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1. Genomic Characterization of Three Novel Bartonella Strains in a Rodent and Two Bat Species from Mexico.

Author

Gonçalves-Oliveira, Jonathan, Gonçalves-Oliveira, Jonathan, Gutierrez, Ricardo, Schlesener, Cory Lee, Jaffe, David A, Aguilar-Setién, Alvaro, Boulouis, Henri-Jean, Nachum-Biala, Yaarit, Huang, Bihua C, Weimer, Bart C, Chomel, Bruno B, Harrus, Shimon, Gonçalves-Oliveira, Jonathan, Gonçalves-Oliveira, Jonathan, Gutierrez, Ricardo, Schlesener, Cory Lee, Jaffe, David A, Aguilar-Setién, Alvaro, Boulouis, Henri-Jean, Nachum-Biala, Yaarit, Huang, Bihua C, Weimer, Bart C, Chomel, Bruno B, and Harrus, Shimon

Abstract

Rodents and bats are the most diverse mammal group that host Bartonella species. In the Americas, they were described as harboring Bartonella species; however, they were mostly characterized to the genotypic level. We describe here Bartonella isolates obtained from blood samples of one rodent (Peromyscus yucatanicus from San José Pibtuch, Yucatan) and two bat species (Desmodus rotundus from Progreso, and Pteronotus parnellii from Chamela-Cuitzmala) from Mexico. We sequenced and described the genomic features of three Bartonella strains and performed phylogenomic and pangenome analyses to decipher their phylogenetic relationships. The mouse-associated genome was closely related to Bartonella vinsonii. The two bat-associated genomes clustered into a single distinct clade in between lineages 3 and 4, suggesting to be an ancestor of the rodent-associated Bartonella clade (lineage 4). These three genomes showed <95% OrthoANI values compared to any other Bartonella genome, and therefore should be considered as novel species. In addition, our analyses suggest that the B. vinsonii complex should be revised, and all B. vinsonii subspecies need to be renamed and considered as full species. The phylogenomic clustering of the bat-associated Bartonella strains and their virulence factor profile (lack of the Vbh/TraG conjugation system remains of the T4SS) suggest that it should be considered as a new lineage clade (L5) within the Bartonella genus.

Published
2023

2. Performance of a Ton-scale Water-based Liquid Scintillator Detector

Author

Zhao, Rong, Bignell, Lindsey, Jaffe, David E., Rosero, Richard, Yeh, Minfang, Wang, Wei, Zhang, Aiwu, Zhao, Rong, Bignell, Lindsey, Jaffe, David E., Rosero, Richard, Yeh, Minfang, Wang, Wei, and Zhang, Aiwu

Abstract

This study reports the performance and light yield of 1% concentration water-based liquid scintillator (WbLS) deployed in a 1000-liter detector. A light yield of 99$\pm$15 photons per MeV is determined by comparing data with simulation. This result aligns with our previous light yield determination using smaller detectors, thus establishing a solid foundation for the ongoing development and deployment of WbLS in larger-scale detectors. The feasibility of in situ preparation and the stability of light yield in WbLS are demonstrated, reinforcing its suitability for long-term experimental endeavors., Comment: Accepted for publication in JINST

Published
2023

3. Dorsal root ganglia control nociceptive input to the central nervous system

Author

Smith, Cody J, Hao, Han, Ramli, Rosmaliza, Wang, Caixue, Liu, Chao, Shah, Shihab, Mullen, Pierce, Lall, Varinder, Jones, Frederick, Shao, Jicheng, Zhang, Hailin, Jaffe, David B, Gamper, Nikita, Du, Xiaona, Smith, Cody J, Hao, Han, Ramli, Rosmaliza, Wang, Caixue, Liu, Chao, Shah, Shihab, Mullen, Pierce, Lall, Varinder, Jones, Frederick, Shao, Jicheng, Zhang, Hailin, Jaffe, David B, Gamper, Nikita, and Du, Xiaona

Abstract

Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support "gating" of pain information by DRGs and suggest new therapeutic approaches for pain relief.

Published
2023

5. Antiphon

Author

Jaffe, David A., Jaffe, David A., Jaffe, David A., and Jaffe, David A.

Published
2020

6. Fox Hollow

Author

Jaffe, David A., Jaffe, David A., Jaffe, David A., and Jaffe, David A.

Published
2020

7. Fox Hollow

Author

Jaffe, David A., Jaffe, David A., Jaffe, David A., and Jaffe, David A.

Published
2020

8. Antiphon

Author

Jaffe, David A., Jaffe, David A., Jaffe, David A., and Jaffe, David A.

Published
2020

9. Fox Hollow

Author

Jaffe, David A., Jaffe, David A., Jaffe, David A., and Jaffe, David A.

Published
2020

11. The Frictionless Organization : Deliver Great Customer Experiences with Less Effort Ed. 1

Author

Jaffe, David, Price, Bill, Jaffe, David, and Price, Bill

Abstract

Learn how frictionless organizations cut costs, grow revenue, and create loyal fans by creating products and services that work so well, their customers never have to contact them for the wrong reasons.This book will help any customer-facing organization deliver better customer experiences, save money, and increase revenue. Veteran customer service experts Bill Price and David Jaffe, coauthors of the bestseller The Best Service Is No Service, explain how organizations can design products, sales, and support so that customer effort is reduced or, better still, removed. This simplicity for the customer is what Price and Jaffe call frictionless. The book defines a straightforward methodology, drawing on more than thirty practical examples from leading companies across four continents. The approach provides a radically different way for the whole business to focus on the customer experience. It explains how any organization can look at all customer interactions as potential opportunities for improvement and question whether they are helpful or represent symptoms of friction. Lower friction innovators are disrupting established businesses in every industry. This detailed guide shows how any business—from start-ups to major multinational corporations—can remove friction. Being frictionless has become a strategic necessity, and now this strategy is available to any organization.

Published
2022

12. The Frictionless Organization : Deliver Great Customer Experiences with Less Effort Ed. 1

Author

Price, Bill, Jaffe, David, Price, Bill, Price, Bill, Jaffe, David, and Price, Bill

Abstract

Learn how frictionless organizations cut costs, grow revenue, and create loyal fans by creating products and services that work so well, their customers never have to contact them for the wrong reasons.This book will help any customer-facing organization deliver better customer experiences, save money, and increase revenue. Veteran customer service experts Bill Price and David Jaffe, coauthors of the bestseller The Best Service Is No Service, explain how organizations can design products, sales, and support so that customer effort is reduced or, better still, removed. This simplicity for the customer is what Price and Jaffe call frictionless. The book defines a straightforward methodology, drawing on more than thirty practical examples from leading companies across four continents. The approach provides a radically different way for the whole business to focus on the customer experience. It explains how any organization can look at all customer interactions as potential opportunities for improvement and question whether they are helpful or represent symptoms of friction. Lower friction innovators are disrupting established businesses in every industry. This detailed guide shows how any business—from start-ups to major multinational corporations—can remove friction. Being frictionless has become a strategic necessity, and now this strategy is available to any organization.

Published
2022

13. The Frictionless Organization : Deliver Great Customer Experiences with Less Effort Ed. 1

Author

Price, Bill, Jaffe, David, Price, Bill, Price, Bill, Jaffe, David, and Price, Bill

Abstract

Learn how frictionless organizations cut costs, grow revenue, and create loyal fans by creating products and services that work so well, their customers never have to contact them for the wrong reasons.This book will help any customer-facing organization deliver better customer experiences, save money, and increase revenue. Veteran customer service experts Bill Price and David Jaffe, coauthors of the bestseller The Best Service Is No Service, explain how organizations can design products, sales, and support so that customer effort is reduced or, better still, removed. This simplicity for the customer is what Price and Jaffe call frictionless. The book defines a straightforward methodology, drawing on more than thirty practical examples from leading companies across four continents. The approach provides a radically different way for the whole business to focus on the customer experience. It explains how any organization can look at all customer interactions as potential opportunities for improvement and question whether they are helpful or represent symptoms of friction. Lower friction innovators are disrupting established businesses in every industry. This detailed guide shows how any business—from start-ups to major multinational corporations—can remove friction. Being frictionless has become a strategic necessity, and now this strategy is available to any organization.

Published
2022

14. The Frictionless Organization : Deliver Great Customer Experiences with Less Effort Ed. 1

Author

Price, Bill, Jaffe, David, Price, Bill, Price, Bill, Jaffe, David, and Price, Bill

Abstract

Learn how frictionless organizations cut costs, grow revenue, and create loyal fans by creating products and services that work so well, their customers never have to contact them for the wrong reasons.This book will help any customer-facing organization deliver better customer experiences, save money, and increase revenue. Veteran customer service experts Bill Price and David Jaffe, coauthors of the bestseller The Best Service Is No Service, explain how organizations can design products, sales, and support so that customer effort is reduced or, better still, removed. This simplicity for the customer is what Price and Jaffe call frictionless. The book defines a straightforward methodology, drawing on more than thirty practical examples from leading companies across four continents. The approach provides a radically different way for the whole business to focus on the customer experience. It explains how any organization can look at all customer interactions as potential opportunities for improvement and question whether they are helpful or represent symptoms of friction. Lower friction innovators are disrupting established businesses in every industry. This detailed guide shows how any business—from start-ups to major multinational corporations—can remove friction. Being frictionless has become a strategic necessity, and now this strategy is available to any organization.

Published
2022

15. The Frictionless Organization : Deliver Great Customer Experiences with Less Effort Ed. 1

Author

Price, Bill, Jaffe, David, Price, Bill, Price, Bill, Jaffe, David, and Price, Bill

Abstract

Learn how frictionless organizations cut costs, grow revenue, and create loyal fans by creating products and services that work so well, their customers never have to contact them for the wrong reasons.This book will help any customer-facing organization deliver better customer experiences, save money, and increase revenue. Veteran customer service experts Bill Price and David Jaffe, coauthors of the bestseller The Best Service Is No Service, explain how organizations can design products, sales, and support so that customer effort is reduced or, better still, removed. This simplicity for the customer is what Price and Jaffe call frictionless. The book defines a straightforward methodology, drawing on more than thirty practical examples from leading companies across four continents. The approach provides a radically different way for the whole business to focus on the customer experience. It explains how any organization can look at all customer interactions as potential opportunities for improvement and question whether they are helpful or represent symptoms of friction. Lower friction innovators are disrupting established businesses in every industry. This detailed guide shows how any business—from start-ups to major multinational corporations—can remove friction. Being frictionless has become a strategic necessity, and now this strategy is available to any organization.

Published
2022

16. Serious Bacterial Infections in Young Febrile Infants With Positive Urinalysis Results.

Author

Cruz, Andrea, Cruz, Andrea, Vitale, Melissa, Powell, Elizabeth, Leetch, Aaron, Pickett, Michelle, Brayer, Anne, Nigrovic, Lise, Dayan, Peter, Atabaki, Shireen, Ruddy, Richard, Rogers, Alexander, Greenberg, Richard, Alpern, Elizabeth, Tunik, Michael, Saunders, Mary, Muenzer, Jared, Levine, Deborah, Hoyle, John, Lillis, Kathleen, Gattu, Rajender, Crain, Ellen, Borgialli, Dominic, Bonsu, Bema, Blumberg, Stephen, Anders, Jennifer, Roosevelt, Genie, Browne, Lorin, Cohen, Daniel, Linakis, James, Jaffe, David, Bennett, Jonathan, Schnadower, David, Park, Grace, Mistry, Rakesh, Glissmeyer, Eric, Cator, Allison, Bogie, Amanda, Quayle, Kimberly, Ellison, Angela, Balamuth, Fran, Richards, Rachel, Ramilo, Octavio, Mahajan, Prashant, VanBuren, John, Kuppermann, Nathan, Tzimenatos, Leah, Cruz, Andrea, Cruz, Andrea, Vitale, Melissa, Powell, Elizabeth, Leetch, Aaron, Pickett, Michelle, Brayer, Anne, Nigrovic, Lise, Dayan, Peter, Atabaki, Shireen, Ruddy, Richard, Rogers, Alexander, Greenberg, Richard, Alpern, Elizabeth, Tunik, Michael, Saunders, Mary, Muenzer, Jared, Levine, Deborah, Hoyle, John, Lillis, Kathleen, Gattu, Rajender, Crain, Ellen, Borgialli, Dominic, Bonsu, Bema, Blumberg, Stephen, Anders, Jennifer, Roosevelt, Genie, Browne, Lorin, Cohen, Daniel, Linakis, James, Jaffe, David, Bennett, Jonathan, Schnadower, David, Park, Grace, Mistry, Rakesh, Glissmeyer, Eric, Cator, Allison, Bogie, Amanda, Quayle, Kimberly, Ellison, Angela, Balamuth, Fran, Richards, Rachel, Ramilo, Octavio, Mahajan, Prashant, VanBuren, John, Kuppermann, Nathan, and Tzimenatos, Leah

Abstract

UNLABELLED: It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis. OBJECTIVE: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results. METHODS: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results. RESULTS: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count <4 × 103 cells/mm3 and procalcitonin <0.5 ng/mL. CONCLUSIONS: Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture

Published
2022

17. Response of Astrocyte Subpopulations Following Spinal Cord Injury.

Author

Allahyari, R Vivian, Heinsinger, Nicolette M, Hwang, Daniel, Jaffe, David A, Rasouli, Javad, Shiers, Stephanie, Thomas, Samantha J, Price, Theodore J, Rostami, Abdolmohamad, Lepore, Angelo C, Allahyari, R Vivian, Heinsinger, Nicolette M, Hwang, Daniel, Jaffe, David A, Rasouli, Javad, Shiers, Stephanie, Thomas, Samantha J, Price, Theodore J, Rostami, Abdolmohamad, and Lepore, Angelo C

Abstract

There is growing appreciation for astrocyte heterogeneity both across and within central nervous system (CNS) regions, as well as between intact and diseased states. Recent work identified multiple astrocyte subpopulations in mature brain. Interestingly, one subpopulation (Population C) was shown to possess significantly enhanced synaptogenic properties in vitro, as compared with other astrocyte subpopulations of adult cortex and spinal cord. Following spinal cord injury (SCI), damaged neurons lose synaptic connections with neuronal partners, resulting in persistent functional loss. We determined whether SCI induces an enhanced synaptomodulatory astrocyte phenotype by shifting toward a greater proportion of Population C cells and/or increasing expression of relevant synapse formation-associated genes within one or more astrocyte subpopulations. Using flow cytometry and RNAscope in situ hybridization, we found that astrocyte subpopulation distribution in the spinal cord did not change to a selectively synaptogenic phenotype following mouse cervical hemisection-type SCI. We also found that spinal cord astrocytes expressed synapse formation-associated genes to a similar degree across subpopulations, as well as in an unchanged manner between uninjured and SCI conditions. Finally, we confirmed these astrocyte subpopulations are also present in the human spinal cord in a similar distribution as mouse, suggesting possible conservation of spinal cord astrocyte heterogeneity across species.

Published
2022

18. Radiographic Pneumonia in Febrile Infants 60 Days and Younger.

Author

Florin, Todd A, Florin, Todd A, Ramilo, Octavio, Hoyle, John D, Jaffe, David M, Tzimenatos, Leah, Atabaki, Shireen M, Cohen, Daniel M, VanBuren, John M, Mahajan, Prashant, Kuppermann, Nathan, Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN), Florin, Todd A, Florin, Todd A, Ramilo, Octavio, Hoyle, John D, Jaffe, David M, Tzimenatos, Leah, Atabaki, Shireen M, Cohen, Daniel M, VanBuren, John M, Mahajan, Prashant, Kuppermann, Nathan, and Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN)

Abstract

ObjectiveFew prospective studies have assessed the occurrence of radiographic pneumonia in young febrile infants. We analyzed factors associated with radiographic pneumonias in febrile infants 60 days or younger evaluated in pediatric emergency departments.Study designWe conducted a planned secondary analysis of a prospective cohort study within 26 emergency departments in a pediatric research network from 2008 to 2013. Febrile (≥38°C) infants 60 days or younger who received chest radiographs were included. Chest radiograph reports were categorized as "no," "possible," or "definite" pneumonia. We compared demographics, Yale Observation Scale scores (>10 implying ill appearance), laboratory markers, blood cultures, and viral testing among groups.ResultsOf 4778 infants, 1724 (36.1%) had chest radiographs performed; 2.7% (n = 46) had definite pneumonias, and 3.9% (n = 67) had possible pneumonias. Patients with definite (13/46 [28.3%]) or possible (15/67 [22.7%]) pneumonias more frequently had Yale Observation Scale score >10 compared with those without pneumonias (210/1611 [13.2%], P = 0.002) in univariable and multivariable analyses. Median white blood cell count (WBC), absolute neutrophil count (ANC), and procalcitonin (PCT) were higher in the definite (WBC, 11.5 [interquartile range, 9.8-15.5]; ANC, 5.0 [3.2-7.6]; PCT, 0.4 [0.2-2.1]) versus no pneumonia (WBC, 10.0 [7.6-13.3]; ANC, 3.4 [2.1-5.4]; PCT, 0.2 [0.2-0.3]; WBC, P = 0.006; ANC, P = 0.002; PCT, P = 0.046) groups, but of unclear clinical significance. There were no cases of bacteremia in the definite pneumonia group. Viral infections were more frequent in groups with definite (25/38 [65.8%]) and possible (28/55 [50.9%]) pneumonias than no pneumonias (534/1185 [45.1%], P = 0.02).ConclusionsRadiographic pneumonias were uncommon, often had viruses detected, and were associated with ill appearance, but few other predictors, in febrile infants 60 days or younger.

Published
2021

20. Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning.

Author

Unger, Elizabeth K, Unger, Elizabeth K, Keller, Jacob P, Altermatt, Michael, Liang, Ruqiang, Matsui, Aya, Dong, Chunyang, Hon, Olivia J, Yao, Zi, Sun, Junqing, Banala, Samba, Flanigan, Meghan E, Jaffe, David A, Hartanto, Samantha, Carlen, Jane, Mizuno, Grace O, Borden, Phillip M, Shivange, Amol V, Cameron, Lindsay P, Sinning, Steffen, Underhill, Suzanne M, Olson, David E, Amara, Susan G, Temple Lang, Duncan, Rudnick, Gary, Marvin, Jonathan S, Lavis, Luke D, Lester, Henry A, Alvarez, Veronica A, Fisher, Andrew J, Prescher, Jennifer A, Kash, Thomas L, Yarov-Yarovoy, Vladimir, Gradinaru, Viviana, Looger, Loren L, Tian, Lin, Unger, Elizabeth K, Unger, Elizabeth K, Keller, Jacob P, Altermatt, Michael, Liang, Ruqiang, Matsui, Aya, Dong, Chunyang, Hon, Olivia J, Yao, Zi, Sun, Junqing, Banala, Samba, Flanigan, Meghan E, Jaffe, David A, Hartanto, Samantha, Carlen, Jane, Mizuno, Grace O, Borden, Phillip M, Shivange, Amol V, Cameron, Lindsay P, Sinning, Steffen, Underhill, Suzanne M, Olson, David E, Amara, Susan G, Temple Lang, Duncan, Rudnick, Gary, Marvin, Jonathan S, Lavis, Luke D, Lester, Henry A, Alvarez, Veronica A, Fisher, Andrew J, Prescher, Jennifer A, Kash, Thomas L, Yarov-Yarovoy, Vladimir, Gradinaru, Viviana, Looger, Loren L, and Tian, Lin

Abstract

Serotonin plays a central role in cognition and is the target of most pharmaceuticals for psychiatric disorders. Existing drugs have limited efficacy; creation of improved versions will require better understanding of serotonergic circuitry, which has been hampered by our inability to monitor serotonin release and transport with high spatial and temporal resolution. We developed and applied a binding-pocket redesign strategy, guided by machine learning, to create a high-performance, soluble, fluorescent serotonin sensor (iSeroSnFR), enabling optical detection of millisecond-scale serotonin transients. We demonstrate that iSeroSnFR can be used to detect serotonin release in freely behaving mice during fear conditioning, social interaction, and sleep/wake transitions. We also developed a robust assay of serotonin transporter function and modulation by drugs. We expect that both machine-learning-guided binding-pocket redesign and iSeroSnFR will have broad utility for the development of other sensors and in vitro and in vivo serotonin detection, respectively.

