2,045 results on '"Richards,P L"'
Search Results
2. Hosts and vectors of scrub typhus in Chile: epidemiological study and molecular analyses of Orientia infection in rodents and rodent-associated mites
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Martínez-Valdebenito, Constanza, Acosta-Jamett, Gerardo, Abello, Rayitray, Jiang, Ju, Richards, Allen L., Abarca, Katia, and Weitzel, Thomas
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- 2024
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3. Complete inhibition of liver acetyl-CoA carboxylase activity is required to exacerbate liver tumorigenesis in mice treated with diethylnitrosamine
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Shrestha, Riya, Vancuylenburg, Calum S., Beretta, Martina, Zhou, Mingyan, Shah, Divya P., Olzomer, Ellen M., Richards, Sian L., Hoehn, Kyle L., and Byrne, Frances L.
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- 2024
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4. What patients with kidney stones believe about their condition
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Richards, Helen L., Fortune, D. G., and Hennessey, D. B.
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- 2024
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5. Rapid phenotypic differentiation in the iconic Japanese knotweed s.l. invading novel habitats
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Yuan, Wei, Pigliucci, Massimo, and Richards, Christina L.
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- 2024
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6. Clinician perspectives of the implementation of an early intervention service for eating disorders in England: a mixed method study
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Richards, Katie L, Phillips, Matthew, Grycuk, Luiza, Hyam, Lucy, Allen, Karina, and Schmidt, Ulrike
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- 2024
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7. Convergent evolution of BRCA2 reversion mutations under therapeutic pressure by PARP inhibition and platinum chemotherapy
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Walmsley, Charlotte S., Jonsson, Philip, Cheng, Michael L., McBride, Sean, Kaeser, Christopher, Vargas, Herbert Alberto, Laudone, Vincent, Taylor, Barry S., Kappagantula, Rajya, Baez, Priscilla, Richards, Allison L., Noronha, Anne Marie, Perera, Dilmi, Berger, Michael, Solit, David B., Iacobuzio-Donahue, Christine A., Scher, Howard I., Donoghue, Mark T. A., Abida, Wassim, and Schram, Alison M.
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- 2024
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8. Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS
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Carnie, Christopher J, Götz, Maximilian J, Palma-Chaundler, Chloe S, Weickert, Pedro, Wanders, Amy, Serrano-Benitez, Almudena, Li, Hao-Yi, Gupta, Vipul, Awwad, Samah W, Blum, Christian J, Sczaniecka-Clift, Matylda, Cordes, Jacqueline, Zagnoli-Vieira, Guido, D’Alessandro, Giuseppina, Richards, Sean L, Gueorguieva, Nadia, Lam, Simon, Beli, Petra, Stingele, Julian, and Jackson, Stephen P
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- 2024
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9. Protect Your Prompts: Protocols for IP Protection in LLM Applications
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van Wyk, M. A., Bekker, M., Richards, X. L., and Nixon, K. J.
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Computer Science - Computation and Language ,Computer Science - Artificial Intelligence ,91D10, 68T10, 03D40 ,I.2.6 ,K.6.5 ,F.3.2 - Abstract
With the rapid adoption of AI in the form of large language models (LLMs), the potential value of carefully engineered prompts has become significant. However, to realize this potential, prompts should be tradable on an open market. Since prompts are, at present, generally economically non-excludable, by virtue of their nature as text, no general competitive market has yet been established. This note discusses two protocols intended to provide protection of prompts, elevating their status as intellectual property, thus confirming the intellectual property rights of prompt engineers, and potentially supporting the flourishing of an open market for LLM prompts., Comment: 5 pages, 2 figures
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- 2023
10. SARS-CoV-2 variants evolve convergent strategies to remodel the host response
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Bouhaddou, Mehdi, Reuschl, Ann-Kathrin, Polacco, Benjamin J, Thorne, Lucy G, Ummadi, Manisha R, Ye, Chengjin, Rosales, Romel, Pelin, Adrian, Batra, Jyoti, Jang, Gwendolyn M, Xu, Jiewei, Moen, Jack M, Richards, Alicia L, Zhou, Yuan, Harjai, Bhavya, Stevenson, Erica, Rojc, Ajda, Ragazzini, Roberta, Whelan, Matthew VX, Furnon, Wilhelm, De Lorenzo, Giuditta, Cowton, Vanessa, Syed, Abdullah M, Ciling, Alison, Deutsch, Noa, Pirak, Daniel, Dowgier, Giulia, Mesner, Dejan, Turner, Jane L, McGovern, Briana L, Rodriguez, M Luis, Leiva-Rebollo, Rocio, Dunham, Alistair S, Zhong, Xiaofang, Eckhardt, Manon, Fossati, Andrea, Liotta, Nicholas F, Kehrer, Thomas, Cupic, Anastasija, Rutkowska, Magdalena, Mena, Ignacio, Aslam, Sadaf, Hoffert, Alyssa, Foussard, Helene, Olwal, Charles Ochieng', Huang, Weiqing, Zwaka, Thomas, Pham, John, Lyons, Molly, Donohue, Laura, Griffin, Aliesha, Nugent, Rebecca, Holden, Kevin, Deans, Robert, Aviles, Pablo, Lopez-Martin, Jose A, Jimeno, Jose M, Obernier, Kirsten, Fabius, Jacqueline M, Soucheray, Margaret, Hüttenhain, Ruth, Jungreis, Irwin, Kellis, Manolis, Echeverria, Ignacia, Verba, Kliment, Bonfanti, Paola, Beltrao, Pedro, Sharan, Roded, Doudna, Jennifer A, Martinez-Sobrido, Luis, Patel, Arvind H, Palmarini, Massimo, Miorin, Lisa, White, Kris, Swaney, Danielle L, Garcia-Sastre, Adolfo, Jolly, Clare, Zuliani-Alvarez, Lorena, Towers, Greg J, and Krogan, Nevan J
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Biological Sciences ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Genetics ,Coronaviruses ,Emerging Infectious Diseases ,Coronaviruses Therapeutics and Interventions ,2.1 Biological and endogenous factors ,Infection ,Humans ,COVID-19 ,Immunity ,Innate ,Pandemics ,SARS-CoV-2 ,innate immunity ,protein-protein interactions ,proteomics ,systems biology ,transcriptomics ,variants ,virus-host interactions ,systems biology. ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.
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- 2023
11. The microenvironment dictates glycocalyx construction and immune surveillance
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Tharp, Kevin M, Park, Sangwoo, Timblin, Greg A, Richards, Alicia L, Berg, Jordan A, Twells, Nicholas M, Riley, Nicholas M, Peltan, Egan L, Shon, D Judy, Stevenson, Erica, Tsui, Kimberly, Palomba, Francesco, Lefebvre, Austin EYT, Soens, Ross W, Ayad, Nadia ME, Hoeve-Scott, Johanna ten, Healy, Kevin, Digman, Michelle, Dillin, Andrew, Bertozzi, Carolyn R, Swaney, Danielle L, Mahal, Lara K, Cantor, Jason R, Paszek, Matthew J, and Weaver, Valerie M
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Biomedical and Clinical Sciences ,Immunology ,Cancer ,ECM ,Mechanopharmacology ,bleb ,glycoform ,glycome ,glycosylation ,immune surveillance ,lectin array ,lectin microarray ,mechano-metabolic ,metabolism ,microenvironment ,sialic acid - Abstract
Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with in vitro models that do not match the microenvironmental characteristics of human tissues. Using in vitro models which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium.
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- 2023
12. The POLARBEAR-2 and Simons Array Focal Plane Fabrication Status
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Westbrook, B., Ade, P. A. R., Aguilar, M., Akiba, Y., Arnold, K., Baccigalupi, C., Barron, D., Beck, D., Beckman, S., Bender, A. N., Bianchini, F., Boettger, D., Borrill, J., Chapman, S., Chinone, Y., Coppi, G., Crowley, K., Cukierman, A., de, T., Dünner, R., Dobbs, M., Elleflot, T., Errard, J., Fabbian, G., Feeney, S. M., Feng, C., Fuller, G., Galitzki, N., Gilbert, A., Goeckner-Wald, N., Groh, J., Halverson, N. W., Hamada, T., Hasegawa, M., Hazumi, M., Hill, C. A., Holzapfel, W., Howe, L., Inoue, Y., Jaehnig, G., Jaffe, A., Jeong, O., Kaneko, D., Katayama, N., Keating, B., Keskitalo, R., Kisner, T., Krachmalnicoff, N., Kusaka, A., Le, M., Lee, A. T., Leon, D., Linder, E., Lowry, L., Madurowicz, A., Mak, D., Matsuda, F., May, A., Miller, N. J., Minami, Y., Montgomery, J., Navaroli, M., Nishino, H., Peloton, J., Pham, A., Piccirillo, L., Plambeck, D., Poletti, D., Puglisi, G., Raum, C., Rebeiz, G., Reichardt, C. L., Richards, P. L., Roberts, H., Ross, C., Rotermund, K. M., Segawa, Y., Sherwin, B., Silva-Feaver, M., Siritanasak, P., Stompor, R., Suzuki, A., Tajima, O., Takakura, S., Takatori, S., Tanabe, D., Tat, R., Teply, G. P., Tikhomirov, A., Tomaru, T., Tsai, C., Whitehorn, N., and Zahn, A.
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We present on the status of POLARBEAR-2 A (PB2-A) focal plane fabrication. The PB2-A is the first of three telescopes in the Simon Array (SA), which is an array of three cosmic microwave background (CMB) polarization sensitive telescopes located at the POLARBEAR (PB) site in Northern Chile. As the successor to the PB experiment, each telescope and receiver combination is named as PB2-A, PB2-B, and PB2-C. PB2-A and -B will have nearly identical receivers operating at 90 and 150 GHz while PB2-C will house a receiver operating at 220 and 270 GHz. Each receiver contains a focal plane consisting of seven close-hex packed lenslet coupled sinuous antenna transition edge sensor bolometer arrays. Each array contains 271 di-chroic optical pixels each of which have four TES bolometers for a total of 7588 detectors per receiver. We have produced a set of two types of candidate arrays for PB2-A. The first we call Version 11 (V11) and uses a silicon oxide (SiOx) for the transmission lines and cross-over process for orthogonal polarizations. The second we call Version 13 (V13) and uses silicon nitride (SiNx) for the transmission lines and cross-under process for orthogonal polarizations. We have produced enough of each type of array to fully populate the focal plane of the PB2-A receiver. The average wirebond yield for V11 and V13 arrays is 93.2% and 95.6% respectively. The V11 arrays had a superconducting transition temperature (Tc) of 452 +/- 15 mK, a normal resistance (Rn) of 1.25 +/- 0.20 Ohms, and saturations powers of 5.2 +/- 1.0 pW and 13 +/- 1.2 pW for the 90 and 150 GHz bands respectively. The V13 arrays had a superconducting transition temperature (Tc) of 456 +/-6 mK, a normal resistance (Rn) of 1.1 +/- 0.2 Ohms, and saturations powers of 10.8 +/- 1.8 pW and 22.9 +/- 2.6 pW for the 90 and 150 GHz bands respectively.
