cheng, Chao Zhang, X. T. Zhang, Baobiao Yue, H. L. Zhuang, Alexander Olshevskiy, J. K. C. Leung, Guey-Lin Lin, Honghan Gong, Shanfeng Li, Jonathan S. Lu, Yaoyu Zhang, Y. B. Huang, E. T. Worcester, F. Z. Qi, Vit Vorobel, Shengxin Lin, H. H. Zhang, Wei Li, S. Jetter, Yi Chen, Yunzhe Liu, Yuhang Guo, Siew Cheng Wong, N. Dash, K. T. McDonald, W. H. Tse, D. C. Jones, Meng Ye, Christopher L. Marshall, J. F. Chang, Jiaheng Zou, Y. K. Hor, J. J. Ling, D. A. Martinez Caicedo, Zhiyong Zhang, B. Roskovec, Zhijian Zhang, Zhibing Li, A. B. Balantekin, Richard Rosero, Z. M. Wang, H. R. Band, Changgen Yang, Jianglai Liu, X. C. Ruan, Mengsu Yang, K. Treskov, X. H. Guo, M. Dvořák, Feiyang Zhang, H. R. Pan, Michael Kramer, V. Pec, L. Lebanowski, Y. Y. Ding, C. Lu, Rui Zhang, S. Hans, R. G. Wang, Xingtao Huang, Simon Blyth, Yixue Chen, M. Z. Wang, Ming Chung Chu, R. W. Hackenburg, Chun S. J. Pun, Liang Zhan, M. Bishai, F. P. An, D. M. Xia, Z. Wang, Zhuojun Hu, K. M. Heeger, Changjian Lin, Shaomin Chen, Jun Cao, Xiaolu Ji, L. S. Littenberg, Z. K. Cheng, Z. P. Zhang, S. F. Li, Y. X. Zhang, W. J. Wu, Dmitry V. Naumov, D. Adey, L. W. Koerner, X. Wang, R. D. McKeown, D. Cao, D. E. Jaffe, C. E. Tull, Miao He, Haoqi Lu, Y. F. Wang, Haosheng Chen, J. M. Link, Yanlin Liu, Hongliang Li, Jing Wang, S. K. Lin, Hai Liang, Liangjian Wen, Guofu Cao, Jingyuan Guo, Juan Pedro Ochoa-Ricoux, Jen-Chieh Peng, Xiaohui Qian, J. Lee, H. Y. Wei, J. Dove, Yuda Zeng, S. Zeng, H. L. H. Wong, Yuman Wang, W. Q. Gu, Zeyuan Yu, S. Kohn, Chunjie Wang, M. V. Diwan, X. Q. Li, Tadeas Dohnal, Lin Yang, Jinmei Liu, Jing Zhao, S. Li, X. Y. Ma, I. Mitchell, Y. B. Hsiung, and Feng Li

Subjects
Physics, Nuclear and High Energy Physics, Physics::Instrumentation and Detectors, Scintillation counter, Detector, Calibration, Daya Bay Reactor Neutrino Experiment, Neutrino, Scintillator, Kinetic energy, Instrumentation, Energy (signal processing), Computational physics
Abstract

A high precision calibration of the nonlinearity in the energy response of the Daya Bay Reactor Neutrino Experiment’s antineutrino detectors is presented in detail. The energy nonlinearity originates from the particle-dependent light yield of the scintillator and charge-dependent electronics response. The nonlinearity model is constrained by γ calibration points from deployed and naturally occurring radioactive sources, the β spectrum from ^(12)B decays, and a direct measurement of the electronics nonlinearity with a new flash analog-to-digital converter readout system. Less than 0.5% uncertainty in the energy nonlinearity calibration is achieved for positrons of kinetic energies greater than 1 MeV.

Published
2019

11. AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells

Author

Shufang Meng, Alexa Jaume, Christopher S. Jetter, Ping Wang, Jason J. Gokey, John T. Benjamin, Jennifer M.S. Sucre, Hayley A. Hanby, Michael S. Marks, Seunghyi Kook, Susan H. Guttentag, and Laura Goetzl

Subjects
Male, Endosome, Adaptor Protein Complex 3, Pulmonary Fibrosis, Cell, Primary Cell Culture, Endosomes, Phosphatidylserines, Lamellar granule, Cell Line, Mice, Cell Movement, Lysosome, Pulmonary fibrosis, Organelle, medicine, Animals, Humans, Phospholipid Transfer Proteins, Lung, Adaptor Proteins, Signal Transducing, Adenosine Triphosphatases, Multidisciplinary, Chemistry, Cell migration, Biological Transport, YAP-Signaling Proteins, Flippase, respiratory system, Biological Sciences, medicine.disease, Cell biology, Mice, Inbred C57BL, Disease Models, Animal, medicine.anatomical_structure, Gene Expression Regulation, Hermanski-Pudlak Syndrome, rab GTP-Binding Proteins, Alveolar Epithelial Cells, Female, Lysosomes, Peroxiredoxin VI, Signal Transduction, Transcription Factors
Abstract

Lamellar bodies (LBs) are lysosome-related organelles (LROs) of surfactant-producing alveolar type 2 (AT2) cells of the distal lung epithelium. Trafficking pathways to LBs have been understudied but are likely critical to AT2 cell homeostasis given associations between genetic defects of endosome to LRO trafficking and pulmonary fibrosis in Hermansky Pudlak syndrome (HPS). Our prior studies uncovered a role for AP-3, defective in HPS type 2, in trafficking Peroxiredoxin-6 to LBs. We now show that the P4-type ATPase ATP8A1 is sorted by AP-3 from early endosomes to LBs through recognition of a C-terminal dileucine-based signal. Disruption of the AP-3/ATP8A1 interaction causes ATP8A1 accumulation in early sorting and/or recycling endosomes, enhancing phosphatidylserine exposure on the cytosolic leaflet. This in turn promotes activation of Yes-activating protein, a transcriptional coactivator, augmenting cell migration and AT2 cell numbers. Together, these studies illuminate a mechanism whereby loss of AP-3-mediated trafficking contributes to a toxic gain-of-function that results in enhanced and sustained activation of a repair pathway associated with pulmonary fibrosis.

Published
2021

12. Fibroblast Heterogeneity in Interstitial Lung Disease

Author

Chase J. Taylor, Jennifer M.S. Sucre, Nichelle I. Winters, Carla L. Calvi, P. Ghattas, Jonathan A. Kropski, Christopher S. Jetter, Timothy S. Blackwell, and Nicholas E. Banovich

Subjects
Pathology, medicine.medical_specialty, medicine.anatomical_structure, business.industry, Interstitial lung disease, Medicine, business, medicine.disease, Fibroblast
Published
2021

13. A Single Cell Atlas of Lung Development

Author

John T. Benjamin, Nicholas E. Banovich, A. Christian Habermann, Peter Gulleman, Jonathan A. Kropski, Chase J. Taylor, Brittany K. Matlock, David E. Nichols, Bryce A. Schuler, Jennifer M.S. Sucre, Christopher S. Jetter, Timothy S. Blackwell, Nicholas M. Negretti, Erin J. Plosa, and Susan H. Guttentag

Subjects
Lung, medicine.anatomical_structure, Parenchyma, Cell, Mesenchymal stem cell, medicine, RNA, Organogenesis, In situ hybridization, respiratory system, Biology, Embryonic stem cell, Cell biology
Abstract

SummaryLung organogenesis requires precisely timed shifts in the spatial organization and function of parenchymal cells, especially during the later stages of lung development. To investigate the mechanisms governing lung parenchymal dynamics during development, we performed a single cell RNA sequencing (scRNA-seq) time-series yielding 92,238 epithelial, endothelial, and mesenchymal cells across 8 time points from embryonic day 12 (E12) to postnatal day 14 (P14) in mice. We combined new computational analyses with RNAin situhybridization to explore transcriptional velocity, fate likelihood prediction, and spatiotemporal localization of cell populations during the transition between the saccular and alveolar stages. We interrogated this atlas to illustrate the complexity of type 1 pneumocyte function during the saccular and alveolar stages, and we demonstrate an integrated view of the cellular dynamics during lung development.

Published
2021

14. Neutrophilic inflammation during lung development disrupts elastin assembly and predisposes adult mice to COPD

Author

Kalsang Dolma, Riet van der Meer, Matthew Xin, J. Edwin Blalock, Seunghyi Kook, Wei Han, Shivangi Dave, John T. Benjamin, Jonathan A. Kropski, David S. Nichols, Peter C. Dinella, Susan H. Guttentag, Erin J. Plosa, Christopher S. Jetter, Timothy S. Blackwell, Jennifer M.S. Sucre, Amit Gaggar, Lisa R. Young, Charitharth Vivek Lal, Ashley Catanzarite, Sergey Gutor, Peter Gulleman, Dawn C. Newcomb, and Bradley W. Richmond

Subjects
0301 basic medicine, Genetically modified mouse, Pathology, medicine.medical_specialty, Neutrophils, Mice, Transgenic, Inflammation, Elastic fiber assembly, Mice, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Animals, Medicine, COPD, Lung, biology, business.industry, General Medicine, respiratory system, medicine.disease, Elastin, respiratory tract diseases, Pulmonary Alveoli, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Neutrophil elastase, biology.protein, Respiratory epithelium, medicine.symptom, Leukocyte Elastase, business, Research Article
Abstract

Emerging evidence indicates that early life events can increase the risk for developing chronic obstructive pulmonary disease (COPD). Using an inducible transgenic mouse model for NF-κB activation in the airway epithelium, we found that a brief period of inflammation during the saccular stage (P3–P5) but not alveolar stage (P10–P12) of lung development disrupted elastic fiber assembly, resulting in permanent reduction in lung function and development of a COPD-like lung phenotype that progressed through 24 months of age. Neutrophil depletion prevented disruption of elastic fiber assembly and restored normal lung development. Mechanistic studies uncovered a role for neutrophil elastase (NE) in downregulating expression of critical elastic fiber assembly components, particularly fibulin-5 and elastin. Further, purified human NE and NE-containing exosomes from tracheal aspirates of premature infants with lung inflammation downregulated elastin and fibulin-5 expression by saccular-stage mouse lung fibroblasts. Together, our studies define a critical developmental window for assembling the elastin scaffold in the distal lung, which is required to support lung structure and function throughout the lifespan. Although neutrophils play a well-recognized role in COPD development in adults, neutrophilic inflammation may also contribute to early-life predisposition to COPD.

Published
2021

15. Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis

Author

Nichelle I. Winters, Jennifer M.S. Sucre, Carla L. Calvi, Linh T. Bui, Ana P. Serezani, Ross M. Bremner, Simon B. Mallal, Rajat Walia, Matthew J. Bacchetta, Lorraine B. Ware, Chase J. Taylor, Jamie Roberson, Wyatt J. McDonnell, Ciara M. Shaver, Bradley W. Richmond, Austin J. Gutierrez, Lance M. Peter, James E. Loyd, Christopher S. Jetter, Timothy S. Blackwell, Jonathan A. Kropski, Nicholas E. Banovich, Stephanie L. Yahn, Latha Raju, Lori Wood, Guixiao Ding, Arun C. Habermann, and Mei-I Chung

Subjects
Cell type, Pulmonary Fibrosis, Cell, Population, Diseases and Disorders, Biology, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Pulmonary fibrosis, medicine, Humans, education, Fibroblast, Lung, Research Articles, 030304 developmental biology, 0303 health sciences, education.field_of_study, Multidisciplinary, Sequence Analysis, RNA, Mesenchymal stem cell, SciAdv r-articles, respiratory system, medicine.disease, Fibrosis, 3. Good health, Cell biology, Extracellular Matrix, medicine.anatomical_structure, 030228 respiratory system, Research Article
Abstract

Single-cell RNA sequencing provides new insights into pathologic epithelial and mesenchymal remodeling in the human lung., Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states. We report that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and identify several previously unrecognized epithelial cell phenotypes, including a KRT5−/KRT17+ pathologic, ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially discrete manner. Together, these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis.

Published
2020

16. Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 infection in the lung epithelium

Author

Meghan E. Kapp, Steven A. Webber, Chase J. Taylor, John T. Benjamin, Jonathan A. Kropski, Erin J. Plosa, Nicholas E. Banovich, Bryce A. Schuler, Lior Z. Braunstein, Susan H. Guttentag, Michael Koval, David S. Nichols, A. Christian Habermann, Christopher S. Jetter, Timothy S. Blackwell, Peter Gulleman, Alice Hackett, and Jennifer M.S. Sucre

Subjects
Lung, Protease, medicine.medical_treatment, RNA, Priming (immunology), Autopsy, respiratory system, Biology, medicine.disease_cause, TMPRSS2, respiratory tract diseases, medicine.anatomical_structure, Immunology, medicine, Respiratory epithelium, Coronavirus
Abstract

The SARS-CoV-2 novel coronavirus global pandemic (COVID-19) has led to millions of cases and hundreds of thousands of deaths around the globe. While the elderly appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of the developing mouse lung with temporally-resolved RNA-in-situ hybridization (ISH) in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primerTMPRSS2was highest in ciliated cells and type I alveolar epithelial cells (AT1), andTMPRSS2expression was increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases revealed SARS-CoV-2 RNA was detected most frequently in ciliated and secretory cells in the airway epithelium and AT1 cells in the peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressingTMPRSS2.Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in the lung epithelium, and suggest that developmental regulation ofTMPRSS2may underlie the relative protection of infants and children from severe respiratory illness.

Published
2020

18. BMPR2 dysfunction impairs insulin signaling and glucose homeostasis in cardiomyocytes

Author

John H. Newman, Shijun Zhu, Niki L Fortune, James West, Anna R. Hemnes, Michael R. Freeman, Joshua P. Fessel, Xinping Chen, Christopher S. Jetter, and M. Talati

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Physiology, 030204 cardiovascular system & hematology, Carbohydrate metabolism, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Physiology (medical), Internal medicine, Medicine, Glucose homeostasis, Myocyte, biology, business.industry, Cell Biology, medicine.disease, BMPR2, Insulin receptor, Endocrinology, 030228 respiratory system, Lipotoxicity, biology.protein, business, Homeostasis, Research Article
Abstract

Insulin resistance and right ventricular (RV) dysfunction are associated with lipotoxicity in heritable forms of pulmonary arterial hypertension (PAH), commonly due to mutations in bone morphogenetic protein receptor type 2 (BMPR2). How BMPR2 dysfunction in cardiomyocytes alters glucose metabolism and the response of these cells to insulin are unknown. We hypothesized that BMPR2 mutation in cardiomyocytes alters glucose-supported mitochondrial respiration and impairs cellular responses to insulin, including glucose and lipid uptake. We performed metabolic assays, immunofluorescence and Western analysis, RNA profiling, and radioactive isotope uptake studies in H9c2 cardiomyocyte cell lines with and without patient-derived BMPR2 mutations (mutant cells), with and without insulin. Unlike control cells, BMPR2 mutant cardiomyocytes have reduced metabolic plasticity as indicated by reduced mitochondrial respiration with increased mitochondrial superoxide production. These mutant cells show enhanced baseline phosphorylation of insulin-signaling protein as indicated by increased Akt, AMPK, and acetyl-CoA carboxylase phosphorylation that may negatively influence fatty acid oxidation and enhance lipid uptake, and are insulin insensitive. Furthermore, mutant cells demonstrate an increase in milk fat globule-EGF factor-8 protein (MFGE8), which influences the insulin-signaling pathway by phosphorylating AktSer473 via phosphatidylinositol 3-kinase and mammalian target of rapamycin. In conclusion, BMPR2 mutant cardiomyocytes have reduced metabolic plasticity and fail to respond to glucose. These cells have enhanced baseline insulin-signaling pattern favoring insulin resistance with failure to augment this pattern in response to insulin. BMPR2 mutation possibly blunts glucose uptake and enhances lipid uptake in these cardiomyocytes. The MFGE8-driven signaling pathway may suggest a new mechanism underlying RV lipotoxicity in PAH.

Published
2019

19. Successful Establishment of Primary Type II Alveolar Epithelium with 3D Organotypic Coculture

Author

John T. Benjamin, Seunghyi Kook, Linda A. Gleaves, Adel Eskaros, Janice A. Williams, Laura Goetzl, Jonathan A. Kropski, Susan H. Guttentag, Christopher S. Jetter, Timothy S. Blackwell, Holli A. Loomans, Lisa R. Young, Andries Zijlstra, Erin J. Plosa, Carla L. Calvi, Jennifer M.S. Sucre, and Ping Wang

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, endocrine system, Alveolar Epithelium, Clinical Biochemistry, Cell Communication, Lamellar granule, Biology, Lung injury, 03 medical and health sciences, Idiopathic pulmonary fibrosis, Pulmonary surfactant, medicine, Humans, Proliferation Marker, Progenitor cell, Lung, Molecular Biology, Cells, Cultured, Epithelial Cells, Lung Injury, Cell Biology, Fibroblasts, respiratory system, medicine.disease, Coculture Techniques, Cell biology, Major Technical Advances, Phenotype, 030104 developmental biology, medicine.anatomical_structure, cardiovascular system, hormones, hormone substitutes, and hormone antagonists, circulatory and respiratory physiology
Abstract

Alveolar type II (AT2) epithelial cells are uniquely specialized to produce surfactant in the lung and act as progenitor cells in the process of repair after lung injury. AT2 cell injury has been implicated in several lung diseases, including idiopathic pulmonary fibrosis and bronchopulmonary dysplasia. The inability to maintain primary AT2 cells in culture has been a significant barrier in the investigation of pulmonary biology. We have addressed this knowledge gap by developing a three-dimensional (3D) organotypic coculture using primary human fetal AT2 cells and pulmonary fibroblasts. Grown on top of matrix-embedded fibroblasts, the primary human AT2 cells establish a monolayer and have direct contact with the underlying pulmonary fibroblasts. Unlike conventional two-dimensional (2D) culture, the structural and functional phenotype of the AT2 cells in our 3D organotypic culture was preserved over 7 days of culture, as evidenced by the presence of lamellar bodies and by production of surfactant proteins B and C. Importantly, the AT2 cells in 3D cocultures maintained the ability to replicate, with approximately 60% of AT2 cells staining positive for the proliferation marker Ki67, whereas no such proliferation is evident in 2D cultures of the same primary AT2 cells. This organotypic culture system enables interrogation of AT2 epithelial biology by providing a reductionist in vitro model in which to investigate the response of AT2 epithelial cells and AT2 cell–fibroblast interactions during lung injury and repair.