Published
2020

21. The Utility of Focused Assessment With Sonography for Trauma Enhanced Physical Examination in Children With Blunt Torso Trauma.

Author

Kornblith, Aaron E, Jang, Timothy B1, Kornblith, Aaron E, Graf, Jahanara, Addo, Newton, Newton, Christopher, Callcut, Rachael, Grupp-Phelan, Jacqueline, Jaffe, David M, Kornblith, Aaron E, Jang, Timothy B1, Kornblith, Aaron E, Graf, Jahanara, Addo, Newton, Newton, Christopher, Callcut, Rachael, Grupp-Phelan, Jacqueline, and Jaffe, David M

Abstract

ObjectivesComputed tomography (CT), the reference standard for diagnosis of intraabdominal injury (IAI), carries risk including ionizing radiation. CT-sparing clinical decision rules for children have relied heavily on physical examination, but they did not include focused assessment with sonography for trauma (FAST), which has emerged into widespread use during the past decade. We sought to determine the independent associations of physical examination, laboratory studies, and FAST with identification of IAI in children and to compare the test characteristics of these diagnostic variables. We hypothesized that FAST may add incremental utility to a physical examination alone to more accurately identify children who could forgo CT scan.MethodsWe reviewed a large trauma database of all children with blunt torso trauma presenting to a freestanding pediatric emergency department during a 20-month period. We used logistic regression to evaluate the association of FAST, physical examination, and selected laboratory data with IAI in children, and we compared the test characteristics of these variables.ResultsAmong 354 children, 50 (14%) had IAI. Positive FAST (odds ratio [OR] = 14.8, 95% confidence interval [CI] = 7.5 to 30.8) and positive physical examination (OR = 15.2, 95% CI = 7.7 to 31.7) were identified as independent predictors for IAI. Physical examination and FAST each had sensitivities of 74% (95% CI = 60% to 85%). Combining FAST and physical examination as FAST-enhanced physical examination (exFAST) improved sensitivity and negative predictive value (NPV) over either test alone (sensitivity = 88%, 95% CI = 76% to 96%) and NPV of 97.3% (95% CI = 94.5% to 98.7%).ConclusionsIn children, FAST and physical examinations each predicted the identification of IAI. However, the combination of the two (exFAST) had greater sensitivity and NPV than either physical examination or FAST alone. This supports the use of exFAST in refining c

Published
2020

22. Genomic architecture and introgression shape a butterfly radiation

Author

Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., Garcia-accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., Mcmillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, Mallet, James, Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., Garcia-accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., Mcmillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, and Mallet, James

Abstract

We used 20 de novo genome assemblies to probe the speciation history and architecture of gene flow in rapidly radiating Heliconius butterflies. Our tests to distinguish incomplete lineage sorting from introgression indicate that gene flow has obscured several ancient phylogenetic relationships in this group over large swathes of the genome. Introgressed loci are underrepresented in low-recombination and gene-rich regions, consistent with the purging of foreign alleles more tightly linked to incompatibility loci. Here, we identify a hitherto unknown inversion that traps a color pattern switch locus. We infer that this inversion was transferred between lineages by introgression and is convergent with a similar rearrangement in another part of the genus. These multiple de novo genome sequences enable improved understanding of the importance of introgression and selective processes in adaptive radiation.

Published
2019
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23. Genomic architecture and introgression shape a butterfly radiation

Author

Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., Garcia-accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., Mcmillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, Mallet, James, Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., Garcia-accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., Mcmillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, and Mallet, James

Abstract

We used 20 de novo genome assemblies to probe the speciation history and architecture of gene flow in rapidly radiating Heliconius butterflies. Our tests to distinguish incomplete lineage sorting from introgression indicate that gene flow has obscured several ancient phylogenetic relationships in this group over large swathes of the genome. Introgressed loci are underrepresented in low-recombination and gene-rich regions, consistent with the purging of foreign alleles more tightly linked to incompatibility loci. Here, we identify a hitherto unknown inversion that traps a color pattern switch locus. We infer that this inversion was transferred between lineages by introgression and is convergent with a similar rearrangement in another part of the genus. These multiple de novo genome sequences enable improved understanding of the importance of introgression and selective processes in adaptive radiation.

Published
2019
Full Text
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24. Aspiration therapy for the treatment of obesity: 4-year results of a multicenter randomized controlled trial.

Author

Thompson, Christopher C, Thompson, Christopher C, Abu Dayyeh, Barham K, Kushnir, Vladimir, Kushner, Robert F, Jirapinyo, Pichamol, Schorr, Alan B, Aronne, Louis J, Amaro, Anastassia, Jaffe, David L, Schulman, Allison R, Early, Dayna, Stein, Adam C, Sharaiha, Reem, Edmundowicz, Steven A, Bohning, J Matthew, Jensen, Michael D, Shukla, Alpana P, Apovian, Caroline, Kim, Dong Wook, Tran, Daniel, Zarrinpar, Amir, Ryan, Michele B, Young, Meredith, Lowe, Abigail, Haas, Miki, Goldsmith, Heidi, McCrea, Jennifer, Sullivan, Shelby, Thompson, Christopher C, Thompson, Christopher C, Abu Dayyeh, Barham K, Kushnir, Vladimir, Kushner, Robert F, Jirapinyo, Pichamol, Schorr, Alan B, Aronne, Louis J, Amaro, Anastassia, Jaffe, David L, Schulman, Allison R, Early, Dayna, Stein, Adam C, Sharaiha, Reem, Edmundowicz, Steven A, Bohning, J Matthew, Jensen, Michael D, Shukla, Alpana P, Apovian, Caroline, Kim, Dong Wook, Tran, Daniel, Zarrinpar, Amir, Ryan, Michele B, Young, Meredith, Lowe, Abigail, Haas, Miki, Goldsmith, Heidi, McCrea, Jennifer, and Sullivan, Shelby

Abstract

BackgroundThe AspireAssist is the first Food and Drug Administration-approved endoluminal device indicated for treatment of class II and III obesity.ObjectivesWe earlier reported 1-year results of the PATHWAY study. Here, we report 4-year outcomes.SettingUnited States-based, 10-center, randomized controlled trial involving 171 participants with the treatment arm receiving Aspiration Therapy (AT) plus Lifestyle Therapy and the control arm receiving Lifestyle Therapy (2:1 randomization).MethodsAT participants were permitted to continue in the study for an additional year up to a maximum of 5 years providing they maintained at least 10% total weight loss (TWL) from baseline at each year end. For AT participants who continued the study, 5 medical monitoring visits were provided at weeks 60, 68, 76, 90, and 104 and thereafter once every 13 weeks up to week 260. Exclusion criteria were a history of eating disorder or evidence of eating disorder on a validated questionnaire. Follow-up weight, quality of life, and co-morbidities were compared with the baseline levels. In addition, rates of serious adverse event, persistent fistula, withdrawal, and A-tube replacement were reported. All analyses were performed using a per-protocol analysis.ResultsOf the 82 AT participants who completed 1 year, 58 continued to this phase of the trial. Mean baseline body mass index of these 58 patients was 41.6 ± 4.5 kg/m2. At the end of first year (at the beginning of the follow-up study), these 58 patients had a body mass index of 34.1 ± 5.4 kg/m2 and had achieved an 18.3 ± 8.0% TWL. On a per protocol basis, patients experienced 14.2%, 15.3%, 16.6%, and 18.7% TWL at 1, 2, 3, and 4 years, respectively (P < .01 for all). Forty of 58 patients (69%) achieved at least 10% TWL at 4 years or at time of study withdrawal. Improvements in quality of life scores and select cardiometabolic parameters were also maintained through 4 years. There were 2 serious adverse events reported in the second throu

Published
2019

25. Genomic architecture and introgression shape a butterfly radiation

Author

Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., Garcia-accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., Mcmillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, Mallet, James, Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., Garcia-accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., Mcmillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, and Mallet, James

Abstract

We used 20 de novo genome assemblies to probe the speciation history and architecture of gene flow in rapidly radiating Heliconius butterflies. Our tests to distinguish incomplete lineage sorting from introgression indicate that gene flow has obscured several ancient phylogenetic relationships in this group over large swathes of the genome. Introgressed loci are underrepresented in low-recombination and gene-rich regions, consistent with the purging of foreign alleles more tightly linked to incompatibility loci. Here, we identify a hitherto unknown inversion that traps a color pattern switch locus. We infer that this inversion was transferred between lineages by introgression and is convergent with a similar rearrangement in another part of the genus. These multiple de novo genome sequences enable improved understanding of the importance of introgression and selective processes in adaptive radiation.

Published
2019
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26. Aspiration therapy for the treatment of obesity: 4-year results of a multicenter randomized controlled trial.

Author

Thompson, Christopher C, Thompson, Christopher C, Abu Dayyeh, Barham K, Kushnir, Vladimir, Kushner, Robert F, Jirapinyo, Pichamol, Schorr, Alan B, Aronne, Louis J, Amaro, Anastassia, Jaffe, David L, Schulman, Allison R, Early, Dayna, Stein, Adam C, Sharaiha, Reem, Edmundowicz, Steven A, Bohning, J Matthew, Jensen, Michael D, Shukla, Alpana P, Apovian, Caroline, Kim, Dong Wook, Tran, Daniel, Zarrinpar, Amir, Ryan, Michele B, Young, Meredith, Lowe, Abigail, Haas, Miki, Goldsmith, Heidi, McCrea, Jennifer, Sullivan, Shelby, Thompson, Christopher C, Thompson, Christopher C, Abu Dayyeh, Barham K, Kushnir, Vladimir, Kushner, Robert F, Jirapinyo, Pichamol, Schorr, Alan B, Aronne, Louis J, Amaro, Anastassia, Jaffe, David L, Schulman, Allison R, Early, Dayna, Stein, Adam C, Sharaiha, Reem, Edmundowicz, Steven A, Bohning, J Matthew, Jensen, Michael D, Shukla, Alpana P, Apovian, Caroline, Kim, Dong Wook, Tran, Daniel, Zarrinpar, Amir, Ryan, Michele B, Young, Meredith, Lowe, Abigail, Haas, Miki, Goldsmith, Heidi, McCrea, Jennifer, and Sullivan, Shelby

Abstract

BackgroundThe AspireAssist is the first Food and Drug Administration-approved endoluminal device indicated for treatment of class II and III obesity.ObjectivesWe earlier reported 1-year results of the PATHWAY study. Here, we report 4-year outcomes.SettingUnited States-based, 10-center, randomized controlled trial involving 171 participants with the treatment arm receiving Aspiration Therapy (AT) plus Lifestyle Therapy and the control arm receiving Lifestyle Therapy (2:1 randomization).MethodsAT participants were permitted to continue in the study for an additional year up to a maximum of 5 years providing they maintained at least 10% total weight loss (TWL) from baseline at each year end. For AT participants who continued the study, 5 medical monitoring visits were provided at weeks 60, 68, 76, 90, and 104 and thereafter once every 13 weeks up to week 260. Exclusion criteria were a history of eating disorder or evidence of eating disorder on a validated questionnaire. Follow-up weight, quality of life, and co-morbidities were compared with the baseline levels. In addition, rates of serious adverse event, persistent fistula, withdrawal, and A-tube replacement were reported. All analyses were performed using a per-protocol analysis.ResultsOf the 82 AT participants who completed 1 year, 58 continued to this phase of the trial. Mean baseline body mass index of these 58 patients was 41.6 ± 4.5 kg/m2. At the end of first year (at the beginning of the follow-up study), these 58 patients had a body mass index of 34.1 ± 5.4 kg/m2 and had achieved an 18.3 ± 8.0% TWL. On a per protocol basis, patients experienced 14.2%, 15.3%, 16.6%, and 18.7% TWL at 1, 2, 3, and 4 years, respectively (P < .01 for all). Forty of 58 patients (69%) achieved at least 10% TWL at 4 years or at time of study withdrawal. Improvements in quality of life scores and select cardiometabolic parameters were also maintained through 4 years. There were 2 serious adverse events reported in the second throu

Published
2019

27. Genomic architecture and introgression shape a butterfly radiation

Author

Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., Garcia-accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., Mcmillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, Mallet, James, Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., Garcia-accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., Mcmillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, and Mallet, James

Abstract

We used 20 de novo genome assemblies to probe the speciation history and architecture of gene flow in rapidly radiating Heliconius butterflies. Our tests to distinguish incomplete lineage sorting from introgression indicate that gene flow has obscured several ancient phylogenetic relationships in this group over large swathes of the genome. Introgressed loci are underrepresented in low-recombination and gene-rich regions, consistent with the purging of foreign alleles more tightly linked to incompatibility loci. Here, we identify a hitherto unknown inversion that traps a color pattern switch locus. We infer that this inversion was transferred between lineages by introgression and is convergent with a similar rearrangement in another part of the genus. These multiple de novo genome sequences enable improved understanding of the importance of introgression and selective processes in adaptive radiation.

Published
2019
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28. Reference quality assembly of the 3.5-Gb genome of Capsicum annuum from a single linked-read library.

Author

Hulse-Kemp, Amanda, Hulse-Kemp, Amanda, Maheshwari, Shamoni, Stoffel, Kevin, Hill, Theresa, Jaffe, David, Williams, Stephen, Weisenfeld, Neil, Ramakrishnan, Srividya, Kumar, Vijay, Shah, Preyas, Schatz, Michael, Church, Deanna, Van Deynze, Allen, Hulse-Kemp, Amanda, Hulse-Kemp, Amanda, Maheshwari, Shamoni, Stoffel, Kevin, Hill, Theresa, Jaffe, David, Williams, Stephen, Weisenfeld, Neil, Ramakrishnan, Srividya, Kumar, Vijay, Shah, Preyas, Schatz, Michael, Church, Deanna, and Van Deynze, Allen

Abstract

Linked-Read sequencing technology has recently been employed successfully for de novo assembly of human genomes, however, the utility of this technology for complex plant genomes is unproven. We evaluated the technology for this purpose by sequencing the 3.5-gigabase (Gb) diploid pepper (Capsicum annuum) genome with a single Linked-Read library. Plant genomes, including pepper, are characterized by long, highly similar repetitive sequences. Accordingly, significant effort is used to ensure that the sequenced plant is highly homozygous and the resulting assembly is a haploid consensus. With a phased assembly approach, we targeted a heterozygous F1 derived from a wide cross to assess the ability to derive both haplotypes and characterize a pungency gene with a large insertion/deletion. The Supernova software generated a highly ordered, more contiguous sequence assembly than all currently available C. annuum reference genomes. Over 83% of the final assembly was anchored and oriented using four publicly available de novo linkage maps. A comparison of the annotation of conserved eukaryotic genes indicated the completeness of assembly. The validity of the phased assembly is further demonstrated with the complete recovery of both 2.5-Kb insertion/deletion haplotypes of the PUN1 locus in the F1 sample that represents pungent and nonpungent peppers, as well as nearly full recovery of the BUSCO2 gene set within each of the two haplotypes. The most contiguous pepper genome assembly to date has been generated which demonstrates that Linked-Read library technology provides a tool to de novo assemble complex highly repetitive heterozygous plant genomes. This technology can provide an opportunity to cost-effectively develop high-quality genome assemblies for other complex plants and compare structural and gene differences through accurate haplotype reconstruction.

Published
2018

29. Epidemiology of Bacteremia in Febrile Infants Aged 60 Days and Younger.

Author

Powell, Elizabeth C, Powell, Elizabeth C, Mahajan, Prashant V, Roosevelt, Genie, Hoyle, John D, Gattu, Rajender, Cruz, Andrea T, Rogers, Alexander J, Atabaki, Shireen M, Jaffe, David M, Casper, T Charles, Ramilo, Octavio, Kuppermann, Nathan, Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN), Powell, Elizabeth C, Powell, Elizabeth C, Mahajan, Prashant V, Roosevelt, Genie, Hoyle, John D, Gattu, Rajender, Cruz, Andrea T, Rogers, Alexander J, Atabaki, Shireen M, Jaffe, David M, Casper, T Charles, Ramilo, Octavio, Kuppermann, Nathan, and Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN)

Abstract

Study objectiveTo describe the current epidemiology of bacteremia in febrile infants 60 days of age and younger in the Pediatric Emergency Care Applied Research Network (PECARN).MethodsWe conducted a planned secondary analysis of a prospective observational study of febrile infants 60 days of age and younger presenting to any of 26 PECARN emergency departments (2008 to 2013) who had blood cultures obtained. We excluded infants with significant comorbidities or critically ill appearance. The primary outcome was prevalence of bacteremia.ResultsOf 7,335 screened infants, 4,778 (65.1%) had blood cultures and were enrolled. Of these patients, 84 had bacteremia (1.8%; 95% confidence interval [CI] 1.4% to 2.2%). The prevalence of bacteremia in infants aged 28 days or younger (47/1,515) was 3.1% (95% CI 2.3% to 4.1%); in infants aged 29 to 60 days (37/3,246), 1.1% (95% CI 0.8% to 1.6%). Prevalence differed by week of age for infants 28 days of age and younger (0 to 7 days: 4/156, 2.6%; 8 to 14 days: 19/356, 5.3%; 15 to 21 days: 15/449, 3.3%; and 22 to 28 days: 9/554, 1.6%). The most common pathogens were Escherichia coli (39.3%; 95% CI 29.5% to 50.0%) and group B streptococcus (23.8%; 95% CI 16.0% to 33.9%). Bacterial meningitis occurred in 19 of 1,515 infants 28 days of age and younger (1.3%; 95% CI 0.8% to 2.0%) and 5 of 3,246 infants aged 29 to 60 days (0.2%; 95% CI 0.1% to 0.4%). Of 84 infants with bacteremia, 36 (42.9%; 95% CI 32.8% to 53.5%) had urinary tract infections (E coli 83%); 11 (13.1%; 95% CI 7.5% to 21.9%) had bacterial meningitis.ConclusionThe prevalence of bacteremia and meningitis among febrile infants 28 days of age and younger is high and exceeds that observed in infants aged 29 to 60 days. E coli and group B streptococcus are the most common bacterial pathogens.

Published
2018

30. Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger.

