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1. Literature Circles Resource Guide: Teaching Suggestions, Forms, Sample Book Lists and Database [with CD-ROM].

Author

Hill, Bonnie Campbell, Noe, Katherine L. Schlick, Johnson, Nancy J., Hill, Bonnie Campbell, Noe, Katherine L. Schlick, and Johnson, Nancy J.

Abstract

This guide provides the practical support teachers need to make literature circles succeed. The information provided in the guide should answer the kinds of questions teachers ask colleagues about implementing literature circles. It is not intended to stand alone. It is designed to supplement and extend two professional books on literature circles: "Getting Started with Literature Circles" (Katherine L. Schlick Noe and Nancy J. Johnson, 1999) and "Literature Circles and Response" (Bonnie Campbell Hill, Nancy J. Johnson, and Katherine L. Schlick Noe, 1995). The guide is divided into three broad sections. The first section--Teaching Suggestions and Forms--contains the following parts: (1) Literature Circles Organization; (2) Oral Response: Discussions; (3) Written Response: Journals; (4) Extension Projects; (5) Families and Literature Circles; and (6) References. Under the second section--Sample Book Lists--contains the following parts: (1) Primary Book Lists; (2) Intermediate Book Lists; (3) Upper Intermediate/Middle School Book Lists; and (4) Sample Author Studies. The third section--Bibliography of Professional Resources for Literature Circles--contains the following parts: (1) Professional Resources on Literature Circles and Response; (2) Professional Book Publishers; and (3) Web Site Resources for Literature Circles. (NKA)

Published
2001

2. Metacognitive Awareness in Job-Related Reading.

Author

Noe, Katherine L. Schlick

Abstract

Research was conducted into the metacognitive awareness of electronics workers in completing job reading tasks. The study examined how successful adult readers make decisions about why, when, and how to use reading on the job. It also identified unique aspects of the job reading context that both require workers to control their reading efficiently and productively and help them to do so. These included the role of workers' job experience as an aid in reading, readers' perceptions of what makes text difficult or easy to use, and the availability and use of sources of information other than print. Suggestions were made for incorporating metacongition training into job training programs to help adult readers make the most effective use of their work environments. Specific recommendations were that (1) job-related reading instruction needs to teach workers to be aware of the interaction of factors that work together to influence reading success; (2) because of the importance of efficiency and productivity on the job, workers need to develop personal strategies for effective use of reading; (3) those who generate materials to be read on the job must consider how, when, and where these materials are used; and (4) job training should include direct experience with and instruction in the specific materials and reading tasks encountered in the job. (YLB)

Published
1988

3. Getting Started with Literature Circles. The Bill Harp Professional Teachers Library Series.

Author

Noe, Katherine L. Schlick, Johnson, Nancy J., Noe, Katherine L. Schlick, and Johnson, Nancy J.

Abstract

Designed to help teachers get started using literature circles in their classrooms, this book gives teachers a boost to begin, offers some insights from other teachers, and helps teachers clarify where to go next. It notes that literature circles (or literature study groups, book clubs, or discussion circles) take many forms and engage students in meaningful response to literature in a variety of ways. After an introduction, the chapters are: (1) Building a Framework for Literature Circles; (2) Classroom Climate; (3) Structure; (4) Good Books for Literature Circles; (5) Discussion; (6) Response Journals; (7) Focus Lessons: Incorporating Literacy Strategies; and (8) Extension Projects. Contains 38 references and a 95-item list of children's literature cited. (RS)

Published
1999

4. Natural Partners: Using Reading and Writing to Promote Social Studies Understanding.

Author

McGuire, Margit E. and Noe, Katherine L. Schlick

Abstract

Asserts that social studies is an integrated field of study that calls for organizing the curriculum in a holistic manner. Maintains that the whole-language movement, which involves thinking about reading and writing as integrated, reciprocal processes, forms a natural partnership with social studies instruction. (CFR)

Published
1993

5. Dual-Surface Modification of the Tobacco Mosaic Virus

Author

Tara L Schlick, Ernest W Kovacs, Matthew B. Francis, and Zhebo Ding

Subjects
Models, Molecular, Stereochemistry, viruses, Glutamic Acid, Sequence (biology), Biochemistry, Catalysis, chemistry.chemical_compound, Capsid, Colloid and Surface Chemistry, Side chain, Tobacco mosaic virus, Carbodiimide, biology, fungi, technology, industry, and agriculture, Chemical modification, Tobamovirus, General Chemistry, biology.organism_classification, Combinatorial chemistry, Tobacco Mosaic Virus, chemistry, Tyrosine, Surface modification
Abstract