Published
2018

20. The Flash ADC system and PMT waveform reconstruction for the Daya Bay experiment

Author

Li Qiuju, Yongbo Huang, Fei Li, Yu Xu, Wei Wang, Yaping Cheng, Xiaolu Ji, S. Jetter, Zeyuan Yu, Xin Qian, Jin Li, Jinfan Chang, Zhang Chen, Zheng Wang, and Jun Hu

Subjects
Physics, Nuclear and High Energy Physics, Physics - Instrumentation and Detectors, Physics::Instrumentation and Detectors, 010308 nuclear & particles physics, business.industry, Monte Carlo method, Detector, Electrical engineering, FOS: Physical sciences, Analog-to-digital converter, Linearity, Instrumentation and Detectors (physics.ins-det), Daya Bay Reactor Neutrino Experiment, Flash ADC, 01 natural sciences, law.invention, Data acquisition, law, 0103 physical sciences, Electronic engineering, Waveform, 010306 general physics, business, Instrumentation
Abstract

To better understand the energy response of the Antineutrino Detector (AD), the Daya Bay Reactor Neutrino Experiment installed a full Flash ADC readout system on one AD that allowed for simultaneous data taking with the current readout system. This paper presents the design, data acquisition, and simulation of the Flash ADC system, and focuses on the PMT waveform reconstruction algorithms. For liquid scintillator calorimetry, the most critical requirement to waveform reconstruction is linearity. Several common reconstruction methods were tested but the linearity performance was not satisfactory. A new method based on the deconvolution technique was developed with 1% residual non-linearity, which fulfills the requirement. The performance was validated with both data and Monte Carlo (MC) simulations, and 1% consistency between them has been achieved.

Published
2018

21. Study of the wave packet treatment of neutrino oscillation at Daya Bay

Author

Ya Ping Cheng, Jie Ren, David E. Jaffe, Xin Qian, Ze Yuan Yu, Qiu Mei Ma, Ji Liang Sun, Christopher G. White, Zhe Ning, Yufeng Li, Wenju Huo, Jia Jie Ling, Meng Ting Yang, Simon Blyth, Ming Chung Chu, Han Yu Wei, Zhi-zhong Xing, Rupert Leitner, Ya Yun Ding, Chang Gen Yang, T. Wise, N. Raper, Simon John Patton, Qiu Ju Li, Jun Cao, Akif Baha Balantekin, Shao Min Chen, S. Jetter, Yu-Cheng Lin, John Kon Chong Leung, Jia Heng Zou, Qun Wu, M. Bishai, Yi Ming Zhang, Yue Kun Heng, William R Edwards, Xiao Lu Ji, Min Fang Yeh, Zhe Wang, Zhaokan Cheng, Hao Liang, Jason C.S. Pun, Ka Vang Tsang, Sam Kohn, Zheng Wang, Wei Wang, Dmitry V. Naumov, Yat Long Chan, Xiang Pan Ji, Yasuhiro Nakajima, de Arcos Jose, Xuantong Zhang, Yu Qian Ma, L. Whitehead, Meng Yun Guan, W. Tang, Yun Chang, Jia Hua Cheng, Vit Vorobel, Zhipeng Lv, Jim Napolitano, Jason Dove, Kin Keung Kwan, Xiao Yan Ma, Yi Xin Zhang, W. J. Wu, Tao Hu, Alexander Olshevskiy, Bing Lin Young, Xi Wang, R. D. McKeown, Zhijian Zhang, Zhimin Wang, J. Joshi, Herbert M Steiner, H. R. Pan, Jia Shu Lu, Ronald Gill, Richard Rosero, K. Treskov, Sheng Chao Li, Yi Fang Wang, Gao Song Li, Chang Guo Lu, Chia-Hao Wu, Ghulam Hussain, Maxim Gonchar, Xing Tao Huang, Hui Gong, Nan Zhou, Zhiyong Zhang, Jian Yi Xu, Han Xiong Huang, Randy Allan Johnson, P. Jaffke, Bedrich Roskovec, David A Martinez Caicedo, D. W. Liu, Li Kang, Tao Xue, B. Viren, Yee Bob Hsiung, Wen Qiang Gu, Shan Zeng, Ran Han, Fei Li, Maria Dolgareva, Jin Fan Chang, Juan Pedro Ochoa-Ricoux, H. H. Zhang, C. E. Tull, M. V. Diwan, H. R. Band, V. Pec, Shanfeng Li, Ziyi Guo, E. T. Worcester, Dong Mei Xia, Zi Ping Zhang, Yu Chen, Wei Hu, Jen-Chieh Peng, M. H. Ye, S. Hans, Ming Qi, Rui Guang Wang, Ian Mitchell, Rui Ting Lei, Deng Jie Li, Meng Wang, Qing Wang Zhao, Kam Biu Luk, Shih Kai Lin, Artem Chukanov, Wei Li Zhong, Chan Fai Wong, He Sheng Chen, Kou Lun Jen, Lawrence Pinsky, Chao Li, Jing Kai Xia, Nai Yan Wang, Michael Mooney, T. Kwok, Guey-Lin Lin, Xue Feng Ding, B. R. Littlejohn, Jia Wen Zhang, Aaron Higuera, Qing Min Zhang, Z. B. Li, Jian Bin Jiao, Jongmin Lee, Marco Grassi, Dmitriy Taychenachev, Miao He, Jiang Lai Liu, Lei Guo, Man-wai Kwok, Hong Lin Zhuang, Jie Cheng, Chao Zhang, Jenny Hc Lee, En Chuan Huang, Yury Malyshkin, Xin Heng Guo, JohnP Cummings, Feng Peng An, Nicolás Viaux, Lei Yang, Jonathan M. Link, K. M. Heeger, JeffJ Cherwinka, Quan You Chen, Joseph Yuen-Keung Hor, Yumei Zhang, S H Kettell, Hao Qi Lu, K. Whisnant, Bei Zhen Hu, Cheng-Ju Stephen Lin, Guang Hua Gong, Matt Kramer, Jimmy Ngai, E. Naumova, D. A. Dwyer, T. J. Langford, Jaewon Park, Xu Bo Ma, Jin Chang Liu, Liangjian Wen, Guofu Cao, Cen Wuron, Gong Xing Sun, Zi Yan Deng, Jie Zhao, Chung Hsiang Wang, Y. Xu, Hin-Lok Henoch Wong, De Wen Cao, R. W. Hackenburg, Weidong Li, Xi Chao Ruan, Fa Zhi Qi, Liang Zhan, Patrick Huber, Shengxin Lin, Li Zhou, Changwei Loh, Ji Lei Xu, Li Chu Chang, Yu Bin Zhao, Zi Ping Ye, Kwong Lau, L. S. Littenberg, Yi Chen, Hai Bo Yang, Ma Sheng Yang, X. N. Li, and L. Lebanowski

Subjects
Physics and Astronomy (miscellaneous), Plane wave, FOS: Physical sciences, lcsh:Astrophysics, Atomic, 01 natural sciences, High Energy Physics - Experiment, Nuclear physics, Momentum, High Energy Physics - Experiment (hep-ex), Particle and Plasma Physics, High Energy Physics - Phenomenology (hep-ph), 0103 physical sciences, lcsh:QB460-466, Nuclear, lcsh:Nuclear and particle physics. Atomic energy. Radioactivity, 010306 general physics, Dispersion (water waves), Neutrino oscillation, Engineering (miscellaneous), Physics, Quantum Physics, hep-ex, 010308 nuclear & particles physics, Oscillation, Detector, Molecular, hep-ph, Nuclear & Particles Physics, High Energy Physics - Phenomenology, lcsh:QC770-798, High Energy Physics::Experiment, Neutrino, Energy (signal processing)
Abstract

The disappearance of reactor $$\bar{\nu }_e$$ ν ¯ e observed by the Daya Bay experiment is examined in the framework of a model in which the neutrino is described by a wave packet with a relative intrinsic momentum dispersion $$\sigma _\mathrm{{rel}}$$ σ rel . Three pairs of nuclear reactors and eight antineutrino detectors, each with good energy resolution, distributed among three experimental halls, supply a high-statistics sample of $$\bar{\nu }_e$$ ν ¯ e acquired at nine different baselines. This provides a unique platform to test the effects which arise from the wave packet treatment of neutrino oscillation. The modified survival probability formula was used to fit Daya Bay data, providing the first experimental limits: $$2.38 \times 10^{-17}< \sigma _\mathrm{{rel}} < 0.23$$ 2.38 × 10 - 17 < σ rel < 0.23 . Treating the dimensions of the reactor cores and detectors as constraints, the limits are improved: $$10^{-14} \lesssim \sigma _\text {rel} < 0.23$$ 10 - 14 ≲ σ rel < 0.23 , and an upper limit of $$\sigma _\text {rel}

Published
2017

22. Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2

Author

Chunhui Xu, Christopher S. Jetter, Timothy J. Kamp, David T. Paik, Cassandra P. Awgulewitsch, Kristof Nolan, Linh T. Trinh, Jeffery B. Bylund, Rajneesh Jha, Jianhua Zhang, Thomas B. Thompson, and Antonis K. Hatzopoulos

Subjects
0301 basic medicine, Mesoderm, Organogenesis, Cellular differentiation, Induced Pluripotent Stem Cells, Biology, Bone morphogenetic protein, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Original Research Reports, medicine, Humans, Myocytes, Cardiac, Induced pluripotent stem cell, Cells, Cultured, Cell Proliferation, Genetics, Gene Expression Profiling, Myocardium, Stem Cells, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Biology, Hematology, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Cell culture, Bone Morphogenetic Proteins, Cytokines, Intercellular Signaling Peptides and Proteins, Stem cell, Signal transduction, Gremlin (protein), 030217 neurology & neurosurgery, Signal Transduction, Developmental Biology
Abstract

Heart development depends on coordinated proliferation and differentiation of cardiac progenitor cells (CPCs), but how the two processes are synchronized is not well understood. Here, we show that the secreted Bone Morphogenetic Protein (BMP) antagonist GREMLIN 2 (GREM2) is induced in CPCs shortly after cardiac mesoderm specification during differentiation of human pluripotent stem cells. GREM2 expression follows cardiac lineage differentiation independently of the differentiation method used, or the origin of the pluripotent stem cells, suggesting that GREM2 is linked to cardiogenesis. Addition of GREM2 protein strongly increases cardiomyocyte output compared to established procardiogenic differentiation methods. Our data show that inhibition of canonical BMP signaling by GREM2 is necessary to promote proliferation of CPCs. However, canonical BMP signaling inhibition alone is not sufficient to induce cardiac differentiation, which depends on subsequent JNK pathway activation specifically by GREM2. These findings may have broader implications in the design of approaches to orchestrate growth and differentiation of pluripotent stem cell-derived lineages that depend on precise regulation of BMP signaling.

Published
2017

23. Seasonal variation of the underground cosmic muon flux observed at Daya Bay

Author

T. J. Langford, K. V. Tsang, H. M. Steiner, Y. Q. Ma, Artem Chukanov, Lawrence Pinsky, Michael Kramer, J. J. Cherwinka, Patrick Huber, S. J. Patton, W. Q. Gu, X. T. Zhang, Qinglong Wu, S. H. Kettell, X. B. Ma, Shengxin Lin, A. Khan, Tian Xue, W. J. Wu, Chang-Wei Loh, R. D. McKeown, Xiaohu Guo, Richard Rosero, L. Lebanowski, H. L. Zhuang, Y. K. Heng, Y. Y. Ding, M. Ye, T. Wise, J. F. Chang, M. Qi, Alexander Olshevskiy, M. T. Yang, Maxim Gonchar, D. C. Jones, D. Taychenachev, S. Hans, Changgen Yang, K. Whisnant, J. Cheng, E. T. Worcester, Y. Xu, E. C. Huang, A. B. Balantekin, G. Hussain, Y. Nakajima, H. S. Chen, C. Li, W. Tang, K. K. Kwan, Y. L. Chan, F. Z. Qi, Chun S. J. Pun, R. A. Johnson, M. W. Kwok, N. Y. Wang, C. Lu, B. Viren, J. J. Ling, Shaomin Chen, Jun Cao, N. Viaux, J. L. Xu, X. L. Ji, Christopher G. White, B. Z. Hu, Xin Qian, Jiawen Zhang, H. H. Zhang, Minfang Yeh, J. B. Jiao, Vit Vorobel, S. F. Li, W. R. Edwards, Guisen Li, Honghan Gong, Rupert Leitner, Zhijian Zhang, Z. Guo, Dmitry V. Naumov, H. R. Band, C. H. Wang, R. T. Lei, Hanxiong Huang, L. Kang, Xingtao Huang, Yang Yang, Y. C. Lin, B. Roskovec, Xiao-yan Li, K. Treskov, Wei Li, A. Higuera, S. Zeng, J. Park, Jen-Chieh Peng, Siew Cheng Wong, L. H. Whitehead, Zhi-zhong Xing, Z. Y. Yu, X. Wang, Li Zhou, H. Y. Wei, F. P. An, Wenju Huo, Yicheng Guo, K. T. McDonald, Haoqi Lu, H. Liang, Yixue Chen, Jiaheng Zou, Jinjuan Ren, D. A. Martinez Caicedo, M. Bishai, J. H. C. Lee, Haijun Yang, Q. J. Li, Dejun Li, Y. F. Wang, Yi Chen, Y. B. Hsiung, Shanfeng Li, Bing-Lin Young, J. Dove, B. R. Littlejohn, Wei Wang, C. C. Zhang, C. H. Wu, M. V. Diwan, L. S. Littenberg, R. M. Qiu, X. Q. Li, T. Kwok, Guey-Lin Lin, R. W. Hackenburg, R. G. Wang, Z. Wang, Simon Blyth, M. Z. Wang, Ming Chung Chu, Yufeng Li, K. L. Jen, N. Raper, Jonathan S. Lu, Z. Ye, Liang Zhan, Marco Grassi, Miao He, Y. X. Zhang, X. C. Ruan, Kam-Biu Luk, S. K. Lin, L. Guo, Y. H. Chang, F. Li, H. R. Pan, D. M. Xia, Chao Zhang, Z. B. Li, Zhiyong Zhang, S. Jetter, Y. Malyshkin, J. L. Sun, Lin Yang, Z. M. Wang, Jinmei Liu, C. Sebastiani, Liangjian Wen, Jing Zhao, X. Y. Ma, Guofu Cao, I. Mitchell, Jianglai Liu, S. Kohn, D. Cao, Guanghua Gong, C. E. Tull, Z. K. Cheng, Z. P. Zhang, D. E. Jaffe, Chi Lin, Juan Pedro Ochoa-Ricoux, Qingmin Zhang, Q. Y. Chen, Jim Napolitano, Y. M. Zhang, J. M. Link, J. P. Cummings, J. Lee, M. Dolgareva, H. L. H. Wong, Kwong Lau, K. M. Heeger, V. Pec, X. P. Ji, Mengsu Yang, J. K. Xia, T. Hu, H. Y. Ngai, R. L. Gill, E. Naumova, and D. A. Dwyer

Subjects
Physics - Instrumentation and Detectors, Correlation coefficient, Physics::Instrumentation and Detectors, cosmic ray experiments, neutrino detectors, neutrino experiments, Flux, FOS: Physical sciences, Atmospheric sciences, 01 natural sciences, High Energy Physics - Experiment, High Energy Physics - Experiment (hep-ex), 0103 physical sciences, medicine, 010306 general physics, Physics, COSMIC cancer database, Muon, 010308 nuclear & particles physics, Astronomy and Astrophysics, Instrumentation and Detectors (physics.ins-det), Seasonality, Atmospheric temperature, medicine.disease, Overburden, Neutrino detector, High Energy Physics::Experiment
Abstract

The Daya Bay Experiment consists of eight identically designed detectors located in three underground experimental halls named as EH1, EH2, EH3, with 250, 265 and 860 meters of water equivalent vertical overburden, respectively. Cosmic muon events have been recorded over a two-year period. The underground muon rate is observed to be positively correlated with the effective atmospheric temperature and to follow a seasonal modulation pattern. The correlation coefficient $\alpha$, describing how a variation in the muon rate relates to a variation in the effective atmospheric temperature, is found to be $\alpha_{\text{EH1}} = 0.362\pm0.031$, $\alpha_{\text{EH2}} = 0.433\pm0.038$ and $\alpha_{\text{EH3}} = 0.641\pm0.057$ for each experimental hall., Comment: Updated to be identical to the published version

Published
2018

24. Novel BAC Mouse Model of Huntington's Disease with 225 CAG Repeats Exhibits an Early Widespread and Stable Degenerative Phenotype

Author

Aaron B. Bowman, Kegang Hua, Terry Jo Bichell, Tomás R. Guilarte, Martin G. Pomper, Jennifer M. Coughlin, Hunter K. Holt, Christopher S. Jetter, Susumu Mori, Fatima S. Alikhan, Meredith K. Loth, Michal Wegrzynowicz, Alexander P. Osmand, Barbara D. Soares, and Jennifer L. McGlothan

Subjects
Genetically modified mouse, congenital, hereditary, and neonatal diseases and abnormalities, Pathology, medicine.medical_specialty, Huntingtin, Neurodegeneration, Neuropathology, Biology, medicine.disease, Phenotype, Cellular and Molecular Neuroscience, Gliosis, Huntington's disease, mental disorders, medicine, Neurology (clinical), medicine.symptom, Trinucleotide repeat expansion
Abstract

Background Unusually large CAG repeat expansions (>60) in exon one of Huntingtin (HTT) are invariably associated with a juvenile-onset form of Huntington's disease (HD), characterized by a more extensive and rapidly progressing neuropathology than the more prevalent adult-onset form. However, existing mouse models of HD that express the full-length Htt gene with CAG repeat lengths associated with juvenile HD (ranging between ~75 to ~150 repeats in published models) exhibit selective neurodegenerative phenotypes more consistent with adult-onset HD. Objective: To determine if a very large CAG repeat (>200) in full-length Htt elicits neurodegenerative phenotypes consistent with juvenile HD. Methods Using a …bacterial artificial chromosome (BAC) system, we generated mice expressing full-length mouse Htt with ~225 CAG repeats under control of the mouse Htt promoter. Mice were characterized using behavioral, neuropathological, biochemical and brain imaging methods. Results BAC-225Q mice exhibit phenotypes consistent with a subset of features seen in juvenile-onset HD: very early motor behavior abnormalities, reduced body weight, widespread and progressive increase in Htt aggregates, gliosis, and neurodegeneration. Early striatal pathology was observed, including reactive gliosis and loss of dopamine receptors, prior to detectable volume loss. HD-related blood markers of impaired energy metabolism and systemic inflammation were also increased. Aside from an age-dependent progression of diffuse nuclear aggregates at 6 months of age to abundant neuropil aggregates at 12 months of age, other pathological and motor phenotypes showed little to no progression. Conclusions The HD phenotypes present in animals 3 to 12 months of age make the BAC-225Q mice a unique and stable model of full-length mutant Htt associated phenotypes, including body weight loss, behavioral impairment and HD-like neurodegenerative phenotypes characteristic of juvenile-onset HD and/or late-stage adult-onset HD.