Author

Mahajan, Prashant, Mahajan, Prashant, Kuppermann, Nathan, Mejias, Asuncion, Suarez, Nicolas, Chaussabel, Damien, Casper, T Charles, Smith, Bennett, Alpern, Elizabeth R, Anders, Jennifer, Atabaki, Shireen M, Bennett, Jonathan E, Blumberg, Stephen, Bonsu, Bema, Borgialli, Dominic, Brayer, Anne, Browne, Lorin, Cohen, Daniel M, Crain, Ellen F, Cruz, Andrea T, Dayan, Peter S, Gattu, Rajender, Greenberg, Richard, Hoyle, John D, Jaffe, David M, Levine, Deborah A, Lillis, Kathleen, Linakis, James G, Muenzer, Jared, Nigrovic, Lise E, Powell, Elizabeth C, Rogers, Alexander J, Roosevelt, Genie, Ruddy, Richard M, Saunders, Mary, Tunik, Michael G, Tzimenatos, Leah, Vitale, Melissa, Dean, J Michael, Ramilo, Octavio, Pediatric Emergency Care Applied Research Network (PECARN), Mahajan, Prashant, Mahajan, Prashant, Kuppermann, Nathan, Mejias, Asuncion, Suarez, Nicolas, Chaussabel, Damien, Casper, T Charles, Smith, Bennett, Alpern, Elizabeth R, Anders, Jennifer, Atabaki, Shireen M, Bennett, Jonathan E, Blumberg, Stephen, Bonsu, Bema, Borgialli, Dominic, Brayer, Anne, Browne, Lorin, Cohen, Daniel M, Crain, Ellen F, Cruz, Andrea T, Dayan, Peter S, Gattu, Rajender, Greenberg, Richard, Hoyle, John D, Jaffe, David M, Levine, Deborah A, Lillis, Kathleen, Linakis, James G, Muenzer, Jared, Nigrovic, Lise E, Powell, Elizabeth C, Rogers, Alexander J, Roosevelt, Genie, Ruddy, Richard M, Saunders, Mary, Tunik, Michael G, Tzimenatos, Leah, Vitale, Melissa, Dean, J Michael, Ramilo, Octavio, and Pediatric Emergency Care Applied Research Network (PECARN)

Abstract

ImportanceYoung febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns ("RNA biosignatures") in response to infections may provide an alternative diagnostic approach.ObjectiveTo assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections.Design, setting, and participantsProspective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature >38° C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type.ExposureRNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections.Main outcomes and measuresBacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores.ResultsOf 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections-including 32 with bacteremia and 15 with urinary tract infections-and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacte

Published
2016

31. Comprehensive variation discovery in single human genomes

Author

Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., Weisenfeld, Neil I, Yin, Shuangye, Sharpe, Ted, Lau, Bayo, Hegarty, Ryan, Holmes, Laurie, Sogoloff, Brian, Tabbaa, Diana, Williams, Louise, Russ, Carsten, Nusbaum, Chad, MacCallum, Iain, Jaffe, David B., Lander, Eric Steven, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., Weisenfeld, Neil I, Yin, Shuangye, Sharpe, Ted, Lau, Bayo, Hegarty, Ryan, Holmes, Laurie, Sogoloff, Brian, Tabbaa, Diana, Williams, Louise, Russ, Carsten, Nusbaum, Chad, MacCallum, Iain, Jaffe, David B., and Lander, Eric Steven

Abstract

Complete knowledge of the genetic variation in individual human genomes is a crucial foundation for understanding the etiology of disease. Genetic variation is typically characterized by sequencing individual genomes and comparing reads to a reference. Existing methods do an excellent job of detecting variants in approximately 90% of the human genome; however, calling variants in the remaining 10% of the genome (largely low-complexity sequence and segmental duplications) is challenging. To improve variant calling, we developed a new algorithm, DISCOVAR, and examined its performance on improved, low-cost sequence data. Using a newly created reference set of variants from the finished sequence of 103 randomly chosen fosmids, we find that some standard variant call sets miss up to 25% of variants. We show that the combination of new methods and improved data increases sensitivity by several fold, with the greatest impact in challenging regions of the human genome., National Human Genome Research Institute (U.S.) (Grant R01HG003474), National Human Genome Research Institute (U.S.) (Grant U54HG003067), National Institute of Allergy and Infectious Diseases (U.S.) (Contract HHSN272200900018C)

Published
2015

32. Characterization and Modeling of a Water-based Liquid Scintillator

Author

Bignell, Lindsey J., Beznosko, Dmitriy, Diwan, Milind V., Hans, Sunej, Jaffe, David E., Kettell, Steven, Rosero, Richard, Themann, Harry W., Viren, Brett, Worcester, Elizabeth, Yeh, Minfang, Zhang, Chao, Bignell, Lindsey J., Beznosko, Dmitriy, Diwan, Milind V., Hans, Sunej, Jaffe, David E., Kettell, Steven, Rosero, Richard, Themann, Harry W., Viren, Brett, Worcester, Elizabeth, Yeh, Minfang, and Zhang, Chao

Abstract

We have characterised Water-based Liquid Scintillator (WbLS) using low energy protons, UV-VIS absorbance, and fluorescence spectroscopy. We have also developed and validated a simulation model that describes the behaviour of WbLS in our detector configurations for proton beam energies of 2 GeV, 475 MeV, and 210 MeV and for two WbLS compositions. Our results have enabled us to estimate the light yield and ionisation quenching of WbLS, as well as to understand the influence of the wavelength shifting of Cerenkov light on our measurements. These results are relevant to the suitability of water-based liquid scintillator materials for next generation intensity frontier experiments.

Published
2015
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33. The genomic substrate for adaptive radiation in African cichlid fish

Author

Brawand, David, Wagner, Catherine E., Li, Yang I., Malinsky, Milan, Keller, Irene, Fan, Shaohua, Simakov, Oleg, Ng, Alvin Y., Lim, Zhi Wei, Bezault, Etienne, Turner-Maier, Jason, Johnson, Jeremy, Alcazar, Rosa, Noh, Hyun Ji, Russell, Pamela, Aken, Bronwen, Alfoeldi, Jessica, Amemiya, Chris, Azzouzi, Naoual, Baroiller, Jean-Francois, Barloy-Hubler, Frederique, Berlin, Aaron, Bloomquist, Ryan, Carleton, Karen L., Conte, Matthew A., D'Cotta, Helena, Eshel, Orly, Gaffney, Leslie, Galibert, Francis, Gante, Hugo F., Gnerre, Sante, Greuter, Lucie, Guyon, Richard, Haddad, Natalie S., Haerty, Wilfried, Harris, Rayna M., Hofmann, Hans A., Hourlier, Thibaut, Hulata, Gideon, Jaffe, David B., Lara, Marcia, Lee, Alison P., MacCallum, Iain, Mwaiko, Salome, Nikaido, Masato, Nishihara, Hidenori, Ozouf-Costaz, Catherine, Penman, David J., Przybylski, Dariusz, Rakotomanga, Michaelle, Renn, Suzy C. P., Ribeiro, Filipe J., Ron, Micha, Salzburger, Walter, Sanchez-Pulido, Luis, Santos, M. Emilia, Searle, Steve, Sharpe, Ted, Swofford, Ross, Tan, Frederick J., Williams, Louise, Young, Sarah, Yin, Shuangye, Okada, Norihiro, Kocher, Thomas D., Miska, Eric A., Lander, Eric S., Venkatesh, Byrappa, Fernald, Russell D., Meyer, Axel, Ponting, Chris P., Streelman, J. Todd, Lindblad-Toh, Kerstin, Seehausen, Ole, Di Palma, Federica, Brawand, David, Wagner, Catherine E., Li, Yang I., Malinsky, Milan, Keller, Irene, Fan, Shaohua, Simakov, Oleg, Ng, Alvin Y., Lim, Zhi Wei, Bezault, Etienne, Turner-Maier, Jason, Johnson, Jeremy, Alcazar, Rosa, Noh, Hyun Ji, Russell, Pamela, Aken, Bronwen, Alfoeldi, Jessica, Amemiya, Chris, Azzouzi, Naoual, Baroiller, Jean-Francois, Barloy-Hubler, Frederique, Berlin, Aaron, Bloomquist, Ryan, Carleton, Karen L., Conte, Matthew A., D'Cotta, Helena, Eshel, Orly, Gaffney, Leslie, Galibert, Francis, Gante, Hugo F., Gnerre, Sante, Greuter, Lucie, Guyon, Richard, Haddad, Natalie S., Haerty, Wilfried, Harris, Rayna M., Hofmann, Hans A., Hourlier, Thibaut, Hulata, Gideon, Jaffe, David B., Lara, Marcia, Lee, Alison P., MacCallum, Iain, Mwaiko, Salome, Nikaido, Masato, Nishihara, Hidenori, Ozouf-Costaz, Catherine, Penman, David J., Przybylski, Dariusz, Rakotomanga, Michaelle, Renn, Suzy C. P., Ribeiro, Filipe J., Ron, Micha, Salzburger, Walter, Sanchez-Pulido, Luis, Santos, M. Emilia, Searle, Steve, Sharpe, Ted, Swofford, Ross, Tan, Frederick J., Williams, Louise, Young, Sarah, Yin, Shuangye, Okada, Norihiro, Kocher, Thomas D., Miska, Eric A., Lander, Eric S., Venkatesh, Byrappa, Fernald, Russell D., Meyer, Axel, Ponting, Chris P., Streelman, J. Todd, Lindblad-Toh, Kerstin, Seehausen, Ole, and Di Palma, Federica

Abstract

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification., De tre sista författarna delar sistaförfattarskapet.

Published
2014
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34. The genomic substrate for adaptive radiation in African cichlid fish.

Author

Brawand, David, Brawand, David, Wagner, Catherine E, Li, Yang I, Malinsky, Milan, Keller, Irene, Fan, Shaohua, Simakov, Oleg, Ng, Alvin Y, Lim, Zhi Wei, Bezault, Etienne, Turner-Maier, Jason, Johnson, Jeremy, Alcazar, Rosa, Noh, Hyun Ji, Russell, Pamela, Aken, Bronwen, Alföldi, Jessica, Amemiya, Chris, Azzouzi, Naoual, Baroiller, Jean-François, Barloy-Hubler, Frederique, Berlin, Aaron, Bloomquist, Ryan, Carleton, Karen L, Conte, Matthew A, D'Cotta, Helena, Eshel, Orly, Gaffney, Leslie, Galibert, Francis, Gante, Hugo F, Gnerre, Sante, Greuter, Lucie, Guyon, Richard, Haddad, Natalie S, Haerty, Wilfried, Harris, Rayna M, Hofmann, Hans A, Hourlier, Thibaut, Hulata, Gideon, Jaffe, David B, Lara, Marcia, Lee, Alison P, MacCallum, Iain, Mwaiko, Salome, Nikaido, Masato, Nishihara, Hidenori, Ozouf-Costaz, Catherine, Penman, David J, Przybylski, Dariusz, Rakotomanga, Michaelle, Renn, Suzy CP, Ribeiro, Filipe J, Ron, Micha, Salzburger, Walter, Sanchez-Pulido, Luis, Santos, M Emilia, Searle, Steve, Sharpe, Ted, Swofford, Ross, Tan, Frederick J, Williams, Louise, Young, Sarah, Yin, Shuangye, Okada, Norihiro, Kocher, Thomas D, Miska, Eric A, Lander, Eric S, Venkatesh, Byrappa, Fernald, Russell D, Meyer, Axel, Ponting, Chris P, Streelman, J Todd, Lindblad-Toh, Kerstin, Seehausen, Ole, Di Palma, Federica, Brawand, David, Brawand, David, Wagner, Catherine E, Li, Yang I, Malinsky, Milan, Keller, Irene, Fan, Shaohua, Simakov, Oleg, Ng, Alvin Y, Lim, Zhi Wei, Bezault, Etienne, Turner-Maier, Jason, Johnson, Jeremy, Alcazar, Rosa, Noh, Hyun Ji, Russell, Pamela, Aken, Bronwen, Alföldi, Jessica, Amemiya, Chris, Azzouzi, Naoual, Baroiller, Jean-François, Barloy-Hubler, Frederique, Berlin, Aaron, Bloomquist, Ryan, Carleton, Karen L, Conte, Matthew A, D'Cotta, Helena, Eshel, Orly, Gaffney, Leslie, Galibert, Francis, Gante, Hugo F, Gnerre, Sante, Greuter, Lucie, Guyon, Richard, Haddad, Natalie S, Haerty, Wilfried, Harris, Rayna M, Hofmann, Hans A, Hourlier, Thibaut, Hulata, Gideon, Jaffe, David B, Lara, Marcia, Lee, Alison P, MacCallum, Iain, Mwaiko, Salome, Nikaido, Masato, Nishihara, Hidenori, Ozouf-Costaz, Catherine, Penman, David J, Przybylski, Dariusz, Rakotomanga, Michaelle, Renn, Suzy CP, Ribeiro, Filipe J, Ron, Micha, Salzburger, Walter, Sanchez-Pulido, Luis, Santos, M Emilia, Searle, Steve, Sharpe, Ted, Swofford, Ross, Tan, Frederick J, Williams, Louise, Young, Sarah, Yin, Shuangye, Okada, Norihiro, Kocher, Thomas D, Miska, Eric A, Lander, Eric S, Venkatesh, Byrappa, Fernald, Russell D, Meyer, Axel, Ponting, Chris P, Streelman, J Todd, Lindblad-Toh, Kerstin, Seehausen, Ole, and Di Palma, Federica

Abstract

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Published
2014

35. The genomic substrate for adaptive radiation in African cichlid fish.

Author

Brawand, David, Brawand, David, Wagner, Catherine E, Li, Yang I, Malinsky, Milan, Keller, Irene, Fan, Shaohua, Simakov, Oleg, Ng, Alvin Y, Lim, Zhi Wei, Bezault, Etienne, Turner-Maier, Jason, Johnson, Jeremy, Alcazar, Rosa, Noh, Hyun Ji, Russell, Pamela, Aken, Bronwen, Alföldi, Jessica, Amemiya, Chris, Azzouzi, Naoual, Baroiller, Jean-François, Barloy-Hubler, Frederique, Berlin, Aaron, Bloomquist, Ryan, Carleton, Karen L, Conte, Matthew A, D'Cotta, Helena, Eshel, Orly, Gaffney, Leslie, Galibert, Francis, Gante, Hugo F, Gnerre, Sante, Greuter, Lucie, Guyon, Richard, Haddad, Natalie S, Haerty, Wilfried, Harris, Rayna M, Hofmann, Hans A, Hourlier, Thibaut, Hulata, Gideon, Jaffe, David B, Lara, Marcia, Lee, Alison P, MacCallum, Iain, Mwaiko, Salome, Nikaido, Masato, Nishihara, Hidenori, Ozouf-Costaz, Catherine, Penman, David J, Przybylski, Dariusz, Rakotomanga, Michaelle, Renn, Suzy CP, Ribeiro, Filipe J, Ron, Micha, Salzburger, Walter, Sanchez-Pulido, Luis, Santos, M Emilia, Searle, Steve, Sharpe, Ted, Swofford, Ross, Tan, Frederick J, Williams, Louise, Young, Sarah, Yin, Shuangye, Okada, Norihiro, Kocher, Thomas D, Miska, Eric A, Lander, Eric S, Venkatesh, Byrappa, Fernald, Russell D, Meyer, Axel, Ponting, Chris P, Streelman, J Todd, Lindblad-Toh, Kerstin, Seehausen, Ole, Di Palma, Federica, Brawand, David, Brawand, David, Wagner, Catherine E, Li, Yang I, Malinsky, Milan, Keller, Irene, Fan, Shaohua, Simakov, Oleg, Ng, Alvin Y, Lim, Zhi Wei, Bezault, Etienne, Turner-Maier, Jason, Johnson, Jeremy, Alcazar, Rosa, Noh, Hyun Ji, Russell, Pamela, Aken, Bronwen, Alföldi, Jessica, Amemiya, Chris, Azzouzi, Naoual, Baroiller, Jean-François, Barloy-Hubler, Frederique, Berlin, Aaron, Bloomquist, Ryan, Carleton, Karen L, Conte, Matthew A, D'Cotta, Helena, Eshel, Orly, Gaffney, Leslie, Galibert, Francis, Gante, Hugo F, Gnerre, Sante, Greuter, Lucie, Guyon, Richard, Haddad, Natalie S, Haerty, Wilfried, Harris, Rayna M, Hofmann, Hans A, Hourlier, Thibaut, Hulata, Gideon, Jaffe, David B, Lara, Marcia, Lee, Alison P, MacCallum, Iain, Mwaiko, Salome, Nikaido, Masato, Nishihara, Hidenori, Ozouf-Costaz, Catherine, Penman, David J, Przybylski, Dariusz, Rakotomanga, Michaelle, Renn, Suzy CP, Ribeiro, Filipe J, Ron, Micha, Salzburger, Walter, Sanchez-Pulido, Luis, Santos, M Emilia, Searle, Steve, Sharpe, Ted, Swofford, Ross, Tan, Frederick J, Williams, Louise, Young, Sarah, Yin, Shuangye, Okada, Norihiro, Kocher, Thomas D, Miska, Eric A, Lander, Eric S, Venkatesh, Byrappa, Fernald, Russell D, Meyer, Axel, Ponting, Chris P, Streelman, J Todd, Lindblad-Toh, Kerstin, Seehausen, Ole, and Di Palma, Federica

Abstract

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Published
2014

36. Cervical spine injury patterns in children.

Author

Leonard, Jeffrey R, Leonard, Jeffrey R, Jaffe, David M, Kuppermann, Nathan, Olsen, Cody S, Leonard, Julie C, Pediatric Emergency Care Applied Research Network (PECARN) Cervical Spine Study Group, Leonard, Jeffrey R, Leonard, Jeffrey R, Jaffe, David M, Kuppermann, Nathan, Olsen, Cody S, Leonard, Julie C, and Pediatric Emergency Care Applied Research Network (PECARN) Cervical Spine Study Group

Abstract

Background and objectivePediatric cervical spine injuries (CSIs) are rare and differ from adult CSIs. Our objective was to describe CSIs in a large, representative cohort of children.MethodsWe conducted a 5-year retrospective review of children <16 years old with CSIs at 17 Pediatric Emergency Care Applied Research Network hospitals. Investigators reviewed imaging reports and consultations to assign CSI type. We described cohort characteristics using means and frequencies and used Fisher's exact test to compare differences between 3 age groups: <2 years, 2 to 7 years, and 8 to 15 years. We used logistic regression to explore the relationship between injury level and age and mechanism of injury and between neurologic outcome and cord involvement, injury level, age, and comorbid injuries.ResultsA total of 540 children with CSIs were included in the study. CSI level was associated with both age and mechanism of injury. For children <2 and 2 to 7 years old, motor vehicle crash (MVC) was the most common injury mechanism (56%, 37%). Children in these age groups more commonly injured the axial (occiput-C2) region (74%, 78%). In children 8 to 15 years old, sports accounted for as many injuries as MVCs (23%, 23%), and 53% of injuries were subaxial (C3-7). CSIs often necessitated surgical intervention (axial, 39%; subaxial, 30%) and often resulted in neurologic deficits (21%) and death (7%). Neurologic outcome was associated with cord involvement, injury level, age, and comorbid injuries.ConclusionsWe demonstrated a high degree of variability of CSI patterns, treatments and outcomes in children. The rarity, variation, and morbidity of pediatric CSIs make prompt recognition and treatment critical.