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- 2022
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13. Genome-wide loss of heterozygosity predicts aggressive, treatment-refractory behavior in pituitary neuroendocrine tumors
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Lin, Andrew L., Rudneva, Vasilisa A., Richards, Allison L., Zhang, Yanming, Woo, Hyung Jun, Cohen, Marc, Tisnado, Jamie, Majd, Nazanin, Wardlaw, Sharon L., Page-Wilson, Gabrielle, Sengupta, Soma, Chow, Frances, Goichot, Bernard, Ozer, Byram H., Dietrich, Jorg, Nachtigall, Lisa, Desai, Arati, Alano, Tina, Ogilive, Shahiba, Solit, David B., Bale, Tejus A., Rosenblum, Marc, Donoghue, Mark T. A., Geer, Eliza B., and Tabar, Viviane
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- 2024
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14. Global detection of human variants and isoforms by deep proteome sequencing
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Sinitcyn, Pavel, Richards, Alicia L., Weatheritt, Robert J., Brademan, Dain R., Marx, Harald, Shishkova, Evgenia, Meyer, Jesse G., Hebert, Alexander S., Westphall, Michael S., Blencowe, Benjamin J., Cox, Jürgen, and Coon, Joshua J.
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- 2023
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15. Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade
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Harrold, Emily C., Foote, Michael B., Rousseau, Benoit, Walch, Henry, Kemel, Yelena, Richards, Allison L., Keane, Fergus, Cercek, Andrea, Yaeger, Rona, Rathkopf, Dana, Segal, Neil H., Patel, Zalak, Maio, Anna, Borio, Matilde, O’Reilly, Eileen M., Reidy, Diane, Desai, Avni, Janjigian, Yelena Y., Murciano-Goroff, Yonina R., Carlo, Maria I., Latham, Alicia, Liu, Ying L., Walsh, Michael F., Ilson, David, Rosenberg, Jonathan E., Markowitz, Arnold J., Weiser, Martin R., Rossi, Anthony M., Vanderbilt, Chad, Mandelker, Diana, Bandlamudi, Chaitanya, Offit, Kenneth, Berger, Michael F., Solit, David B., Saltz, Leonard, Shia, Jinru, Diaz, Jr., Luis A., and Stadler, Zsofia K.
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- 2023
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16. Mapping genomic loci implicates genes and synaptic biology in schizophrenia
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Trubetskoy, Vassily, Pardiñas, Antonio F, Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B, Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A, Hall, Lynsey S, Lam, Max, Watanabe, Kyoko, Frei, Oleksandr, Ge, Tian, Harwood, Janet C, Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L, Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G, Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z, Alptekin, Köksal, Als, Thomas D, Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A, Bass, Nicholas J, Begemann, Martin, Belliveau, Richard A, Bene, Judit, Benyamin, Beben, Bergen, Sarah E, Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Bressan, Rodrigo Affonseca, Bromet, Evelyn J, Bruggeman, Richard, Buckley, Peter F, Buckner, Randy L, Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J, Calkins, Monica E, Carr, Vaughan J, Castle, David, Catts, Stanley V, Chambert, Kimberley D, Chan, Raymond CK, Chaumette, Boris, Cheng, Wei, Cheung, Eric FC, Chong, Siow Ann, Cohen, David, Consoli, Angèle, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L, de Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E, Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G, Fañanás, Lourdes, Faraone, Stephen V, Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B, Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, and Gershon, Elliot S
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Brain Disorders ,Human Genome ,Mental Health ,Schizophrenia ,Serious Mental Illness ,Biotechnology ,Neurosciences ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Alleles ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genomics ,Humans ,Polymorphism ,Single Nucleotide ,Indonesia Schizophrenia Consortium ,PsychENCODE ,Psychosis Endophenotypes International Consortium ,SynGO Consortium ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,General Science & Technology - Abstract
Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.
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- 2022
17. Conservation genomics of an exploited, popular aquarium trade species: the giant Caribbean sea anemone Condylactis gigantea (Anthozoa: Actiniidae)
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Sheridan, Nancy E., Seyoum, Seifu, Sharp, William C., Titus, Benjamin M., Daly, Marymegan, Richards, Christina L., and Schrey, Aaron W.
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- 2023
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18. Biological sex does not influence the peak cardiac output response to twelve weeks of sprint interval training
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Bostad, William, Williams, Jennifer S., Van Berkel, Emily K., Richards, Douglas L., MacDonald, Maureen J., and Gibala, Martin J.
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- 2023
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19. The effect of bodyweight exercise on 24-h glycemic responses determined by continuous glucose monitoring in healthy inactive adults: a randomized crossover study
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Babir, Fiona J., Riddell, Michael C., Adamo, Larissa M., Richards, Douglas L., and Gibala, Martin J.
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- 2023
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20. The context-specific role of germline pathogenicity in tumorigenesis
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Srinivasan, Preethi, Bandlamudi, Chaitanya, Jonsson, Philip, Kemel, Yelena, Chavan, Shweta S, Richards, Allison L, Penson, Alexander V, Bielski, Craig M, Fong, Christopher, Syed, Aijazuddin, Jayakumaran, Gowtham, Prasad, Meera, Hwee, Jason, Sumer, Selcuk Onur, de Bruijn, Ino, Li, Xiang, Gao, JianJiong, Schultz, Nikolaus, Cambria, Roy, Galle, Jesse, Mukherjee, Semanti, Vijai, Joseph, Cadoo, Karen A, Carlo, Maria I, Walsh, Michael F, Mandelker, Diana, Ceyhan-Birsoy, Ozge, Shia, Jinru, Zehir, Ahmet, Ladanyi, Marc, Hyman, David M, Zhang, Liying, Offit, Kenneth, Robson, Mark E, Solit, David B, Stadler, Zsofia K, Berger, Michael F, and Taylor, Barry S
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Biological Sciences ,Genetics ,Human Genome ,Rare Diseases ,Cancer ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Carcinogenesis ,DNA Copy Number Variations ,DNA Mismatch Repair ,Genetic Predisposition to Disease ,Germ-Line Mutation ,Heterozygote ,Humans ,Neoplasms ,Phenotype ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Human cancers arise from environmental, heritable and somatic factors, but how these mechanisms interact in tumorigenesis is poorly understood. Studying 17,152 prospectively sequenced patients with cancer, we identified pathogenic germline variants in cancer predisposition genes, and assessed their zygosity and co-occurring somatic alterations in the concomitant tumors. Two major routes to tumorigenesis were apparent. In carriers of pathogenic germline variants in high-penetrance genes (5.1% overall), lineage-dependent patterns of biallelic inactivation led to tumors exhibiting mechanism-specific somatic phenotypes and fewer additional somatic oncogenic drivers. Nevertheless, 27% of cancers in these patients, and most tumors in patients with pathogenic germline variants in lower-penetrance genes, lacked particular hallmarks of tumorigenesis associated with the germline allele. The dependence of tumors on pathogenic germline variants is variable and often dictated by both penetrance and lineage, a finding with implications for clinical management.
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- 2021
21. Toward Comprehensive Plasma Proteomics by Orthogonal Protease Digestion
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Fossati, Andrea, Richards, Alicia L, Chen, Kuei-Ho, Jaganath, Devan, Cattamanchi, Adithya, Ernst, Joel D, and Swaney, Danielle L
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Analytical Chemistry ,Biochemistry and Cell Biology ,Chemical Sciences ,Biological Sciences ,Emerging Infectious Diseases ,Biodefense ,Infectious Diseases ,Biotechnology ,Rare Diseases ,Tuberculosis ,Lung ,Infection ,Good Health and Well Being ,Digestion ,Humans ,Peptide Hydrolases ,Proteome ,Proteomics ,Reproducibility of Results ,DIA-MS ,clinical proteomics ,label-free quantification ,proteases ,Biochemistry & Molecular Biology ,Biological sciences ,Chemical sciences - Abstract
Rapid and consistent protein identification across large clinical cohorts is an important goal for clinical proteomics. With the development of data-independent technologies (DIA/SWATH-MS), it is now possible to analyze hundreds of samples with great reproducibility and quantitative accuracy. However, this technology benefits from empirically derived spectral libraries that define the detectable set of peptides and proteins. Here, we apply a simple and accessible tip-based workflow for the generation of spectral libraries to provide a comprehensive overview on the plasma proteome in individuals with and without active tuberculosis (TB). To boost protein coverage, we utilized nonconventional proteases such as GluC and AspN together with the gold standard trypsin, identifying more than 30,000 peptides mapping to 3309 proteins. Application of this library to quantify plasma proteome differences in TB infection recovered more than 400 proteins in 50 min of MS acquisition, including diagnostic Mycobacterium tuberculosis (Mtb) proteins that have previously been detectable primarily by antibody-based assays and intracellular proteins not previously described to be in plasma.
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- 2021
22. Adhesion-mediated mechanosignaling forces mitohormesis
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Tharp, Kevin M, Higuchi-Sanabria, Ryo, Timblin, Greg A, Ford, Breanna, Garzon-Coral, Carlos, Schneider, Catherine, Muncie, Jonathon M, Stashko, Connor, Daniele, Joseph R, Moore, Andrew S, Frankino, Phillip A, Homentcovschi, Stefan, Manoli, Sagar S, Shao, Hao, Richards, Alicia L, Chen, Kuei-Ho, Hoeve, Johanna Ten, Ku, Gregory M, Hellerstein, Marc, Nomura, Daniel K, Saijo, Karou, Gestwicki, Jason, Dunn, Alexander R, Krogan, Nevan J, Swaney, Danielle L, Dillin, Andrew, and Weaver, Valerie M
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Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,Aging ,1.1 Normal biological development and functioning ,Generic health relevance ,Adult ,Animals ,Animals ,Genetically Modified ,Caenorhabditis elegans ,Cell Adhesion ,Cell Respiration ,Cells ,Cultured ,Extracellular Matrix ,Female ,HEK293 Cells ,Humans ,Hyperglycemia ,Integrins ,Ion Exchange ,Mechanotransduction ,Cellular ,Mice ,Microscopy ,Confocal ,Middle Aged ,Mitochondria ,Mitochondrial Dynamics ,Oxidative Stress ,Reactive Oxygen Species ,Signal Transduction ,Sodium-Hydrogen Exchanger 1 ,Time-Lapse Imaging ,UPRmt ,adhesion ,aging ,cancer ,extracellular matrix ,mechanical stress ,mechanotabolism ,metabolism ,oxidative stress ,tension ,Medical Biochemistry and Metabolomics ,Endocrinology & Metabolism ,Biochemistry and cell biology ,Medical biochemistry and metabolomics - Abstract
Mitochondria control eukaryotic cell fate by producing the energy needed to support life and the signals required to execute programed cell death. The biochemical milieu is known to affect mitochondrial function and contribute to the dysfunctional mitochondrial phenotypes implicated in cancer and the morbidities of aging. However, the physical characteristics of the extracellular matrix are also altered in cancerous and aging tissues. Here, we demonstrate that cells sense the physical properties of the extracellular matrix and activate a mitochondrial stress response that adaptively tunes mitochondrial function via solute carrier family 9 member A1-dependent ion exchange and heat shock factor 1-dependent transcription. Overall, our data indicate that adhesion-mediated mechanosignaling may play an unappreciated role in the altered mitochondrial functions observed in aging and cancer.
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- 2021
23. Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta-analysis.