Published
2015

25. A Shared Pattern of β-Catenin Activation in Bronchopulmonary Dysplasia and Idiopathic Pulmonary Fibrosis

Author

Linda A. Gleaves, Bryan A. Millis, Christopher S. Jetter, Susan H. Guttentag, Timothy S. Blackwell, Jonathan A. Kropski, Lisa R. Young, Namasivayam Ambalavanan, Jennifer M.S. Sucre, John T. Benjamin, and Gail H. Deutsch

Subjects
0301 basic medicine, Adult, Mesenchyme, Lung injury, Article, Pathology and Forensic Medicine, 03 medical and health sciences, Idiopathic pulmonary fibrosis, Fetus, Axin Protein, Pregnancy, AXIN2, Medicine, Animals, Humans, Phosphorylation, Lung, beta Catenin, Bronchopulmonary Dysplasia, Cell Nucleus, business.industry, Wnt signaling pathway, Epithelial Cells, respiratory system, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Bronchopulmonary dysplasia, Animals, Newborn, A549 Cells, Catenin, Pregnancy Trimester, Second, Cancer research, Tyrosine, Female, business, Protein Processing, Post-Translational, Signal Transduction
Abstract

Wnt/β-catenin signaling is necessary for normal lung development, and abnormal Wnt signaling contributes to the pathogenesis of both bronchopulmonary dysplasia (BPD) and idiopathic pulmonary fibrosis (IPF), fibrotic lung diseases that occur during infancy and aging, respectively. Using a library of human normal and diseased human lung samples, we identified a distinct signature of nuclear accumulation of β-catenin phosphorylated at tyrosine 489 and epithelial cell cytosolic localization of β-catenin phosphorylated at tyrosine 654 in early normal lung development and fibrotic lung diseases BPD and IPF. Furthermore, this signature was recapitulated in murine models of BPD and IPF. Image analysis of immunofluorescence colocalization demonstrated a consistent pattern of elevated nuclear phosphorylated β-catenin in the lung epithelium and surrounding mesenchyme in BPD and IPF, closely resembling the pattern observed in 18-week fetal lung. Nuclear β-catenin phosphorylated at tyrosine 489 associated with an increased expression of Wnt target gene AXIN2, suggesting that the observed β-catenin signature is of functional significance during normal development and injury repair. The association of specific modifications of β-catenin during normal lung development and again in response to lung injury supports the widely held concept that repair of lung injury involves the recapitulation of developmental programs. Furthermore, these observations suggest that β-catenin phosphorylation has potential as a therapeutic target for the treatment and prevention of both BPD and IPF.

Published
2017

26. Improved measurement of the reactor antineutrino flux and spectrum at Daya Bay

Author

P. Jaffke, Y. K. Hor, L. Guo, H. H. Zhang, J. Lee, F. Li, Chao Zhang, S. Zeng, M. Dolgareva, Jen-Chieh Peng, C. Li, H. L. H. Wong, Y. X. Zhang, Marco Grassi, Miao He, J. Dove, J. P. Cummings, S. H. Kettell, X. B. Ma, J. J. Cherwinka, Z. M. Wang, S. J. Patton, W. Q. Gu, X. P. Ji, X. C. Ruan, J. B. Jiao, J. Joshi, Z. Guo, Michael Kramer, Chun S. J. Pun, Hanxiong Huang, L. Kang, Yi-Fang Zhao, Maxim Gonchar, K. M. Heeger, W. Tang, H. L. Zhuang, M. V. Diwan, Haosheng Chen, Shaomin Chen, Jun Cao, Rupert Leitner, K. T. McDonald, J. M. Link, S. K. Lin, R. A. Johnson, N. Y. Wang, M. Qi, Vit Vorobel, S. F. Li, C. H. Wu, W. J. Wu, Changgen Yang, Changjian Lin, B. Viren, Richard Rosero, R. D. McKeown, J. K. Xia, Jiawen Zhang, Yanchu Wang, Y. Malyshkin, Dmitry V. Naumov, R. T. Lei, H. R. Band, D. C. Jones, Wei Li, A. B. Balantekin, Kwong Lau, X. L. Ji, C. Lu, J. L. Xu, H. Y. Ngai, R. L. Gill, Meng Wang, H. Liang, Yixue Chen, G. X. Sun, N. Viaux, Liangjian Wen, Y. C. Lin, Guofu Cao, H. Y. Wei, T. Hu, Y. L. Chan, Mengsu Yang, Bing-Lin Young, Haijun Yang, X. Wang, M. Mooney, W. R. Cen, Xingtao Huang, D. W. Liu, Minfang Yeh, T. Kwok, M. Bishai, Qinglong Wu, Kam Biu Luk, D. M. Xia, Zhiyong Zhang, Haoqi Lu, Dejun Li, Guey-Lin Lin, Y. Nakajima, Jonathan S. Lu, Z. Ye, H. R. Pan, L. S. Littenberg, L. H. Whitehead, Yi Chen, Chunjie Wang, N. Raper, Tian Xue, J. H. Cheng, M. W. Kwok, E. Naumova, D. A. Dwyer, B. Roskovec, Zhi Ning, Y. Chang, Q. J. Li, Xiaohu Guo, M. T. Yang, Chang-Wei Loh, Xuefeng Ding, T. J. Langford, Y. K. Heng, Mengyun Guan, K. V. Tsang, Yufeng Li, K. L. Jen, Li Zhou, B. R. Littlejohn, C. E. Tull, Shanfeng Li, H. M. Steiner, L. Lebanowski, Y. Y. Ding, Z. K. Cheng, D. Cao, Y. Q. Ma, Z. P. Zhang, Zhijian Zhang, M. Ye, K. Whisnant, J. Cheng, Artem Chukanov, Juan Pedro Ochoa-Ricoux, Nan Zhou, Zhibing Li, K. Treskov, D. Taychenachev, Alexander Olshevskiy, Lawrence Pinsky, K. K. Kwan, G. Hussain, R. P. Guo, Y. Xu, E. C. Huang, Yaping Cheng, Qingmin Zhang, V. Pec, J. J. Ling, Q. W. Zhao, Q. Y. Chen, S. Hans, B. Z. Hu, Guisen Li, Jim Napolitano, Li Chang, W. L. Zhong, F. P. An, Honghan Gong, Qingming Ma, Siew Cheng Wong, W. R. Edwards, Y. B. Hsiung, Ran Han, Jiaheng Zou, Lin Yang, Jinmei Liu, Jing Zhao, X. Y. Ma, J. Y. Xu, I. Mitchell, S. Jetter, Wenju Huo, Simon Blyth, Ming Chung Chu, W. Hu, Zeyuan Yu, Xin Qian, S. Kohn, Xiao-yan Li, A. Higuera, Zhi-zhong Xing, Ziyan Deng, Jianglai Liu, Jinjuan Ren, W. H. Wang, R. W. Hackenburg, Z. Wang, Guanghua Gong, Y. M. Zhang, D. E. Jaffe, T. Wise, Patrick Huber, J. F. Chang, X. T. Zhang, Shengxin Lin, D. A. Martinez Caicedo, J. L. Sun, R. G. Wang, J. Park, J. H. C. Lee, Liang Zhan, E. T. Worcester, Z. Lv, F. Z. Qi, J. de Arcos, and Christopher G. White

Subjects
Nuclear and High Energy Physics, Physics - Instrumentation and Detectors, Daya bay, energy spectrum, Flux, FOS: Physical sciences, Daya Bay Reactor Neutrino Experiment, antineutrino flux, Daya Bay, reactor, 01 natural sciences, High Energy Physics - Experiment, Positron energy, Physics::Geophysics, Nuclear physics, High Energy Physics - Experiment (hep-ex), 0103 physical sciences, Energy spectrum, Nuclear Experiment (nucl-ex), 010306 general physics, Nuclear Experiment, Instrumentation, Physics, 010308 nuclear & particles physics, Astronomy and Astrophysics, Instrumentation and Detectors (physics.ins-det), Inverse beta decay, High Energy Physics::Experiment
Abstract

A new measurement of the reactor antineutrino flux and energy spectrum by the Daya Bay reactor neutrino experiment is reported. The antineutrinos were generated by six 2.9~GW$_{\mathrm{th}}$ nuclear reactors and detected by eight antineutrino detectors deployed in two near (560~m and 600~m flux-weighted baselines) and one far (1640~m flux-weighted baseline) underground experimental halls. With 621 days of data, more than 1.2 million inverse beta decay (IBD) candidates were detected. The IBD yield in the eight detectors was measured, and the ratio of measured to predicted flux was found to be $0.946\pm0.020$ ($0.992\pm0.021$) for the Huber+Mueller (ILL+Vogel) model. A 2.9~$\sigma$ deviation was found in the measured IBD positron energy spectrum compared to the predictions. In particular, an excess of events in the region of 4-6~MeV was found in the measured spectrum, with a local significance of 4.4~$\sigma$. A reactor antineutrino spectrum weighted by the IBD cross section is extracted for model-independent predictions., Comment: version published in Chinese Physics C

Published
2017

27. Limits on Active to Sterile Neutrino Oscillations from Disappearance Searches in the MINOS, Daya Bay, and Bugey-3 Experiments

Author

Rakesh Sharma, S. Childress, Wenju Huo, H. H. Zhang, D. Cao, A. Schreckenberger, N. Graf, C. D. Moore, R. Gran, Carlos Escobar, Simon Blyth, R. K. Plunkett, X. L. Ji, S. Moed Sher, Haosheng Chen, M. Z. Wang, Ming Chung Chu, D. Torretta, W. Hu, G. J. Bock, J. M. Link, N. Poonthottathil, Jen-Chieh Peng, J. K. Xia, J. Lee, R. W. Hackenburg, S. Zeng, X. Qiu, M. Dolgareva, Carl White, Z. Wang, J. Dove, Chun S. J. Pun, C. M. Castromonte, J. Joshi, J. P. Cummings, M. M. Medeiros, Michael Kramer, L. Corwin, W. J. Wu, R. D. McKeown, P. Sail, Shaomin Chen, Jun Cao, Xuefeng Ding, Z. K. Cheng, Z. P. Zhang, H. L. H. Wong, Y. X. Zhang, X. P. Ji, J. Hartnell, P. Lucas, Hanxiong Huang, S. C. Tognini, Rupert Leitner, M. Qi, Changjian Lin, Gregory J Pawloski, J. Park, L. Kang, J. K. C. Leung, Li Zhou, R. Mehdiyev, K. L. Jen, S. H. Kettell, Yaping Cheng, T. Hu, X. B. Ma, R. B. Patterson, Zhijian Zhang, T. Wise, A. B. Balantekin, S. F. Li, C. Li, Lin Yang, S. R. Mishra, C. James, Yanchu Wang, C. Rosenfeld, X. T. Zhang, M. Mooney, Vit Vorobel, K. Treskov, Dmitry V. Naumov, M. Orchanian, H. Y. Ngai, R. L. Gill, Marco Grassi, Miao He, A. E. Kreymer, D. D. Phan, N. Viaux, S. R. Hahn, Kwong Lau, P. Schreiner, Y. L. Chan, R. Toner, B. Z. Hu, R. Hatcher, D. Cronin-Hennessy, G. X. Sun, B. Rebel, H. A. Rubin, S. K. Lin, J. H. C. Lee, T. Kafka, Jinmei Liu, Jing Zhao, Alec Habig, K. Grzelak, Z. Isvan, L. Mualem, X. Y. Ma, J. Y. Xu, Wei Li, W. A. Mann, F. P. An, T. J. Carroll, P. Adamson, Yanfeng Zhang, S. J. Patton, W. Q. Gu, Y. C. Lin, Mengsu Yang, H. R. Gallagher, Maxim Gonchar, D. W. Liu, Minfang Yeh, Y. Malyshkin, A. Perch, A. Radovic, J. Schneps, I. Mitchell, Harvey B Newman, W. Tang, S. M. S. Kasahara, Marvin L Marshak, X. Wang, P. Gouffon, Liangjian Wen, S. De Rijck, R. A. Johnson, A. Holin, Guofu Cao, Guanghua Gong, X. Tian, Alexander Olshevskiy, M. Bishai, K. T. McDonald, S. Jetter, Haoqi Lu, Dejun Li, W. Flanagan, Wei Wang, B. Roskovec, Jiawen Zhang, Zengcai V. Guo, Y. K. Hor, L. Guo, J. Cheng, Chao Zhang, Jianglai Liu, E. T. Worcester, Z. Lv, F. Z. Qi, H. L. Zhuang, E. Falk, Haijun Yang, J. de Arcos, J. Urheim, Guisen Li, J. J. Cherwinka, G. M. Irwin, Zhiyong Zhang, Honghan Gong, Z. Y. Deng, C. E. Tull, N. Y. Wang, Jinjuan Ren, B. Viren, J. H. Cheng, G. J. Feldman, L. S. Littenberg, C. H. Wu, Zhi Ning, I. Anghel, M. A. Thomson, D. Naples, Stanley G. Wojcicki, Li Chang, Y. Xu, E. C. Huang, Karol Lang, Q. W. Zhao, F. Li, B. R. Littlejohn, H. Y. Wei, Yi-Fang Zhao, G. Koizumi, Qingming Ma, V. Pec, R. L. Talaga, J. J. Ling, Yufeng Li, J. O'Connor, J. Hylen, Y. B. Hsiung, R. J. Nichol, W. L. Zhong, M. C. Goodman, M. V. Frohne, T. Kwok, N. Tagg, N. Mayer, J. B. Jiao, R. A. Gomes, M. C. Sanchez, M. V. Diwan, Guey-Lin Lin, Jonathan S. Lu, Z. Ye, R. B. Pahlka, Qinglong Wu, G.D. Barr, Junwei Huang, Leigh H. Whitehead, Kam Biu Luk, Chunjie Wang, M. Y. Gabrielyan, Siew Cheng Wong, Tian Xue, W. R. Cen, R. T. Lei, K. M. Heeger, J. R. Meier, Xin Qian, Juergen Thomas, Y. K. Heng, Z. M. Wang, Q. J. Li, S. V. Cao, J. A. Nowak, Ran Han, Jiaheng Zou, S. Hans, Mengyun Guan, J. A. Musser, Xiao-yan Li, A. Higuera, X. T. Huang, J. M. Paley, K. Whisnant, Zhi-zhong Xing, Joao A B Coelho, Juan Pedro Ochoa-Ricoux, H. R. Band, K. V. Tsang, H. Liang, Yixue Chen, M. Kordosky, Andrew Blake, J. L. Sun, Artem Chukanov, Lawrence Pinsky, A. Timmons, N. Raper, Richard Rosero, J. F. Chang, Changgen Yang, C. Lu, J. L. Xu, L. H. Whitehead, Ning Zhou, Y. Chang, Shanfeng Li, J. J. Evans, M. M. Pfützner, D. E. Jaffe, Y. Nakajima, Yi Chen, R. C. Webb, M. W. Kwok, L. Lebanowski, Y. Y. Ding, D. M. Xia, J. K. De Jong, S. Phan-Budd, A. Sousa, K. K. Kwan, N. E. Devenish, P. J. Litchfield, R. P. Guo, G. Tzanakos, C. L. McGivern, S. Kohn, S. Germani, Warner A. Miller, A. V. Devan, Bing-Lin Young, D. Bogert, A. Aurisano, W. R. Edwards, E. Naumova, D. A. Dwyer, T. J. Langford, H. M. Steiner, P. Vahle, Y. Q. Ma, Patrick Huber, Shengxin Lin, D. A. Martinez Caicedo, J. K. Nelson, R. G. Wang, D. A. Jensen, Liang Zhan, M. D. Messier, A. C. Weber, X. C. Ruan, Qingmin Zhang, Q. Y. Chen, Jim Napolitano, Xiaohu Guo, M. T. Yang, Hao Pan, C. W. Loh, Z. Y. Yu, Zhibing Li, M. Ye, D. Taychenachev, G. Hussain, J. Todd, P. Jaffke, and R. Chen

Subjects
Physics, Particle physics, Sterile neutrino, Liquid Scintillator Neutrino Detector, 010308 nuclear & particles physics, Physics::Instrumentation and Detectors, High Energy Physics::Phenomenology, General Physics and Astronomy, FOS: Physical sciences, 01 natural sciences, High Energy Physics - Experiment, Nuclear physics, MiniBooNE, High Energy Physics - Experiment (hep-ex), MINOS, 0103 physical sciences, Measurements of neutrino speed, High Energy Physics::Experiment, Neutrino, 010306 general physics, Neutrino oscillation, Electron neutrino, QC
Abstract

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the LSND and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on $\sin^2 2\theta_{\mu e}$ are set over 6 orders of magnitude in the sterile mass-squared splitting $\Delta m^2_{41}$. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for $\Delta m^2_{41} < 0.8$ eV$^2$ at 95% CL$_s$., Comment: 8 pages, 4 figures, published in Physical Review Letters. Data release found at http://www-numi.fnal.gov/PublicInfo/forscientists.html and at https://wiki.bnl.gov/dayabay/index.php?title=Daya_Bay%27s_Sterile_Neutrino_Results_in_2016