Published
2014

37. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples

Author

Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., Cibulskis, Kristian, Sivachenko, Andrey, Jaffe, David B., Sougnez, Carrie, Gabriel, Stacey B., Meyerson, Matthew L., Getz, Gad, Lawrence, Michael S., Carter, Scott L., Lander, Eric Steven, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., Cibulskis, Kristian, Sivachenko, Andrey, Jaffe, David B., Sougnez, Carrie, Gabriel, Stacey B., Meyerson, Matthew L., Getz, Gad, Lawrence, Michael S., Carter, Scott L., and Lander, Eric Steven

Abstract

Detection of somatic point substitutions is a key step in characterizing the cancer genome. However, existing methods typically miss low-allelic-fraction mutations that occur in only a subset of the sequenced cells owing to either tumor heterogeneity or contamination by normal cells. Here we present MuTect, a method that applies a Bayesian classifier to detect somatic mutations with very low allele fractions, requiring only a few supporting reads, followed by carefully tuned filters that ensure high specificity. We also describe benchmarking approaches that use real, rather than simulated, sequencing data to evaluate the sensitivity and specificity as a function of sequencing depth, base quality and allelic fraction. Compared with other methods, MuTect has higher sensitivity with similar specificity, especially for mutations with allelic fractions as low as 0.1 and below, making MuTect particularly useful for studying cancer subclones and their evolution in standard exome and genome sequencing data., National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U24CA143845)

Published
2014

38. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing

Author

Kirby, Andrew, Gnirke, Andreas, Jaffe, David B., Baresova, Veronika, Pochet, Nathalie, Blumenstiel, Brendan, Ye, Chun, Aird, Daniel, Stevens, Christine, Robinson, James T., Cabili, Moran N., Gat-Viks, Irit, Kelliher, Edward, Daza, Riza, DeFelice, Matthew, Hulkova, Helena, Sovova, Jana, Vylet'al, Petr, Antignac, Corinne, Guttman, Mitchell, Handsaker, Robert E., Perrin, Danielle, Steelman, Scott, Sigurdsson, Snaevar, Scheinman, Steven J., Sougnez, Carrie, Cibulskis, Kristian, Parkin, Melissa, Green, Todd, Rossin, Elizabeth, Zody, Michael C., Xavier, Ramnik J., Pollak, Martin R., Alper, Seth L., Lindblad-Toh, Kerstin, Gabriel, Stacey, Hart, P. Suzanne, Regev, Aviv, Nusbaum, Chad, Kmoch, Stanislav, Bleyer, Anthony J., Lander, Eric S., Daly, Mark J., Kirby, Andrew, Gnirke, Andreas, Jaffe, David B., Baresova, Veronika, Pochet, Nathalie, Blumenstiel, Brendan, Ye, Chun, Aird, Daniel, Stevens, Christine, Robinson, James T., Cabili, Moran N., Gat-Viks, Irit, Kelliher, Edward, Daza, Riza, DeFelice, Matthew, Hulkova, Helena, Sovova, Jana, Vylet'al, Petr, Antignac, Corinne, Guttman, Mitchell, Handsaker, Robert E., Perrin, Danielle, Steelman, Scott, Sigurdsson, Snaevar, Scheinman, Steven J., Sougnez, Carrie, Cibulskis, Kristian, Parkin, Melissa, Green, Todd, Rossin, Elizabeth, Zody, Michael C., Xavier, Ramnik J., Pollak, Martin R., Alper, Seth L., Lindblad-Toh, Kerstin, Gabriel, Stacey, Hart, P. Suzanne, Regev, Aviv, Nusbaum, Chad, Kmoch, Stanislav, Bleyer, Anthony J., Lander, Eric S., and Daly, Mark J.

Abstract

Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (similar to 1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.

Published
2013
Full Text
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39. The African coelacanth genome provides insights into tetrapod evolution

Author

Amemiya, Chris T., Alfoeldi, Jessica, Lee, Alison P., Fan, Shaohua, Philippe, Herve, MacCallum, Iain, Braasch, Ingo, Manousaki, Tereza, Schneider, Igor, Rohner, Nicolas, Organ, Chris, Chalopin, Domitille, Smith, Jeramiah J., Robinson, Mark, Dorrington, Rosemary A., Gerdol, Marco, Aken, Bronwen, Biscotti, Maria Assunta, Barucca, Marco, Baurain, Denis, Berlin, Aaron M., Blatch, Gregory L., Buonocore, Francesco, Burmester, Thorsten, Campbell, Michael S., Canapa, Adriana, Cannon, John P., Christoffels, Alan, De Moro, Gianluca, Edkins, Adrienne L., Fan, Lin, Fausto, Anna Maria, Feiner, Nathalie, Forconi, Mariko, Gamieldien, Junaid, Gnerre, Sante, Gnirke, Andreas, Goldstone, Jared V., Haerty, Wilfried, Hahn, Mark E., Hesse, Uljana, Hoffmann, Steve, Johnson, Jeremy, Karchner, Sibel I., Kuraku, Shigehiro, Lara, Marcia, Levin, Joshua Z., Litman, Gary W., Mauceli, Evan, Miyake, Tsutomu, Mueller, M. Gail, Nelson, David R., Nitsche, Anne, Olmo, Ettore, Ota, Tatsuya, Pallavicini, Alberto, Panji, Sumir, Picone, Barbara, Ponting, Chris P., Prohaska, Sonja J., Przybylski, Dariusz, Saha, Nil Ratan, Ravi, Vydianathan, Ribeiro, Filipe J., Sauka-Spengler, Tatjana, Scapigliati, Giuseppe, Searle, Stephen M. J., Sharpe, Ted, Simakov, Oleg, Stadler, Peter F., Stegeman, John J., Sumiyama, Kenta, Tabbaa, Diana, Tafer, Hakim, Turner-Maier, Jason, van Heusden, Peter, White, Simon, Williams, Louise, Yandell, Mark, Brinkmann, Henner, Volff, Jean-Nicolas, Tabin, Clifford J., Shubin, Neil, Schartl, Manfred, Jaffe, David B., Postlethwait, John H., Venkatesh, Byrappa, Di Palma, Federica, Lander, Eric S., Meyer, Axel, Lindblad-Toh, Kerstin, Amemiya, Chris T., Alfoeldi, Jessica, Lee, Alison P., Fan, Shaohua, Philippe, Herve, MacCallum, Iain, Braasch, Ingo, Manousaki, Tereza, Schneider, Igor, Rohner, Nicolas, Organ, Chris, Chalopin, Domitille, Smith, Jeramiah J., Robinson, Mark, Dorrington, Rosemary A., Gerdol, Marco, Aken, Bronwen, Biscotti, Maria Assunta, Barucca, Marco, Baurain, Denis, Berlin, Aaron M., Blatch, Gregory L., Buonocore, Francesco, Burmester, Thorsten, Campbell, Michael S., Canapa, Adriana, Cannon, John P., Christoffels, Alan, De Moro, Gianluca, Edkins, Adrienne L., Fan, Lin, Fausto, Anna Maria, Feiner, Nathalie, Forconi, Mariko, Gamieldien, Junaid, Gnerre, Sante, Gnirke, Andreas, Goldstone, Jared V., Haerty, Wilfried, Hahn, Mark E., Hesse, Uljana, Hoffmann, Steve, Johnson, Jeremy, Karchner, Sibel I., Kuraku, Shigehiro, Lara, Marcia, Levin, Joshua Z., Litman, Gary W., Mauceli, Evan, Miyake, Tsutomu, Mueller, M. Gail, Nelson, David R., Nitsche, Anne, Olmo, Ettore, Ota, Tatsuya, Pallavicini, Alberto, Panji, Sumir, Picone, Barbara, Ponting, Chris P., Prohaska, Sonja J., Przybylski, Dariusz, Saha, Nil Ratan, Ravi, Vydianathan, Ribeiro, Filipe J., Sauka-Spengler, Tatjana, Scapigliati, Giuseppe, Searle, Stephen M. J., Sharpe, Ted, Simakov, Oleg, Stadler, Peter F., Stegeman, John J., Sumiyama, Kenta, Tabbaa, Diana, Tafer, Hakim, Turner-Maier, Jason, van Heusden, Peter, White, Simon, Williams, Louise, Yandell, Mark, Brinkmann, Henner, Volff, Jean-Nicolas, Tabin, Clifford J., Shubin, Neil, Schartl, Manfred, Jaffe, David B., Postlethwait, John H., Venkatesh, Byrappa, Di Palma, Federica, Lander, Eric S., Meyer, Axel, and Lindblad-Toh, Kerstin

Abstract

The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.

Published
2013
Full Text
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40. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing.

Author

Kirby, Andrew, Kirby, Andrew, Gnirke, Andreas, Jaffe, David B, Barešová, Veronika, Pochet, Nathalie, Blumenstiel, Brendan, Ye, Chun, Aird, Daniel, Stevens, Christine, Robinson, James T, Cabili, Moran N, Gat-Viks, Irit, Kelliher, Edward, Daza, Riza, DeFelice, Matthew, Hůlková, Helena, Sovová, Jana, Vylet'al, Petr, Antignac, Corinne, Guttman, Mitchell, Handsaker, Robert E, Perrin, Danielle, Steelman, Scott, Sigurdsson, Snaevar, Scheinman, Steven J, Sougnez, Carrie, Cibulskis, Kristian, Parkin, Melissa, Green, Todd, Rossin, Elizabeth, Zody, Michael C, Xavier, Ramnik J, Pollak, Martin R, Alper, Seth L, Lindblad-Toh, Kerstin, Gabriel, Stacey, Hart, P Suzanne, Regev, Aviv, Nusbaum, Chad, Kmoch, Stanislav, Bleyer, Anthony J, Lander, Eric S, Daly, Mark J, Kirby, Andrew, Kirby, Andrew, Gnirke, Andreas, Jaffe, David B, Barešová, Veronika, Pochet, Nathalie, Blumenstiel, Brendan, Ye, Chun, Aird, Daniel, Stevens, Christine, Robinson, James T, Cabili, Moran N, Gat-Viks, Irit, Kelliher, Edward, Daza, Riza, DeFelice, Matthew, Hůlková, Helena, Sovová, Jana, Vylet'al, Petr, Antignac, Corinne, Guttman, Mitchell, Handsaker, Robert E, Perrin, Danielle, Steelman, Scott, Sigurdsson, Snaevar, Scheinman, Steven J, Sougnez, Carrie, Cibulskis, Kristian, Parkin, Melissa, Green, Todd, Rossin, Elizabeth, Zody, Michael C, Xavier, Ramnik J, Pollak, Martin R, Alper, Seth L, Lindblad-Toh, Kerstin, Gabriel, Stacey, Hart, P Suzanne, Regev, Aviv, Nusbaum, Chad, Kmoch, Stanislav, Bleyer, Anthony J, Lander, Eric S, and Daly, Mark J

Abstract

Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (∼1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.

Published
2013

41. Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Author

Bradnam, Keith R, Bradnam, Keith R, Fass, Joseph N, Alexandrov, Anton, Baranay, Paul, Bechner, Michael, Birol, Inanç, Boisvert, Sébastien, Chapman, Jarrod A, Chapuis, Guillaume, Chikhi, Rayan, Chitsaz, Hamidreza, Chou, Wen-Chi, Corbeil, Jacques, Del Fabbro, Cristian, Docking, T, Durbin, Richard, Earl, Dent, Emrich, Scott, Fedotov, Pavel, Fonseca, Nuno A, Ganapathy, Ganeshkumar, Gibbs, Richard A, Gnerre, Sante, Godzaridis, Élénie, Goldstein, Steve, Haimel, Matthias, Hall, Giles, Haussler, David, Hiatt, Joseph B, Ho, Isaac Y, Howard, Jason, Hunt, Martin, Jackman, Shaun D, Jaffe, David B, Jarvis, Erich D, Jiang, Huaiyang, Kazakov, Sergey, Kersey, Paul J, Kitzman, Jacob O, Knight, James R, Koren, Sergey, Lam, Tak-Wah, Lavenier, Dominique, Laviolette, François, Li, Yingrui, Li, Zhenyu, Liu, Binghang, Liu, Yue, Luo, Ruibang, MacCallum, Iain, MacManes, Matthew D, Maillet, Nicolas, Melnikov, Sergey, Naquin, Delphine, Ning, Zemin, Otto, Thomas D, Paten, Benedict, Paulo, Octávio S, Phillippy, Adam M, Pina-Martins, Francisco, Place, Michael, Przybylski, Dariusz, Qin, Xiang, Qu, Carson, Ribeiro, Filipe J, Richards, Stephen, Rokhsar, Daniel S, Ruby, J, Scalabrin, Simone, Schatz, Michael C, Schwartz, David C, Sergushichev, Alexey, Sharpe, Ted, Shaw, Timothy I, Shendure, Jay, Shi, Yujian, Simpson, Jared T, Song, Henry, Tsarev, Fedor, Vezzi, Francesco, Vicedomini, Riccardo, Vieira, Bruno M, Wang, Jun, Worley, Kim C, Yin, Shuangye, Yiu, Siu-Ming, Yuan, Jianying, Zhang, Guojie, Zhang, Hao, Zhou, Shiguo, Korf, Ian F, Bradnam, Keith R, Bradnam, Keith R, Fass, Joseph N, Alexandrov, Anton, Baranay, Paul, Bechner, Michael, Birol, Inanç, Boisvert, Sébastien, Chapman, Jarrod A, Chapuis, Guillaume, Chikhi, Rayan, Chitsaz, Hamidreza, Chou, Wen-Chi, Corbeil, Jacques, Del Fabbro, Cristian, Docking, T, Durbin, Richard, Earl, Dent, Emrich, Scott, Fedotov, Pavel, Fonseca, Nuno A, Ganapathy, Ganeshkumar, Gibbs, Richard A, Gnerre, Sante, Godzaridis, Élénie, Goldstein, Steve, Haimel, Matthias, Hall, Giles, Haussler, David, Hiatt, Joseph B, Ho, Isaac Y, Howard, Jason, Hunt, Martin, Jackman, Shaun D, Jaffe, David B, Jarvis, Erich D, Jiang, Huaiyang, Kazakov, Sergey, Kersey, Paul J, Kitzman, Jacob O, Knight, James R, Koren, Sergey, Lam, Tak-Wah, Lavenier, Dominique, Laviolette, François, Li, Yingrui, Li, Zhenyu, Liu, Binghang, Liu, Yue, Luo, Ruibang, MacCallum, Iain, MacManes, Matthew D, Maillet, Nicolas, Melnikov, Sergey, Naquin, Delphine, Ning, Zemin, Otto, Thomas D, Paten, Benedict, Paulo, Octávio S, Phillippy, Adam M, Pina-Martins, Francisco, Place, Michael, Przybylski, Dariusz, Qin, Xiang, Qu, Carson, Ribeiro, Filipe J, Richards, Stephen, Rokhsar, Daniel S, Ruby, J, Scalabrin, Simone, Schatz, Michael C, Schwartz, David C, Sergushichev, Alexey, Sharpe, Ted, Shaw, Timothy I, Shendure, Jay, Shi, Yujian, Simpson, Jared T, Song, Henry, Tsarev, Fedor, Vezzi, Francesco, Vicedomini, Riccardo, Vieira, Bruno M, Wang, Jun, Worley, Kim C, Yin, Shuangye, Yiu, Siu-Ming, Yuan, Jianying, Zhang, Guojie, Zhang, Hao, Zhou, Shiguo, and Korf, Ian F

Abstract

Background The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.

Published
2013

42. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing

Author

Massachusetts Institute of Technology. Department of Biology, Regev, Aviv, Lander, Eric S., Kirby, Andrew, Gnirke, Andreas, Jaffe, David B., Baresova, Veronika, Pochet, Nathalie, Blumenstiel, Brendan, Ye, Chun, Aird, Daniel, Stevens, Christine, Robinson, James T., Cabili, Moran N., Gat-Viks, Irit, Kelliher, Edward, Daza, Riza, DeFelice, Matthew, Hulkova, Helena, Sovova, Jana, Vylet'al, Petr, Antignac, Corinne, Guttman, Mitchell, Handsaker, Robert E., Perrin, Danielle, Steelman, Scott, Sigurdsson, Snaevar, Scheinman, Steven J., Sougnez, Carrie, Cibulskis, Kristian, Parkin, Melissa, Green, Todd, Rossin, Elizabeth, Zody, Michael C., Xavier, Ramnik J., Pollak, Martin R., Alper, Seth L., Lindblad-Toh, Kerstin, Gabriel, Stacey B., Hart, P. Suzanne, Nusbaum, Chad, Kmoch, Stanislav, Bleyer, Anthony J., Daly, Mark J., Massachusetts Institute of Technology. Department of Biology, Regev, Aviv, Lander, Eric S., Kirby, Andrew, Gnirke, Andreas, Jaffe, David B., Baresova, Veronika, Pochet, Nathalie, Blumenstiel, Brendan, Ye, Chun, Aird, Daniel, Stevens, Christine, Robinson, James T., Cabili, Moran N., Gat-Viks, Irit, Kelliher, Edward, Daza, Riza, DeFelice, Matthew, Hulkova, Helena, Sovova, Jana, Vylet'al, Petr, Antignac, Corinne, Guttman, Mitchell, Handsaker, Robert E., Perrin, Danielle, Steelman, Scott, Sigurdsson, Snaevar, Scheinman, Steven J., Sougnez, Carrie, Cibulskis, Kristian, Parkin, Melissa, Green, Todd, Rossin, Elizabeth, Zody, Michael C., Xavier, Ramnik J., Pollak, Martin R., Alper, Seth L., Lindblad-Toh, Kerstin, Gabriel, Stacey B., Hart, P. Suzanne, Nusbaum, Chad, Kmoch, Stanislav, Bleyer, Anthony J., and Daly, Mark J.