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Hahn, Judith A, Murnane, Pamela M, Vittinghoff, Eric, Muyindike, Winnie R, Emenyonu, Nneka I, Fatch, Robin, Chamie, Gabriel, Haberer, Jessica E, Francis, Joel M, Kapiga, Saidi, Jacobson, Karen, Myers, Bronwyn, Couture, Marie Claude, DiClemente, Ralph J, Brown, Jennifer L, So-Armah, Kaku, Sulkowski, Mark, Marcus, Gregory M, Woolf-King, Sarah, Cook, Robert L, Richards, Veronica L, Molina, Patricia, Ferguson, Tekeda, Welsh, David, Piano, Mariann R, Phillips, Shane A, Stewart, Scott, Afshar, Majid, Page, Kimberly, McGinnis, Kathleen, Fiellin, David A, Justice, Amy C, Bryant, Kendall, and Saitz, Richard
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alcohol ,individual participant data meta-analysis ,phosphatidylethanol ,sensitivity ,individual participant data meta‐ ,analysis ,Substance Abuse ,Liver Disease ,Alcoholism ,Alcohol Use and Health ,Clinical Research ,Digestive Diseases ,Oral and gastrointestinal ,Clinical Sciences ,Neurosciences ,Psychology - Abstract
BackgroundObjective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption.MethodsWe identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score.ResultsOne third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.ConclusionsAmong people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.
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- 2021
24. Inferring the palaeobiology of palorchestid marsupials through analysis of mammalian humeral and femoral shape
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Richards, Hazel L., Rovinsky, Douglass S., Adams, Justin W., and Evans, Alistair R.
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- 2023
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25. The Great Markarian 421 Flare of February 2010: Multiwavelength variability and correlation studies
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Abeysekara, A. U., Benbow, W., Bird, R., Brill, A., Brose, R., Buchovecky, M., Buckley, J. H., Christiansen, J. L., Chromey, A. J., Daniel, M. K., Dumm, J., Falcone, A., Feng, Q., Finley, J. P., Fortson, L., Furniss, A., Galante, N., Gent, A., Gillanders, G. H., Giuri, C., Gueta, O., Hassan, T., Hervet, O., Holder, J., Hughes, G., Humensky, T. B., Johnson, C. A., Kaaret, P., Kar, P., Kelley-Hoskins, N., Kertzman, M., Kieda, D., Krause, M., Krennrich, F., Kumar, S., Lang, M. J., Moriarty, P., Mukherjee, R., Nelson, T., Nieto, D., Nievas-Rosillo, M., O'Brien, S., Ong, R. A., Otte, A. N., Park, N., Petrashyk, A., Pichel, A., Pohl, M., Prado, R. R., Pueschel, E., Quinn, J., Ragan, K., Reynolds, P. T., Richards, G. T., Roache, E., Rovero, A. C., Rulten, C., Sadeh, I., Santander, M., Sembroski, G. H., Shahinyan, K., Stevenson, B., Sushch, I., Tyler, J., Vassiliev, V. V., Wakely, S. P., Weinstein, A., Wells, R. M., Wilcox, P., Wilhelm, A., Williams, D. A., Zitzer, B., Acciari, V. A., Ansoldi, S., Antonelli, L. A., Engels, A. Arbet, Baack, D., Babić, A., Banerjee, B., de Almeida, U. Barres, Barrio, J. A., González, J. Becerra, Bednarek, W., Bellizzi, L., Bernardini, E., Berti, A., Besenrieder, J., Bhattacharyya, W., Bigongiari, C., Biland, A., Blanch, O., Bonnoli, G., Busetto, G., Carosi, R., Ceribella, G., Chai, Y., Cikota, S., Colak, S. M., Colin, U., Colombo, E., Contreras, J. L., Cortina, J., Covino, S., D'Elia, V., Da Vela, P., Dazzi, F., De Angelis, A., De Lotto, B., Delfino, M., Delgado, J., Di Pierro, F., Espiñera, E. Do Souto, Prester, D. Dominis, Dorner, D., Doro, M., Einecke, S., Elsaesser, D., Ramazani, V. Fallah, Fattorini, A., Fernández-Barral, A., Ferrara, G., Fidalgo, D., Foffano, L., Fonseca, M. V., Font, L., Fruck, C., Galindo, D., Gallozzi, S., López, R. J. García, Garczarczyk, M., Gasparyan, S., Gaug, M., Godinović, N., Green, D., Guberman, D., Hadasch, D., Hahn, A., Herrera, J., Hoang, J., Hrupec, D., Inoue, S., Ishio, K., Iwamura, Y., Kubo, H., Kushida, J., Lamastra, A., Lelas, D., Leone, F., Lindfors, E., Lombardi, S., Longo, F., López, M., López-Coto, R., López-Oramas, A., Fraga, B. Machado de Oliveira, Maggio, C., Majumdar, P., Makariev, M., Mallamaci, M., Maneva, G., Manganaro, M., Mannheim, K., Maraschi, L., Mariotti, M., Martínez, M., Masuda, S., Mazin, D., Miceli, D., Minev, M., Miranda, J. M., Mirzoyan, R., Molina, E., Moralejo, A., Morcuende, D., Moreno, V., Moretti, E., Munar-Adrover, P., Neustroev, V., Niedzwiecki, A., Rosillo, M. Nievas, Nigro, C., Nilsson, K., Ninci, D., Nishijima, K., Noda, K., Nogués, L., Nöthe, M., Paiano, S., Palacio, J., Palatiello, M., Paneque, D., Paoletti, R., Paredes, J. M., Peñil, P., Peresano, M., Persic, M., Moroni, P. G. Prada, Prandini, E., Puljak, I., Rhode, W., Ribó, M., Rico, J., Righi, C., Rugliancich, A., Saha, L., Sahakyan, N., Saito, T., Satalecka, K., Schweizer, T., Sitarek, J., Šnidarić, I., Sobczynska, D., Somero, A., Stamerra, A., Strom, D., Strzys, M., Sun, S., Surić, T., Tavecchio, F., Temnikov, P., Terzić, T., Teshima, M., Torres-Albà, N., Tsujimoto, S., van Scherpenberg, J., Vanzo, G., Acosta, M. Vazquez, Vovk, I., Will, M., Zarić, D., Aller, H. D., Aller, M. F., Carini, M. T., Horan, D., Jordan, B., Jorstad, Svetlana G., Kurtanidze, O. M., Kurtanidze, S. O., Lähteenmäki, A., Larionov, V. M., Larionova, E. G., Madejski, G., Marscher, Alan P., Max-Moerbeck, W., Moody, J. Ward, Morozova, D. A., Nikolashvili, M. G., Raiteri, C. M., Readhead, A. C. S., Richards, J. L., Sadun, Alberto C., Sakamoto, T., Sigua, L. A., Smith, P. S., Talvikki, H., Tammi, J., Tornikoski, M., Troitsky, I. S., and Villata, M.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
We report on variability and correlation studies using multiwavelength observations of the blazar Mrk 421 during the month of February, 2010 when an extraordinary flare reaching a level of $\sim$27~Crab Units above 1~TeV was measured in very-high-energy (VHE) $\gamma$-rays with the VERITAS observatory. This is the highest flux state for Mrk 421 ever observed in VHE $\gamma$-rays. Data are analyzed from a coordinated campaign across multiple instruments including VHE $\gamma$-ray (VERITAS, MAGIC), high-energy (HE) $\gamma$-ray (Fermi-LAT), X-ray (Swift}, RXTE, MAXI), optical (including the GASP-WEBT collaboration and polarization data) and radio (Mets\"ahovi, OVRO, UMRAO). Light curves are produced spanning multiple days before and after the peak of the VHE flare, including over several flare `decline' epochs. The main flare statistics allow 2-minute time bins to be constructed in both the VHE and optical bands enabling a cross-correlation analysis that shows evidence for an optical lag of $\sim$25-55 minutes, the first time-lagged correlation between these bands reported on such short timescales. Limits on the Doppler factor ($\delta \gtrsim 33$) and the size of the emission region ($ \delta^{-1}R_B \lesssim 3.8\times 10^{13}\,\,\mbox{cm}$) are obtained from the fast variability observed by VERITAS during the main flare. Analysis of 10-minute-binned VHE and X-ray data over the decline epochs shows an extraordinary range of behavior in the flux-flux relationship: from linear to quadratic to lack of correlation to anti-correlation. Taken together, these detailed observations of an unprecedented flare seen in Mrk 421 are difficult to explain by the classic single-zone synchrotron self-Compton model., Comment: 41 pages including 3 appendices, 13 figures; version accepted to Astrophysical Journal
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- 2020
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26. Unravelling the complex behavior of Mrk 421 with simultaneous X-ray and VHE observations during an extreme flaring activity in April 2013
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MAGIC collaboration, Acciari, V. A., Ansoldi, S., Antonelli, L. A., Engels, A. Arbet, Baack, D., Babic, A., Banerjee, B., de Almeida, U. Barres, Barrio, J. A., Gonzalez, J. Becerra, Bednarek, W., Bellizzi, L., Bernardini, E., Berti, A., Besenrieder, J., Bhattacharyya, W., Bigongiari, C., Biland, A., Blanch, O., Bonnoli, G., Bosnjak, Z., Busetto, G., Carosi, R., Ceribella, G., Cerruti, M., Chai, Y., Chilingarian, A., Cikota, S., Colak, S. M., Colin, U., Colombo, E., Contreras, J. L., Cortina, J., Covino, S., D'Elia, V., Da Vela, P., Dazzi, F., De Angelis, A., De Lotto, B., Del Puppo, F., Delfino, M., Delgado, J., Depaoli, D., Di Pierro, F., Di Venere, L., Espineira, E. Do Souto, Prester, D. Dominis, Donini, A., Dorner, D., Doro, M., Elsaesser, D., Ramazani, V. Fallah, Fattorini, A., Ferrara, G., Foffano, L., Fonseca, M. V., Font, L., Fruck, C., Fukami, S., Lopez, R. J. Garcia, Garczarczyk, M., Gasparyan, S., Gaug, M., Giglietto, N., Giordano, F., Gliwny, P., Godinovic, N., Green, D., Hadasch, D., Hahn, A., Herrera, J., Hoang, J., Hrupec, D., Hutten, M., Inada, T., Inoue, S., Ishio, K., Iwamura, Y., Jouvin, L., Kajiwara, Y., Kerszberg, D., Kobayashi, Y., Kubo, H., Kushida, J., Lamastra, A., Lelas, D., Leone, F., Lindfors, E., Lombardi, S., Longo, F., Lopez, M., Lopez-Coto, R., Lopez-Oramas, A., Loporchio, S., Fraga, B. Machado de Oliveira, Maggio, C., Majumdar, P., Makariev, M., Mallamaci, M., Maneva, G., Manganaro, M., Mannheim, K., Maraschi, L., Mariotti, M., Martinez, M., Mazin, D., Mender, S., Micanovic, S., Miceli, D., Miener, T., Minev, M., Miranda, J. M., Mirzoyan, R., Molina, E., Moralejo, A., Morcuende, D., Moreno, V., Moretti, E., Munar-Adrover, P., Neustroev, V., Nigro, C., Nilsson, K., Ninci, D., Nishijima, K., Noda, K., Nogues, L., Nozaki, S., Ohtani, Y., Oka, T., Otero-Santos, J., Palatiello, M., Paneque, D., Paoletti, R., Paredes, J. M., Pavletic, L., Penil, P., Peresano, M., Persic, M., Moroni, P. G. Prada, Prandini, E., Puljak, I., Rhode, W., Ribo, M., Rico, J., Righi, C., Rugliancich, A., Saha, L., Sahakyan, N., Saito, T., Sakurai, S., Satalecka, K., Schleicher, B., Schmidt, K., Schweizer, T., Sitarek, J., Snidaric, I., Sobczynska, D., Spolon, A., Stamerra, A., Strom, D., Strzys, M., Suda, Y., Suric, T., Takahashi, M., Tavecchio, F., Temnikov, P., Terzic, T., Teshima, M., Torres-Alba, N., Tosti, L., van Scherpenberg, J., Vanzo, G., Acosta, M. Vazquez, Ventura, S., Verguilov, V., Vigorito, C. F., Vitale, V., Vovk, I., Will, M., Zaric, D., groups, Other, Petropoulou, M., Finke, J., D'Ammando, F., Balokovic, M., Madejski, G., Mori, K., Puccetti, Simonetta, Leto, C., Perri, M., Verrecchia, F., Villata, M., Raiteri, C. M., Agudo, I., Bachev, R., Berdyugin, A., Blinov, D. A., Chanishvili, R., Chen, W. P., Chigladze, R., Damljanovic, G., Eswaraiah, C., Grishina, T. S., Ibryamov, S., Jordan, B., Jorstad, S. G., Joshi, M., Kopatskaya, E. N., Kurtanidze, O. M., Kurtanidze, S. O., Larionova, E. G., Larionova, L. V., Larionov, V. M., Latev, G., Lin, H. C., Marscher, A. P., Mokrushina, A. A., Morozova, D. A., Nikolashvili, M. G., Semkov, E., Smith, P. S., Strigachev, A., Troitskaya, Yu. V., Troitsky, I. S., Vince, O., Barnes, J., Guever, T., Moody, J. W., Sadun, A. C., Hovatta, T., Richards, J. L., Max-Moerbeck, W., Readhead, A. C. R., Lahteenmaki, A., Tornikoski, M., Tammi, J., Ramakrishnan, V., and Reinthal, R.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