Published
2016

28. Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment

Author

W. Tang, Hanxiong Huang, L. Kang, J. K. C. Leung, Simon Blyth, M. Z. Wang, Ming Chung Chu, N. Y. Wang, Jiawen Zhang, B. Viren, W. Hu, Jen-Chieh Peng, Yanchu Wang, Vit Vorobel, Guisen Li, Wei Li, J. J. Cherwinka, J. Dove, X. C. Ruan, J. P. Cummings, Honghan Gong, D. Cao, H. Y. Wei, Zhijian Zhang, Qingming Ma, M. Qi, C. Li, Kwong Lau, Qinglong Wu, Kam Biu Luk, K. Treskov, Bing-Lin Young, Y. K. Hor, Siew Cheng Wong, K. T. McDonald, G. X. Sun, Tian Xue, Guanghua Gong, D. A. Martinez Caicedo, Ning Zhou, L. Guo, Ran Han, Jiaheng Zou, J. Cheng, Michael Kramer, Mengsu Yang, Zhiyong Zhang, Y. K. Heng, F. P. An, S. Hans, Mengyun Guan, L. Lebanowski, Y. Y. Ding, Y. M. Zhang, F. Li, T. Kwok, Chao Zhang, Guey-Lin Lin, M. Ye, S. J. Patton, W. Q. Gu, Jonathan S. Lu, Dongmei Xia, C. H. Wu, D. E. Jaffe, Li Chang, Z. Ye, Yi-Fang Zhao, W. J. Wu, R. D. McKeown, Richard Rosero, Ziyan Deng, K. K. Kwan, K. Whisnant, R. G. Wang, Jianglai Liu, D. Taychenachev, T. Wise, Chunjie Wang, Qingmin Zhang, Y. B. Hsiung, G. Hussain, R. P. Guo, H. L. Zhuang, Xin Qian, Q. Y. Chen, Liang Zhan, B. Z. Hu, M. V. Diwan, P. Jaffke, J. L. Sun, Alexander Olshevskiy, Z. K. Cheng, Z. P. Zhang, Jim Napolitano, Y. Nakajima, Xiao-yan Li, A. Higuera, Haosheng Chen, Juan Pedro Ochoa-Ricoux, E. T. Worcester, Z. Lv, Y. Xu, Zhi-zhong Xing, E. C. Huang, F. Z. Qi, S. H. Kettell, M. W. Kwok, X. B. Ma, Jinjuan Ren, Xiaohu Guo, M. T. Yang, H. H. Zhang, X. L. Ji, J. M. Link, J. de Arcos, Marco Grassi, J. J. Ling, Miao He, W. R. Cen, W. R. Edwards, H. R. Pan, K. V. Tsang, Xingtao Huang, Q. W. Zhao, Yi Chen, E. Naumova, D. A. Dwyer, Q. J. Li, C. W. Loh, M. Bishai, Artem Chukanov, T. J. Langford, K. L. Jen, V. Pec, Yaping Cheng, Lin Yang, J. Joshi, R. W. Hackenburg, Maxim Gonchar, Z. Y. Yu, L. S. Littenberg, Lawrence Pinsky, J. B. Jiao, Z. Wang, H. M. Steiner, Y. Q. Ma, C. E. Tull, J. Park, Jinmei Liu, Rupert Leitner, Jing Zhao, Zhibing Li, X. Y. Ma, J. Y. Xu, Christopher G. White, Zhi Ning, Xuefeng Ding, S. Kohn, S. Jetter, W. L. Zhong, Li Zhou, I. Mitchell, R. A. Johnson, J. H. C. Lee, R. T. Lei, J. Lee, H. R. Band, K. M. Heeger, Y. L. Chan, H. Liang, Yixue Chen, A. B. Balantekin, S. K. Lin, Wei Wang, S. Zeng, M. Dolgareva, H. L. H. Wong, Y. X. Zhang, N. Raper, Y. Malyshkin, D. W. Liu, Liangjian Wen, Guofu Cao, Zengcai V. Guo, X. P. Ji, Minfang Yeh, B. Roskovec, Patrick Huber, X. T. Zhang, H. Y. Ngai, R. L. Gill, N. Viaux, J. K. Xia, T. Hu, Shengxin Lin, Changjian Lin, Haijun Yang, L. H. Whitehead, Yufeng Li, M. Mooney, Y. Chang, Chun S. J. Pun, Shaomin Chen, Jun Cao, Shanfeng Li, S. F. Li, Dmitry V. Naumov, J. H. Cheng, Y. C. Lin, J. F. Chang, B. R. Littlejohn, X. Wang, Changgen Yang, Haoqi Lu, Dejun Li, C. Lu, J. L. Xu, Zhiyuan Wang, and Wenju Huo

Subjects
Physics, Range (particle radiation), Sterile neutrino, Particle physics, 010308 nuclear & particles physics, Daya bay, General Physics and Astronomy, FOS: Physical sciences, Daya Bay Reactor Neutrino Experiment, 01 natural sciences, High Energy Physics - Experiment, Nuclear physics, High Energy Physics - Experiment (hep-ex), 0103 physical sciences, Calibration, Neutrino, 010306 general physics, Electron neutrino, Mixing (physics)
Abstract

This Letter reports an improved search for light sterile neutrino mixing in the electron antineutrino disappearance channel with the full configuration of the Daya Bay Reactor Neutrino Experiment. With an additional 404 days of data collected in eight antineutrino detectors, this search benefits from 3.6 times the statistics available to the previous publication, as well as from improvements in energy calibration and background reduction. A relative comparison of the rate and energy spectrum of reactor antineutrinos in the three experimental halls yields no evidence of sterile neutrino mixing in the $2\times10^{-4} \lesssim |\Delta m^{2}_{41}| \lesssim 0.3$ eV$^{2}$ mass range. The resulting limits on $\sin^{2}2\theta_{14}$ are improved by approximately a factor of 2 over previous results and constitute the most stringent constraints to date in the $|\Delta m^{2}_{41}| \lesssim 0.2$ eV$^{2}$ region., Comment: 6 pages, 3 figures, 1 table

Published
2016
Full Text
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29. A new measurement of antineutrino oscillation with the full detector configuration at Daya Bay

Author

X. C. Ruan, S. H. Kettell, X. B. Ma, Maxim Gonchar, H. S. Chen, M. Ye, R. A. Johnson, S. K. Lin, D. Taychenachev, S. C. Li, Liangjian Wen, K. T. McDonald, G. Hussain, Guofu Cao, J. H. Cheng, Min-Xin Guan, X. Wang, Xiaohu Guo, Jinjuan Ren, Q. J. Li, Y. F. Zhao, M. T. Yang, Jianglai Liu, R. Han, D. W. Liu, Minfang Yeh, G. Y. Yu, Dejun Li, L. H. Whitehead, Guisen Li, Li Chang, Y. B. Hsiung, S. S. Liu, Jiawen Zhang, Z. Y. Yu, Y. Ma, Honghan Gong, Z. Y. Deng, Xin Qian, Y. S. Yeh, Xiao-yan Li, B. Roskovec, A. Higuera, Zhi-zhong Xing, J. Lee, Jen-Chieh Peng, X. Xia, Z. P. Zhang, X. L. Ji, Siew Cheng Wong, Lin Yang, J. B. Jiao, J. F. Chang, H. L. H. Wong, Y. X. Zhang, X. P. Ji, L. E. Piilonen, H. Y. Wei, J. J. Cherwinka, Xingtao Huang, Jiaheng Zou, Qingmin Zhang, K. L. Jen, Jinmei Liu, Jing Zhao, M. Bishai, Y. H. Chang, Changgen Yang, L. Lebanowski, Y. Wang, B. B. Shao, Yaping Cheng, Q. Y. Chen, Y. Y. Ding, X. Y. Ma, J. Y. Xu, H. Q. Lu, K. V. Tsang, E. T. Worcester, C. Lu, J. L. Xu, Jim Napolitano, Patrick Huber, J. Yan, J. K. Xia, F. Z. Qi, H. Y. Ngai, R. L. Gill, I. Mitchell, Y. C. Tung, L. M. Hu, Qinglong Wu, Kam Biu Luk, E. Naumova, D. A. Dwyer, T. Kwok, Guey-Lin Lin, L. S. Littenberg, J. de Arcos, T. J. Langford, Lawrence Pinsky, P. Jaffke, R. T. Lei, S. Jetter, Zhiyuan Wang, Jonathan S. Lu, Xuefeng Ding, Li Zhou, H. M. Steiner, K. K. Kwan, Ilya Butorov, T. Hu, Tian Xue, Rupert Leitner, Zhi Ning, A. B. Balantekin, H. H. Zhang, M. V. Diwan, Richard Rosero, J. Xu, D. M. Xia, C. H. Wang, F. Li, C. E. Tull, Michael Kramer, V. Pec, P. Y. Lin, X. Q. Li, Y. K. Heng, Qiumei Ma, S. Hans, A. G. Olshevski, Chun S. J. Pun, Y. Nakajima, J. Park, N. Viaux, B. R. Littlejohn, Shaomin Chen, Jun Cao, W. R. Cen, S. J. Patton, M. W. Kwok, Wenjie Wang, W. Q. Gu, Hanxiong Huang, L. Kang, J. Cummings, R. D. McKeown, J. K. C. Leung, Changjian Lin, C. A. Lewis, W. L. Zhong, Kwok Yin Leung, Dmitry V. Naumov, J. Monari Kebwaro, B. Z. Hu, Vit Vorobel, H. Liu, K. Whisnant, Z. B. Li, H. L. Zhuang, M. Qi, S. R. Ely, E. Draeger, G. X. Sun, Yi Chen, Wei Li, K. M. Heeger, Mengsu Yang, Zhijian Zhang, L. Zheng, Y. Xu, E. C. Huang, J. J. Ling, Yu-leung Chan, K. Lau, W. Tang, Christopher G. White, Q. W. Zhao, Yufeng Li, Bing-Lin Young, N. Y. Wang, B. Viren, Zhiyong Zhang, J. L. Sun, D. E. Jaffe, F. P. An, B. Ren, S. L. Zang, J. M. Link, Y. K. Hor, L. Guo, J. Cheng, D. A. Martinez Caicedo, Yaolin Zhao, Yue Meng, Chao Zhang, L. J. Hu, R. G. Wang, Liang Zhan, W. R. Edwards, Simon Blyth, M. Z. Wang, Ming Chung Chu, W. Hu, Juan Pedro Ochoa-Ricoux, H. R. Band, H. Liang, Yixue Chen, N. Raper, Marco Grassi, Miao He, T. Wise, H. Themann, Guanghua Gong, Ning Zhou, Y. M. Zhang, W. H. Wang, R. W. Hackenburg, and Z. Wang

Subjects
Physics, Particle physics, Physics - Instrumentation and Detectors, Oscillation, Detector, General Physics and Astronomy, FOS: Physical sciences, Daya Bay Reactor Neutrino Experiment, Instrumentation and Detectors (physics.ins-det), Spectral line, High Energy Physics - Experiment, Nuclear physics, High Energy Physics - Experiment (hep-ex), Calibration, Nuclear Experiment (nucl-ex), Neutrino oscillation, Electron neutrino, Nuclear Experiment, Energy (signal processing)
Abstract

We report a new measurement of electron antineutrino disappearance using the fully-constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9$\times$10$^5$ GW$_{\rm th}$-ton-days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six $^{241}$Am-$^{13}$C radioactive calibration sources reduced the background by a factor of two for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of $\sin^{2}2\theta_{13}$ and $|\Delta m^2_{ee}|$ were halved as a result of these improvements. Analysis of the relative antineutrino rates and energy spectra between detectors gave $\sin^{2}2\theta_{13} = 0.084\pm0.005$ and $|\Delta m^{2}_{ee}|= (2.42\pm0.11) \times 10^{-3}$ eV$^2$ in the three-neutrino framework., Comment: Updated to match final published version

Published
2015

30. The muon system of the Daya Bay Reactor antineutrino experiment

Author

A. B. Balantekin, V. Pec, P. Y. Lin, S. Hans, I. Mitchell, Li Chang, Yi Wei, W. R. Edwards, Juan Pedro Ochoa-Ricoux, H. Liu, Y. B. Hsiung, Christopher G. White, E. Dale, Changgen Yang, K. Zhang, E. C. Huang, Miao He, X. C. Chen, E. Naumova, D. A. Dwyer, Jiawen Zhang, H. M. Steiner, W. C. Lai, Lin Yang, P. Hinrichs, C. Pearson, Jing Zhao, Q. W. Zhao, Bing-Lin Young, Jeremiah Monari Kebwaro, Xin Qian, X. Y. Ma, H. Themann, C. Lu, Zhongyuan Zhou, J. L. Xu, G. X. Sun, Chun S. J. Pun, H. Z. Huang, Guanghua Gong, J. Goett, J. Y. Xu, B. B. Shao, Tao Hu, H. Y. Wei, Y. C. Tung, S. K. Lin, Shaomin Chen, X. C. Ruan, Jun Cao, Xiao-yan Li, Steve Virostek, S. J. Patton, W. Q. Gu, L. Kang, Y. Xu, Y. M. Zhang, H. R. Band, J. K. C. Leung, N. Y. Wang, B. Viren, Vit Vorobel, Zhi-zhong Xing, H. Liang, Yixue Chen, H. S. Chen, Rupert Leitner, M. C. McFarlane, Z. Isvan, Dmitry V. Naumov, Wei Li, R. G. Wang, L. S. Wang, T. Kwok, Guey-Lin Lin, Zeyuan Yu, J. B. Jiao, H. Q. Lu, Liangjian Wen, Guofu Cao, M. V. Diwan, Xiaohu Guo, Y. H. Zhang, Liang Zhan, L. H. Whitehead, J. Y. Fu, N. Raper, T. Wise, Zhiyong Zhang, K. T. McDonald, R. T. Lei, X. Q. Li, M. T. Yang, B. R. Littlejohn, G. Y. Yu, E. Draeger, Qinglong Wu, Kam Biu Luk, D. M. Webber, S. J. Chen, X. P. Ji, R. H.M. Tsang, S. H. Kettell, X. B. Ma, X. F. Du, Wei Wang, Y. K. Hor, Patrick Huber, H. L. Zhuang, Jianglai Liu, X. L. Ji, Y. Ma, L. Z. Wang, J. Xu, Y. H. Tam, Jinjuan Ren, X. Wang, J. J. Cherwinka, X. Tang, J. F. Chang, Min-Xin Guan, Chao Zhang, Yu-leung Chan, S. H. Zhang, D. M. Xia, Z. D. Wang, Y. Wang, Q. J. Li, G. H. Han, Dejun Li, Y. Zhao, J. L. Sun, Qingmin Zhang, D. Mohapatra, Maxim Gonchar, Tian Xue, Q. Y. Chen, C. R. Newsom, Li Zhou, C. Chasman, Y. P. Cheng, F. H. Zhang, E. T. Worcester, Jim Napolitano, Y. H. Chang, Guisen Li, H. X. Huang, Honghan Gong, Z. Y. Deng, Z. P. Zhang, Y. B. Liu, J. de Arcos, R. A. Johnson, H. J. Jiang, Y. K. Heng, R. W. Hackenburg, W. K. Ngai, Z. Wang, Changjian Lin, R. Carr, Qingming Ma, D. E. Jaffe, J. L. Liu, Siew Cheng Wong, C. A. Lewis, S. L. Zang, Jiaheng Zou, K. Whisnant, L. Q. Ge, C. H. Wang, Richard Rosero, Y. Nakajima, M. W. Kwok, Wenjie Wang, K. V. Tsang, Lawrence Pinsky, L. Y. Wang, Yue Meng, L. J. Hu, S. S. Liu, Igor Nemchenok, Zhijian Zhang, L. Zheng, J. Lee, F. P. An, B. Ren, H. L. H. Wong, Y. X. Zhang, A. Leung, M. H. Ye, J. Yan, H. Y. Ngai, R. L. Gill, G. Hussain, Michael Kramer, C. E. Tull, Jin Yu, R. D. McKeown, F. Z. Qi, J. E. Morgan, Jen-Chieh Peng, X. Xia, J. M. Link, J. P. Cummings, L. M. Hu, P. Jaffke, W. Beriguete, R. E. Brown, Huo Yan Chen, Xingtao Huang, Y. Z.B. Li, L. S. Littenberg, Zhi Ning, L. Lebanowski, Y. Y. Ding, Kwong Lau, J. Wilhelmi, Xiaoyuan Chen, K. K. Kwan, Ilya Butorov, Mengsu Yang, W. Zhong, A. G. Olshevski, Guo-Lin Xu, Yi Chen, Q. He, B. Z. Hu, F. Li, Simon Blyth, M. Z. Wang, Ming Chung Chu, W. Hu, K. M. Heeger, J. K. Xia, Wing-Hon Lai, M. Qi, S. R. Ely, D. W. Liu, Minfang Yeh, M. Bishai, B. Roskovec, Yaolin Zhao, L. E. Piilonen, S. Jetter, and Y. S. Yeh

Subjects
Physics, Nuclear and High Energy Physics, Photomultiplier, Physics - Instrumentation and Detectors, Muon, Physics::Instrumentation and Detectors, Shields, FOS: Physical sciences, Cosmic ray, Daya Bay Reactor Neutrino Experiment, Instrumentation and Detectors (physics.ins-det), Nuclear reactor, High Energy Physics - Experiment, law.invention, Nuclear physics, High Energy Physics - Experiment (hep-ex), law, High Energy Physics::Experiment, Neutrino, Instrumentation, Cherenkov radiation
Abstract

The Daya Bay experiment consists of functionally identical antineutrino detectors immersed in pools of ultrapure water in three well-separated underground experimental halls near two nuclear reactor complexes. These pools serve both as shields against natural, low-energy radiation, and as water Cherenkov detectors that efficiently detect cosmic muons using arrays of photomultiplier tubes. Each pool is covered by a plane of resistive plate chambers as an additional means of detecting muons. Design, construction, operation, and performance of these muon detectors are described., Comment: 13 pages, 22 figures, to appear as NIM-A 773 (2015) 8-20

Published
2015

31. Independent measurement of the neutrino mixing angleθ13via neutron capture on hydrogen at Daya Bay

Author

S. S. Liu, Xiaohui Qian, J. Lee, H. L. H. Wong, C. E. Tull, A. Leung, Y. C. Lin, J. Yan, H. Y. Ngai, R. L. Gill, M. Ye, G. Hussain, Richard Rosero, E. Naumova, D. A. Dwyer, L. S. Wang, Y. L. Chan, Y. S. Yeh, D. M. Webber, X. L. Ji, Jen-Chieh Peng, Lin Yang, X. Xia, Yi Wei, J. K. C. Leung, J. Y. Fu, T. Wise, H. M. Steiner, D. W. Liu, Minfang Yeh, Qiumei Ma, Jinmei Liu, Jing Zhao, X. Y. Ma, Y. Q. Ma, Qinglong Wu, Y. H. Tam, V. Pec, P. Y. Lin, S. Hans, Z. P. Zhang, Y. B. Liu, H. J. Jiang, Christopher C. Yang, M. Qi, S. R. Ely, J. Y. Xu, S. H. Kettell, X. B. Ma, X. Wang, M. W. Kwok, Wenjie Wang, B. Roskovec, Baoqing Zeng, I. Mitchell, M. Bishai, Z. M. Wang, Li Zhou, Qingmin Zhang, Xi Chen, H. S. Chen, Guisen Li, Haoqi Lu, Juan Pedro Ochoa-Ricoux, L. M. Hu, Tian Xue, W. L. Zhong, J. P. Cummings, Vit Vorobel, L. H. Whitehead, Michael Kramer, Q. Y. Chen, Dejun Li, Honghan Gong, Maxim Gonchar, D. E. Jaffe, Y. F. Wang, Z. Isvan, Ziyan Deng, Xinglong Li, Wei Li, H. Z. Huang, Jianglai Liu, L. S. Pinsky, R. A. Johnson, Chun S. J. Pun, Miao He, Yaping Cheng, Siew Cheng Wong, Jiawen Zhang, Y. K. Heng, S. J. Patton, W. Q. Gu, Christopher G. White, Shaomin Chen, Jun Cao, Jiaheng Zou, W. Wang, B. B. Shao, Mengyun Guan, W. C. Lai, S. L. Zang, Jin Yu, Yaolin Zhao, K. T. McDonald, Bin Ren, Jim Napolitano, H. Y. Wei, H. L. Zhuang, M. C. McFarlane, K. V. Tsang, R. H.M. Tsang, Li Chang, Zhiyong Zhang, H. Themann, Xiao Tang, Dmitry V. Naumov, Rupert Leitner, C. A. Lewis, Guanghua Gong, Y. B. Hsiung, R. D. McKeown, E. Draeger, Chi Lin, W. R. Edwards, J. F. Chang, T. Kwok, Guey-Lin Lin, K. Whisnant, M. V. Diwan, L. Y. Wang, Y. C. Tung, Y. Xu, Y. M. Zhang, X. T. Huang, F. Li, Y. K. Hor, J. J. Cherwinka, S. K. Lin, X. Q. Li, Zhongyuan Zhou, B. R. Littlejohn, Zhi-zhong Xing, P. Hinrichs, K. M. Heeger, Patrick Huber, Jinjuan Ren, Q. J. Li, C. Lu, X. C. Ruan, Y. Zhao, Jia Xu, Chao Zhang, X. F. Du, Bing-Lin Young, X. P. Ji, Yufeng Li, J. L. Xu, K. L. Jen, J. K. Xia, H. Liang, Yixue Chen, P. Jaffke, G. H. Han, B. Z. Hu, H. R. Band, Z. B. Li, W. Beriguete, Liangjian Wen, Guofu Cao, J. L. Sun, Simon Blyth, R. W. Hackenburg, Z. Wang, E. T. Worcester, F. Z. Qi, M. Z. Wang, Ming Chung Chu, J. de Arcos, T. Hu, W. Hu, Yan Zhang, A. B. Balantekin, L. Kang, N. Raper, L. E. Piilonen, F. H. Zhang, N. Y. Wang, B. Viren, H. Liu, X. H. Guo, C. H. Wang, S. Jetter, R. G. Wang, Y. H. Chang, Liang Zhan, Qingxian Zhang, M. T. Yang, Y. Nakajima, G. Y. Yu, Z. Y. Yu, S. H. Zhang, D. M. Xia, C. Chasman, J. B. Jiao, R. T. Lei, E. C. Huang, J. J. Ling, Q. W. Zhao, L. Q. Ge, Y. C. Zhang, Y. X. Zhang, L. Lebanowski, Y. Y. Ding, Yue Meng, Kam-Biu Luk, K. K. Kwan, L. J. Hu, Ilya Butorov, Fengpeng An, A. G. Olshevski, J. Monari Kebwaro, Yi Chen, Kwong Lau, G. X. Sun, Mengsu Yang, Igor Nemchenok, Zhijian Zhang, L. Zheng, J. M. Link, L. S. Littenberg, and Zhi Ning