Abstract

Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (~1.5–5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing., National Institutes of Health (U.S.) (Intramural Research Program), National Human Genome Research Institute (U.S.), Charles University (program UNCE 204011), Charles University (program PRVOUK-P24/LF1/3), Czech Republic. Ministry of Education, Youth, and Sports (grant NT13116-4/2012), Czech Republic. Ministry of Health (grant NT13116-4/2012), Czech Republic. Ministry of Health (grant LH12015), National Institutes of Health (U.S.) (Harvard Digestive Diseases Center, grant DK34854)

Published
2013

43. The African coelacanth genome provides insights into tetrapod evolution

Author

Amemiya, Chris T., Alfoldi, Jessica, Lee, Alison P., Fan, Shaohua, Philippe, Herve, MacCallum, Iain, Braasch, Ingo, Manousaki, Tereza, Schneider, Igor, Rohner, Nicolas, Organ, Chris, Chalopin, Domitille, Smith, Jeramiah J., Robinson, Mark, Dorrington, Rosemary A., Gerdol, Marco, Aken, Bronwen, Assunta Biscotti, Maria, Barucca, Marco, Baurain, Denis, Berlin, Aaron M., Blatch, Gregory L., Buonocore, Francesco, Burmester, Thorsten, Campbell, Michael S., Canapa, Adriana, Cannon, John P., Christoffels, Alan, De Moro, Gianluca, Edkins, Adrienne L., Fan, Lin, Fausto, Anna Maria, Feiner, Nathalie, Forconi, Mariko, Gamieldien, Junaid, Gnerre, Sante, Gnirke, Andreas, Goldstone, Jared V., Haerty, Wilfried, Hahn, Mark E., Hesse, Uljana, Hoffmann, Steve, Johnson, Jeremy, Karchner, Sibel I., Kuraku, Shigehiro, Lara, Marcia, Levin, Joshua Z., Litman, Gary W., Mauceli, Evan, Miyake, Tsutomu, Mueller, M. Gail, Nelson, David R., Nitsche, Anne, Olmo, Ettore, Ota, Tatsuya, Pallavicini, Alberto, Panji, Sumir, Picone, Barbara, Ponting, Chris P., Prohaska, Sonja J., Przybylski, Dariusz, Ratan Saha, Nil, Ravi, Vydianathan, Ribeiro, Filipe J., Sauka-Spengler, Tatjana, Scapigliati, Giuseppe, Searle, Stephen M. J., Sharpe, Ted, Simakov, Oleg, Stadler, Peter F., Stegeman, John J., Sumiyama, Kenta, Tabbaa, Diana, Tafer, Hakim, Turner-Maier, Jason, van Heusden, Peter, White, Simon, Williams, Louise, Yandell, Mark, Brinkmann, Henner, Volff, Jean-Nicolas, Tabin, Clifford J., Shubin, Neil, Schartl, Manfred, Jaffe, David B., Postlethwait, John H., Venkatesh, Byrappa, Di Palma, Federica, Lander, Eric S., Meyer, Axel, Lindblad-Toh, Kerstin, Amemiya, Chris T., Alfoldi, Jessica, Lee, Alison P., Fan, Shaohua, Philippe, Herve, MacCallum, Iain, Braasch, Ingo, Manousaki, Tereza, Schneider, Igor, Rohner, Nicolas, Organ, Chris, Chalopin, Domitille, Smith, Jeramiah J., Robinson, Mark, Dorrington, Rosemary A., Gerdol, Marco, Aken, Bronwen, Assunta Biscotti, Maria, Barucca, Marco, Baurain, Denis, Berlin, Aaron M., Blatch, Gregory L., Buonocore, Francesco, Burmester, Thorsten, Campbell, Michael S., Canapa, Adriana, Cannon, John P., Christoffels, Alan, De Moro, Gianluca, Edkins, Adrienne L., Fan, Lin, Fausto, Anna Maria, Feiner, Nathalie, Forconi, Mariko, Gamieldien, Junaid, Gnerre, Sante, Gnirke, Andreas, Goldstone, Jared V., Haerty, Wilfried, Hahn, Mark E., Hesse, Uljana, Hoffmann, Steve, Johnson, Jeremy, Karchner, Sibel I., Kuraku, Shigehiro, Lara, Marcia, Levin, Joshua Z., Litman, Gary W., Mauceli, Evan, Miyake, Tsutomu, Mueller, M. Gail, Nelson, David R., Nitsche, Anne, Olmo, Ettore, Ota, Tatsuya, Pallavicini, Alberto, Panji, Sumir, Picone, Barbara, Ponting, Chris P., Prohaska, Sonja J., Przybylski, Dariusz, Ratan Saha, Nil, Ravi, Vydianathan, Ribeiro, Filipe J., Sauka-Spengler, Tatjana, Scapigliati, Giuseppe, Searle, Stephen M. J., Sharpe, Ted, Simakov, Oleg, Stadler, Peter F., Stegeman, John J., Sumiyama, Kenta, Tabbaa, Diana, Tafer, Hakim, Turner-Maier, Jason, van Heusden, Peter, White, Simon, Williams, Louise, Yandell, Mark, Brinkmann, Henner, Volff, Jean-Nicolas, Tabin, Clifford J., Shubin, Neil, Schartl, Manfred, Jaffe, David B., Postlethwait, John H., Venkatesh, Byrappa, Di Palma, Federica, Lander, Eric S., Meyer, Axel, and Lindblad-Toh, Kerstin

Abstract

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature 496 (2013): 311-316, doi:10.1038/nature12027., The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution., cquisition and storage of Latimeria chalumnae samples was supported by grants from the African Coelacanth Ecosystem Programme of the South African National Department of Science and Technology. Generation of the Latimeria chalumnae and Protopterus annectens sequences by the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University was supported by grants from the National Human Genome Research Institute (NHGRI). K.L.T. is the recipient of a EURYI award from the European Science Foundation.

Published
2013

44. The African coelacanth genome provides insights into tetrapod evolution

Author

Amemiya, Chris T., Alfoldi, Jessica, Lee, Alison P., Fan, Shaohua, Philippe, Herve, MacCallum, Iain, Braasch, Ingo, Manousaki, Tereza, Schneider, Igor, Rohner, Nicolas, Organ, Chris, Chalopin, Domitille, Smith, Jeramiah J., Robinson, Mark, Dorrington, Rosemary A., Gerdol, Marco, Aken, Bronwen, Assunta Biscotti, Maria, Barucca, Marco, Baurain, Denis, Berlin, Aaron M., Blatch, Gregory L., Buonocore, Francesco, Burmester, Thorsten, Campbell, Michael S., Canapa, Adriana, Cannon, John P., Christoffels, Alan, De Moro, Gianluca, Edkins, Adrienne L., Fan, Lin, Fausto, Anna Maria, Feiner, Nathalie, Forconi, Mariko, Gamieldien, Junaid, Gnerre, Sante, Gnirke, Andreas, Goldstone, Jared V., Haerty, Wilfried, Hahn, Mark E., Hesse, Uljana, Hoffmann, Steve, Johnson, Jeremy, Karchner, Sibel I., Kuraku, Shigehiro, Lara, Marcia, Levin, Joshua Z., Litman, Gary W., Mauceli, Evan, Miyake, Tsutomu, Mueller, M. Gail, Nelson, David R., Nitsche, Anne, Olmo, Ettore, Ota, Tatsuya, Pallavicini, Alberto, Panji, Sumir, Picone, Barbara, Ponting, Chris P., Prohaska, Sonja J., Przybylski, Dariusz, Ratan Saha, Nil, Ravi, Vydianathan, Ribeiro, Filipe J., Sauka-Spengler, Tatjana, Scapigliati, Giuseppe, Searle, Stephen M. J., Sharpe, Ted, Simakov, Oleg, Stadler, Peter F., Stegeman, John J., Sumiyama, Kenta, Tabbaa, Diana, Tafer, Hakim, Turner-Maier, Jason, van Heusden, Peter, White, Simon, Williams, Louise, Yandell, Mark, Brinkmann, Henner, Volff, Jean-Nicolas, Tabin, Clifford J., Shubin, Neil, Schartl, Manfred, Jaffe, David B., Postlethwait, John H., Venkatesh, Byrappa, Di Palma, Federica, Lander, Eric S., Meyer, Axel, Lindblad-Toh, Kerstin, Amemiya, Chris T., Alfoldi, Jessica, Lee, Alison P., Fan, Shaohua, Philippe, Herve, MacCallum, Iain, Braasch, Ingo, Manousaki, Tereza, Schneider, Igor, Rohner, Nicolas, Organ, Chris, Chalopin, Domitille, Smith, Jeramiah J., Robinson, Mark, Dorrington, Rosemary A., Gerdol, Marco, Aken, Bronwen, Assunta Biscotti, Maria, Barucca, Marco, Baurain, Denis, Berlin, Aaron M., Blatch, Gregory L., Buonocore, Francesco, Burmester, Thorsten, Campbell, Michael S., Canapa, Adriana, Cannon, John P., Christoffels, Alan, De Moro, Gianluca, Edkins, Adrienne L., Fan, Lin, Fausto, Anna Maria, Feiner, Nathalie, Forconi, Mariko, Gamieldien, Junaid, Gnerre, Sante, Gnirke, Andreas, Goldstone, Jared V., Haerty, Wilfried, Hahn, Mark E., Hesse, Uljana, Hoffmann, Steve, Johnson, Jeremy, Karchner, Sibel I., Kuraku, Shigehiro, Lara, Marcia, Levin, Joshua Z., Litman, Gary W., Mauceli, Evan, Miyake, Tsutomu, Mueller, M. Gail, Nelson, David R., Nitsche, Anne, Olmo, Ettore, Ota, Tatsuya, Pallavicini, Alberto, Panji, Sumir, Picone, Barbara, Ponting, Chris P., Prohaska, Sonja J., Przybylski, Dariusz, Ratan Saha, Nil, Ravi, Vydianathan, Ribeiro, Filipe J., Sauka-Spengler, Tatjana, Scapigliati, Giuseppe, Searle, Stephen M. J., Sharpe, Ted, Simakov, Oleg, Stadler, Peter F., Stegeman, John J., Sumiyama, Kenta, Tabbaa, Diana, Tafer, Hakim, Turner-Maier, Jason, van Heusden, Peter, White, Simon, Williams, Louise, Yandell, Mark, Brinkmann, Henner, Volff, Jean-Nicolas, Tabin, Clifford J., Shubin, Neil, Schartl, Manfred, Jaffe, David B., Postlethwait, John H., Venkatesh, Byrappa, Di Palma, Federica, Lander, Eric S., Meyer, Axel, and Lindblad-Toh, Kerstin

Abstract

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature 496 (2013): 311-316, doi:10.1038/nature12027., The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution., cquisition and storage of Latimeria chalumnae samples was supported by grants from the African Coelacanth Ecosystem Programme of the South African National Department of Science and Technology. Generation of the Latimeria chalumnae and Protopterus annectens sequences by the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University was supported by grants from the National Human Genome Research Institute (NHGRI). K.L.T. is the recipient of a EURYI award from the European Science Foundation.

Published
2013

45. Project X: Physics Opportunities

Author

Kronfeld, Andreas S., Tschirhart, Robert S., Al-Binni, Usama, Altmannshofer, Wolfgang, Ankenbrandt, Charles, Babu, Kaladi, Banerjee, Sunanda, Bass, Matthew, Batell, Brian, Baxter, David V., Berezhiani, Zurab, Bergevin, Marc, Bernstein, Robert, Bhattacharya, Sudeb, Bishai, Mary, Blum, Thomas, Bogacz, S. Alex, Brice, Stephen J., Brod, Joachim, Bross, Alan, Buchoff, Michael, Burgess, Thomas W., Carena, Marcela, Castellanos, Luis A., Chattopadhyay, Subhasis, Chen, Mu-Chun, Cherdack, Daniel, Christ, Norman H., Chupp, Tim, Cirigliano, Vincenzo, Coloma, Pilar, Coppola, Christopher E., Cowsik, Ramanath, Crabtree, J. Allen, de Gouvêa, André, Delahaye, Jean-Pierre, Denisov, Dmitri, deNiverville, Patrick, Dharmapalan, Ranjan, Diefenthaler, Markus, Dolgov, Alexander, Dvali, Georgi, Eichten, Estia, Engelfried, Jürgen, Ferguson, Phillip D., Gabriel, Tony, Gal, Avraham, Gallmeier, Franz, Ganezer, Kenneth S., Gardner, Susan, Glenzinski, Douglas, Godfrey, Stephen, Golubeva, Elena S., Gori, Stefania, Graves, Van B., Greene, Geoffrey, Griffard, Cory L., Haisch, Ulrich, Handler, Thomas, Hartfiel, Brandon, Hatzikoutelis, Athanasios, Hawari, Ayman, Heilbronn, Lawrence, Hill, James E., Huber, Patrick, Jaffe, David E., Jiang, Xiaodong, Johnson, Christian, Kamyshkov, Yuri, Kaplan, Daniel M., Kerbikov, Boris, Kiburg, Brendan, Kirk, Harold G., Klein, Andreas, Knoepfel, Kyle, Kopeliovich, Boris, Kopeliovich, Vladimir, Kopp, Joachim, Korsch, Wolfgang, Kribs, Graham, Lipton, Ronald, Liu, Chen-Yu, Lorenzon, Wolfgang, Lu, Zheng-Tian, Makins, Naomi C. R., McKeen, David, Mills, Geoffrey, Mocko, Michael, Mohapatra, Rabindra, Mokhov, Nikolai V., Muhrer, Guenter, Mumm, Pieter, Neuffer, David, Okun, Lev, Palmer, Mark A., Palmer, Robert, Pattie Jr., Robert W., Phillips II, David G., Pitts, Kevin, Pospelov, Maxim, Pronskikh, Vitaly S., Quigg, Chris, Ramberg, Erik, Ray, Amlan, Reimer, Paul E., Richards, David G., Ritz, Adam, Roy, Amit, Ruggles, Arthur, Ryne, Robert, Sarkar, Utpal, Saunders, Andy, Semertzidis, Yannis K., Serebrov, Anatoly, Shimizu, Hirohiko, Shrock, Robert, Sikdar, Arindam K., Snopok, Pavel V., Snow, William M., Soha, Aria, Spanier, Stefan, Striganov, Sergei, Tang, Zhaowen, Townsend, Lawrence, Urheim, Jon, Vainshtein, Arkady, Van de Water, Richard, Van de Water, Ruth S., Van Kooten, Richard J., Wehring, Bernard, Wester III, William C., Whitehead, Lisa, Wilson, Robert J., Worcester, Elizabeth, Young, Albert R., Zeller, Geralyn, Kronfeld, Andreas S., Tschirhart, Robert S., Al-Binni, Usama, Altmannshofer, Wolfgang, Ankenbrandt, Charles, Babu, Kaladi, Banerjee, Sunanda, Bass, Matthew, Batell, Brian, Baxter, David V., Berezhiani, Zurab, Bergevin, Marc, Bernstein, Robert, Bhattacharya, Sudeb, Bishai, Mary, Blum, Thomas, Bogacz, S. Alex, Brice, Stephen J., Brod, Joachim, Bross, Alan, Buchoff, Michael, Burgess, Thomas W., Carena, Marcela, Castellanos, Luis A., Chattopadhyay, Subhasis, Chen, Mu-Chun, Cherdack, Daniel, Christ, Norman H., Chupp, Tim, Cirigliano, Vincenzo, Coloma, Pilar, Coppola, Christopher E., Cowsik, Ramanath, Crabtree, J. Allen, de Gouvêa, André, Delahaye, Jean-Pierre, Denisov, Dmitri, deNiverville, Patrick, Dharmapalan, Ranjan, Diefenthaler, Markus, Dolgov, Alexander, Dvali, Georgi, Eichten, Estia, Engelfried, Jürgen, Ferguson, Phillip D., Gabriel, Tony, Gal, Avraham, Gallmeier, Franz, Ganezer, Kenneth S., Gardner, Susan, Glenzinski, Douglas, Godfrey, Stephen, Golubeva, Elena S., Gori, Stefania, Graves, Van B., Greene, Geoffrey, Griffard, Cory L., Haisch, Ulrich, Handler, Thomas, Hartfiel, Brandon, Hatzikoutelis, Athanasios, Hawari, Ayman, Heilbronn, Lawrence, Hill, James E., Huber, Patrick, Jaffe, David E., Jiang, Xiaodong, Johnson, Christian, Kamyshkov, Yuri, Kaplan, Daniel M., Kerbikov, Boris, Kiburg, Brendan, Kirk, Harold G., Klein, Andreas, Knoepfel, Kyle, Kopeliovich, Boris, Kopeliovich, Vladimir, Kopp, Joachim, Korsch, Wolfgang, Kribs, Graham, Lipton, Ronald, Liu, Chen-Yu, Lorenzon, Wolfgang, Lu, Zheng-Tian, Makins, Naomi C. R., McKeen, David, Mills, Geoffrey, Mocko, Michael, Mohapatra, Rabindra, Mokhov, Nikolai V., Muhrer, Guenter, Mumm, Pieter, Neuffer, David, Okun, Lev, Palmer, Mark A., Palmer, Robert, Pattie Jr., Robert W., Phillips II, David G., Pitts, Kevin, Pospelov, Maxim, Pronskikh, Vitaly S., Quigg, Chris, Ramberg, Erik, Ray, Amlan, Reimer, Paul E., Richards, David G., Ritz, Adam, Roy, Amit, Ruggles, Arthur, Ryne, Robert, Sarkar, Utpal, Saunders, Andy, Semertzidis, Yannis K., Serebrov, Anatoly, Shimizu, Hirohiko, Shrock, Robert, Sikdar, Arindam K., Snopok, Pavel V., Snow, William M., Soha, Aria, Spanier, Stefan, Striganov, Sergei, Tang, Zhaowen, Townsend, Lawrence, Urheim, Jon, Vainshtein, Arkady, Van de Water, Richard, Van de Water, Ruth S., Van Kooten, Richard J., Wehring, Bernard, Wester III, William C., Whitehead, Lisa, Wilson, Robert J., Worcester, Elizabeth, Young, Albert R., and Zeller, Geralyn

Abstract

Part 2 of "Project X: Accelerator Reference Design, Physics Opportunities, Broader Impacts". In this Part, we outline the particle-physics program that can be achieved with Project X, a staged superconducting linac for intensity-frontier particle physics. Topics include neutrino physics, kaon physics, muon physics, electric dipole moments, neutron-antineutron oscillations, new light particles, hadron structure, hadron spectroscopy, and lattice-QCD calculations. Part 1 is available as arXiv:1306.5022 [physics.acc-ph] and Part 3 is available as arXiv:1306.5024 [physics.acc-ph]., Comment: 209 pp. with many figures; prepared in part for the DPF Community Summer Study; v2 corrects typos (including one author surname), adds an author, and conforms with the version being printed; v3 includes two more chapter authors in full list at the top

Published
2013

46. Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Author

Bradnam, Keith R, Bradnam, Keith R, Fass, Joseph N, Alexandrov, Anton, Baranay, Paul, Bechner, Michael, Birol, Inanç, Boisvert, Sébastien, Chapman, Jarrod A, Chapuis, Guillaume, Chikhi, Rayan, Chitsaz, Hamidreza, Chou, Wen-Chi, Corbeil, Jacques, Del Fabbro, Cristian, Docking, T, Durbin, Richard, Earl, Dent, Emrich, Scott, Fedotov, Pavel, Fonseca, Nuno A, Ganapathy, Ganeshkumar, Gibbs, Richard A, Gnerre, Sante, Godzaridis, Élénie, Goldstein, Steve, Haimel, Matthias, Hall, Giles, Haussler, David, Hiatt, Joseph B, Ho, Isaac Y, Howard, Jason, Hunt, Martin, Jackman, Shaun D, Jaffe, David B, Jarvis, Erich D, Jiang, Huaiyang, Kazakov, Sergey, Kersey, Paul J, Kitzman, Jacob O, Knight, James R, Koren, Sergey, Lam, Tak-Wah, Lavenier, Dominique, Laviolette, François, Li, Yingrui, Li, Zhenyu, Liu, Binghang, Liu, Yue, Luo, Ruibang, MacCallum, Iain, MacManes, Matthew D, Maillet, Nicolas, Melnikov, Sergey, Naquin, Delphine, Ning, Zemin, Otto, Thomas D, Paten, Benedict, Paulo, Octávio S, Phillippy, Adam M, Pina-Martins, Francisco, Place, Michael, Przybylski, Dariusz, Qin, Xiang, Qu, Carson, Ribeiro, Filipe J, Richards, Stephen, Rokhsar, Daniel S, Ruby, J, Scalabrin, Simone, Schatz, Michael C, Schwartz, David C, Sergushichev, Alexey, Sharpe, Ted, Shaw, Timothy I, Shendure, Jay, Shi, Yujian, Simpson, Jared T, Song, Henry, Tsarev, Fedor, Vezzi, Francesco, Vicedomini, Riccardo, Vieira, Bruno M, Wang, Jun, Worley, Kim C, Yin, Shuangye, Yiu, Siu-Ming, Yuan, Jianying, Zhang, Guojie, Zhang, Hao, Zhou, Shiguo, Korf, Ian F, Bradnam, Keith R, Bradnam, Keith R, Fass, Joseph N, Alexandrov, Anton, Baranay, Paul, Bechner, Michael, Birol, Inanç, Boisvert, Sébastien, Chapman, Jarrod A, Chapuis, Guillaume, Chikhi, Rayan, Chitsaz, Hamidreza, Chou, Wen-Chi, Corbeil, Jacques, Del Fabbro, Cristian, Docking, T, Durbin, Richard, Earl, Dent, Emrich, Scott, Fedotov, Pavel, Fonseca, Nuno A, Ganapathy, Ganeshkumar, Gibbs, Richard A, Gnerre, Sante, Godzaridis, Élénie, Goldstein, Steve, Haimel, Matthias, Hall, Giles, Haussler, David, Hiatt, Joseph B, Ho, Isaac Y, Howard, Jason, Hunt, Martin, Jackman, Shaun D, Jaffe, David B, Jarvis, Erich D, Jiang, Huaiyang, Kazakov, Sergey, Kersey, Paul J, Kitzman, Jacob O, Knight, James R, Koren, Sergey, Lam, Tak-Wah, Lavenier, Dominique, Laviolette, François, Li, Yingrui, Li, Zhenyu, Liu, Binghang, Liu, Yue, Luo, Ruibang, MacCallum, Iain, MacManes, Matthew D, Maillet, Nicolas, Melnikov, Sergey, Naquin, Delphine, Ning, Zemin, Otto, Thomas D, Paten, Benedict, Paulo, Octávio S, Phillippy, Adam M, Pina-Martins, Francisco, Place, Michael, Przybylski, Dariusz, Qin, Xiang, Qu, Carson, Ribeiro, Filipe J, Richards, Stephen, Rokhsar, Daniel S, Ruby, J, Scalabrin, Simone, Schatz, Michael C, Schwartz, David C, Sergushichev, Alexey, Sharpe, Ted, Shaw, Timothy I, Shendure, Jay, Shi, Yujian, Simpson, Jared T, Song, Henry, Tsarev, Fedor, Vezzi, Francesco, Vicedomini, Riccardo, Vieira, Bruno M, Wang, Jun, Worley, Kim C, Yin, Shuangye, Yiu, Siu-Ming, Yuan, Jianying, Zhang, Guojie, Zhang, Hao, Zhou, Shiguo, and Korf, Ian F

Abstract

Background The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.