We report on a multi-band variability and correlation study of the TeV blazar Mrk 421 during an exceptional flaring activity observed from 2013 April 11 to 2013 April 19. The study uses, among others, data from GASP-WEBT, Swift, NuSTAR, Fermi-LAT, VERITAS, and MAGIC. The large blazar activity, and the 43 hours of simultaneous NuSTAR and MAGIC/VERITAS observations, permitted variability studies on 15 minute time bins, and over three X-ray bands (3-7 keV, 7-30 keV and 30-80 keV) and three very-high-energy (>0.1 TeV, hereafter VHE) gamma-ray bands (0.2-0.4 TeV, 0.4-0.8 TeV and >0.8 TeV). We detected substantial flux variations on multi-hour and sub-hour timescales in all the X-ray and VHE gamma-ray bands. The characteristics of the sub-hour flux variations are essentially energy-independent, while the multi-hour flux variations can have a strong dependence on the energy of the X-ray and the VHE gamma rays. The three VHE bands and the three X-ray bands are positively correlated with no time-lag, but the strength and the characteristics of the correlation changes substantially over time and across energy bands. Our findings favour multi-zone scenarios for explaining the achromatic/chromatic variability of the fast/slow components of the light curves, as well as the changes in the flux-flux correlation on day-long timescales. We interpret these results within a magnetic reconnection scenario, where the multi-hour flux variations are dominated by the combined emission from various plasmoids of different sizes and velocities, while the sub-hour flux variations are dominated by the emission from a single small plasmoid moving across the magnetic reconnection layer., Comment: 46 pages, 17 figures, 9 tables, accepted for publication in ApJ Supplements
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- 2020
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27. Mass spectrometry‐based protein–protein interaction networks for the study of human diseases
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Richards, Alicia L, Eckhardt, Manon, and Krogan, Nevan J
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Biochemistry and Cell Biology ,Biological Sciences ,Biotechnology ,2.1 Biological and endogenous factors ,Generic health relevance ,Neurological ,Good Health and Well Being ,Disease ,Gene Regulatory Networks ,Humans ,Mass Spectrometry ,Protein Interaction Mapping ,affinity purification ,mass spectrometry ,networks ,protein-protein interactions ,proximity labeling ,Other Biological Sciences ,Bioinformatics ,Biochemistry and cell biology - Abstract
A better understanding of the molecular mechanisms underlying disease is key for expediting the development of novel therapeutic interventions. Disease mechanisms are often mediated by interactions between proteins. Insights into the physical rewiring of protein-protein interactions in response to mutations, pathological conditions, or pathogen infection can advance our understanding of disease etiology, progression, and pathogenesis and can lead to the identification of potential druggable targets. Advances in quantitative mass spectrometry (MS)-based approaches have allowed unbiased mapping of these disease-mediated changes in protein-protein interactions on a global scale. Here, we review MS techniques that have been instrumental for the identification of protein-protein interactions at a system-level, and we discuss the challenges associated with these methodologies as well as novel MS advancements that aim to address these challenges. An overview of examples from diverse disease contexts illustrates the potential of MS-based protein-protein interaction mapping approaches for revealing disease mechanisms, pinpointing new therapeutic targets, and eventually moving toward personalized applications.
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- 2021
28. Secondary Analysis of a Randomized Clinical Trial of Naltrexone Among Women Living With HIV: Correlations Between Reductions in Self‐Reported Alcohol Use and Changes in Phosphatidylethanol
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Richards, Veronica L, Sajdeya, Ruba, Villalba, Karina, Wang, Yan, Bryant, Vaughn, Brumback, Babette, Bryant, Kendall, Hahn, Judith A, and Cook, Robert L
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Brain Disorders ,Clinical Trials and Supportive Activities ,Alcoholism ,Alcohol Use and Health ,Substance Misuse ,Clinical Research ,Good Health and Well Being ,Adult ,Alcohol Deterrents ,Alcohol Drinking ,Female ,Florida ,Glycerophospholipids ,HIV Infections ,Humans ,Middle Aged ,Naltrexone ,Self Report ,Phosphatidylethanol ,Alcohol ,Heavy Drinking ,HIV ,Women Living With HIV ,Clinical Sciences ,Neurosciences ,Psychology ,Substance Abuse - Abstract
BackgroundDirect biomarkers such as phosphatidylethanol (PEth) have the capability to detect heavy alcohol use, but it is unclear how strongly self-reported reduction in alcohol use correlates with reduction in PEth. We sought to explore the strength of correlation between reductions in self-reported alcohol use and change in PEth among a sample of women living with HIV (WLWH) who participated in a clinical trial to reduce heavy alcohol use. We also sought to determine whether this correlation was stronger in women with lower body mass index (BMI) and women without an alcohol use disorder (AUD).Methods81 WLWH (mean age = 48.7, 80% Black) engaging in a randomized trial of naltrexone versus placebo with a positive baseline PEth (≥8 ng/ml), and alcohol use data at baseline, 2, and 7 months were included in this analysis. Spearman correlation coefficients were compared to measure the correlation between baseline PEth and number of drinks per week by demographic, biological, and alcohol use factors. Mini-International Neuropsychiatric Interview was used to screen for AUD. Further analyses were stratified by BMI and AUD. Spearman correlation coefficients were calculated for the change in PEth and the change in number of drinks per week over 7 months, including 3 time-points: baseline, 2, and 7 months.ResultsAt baseline, the correlation between baseline PEth and the number of drinks per week was significantly stronger for those with a BMI ≤25 compared to those with a BMI > 25 (r = 0.66; r = 0.26, respectively). Similarly, the correlation between baseline PEth and number of drinks was stronger for those who did not screen positive for AUD compared with those who did (r = 0.66; r = 0.25, respectively). When stratifying by BMI, a low-to-moderate correlation (r = 0.32, p = 0.02) was present for persons with a BMI > 25; when stratifying by AUD, a moderate correlation (r = 0.50, p
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- 2021
29. The Global Phosphorylation Landscape of SARS-CoV-2 Infection.
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Bouhaddou, Mehdi, Memon, Danish, Meyer, Bjoern, White, Kris M, Rezelj, Veronica V, Correa Marrero, Miguel, Polacco, Benjamin J, Melnyk, James E, Ulferts, Svenja, Kaake, Robyn M, Batra, Jyoti, Richards, Alicia L, Stevenson, Erica, Gordon, David E, Rojc, Ajda, Obernier, Kirsten, Fabius, Jacqueline M, Soucheray, Margaret, Miorin, Lisa, Moreno, Elena, Koh, Cassandra, Tran, Quang Dinh, Hardy, Alexandra, Robinot, Rémy, Vallet, Thomas, Nilsson-Payant, Benjamin E, Hernandez-Armenta, Claudia, Dunham, Alistair, Weigang, Sebastian, Knerr, Julian, Modak, Maya, Quintero, Diego, Zhou, Yuan, Dugourd, Aurelien, Valdeolivas, Alberto, Patil, Trupti, Li, Qiongyu, Hüttenhain, Ruth, Cakir, Merve, Muralidharan, Monita, Kim, Minkyu, Jang, Gwendolyn, Tutuncuoglu, Beril, Hiatt, Joseph, Guo, Jeffrey Z, Xu, Jiewei, Bouhaddou, Sophia, Mathy, Christopher JP, Gaulton, Anna, Manners, Emma J, Félix, Eloy, Shi, Ying, Goff, Marisa, Lim, Jean K, McBride, Timothy, O'Neal, Michael C, Cai, Yiming, Chang, Jason CJ, Broadhurst, David J, Klippsten, Saker, De Wit, Emmie, Leach, Andrew R, Kortemme, Tanja, Shoichet, Brian, Ott, Melanie, Saez-Rodriguez, Julio, tenOever, Benjamin R, Mullins, R Dyche, Fischer, Elizabeth R, Kochs, Georg, Grosse, Robert, García-Sastre, Adolfo, Vignuzzi, Marco, Johnson, Jeffery R, Shokat, Kevan M, Swaney, Danielle L, Beltrao, Pedro, and Krogan, Nevan J
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Caco-2 Cells ,Vero Cells ,Animals ,Humans ,Pneumonia ,Viral ,Coronavirus Infections ,Peptidyl-Dipeptidase A ,Casein Kinase II ,Cyclin-Dependent Kinases ,p38 Mitogen-Activated Protein Kinases ,Receptor Protein-Tyrosine Kinases ,Proto-Oncogene Proteins ,Protein Kinase Inhibitors ,Antiviral Agents ,Drug Evaluation ,Preclinical ,Proteomics ,Phosphorylation ,Host-Pathogen Interactions ,Phosphatidylinositol 3-Kinases ,HEK293 Cells ,Pandemics ,Spike Glycoprotein ,Coronavirus ,A549 Cells ,Betacoronavirus ,Phosphoinositide-3 Kinase Inhibitors ,Chlorocebus aethiops ,COVID-19 ,Angiotensin-Converting Enzyme 2 ,SARS-CoV-2 ,AXL ,CDK ,MAPK ,PIKFYVE ,antiviral ,casein kinase II ,mass spectrometry ,p38 ,phosphoproteomics ,Infectious Diseases ,Prevention ,Biodefense ,Emerging Infectious Diseases ,Vaccine Related ,Lung ,Infection ,Developmental Biology ,Biological Sciences ,Medical and Health Sciences - Abstract
The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.