Subjects
Physics, Nuclear and High Energy Physics, Particle physics, Hydrogen, Oscillation, Gamma ray, chemistry.chemical_element, Daya Bay Reactor Neutrino Experiment, Nuclear physics, Neutron capture, chemistry, Neutrino, Neutrino oscillation, Charged current
Abstract

A new measurement of the θ_(13) mixing angle has been obtained at the Daya Bay Reactor Neutrino Experiment via the detection of inverse beta decays tagged by neutron capture on hydrogen. The antineutrino events for hydrogen capture are distinct from those for gadolinium capture with largely different systematic uncertainties, allowing a determination independent of the gadolinium-capture result and an improvement on the precision of the θ_(13) measurement. With a 217-day antineutrino data set obtained with six antineutrino detectors and from six 2.9 GW_(th) reactors, the rate deficit observed at the far hall is interpreted as sin^2 2θ_(13) = 0.083±0.018 in the three-flavor oscillation model. When combined with the gadolinium-capture result from Daya Bay, we obtain sin^2 2θ_(13) = 0.089±0.008 as the final result for the six-antineutrino-detector configuration of the Daya Bay experiment.

Published
2014

32. Spectral Measurement of Electron Antineutrino Oscillation Amplitude and Frequency at Daya Bay

Author

J. B. Jiao, M. Qi, S. R. Ely, R. T. Lei, H. Z. Huang, M. Bishai, D. W. Liu, Minfang Yeh, V. Pec, S. Hans, Yk Hor, S. J. Patton, W. Q. Gu, H. S. Chen, W. L. Zhong, B. Roskovec, F. H. Zhang, H. X. Huang, F. Li, Jiawen Zhang, Xin Heng Guo, K. M. Heeger, Yi Wei, K. V. Tsang, Miao He, Michael Kramer, Z. P. Zhang, Y. B. Liu, H. J. Jiang, H. Y. Wei, Huo Yan Chen, Igor Nemchenok, Zhijian Zhang, L. Zheng, R. Carr, Y. P. Cheng, J. K. Xia, Xingtao Huang, R. G. Wang, Wing-Hon Lai, D. M. Webber, Changgen Yang, Y. Zhang, Xubo Ma, Jinjuan Ren, Q. J. Li, J. Napolitano, F. P. An, B. Ren, X. C. Chen, Y. H. Zhang, X. L. Ji, P. Hinrichs, Liang Zhan, R. W. Hackenburg, Z. Wang, Zheng Wang, Jin Yu, L. Q. Ge, B. B. Shao, Y. H. Tam, X. Wang, Zhongyuan Zhou, J. J. Cherwinka, T. Kwok, Guey-Lin Lin, Chun S. J. Pun, Haoqi Lu, Dejun Li, B. Z. Hu, Simon Blyth, K. Lau, Tao Hu, Rupert Leitner, Yue Meng, Kam-Biu Luk, S. H. Kettell, C. Lu, J. L. Xu, X. P. Ji, Y. A. Gornushkin, S. K. Lin, R. L. Brown, Y. C. Zhang, M. Z. Wang, L. J. Hu, L. S. Littenberg, Zhi Ning, Ming Chung Chu, W. Hu, Lawrence Pinsky, L. Lebanowski, Y. Y. Ding, Liangjian Wen, Qingmin Zhang, B. R. Littlejohn, X. F. Du, Shaomin Chen, Jun Cao, A. B. Balantekin, Zeyuan Yu, Y. Xu, E. C. Huang, Li Zhou, N. Y. Wang, J. L. Sun, L. E. Piilonen, K. T. McDonald, L. Y. Wang, Guofu Cao, M. C. McFarlane, Dmitry V. Naumov, L. Kang, W. C. Lai, B. Viren, Vit Vorobel, Q. W. Zhao, Maxim Gonchar, Z. Isvan, Wei Li, S. Jetter, R. A. Johnson, L. H. Whitehead, Xiaoyuan Chen, X. N. Li, R. H.M. Tsang, Richard Rosero, Yanchu Wang, X. Q. Li, H. Liu, J. M. Link, J. P. Cummings, K. K. Kwan, Ilya Butorov, M. V. Diwan, E. Draeger, J. J. Ling, Zhiyong Zhang, C. A. Lewis, H. L. Zhuang, A. G. Olshevski, Y. Nakajima, M. W. Kwok, Wenjie Wang, Mengsu Yang, K. Whisnant, E. T. Worcester, J. de Arcos, S. Trentalange, Guisen Li, Honghan Gong, Z. Y. Deng, W. K. Ngai, Qingming Ma, H. K. Tanaka, Yu-leung Chan, Qinglong Wu, Siew Cheng Wong, Min-Xin Guan, X. Tang, Yi Chen, W. P. Wang, Jiaheng Zou, Tian Xue, C. White, C. H. Wang, D. E. Jaffe, G. Y. Yu, Yufeng Li, Y. K. Heng, W. R. Edwards, Y. S. Yeh, S. L. Zang, J. K. C. Leung, Y. H. Chang, Zhibing Li, G. X. Sun, X. C. Ruan, L. M. Hu, Chao Zhang, G. H. Han, S. H. Zhang, D. M. Xia, C. Chasman, Y. B. Hsiung, Lin Yang, O. D. Tsai, Jinmei Liu, Jing Zhao, X. Y. Ma, J. Y. Xu, I. Mitchell, Y. C. Tung, L. S. Wang, S. J. Chen, Jianglai Liu, Xin Qian, R. L. Hahn, Zhi-zhong Xing, J. Y. Fu, T. Wise, L. Z. Wang, F. Z. Qi, J. F. Chang, Jen-Chieh Peng, X. Xia, H. Themann, Guanghua Gong, Chi Lin, P. Jaffke, W. Beriguete, Yi-Fang Zhao, M. H. Ye, Juan Pedro Ochoa-Ricoux, H. R. Band, H. Liang, Yixue Chen, N. Raper, C. E. Tull, G. Hussain, S. S. Liu, J. Lee, H. L. H. Wong, Y. X. Zhang, J. Xu, A. Leung, Y. C. Lin, J. Yan, R. D. McKeown, H. Y. Ngai, R. L. Gill, Patrick Huber, Bing-Lin Young, E. Naumova, D. A. Dwyer, H. M. Steiner, and Y. Q. Ma

Subjects
Physics, Oscillation, FOS: Physical sciences, General Physics and Astronomy, Daya Bay Reactor Neutrino Experiment, Electron, Spectral line, High Energy Physics - Experiment, Nuclear physics, High Energy Physics - Experiment (hep-ex), Muon neutrino, Nuclear Experiment (nucl-ex), Nuclear Experiment, Oscillation amplitude, Electron neutrino, Energy (signal processing)
Abstract

A measurement of the energy dependence of antineutrino disappearance at the Daya Bay Reactor Neutrino Experiment is reported. Electron antineutrinos ($\overline{\nu}_{e}$) from six $2.9$ GW$_{\rm th}$ reactors were detected with six detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls. Using 217 days of data, 41589 (203809 and 92912) antineutrino candidates were detected in the far hall (near halls). An improved measurement of the oscillation amplitude $\sin^{2}2\theta_{13} = 0.090^{+0.008}_{-0.009} $ and the first direct measurement of the $\overline{\nu}_{e}$ mass-squared difference $|\Delta m^{2}_{ee}|= (2.59_{-0.20}^{+0.19}) \times 10^{-3}\ {\rm eV}^2 $ is obtained using the observed $\overline{\nu}_{e}$ rates and energy spectra in a three-neutrino framework. This value of $|\Delta m^{2}_{ee}|$ is consistent with $|\Delta m^{2}_{\mu\mu}|$ measured by muon neutrino disappearance, supporting the three-flavor oscillation model., Comment: As accepted for publication by Phys. Rev. Lett. including ancillary table

Published
2014

33. Search for a light sterile neutrino at daya bay

Author

Kirk T. McDonald, L. S. Wang, J. Y. Fu, A. G. Olshevski, E. Draeger, T. Wise, M. V. Diwan, H. L. Zhuang, Xi Chen, X. Q. Li, W. C. Lai, E. T. Worcester, F. Li, J. de Arcos, J. Monari Kebwaro, J. J. Cherwinka, Bing-Lin Young, Yi Chen, J. F. Chang, X. Tang, Jianglai Liu, R. H.M. Tsang, Y. Xu, E. C. Huang, Yu Zhang, Juan Pedro Ochoa-Ricoux, Yu-leung Chan, L. Lebanowski, Y. Y. Ding, Y. Zhao, C. H. Wang, Z. B. Li, S. H. Kettell, Yufeng Li, V. Pec, P. Y. Lin, J. J. Ling, E. Naumova, D. A. Dwyer, Q. W. Zhao, Yi Wei, S. Hans, Y. K. Hor, Marco Grassi, Miao He, K. K. Kwan, Ilya Butorov, Patrick Huber, G. X. Sun, Christopher C. Yang, Jen-Chieh Peng, X. C. Ruan, Y. S. Yeh, H. M. Steiner, Chao Zhang, Xin Qian, W. Zhong, C. A. Lewis, X. Xia, L. M. Hu, Lin Yang, G. H. Han, H. Themann, Jinmei Liu, K. B. Luk, Baoqing Zeng, J. B. Jiao, K. Whisnant, Maxim Gonchar, Xiao-yan Li, Guanghua Gong, Jing Zhao, D. E. Jaffe, Vit Vorobel, Z. Isvan, Chi Lin, Zhi-zhong Xing, X. Y. Ma, J. Y. Xu, S. L. Zang, A. B. Balantekin, Wei Li, I. Mitchell, R. A. Johnson, J. K. C. Leung, H. S. Chen, Jinjuan Ren, Q. J. Li, J. Xu, Y. C. Tung, X. P. Ji, Jiawen Zhang, H. Liu, Y. H. Tam, X. Wang, J. L. Sun, R. T. Lei, Qingmin Zhang, H. R. Band, H. Liang, Yixue Chen, Chun S. J. Pun, B. B. Shao, Haoqi Lu, Dejun Li, Q. X. Zhang, Shaomin Chen, Jun Cao, Q. Y. Chen, J. Cummings, H. Y. Wei, Zhiyong Zhang, Min-Xin Guan, Y. P. Cheng, Jim Napolitano, S. H. Zhang, Michael Kramer, D. M. Xia, M. C. McFarlane, Xubo Ma, R. W. Hackenburg, Li Chang, N. Raper, Dmitry V. Naumov, Xiaohu Guo, Z. Wang, Rupert Leitner, M. T. Yang, C. Chasman, Zeyuan Yu, W. R. Edwards, Jin Yu, Y. B. Hsiung, G. Y. Yu, T. Kwok, Guey-Lin Lin, L. Q. Ge, Qinglong Wu, R. D. McKeown, F. Z. Qi, Y. Ma, Zhongyuan Zhou, L. Kang, B. R. Littlejohn, Y. H. Chang, P. Jaffke, W. Beriguete, Y. Wang, X. F. Du, Tian Xue, Wei Wang, F. H. Zhang, Christopher G. White, Z. P. Zhang, Y. B. Liu, H. J. Jiang, H. Z. Huang, K. L. Jen, Y. K. Heng, Zheng Wang, S. J. Patton, W. Q. Gu, S. K. Lin, Liangjian Wen, Guofu Cao, Tao Hu, N. Y. Wang, R. G. Wang, D. M. Webber, X. L. Ji, Y. H. Zhang, Liang Zhan, G. Hussain, B. Viren, Li Zhou, C. E. Tull, S. S. Liu, J. Lee, H. L. H. Wong, Y. X. Zhang, A. Leung, Y. C. Lin, J. Yan, H. Y. Ngai, R. L. Gill, Richard Rosero, Y. Nakajima, M. W. Kwok, Wenjie Wang, K. V. Tsang, Lawrence Pinsky, L. Y. Wang, M. H. Ye, Guisen Li, Honghan Gong, Z. Y. Deng, Qingming Ma, Siew Cheng Wong, Jiaheng Zou, Igor Nemchenok, Zhijian Zhang, L. Zheng, F. P. An, B. Ren, Yue Meng, L. J. Hu, D. W. Liu, Minfang Yeh, B. Roskovec, J. K. Xia, K. M. Heeger, Kwong Lau, Mengsu Yang, Y. Zhang, P. Hinrichs, C. Lu, J. L. Xu, L. H. Whitehead, J. M. Link, Xingtao Huang, M. Qi, S. R. Ely, M. Bishai, Yaolin Zhao, L. S. Littenberg, Zhi Ning, B. Z. Hu, Simon Blyth, M. Z. Wang, Ming Chung Chu, W. Hu, L. E. Piilonen, and S. Jetter

Subjects
Physics, Sterile neutrino, Oscillation, Daya bay, FOS: Physical sciences, General Physics and Astronomy, Spectral distortion, Daya Bay Reactor Neutrino Experiment, Electron, High Energy Physics - Experiment, Nuclear physics, High Energy Physics - Experiment (hep-ex), Neutrino, Neutrino oscillation
Abstract

A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines from six 2.9~GW$_{\rm th}$ nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512~m and 561~m) and one far (1579~m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the $10^{\rm -3}~{\rm eV}^{2} < |\Delta m_{41}^{2}| < 0.3~{\rm eV}^{2}$ range. The relative spectral distortion due to electron antineutrino disappearance was found to be consistent with that of the three-flavor oscillation model. The derived limits on $\sin^22\theta_{14}$ cover the $10^{-3}~{\rm eV}^{2} \lesssim |\Delta m^{2}_{41}| \lesssim 0.1~{\rm eV}^{2}$ region, which was largely unexplored., Comment: 7 pages, 4 figures

Published
2014

34. Observation of electron-antineutrino disappearance at Daya Bay

Author

D. M. Webber, X. Huang, A. Pagac, Y. Wang, Pu Huang, W. Q. Jiang, F. H. Zhang, L. Lebanowski, Y. Y. Ding, M. Qi, S. R. Ely, M. Bishai, H. X. Huang, J. J. Cherwinka, Tian Xue, H. C. Wong, Xuejun Liu, Y. A. Gornushkin, Guisen Li, Y. K. Heng, A. G. Olshevski, Xiaoyuan Chen, Yaolong Zhang, Yi Wei, Meng Wang, X. C. Chen, K. K. Kwan, Jianbin Xu, C. E. Tull, Yi Chen, Q. He, Li Zhou, Honghan Gong, Z. Y. Deng, E. Draeger, H. Themann, Guanghua Gong, P. Stoler, M. V. Diwan, W. K. Ngai, S. D. Fang, W. Zhong, H. L. Zhuang, K. T. McDonald, E. T. Worcester, Qingming Ma, J. K. C. Leung, Min-Xin Guan, B. R. Littlejohn, Chi Lin, L. E. Piilonen, T. Wise, Y. X. Chen, R. H.M. Tsang, W. C. Lai, Zhongyuan Zhou, S. Jetter, Q. J. Li, S. H. Kettell, K. Shih, Jiaheng Zou, Wai Ting Chan, C. White, H. Z. Huang, W. P. Wang, Igor Nemchenok, Zhijian Zhang, A. B. Balantekin, L. Zheng, Michael Kramer, C. A. Lewis, Xiaoyan Ma, B. Viren, Yufeng Li, L. Kang, B. B. Shao, C. R. Newsom, Vit Vorobel, S. J. Patton, W. Q. Gu, Richard Rosero, Lei Yang, Z. Isvan, K. Y. Leung, L. Q. Ge, D. Wenman, Guo-Lin Xu, Wei Li, J. E. Morgan, K. Whisnant, Y. H. Chang, D. Mohapatra, Maxim Gonchar, Joonho Lee, X. L. Ji, W. S. He, J. Napolitano, F. P. An, Wing-Hon Lai, X. B. Li, D. R. Beavis, L. S. Wang, Rupert Leitner, Zeyuan Yu, B. Z. Hu, T. Luo, Y. Xu, Chun S. J. Pun, S. Blyth, J. Goett, C. H. Wang, R. A. Johnson, K. Zhang, Shaomin Chen, Jun Cao, H. S. Chen, Zhenyu Zhang, Zhiyong Zhang, Ming Chung Chu, Bei Cai, V. Ghazikhanian, Changgen Yang, Y. Nakajima, Jiawen Zhang, M. W. Kwok, P. Hinrichs, K. Lau, Q. W. Zhao, S. F. Li, B. Seilhan, M. C. McFarlane, Y. B. Hsiung, R. W. Hackenburg, V. Pec, S. J. Chen, C. Liu, J. Cummings, Sa Liu, Yue Meng, Ching-Yao Lai, R. D. McKeown, Tao Hu, F. F. Wu, S. Hans, Jianglai Liu, T. H. Ho, F. Z. Qi, Dmitry V. Naumov, C. Lu, Minfang Yeh, J. Z. Bai, N. Y. Wang, X. N. Li, J. M. Link, J. J. Ling, Kam-Biu Luk, R. L. Brown, S. Trentalange, K. V. Tsang, J. B. Jiao, J. L. Xu, C. Pearson, Z. Wang, Y. S. Yeh, Xin Qian, Huo Yan Chen, X. F. Du, H. L. H. Wong, Y. X. Zhang, J. Wong, Zai-Wei Fu, Q. Wu, B. L. Young, B. Roskovec, Y. C. Lin, Lawrence S. Pinsky, Steve Virostek, Y. H. Tam, Y. K. Hor, T. Kwok, X. T. Huang, Guey-Lin Lin, Liangjian Wen, S. H. Zhang, D. M. Xia, Guofu Cao, W. Beriguete, Zhi-zhong Xing, L. S. Littenberg, Yi-Fang Zhao, L. Y. Wang, Chao Zhang, Patrick Huber, Zhi Ning, H. Y. Ngai, R. L. Gill, Jennifer S. Li, R. Carr, Y. B. Nie, X. Tang, Zhenyu Wang, J. Y. Fu, Xiang Li, F. Li, C. Chasman, Haoqi Lu, Jingjing Liang, Jen-Chieh Peng, B. W. Mayes, Lixin Dong, W. Xu, M. H. Ye, Y. B. Liu, J. Wilhelmi, H. J. Jiang, L. Z. Wang, X. P. Ji, J. L. Sun, J. F. Chang, O. D. Tsai, X. L. Luo, Xuan Wang, Jinmei Liu, Jing Zhao, X. Y. Ma, L. H. Ma, D. E. Jaffe, L. H. Whitehead, Q. Xiao, Shengxin Lin, K. M. Heeger, W. R. Edwards, K. Yip, Juan Pedro Ochoa-Ricoux, M. K.P. Lee, D. Oh, Miao He, B. Li, Y. Torun, C. A. Whitten, L. Greenler, R. G. Wang, Y. H. Zhang, Ting-Chi Wang, Liang Zhan, A. Luk, D. A. Dwyer, H. R. Band, H. Liang, H. M. Steiner, Q. X. Zhang, Y. Q. Ma, S. K. Lin, N. Raper, Brent J. Liu, H. K. Tanaka, Xiaohu Guo, X. S. Chen, Hongjun Liu, Zhibing Li, K. Boddy, R. L. Hahn, Qingmin Zhang, S. T. Xiang, G. X. Sun, X. C. Ruan, and D. W. Liu