Published
2013

47. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing.

Author

Kirby, Andrew, Kirby, Andrew, Gnirke, Andreas, Jaffe, David B, Barešová, Veronika, Pochet, Nathalie, Blumenstiel, Brendan, Ye, Chun, Aird, Daniel, Stevens, Christine, Robinson, James T, Cabili, Moran N, Gat-Viks, Irit, Kelliher, Edward, Daza, Riza, DeFelice, Matthew, Hůlková, Helena, Sovová, Jana, Vylet'al, Petr, Antignac, Corinne, Guttman, Mitchell, Handsaker, Robert E, Perrin, Danielle, Steelman, Scott, Sigurdsson, Snaevar, Scheinman, Steven J, Sougnez, Carrie, Cibulskis, Kristian, Parkin, Melissa, Green, Todd, Rossin, Elizabeth, Zody, Michael C, Xavier, Ramnik J, Pollak, Martin R, Alper, Seth L, Lindblad-Toh, Kerstin, Gabriel, Stacey, Hart, P Suzanne, Regev, Aviv, Nusbaum, Chad, Kmoch, Stanislav, Bleyer, Anthony J, Lander, Eric S, Daly, Mark J, Kirby, Andrew, Kirby, Andrew, Gnirke, Andreas, Jaffe, David B, Barešová, Veronika, Pochet, Nathalie, Blumenstiel, Brendan, Ye, Chun, Aird, Daniel, Stevens, Christine, Robinson, James T, Cabili, Moran N, Gat-Viks, Irit, Kelliher, Edward, Daza, Riza, DeFelice, Matthew, Hůlková, Helena, Sovová, Jana, Vylet'al, Petr, Antignac, Corinne, Guttman, Mitchell, Handsaker, Robert E, Perrin, Danielle, Steelman, Scott, Sigurdsson, Snaevar, Scheinman, Steven J, Sougnez, Carrie, Cibulskis, Kristian, Parkin, Melissa, Green, Todd, Rossin, Elizabeth, Zody, Michael C, Xavier, Ramnik J, Pollak, Martin R, Alper, Seth L, Lindblad-Toh, Kerstin, Gabriel, Stacey, Hart, P Suzanne, Regev, Aviv, Nusbaum, Chad, Kmoch, Stanislav, Bleyer, Anthony J, Lander, Eric S, and Daly, Mark J

Abstract

Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (∼1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.

Published
2013

48. The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

Author

LBNE Collaboration, Adams, Corey, Adams, David, Akiri, Tarek, Alion, Tyler, Anderson, Kris, Andreopoulos, Costas, Andrews, Mike, Anghel, Ioana, Anjos, João Carlos Costa dos, Antonello, Maddalena, Arrieta-Diaz, Enrique, Artuso, Marina, Asaadi, Jonathan, Bai, Xinhua, Baibussinov, Bagdat, Baird, Michael, Balantekin, Baha, Baller, Bruce, Baptista, Brian, Barker, D'Ann, Barker, Gary, Barletta, William A., Barr, Giles, Bartoszek, Larry, Bashyal, Amit, Bass, Matt, Bellini, Vincenzo, Benetti, Pietro Angelo, Berger, Bruce E., Bergevin, Marc, Berman, Eileen, Berns, Hans-Gerd, Bernstein, Adam, Bernstein, Robert, Bhandari, Babu, Bhatnagar, Vipin, Bhuyan, Bipul, Bian, Jianming, Bishai, Mary, Blake, Andrew, Blaszczyk, Flor, Blaufuss, Erik, Bleakley, Bruce, Blucher, Edward, Blusk, Steve, Bocean, Virgil, Boffelli, F., Boissevain, Jan, Bolton, Timothy, Bonesini, Maurizio, Boyd, Steve, Brandt, Andrew, Breedon, Richard, Bromberg, Carl, Brown, Ralph, Brunetti, Giullia, Buchanan, Norman, Bugg, Bill, Busenitz, Jerome, Calligarich, E., Camilleri, Leslie, Carminati, Giada, Carr, Rachel, Castromonte, Cesar, Cavanna, Flavio, Centro, Sandro, Chen, Alex, Chen, Hucheng, Chen, Kai, Cherdack, Daniel, Chi, Cheng-Yi, Childress, Sam, Choudhary, Brajesh Chandra, Christodoulou, Georgios, Christofferson, Cabot-Ann, Church, Eric, Cline, David, Coan, Thomas, Cocco, Alfredo, Coelho, Joao, Coleman, Stephen, Conrad, Janet M., Convery, Mark, Corey, Robert, Corwin, Luke, Cranshaw, Jack, Cronin-Hennessy, Daniel, Curioni, A., da Motta, Helio, Davenne, Tristan, Davies, Gavin S., Dazeley, Steven, De, Kaushik, de Gouvea, Andre, de Jong, Jeffrey K., Demuth, David, Densham, Chris, Diwan, Milind, Djurcic, Zelimir, Dolfini, R., Dolph, Jeffrey, Drake, Gary, Dye, Stephen, Dyuang, Hongue, Edmunds, Daniel, Elliott, Steven, Elnimr, Muhammad, Eno, Sarah, Enomoto, Sanshiro, Escobar, Carlos O., Evans, Justin, Falcone, A., Falk, Lisa, Farbin, Amir, Farnese, Christian, Fava, Angela, Felde, John, Fernandes, S., Ferroni, Fernando, Feyzi, Farshid, Fields, Laura, Finch, Alex, Fitton, Mike, Fleming, Bonnie, Fowler, Jack, Fox, Walt, Friedland, Alex, Fuess, Stu, Fujikawa, Brian, Gallagher, Hugh, Gandhi, Raj, Garvey, Gerald, Gehman, Victor M., de Geronimo, Gianluigi, Gibin, Daniele, Gill, Ronald, Gomes, Ricardo A., Goodman, Maury C., Goon, Jason, Graf, Nicholas, Graham, Mathew, Gran, Rik, Grant, Christopher, Grant, Nick, Greenlee, Herbert, Greenler, Leland, Grullon, Sean, Guardincerri, Elena, Guarino, Victor, Guarnaccia, Evan, Guedes, Germano, Guenette, Roxanne, Guglielmi, Alberto, Guzzo, Marcelo M., Habig, Alec T., Hackenburg, Robert W., Hadavand, Haleh, Hahn, Alan, Haigh, Martin, Haines, Todd, Handler, Thomas, Hans, Sunej, Hartnell, Jeff, Harton, John, Hatcher, Robert, Hatzikoutelis, Athans, Hays, Steven, Hazen, Eric, Headley, Mike, Heavey, Anne, Heeger, Karsten, Heise, Jaret, Hellauer, Robert, Hewes, V, Himmel, Alexander, Hogan, Matthew, Holanda, Pedro, Holin, Anna, Horton-Smith, Glenn, Howell, Joe, Hurh, Patrick, Huston, Joey, Hylen, James, Imlay, Richard, Insler, Jonathan, Introzzi, G., Isvan, Zeynep, Jackson, Chris, Jacobsen, John, Jaffe, David E., James, Cat, Jen, Chun-Min, Johnson, Marvin, Johnson, Randy, Johnson, Robert, Johnson, Scott, Johnston, William, Johnstone, John, Jones, Ben J. P., Jostlein, H., Junk, Thomas, Kadel, Richard, Kaess, Karl, Karagiorgi, Georgia, Kaspar, Jarek, Katori, Teppei, Kayser, Boris, Kearns, Edward, Keener, Paul, Kemp, Ernesto, Kettell, Steve H., Kirby, Mike, Klein, Joshua, Koizumi, Gordon, Kopp, Sacha, Kormos, Laura, Kropp, William, Kudryavtsev, Vitaly A., Kumar, Ashok, Kumar, Jason, Kutter, Thomas, La Zia, Franco, Lande, Kenneth, Lane, Charles, Lang, Karol, Lanni, Francesco, Lanza, Richard, Latorre, Tony, Learned, John, Lee, David, Lee, Kevin, Li, Qizhong, Li, Shaorui, Li, Yichen, Li, Zepeng, Libo, Jiang, Linden, Steve, Ling, Jiajie, Link, Jonathan, Littenberg, Laurence, Liu, Hu, Liu, Qiuguang, Liu, Tiankuan, Losecco, John, Louis, William, Lundberg, Byron, Lundin, Tracy, Lundy, Jay, Machado, Ana Amelia, Maesano, Cara, Magill, Steve, Mahler, George, Malon, David, Malys, Stephen, Mammoliti, Francesco, Mandal, Samit Kumar, Mann, Anthony, Mantsch, Paul, Marchionni, Alberto, Marciano, William, Mariani, Camillo, Maricic, Jelena, Marino, Alysia, Marshak, Marvin, Marshall, John, Matsuno, Shiegenobu, Mauger, Christopher, Mavrokoridis, Konstantinos, Mayer, Nate, McCauley, Neil, McCluskey, Elaine, McDonald, Kirk, McFarland, Kevin, McKee, David, McKeown, Robert, McTaggart, Robert, Mehdiyev, Rashid, Mei, Dongming, Menegolli, A., Meng, Guang, Meng, Yixiong, Mertins, David, Messier, Mark, Metcalf, William, Milincic, Radovan, Miller, William, Mills, Geoff, Mishra, Sanjib R., Mokhov, Nikolai, Montanari, Claudio, Montanari, David, Moore, Craig, Morfin, Jorge, Morgan, Ben, Morse, William, Moss, Zander, Moura, Célio A., Mufson, Stuart, Muller, David, Musser, Jim, Naples, Donna, Napolitano, Jim, Newcomer, Mitch, Nichol, Ryan, Nicholls, Tim, Niner, Evan, Norris, Barry, Nowak, Jaroslaw, O'Keeffe, Helen, Oliveira, Roberto, Olson, Travis, Page, Brian, Pakvasa, Sandip, Palamara, Ornella, Paley, Jon, Paolone, Vittorio, Papadimitriou, Vaia, Park, Seongtae, Parsa, Zohreh, Partyka, Kinga, Paulos, Bob, Pavlovic, Zarko, Peeters, Simon, Perch, Andy, Perkin, Jon D., Petti, Roberto, Petukhov, Andre, Pietropaolo, Francesco, Plunkett, Robert, Polly, Chris, Pordes, Stephen, Potekhin, Maxim, Potenza, Renato, Prakash, Arati, Prokofiev, Oleg, Qian, Xin, Raaf, Jennifer L., Radeka, Veljko, Rakhno, Igor, Ramachers, Yorck, Rameika, Regina, Ramsey, John, Rappoldi, A., Raselli, G. L., Ratoff, Peter, Ravindra, Shreyas, Rebel, Brian, Reichenbacher, Juergen, Reitzner, Dianne, Rescia, Sergio, Richardson, Martin, Rielage, Kieth, Riesselmann, Kurt, Robinson, Matt, Rochester, Leon, Ronquest, Michael, Rosen, Marc, Rossella, M., Rubbia, Carlo, Rucinski, Russ, Sahijpal, Sandeep, Sahoo, Himansu, Sala, Paola, Salmiera, Delia, Samios, Nicholas, Sanchez, Mayly, Scaramelli, Alberto, Schellman, Heidi, Schmitt, Richard, Schmitz, David, Schneps, Jack, Scholberg, Kate, Segreto, Ettore, Seibert, Stanley, Sexton-Kennedy, Liz, Shaevitz, Mike, Shanahan, Peter, Sharma, Rahul, Shaw, Terri, Simos, Nikolaos, Singh, Venktesh, Sinnis, Gus, Sippach, William, Skwarnicki, Tomasz, Smy, Michael, Sobel, Henry, Soderberg, Mitch, Sondericker, John, Sondheim, Walter, Sousa, Alexandre, Spooner, Neil J. C., Stancari, Michelle, Stancu, Ion, Stefan, Dorota, Stefanik, Andy, Stewart, James, Stone, Sheldon, Strait, James, Strait, Matthew, Striganov, Sergei, Sullivan, Gregory, Sun, Yujing, Suter, Louise, Svenson, Andrew, Svoboda, Robert, Szczerbinska, Barbara, Szelc, Andrzej, Szydagis, Matthew, Söldner-Rembold, Stefan, Talaga, Richard, Tamsett, Matthew, Tariq, Salman, Tayloe, Rex, Taylor, Charles, Taylor, David, Teymourian, Artin, Themann, Harry, Thiesse, Matthew, Thomas, Jenny, Thompson, Lee F., Thomson, Mark, Thorn, Craig, Thorpe, Matt, Tian, Xinchun, Tiedt, Doug, Toki, Walter, Tolich, Nikolai, Torti, M., Toups, Matt, Touramanis, Christos, Tripathi, Mani, Tropin, Igor, Tsai, Yun-Tse, Tull, Craig, Tzanov, Martin, Urheim, Jon, Usman, Shawn, Vagins, Mark, Valdiviesso, Gustavo, Van Berg, Rick, Van de Water, Richard, Van Gemmeren, Peter, Varanini, Filippo, Varner, Gary, Vaziri, Kamran, Velev, Gueorgui, Ventura, Sandro, Vignoli, Chiara, Viren, Brett, Wahl, Dan, Waldron, Abby, Walter, Christopher W., Wang, Hanguo, Wang, Wei, Warburton, Karl, Warner, David, Wasserman, Ryan, Watson, Blake, Weber, Alfons, Wei, Wenzhao, Wells, Douglas, Wetstein, Matthew, White, Andy, White, Hywel, Whitehead, Lisa, Whittington, Denver, Willhite, Joshua, Wilson, Robert J., Winslow, Lindley, Wood, Kevin, Worcester, Elizabeth, Worcester, Matthew, Xin, Tian, Yarritu, Kevin, Ye, Jingbo, Yeh, Minfang, Yu, Bo, Yu, Jae, Yuan, Tianlu, Zani, A., Zeller, Geralyn P., Zhang, Chao, Zimmerman, Eric D., Zwaska, Robert, LBNE Collaboration, Adams, Corey, Adams, David, Akiri, Tarek, Alion, Tyler, Anderson, Kris, Andreopoulos, Costas, Andrews, Mike, Anghel, Ioana, Anjos, João Carlos Costa dos, Antonello, Maddalena, Arrieta-Diaz, Enrique, Artuso, Marina, Asaadi, Jonathan, Bai, Xinhua, Baibussinov, Bagdat, Baird, Michael, Balantekin, Baha, Baller, Bruce, Baptista, Brian, Barker, D'Ann, Barker, Gary, Barletta, William A., Barr, Giles, Bartoszek, Larry, Bashyal, Amit, Bass, Matt, Bellini, Vincenzo, Benetti, Pietro Angelo, Berger, Bruce E., Bergevin, Marc, Berman, Eileen, Berns, Hans-Gerd, Bernstein, Adam, Bernstein, Robert, Bhandari, Babu, Bhatnagar, Vipin, Bhuyan, Bipul, Bian, Jianming, Bishai, Mary, Blake, Andrew, Blaszczyk, Flor, Blaufuss, Erik, Bleakley, Bruce, Blucher, Edward, Blusk, Steve, Bocean, Virgil, Boffelli, F., Boissevain, Jan, Bolton, Timothy, Bonesini, Maurizio, Boyd, Steve, Brandt, Andrew, Breedon, Richard, Bromberg, Carl, Brown, Ralph, Brunetti, Giullia, Buchanan, Norman, Bugg, Bill, Busenitz, Jerome, Calligarich, E., Camilleri, Leslie, Carminati, Giada, Carr, Rachel, Castromonte, Cesar, Cavanna, Flavio, Centro, Sandro, Chen, Alex, Chen, Hucheng, Chen, Kai, Cherdack, Daniel, Chi, Cheng-Yi, Childress, Sam, Choudhary, Brajesh Chandra, Christodoulou, Georgios, Christofferson, Cabot-Ann, Church, Eric, Cline, David, Coan, Thomas, Cocco, Alfredo, Coelho, Joao, Coleman, Stephen, Conrad, Janet M., Convery, Mark, Corey, Robert, Corwin, Luke, Cranshaw, Jack, Cronin-Hennessy, Daniel, Curioni, A., da Motta, Helio, Davenne, Tristan, Davies, Gavin S., Dazeley, Steven, De, Kaushik, de Gouvea, Andre, de Jong, Jeffrey K., Demuth, David, Densham, Chris, Diwan, Milind, Djurcic, Zelimir, Dolfini, R., Dolph, Jeffrey, Drake, Gary, Dye, Stephen, Dyuang, Hongue, Edmunds, Daniel, Elliott, Steven, Elnimr, Muhammad, Eno, Sarah, Enomoto, Sanshiro, Escobar, Carlos O., Evans, Justin, Falcone, A., Falk, Lisa, Farbin, Amir, Farnese, Christian, Fava, Angela, Felde, John, Fernandes, S., Ferroni, Fernando, Feyzi, Farshid, Fields, Laura, Finch, Alex, Fitton, Mike, Fleming, Bonnie, Fowler, Jack, Fox, Walt, Friedland, Alex, Fuess, Stu, Fujikawa, Brian, Gallagher, Hugh, Gandhi, Raj, Garvey, Gerald, Gehman, Victor M., de Geronimo, Gianluigi, Gibin, Daniele, Gill, Ronald, Gomes, Ricardo A., Goodman, Maury C., Goon, Jason, Graf, Nicholas, Graham, Mathew, Gran, Rik, Grant, Christopher, Grant, Nick, Greenlee, Herbert, Greenler, Leland, Grullon, Sean, Guardincerri, Elena, Guarino, Victor, Guarnaccia, Evan, Guedes, Germano, Guenette, Roxanne, Guglielmi, Alberto, Guzzo, Marcelo M., Habig, Alec T., Hackenburg, Robert W., Hadavand, Haleh, Hahn, Alan, Haigh, Martin, Haines, Todd, Handler, Thomas, Hans, Sunej, Hartnell, Jeff, Harton, John, Hatcher, Robert, Hatzikoutelis, Athans, Hays, Steven, Hazen, Eric, Headley, Mike, Heavey, Anne, Heeger, Karsten, Heise, Jaret, Hellauer, Robert, Hewes, V, Himmel, Alexander, Hogan, Matthew, Holanda, Pedro, Holin, Anna, Horton-Smith, Glenn, Howell, Joe, Hurh, Patrick, Huston, Joey, Hylen, James, Imlay, Richard, Insler, Jonathan, Introzzi, G., Isvan, Zeynep, Jackson, Chris, Jacobsen, John, Jaffe, David E., James, Cat, Jen, Chun-Min, Johnson, Marvin, Johnson, Randy, Johnson, Robert, Johnson, Scott, Johnston, William, Johnstone, John, Jones, Ben J. P., Jostlein, H., Junk, Thomas, Kadel, Richard, Kaess, Karl, Karagiorgi, Georgia, Kaspar, Jarek, Katori, Teppei, Kayser, Boris, Kearns, Edward, Keener, Paul, Kemp, Ernesto, Kettell, Steve H., Kirby, Mike, Klein, Joshua, Koizumi, Gordon, Kopp, Sacha, Kormos, Laura, Kropp, William, Kudryavtsev, Vitaly A., Kumar, Ashok, Kumar, Jason, Kutter, Thomas, La Zia, Franco, Lande, Kenneth, Lane, Charles, Lang, Karol, Lanni, Francesco, Lanza, Richard, Latorre, Tony, Learned, John, Lee, David, Lee, Kevin, Li, Qizhong, Li, Shaorui, Li, Yichen, Li, Zepeng, Libo, Jiang, Linden, Steve, Ling, Jiajie, Link, Jonathan, Littenberg, Laurence, Liu, Hu, Liu, Qiuguang, Liu, Tiankuan, Losecco, John, Louis, William, Lundberg, Byron, Lundin, Tracy, Lundy, Jay, Machado, Ana Amelia, Maesano, Cara, Magill, Steve, Mahler, George, Malon, David, Malys, Stephen, Mammoliti, Francesco, Mandal, Samit Kumar, Mann, Anthony, Mantsch, Paul, Marchionni, Alberto, Marciano, William, Mariani, Camillo, Maricic, Jelena, Marino, Alysia, Marshak, Marvin, Marshall, John, Matsuno, Shiegenobu, Mauger, Christopher, Mavrokoridis, Konstantinos, Mayer, Nate, McCauley, Neil, McCluskey, Elaine, McDonald, Kirk, McFarland, Kevin, McKee, David, McKeown, Robert, McTaggart, Robert, Mehdiyev, Rashid, Mei, Dongming, Menegolli, A., Meng, Guang, Meng, Yixiong, Mertins, David, Messier, Mark, Metcalf, William, Milincic, Radovan, Miller, William, Mills, Geoff, Mishra, Sanjib R., Mokhov, Nikolai, Montanari, Claudio, Montanari, David, Moore, Craig, Morfin, Jorge, Morgan, Ben, Morse, William, Moss, Zander, Moura, Célio A., Mufson, Stuart, Muller, David, Musser, Jim, Naples, Donna, Napolitano, Jim, Newcomer, Mitch, Nichol, Ryan, Nicholls, Tim, Niner, Evan, Norris, Barry, Nowak, Jaroslaw, O'Keeffe, Helen, Oliveira, Roberto, Olson, Travis, Page, Brian, Pakvasa, Sandip, Palamara, Ornella, Paley, Jon, Paolone, Vittorio, Papadimitriou, Vaia, Park, Seongtae, Parsa, Zohreh, Partyka, Kinga, Paulos, Bob, Pavlovic, Zarko, Peeters, Simon, Perch, Andy, Perkin, Jon D., Petti, Roberto, Petukhov, Andre, Pietropaolo, Francesco, Plunkett, Robert, Polly, Chris, Pordes, Stephen, Potekhin, Maxim, Potenza, Renato, Prakash, Arati, Prokofiev, Oleg, Qian, Xin, Raaf, Jennifer L., Radeka, Veljko, Rakhno, Igor, Ramachers, Yorck, Rameika, Regina, Ramsey, John, Rappoldi, A., Raselli, G. L., Ratoff, Peter, Ravindra, Shreyas, Rebel, Brian, Reichenbacher, Juergen, Reitzner, Dianne, Rescia, Sergio, Richardson, Martin, Rielage, Kieth, Riesselmann, Kurt, Robinson, Matt, Rochester, Leon, Ronquest, Michael, Rosen, Marc, Rossella, M., Rubbia, Carlo, Rucinski, Russ, Sahijpal, Sandeep, Sahoo, Himansu, Sala, Paola, Salmiera, Delia, Samios, Nicholas, Sanchez, Mayly, Scaramelli, Alberto, Schellman, Heidi, Schmitt, Richard, Schmitz, David, Schneps, Jack, Scholberg, Kate, Segreto, Ettore, Seibert, Stanley, Sexton-Kennedy, Liz, Shaevitz, Mike, Shanahan, Peter, Sharma, Rahul, Shaw, Terri, Simos, Nikolaos, Singh, Venktesh, Sinnis, Gus, Sippach, William, Skwarnicki, Tomasz, Smy, Michael, Sobel, Henry, Soderberg, Mitch, Sondericker, John, Sondheim, Walter, Sousa, Alexandre, Spooner, Neil J. C., Stancari, Michelle, Stancu, Ion, Stefan, Dorota, Stefanik, Andy, Stewart, James, Stone, Sheldon, Strait, James, Strait, Matthew, Striganov, Sergei, Sullivan, Gregory, Sun, Yujing, Suter, Louise, Svenson, Andrew, Svoboda, Robert, Szczerbinska, Barbara, Szelc, Andrzej, Szydagis, Matthew, Söldner-Rembold, Stefan, Talaga, Richard, Tamsett, Matthew, Tariq, Salman, Tayloe, Rex, Taylor, Charles, Taylor, David, Teymourian, Artin, Themann, Harry, Thiesse, Matthew, Thomas, Jenny, Thompson, Lee F., Thomson, Mark, Thorn, Craig, Thorpe, Matt, Tian, Xinchun, Tiedt, Doug, Toki, Walter, Tolich, Nikolai, Torti, M., Toups, Matt, Touramanis, Christos, Tripathi, Mani, Tropin, Igor, Tsai, Yun-Tse, Tull, Craig, Tzanov, Martin, Urheim, Jon, Usman, Shawn, Vagins, Mark, Valdiviesso, Gustavo, Van Berg, Rick, Van de Water, Richard, Van Gemmeren, Peter, Varanini, Filippo, Varner, Gary, Vaziri, Kamran, Velev, Gueorgui, Ventura, Sandro, Vignoli, Chiara, Viren, Brett, Wahl, Dan, Waldron, Abby, Walter, Christopher W., Wang, Hanguo, Wang, Wei, Warburton, Karl, Warner, David, Wasserman, Ryan, Watson, Blake, Weber, Alfons, Wei, Wenzhao, Wells, Douglas, Wetstein, Matthew, White, Andy, White, Hywel, Whitehead, Lisa, Whittington, Denver, Willhite, Joshua, Wilson, Robert J., Winslow, Lindley, Wood, Kevin, Worcester, Elizabeth, Worcester, Matthew, Xin, Tian, Yarritu, Kevin, Ye, Jingbo, Yeh, Minfang, Yu, Bo, Yu, Jae, Yuan, Tianlu, Zani, A., Zeller, Geralyn P., Zhang, Chao, Zimmerman, Eric D., and Zwaska, Robert