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- 2020
30. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
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Gordon, David E, Jang, Gwendolyn M, Bouhaddou, Mehdi, Xu, Jiewei, Obernier, Kirsten, White, Kris M, O’Meara, Matthew J, Rezelj, Veronica V, Guo, Jeffrey Z, Swaney, Danielle L, Tummino, Tia A, Hüttenhain, Ruth, Kaake, Robyn M, Richards, Alicia L, Tutuncuoglu, Beril, Foussard, Helene, Batra, Jyoti, Haas, Kelsey, Modak, Maya, Kim, Minkyu, Haas, Paige, Polacco, Benjamin J, Braberg, Hannes, Fabius, Jacqueline M, Eckhardt, Manon, Soucheray, Margaret, Bennett, Melanie J, Cakir, Merve, McGregor, Michael J, Li, Qiongyu, Meyer, Bjoern, Roesch, Ferdinand, Vallet, Thomas, Mac Kain, Alice, Miorin, Lisa, Moreno, Elena, Naing, Zun Zar Chi, Zhou, Yuan, Peng, Shiming, Shi, Ying, Zhang, Ziyang, Shen, Wenqi, Kirby, Ilsa T, Melnyk, James E, Chorba, John S, Lou, Kevin, Dai, Shizhong A, Barrio-Hernandez, Inigo, Memon, Danish, Hernandez-Armenta, Claudia, Lyu, Jiankun, Mathy, Christopher JP, Perica, Tina, Pilla, Kala Bharath, Ganesan, Sai J, Saltzberg, Daniel J, Rakesh, Ramachandran, Liu, Xi, Rosenthal, Sara B, Calviello, Lorenzo, Venkataramanan, Srivats, Liboy-Lugo, Jose, Lin, Yizhu, Huang, Xi-Ping, Liu, YongFeng, Wankowicz, Stephanie A, Bohn, Markus, Safari, Maliheh, Ugur, Fatima S, Koh, Cassandra, Savar, Nastaran Sadat, Tran, Quang Dinh, Shengjuler, Djoshkun, Fletcher, Sabrina J, O’Neal, Michael C, Cai, Yiming, Chang, Jason CJ, Broadhurst, David J, Klippsten, Saker, Sharp, Phillip P, Wenzell, Nicole A, Kuzuoglu-Ozturk, Duygu, Wang, Hao-Yuan, Trenker, Raphael, Young, Janet M, Cavero, Devin A, Hiatt, Joseph, Roth, Theodore L, Rathore, Ujjwal, Subramanian, Advait, Noack, Julia, Hubert, Mathieu, Stroud, Robert M, Frankel, Alan D, Rosenberg, Oren S, Verba, Kliment A, Agard, David A, Ott, Melanie, Emerman, Michael, and Jura, Natalia
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Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Coronaviruses Therapeutics and Interventions ,Emerging Infectious Diseases ,Infectious Diseases ,Coronaviruses ,5.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Animals ,Antiviral Agents ,Betacoronavirus ,COVID-19 ,Chlorocebus aethiops ,Cloning ,Molecular ,Coronavirus Infections ,Drug Evaluation ,Preclinical ,Drug Repositioning ,HEK293 Cells ,Host-Pathogen Interactions ,Humans ,Immunity ,Innate ,Mass Spectrometry ,Molecular Targeted Therapy ,Pandemics ,Pneumonia ,Viral ,Protein Binding ,Protein Biosynthesis ,Protein Domains ,Protein Interaction Mapping ,Protein Interaction Maps ,Receptors ,sigma ,SARS-CoV-2 ,SKP Cullin F-Box Protein Ligases ,Vero Cells ,Viral Proteins ,COVID-19 Drug Treatment ,General Science & Technology - Abstract
A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.
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- 2020
31. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.
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Gordon, David E, Jang, Gwendolyn M, Bouhaddou, Mehdi, Xu, Jiewei, Obernier, Kirsten, O'Meara, Matthew J, Guo, Jeffrey Z, Swaney, Danielle L, Tummino, Tia A, Hüttenhain, Ruth, Kaake, Robyn M, Richards, Alicia L, Tutuncuoglu, Beril, Foussard, Helene, Batra, Jyoti, Haas, Kelsey, Modak, Maya, Kim, Minkyu, Haas, Paige, Polacco, Benjamin J, Braberg, Hannes, Fabius, Jacqueline M, Eckhardt, Manon, Soucheray, Margaret, Bennett, Melanie J, Cakir, Merve, McGregor, Michael J, Li, Qiongyu, Naing, Zun Zar Chi, Zhou, Yuan, Peng, Shiming, Kirby, Ilsa T, Melnyk, James E, Chorba, John S, Lou, Kevin, Dai, Shizhong A, Shen, Wenqi, Shi, Ying, Zhang, Ziyang, Barrio-Hernandez, Inigo, Memon, Danish, Hernandez-Armenta, Claudia, Mathy, Christopher JP, Perica, Tina, Pilla, Kala B, Ganesan, Sai J, Saltzberg, Daniel J, Ramachandran, Rakesh, Liu, Xi, Rosenthal, Sara B, Calviello, Lorenzo, Venkataramanan, Srivats, Lin, Yizhu, Wankowicz, Stephanie A, Bohn, Markus, Trenker, Raphael, Young, Janet M, Cavero, Devin, Hiatt, Joe, Roth, Theo, Rathore, Ujjwal, Subramanian, Advait, Noack, Julia, Hubert, Mathieu, Roesch, Ferdinand, Vallet, Thomas, Meyer, Björn, White, Kris M, Miorin, Lisa, Agard, David, Emerman, Michael, Ruggero, Davide, García-Sastre, Adolfo, Jura, Natalia, von Zastrow, Mark, Taunton, Jack, Schwartz, Olivier, Vignuzzi, Marco, d'Enfert, Christophe, Mukherjee, Shaeri, Jacobson, Matt, Malik, Harmit S, Fujimori, Danica G, Ideker, Trey, Craik, Charles S, Floor, Stephen, Fraser, James S, Gross, John, Sali, Andrej, Kortemme, Tanja, Beltrao, Pedro, Shokat, Kevan, Shoichet, Brian K, and Krogan, Nevan J
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Prevention ,Vaccine Related ,Biodefense ,Infectious Diseases ,Rare Diseases ,Pneumonia & Influenza ,Emerging Infectious Diseases ,Lung ,Pneumonia ,5.1 Pharmaceuticals ,2.2 Factors relating to the physical environment ,Infection - Abstract
An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity- purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.
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- 2020
32. Season and prey identity mediate the effect of predators on parasites in rodents: a test of the healthy herds hypothesis
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Richards, Robert L., Conner, L. Mike, Morris, Gail, Drake, John M., and Ezenwa, Vanessa O.
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- 2023
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33. Identifying the best measures of alcohol consumption to predict future HIV viral suppression trajectories
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Richards, Veronica L., Leeman, Robert F., Wang, Yan, Cook, Christa, Prins, Cindy, Ennis, Nicole, Spencer, Emma C., and Cook, Robert L.
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- 2022
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34. The extreme HBL behaviour of Markarian 501 during 2012
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Ahnen, M. L., Ansoldi, S., Antonelli, L. A., Arcaro, C., Babić, A., Banerjee, B., Bangale, P., de Almeida, U. Barres, Barrio, J. A., González, J. Becerra, Bednarek, W., Bernardini, E., Berti, A., Bhattacharyya, W., Blanch, O., Bonnoli, G., Carosi, R., Carosi, A., Chatterjee, A., Colak, S. M., Colin, P., Colombo, E., Contreras, J. L., Cortina, J., Covino, S., Cumani, P., Da Vela, P., Dazzi, F., De Angelis, A., De Lotto, B., Delfino, M., Delgado, J., Di Pierro, F., Doert, M., Domínguez, A., Prester, D. Dominis, Doro, M., Glawion, D. Eisenacher, Engelkemeier, M., Ramazani, V. Fallah, Fernández-Barral, A., Fidalgo, D., Fonseca, M. V., Font, L., Fruck, C., Galindo, D., López, R. J. García, Garczarczyk, M., Gaug, M., Giammaria, P., Godinović, N., Gora, D., Guberman, D., Hadasch, D., Hahn, A., Hassan, T., Hayashida, M., Herrera, J., Hose, J., Hrupec, D., Ishio, K., Konno, Y., Kubo, H., Kushida, J., Kuveždić, D., Lelas, D., Lindfors, E., Lombardi, S., Longo, F., López, M., Maggio, C., Majumdar, P., Makariev, M., Maneva, G., Manganaro, M., Maraschi, L., Mariotti, M., Martínez, M., Mazin, D., Menzel, U., Minev, M., Miranda, J. M., Mirzoyan, R., Moralejo, A., Moreno, V., Moretti, E., Nagayoshi, T., Neustroev, V., Niedzwiecki, A., Rosillo, M. Nievas, Nigro, C., Nilsson, K., Ninci, D., Nishijima, K., Noda, K., Nogués, L., Paiano, S., Palacio, J., Paneque, D., Paoletti, R., Paredes, J. M., Pedaletti, G., Peresano, M., Perri, L., Persic, M., Moroni, P. G. Prada, Prandini, E., Puljak, I., Garcia, J. R., Reichardt, I., Ribó, M., Rico, J., Righi, C., Rugliancich, A., Saito, T., Satalecka, K., Schroeder, S., Schweizer, T., Shore, S. N., Sitarek, J., Šnidarić, I., Sobczynska, D., Stamerra, A., Strzys, M., Surić, T., Takalo, L., Tavecchio, F., Temnikov, P., Terzić, T., Teshima, M., Torres-Albà, N., Treves, A., Tsujimoto, S., Vanzo, G., Acosta, M. Vazquez, Vovk, I., Ward, J. E., Will, M., Zarić, D., Arbet-Engels, A., Baack, D., Balbo, M., Biland, A., Blank, M., Bretz, T., Bruegge, K., Bulinski, M., Buss, J., Dmytriiev, A., Dorner, D., Einecke, S., Elsaesser, D., Herbst, T., Hildebrand, D., Kortmann, L., Linhoff, L., Mahlke, M., Mannheim, K., Mueller, S. A., Neise, D., Neronov, A., Noethe, M., Oberkirch, J., Paravac, A., Rhode, W., Schleicher, B., Schulz, F., Sedlaczek, K., Shukla, A., Sliusar, V., Walter, R., Archer, A., Benbow, W., Bird, R., Brose, R., Buckley, J. H., Bugaev, V., Christiansen, J. L., Cui, W., Daniel, M. K., Falcone, A., Feng, Q., Finley, J. P., Gillanders, G. H., Gueta, O., Hanna, D., Hervet, O., Holder, J., Hughes, G., Hütten, M., Humensky, T. B., Johnson, C. A., Kaaret, P., Kar, P., Kelley-Hoskins, N., Kertzman, M., Kieda, D., Krause, M., Krennrich, F., Kumar, S., Lang, M. J., Lin, T. T. Y., Maier, G., McArthur, S., Moriarty, P., Mukherjee, R., O'Brien, S., Ong, R. A., Otte, A. N., Park, N., Petrashyk, A., Pichel, A., Pohl, M., Quinn, J., Ragan, K., Reynolds, P. T., Richards, G. T., Roache, E., Rovero, A. C., Rulten, C., Sadeh, I., Santander, M., Sembroski, G. H., Shahinyan, K., Sushch, I., Tyler, J., Wakely, S. P., Weinstein, A., Wells, R. M., Wilcox, P., Wilhel, A., Williams, D. A., Williamson, T. J, Zitzer, B., Perri, M., Verrecchia, F., Leto, C., Villata, M., Raiteri, C. M., Jorstad, S. G., Larionov, V. M., Blinov, D. A., Grishina, T. S., Kopatskaya, E. N., Larionova, E. G., Nikiforova, A. A., Morozova, D. A., Troitskaya, Yu. V., Troitsky, I. S., Kurtanidze, O. M., Nikolashvili, M. G., Kurtanidze, S. O., Kimeridze, G. N., Chigladze, R. A., Strigachev, A., Sadun, A. C., Moody, J. W., Chen, W. P., Lin, H. C., Acosta-Pulido, J. A., Arévalo, M. J., Carnerero, M. I., González-Morales, P. A., Manilla-Robles, A., Jermak, H., Steele, I., Mundel, C., Benítez, E., Hiriart, D., Smith, P. S., Max-Moerbeck, W., Readhead, A. C. S., Richards, J. L., Hovatta, T., Lähteenmäki, A., Tornikoski, M., Tammi, J., Georganopoulos, M., and Baring, M. G.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