The protein shell of the tobacco mosaic virus (TMV) provides a robust and practical tubelike scaffold for the preparation of nanoscale materials. To expand the range of applications for which the capsid can be used, two synthetic strategies have been developed for the attachment of new functionality to either the exterior or the interior surface of the virus. The first of these is accomplished using a highly efficient diazonium coupling/oxime formation sequence, which installs >2000 copies of a material component on the capsid exterior. Alternatively, the inner cavity of the tube can be modified by attaching amines to glutamic acid side chains through a carbodiimide coupling reaction. Both of these reactions have been demonstrated for a series of substrates, including biotin, chromophores, and crown ethers. Through the attachment of PEG polymers to the capsid exterior, organic-soluble TMV rods have been prepared. Finally, the orthogonality of these reactions has been demonstrated by installing different functional groups on the exterior and interior surfaces of the same capsid assemblies.

Published
2005
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6. Search for Galactic Core-collapse Supernovae in a Decade of Data Taken with the IceCube Neutrino Observatory

Author

R. Abbasi, M. Ackermann, J. Adams, S. K. Agarwalla, J. A. Aguilar, M. Ahlers, J. M. Alameddine, N. M. Amin, K. Andeen, G. Anton, C. Argüelles, Y. Ashida, S. Athanasiadou, S. N. Axani, X. Bai, A. Balagopal V., M. Baricevic, S. W. Barwick, V. Basu, R. Bay, J. J. Beatty, J. Becker Tjus, J. Beise, C. Bellenghi, C. Benning, S. BenZvi, D. Berley, E. Bernardini, D. Z. Besson, G. Binder, E. Blaufuss, S. Blot, F. Bontempo, J. Y. Book, C. Boscolo Meneguolo, S. Böser, O. Botner, J. Böttcher, E. Bourbeau, J. Braun, B. Brinson, J. Brostean-Kaiser, R. T. Burley, R. S. Busse, D. Butterfield, M. A. Campana, K. Carloni, E. G. Carnie-Bronca, S. Chattopadhyay, N. Chau, C. Chen, Z. Chen, D. Chirkin, S. Choi, B. A. Clark, L. Classen, A. Coleman, G. H. Collin, A. Connolly, J. M. Conrad, P. Coppin, P. Correa, S. Countryman, D. F. Cowen, P. Dave, C. De Clercq, J. J. DeLaunay, D. Delgado, S. Deng, K. Deoskar, A. Desai, P. Desiati, K. D. de Vries, G. de Wasseige, T. DeYoung, A. Diaz, J. C. Díaz-Vélez, M. Dittmer, A. Domi, H. Dujmovic, M. A. DuVernois, T. Ehrhardt, P. Eller, E. Ellinger, S. El Mentawi, D. Elsässer, R. Engel, H. Erpenbeck, J. Evans, P. A. Evenson, K. L. Fan, K. Fang, K. Farrag, A. R. Fazely, A. Fedynitch, N. Feigl, S. Fiedlschuster, C. Finley, L. Fischer, D. Fox, A. Franckowiak, A. Fritz, P. Fürst, J. Gallagher, E. Ganster, A. Garcia, L. Gerhardt, A. Ghadimi, C. Glaser, T. Glauch, T. Glüsenkamp, N. Goehlke, J. G. Gonzalez, S. Goswami, D. Grant, S. J. Gray, O. Gries, S. Griffin, S. Griswold, K. M. Groth, C. Günther, P. Gutjahr, C. Haack, A. Hallgren, R. Halliday, L. Halve, F. Halzen, H. Hamdaoui, M. Ha Minh, K. Hanson, J. Hardin, A. A. Harnisch, P. Hatch, A. Haungs, K. Helbing, J. Hellrung, F. Henningsen, L. Heuermann, N. Heyer, S. Hickford, A. Hidvegi, C. Hill, G. C. Hill, K. D. Hoffman, S. Hori, K. Hoshina, W. Hou, T. Huber, K. Hultqvist, M. Hünnefeld, R. Hussain, K. Hymon, S. In, A. Ishihara, M. Jacquart, O. Janik, M. Jansson, G. S. Japaridze, M. Jeong, M. Jin, B. J. P. Jones, D. Kang, W. Kang, X. Kang, A. Kappes, D. Kappesser, L. Kardum, T. Karg, M. Karl, A. Karle, U. Katz, M. Kauer, J. L. Kelley, A. Khatee