Abstract

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess., Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figures

Published
2013

49. The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

Author

LBNE Collaboration, Adams, Corey, Adams, David, Akiri, Tarek, Alion, Tyler, Anderson, Kris, Andreopoulos, Costas, Andrews, Mike, Anghel, Ioana, Anjos, João Carlos Costa dos, Antonello, Maddalena, Arrieta-Diaz, Enrique, Artuso, Marina, Asaadi, Jonathan, Bai, Xinhua, Baibussinov, Bagdat, Baird, Michael, Balantekin, Baha, Baller, Bruce, Baptista, Brian, Barker, D'Ann, Barker, Gary, Barletta, William A., Barr, Giles, Bartoszek, Larry, Bashyal, Amit, Bass, Matt, Bellini, Vincenzo, Benetti, Pietro Angelo, Berger, Bruce E., Bergevin, Marc, Berman, Eileen, Berns, Hans-Gerd, Bernstein, Adam, Bernstein, Robert, Bhandari, Babu, Bhatnagar, Vipin, Bhuyan, Bipul, Bian, Jianming, Bishai, Mary, Blake, Andrew, Blaszczyk, Flor, Blaufuss, Erik, Bleakley, Bruce, Blucher, Edward, Blusk, Steve, Bocean, Virgil, Boffelli, F., Boissevain, Jan, Bolton, Timothy, Bonesini, Maurizio, Boyd, Steve, Brandt, Andrew, Breedon, Richard, Bromberg, Carl, Brown, Ralph, Brunetti, Giullia, Buchanan, Norman, Bugg, Bill, Busenitz, Jerome, Calligarich, E., Camilleri, Leslie, Carminati, Giada, Carr, Rachel, Castromonte, Cesar, Cavanna, Flavio, Centro, Sandro, Chen, Alex, Chen, Hucheng, Chen, Kai, Cherdack, Daniel, Chi, Cheng-Yi, Childress, Sam, Choudhary, Brajesh Chandra, Christodoulou, Georgios, Christofferson, Cabot-Ann, Church, Eric, Cline, David, Coan, Thomas, Cocco, Alfredo, Coelho, Joao, Coleman, Stephen, Conrad, Janet M., Convery, Mark, Corey, Robert, Corwin, Luke, Cranshaw, Jack, Cronin-Hennessy, Daniel, Curioni, A., da Motta, Helio, Davenne, Tristan, Davies, Gavin S., Dazeley, Steven, De, Kaushik, de Gouvea, Andre, de Jong, Jeffrey K., Demuth, David, Densham, Chris, Diwan, Milind, Djurcic, Zelimir, Dolfini, R., Dolph, Jeffrey, Drake, Gary, Dye, Stephen, Dyuang, Hongue, Edmunds, Daniel, Elliott, Steven, Elnimr, Muhammad, Eno, Sarah, Enomoto, Sanshiro, Escobar, Carlos O., Evans, Justin, Falcone, A., Falk, Lisa, Farbin, Amir, Farnese, Christian, Fava, Angela, Felde, John, Fernandes, S., Ferroni, Fernando, Feyzi, Farshid, Fields, Laura, Finch, Alex, Fitton, Mike, Fleming, Bonnie, Fowler, Jack, Fox, Walt, Friedland, Alex, Fuess, Stu, Fujikawa, Brian, Gallagher, Hugh, Gandhi, Raj, Garvey, Gerald, Gehman, Victor M., de Geronimo, Gianluigi, Gibin, Daniele, Gill, Ronald, Gomes, Ricardo A., Goodman, Maury C., Goon, Jason, Graf, Nicholas, Graham, Mathew, Gran, Rik, Grant, Christopher, Grant, Nick, Greenlee, Herbert, Greenler, Leland, Grullon, Sean, Guardincerri, Elena, Guarino, Victor, Guarnaccia, Evan, Guedes, Germano, Guenette, Roxanne, Guglielmi, Alberto, Guzzo, Marcelo M., Habig, Alec T., Hackenburg, Robert W., Hadavand, Haleh, Hahn, Alan, Haigh, Martin, Haines, Todd, Handler, Thomas, Hans, Sunej, Hartnell, Jeff, Harton, John, Hatcher, Robert, Hatzikoutelis, Athans, Hays, Steven, Hazen, Eric, Headley, Mike, Heavey, Anne, Heeger, Karsten, Heise, Jaret, Hellauer, Robert, Hewes, V, Himmel, Alexander, Hogan, Matthew, Holanda, Pedro, Holin, Anna, Horton-Smith, Glenn, Howell, Joe, Hurh, Patrick, Huston, Joey, Hylen, James, Imlay, Richard, Insler, Jonathan, Introzzi, G., Isvan, Zeynep, Jackson, Chris, Jacobsen, John, Jaffe, David E., James, Cat, Jen, Chun-Min, Johnson, Marvin, Johnson, Randy, Johnson, Robert, Johnson, Scott, Johnston, William, Johnstone, John, Jones, Ben J. P., Jostlein, H., Junk, Thomas, Kadel, Richard, Kaess, Karl, Karagiorgi, Georgia, Kaspar, Jarek, Katori, Teppei, Kayser, Boris, Kearns, Edward, Keener, Paul, Kemp, Ernesto, Kettell, Steve H., Kirby, Mike, Klein, Joshua, Koizumi, Gordon, Kopp, Sacha, Kormos, Laura, Kropp, William, Kudryavtsev, Vitaly A., Kumar, Ashok, Kumar, Jason, Kutter, Thomas, La Zia, Franco, Lande, Kenneth, Lane, Charles, Lang, Karol, Lanni, Francesco, Lanza, Richard, Latorre, Tony, Learned, John, Lee, David, Lee, Kevin, Li, Qizhong, Li, Shaorui, Li, Yichen, Li, Zepeng, Libo, Jiang, Linden, Steve, Ling, Jiajie, Link, Jonathan, Littenberg, Laurence, Liu, Hu, Liu, Qiuguang, Liu, Tiankuan, Losecco, John, Louis, William, Lundberg, Byron, Lundin, Tracy, Lundy, Jay, Machado, Ana Amelia, Maesano, Cara, Magill, Steve, Mahler, George, Malon, David, Malys, Stephen, Mammoliti, Francesco, Mandal, Samit Kumar, Mann, Anthony, Mantsch, Paul, Marchionni, Alberto, Marciano, William, Mariani, Camillo, Maricic, Jelena, Marino, Alysia, Marshak, Marvin, Marshall, John, Matsuno, Shiegenobu, Mauger, Christopher, Mavrokoridis, Konstantinos, Mayer, Nate, McCauley, Neil, McCluskey, Elaine, McDonald, Kirk, McFarland, Kevin, McKee, David, McKeown, Robert, McTaggart, Robert, Mehdiyev, Rashid, Mei, Dongming, Menegolli, A., Meng, Guang, Meng, Yixiong, Mertins, David, Messier, Mark, Metcalf, William, Milincic, Radovan, Miller, William, Mills, Geoff, Mishra, Sanjib R., Mokhov, Nikolai, Montanari, Claudio, Montanari, David, Moore, Craig, Morfin, Jorge, Morgan, Ben, Morse, William, Moss, Zander, Moura, Célio A., Mufson, Stuart, Muller, David, Musser, Jim, Naples, Donna, Napolitano, Jim, Newcomer, Mitch, Nichol, Ryan, Nicholls, Tim, Niner, Evan, Norris, Barry, Nowak, Jaroslaw, O'Keeffe, Helen, Oliveira, Roberto, Olson, Travis, Page, Brian, Pakvasa, Sandip, Palamara, Ornella, Paley, Jon, Paolone, Vittorio, Papadimitriou, Vaia, Park, Seongtae, Parsa, Zohreh, Partyka, Kinga, Paulos, Bob, Pavlovic, Zarko, Peeters, Simon, Perch, Andy, Perkin, Jon D., Petti, Roberto, Petukhov, Andre, Pietropaolo, Francesco, Plunkett, Robert, Polly, Chris, Pordes, Stephen, Potekhin, Maxim, Potenza, Renato, Prakash, Arati, Prokofiev, Oleg, Qian, Xin, Raaf, Jennifer L., Radeka, Veljko, Rakhno, Igor, Ramachers, Yorck, Rameika, Regina, Ramsey, John, Rappoldi, A., Raselli, G. L., Ratoff, Peter, Ravindra, Shreyas, Rebel, Brian, Reichenbacher, Juergen, Reitzner, Dianne, Rescia, Sergio, Richardson, Martin, Rielage, Kieth, Riesselmann, Kurt, Robinson, Matt, Rochester, Leon, Ronquest, Michael, Rosen, Marc, Rossella, M., Rubbia, Carlo, Rucinski, Russ, Sahijpal, Sandeep, Sahoo, Himansu, Sala, Paola, Salmiera, Delia, Samios, Nicholas, Sanchez, Mayly, Scaramelli, Alberto, Schellman, Heidi, Schmitt, Richard, Schmitz, David, Schneps, Jack, Scholberg, Kate, Segreto, Ettore, Seibert, Stanley, Sexton-Kennedy, Liz, Shaevitz, Mike, Shanahan, Peter, Sharma, Rahul, Shaw, Terri, Simos, Nikolaos, Singh, Venktesh, Sinnis, Gus, Sippach, William, Skwarnicki, Tomasz, Smy, Michael, Sobel, Henry, Soderberg, Mitch, Sondericker, John, Sondheim, Walter, Sousa, Alexandre, Spooner, Neil J. C., Stancari, Michelle, Stancu, Ion, Stefan, Dorota, Stefanik, Andy, Stewart, James, Stone, Sheldon, Strait, James, Strait, Matthew, Striganov, Sergei, Sullivan, Gregory, Sun, Yujing, Suter, Louise, Svenson, Andrew, Svoboda, Robert, Szczerbinska, Barbara, Szelc, Andrzej, Szydagis, Matthew, Söldner-Rembold, Stefan, Talaga, Richard, Tamsett, Matthew, Tariq, Salman, Tayloe, Rex, Taylor, Charles, Taylor, David, Teymourian, Artin, Themann, Harry, Thiesse, Matthew, Thomas, Jenny, Thompson, Lee F., Thomson, Mark, Thorn, Craig, Thorpe, Matt, Tian, Xinchun, Tiedt, Doug, Toki, Walter, Tolich, Nikolai, Torti, M., Toups, Matt, Touramanis, Christos, Tripathi, Mani, Tropin, Igor, Tsai, Yun-Tse, Tull, Craig, Tzanov, Martin, Urheim, Jon, Usman, Shawn, Vagins, Mark, Valdiviesso, Gustavo, Van Berg, Rick, Van de Water, Richard, Van Gemmeren, Peter, Varanini, Filippo, Varner, Gary, Vaziri, Kamran, Velev, Gueorgui, Ventura, Sandro, Vignoli, Chiara, Viren, Brett, Wahl, Dan, Waldron, Abby, Walter, Christopher W., Wang, Hanguo, Wang, Wei, Warburton, Karl, Warner, David, Wasserman, Ryan, Watson, Blake, Weber, Alfons, Wei, Wenzhao, Wells, Douglas, Wetstein, Matthew, White, Andy, White, Hywel, Whitehead, Lisa, Whittington, Denver, Willhite, Joshua, Wilson, Robert J., Winslow, Lindley, Wood, Kevin, Worcester, Elizabeth, Worcester, Matthew, Xin, Tian, Yarritu, Kevin, Ye, Jingbo, Yeh, Minfang, Yu, Bo, Yu, Jae, Yuan, Tianlu, Zani, A., Zeller, Geralyn P., Zhang, Chao, Zimmerman, Eric D., Zwaska, Robert, LBNE Collaboration, Adams, Corey, Adams, David, Akiri, Tarek, Alion, Tyler, Anderson, Kris, Andreopoulos, Costas, Andrews, Mike, Anghel, Ioana, Anjos, João Carlos Costa dos, Antonello, Maddalena, Arrieta-Diaz, Enrique, Artuso, Marina, Asaadi, Jonathan, Bai, Xinhua, Baibussinov, Bagdat, Baird, Michael, Balantekin, Baha, Baller, Bruce, Baptista, Brian, Barker, D'Ann, Barker, Gary, Barletta, William A., Barr, Giles, Bartoszek, Larry, Bashyal, Amit, Bass, Matt, Bellini, Vincenzo, Benetti, Pietro Angelo, Berger, Bruce E., Bergevin, Marc, Berman, Eileen, Berns, Hans-Gerd, Bernstein, Adam, Bernstein, Robert, Bhandari, Babu, Bhatnagar, Vipin, Bhuyan, Bipul, Bian, Jianming, Bishai, Mary, Blake, Andrew, Blaszczyk, Flor, Blaufuss, Erik, Bleakley, Bruce, Blucher, Edward, Blusk, Steve, Bocean, Virgil, Boffelli, F., Boissevain, Jan, Bolton, Timothy, Bonesini, Maurizio, Boyd, Steve, Brandt, Andrew, Breedon, Richard, Bromberg, Carl, Brown, Ralph, Brunetti, Giullia, Buchanan, Norman, Bugg, Bill, Busenitz, Jerome, Calligarich, E., Camilleri, Leslie, Carminati, Giada, Carr, Rachel, Castromonte, Cesar, Cavanna, Flavio, Centro, Sandro, Chen, Alex, Chen, Hucheng, Chen, Kai, Cherdack, Daniel, Chi, Cheng-Yi, Childress, Sam, Choudhary, Brajesh Chandra, Christodoulou, Georgios, Christofferson, Cabot-Ann, Church, Eric, Cline, David, Coan, Thomas, Cocco, Alfredo, Coelho, Joao, Coleman, Stephen, Conrad, Janet M., Convery, Mark, Corey, Robert, Corwin, Luke, Cranshaw, Jack, Cronin-Hennessy, Daniel, Curioni, A., da Motta, Helio, Davenne, Tristan, Davies, Gavin S., Dazeley, Steven, De, Kaushik, de Gouvea, Andre, de Jong, Jeffrey K., Demuth, David, Densham, Chris, Diwan, Milind, Djurcic, Zelimir, Dolfini, R., Dolph, Jeffrey, Drake, Gary, Dye, Stephen, Dyuang, Hongue, Edmunds, Daniel, Elliott, Steven, Elnimr, Muhammad, Eno, Sarah, Enomoto, Sanshiro, Escobar, Carlos O., Evans, Justin, Falcone, A., Falk, Lisa, Farbin, Amir, Farnese, Christian, Fava, Angela, Felde, John, Fernandes, S., Ferroni, Fernando, Feyzi, Farshid, Fields, Laura, Finch, Alex, Fitton, Mike, Fleming, Bonnie, Fowler, Jack, Fox, Walt, Friedland, Alex, Fuess, Stu, Fujikawa, Brian, Gallagher, Hugh, Gandhi, Raj, Garvey, Gerald, Gehman, Victor M., de Geronimo, Gianluigi, Gibin, Daniele, Gill, Ronald, Gomes, Ricardo A., Goodman, Maury C., Goon, Jason, Graf, Nicholas, Graham, Mathew, Gran, Rik, Grant, Christopher, Grant, Nick, Greenlee, Herbert, Greenler, Leland, Grullon, Sean, Guardincerri, Elena, Guarino, Victor, Guarnaccia, Evan, Guedes, Germano, Guenette, Roxanne, Guglielmi, Alberto, Guzzo, Marcelo M., Habig, Alec T., Hackenburg, Robert W., Hadavand, Haleh, Hahn, Alan, Haigh, Martin, Haines, Todd, Handler, Thomas, Hans, Sunej, Hartnell, Jeff, Harton, John, Hatcher, Robert, Hatzikoutelis, Athans, Hays, Steven, Hazen, Eric, Headley, Mike, Heavey, Anne, Heeger, Karsten, Heise, Jaret, Hellauer, Robert, Hewes, V, Himmel, Alexander, Hogan, Matthew, Holanda, Pedro, Holin, Anna, Horton-Smith, Glenn, Howell, Joe, Hurh, Patrick, Huston, Joey, Hylen, James, Imlay, Richard, Insler, Jonathan, Introzzi, G., Isvan, Zeynep, Jackson, Chris, Jacobsen, John, Jaffe, David