Subjects
NOνA, Physics, Particle physics, T2K experiment, General Physics and Astronomy, FOS: Physical sciences, Daya Bay Reactor Neutrino Experiment, High Energy Physics - Experiment, Nuclear physics, High Energy Physics - Experiment (hep-ex), Inverse beta decay, Neutrino, Neutrino oscillation, Electron neutrino, Jiangmen Underground Neutrino Observatory
Abstract

The Daya Bay Reactor Neutrino Experiment has measured a non-zero value for the neutrino mixing angle $\theta_{13}$ with a significance of 5.2 standard deviations. Antineutrinos from six 2.9 GW$_{\rm th}$ reactors were detected in six antineutrino detectors deployed in two near (flux-weighted baseline 470 m and 576 m) and one far (1648 m) underground experimental halls. With a 43,000 ton-GW_{\rm th}-day livetime exposure in 55 days, 10416 (80376) electron antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to expected number of antineutrinos at the far hall is $R=0.940\pm 0.011({\rm stat}) \pm 0.004({\rm syst})$. A rate-only analysis finds $\sin^22\theta_{13}=0.092\pm 0.016({\rm stat})\pm0.005({\rm syst})$ in a three-neutrino framework., Comment: 5 figures. Version to appear in Phys. Rev. Lett

Published
2012

35. A side-by-side comparison of Daya Bay antineutrino detectors

Author

O. D. Tsai, H. F. Hao, Jinmei Liu, Jing Zhao, X. Y. Ma, A. B. Balantekin, Minfang Yeh, J. Z. Bai, L. Kang, J. Y. Fu, Jiawen Zhang, Q. An, B. Roskovec, Liangquan Ge, D. Wenman, Sa Liu, C. H. Wang, Guisen Li, H. S. Chen, J. F. Chang, Honghan Gong, Z. Y. Deng, Patrick Huber, Q. Xiao, Shengxin Lin, Zai-Wei Fu, W. K. Ngai, Qingming Ma, F. Li, Rupert Leitner, Bing-Lin Young, T. Kwok, Guey-Lin Lin, J. Wilhelmi, Jiaheng Zou, D. E. Jaffe, Y. K. Hor, Vit Vorobel, L. Lebanowski, Y. Y. Ding, Guanghua Gong, Y. B. Hsiung, F. F. Wu, P. Stoler, Chi Lin, W. Beriguete, D. M. Webber, X. L. Ji, J. K. C. Leung, Chao Zhang, Wei Li, Xurong Chen, Xiaoyuan Chen, M. V. Diwan, X. Q. Li, S. D. Fang, G. X. Sun, X. C. Ruan, Y. S. Yeh, K. K. Kwan, X. L. Luo, L. H. Whitehead, S. Blyth, Y. Zhou, Zhiyong Zhang, R. G. Wang, Y. H. Zhang, Liang Zhan, A. Luk, J. J. Cherwinka, X. Tang, K. M. Heeger, K. V. Tsang, S. H. Kettell, L. H. Ma, Xuan Wang, X. C. Chen, A. G. Olshevski, D. W. Liu, Xuejun Liu, Z. B. Li, Kirk T. McDonald, R. W. Hackenburg, W. R. Edwards, Y. A. Gornushkin, T. Wise, Juan Pedro Ochoa-Ricoux, D. A. Dwyer, Z. Wang, Zhiyuan Wang, Zhongyuan Zhou, X. P. Ji, Li Zhou, X. F. Du, H. R. Band, Wei Wang, S. H. Zhang, D. Mohapatra, Maxim Gonchar, Lawrence Pinsky, D. M. Xia, H. M. Steiner, J. L. Sun, H. Liang, Y. Q. Ma, Y. C. Lin, Xiaohu Guo, L. Y. Wang, Yi Chen, Q. He, C. Chasman, R. A. Johnson, Wing-Hon Lai, X. B. Li, Yi Wei, Brent J. Liu, Jen-Chieh Peng, H. Z. Huang, V. Pec, Changgen Yang, P. Hinrichs, S. Trentalange, Richard Rosero, S. J. Patton, S. Hans, W. Q. Gu, Miao He, C. Lu, J. L. Xu, J. B. Xi, W. L. Zhong, Y. H. Sun, L. Greenler, B. B. Shao, J. Wong, Michael Kramer, Y. Nakajima, Min-Xin Guan, B. R. Littlejohn, M. W. Kwok, Haoqi Lu, Yagmur Torun, Qingmin Zhang, R. D. McKeown, T. H. Ho, F. Z. Qi, J. B. Jiao, Y. H. Chang, W. C. Lai, M. K.P. Lee, W. S. He, Chun S. J. Pun, Shaomin Chen, Jun Cao, S. F. Li, M. C. McFarlane, Ching-Yao Lai, Dmitry V. Naumov, E. Draeger, H. L. Zhuang, Christopher G. White, Yufeng Li, Jun Li, J. M. Link, J. P. Cummings, C. A. Lewis, K. Whisnant, L. S. Littenberg, H. K. Tanaka, Zhi Ning, Tian Xue, Y. K. Heng, Zhenyu Zhang, K. Lau, Tao Hu, N. Y. Wang, B. Viren, Kwok Yin Leung, Y. Xu, Q. W. Zhao, R. Carr, Y. B. Nie, B. W. Mayes, X. Huang, L. E. Piilonen, S. Jetter, K. Shih, R. H.M. Tsang, J. J. Ling, Guo-Lin Xu, W. Q. Jiang, Xin Qian, B. Z. Hu, Xiao-yan Li, R. L. Hahn, X. T. Huang, Zhi-zhong Xing, M. Z. Wang, Ming Chung Chu, Q. J. Li, Yaolong Zhang, C. E. Tull, M. Qi, S. R. Ely, C. R. Newsom, M. Bishai, Yaolin Zhao, Jianbin Xu, L. S. Wang, Zeyuan Yu, H. L. H. Wong, Y. X. Zhang, A. Pagac, B. Seilhan, Y. Wang, Pu Huang, S. J. Chen, Q. Wu, F. H. Zhang, H. X. Huang, Jianglai Liu, H. Y. Ngai, R. L. Gill, Igor Nemchenok, Zhijian Zhang, L. Zheng, J. Napolitano, F. P. An, Yue Meng, Kam-Biu Luk, Haifeng Zhao, M. H. Ye, S. K. Lin, R. L. Brown, Liangjian Wen, Guofu Cao, Y. B. Liu, H. J. Jiang, and Lin Yang

Subjects
Physics, Nuclear and High Energy Physics, Particle physics, Physics - Instrumentation and Detectors, 010308 nuclear & particles physics, Daya bay, Detector, FOS: Physical sciences, Daya Bay Reactor Neutrino Experiment, Instrumentation and Detectors (physics.ins-det), 01 natural sciences, 7. Clean energy, High Energy Physics - Experiment, Nuclear physics, High Energy Physics - Experiment (hep-ex), 0103 physical sciences, Calibration, Neutrino, Nuclear Experiment (nucl-ex), 010306 general physics, Neutrino oscillation, Instrumentation, Nuclear Experiment
Abstract

The Daya Bay Reactor Neutrino Experiment is designed to determine precisely the neutrino mixing angle $\theta_{13}$ with a sensitivity better than 0.01 in the parameter sin$^22\theta_{13}$ at the 90% confidence level. To achieve this goal, the collaboration will build eight functionally identical antineutrino detectors. The first two detectors have been constructed, installed and commissioned in Experimental Hall 1, with steady data-taking beginning September 23, 2011. A comparison of the data collected over the subsequent three months indicates that the detectors are functionally identical, and that detector-related systematic uncertainties exceed requirements., Comment: 24 pages, 36 figures

Published
2012

36. Elimination of radon from the body

Author

Norton Nelson, Evelyn S. Jetter, and John H. Harley

Subjects
lcsh:GE1-350, business.industry, Radiochemistry, digestive, oral, and skin physiology, chemistry.chemical_element, Radon, Total body, Radon exposure, respiratory tract diseases, Radium, chemistry, Radioactive contamination, Dosimetry, Nuclear medicine, business, lcsh:Environmental sciences, General Environmental Science
Abstract

A series of experiments were run on the retention of inhaled radon. The radon absorbed by the body is present in a multiphase system, showing five distinct elimination coefficients. After high-level radon exposure for a normal working day, an appreciable breath radon output is found 72 h after removal from exposure. This is a practical consideration in breath radon sampling, and it must be realized that the breath measurement may indicate a higher body radium content than that actually present. Another valuable result is that the radon retention figures allow us to reconcile the results of breath radon analyses and total body radium analyses on unexposed persons. The results of our breath measurements averaged 6[times]10[sup [minus]9] g on ten unexposed individuals. It is apparent that the breath radon measurement is not capable of measuring normal body radium, due both to the small quantity present, and to the interference of radon absorbed by the body from the normal environment. 2 refs., 3 figs., 4 tab.

Published
1994

38. Cryopreservation of peripheral blood progenitor cells: characteristics of suitable techniques

Author

A, Sputtek, S, Jetter, K, Hummel, and P, Kühnl

Subjects
Cryopreservation, Dose-Response Relationship, Drug, Cell Survival, Macrophages, Hematopoietic Stem Cell Transplantation, Colony-Forming Units Assay, Hydroxyethyl Starch Derivatives, Cryoprotective Agents, Blood Preservation, Hematologic Neoplasms, Humans, Dimethyl Sulfoxide, Leukapheresis, Granulocytes
Abstract

The influence of 6 different cooling rates (1.4, 5, 10, 15, 20, 160 K/min) and 5 different compositions of the suspensions to be frozen (% DMSO/% HES: 10/0, 7.5/2.5, 5/6, 2.5/7.5, 0/10) were investigated in 30 aliquots from each of 12 peripheral blood progenitor cells (PBSC) products which had been obtained by leukapheresis from 11 patients with hematological malignancies and solid tumors and 1 healthy donor treated with 5-24 micrograms/kg body weight/day granulocyte colony stimulating factor (G-CSF) over 5 days. The MNC concentration in the products obtained amounted to 4.51 +/- 1.55 x 10(7)/ml (mean +/- SEM), range: 2.10-7.65 x 10(7)/ml). For freezing, cooling rates were generated by means of a liquid nitrogen(LN2)-operated, computer-controlled freezer, a mechanical -80 degrees C freezer, in the vapor phase over LN2, and by submerging into LN2. The statistical analysis of the results clearly indicates that optimum results compared with the prefreeze values for numerical recovery (80.6 +/- 20.1%, Coulter counter), viability (membrane integrity by Trypan blue exclusion 91.6 +/- 4.1%), and colony-forming potential (56.2 +/- 45.8% erythroid burst-forming units [BFU-E], 63.4 +/- 72.8% myeloid colonies [CFU-GM]) were achieved at a cooling rate of 1.4 K/min with 10% DMSO being present. The values obtained at a cooling rate of 5 K/min (-80 degrees C mechanical refrigerator) in the presence of 5% DMSO and 6% HES did not differ significantly (i.e., membrane integrity 91.8 +/- 3.9%, BFU-E 53.0 +/- 37.4%, CFU-GM 47.8 +/- 58.2%). At cooling rates above 5 K/min and DMSO concentrations lower than 5% (in spite of higher HES concentrations) there was a significant drop of CFU recovery (CFU-GM plus BFU-E) to almost 0%. In parallel, numerical recovery and viability dropped as well, but less pronounced, indicating that both methods are unsuitable for the prediction of CFU recovery when different freezing protocols are applied. We need at least 5% DMSO (in the presence of 6% HES) in spite of the undesirable histamine-releasing effect of this compound. The cooling rate is not critical in the range from 1 to 5 K/min and can easily be achieved by -80 degrees C freezers.

Published
1997

39. The Effect of agr-Tocopheryl Phosphate on Diphosphopyridine Nucleotidase

Author

Naomi S. Jetter and Wm. M. Govier

Subjects
chemistry.chemical_classification, Multidisciplinary, Vitamin E, medicine.medical_treatment, alpha-Tocopherol, Vitamins, Tocopheryl phosphate, chemistry.chemical_compound, NAD+ Nucleosidase, Biochemistry, chemistry, Diphosphopyridine Nucleotidase, Nucleotidases, Nucleotidase, medicine, Humans, Nucleotide
Published
1948

40. Genetic background modulates phenotypes of serotonin transporter Ala56 knock-in mice

Author

James S. Sutcliffe, Nicole L. Baganz, Randy D. Blakely, Christopher L. Muller, Jacqueline N. Crawley, Christopher S. Jetter, Travis M. Kerr, Charisma R. Shah, Jeremy Veenstra-VanderWeele, Rita Pfeiffer, George M. Anderson, and Mahfuzur Miah

Subjects
Serotonin, Autism, Congenic, Transporter, medicine.disease_cause, Serotonergic, 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, Gene knockin, Genetic variation, medicine, Compulsive, Molecular Biology, Serotonin transporter, 030304 developmental biology, Genetics, 0303 health sciences, Mutation, biology, Monoamine, Research, Phenotype, Psychiatry and Mental health, biology.protein, Psychology, Neuroscience, 030217 neurology & neurosurgery, Receptor, Developmental Biology
Abstract

Background Previously, we identified multiple, rare serotonin (5-HT) transporter (SERT) variants in children with autism spectrum disorder (ASD). Although in our study the SERT Ala56 variant was over-transmitted to ASD probands, it was also seen in some unaffected individuals, suggesting that associated ASD risk is influenced by the epistatic effects of other genetic variation. Subsequently, we established that mice expressing the SERT Ala56 variant on a 129S6/S4 genetic background display multiple biochemical, physiological and behavioral changes, including hyperserotonemia, altered 5-HT receptor sensitivity, and altered social, communication, and repetitive behavior. Here we explore the effects of genetic background on SERT Ala56 knock-in phenotypes. Methods To explore the effects of genetic background, we backcrossed SERT Ala56 mice on the 129 background into a C57BL/6 (B6) background to achieve congenic B6 SERT Ala56 mice, and assessed autism-relevant behavior, including sociability, ultrasonic vocalizations, and repetitive behavior in the home cage, as well as serotonergic phenotypes, including whole blood serotonin levels and serotonin receptor sensitivity. Results One consistent phenotype between the two strains was performance in the tube test for dominance, where mutant mice displayed a greater tendency to withdraw from a social encounter in a narrow tube as compared to wildtype littermate controls. On the B6 background, mutant pup ultrasonic vocalizations were significantly increased, in contrast to decreased vocalizations seen previously on the 129 background. Several phenotypes seen on the 129 background were reduced or absent when the mutation was placed on the B6 background, including hyperserotonemia, 5-HT receptor hypersensivity, and repetitive behavior. Conclusions Our findings provide a cogent example of how epistatic interactions can modulate the impact of functional genetic variation and suggest that some aspects of social behavior may be especially sensitive to changes in SERT function. Finally, these results provide a platform for the identification of genes that may modulate the risk of ASD in humans.

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41. Limits on Active to Sterile Neutrino Oscillations from Disappearance Searches in the MINOS, Daya Bay, and Bugey-3 Experiments.