Zathul, A. Kheirandish, J. Kiryluk, S. R. Klein, A. Kochocki, R. Koirala, H. Kolanoski, T. Kontrimas, L. Köpke, C. Kopper, D. J. Koskinen, P. Koundal, M. Kovacevich, M. Kowalski, T. Kozynets, J. Krishnamoorthi, K. Kruiswijk, E. Krupczak, A. Kumar, E. Kun, N. Kurahashi, N. Lad, C. Lagunas Gualda, M. Lamoureux, M. J. Larson, S. Latseva, F. Lauber, J. P. Lazar, J. W. Lee, K. Leonard DeHolton, A. Leszczyńska, M. Lincetto, Q. R. Liu, M. Liubarska, E. Lohfink, C. Love, C. J. Lozano Mariscal, L. Lu, F. Lucarelli, W. Luszczak, Y. Lyu, J. Madsen, K. B. M. Mahn, Y. Makino, E. Manao, S. Mancina, W. Marie Sainte, I. C. Mariş, S. Marka, Z. Marka, M. Marsee, I. Martinez-Soler, R. Maruyama, F. Mayhew, T. McElroy, F. McNally, J. V. Mead, K. Meagher, S. Mechbal, A. Medina, M. Meier, Y. Merckx, L. Merten, J. Micallef, J. Mitchell, T. Montaruli, R. W. Moore, Y. Morii, R. Morse, M. Moulai, T. Mukherjee, R. Naab, R. Nagai, M. Nakos, U. Naumann, J. Necker, A. Negi, M. Neumann, H. Niederhausen, M. U. Nisa, A. Noell, A. Novikov, S. C. Nowicki, A. Obertacke Pollmann, V. O’Dell, M. Oehler, B. Oeyen, A. Olivas, R. Orsoe, J. Osborn, E. O’Sullivan, H. Pandya, N. Park, G. K. Parker, E. N. Paudel, L. Paul, C. Pérez de los Heros, J. Peterson, S. Philippen, A. Pizzuto, M. Plum, A. Pontén, Y. Popovych, M. Prado Rodriguez, B. Pries, R. Procter-Murphy, G. T. Przybylski, C. Raab, J. Rack-Helleis, K. Rawlins, Z. Rechav, A. Rehman, P. Reichherzer, G. Renzi, E. Resconi, S. Reusch, W. Rhode, B. Riedel, A. Rifaie, E. J. Roberts, S. Robertson, S. Rodan, G. Roellinghoff, M. Rongen, C. Rott, T. Ruhe, L. Ruohan, D. Ryckbosch, I. Safa, J. Saffer, D. Salazar-Gallegos, P. Sampathkumar, S. E. Sanchez Herrera, A. Sandrock, M. Santander, S. Sarkar, J. Savelberg, P. Savina, M. Schaufel, H. Schieler, S. Schindler, L. Schlickmann, B. Schlüter, F. Schlüter, N. Schmeisser, T. Schmidt, J. Schneider, F. G. Schröder, L. Schumacher, G. Schwefer, S. Sclafani, D. Seckel, M. Seikh, S. Seunarine, R. Shah, A. Sharma, S. Shefali, N. Shimizu, M. Silva, B. Skrzypek, B. Smithers, R. Snihur, J. Soedingrekso, A. Søgaard, D. Soldin, P. Soldin, G. Sommani, C. Spannfellner, G. M. Spiczak, C. Spiering, M. Stamatikos, T. Stanev, T. Stezelberger, T. Stürwald, T. Stuttard, G. W. Sullivan, I. Taboada, S. Ter-Antonyan, M. Thiesmeyer, W. G. Thompson, J. Thwaites, S. Tilav, K. Tollefson, C. Tönnis, S. Toscano, D. Tosi, A. Trettin, C. F. Tung, R. Turcotte, J. P. Twagirayezu, B. Ty, M. A. Unland Elorrieta, A. K. Upadhyay, K. Upshaw, N. Valtonen-Mattila, J. Vandenbroucke, N. van Eijndhoven, D. Vannerom, J. van Santen, J. Vara, J. Veitch-Michaelis, M. Venugopal, M. Vereecken, S. Verpoest, D. Veske, A. Vijai, C. Walck, C. Weaver, P. Weigel, A. Weindl, J. Weldert, C. Wendt, J. Werthebach, M. Weyrauch, N. Whitehorn, C. H. Wiebusch, N. Willey, D. R. Williams, A. Wolf, M. Wolf, G. Wrede, X. W. Xu, J. P. Yanez, E. Yildizci, S. Yoshida, R. Young, F. Yu, S. Yu, T. Yuan, Z. Zhang, and P. Zhelnin