A multiwavelength campaign was organized to take place between March and July of 2012. Excellent temporal coverage was obtained with more than 25 instruments, including the MAGIC, FACT and VERITAS Cherenkov telescopes, the instruments on board the Swift and Fermi spacecraft, and the telescopes operated by the GASP-WEBT collaboration. Mrk 501 showed a very high energy (VHE) gamma-ray flux above 0.2 TeV of $\sim$0.5 times the Crab Nebula flux (CU) for most of the campaign. The highest activity occurred on 2012 June 9, when the VHE flux was $\sim$3 CU, and the peak of the high-energy spectral component was found to be at $\sim$2 TeV. This study reports very hard X-ray spectra, and the hardest VHE spectra measured to date for Mrk 501. The fractional variability was found to increase with energy, with the highest variability occurring at VHE, and a significant correlation between the X-ray and VHE bands. The unprecedentedly hard X-ray and VHE spectra measured imply that their low- and high-energy components peaked above 5 keV and 0.5 TeV, respectively, during a large fraction of the observing campaign, and hence that Mrk 501 behaved like an extreme high-frequency- peaked blazar (EHBL) throughout the 2012 observing season. This suggests that being an EHBL may not be a permanent characteristic of a blazar, but rather a state which may change over time. The one-zone synchrotron self-Compton (SSC) scenario can successfully describe the segments of the SED where most energy is emitted, with a significant correlation between the electron energy density and the VHE gamma-ray activity, suggesting that most of the variability may be explained by the injection of high-energy electrons. The one-zone SSC scenario used reproduces the behaviour seen between the measured X-ray and VHE gamma-ray fluxes, and predicts that the correlation becomes stronger with increasing energy of the X-rays., Comment: 25 pages, 9 figures, accepted for publication in A&A. Corresponding authors: Gareth Hughes (gareth.hughes@cfa.harvard.edu), David Paneque (dpaneque@mppmu.mpg.de), Amit Shukla (amit.shukla@astro.uni-wuerzburg.de)
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- 2018
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35. The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia
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Richards, Alexander L, Pardiñas, Antonio F, Frizzati, Aura, Tansey, Katherine E, Lynham, Amy J, Holmans, Peter, Legge, Sophie E, Savage, Jeanne E, Agartz, Ingrid, Andreassen, Ole A, Blokland, Gabriella AM, Corvin, Aiden, Cosgrove, Donna, Degenhardt, Franziska, Djurovic, Srdjan, Espeseth, Thomas, Ferraro, Laura, Gayer-Anderson, Charlotte, Giegling, Ina, van Haren, Neeltje E, Hartmann, Annette M, Hubert, John J, Jönsson, Erik G, Konte, Bettina, Lennertz, Leonhard, Olde Loohuis, Loes M, Melle, Ingrid, Morgan, Craig, Morris, Derek W, Murray, Robin M, Nyman, Håkan, Ophoff, Roel A, van Os, Jim, Petryshen, Tracey L, Quattrone, Diego, Rietschel, Marcella, Rujescu, Dan, Rutten, Bart PF, Streit, Fabian, Strohmaier, Jana, Sullivan, Patrick F, Sundet, Kjetil, Wagner, Michael, Escott-Price, Valentina, Owen, Michael J, Donohoe, Gary, O’Donovan, Michael C, and Walters, James TR
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Genetics ,Prevention ,Schizophrenia ,Depression ,Behavioral and Social Science ,Mental Health ,Brain Disorders ,Serious Mental Illness ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,2.3 Psychological ,social and economic factors ,Mental health ,Bipolar Disorder ,Datasets as Topic ,Depressive Disorder ,Major ,Educational Status ,Genome-Wide Association Study ,Humans ,Intelligence ,Multifactorial Inheritance ,Psychotic Disorders ,psychiatry ,genomics ,intelligence ,bioinformatics ,GROUP Investigators ,EUGEI WP2 Group ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
BackgroundCognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases.MethodsWe combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases.ResultsPRS for both population IQ (P = 4.39 × 10-28) and EA (P = 1.27 × 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS.ConclusionsCognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.
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- 2020
36. Acquisition of visual priors and induced hallucinations in chronic schizophrenia
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Valton, Vincent, Karvelis, Povilas, Richards, Katie L, Seitz, Aaron R, Lawrie, Stephen M, and Seriès, Peggy
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Schizophrenia ,Brain Disorders ,Clinical Research ,Mental Health ,Mental health ,Adult ,Bayes Theorem ,Female ,Hallucinations ,Humans ,Male ,Middle Aged ,Models ,Neurological ,Motion Perception ,schizophrenia ,inference ,statistical learning ,hallucinations ,Bayes ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery - Abstract
Prominent theories suggest that symptoms of schizophrenia stem from learning deficiencies resulting in distorted internal models of the world. To test these theories further, we used a visual statistical learning task known to induce rapid implicit learning of the stimulus statistics. In this task, participants are presented with a field of coherently moving dots and are asked to report the presented direction of the dots (estimation task), and whether they saw any dots or not (detection task). Two of the directions were more frequently presented than the others. In controls, the implicit acquisition of the stimuli statistics influences their perception in two ways: (i) motion directions are perceived as being more similar to the most frequently presented directions than they really are (estimation biases); and (ii) in the absence of stimuli, participants sometimes report perceiving the most frequently presented directions (a form of hallucinations). Such behaviour is consistent with probabilistic inference, i.e. combining learnt perceptual priors with sensory evidence. We investigated whether patients with chronic, stable, treated schizophrenia (n = 20) differ from controls (n = 23) in the acquisition of the perceptual priors and/or their influence on perception. We found that although patients were slower than controls, they showed comparable acquisition of perceptual priors, approximating the stimulus statistics. This suggests that patients have no statistical learning deficits in our task. This may reflect our patients' relative wellbeing on antipsychotic medication. Intriguingly, however, patients experienced significantly fewer (P = 0.016) hallucinations of the most frequently presented directions than controls when the stimulus was absent or when it was very weak (prior-based lapse estimations). This suggests that prior expectations had less influence on patients' perception than on controls when stimuli were absent or below perceptual threshold.
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- 2019
37. Genome-wide association study identifies 30 loci associated with bipolar disorder
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Stahl, Eli A, Breen, Gerome, Forstner, Andreas J, McQuillin, Andrew, Ripke, Stephan, Trubetskoy, Vassily, Mattheisen, Manuel, Wang, Yunpeng, Coleman, Jonathan RI, Gaspar, Héléna A, de Leeuw, Christiaan A, Steinberg, Stacy, Pavlides, Jennifer M Whitehead, Trzaskowski, Maciej, Byrne, Enda M, Pers, Tune H, Holmans, Peter A, Richards, Alexander L, Abbott, Liam, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Bækvad-Hansen, Marie, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Belliveau, Richard, Bergen, Sarah E, Pedersen, Carsten Bøcker, Bøen, Erlend, Boks, Marco P, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Bybjerg-Grauholm, Jonas, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Clarke, Toni-Kim, Coryell, William, Craig, David W, Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Djurovic, Srdjan, Dobbyn, Amanda L, Dumont, Ashley, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Guzman-Parra, José, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Juréus, Anders
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Biological Sciences ,Genetics ,Mental Health ,Mental Illness ,Human Genome ,Biotechnology ,Bipolar Disorder ,Brain Disorders ,Schizophrenia ,Serious Mental Illness ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Mental health ,Case-Control Studies ,Depressive Disorder ,Major ,Female ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Psychotic Disorders ,Systems Biology ,eQTLGen Consortium ,BIOS Consortium ,Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P
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- 2019
38. The LiteBIRD Satellite Mission - Sub-Kelvin Instrument
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Suzuki, A., Ade, P. A. R., Akiba, Y., Alonso, D., Arnold, K., Aumont, J., Baccigalupi, C., Barron, D., Basak, S., Beckman, S., Borrill, J., Boulanger, F., Bucher, M., Calabrese, E., Chinone, Y., Cho, H-M., Cukierman, A., Curtis, D. W., de Haan, T., Dobbs, M., Dominjon, A., Dotani, T., Duband, L., Ducout, A., Dunkley, J., Duval, J. M., Elleflot, T., Eriksen, H. K., Errard, J., Fischer, J., Fujino, T., Funaki, T., Fuskeland, U., Ganga, K., Goeckner-Wald, N., Grain, J., Halverson, N. W., Hamada, T., Hasebe, T., Hasegawa, M., Hattori, K., Hattori, M., Hayes, L., Hazumi, M., Hidehira, N., Hill, C. A., Hilton, G., Hubmayr, J., Ichiki, K., Iida, T., Imada, H., Inoue, M., Inoue, Y., D., K., Ishino, H., Jeong, O., Kanai, H., Kaneko, D., Kashima, S., Katayama, N., Kawasaki, T., Kernasovskiy, S. A., Keskitalo, R., Kibayashi, A., Kida, Y., Kimura, K., Kisner, T., Kohri, K., Komatsu, E., Komatsu, K., Kuo, C. L., Kurinsky, N. A., Kusaka, A., Lazarian, A., Lee, A. T., Li, D., Linder, E., Maffei, B., Mangilli, A., Maki, M., Matsumura, T., Matsuura, S., Meilhan, D., Mima, S., Minami, Y., Mitsuda, K., Montier, L., Nagai, M., Nagasaki, T., Nagata, R., Nakajima, M., Nakamura, S., Namikawa, T., Naruse, M., Nishino, H., Nitta, T., Noguchi, T., Ogawa, H., Oguri, S., Okada, N., Okamoto, A., Okamura, T., Otani, C., Patanchon, G., Pisano, G., Rebeiz, G., Remazeilles, M., Richards, P. L., Sakai, S., Sakurai, Y., Sato, Y., Sato, N., Sawada, M., Segawa, Y., Sekimoto, Y., Seljak, U., Sherwin, B. D., Shimizu, T., Shinozaki, K., Stompor, R., Sugai, H., Sugita, H., Suzuki, J., Tajima, O., Takada, S., Takaku, R., Takakura, S., Takatori, S., Tanabe, D., Taylor, E., Thompson, K. L., Thorne, B., Tomaru, T., Tomida, T., Tomita, N., Tristram, M., Tucker, C., Turin, P., Tsujimoto, M., Uozumi, S., Utsunomiya, S., Uzawa, Y., Vansyngel, F., Wehus, I. K., Westbrook, B., Willer, M., Whitehorn, N., Yamada, Y., Yamamoto, R., Yamasaki, N., Yamashita, T., and Yoshida, M.