Author

Adamson P, An FP, Anghel I, Aurisano A, Balantekin AB, Band HR, Barr G, Bishai M, Blake A, Blyth S, Bock GJ, Bogert D, Cao D, Cao GF, Cao J, Cao SV, Carroll TJ, Castromonte CM, Cen WR, Chan YL, Chang JF, Chang LC, Chang Y, Chen HS, Chen QY, Chen R, Chen SM, Chen Y, Chen YX, Cheng J, Cheng JH, Cheng YP, Cheng ZK, Cherwinka JJ, Childress S, Chu MC, Chukanov A, Coelho JA, Corwin L, Cronin-Hennessy D, Cummings JP, de Arcos J, De Rijck S, Deng ZY, Devan AV, Devenish NE, Ding XF, Ding YY, Diwan MV, Dolgareva M, Dove J, Dwyer DA, Edwards WR, Escobar CO, Evans JJ, Falk E, Feldman GJ, Flanagan W, Frohne MV, Gabrielyan M, Gallagher HR, Germani S, Gill R, Gomes RA, Gonchar M, Gong GH, Gong H, Goodman MC, Gouffon P, Graf N, Gran R, Grassi M, Grzelak K, Gu WQ, Guan MY, Guo L, Guo RP, Guo XH, Guo Z, Habig A, Hackenburg RW, Hahn SR, Han R, Hans S, Hartnell J, Hatcher R, He M, Heeger KM, Heng YK, Higuera A, Holin A, Hor YK, Hsiung YB, Hu BZ, Hu T, Hu W, Huang EC, Huang HX, Huang J, Huang XT, Huber P, Huo W, Hussain G, Hylen J, Irwin GM, Isvan Z, Jaffe DE, Jaffke P, James C, Jen KL, Jensen D, Jetter S, Ji XL, Ji XP, Jiao JB, Johnson RA, de Jong JK, Joshi J, Kafka T, Kang L, Kasahara SM, Kettell SH, Kohn S, Koizumi G, Kordosky M, Kramer M, Kreymer A, Kwan KK, Kwok MW, Kwok T, Lang K, Langford TJ, Lau K, Lebanowski L, Lee J, Lee JH, Lei RT, Leitner R, Leung JK, Li C, Li DJ, Li F, Li GS, Li QJ, Li S, Li SC, Li WD, Li XN, Li YF, Li ZB, Liang H, Lin CJ, Lin GL, Lin S, Lin SK, Lin YC, Ling JJ, Link JM, Litchfield PJ, Littenberg L, Littlejohn BR, Liu DW, Liu JC, Liu JL, Loh CW, Lu C, Lu HQ, Lu JS, Lucas P, Luk KB, Lv Z, Ma QM, Ma XB, Ma XY, Ma YQ, Malyshkin Y, Mann WA, Marshak ML, Martinez Caicedo DA, Mayer N, McDonald KT, McGivern C, McKeown RD, Medeiros MM, Mehdiyev R, Meier JR, Messier MD, Miller WH, Mishra SR, Mitchell I, Mooney M, Moore CD, Mualem L, Musser J, Nakajima Y, Naples D, Napolitano J, Naumov D, Naumova E, Nelson JK, Newman HB, Ngai HY, Nichol RJ, Ning Z, Nowak JA, O'Connor J, Ochoa-Ricoux JP, Olshevskiy A, Orchanian M, Pahlka RB, Paley J, Pan HR, Park J, Patterson RB, Patton S, Pawloski G, Pec V, Peng JC, Perch A, Pfützner MM, Phan DD, Phan-Budd S, Pinsky L, Plunkett RK, Poonthottathil N, Pun CS, Qi FZ, Qi M, Qian X, Qiu X, Radovic A, Raper N, Rebel B, Ren J, Rosenfeld C, Rosero R, Roskovec B, Ruan XC, Rubin HA, Sail P, Sanchez MC, Schneps J, Schreckenberger A, Schreiner P, Sharma R, Moed Sher S, Sousa A, Steiner H, Sun GX, Sun JL, Tagg N, Talaga RL, Tang W, Taychenachev D, Thomas J, Thomson MA, Tian X, Timmons A, Todd J, Tognini SC, Toner R, Torretta D, Treskov K, Tsang KV, Tull CE, Tzanakos G, Urheim J, Vahle P, Viaux N, Viren B, Vorobel V, Wang CH, Wang M, Wang NY, Wang RG, Wang W, Wang X, Wang YF, Wang Z, Wang ZM, Webb RC, Weber A, Wei HY, Wen LJ, Whisnant K, White C, Whitehead L, Whitehead LH, Wise T, Wojcicki SG, Wong HL, Wong SC, Worcester E, Wu CH, Wu Q, Wu WJ, Xia DM, Xia JK, Xing ZZ, Xu JL, Xu JY, Xu Y, Xue T, Yang CG, Yang H, Yang L, Yang MS, Yang MT, Ye M, Ye Z, Yeh M, Young BL, Yu ZY, Zeng S, Zhan L, Zhang C, Zhang HH, Zhang JW, Zhang QM, Zhang XT, Zhang YM, Zhang YX, Zhang ZJ, Zhang ZP, Zhang ZY, Zhao J, Zhao QW, Zhao YB, Zhong WL, Zhou L, Zhou N, Zhuang HL, and Zou JH

Abstract

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^{2}2θ&#95;{μe} are set over 6 orders of magnitude in the sterile mass-squared splitting Δm&#95;{41}^{2}. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Δm&#95;{41}^{2}<0.8  eV^{2} at 95%  CL&#95;{s}.

Published
2016
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42. Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment.

Author

An FP, Balantekin AB, Band HR, Bishai M, Blyth S, Cao D, Cao GF, Cao J, Cen WR, Chan YL, Chang JF, Chang LC, Chang Y, Chen HS, Chen QY, Chen SM, Chen YX, Chen Y, Cheng JH, Cheng J, Cheng YP, Cheng ZK, Cherwinka JJ, Chu MC, Chukanov A, Cummings JP, de Arcos J, Deng ZY, Ding XF, Ding YY, Diwan MV, Dolgareva M, Dove J, Dwyer DA, Edwards WR, Gill R, Gonchar M, Gong GH, Gong H, Grassi M, Gu WQ, Guan MY, Guo L, Guo RP, Guo XH, Guo Z, Hackenburg RW, Han R, Hans S, He M, Heeger KM, Heng YK, Higuera A, Hor YK, Hsiung YB, Hu BZ, Hu T, Hu W, Huang EC, Huang HX, Huang XT, Huber P, Huo W, Hussain G, Jaffe DE, Jaffke P, Jen KL, Jetter S, Ji XP, Ji XL, Jiao JB, Johnson RA, Joshi J, Kang L, Kettell SH, Kohn S, Kramer M, Kwan KK, Kwok MW, Kwok T, Langford TJ, Lau K, Lebanowski L, Lee J, Lee JH, Lei RT, Leitner R, Leung JK, Li C, Li DJ, Li F, Li GS, Li QJ, Li S, Li SC, Li WD, Li XN, Li YF, Li ZB, Liang H, Lin CJ, Lin GL, Lin S, Lin SK, Lin YC, Ling JJ, Link JM, Littenberg L, Littlejohn BR, Liu DW, Liu JL, Liu JC, Loh CW, Lu C, Lu HQ, Lu JS, Luk KB, Lv Z, Ma QM, Ma XY, Ma XB, Ma YQ, Malyshkin Y, Martinez Caicedo DA, McDonald KT, McKeown RD, Mitchell I, Mooney M, Nakajima Y, Napolitano J, Naumov D, Naumova E, Ngai HY, Ning Z, Ochoa-Ricoux JP, Olshevskiy A, Pan HR, Park J, Patton S, Pec V, Peng JC, Pinsky L, Pun CS, Qi FZ, Qi M, Qian X, Raper N, Ren J, Rosero R, Roskovec B, Ruan XC, Steiner H, Sun GX, Sun JL, Tang W, Taychenachev D, Treskov K, Tsang KV, Tull CE, Viaux N, Viren B, Vorobel V, Wang CH, Wang M, Wang NY, Wang RG, Wang W, Wang X, Wang YF, Wang Z, Wang Z, Wang ZM, Wei HY, Wen LJ, Whisnant K, White CG, Whitehead L, Wise T, Wong HL, Wong SC, Worcester E, Wu CH, Wu Q, Wu WJ, Xia DM, Xia JK, Xing ZZ, Xu JY, Xu JL, Xu Y, Xue T, Yang CG, Yang H, Yang L, Yang MS, Yang MT, Ye M, Ye Z, Yeh M, Young BL, Yu ZY, Zeng S, Zhan L, Zhang C, Zhang HH, Zhang JW, Zhang QM, Zhang XT, Zhang YM, Zhang YX, Zhang YM, Zhang ZJ, Zhang ZY, Zhang ZP, Zhao J, Zhao QW, Zhao YB, Zhong WL, Zhou L, Zhou N, Zhuang HL, and Zou JH

Abstract

This Letter reports an improved search for light sterile neutrino mixing in the electron antineutrino disappearance channel with the full configuration of the Daya Bay Reactor Neutrino Experiment. With an additional 404 days of data collected in eight antineutrino detectors, this search benefits from 3.6 times the statistics available to the previous publication, as well as from improvements in energy calibration and background reduction. A relative comparison of the rate and energy spectrum of reactor antineutrinos in the three experimental halls yields no evidence of sterile neutrino mixing in the 2×10^{-4}≲|Δm&#95;{41}^{2}|≲0.3  eV^{2} mass range. The resulting limits on sin^{2}2θ&#95;{14} are improved by approx imately a factor of 2 over previous results and constitute the most stringent constraints to date in the |Δm&#95;{41}^{2}|≲0.2  eV^{2} region.

Published
2016
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43. Measurement of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

Author

An FP, Balantekin AB, Band HR, Bishai M, Blyth S, Butorov I, Cao D, Cao GF, Cao J, Cen WR, Chan YL, Chang JF, Chang LC, Chang Y, Chen HS, Chen QY, Chen SM, Chen YX, Chen Y, Cheng JH, Cheng J, Cheng YP, Cherwinka JJ, Chu MC, Cummings JP, de Arcos J, Deng ZY, Ding XF, Ding YY, Diwan MV, Dove J, Draeger E, Dwyer DA, Edwards WR, Ely SR, Gill R, Gonchar M, Gong GH, Gong H, Grassi M, Gu WQ, Guan MY, Guo L, Guo XH, Hackenburg RW, Han R, Hans S, He M, Heeger KM, Heng YK, Higuera A, Hor YK, Hsiung YB, Hu BZ, Hu LM, Hu LJ, Hu T, Hu W, Huang EC, Huang HX, Huang XT, Huber P, Hussain G, Jaffe DE, Jaffke P, Jen KL, Jetter S, Ji XP, Ji XL, Jiao JB, Johnson RA, Kang L, Kettell SH, Kohn S, Kramer M, Kwan KK, Kwok MW, Kwok T, Langford TJ, Lau K, Lebanowski L, Lee J, Lei RT, Leitner R, Leung KY, Leung JK, Lewis CA, Li DJ, Li F, Li GS, Li QJ, Li SC, Li WD, Li XN, Li XQ, Li YF, Li ZB, Liang H, Lin CJ, Lin GL, Lin PY, Lin SK, Ling JJ, Link JM, Littenberg L, Littlejohn BR, Liu DW, Liu H, Liu JL, Liu JC, Liu SS, Lu C, Lu HQ, Lu JS, Luk KB, Ma QM, Ma XY, Ma XB, Ma YQ, Martinez Caicedo DA, McDonald KT, McKeown RD, Meng Y, Mitchell I, Monari Kebwaro J, Nakajima Y, Napolitano J, Naumov D, Naumova E, Ngai HY, Ning Z, Ochoa-Ricoux JP, Olshevski A, Pan HR, Park J, Patton S, Pec V, Peng JC, Piilonen LE, Pinsky L, Pun CS, Qi FZ, Qi M, Qian X, Raper N, Ren B, Ren J, Rosero R, Roskovec B, Ruan XC, Shao BB, Steiner H, Sun GX, Sun JL, Tang W, Taychenachev D, Tsang KV, Tull CE, Tung YC, Viaux N, Viren B, Vorobel V, Wang CH, Wang M, Wang NY, Wang RG, Wang W, Wang WW, Wang X, Wang YF, Wang Z, Wang Z, Wang ZM, Wei HY, Wen LJ, Whisnant K, White CG, Whitehead L, Wise T, Wong HL, Wong SC, Worcester E, Wu Q, Xia DM, Xia JK, Xia X, Xing ZZ, Xu JY, Xu JL, Xu J, Xu Y, Xue T, Yan J, Yang CG, Yang L, Yang MS, Yang MT, Ye M, Yeh M, Young BL, Yu GY, Yu ZY, Zang SL, Zhan L, Zhang C, Zhang HH, Zhang JW, Zhang QM, Zhang YM, Zhang YX, Zhang YM, Zhang ZJ, Zhang ZY, Zhang ZP, Zhao J, Zhao QW, Zhao YF, Zhao YB, Zheng L, Zhong WL, Zhou L, Zhou N, Zhuang HL, and Zou JH

Abstract

This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18)  cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43)  cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.

Published
2016
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44. New measurement of antineutrino oscillation with the full detector configuration at Daya Bay.

Author

An FP, Balantekin AB, Band HR, Bishai M, Blyth S, Butorov I, Cao GF, Cao J, Cen WR, Chan YL, Chang JF, Chang LC, Chang Y, Chen HS, Chen QY, Chen SM, Chen YX, Chen Y, Cheng JH, Cheng J, Cheng YP, Cherwinka JJ, Chu MC, Cummings JP, de Arcos J, Deng ZY, Ding XF, Ding YY, Diwan MV, Draeger E, Dwyer DA, Edwards WR, Ely SR, Gill R, Gonchar M, Gong GH, Gong H, Grassi M, Gu WQ, Guan MY, Guo L, Guo XH, Hackenburg RW, Han R, Hans S, He M, Heeger KM, Heng YK, Higuera A, Hor YK, Hsiung YB, Hu BZ, Hu LM, Hu LJ, Hu T, Hu W, Huang EC, Huang HX, Huang XT, Huber P, Hussain G, Jaffe DE, Jaffke P, Jen KL, Jetter S, Ji XP, Ji XL, Jiao JB, Johnson RA, Kang L, Kettell SH, Kramer M, Kwan KK, Kwok MW, Kwok T, Langford TJ, Lau K, Lebanowski L, Lee J, Lei RT, Leitner R, Leung KY, Leung JK, Lewis CA, Li DJ, Li F, Li GS, Li QJ, Li SC, Li WD, Li XN, Li XQ, Li YF, Li ZB, Liang H, Lin CJ, Lin GL, Lin PY, Lin SK, Ling JJ, Link JM, Littenberg L, Littlejohn BR, Liu DW, Liu H, Liu JL, Liu JC, Liu SS, Lu C, Lu HQ, Lu JS, Luk KB, Ma QM, Ma XY, Ma XB, Ma YQ, Martinez Caicedo DA, McDonald KT, McKeown RD, Meng Y, Mitchell I, Monari Kebwaro J, Nakajima Y, Napolitano J, Naumov D, Naumova E, Ngai HY, Ning Z, Ochoa-Ricoux JP, Olshevski A, Park J, Patton S, Pec V, Peng JC, Piilonen LE, Pinsky L, Pun CS, Qi FZ, Qi M, Qian X, Raper N, Ren B, Ren J, Rosero R, Roskovec B, Ruan XC, Shao BB, Steiner H, Sun GX, Sun JL, Tang W, Taychenachev D, Themann H, Tsang KV, Tull CE, Tung YC, Viaux N, Viren B, Vorobel V, Wang CH, Wang M, Wang NY, Wang RG, Wang W, Wang WW, Wang X, Wang YF, Wang Z, Wang Z, Wang ZM, Wei HY, Wen LJ, Whisnant K, White CG, Whitehead L, Wise T, Wong HL, Wong SC, Worcester E, Wu Q, Xia DM, Xia JK, Xia X, Xing ZZ, Xu JY, Xu JL, Xu J, Xu Y, Xue T, Yan J, Yang CG, Yang L, Yang MS, Yang MT, Ye M, Yeh M, Yeh YS, Young BL, Yu GY, Yu ZY, Zang SL, Zhan L, Zhang C, Zhang HH, Zhang JW, Zhang QM, Zhang YM, Zhang YX, Zhang YM, Zhang ZJ, Zhang ZY, Zhang ZP, Zhao J, Zhao QW, Zhao YF, Zhao YB, Zheng L, Zhong WL, Zhou L, Zhou N, Zhuang HL, and Zou JH

Abstract

We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW&#95;{th}  ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ&#95;{13} and |Δm&#95;{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ&#95;{13}=0.084±0.005 and |Δm&#95;{ee}^{2}|=(2.42±0.11)×10^{-3}  eV^{2} in the three-neutrino framework.

Published
2015
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45. Search for a light sterile neutrino at Daya Bay.

Author

An FP, Balantekin AB, Band HR, Beriguete W, Bishai M, Blyth S, Butorov I, Cao GF, Cao J, Chan YL, Chang JF, Chang LC, Chang Y, Chasman C, Chen H, Chen QY, Chen SM, Chen X, Chen X, Chen YX, Chen Y, Cheng YP, Cherwinka JJ, Chu MC, Cummings JP, de Arcos J, Deng ZY, Ding YY, Diwan MV, Draeger E, Du XF, Dwyer DA, Edwards WR, Ely SR, Fu JY, Ge LQ, Gill R, Gonchar M, Gong GH, Gong H, Grassi M, Gu WQ, Guan MY, Guo XH, Hackenburg RW, Han GH, Hans S, He M, Heeger KM, Heng YK, Hinrichs P, Hor YK, Hsiung YB, Hu BZ, Hu LM, Hu LJ, Hu T, Hu W, Huang EC, Huang H, Huang XT, Huber P, Hussain G, Isvan Z, Jaffe DE, Jaffke P, Jen KL, Jetter S, Ji XP, Ji XL, Jiang HJ, Jiao JB, Johnson RA, Kang L, Kettell SH, Kramer M, Kwan KK, Kwok MW, Kwok T, Lai WC, Lau K, Lebanowski L, Lee J, Lei RT, Leitner R, Leung A, Leung JK, Lewis CA, Li DJ, Li F, Li GS, Li QJ, Li WD, Li XN, Li XQ, Li YF, Li ZB, Liang H, Lin CJ, Lin GL, Lin PY, Lin SK, Lin YC, Ling JJ, Link JM, Littenberg L, Littlejohn BR, Liu DW, Liu H, Liu JL, Liu JC, Liu SS, Liu YB, Lu C, Lu HQ, Luk KB, Ma QM, Ma XY, Ma XB, Ma YQ, McDonald KT, McFarlane MC, McKeown RD, Meng Y, Mitchell I, Monari Kebwaro J, Nakajima Y, Napolitano J, Naumov D, Naumova E, Nemchenok I, Ngai HY, Ning Z, Ochoa-Ricoux JP, Olshevski A, Patton S, Pec V, Peng JC, Piilonen LE, Pinsky L, Pun CS, Qi FZ, Qi M, Qian X, Raper N, Ren B, Ren J, Rosero R, Roskovec B, Ruan XC, Shao BB, Steiner H, Sun GX, Sun JL, Tam YH, Tang X, Themann H, Tsang KV, Tsang RH, Tull CE, Tung YC, Viren B, Vorobel V, Wang CH, Wang LS, Wang LY, Wang M, Wang NY, Wang RG, Wang W, Wang WW, Wang X, Wang YF, Wang Z, Wang Z, Wang ZM, Webber DM, Wei HY, Wei YD, Wen LJ, Whisnant K, White CG, Whitehead L, Wise T, Wong HL, Wong SC, Worcester E, Wu Q, Xia DM, Xia JK, Xia X, Xing ZZ, Xu JY, Xu JL, Xu J, Xu Y, Xue T, Yan J, Yang CC, Yang L, Yang MS, Yang MT, Ye M, Yeh M, Yeh YS, Young BL, Yu GY, Yu JY, Yu ZY, Zang SL, Zeng B, Zhan L, Zhang C, Zhang FH, Zhang JW, Zhang QM, Zhang Q, Zhang SH, Zhang YC, Zhang YM, Zhang YH, Zhang YX, Zhang ZJ, Zhang ZY, Zhang ZP, Zhao J, Zhao QW, Zhao Y, Zhao YB, Zheng L, Zhong WL, Zhou L, Zhou ZY, Zhuang HL, and Zou JH

Abstract

A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)<|Δm(41)(2) |< 0.3 eV(2) range. The relative spectral distortion due to the disappearance of electron antineutrinos was found to be consistent with that of the three-flavor oscillation model. The derived limits on sin(2) 2θ(14) cover the 10(-3) eV(2) ≲ |Δm(41)(2)| ≲ 0.1 eV(2) region, which was largely unexplored.