E., James, Cat, Jen, Chun-Min, Johnson, Marvin, Johnson, Randy, Johnson, Robert, Johnson, Scott, Johnston, William, Johnstone, John, Jones, Ben J. P., Jostlein, H., Junk, Thomas, Kadel, Richard, Kaess, Karl, Karagiorgi, Georgia, Kaspar, Jarek, Katori, Teppei, Kayser, Boris, Kearns, Edward, Keener, Paul, Kemp, Ernesto, Kettell, Steve H., Kirby, Mike, Klein, Joshua, Koizumi, Gordon, Kopp, Sacha, Kormos, Laura, Kropp, William, Kudryavtsev, Vitaly A., Kumar, Ashok, Kumar, Jason, Kutter, Thomas, La Zia, Franco, Lande, Kenneth, Lane, Charles, Lang, Karol, Lanni, Francesco, Lanza, Richard, Latorre, Tony, Learned, John, Lee, David, Lee, Kevin, Li, Qizhong, Li, Shaorui, Li, Yichen, Li, Zepeng, Libo, Jiang, Linden, Steve, Ling, Jiajie, Link, Jonathan, Littenberg, Laurence, Liu, Hu, Liu, Qiuguang, Liu, Tiankuan, Losecco, John, Louis, William, Lundberg, Byron, Lundin, Tracy, Lundy, Jay, Machado, Ana Amelia, Maesano, Cara, Magill, Steve, Mahler, George, Malon, David, Malys, Stephen, Mammoliti, Francesco, Mandal, Samit Kumar, Mann, Anthony, Mantsch, Paul, Marchionni, Alberto, Marciano, William, Mariani, Camillo, Maricic, Jelena, Marino, Alysia, Marshak, Marvin, Marshall, John, Matsuno, Shiegenobu, Mauger, Christopher, Mavrokoridis, Konstantinos, Mayer, Nate, McCauley, Neil, McCluskey, Elaine, McDonald, Kirk, McFarland, Kevin, McKee, David, McKeown, Robert, McTaggart, Robert, Mehdiyev, Rashid, Mei, Dongming, Menegolli, A., Meng, Guang, Meng, Yixiong, Mertins, David, Messier, Mark, Metcalf, William, Milincic, Radovan, Miller, William, Mills, Geoff, Mishra, Sanjib R., Mokhov, Nikolai, Montanari, Claudio, Montanari, David, Moore, Craig, Morfin, Jorge, Morgan, Ben, Morse, William, Moss, Zander, Moura, Célio A., Mufson, Stuart, Muller, David, Musser, Jim, Naples, Donna, Napolitano, Jim, Newcomer, Mitch, Nichol, Ryan, Nicholls, Tim, Niner, Evan, Norris, Barry, Nowak, Jaroslaw, O'Keeffe, Helen, Oliveira, Roberto, Olson, Travis, Page, Brian, Pakvasa, Sandip, Palamara, Ornella, Paley, Jon, Paolone, Vittorio, Papadimitriou, Vaia, Park, Seongtae, Parsa, Zohreh, Partyka, Kinga, Paulos, Bob, Pavlovic, Zarko, Peeters, Simon, Perch, Andy, Perkin, Jon D., Petti, Roberto, Petukhov, Andre, Pietropaolo, Francesco, Plunkett, Robert, Polly, Chris, Pordes, Stephen, Potekhin, Maxim, Potenza, Renato, Prakash, Arati, Prokofiev, Oleg, Qian, Xin, Raaf, Jennifer L., Radeka, Veljko, Rakhno, Igor, Ramachers, Yorck, Rameika, Regina, Ramsey, John, Rappoldi, A., Raselli, G. L., Ratoff, Peter, Ravindra, Shreyas, Rebel, Brian, Reichenbacher, Juergen, Reitzner, Dianne, Rescia, Sergio, Richardson, Martin, Rielage, Kieth, Riesselmann, Kurt, Robinson, Matt, Rochester, Leon, Ronquest, Michael, Rosen, Marc, Rossella, M., Rubbia, Carlo, Rucinski, Russ, Sahijpal, Sandeep, Sahoo, Himansu, Sala, Paola, Salmiera, Delia, Samios, Nicholas, Sanchez, Mayly, Scaramelli, Alberto, Schellman, Heidi, Schmitt, Richard, Schmitz, David, Schneps, Jack, Scholberg, Kate, Segreto, Ettore, Seibert, Stanley, Sexton-Kennedy, Liz, Shaevitz, Mike, Shanahan, Peter, Sharma, Rahul, Shaw, Terri, Simos, Nikolaos, Singh, Venktesh, Sinnis, Gus, Sippach, William, Skwarnicki, Tomasz, Smy, Michael, Sobel, Henry, Soderberg, Mitch, Sondericker, John, Sondheim, Walter, Sousa, Alexandre, Spooner, Neil J. C., Stancari, Michelle, Stancu, Ion, Stefan, Dorota, Stefanik, Andy, Stewart, James, Stone, Sheldon, Strait, James, Strait, Matthew, Striganov, Sergei, Sullivan, Gregory, Sun, Yujing, Suter, Louise, Svenson, Andrew, Svoboda, Robert, Szczerbinska, Barbara, Szelc, Andrzej, Szydagis, Matthew, Söldner-Rembold, Stefan, Talaga, Richard, Tamsett, Matthew, Tariq, Salman, Tayloe, Rex, Taylor, Charles, Taylor, David, Teymourian, Artin, Themann, Harry, Thiesse, Matthew, Thomas, Jenny, Thompson, Lee F., Thomson, Mark, Thorn, Craig, Thorpe, Matt, Tian, Xinchun, Tiedt, Doug, Toki, Walter, Tolich, Nikolai, Torti, M., Toups, Matt, Touramanis, Christos, Tripathi, Mani, Tropin, Igor, Tsai, Yun-Tse, Tull, Craig, Tzanov, Martin, Urheim, Jon, Usman, Shawn, Vagins, Mark, Valdiviesso, Gustavo, Van Berg, Rick, Van de Water, Richard, Van Gemmeren, Peter, Varanini, Filippo, Varner, Gary, Vaziri, Kamran, Velev, Gueorgui, Ventura, Sandro, Vignoli, Chiara, Viren, Brett, Wahl, Dan, Waldron, Abby, Walter, Christopher W., Wang, Hanguo, Wang, Wei, Warburton, Karl, Warner, David, Wasserman, Ryan, Watson, Blake, Weber, Alfons, Wei, Wenzhao, Wells, Douglas, Wetstein, Matthew, White, Andy, White, Hywel, Whitehead, Lisa, Whittington, Denver, Willhite, Joshua, Wilson, Robert J., Winslow, Lindley, Wood, Kevin, Worcester, Elizabeth, Worcester, Matthew, Xin, Tian, Yarritu, Kevin, Ye, Jingbo, Yeh, Minfang, Yu, Bo, Yu, Jae, Yuan, Tianlu, Zani, A., Zeller, Geralyn P., Zhang, Chao, Zimmerman, Eric D., and Zwaska, Robert

Abstract

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess., Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figures

Published
2013

50. Project X: Physics Opportunities

Author

Kronfeld, Andreas S., Tschirhart, Robert S., Al-Binni, Usama, Altmannshofer, Wolfgang, Ankenbrandt, Charles, Babu, Kaladi, Banerjee, Sunanda, Bass, Matthew, Batell, Brian, Baxter, David V., Berezhiani, Zurab, Bergevin, Marc, Bernstein, Robert, Bhattacharya, Sudeb, Bishai, Mary, Blum, Thomas, Bogacz, S. Alex, Brice, Stephen J., Brod, Joachim, Bross, Alan, Buchoff, Michael, Burgess, Thomas W., Carena, Marcela, Castellanos, Luis A., Chattopadhyay, Subhasis, Chen, Mu-Chun, Cherdack, Daniel, Christ, Norman H., Chupp, Tim, Cirigliano, Vincenzo, Coloma, Pilar, Coppola, Christopher E., Cowsik, Ramanath, Crabtree, J. Allen, de Gouvêa, André, Delahaye, Jean-Pierre, Denisov, Dmitri, deNiverville, Patrick, Dharmapalan, Ranjan, Diefenthaler, Markus, Dolgov, Alexander, Dvali, Georgi, Eichten, Estia, Engelfried, Jürgen, Ferguson, Phillip D., Gabriel, Tony, Gal, Avraham, Gallmeier, Franz, Ganezer, Kenneth S., Gardner, Susan, Glenzinski, Douglas, Godfrey, Stephen, Golubeva, Elena S., Gori, Stefania, Graves, Van B., Greene, Geoffrey, Griffard, Cory L., Haisch, Ulrich, Handler, Thomas, Hartfiel, Brandon, Hatzikoutelis, Athanasios, Hawari, Ayman, Heilbronn, Lawrence, Hill, James E., Huber, Patrick, Jaffe, David E., Jiang, Xiaodong, Johnson, Christian, Kamyshkov, Yuri, Kaplan, Daniel M., Kerbikov, Boris, Kiburg, Brendan, Kirk, Harold G., Klein, Andreas, Knoepfel, Kyle, Kopeliovich, Boris, Kopeliovich, Vladimir, Kopp, Joachim, Korsch, Wolfgang, Kribs, Graham, Lipton, Ronald, Liu, Chen-Yu, Lorenzon, Wolfgang, Lu, Zheng-Tian, Makins, Naomi C. R., McKeen, David, Mills, Geoffrey, Mocko, Michael, Mohapatra, Rabindra, Mokhov, Nikolai V., Muhrer, Guenter, Mumm, Pieter, Neuffer, David, Okun, Lev, Palmer, Mark A., Palmer, Robert, Pattie Jr., Robert W., Phillips II, David G., Pitts, Kevin, Pospelov, Maxim, Pronskikh, Vitaly S., Quigg, Chris, Ramberg, Erik, Ray, Amlan, Reimer, Paul E., Richards, David G., Ritz, Adam, Roy, Amit, Ruggles, Arthur, Ryne, Robert, Sarkar, Utpal, Saunders, Andy, Semertzidis, Yannis K., Serebrov, Anatoly, Shimizu, Hirohiko, Shrock, Robert, Sikdar, Arindam K., Snopok, Pavel V., Snow, William M., Soha, Aria, Spanier, Stefan, Striganov, Sergei, Tang, Zhaowen, Townsend, Lawrence, Urheim, Jon, Vainshtein, Arkady, Van de Water, Richard, Van de Water, Ruth S., Van Kooten, Richard J., Wehring, Bernard, Wester III, William C., Whitehead, Lisa, Wilson, Robert J., Worcester, Elizabeth, Young, Albert R., Zeller, Geralyn, Kronfeld, Andreas S., Tschirhart, Robert S., Al-Binni, Usama, Altmannshofer, Wolfgang, Ankenbrandt, Charles, Babu, Kaladi, Banerjee, Sunanda, Bass, Matthew, Batell, Brian, Baxter, David V., Berezhiani, Zurab, Bergevin, Marc, Bernstein, Robert, Bhattacharya, Sudeb, Bishai, Mary, Blum, Thomas, Bogacz, S. Alex, Brice, Stephen J., Brod, Joachim, Bross, Alan, Buchoff, Michael, Burgess, Thomas W., Carena, Marcela, Castellanos, Luis A., Chattopadhyay, Subhasis, Chen, Mu-Chun, Cherdack, Daniel, Christ, Norman H., Chupp, Tim, Cirigliano, Vincenzo, Coloma, Pilar, Coppola, Christopher E., Cowsik, Ramanath, Crabtree, J. Allen, de Gouvêa, André, Delahaye, Jean-Pierre, Denisov, Dmitri, deNiverville, Patrick, Dharmapalan, Ranjan, Diefenthaler, Markus, Dolgov, Alexander, Dvali, Georgi, Eichten, Estia, Engelfried, Jürgen, Ferguson, Phillip D., Gabriel, Tony, Gal, Avraham, Gallmeier, Franz, Ganezer, Kenneth S., Gardner, Susan, Glenzinski, Douglas, Godfrey, Stephen, Golubeva, Elena S., Gori, Stefania, Graves, Van B., Greene, Geoffrey, Griffard, Cory L., Haisch, Ulrich, Handler, Thomas, Hartfiel, Brandon, Hatzikoutelis, Athanasios, Hawari, Ayman, Heilbronn, Lawrence, Hill, James E., Huber, Patrick, Jaffe, David E., Jiang, Xiaodong, Johnson, Christian, Kamyshkov, Yuri, Kaplan, Daniel M., Kerbikov, Boris, Kiburg, Brendan, Kirk, Harold G., Klein, Andreas, Knoepfel, Kyle, Kopeliovich, Boris, Kopeliovich, Vladimir, Kopp, Joachim, Korsch, Wolfgang, Kribs, Graham, Lipton, Ronald, Liu, Chen-Yu, Lorenzon, Wolfgang, Lu, Zheng-Tian, Makins, Naomi C. R., McKeen, David, Mills, Geoffrey, Mocko, Michael, Mohapatra, Rabindra, Mokhov, Nikolai V., Muhrer, Guenter, Mumm, Pieter, Neuffer, David, Okun, Lev, Palmer, Mark A., Palmer, Robert, Pattie Jr., Robert W., Phillips II, David G., Pitts, Kevin, Pospelov, Maxim, Pronskikh, Vitaly S., Quigg, Chris, Ramberg, Erik, Ray, Amlan, Reimer, Paul E., Richards, David G., Ritz, Adam, Roy, Amit, Ruggles, Arthur, Ryne, Robert, Sarkar, Utpal, Saunders, Andy, Semertzidis, Yannis K., Serebrov, Anatoly, Shimizu, Hirohiko, Shrock, Robert, Sikdar, Arindam K., Snopok, Pavel V., Snow, William M., Soha, Aria, Spanier, Stefan, Striganov, Sergei, Tang, Zhaowen, Townsend, Lawrence, Urheim, Jon, Vainshtein, Arkady, Van de Water, Richard, Van de Water, Ruth S., Van Kooten, Richard J., Wehring, Bernard, Wester III, William C., Whitehead, Lisa, Wilson, Robert J., Worcester, Elizabeth, Young, Albert R., and Zeller, Geralyn

Abstract

Part 2 of "Project X: Accelerator Reference Design, Physics Opportunities, Broader Impacts". In this Part, we outline the particle-physics program that can be achieved with Project X, a staged superconducting linac for intensity-frontier particle physics. Topics include neutrino physics, kaon physics, muon physics, electric dipole moments, neutron-antineutron oscillations, new light particles, hadron structure, hadron spectroscopy, and lattice-QCD calculations. Part 1 is available as arXiv:1306.5022 [physics.acc-ph] and Part 3 is available as arXiv:1306.5024 [physics.acc-ph]., Comment: 209 pp. with many figures; prepared in part for the DPF Community Summer Study; v2 corrects typos (including one author surname), adds an author, and conforms with the version being printed; v3 includes two more chapter authors in full list at the top

Published
2013

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