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Astrophysics of Galaxies - Abstract
Inflation is the leading theory of the first instant of the universe. Inflation, which postulates that the universe underwent a period of rapid expansion an instant after its birth, provides convincing explanation for cosmological observations. Recent advancements in detector technology have opened opportunities to explore primordial gravitational waves generated by the inflation through B-mode (divergent-free) polarization pattern embedded in the Cosmic Microwave Background anisotropies. If detected, these signals would provide strong evidence for inflation, point to the correct model for inflation, and open a window to physics at ultra-high energies. LiteBIRD is a satellite mission with a goal of detecting degree-and-larger-angular-scale B-mode polarization. LiteBIRD will observe at the second Lagrange point with a 400 mm diameter telescope and 2,622 detectors. It will survey the entire sky with 15 frequency bands from 40 to 400 GHz to measure and subtract foregrounds. The U.S. LiteBIRD team is proposing to deliver sub-Kelvin instruments that include detectors and readout electronics. A lenslet-coupled sinuous antenna array will cover low-frequency bands (40 GHz to 235 GHz) with four frequency arrangements of trichroic pixels. An orthomode-transducer-coupled corrugated horn array will cover high-frequency bands (280 GHz to 402 GHz) with three types of single frequency detectors. The detectors will be made with Transition Edge Sensor (TES) bolometers cooled to a 100 milli-Kelvin base temperature by an adiabatic demagnetization refrigerator.The TES bolometers will be read out using digital frequency multiplexing with Superconducting QUantum Interference Device (SQUID) amplifiers. Up to 78 bolometers will be multiplexed with a single SQUID amplidier. We report on the sub-Kelvin instrument design and ongoing developments for the LiteBIRD mission., Comment: 7 pages 2 figures Journal of Low Temperature Physics - Special edition - LTD17 Proceeding
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- 2018
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39. Radio-emitting narrow-line Seyfert 1 galaxies in the JVLA perspective
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Berton, M., Congiu, E., Järvelä, E., Antonucci, R., Kharb, P., Lister, M. L., Tarchi, A., Caccianiga, A., Chen, S., Foschini, L., Lähteenmäki, A., Richards, J. L., Ciroi, S., Cracco, V., Frezzato, M., La Mura, G., and Rafanelli, P.
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Astrophysics - Astrophysics of Galaxies - Abstract
We report the first results of a survey on 74 narrow-line Seyfert 1 galaxies (NLS1s) carried out in 2015 with the Karl G. Jansky Very Large Array (JVLA) at 5 GHz in A-configuration. So far, this is the largest survey aimed to image the radio continuum of NLS1s. We produced radio maps in order to compare the general properties of three different samples of objects: radio-quiet NLS1s (RQNLS1s), steep-spectrum radio-loud NLS1s (S-NLS1s), and flat-spectrum radio-loud NLS1s (F-NLS1s). We find that the three classes correspond to different radio morphologies, with F-NLS1s being more compact, and RQNLS1s often showing diffuse emission on kpc scales. We also find that F-NLS1s might be low-luminosity and possibly young blazars, and that S-NLS1s are part of the parent population of F-NLS1s. Dedicated studies to RQNLS1s are needed in order to fully understand their role in the unification pictures., Comment: 36 pages, 45 figures, 10 tables, accepted for publication by Astronomy & Astrophysics
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- 2018
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40. Genomic analysis of paired primary and metastatic pancreatic ductal adenocarcinoma tumors.
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McIntyre, Caitlin A, Rudneva, Vasilisa, Richards, Allison L., Park, Wungki, Jarnagin, William R., Donoghue, Mark, and O'Reilly, Eileen M.
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- 2025
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41. A Measurement of the Cosmic Microwave Background $B$-Mode Polarization Power Spectrum at Sub-Degree Scales from 2 years of POLARBEAR Data
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The POLARBEAR Collaboration, Ade, P. A. R., Aguilar, M., Akiba, Y., Arnold, K., Baccigalupi, C., Barron, D., Beck, D., Bianchini, F., Boettger, D., Borrill, J., Chapman, S., Chinone, Y., Crowley, K., Cukierman, A., Dobbs, M., Ducout, A., Dünner, R., Elleflot, T., Errard, J., Fabbian, G., Feeney, S. M., Feng, C., Fujino, T., Galitzki, N., Gilbert, A., Goeckner-Wald, N., Groh, J., Hamada, T., Hall, G., Halverson, N. W., Hasegawa, M., Hazumi, M., Hill, C., Howe, L., Inoue, Y., Jaehnig, G. C., Jaffe, A. H., Jeong, O., Kaneko, D., Katayama, N., Keating, B., Keskitalo, R., Kisner, T., Krachmalnicoff, N., Kusaka, A., Jeune, M. Le, Lee, A. T., Leitch, E. M., Leon, D., Linder, E., Lowry, L., Matsuda, F., Matsumura, T., Minami, Y., Montgomery, J., Navaroli, M., Nishino, H., Paar, H., Peloton, J., Pham, A. T. P., Poletti, D., Puglisi, G., Reichardt, C. L., Richards, P. L., Ross, C., Segawa, Y., Sherwin, B. D., Silva-Feaver, M., Siritanasak, P., Stebor, N., Stompor, R., Suzuki, A., Tajima, O., Takakura, S., Takatori, S., Tanabe, D., Teply, G. P., Tomaru, T., Tucker, C., Whitehorn, N., and Zahn, A.
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Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We report an improved measurement of the cosmic microwave background (CMB) $B$-mode polarization power spectrum with the POLARBEAR experiment at 150 GHz. By adding new data collected during the second season of observations (2013-2014) to re-analyzed data from the first season (2012-2013), we have reduced twofold the band-power uncertainties. The band powers are reported over angular multipoles $500 \leq \ell \leq 2100$, where the dominant $B$-mode signal is expected to be due to the gravitational lensing of $E$-modes. We reject the null hypothesis of no $B$-mode polarization at a confidence of 3.1$\sigma$ including both statistical and systematic uncertainties. We test the consistency of the measured $B$-modes with the $\Lambda$ Cold Dark Matter ($\Lambda$CDM) framework by fitting for a single lensing amplitude parameter $A_L$ relative to the Planck best-fit model prediction. We obtain $A_L = 0.60 ^{+0.26} _{-0.24} ({\rm stat}) ^{+0.00} _{-0.04}({\rm inst}) \pm 0.14 ({\rm foreground}) \pm 0.04 ({\rm multi})$, where $A_{L}=1$ is the fiducial $\Lambda$CDM value, and the details of the reported uncertainties are explained later in the manuscript., Comment: 16 pages, 10 figures. Minor changes to match the published version. For data and figures, see http://bolo.berkeley.edu/polarbear/data/polarbear_BB_2017/
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- 2017
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42. Kiloparsec-scale emission in the narrow-line Seyfert 1 galaxy Mrk 783
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Congiu, E., Berton, M., Giroletti, M., Antonucci, R., Caccianiga, A., Kharb, P., Lister, M. L., Foschini, L., Ciroi, S., Cracco, V., Frezzato, M., Järvelä, E., La Mura, G., Richards, J. L., and Rafanelli, P.
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Astrophysics - Astrophysics of Galaxies - Abstract
We present the first results of a radio survey of 79 narrow-line Seyfert 1 (NLS1) carried out with the Karl G. Jansky Very Large Array (JVLA) at 5 GHz in A configuration aimed at studying the radio properties of these sources. We report the detection of extended emission in one object: Mrk 783. This is intriguing, since the radio-loudness parameter R of this object is close to the threshold between radio-quiet and radio-loud active galactic nuclei (AGN). The galaxy is one of the few NLS1 showing such an extended emission at z < 0.1. The radio emission is divided in a compact core component and an extended component, observed on both sides of the nucleus and extending from 14 kpc south-east to 12 kpc north-west. There is no sign of a collimated jet, and the shape of the extended component is similar to those of some Seyfert galaxies. The properties of the emission are compatible with a relic produced by the intermittent activity cycle of the AGN., Comment: 5 pages, 1 figure, accepted for publication in Astronomy & Astrophysics
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- 2017
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43. 37 GHz observations of narrow-line Seyfert 1 galaxies
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Lähteenmäki, A., Järvelä, E., Hovatta, T., Tornikoski, M., Harrison, D. L., López-Caniego, M., Max-Moerbeck, W., Mingaliev, M., Pearson, T. J., Ramakrishnan, V., Readhead, A. C. S., Reeves, R. A., Richards, J. L., Sotnikova, Y., and Tammi, J.
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - High Energy Astrophysical Phenomena - Abstract
Observations at 37 GHz, performed at Mets\"ahovi Radio Observatory, are presented for a sample of 78 radio-loud and radio-quiet narrow-line Seyfert 1 (NLS1) galaxies, together with additional lower and higher frequency radio data from RATAN-600, Owens Valley Radio Observatory, and the Planck satellite. Most of the data have been gathered between February 2012 and April 2015 but for some sources even longer lightcurves exist. The detection rate at 37 GHz is around 19%, comparable to other populations of active galactic nuclei presumed to be faint at radio frequencies, such as BL Lac objects. Variability and spectral indices are determined for sources with enough detections. Based on the radio data, many NLS1 galaxies show a blazar-like radio spectra exhibiting significant variability. The spectra at a given time are often inverted or convex. The source of the high-frequency radio emission in NLS1 galaxies, detected at 37 GHz, is most probably a relativistic jet rather than star formation. Jets in NLS1 galaxies are therefore expected to be a much more common phenomenon than earlier assumed., Comment: Accepted for publication in A&A. Table of 37 GHz data will be available at the CDS soon
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- 2017
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44. Subjective Cognitive Complaints: Predictors and Health Outcomes in People Living with HIV
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Bryant, Vaughn E., Fieo, Robert A., Fiore, Andrew J., Richards, Veronica L., Porges, Eric C., Williams, Renessa, Lu, Huiyin, Zhou, Zhi, and Cook, Robert L.
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- 2022
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45. Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma
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D’Angelo, Sandra P., Richards, Allison L., Conley, Anthony P., Woo, Hyung Jun, Dickson, Mark A., Gounder, Mrinal, Kelly, Ciara, Keohan, Mary Louise, Movva, Sujana, Thornton, Katherine, Rosenbaum, Evan, Chi, Ping, Nacev, Benjamin, Chan, Jason E., Slotkin, Emily K., Kiesler, Hannah, Adamson, Travis, Ling, Lilan, Rao, Pavitra, Patel, Shreyaskumar, Livingston, Jonathan A., Singer, Samuel, Agaram, Narasimhan P., Antonescu, Cristina R., Koff, Andrew, Erinjeri, Joseph P., Hwang, Sinchun, Qin, Li-Xuan, Donoghue, Mark T. A., and Tap, William D.