Published
2014
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46. Spectral measurement of electron antineutrino oscillation amplitude and frequency at Daya Bay.

Author

An FP, Balantekin AB, Band HR, Beriguete W, Bishai M, Blyth S, Brown RL, Butorov I, Cao GF, Cao J, Carr R, Chan YL, Chang JF, Chang Y, Chasman C, Chen HS, Chen HY, Chen SJ, Chen SM, Chen XC, Chen XH, Chen Y, Chen YX, Cheng YP, Cherwinka JJ, Chu MC, Cummings JP, de Arcos J, Deng ZY, Ding YY, Diwan MV, Draeger E, Du XF, Dwyer DA, Edwards WR, Ely SR, Fu JY, Ge LQ, Gill R, Gonchar M, Gong GH, Gong H, Gornushkin YA, Gu WQ, Guan MY, Guo XH, Hackenburg RW, Hahn RL, Han GH, Hans S, He M, Heeger KM, Heng YK, Hinrichs P, Hor Y, Hsiung YB, Hu BZ, Hu LJ, Hu LM, Hu T, Hu W, Huang EC, Huang HX, Huang HZ, Huang XT, Huber P, Hussain G, Isvan Z, Jaffe DE, Jaffke P, Jetter S, Ji XL, Ji XP, Jiang HJ, Jiao JB, Johnson RA, Kang L, Kettell SH, Kramer M, Kwan KK, Kwok MW, Kwok T, Lai WC, Lai WH, Lau K, Lebanowski L, Lee J, Lei RT, Leitner R, Leung A, Leung JK, Lewis CA, Li DJ, Li F, Li GS, Li QJ, Li WD, Li XN, Li XQ, Li YF, Li ZB, Liang H, Lin CJ, Lin GL, Lin SK, Lin YC, Ling JJ, Link JM, Littenberg L, Littlejohn BR, Liu DW, Liu H, Liu JC, Liu JL, Liu SS, Liu YB, Lu C, Lu HQ, Luk KB, Ma QM, Ma XB, Ma XY, Ma YQ, McDonald KT, McFarlane MC, McKeown RD, Meng Y, Mitchell I, Nakajima Y, Napolitano J, Naumov D, Naumova E, Nemchenok I, Ngai HY, Ngai WK, Ning Z, Ochoa-Ricoux JP, Olshevski A, Patton S, Pec V, Peng JC, Piilonen LE, Pinsky L, Pun CS, Qi FZ, Qi M, Qian X, Raper N, Ren B, Ren J, Rosero R, Roskovec B, Ruan XC, Shao BB, Steiner H, Sun GX, Sun JL, Tam YH, Tanaka HK, Tang X, Themann H, Trentalange S, Tsai O, Tsang KV, Tsang RH, Tull CE, Tung YC, Viren B, Vorobel V, Wang CH, Wang LS, Wang LY, Wang LZ, Wang M, Wang NY, Wang RG, Wang W, Wang WW, Wang X, Wang YF, Wang Z, Wang Z, Wang ZM, Webber DM, Wei H, Wei YD, Wen LJ, Whisnant K, White CG, Whitehead L, Wise T, Wong HL, Wong SC, Worcester E, Wu Q, Xia DM, Xia JK, Xia X, Xing ZZ, Xu J, Xu JL, Xu JY, Xu Y, Xue T, Yan J, Yang CG, Yang L, Yang MS, Ye M, Yeh M, Yeh YS, Young BL, Yu GY, Yu JY, Yu ZY, Zang SL, Zhan L, Zhang C, Zhang FH, Zhang JW, Zhang QM, Zhang SH, Zhang YC, Zhang YH, Zhang YM, Zhang YX, Zhang ZJ, Zhang ZP, Zhang ZY, Zhao J, Zhao QW, Zhao YB, Zheng L, Zhong WL, Zhou L, Zhou ZY, Zhuang HL, and Zou JH

Abstract

A measurement of the energy dependence of antineutrino disappearance at the Daya Bay reactor neutrino experiment is reported. Electron antineutrinos (ν¯(e)) from six 2.9  GW(th) reactors were detected with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls. Using 217 days of data, 41 589 (203 809 and 92 912) antineutrino candidates were detected in the far hall (near halls). An improved measurement of the oscillation amplitude sin(2)2θ(13)=0.090(-0.009)(+0.008) and the first direct measurement of the ν¯(e) mass-squared difference |Δm(ee)2|=(2.59(-0.20)(+0.19))×10(-3)  eV2 is obtained using the observed ν¯(e) rates and energy spectra in a three-neutrino framework. This value of |Δm(ee)2| is consistent with |Δm(μμ)2| measured by muon neutrino disappearance, supporting the three-flavor oscillation model.

Published
2014
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47. Observation of electron-antineutrino disappearance at Daya Bay.

Author

An FP, Bai JZ, Balantekin AB, Band HR, Beavis D, Beriguete W, Bishai M, Blyth S, Boddy K, Brown RL, Cai B, Cao GF, Cao J, Carr R, Chan WT, Chang JF, Chang Y, Chasman C, Chen HS, Chen HY, Chen SJ, Chen SM, Chen XC, Chen XH, Chen XS, Chen Y, Chen YX, Cherwinka JJ, Chu MC, Cummings JP, Deng ZY, Ding YY, Diwan MV, Dong L, Draeger E, Du XF, Dwyer DA, Edwards WR, Ely SR, Fang SD, Fu JY, Fu ZW, Ge LQ, Ghazikhanian V, Gill RL, Goett J, Gonchar M, Gong GH, Gong H, Gornushkin YA, Greenler LS, Gu WQ, Guan MY, Guo XH, Hackenburg RW, Hahn RL, Hans S, He M, He Q, He WS, Heeger KM, Heng YK, Hinrichs P, Ho TH, Hor YK, Hsiung YB, Hu BZ, Hu T, Hu T, Huang HX, Huang HZ, Huang PW, Huang X, Huang XT, Huber P, Isvan Z, Jaffe DE, Jetter S, Ji XL, Ji XP, Jiang HJ, Jiang WQ, Jiao JB, Johnson RA, Kang L, Kettell SH, Kramer M, Kwan KK, Kwok MW, Kwok T, Lai CY, Lai WC, Lai WH, Lau K, Lebanowski L, Lee J, Lee MK, Leitner R, Leung JK, Leung KY, Lewis CA, Li B, Li F, Li GS, Li J, Li QJ, Li SF, Li WD, Li XB, Li XN, Li XQ, Li Y, Li ZB, Liang H, Liang J, Lin CJ, Lin GL, Lin SK, Lin SX, Lin YC, Ling JJ, Link JM, Littenberg L, Littlejohn BR, Liu BJ, Liu C, Liu DW, Liu H, Liu JC, Liu JL, Liu S, Liu X, Liu YB, Lu C, Lu HQ, Luk A, Luk KB, Luo T, Luo XL, Ma LH, Ma QM, Ma XB, Ma XY, Ma YQ, Mayes B, McDonald KT, McFarlane MC, McKeown RD, Meng Y, Mohapatra D, Morgan JE, Nakajima Y, Napolitano J, Naumov D, Nemchenok I, Newsom C, Ngai HY, Ngai WK, Nie YB, Ning Z, Ochoa-Ricoux JP, Oh D, Olshevski A, Pagac A, Patton S, Pearson C, Pec V, Peng JC, Piilonen LE, Pinsky L, Pun CS, Qi FZ, Qi M, Qian X, Raper N, Rosero R, Roskovec B, Ruan XC, Seilhan B, Shao BB, Shih K, Steiner H, Stoler P, Sun GX, Sun JL, Tam YH, Tanaka HK, Tang X, Themann H, Torun Y, Trentalange S, Tsai O, Tsang KV, Tsang RH, Tull C, Viren B, Virostek S, Vorobel V, Wang CH, Wang LS, Wang LY, Wang LZ, Wang M, Wang NY, Wang RG, Wang T, Wang W, Wang X, Wang X, Wang YF, Wang Z, Wang Z, Wang ZM, Webber DM, Wei YD, Wen LJ, Wenman DL, Whisnant K, White CG, Whitehead L, Whitten CA Jr, Wilhelmi J, Wise T, Wong HC, Wong HL, Wong J, Worcester ET, Wu FF, Wu Q, Xia DM, Xiang ST, Xiao Q, Xing ZZ, Xu G, Xu J, Xu J, Xu JL, Xu W, Xu Y, Xue T, Yang CG, Yang L, Ye M, Yeh M, Yeh YS, Yip K, Young BL, Yu ZY, Zhan L, Zhang C, Zhang FH, Zhang JW, Zhang QM, Zhang K, Zhang QX, Zhang SH, Zhang YC, Zhang YH, Zhang YX, Zhang ZJ, Zhang ZP, Zhang ZY, Zhao J, Zhao QW, Zhao YB, Zheng L, Zhong WL, Zhou L, Zhou ZY, Zhuang HL, and Zou JH

Abstract

The Daya Bay Reactor Neutrino Experiment has measured a nonzero value for the neutrino mixing angle θ(13) with a significance of 5.2 standard deviations. Antineutrinos from six 2.9 GWth reactors were detected in six antineutrino detectors deployed in two near (flux-weighted baseline 470 m and 576 m) and one far (1648 m) underground experimental halls. With a 43,000 ton-GWth-day live-time exposure in 55 days, 10,416 (80,376) electron-antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to expected number of antineutrinos at the far hall is R=0.940±0.011(stat.)±0.004(syst.). A rate-only analysis finds sin(2)2θ(13)=0.092±0.016(stat.)±0.005(syst.) in a three-neutrino framework.

Published
2012
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48. 4D-Imaging of the lung: reproducibility of lesion size and displacement on helical CT, MRI, and cone beam CT in a ventilated ex vivo system.

Author

Biederer J, Dinkel J, Remmert G, Jetter S, Nill S, Moser T, Bendl R, Thierfelder C, Fabel M, Oelfke U, Bock M, Plathow C, Bolte H, Welzel T, Hoffmann B, Hartmann G, Schlegel W, Debus J, Heller M, and Kauczor HU

Subjects
Animals, Cone-Beam Computed Tomography methods, Equipment Design, Magnetic Resonance Imaging methods, Observer Variation, Particle Accelerators, Phantoms, Imaging, Reproducibility of Results, Swine, Tomography, Spiral Computed methods, Lung diagnostic imaging, Lung pathology, Lung Neoplasms diagnostic imaging, Lung Neoplasms pathology, Movement, Multiple Pulmonary Nodules diagnostic imaging, Multiple Pulmonary Nodules pathology, Respiration
Abstract

Purpose: Four-dimensional (4D) imaging is a key to motion-adapted radiotherapy of lung tumors. We evaluated in a ventilated ex vivo system how size and displacement of artificial pulmonary nodules are reproduced with helical 4D-CT, 4D-MRI, and linac-integrated cone beam CT (CBCT)., Methods and Materials: Four porcine lungs with 18 agarose nodules (mean diameters 1.3-1.9 cm), were ventilated inside a chest phantom at 8/min and subject to 4D-CT (collimation 24 x 1.2 mm, pitch 0.1, slice/increment 24 x 10(2)/1.5/0.8 mm, pitch 0.1, temporal resolution 0.5 s), 4D-MRI (echo-shared dynamic three-dimensional-flash; repetition/echo time 2.13/0.72 ms, voxel size 2.7 x 2.7 x 4.0 mm, temporal resolution 1.4 s) and linac-integrated 4D-CBCT (720 projections, 3-min rotation, temporal resolution approximately 1 s). Static CT without respiration served as control. Three observers recorded lesion size (RECIST-diameters x/y/z) and axial displacement. Interobserver- and interphase-variation coefficients (IO/IP VC) of measurements indicated reproducibility., Results: Mean x/y/z lesion diameters in cm were equal on static and dynamic CT (1.88/1.87; 1.30/1.39; 1.71/1.73; p > 0.05), but appeared larger on MRI and CBCT (2.06/1.95 [p < 0.05 vs. CT]; 1.47/1.28 [MRI vs. CT/CBCT p < 0.05]; 1.86/1.83 [CT vs. CBCT p < 0.05]). Interobserver-VC for lesion sizes were 2.54-4.47% (CT), 2.29-4.48% (4D-CT); 5.44-6.22% (MRI) and 4.86-6.97% (CBCT). Interphase-VC for lesion sizes ranged from 2.28% (4D-CT) to 10.0% (CBCT). Mean displacement in cm decreased from static CT (1.65) to 4D-CT (1.40), CBCT (1.23) and MRI (1.16)., Conclusions: Lesion sizes are exactly reproduced with 4D-CT but overestimated on 4D-MRI and CBCT with a larger variability due to limited temporal and spatial resolution. All 4D-modalities underestimate lesion displacement.

Published
2009
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49. Linac-integrated 4D cone beam CT: first experimental results.

Author

Dietrich L, Jetter S, Tücking T, Nill S, and Oelfke U

Subjects
Algorithms, Humans, Imaging, Three-Dimensional instrumentation, Models, Theoretical, Movement physiology, Phantoms, Imaging, Reproducibility of Results, Tomography, X-Ray Computed instrumentation, Imaging, Three-Dimensional methods, Radiographic Image Enhancement methods, Radiography, Thoracic methods, Respiratory Mechanics, Tomography, X-Ray Computed methods
Abstract

A new online imaging approach, linac-integrated cone beam CT (CBCT), has been developed over the past few years. It has the advantage that a patient can be examined in their treatment position directly before or during a radiotherapy treatment. Unfortunately, respiratory organ motion, one of the largest intrafractional organ motions, often leads to artefacts in the reconstructed 3D images. One way to take this into account is to register the breathing phase during image acquisition for a phase-correlated image reconstruction. Therefore, the main focus of this work is to present a system which has the potential to investigate the correlation between internal (movement of the diaphragm) and external (data of a respiratory gating system) information about breathing phase and amplitude using an inline CBCT scanner. This also includes a feasibility study about using the acquired information for a respiratory-correlated 4D CBCT reconstruction. First, a moving lung phantom was used to develop and to specify the required methods which are based on an image reconstruction using only projections belonging to a certain moving phase. For that purpose, the corresponding phase has to be detected for each projection. In the case of the phantom, an electrical signal allows one to track the movement in real time. The number of projections available for the image reconstruction depends on the breathing phase and the size of the position range from which projections should be used for the reconstruction. The narrower this range is, the better the inner structures can be located, but also the noise of the images increases due to the limited number of projections. This correlation has also been analysed. In a second step, the methods were clinically applied using data sets of patients with lung tumours. In this case, the breathing phase was detected by an external gating system (AZ-733V, Anzai Medical Co.) based on a pressure sensor attached to the patient's abdominal region with a fixation belt. The comparison of the reconstructed 4D CBCT images and the corresponding 4D CT images used for the treatment planning provides the required information for the calculation of possible setup errors. So, a repositioning of the patient is feasible even though the patient moves due to respiration. In addition to the external signal, the position of the diaphragm in the cranial-caudal direction could be extracted from each projection. Both independent sources of information show a very good agreement of the phase and even the amplitude of the movement and the external signal respectively. This suggests the usability of such a system for a gated dose delivery approach. However, more studies involving patients with different incidences have to be carried out to confirm these first results.

Published
2006
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50. Cryopreservation of peripheral blood progenitor cells: characteristics of suitable techniques.

Author

Sputtek A, Jetter S, Hummel K, and Kühnl P

Subjects
Cell Survival drug effects, Colony-Forming Units Assay, Cryoprotective Agents pharmacology, Dimethyl Sulfoxide pharmacology, Dose-Response Relationship, Drug, Granulocytes drug effects, Hematologic Neoplasms blood, Humans, Hydroxyethyl Starch Derivatives pharmacology, Macrophages drug effects, Blood Preservation methods, Cryopreservation methods, Hematopoietic Stem Cell Transplantation, Leukapheresis
Abstract

The influence of 6 different cooling rates (1.4, 5, 10, 15, 20, 160 K/min) and 5 different compositions of the suspensions to be frozen (% DMSO/% HES: 10/0, 7.5/2.5, 5/6, 2.5/7.5, 0/10) were investigated in 30 aliquots from each of 12 peripheral blood progenitor cells (PBSC) products which had been obtained by leukapheresis from 11 patients with hematological malignancies and solid tumors and 1 healthy donor treated with 5-24 micrograms/kg body weight/day granulocyte colony stimulating factor (G-CSF) over 5 days. The MNC concentration in the products obtained amounted to 4.51 +/- 1.55 x 10(7)/ml (mean +/- SEM), range: 2.10-7.65 x 10(7)/ml). For freezing, cooling rates were generated by means of a liquid nitrogen(LN2)-operated, computer-controlled freezer, a mechanical -80 degrees C freezer, in the vapor phase over LN2, and by submerging into LN2. The statistical analysis of the results clearly indicates that optimum results compared with the prefreeze values for numerical recovery (80.6 +/- 20.1%, Coulter counter), viability (membrane integrity by Trypan blue exclusion 91.6 +/- 4.1%), and colony-forming potential (56.2 +/- 45.8% erythroid burst-forming units [BFU-E], 63.4 +/- 72.8% myeloid colonies [CFU-GM]) were achieved at a cooling rate of 1.4 K/min with 10% DMSO being present. The values obtained at a cooling rate of 5 K/min (-80 degrees C mechanical refrigerator) in the presence of 5% DMSO and 6% HES did not differ significantly (i.e., membrane integrity 91.8 +/- 3.9%, BFU-E 53.0 +/- 37.4%, CFU-GM 47.8 +/- 58.2%). At cooling rates above 5 K/min and DMSO concentrations lower than 5% (in spite of higher HES concentrations) there was a significant drop of CFU recovery (CFU-GM plus BFU-E) to almost 0%. In parallel, numerical recovery and viability dropped as well, but less pronounced, indicating that both methods are unsuitable for the prediction of CFU recovery when different freezing protocols are applied. We need at least 5% DMSO (in the presence of 6% HES) in spite of the undesirable histamine-releasing effect of this compound. The cooling rate is not critical in the range from 1 to 5 K/min and can easily be achieved by -80 degrees C freezers.

Published
1997

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