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- 2022
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46. A Delphi study to explore clinician and lived experience perspectives on setting priorities in eating disorder services
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Richards, Katie L., Woolrych, Isabel, Allen, Karina L., and Schmidt, Ulrike
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- 2022
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47. Bimodal radio variability in OVRO-40m-monitored blazars
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Liodakis, I., Pavlidou, V., Hovatta, T., Max-Moerbeck, W., Pearson, T. J., Richards, J. L., and Readhead, A. C. S.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
Blazars are known to show periods of quiescence followed by outbursts visible throughout the electromagnetic spectrum. We present a novel maximum likelihood approach to capture this bimodal behavior by examining blazar radio variability in the flux-density domain. We separate quiescent and flaring components of a source's light curve by modeling its flux-density distribution as a series of "off" and "on" states. Our modeling allows us to extract information regarding the flaring ratio, duty cycle, and the modulation index in the "off"-state, in the "on"-state, as well as throughout the monitoring period of each blazar. We apply our method to a flux-density-limited subsample from the Owens Valley Radio observatory's 15 GHz blazar monitoring program, and explore differences in the variability characteristics between BL Lacs and FSRQs as well as between $\gamma$-ray detected and non-detected sources. We find that: (1) BL Lacs are more variable and have relatively larger outbursts than the FSRQs, (2) unclassified blazar candidates in our sample show similar variability characteristics as the FSRQs, and (3) $\gamma$-ray detected differ from the $\gamma$-ray non-detected sources in all their variability properties, suggesting a link between the production of $\gamma$-rays and the mechanism responsible for the radio variability. Finally, we fit distributions for blazar flaring ratios, duty cycles, and on- and off- modulation indices that can be used in population studies of variability-dependent blazar properties., Comment: 13 pages, 18 figures, published in MNRAS
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- 2017
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48. Symmetric Achromatic Variability in Active Galaxies -- A Powerful New Gravitational Lensing Probe?
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Vedantham, H. K., Readhead, A. C. S., Hovatta, T., Pearson, T. J., Blandford, R. D., Gurwell, M. A., Lähteenmäki, A., Max-Moerbeck, W., Pavlidou, V., Ravi, V., Reeves, R. A., Richards, J. L., Tornikoski, M., and Zensus, J. A.
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Astrophysics of Galaxies - Abstract
We report the discovery of a rare new form of long-term radio variability in the light-curves of active galaxies (AG) --- Symmetric Achromatic Variability (SAV) --- a pair of opposed and strongly skewed peaks in the radio flux density observed over a broad frequency range. We propose that SAV arises through gravitational milli-lensing when relativistically moving features in AG jets move through gravitational lensing caustics created by $10^3-10^6 \;{\rm M}_{\odot}$ subhalo condensates or black holes located within intervening galaxies. The lower end of this mass range has been inaccessible with previous gravitational lensing techniques. This new interpretation of some AG variability can easily be tested and if it passes these tests, will enable a new and powerful probe of cosmological matter distribution on these intermediate mass scales, as well as provide, for the first time, micro-arcsecond resolution of the nuclei of AG --- a factor of 30--100 greater resolution than is possible with ground-based millimeter VLBI., Comment: Submitted version
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- 2017
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49. The peculiar light-curve of J1415+1320: A case study in extreme scattering events
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Vedantham, H. K., Readhead, A. C. S., Hovatta, T., Koopmans, L. V. E., Pearson, T. J., Blandford, R. D., Gurwell, M. A., Lähteenmäki, A., Max-Moerbeck, W., Pavlidou, V., Ravi, V., Reeves, R. A., Richards, J. L., Tornikoski, M., and Zensus, J. A.
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - High Energy Astrophysical Phenomena - Abstract
The radio light-curve of J1415+1320 (PKS 1413+135) shows time-symmetric and recurring U-shaped features across the cm-wave and mm-wave bands. The symmetry of these features points to lensing by an intervening object as the cause. U-shaped events in radio light curves in the cm-wave band have previously been attributed to Extreme scattering events (ESE). ESEs are thought to be the result of lensing by compact plasma structures in the Galactic interstellar medium, but the precise nature of these plasma structures remains unknown. Since the strength of a plasma lens evolves with wavelength $\lambda$ as $\lambda^2$, the presence of correlated variations at over a wide wavelength range casts doubt on the canonical ESE interpretation for J1415+1320. In this paper, we critically examine the evidence for plasma lensing in J1415+1320. We compute limits on the lensing strength, and the associated free-free opacity of the putative plasma lenses. We compare the observed and model ESE light curves, and also derive a lower limit on the lens distance based on the effects of parallax due to the Earth's orbit around the Sun. We conclude that plasma lensing is not a viable interpretation for J1415+1320's light curves and that symmetric U-shaped features in the radio light curves of extragalactic sources do not present {\em prima facie} evidence for ESEs. The methodology presented here is generic enough to be applicable to any plasma lensing candidate., Comment: Submitted version
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- 2017
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50. Multiband variability studies and novel broadband SED modeling of Mrk 501 in 2009
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Ahnen, M. L., Ansoldi, S., Antonelli, L. A., Antoranz, P., Babic, A., Banerjee, B., Bangale, P., de Almeida, U. Barres, Barrio, J. A., González, J. Becerra, Bednarek, W., Bernardini, E., Berti, A., Biasuzzi, B., Biland, A., Blanch, O., Bonnefoy, S., Bonnoli, G., Borracci, F., Bretz, T., Buson, S., Carosi, A., Chatterjee, A., Clavero, R., Colin, P., Colombo, E., Contreras, J. L., Cortina, J., Covino, S., Da Vela, P., Dazzi, F., De Angelis, A., De Lotto, B., Wilhelmi, E. de Ona, Di Pierro, F., Doert, M., Domínguez, A., Prester, D. Dominis, Dorner, D., Doro, M., Einecke, S., Glawion, D. Eisenacher, Elsaesser, D., Engelkemeier, M., Ramazani, V. Fallah, Fernández-Barral, A., Fidalgo, D., Fonseca, M. V., Font, L., Frantzen, K., Fruck, C., Galindo, D., López, R. J. García, Garczarczyk, M., Terrats, D. Garrido, Gaug, M., Giammaria, P., Godinović, N., Munoz, A. González, Gora, D., Guberman, D., Hadasch, D., Hahn, A., Hanabata, Y., Hayashida, M., Herrera, J., Hose, J., Hrupec, D., Hughes, G., Idec, W., Kodani, K., Konno, Y., Kubo, H., Kushida, J., La Barbera, A., Lelas, D., Lindfors, E., Lombardi, S., Longo, F., López, M., López-Coto, R., Majumdar, P., Makariev, M., Mallot, K., Maneva, G., Manganaro, M., Mannheim, K., Maraschi, L., Marcote, B., Mariotti, M., Martínez, M., Mazin, D., Menzel, U., Miranda, J. M., Mirzoyan, R., Moralejo, A., Moretti, E., Nakajima, D., Neustroev, V., Niedzwiecki, A., Rosillo, M. Nievas, Nilsson, K., Nishijima, K., Noda, K., Nogués, L., Overkemping, A., Paiano, S., Palacio, J., Palatiello, M., Paneque, D., Paoletti, R., Paredes, J. M., Paredes-Fortuny, X., Pedaletti, G., Peresano, M., Perri, L., Persic, M., Poutanen, J., Moroni, P. G. Prada, Prandini, E., Puljak, I., Reichardt, I., Rhode, W., Ribó, M., Rico, J., Garcia, J. Rodriguez, Saito, T., Satalecka, K., Schröder, S., Schultz, C., Schweizer, T., Shore, S. N., Sillanpää, A., Sitarek, J., Snidaric, I., Sobczynska, D., Stamerra, A., Steinbring, T., Strzys, M., Surić, T., Takalo, L., Tavecchio, F., Temnikov, P., Terzić, T., Tescaro, D., Teshima, M., Thaele, J., Torres, D. F., Toyama, T., Treves, A., Vanzo, G., Verguilov, V., Vovk, I., Ward, J. E., Will, M., Wu, M. H., Zanin, R., Abeysekara, A. U., Archambault, S., Archer, A., Benbow, W., Bird, R., Buchovecky, M., Buckley, J. H., Bugaev, V., Connolly, M. P., Cui, W., Dickinson, H. J., Falcone, A., Feng, Q., Finley, J. P., Fleischhack, H., Flinders, A., Fortson, L., Gillanders, G. H., Griffin, S., Grube, J., Hütten, M., Hanna, D., Holder, J., Humensky, T. B., Kaaret, P., Kar, P., Kelley-Hoskins, N., Kertzman, M., Kieda, D., Krause, M., Krennrich, F., Lang, M. J., Maier, G., McCann, A., Moriarty, P., Mukherjee, R., Nieto, D., O'Brien, S., Ong, R. A., Otte, N., Park, N., Perkins, J., Pichel, A., Pohl, M., Popkow, A., Pueschel, E., Quinn, J., Ragan, K., Reynolds, P. T., Richards, G. T., Roache, E., Rovero, A. C., Rulten, C., Sadeh, I., Santander, M., Sembroski, G. H., Shahinyan, K., Telezhinsky, I., Tucci, J. V., Tyler, J., Wakely, S. P., Weinstein, A., Wilcox, P., Wilhelm, A., Williams, D. A., Zitzer, B., Razzaque, S., Villata, M., Raiteri, C. M., Aller, H. D., Aller, M. F., Larionov, V. M., Arkharov, A. A., Blinov, D. A., Efimova, N. V., Grishina, T. S., Hagen-Thorn, V. A., Kopatskaya, E. N., Larionova, L. V., Larionova, E. G., Morozova, D. A., Troitsky, I. S., Ligustri, R., Calcidese, P., Berdyugin, A., Kurtanidze, O. M., Nikolashvili, M. G., Kimeridze, G. N., Sigua, L. A., Kurtanidze, S. O., Chigladze, R. A., Chen, W. P., Koptelova, E., Sakamoto, T., Sadun, A. C., Moody, J. W., Pace, C., Pearson III, R., Yatsu, Y., Mori, Y., Carraminyana, A., Carrasco, L., de la Fuente, E., Norris, J. P., Smith, P. S., Wehrle, A., Gurwell, M. A., Zook, Alma, Pagani, C., Perri, M., Capalbi, M., Cesarini, A., Krimm, H. A., Kovalev, Y. Y., Kovalev, Yu. A., Ros, E., Pushkarev, A. B., Lister, M. L., Sokolovsky, K. V., Kadler, M., Piner, G., Lähteenmäki, A., Tornikoski, M., Angelakis, E., Krichbaum, T. P., Nestoras, I., Fuhrmann, L, Zensus, J. A., Cassaro, P., Orlati, A., Maccaferri, G., Leto, P., Giroletti, M., Richards, J. L., Max-Moerbeck, W., and Readhead, A. C. S.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1 which includes, among other instruments, MAGIC, VERITAS, Whipple 10-m, Fermi-LAT, RXTE, Swift, GASP-WEBT and VLBA. We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found in the acquired data set. The higher variability in the very high energy (>100 GeV, VHE) gamma-ray emission and the lack of correlation with the X-ray emission indicate that the highest-energy electrons that are responsible for the VHE gamma-rays do not make a dominant contribution to the ~1 keV emission. Alternatively, there could be a very variable component contributing to the VHE gamma-ray emission in addition to that coming from the synchrotron self-Compton (SSC) scenarios. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters. We find that there is some degeneracy in both the one-zone and the two-zone SSC scenarios that were probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The SSC model grid-scan shows that the flaring activity around 2009 May 22 cannot be modeled adequately with a one-zone SSC scenario, while it can be suitably described within a two-independent-zone SSC scenario. The observation of an electric vector polarization angle rotation coincident with the gamma-ray flare from 2009 May 1 resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties., Comment: 33 pages, 15 figures, accepted for publication in A&A. Corresponding authors: Marlene Doert (marlene.doert@tu-dortmund.de) and David Paneque (dpaneque@mppmu.mpg.de)
- Published
- 2016
- Full Text
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