Subjects
Core-collapse supernovae, Supernova neutrinos, Neutrino telescopes, Astrophysics, QB460-466
Abstract

The IceCube Neutrino Observatory has been continuously taking data to search for ${ \mathcal O }(0.5\mbox{--}10)$ s long neutrino bursts since 2007. Even if a Galactic core-collapse supernova is optically obscured or collapses to a black hole instead of exploding, it will be detectable via the ${ \mathcal O }(10)$ MeV neutrino burst emitted during the collapse. We discuss a search for such events covering the time between 2008 April 17 and 2019 December 31. Considering the average data taking and analysis uptime of 91.7% after all selection cuts, this is equivalent to 10.735 yr of continuous data taking. In order to test the most conservative neutrino production scenario, the selection cuts were optimized for a model based on an 8.8 solar mass progenitor collapsing to an O–Ne–Mg core. Conservative assumptions on the effects of neutrino oscillations in the exploding star were made. The final selection cut was set to ensure that the probability to detect such a supernova within the Milky Way exceeds 99%. No such neutrino burst was found in the data after performing a blind analysis. Hence, a 90% C.L. upper limit on the rate of core-collapse supernovae out to distances of ≈25 kpc was determined to be 0.23 yr ^−1 . For the more distant Magellanic Clouds, only high neutrino luminosity supernovae will be detectable by IceCube, unless external information on the burst time is available. We determined a model-independent limit by parameterizing the dependence on the neutrino luminosity and the energy spectrum.

Published
2024
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7. Search for Continuous and Transient Neutrino Emission Associated with IceCube’s Highest-energy Tracks: An 11 yr Analysis

Author

R. Abbasi, M. Ackermann, J. Adams, S. K. Agarwalla, J. A. Aguilar, M. Ahlers, J. M. Alameddine, N. M. Amin, K. Andeen, G. Anton, C. Argüelles, Y. Ashida, S. Athanasiadou, S. N. Axani, X. Bai, A. Balagopal V., M. Baricevic, S. W. Barwick, V. Basu, R. Bay, J. J. Beatty, J. Becker Tjus, J. Beise, C. Bellenghi, C. Benning, S. BenZvi, D. Berley, E. Bernardini, D. Z. Besson, E. Blaufuss, S. Blot, F. Bontempo, J. Y. Book, C. Boscolo Meneguolo, S. Böser, O. Botner, J. Böttcher, E. Bourbeau, J. Braun, B. Brinson, J. Brostean-Kaiser, R. T. Burley, R. S. Busse, D. Butterfield, M. A. Campana, K. Carloni, E. G. Carnie-Bronca, S. Chattopadhyay, N. Chau, C. Chen, Z. Chen, D. Chirkin, S. Choi, B. A. Clark, S. Coenders, A. Coleman, G. H. Collin, A. Connolly, J. M. Conrad, P. Coppin, P. Correa, D. F. Cowen, P. Dave, C. De Clercq, J. J. DeLaunay, D. Delgado, S. Deng, K. Deoskar, A. Desai, P. Desiati, K. D. de Vries, G. de Wasseige, T. DeYoung, A. Diaz, J. C. Díaz-Vélez, M. Dittmer, A. Domi, H. Dujmovic, M. A. DuVernois, T. Ehrhardt, A. Eimer, P. Eller, E. Ellinger, S. El Mentawi, D. Elsässer, R. Engel, H. Erpenbeck, J. Evans, P. A. Evenson, K. L. Fan, K. Fang, K. Farrag, A. R. Fazely, A. Fedynitch, N. Feigl, S. Fiedlschuster, C. Finley, L. Fischer, D. Fox, A. Franckowiak, A. Fritz, P. Fürst, J. Gallagher, E. Ganster, A. Garcia, L. Gerhardt, A. Ghadimi, C. Glaser, T. Glauch, T. Glüsenkamp, N. Goehlke, J. G. Gonzalez, S. Goswami, D. Grant, S. J. Gray, O. Gries, S. Griffin, S. Griswold, K. M. Groth, C. Günther, P. Gutjahr, C. Haack, A. Hallgren, R. Halliday, L. Halve, F. Halzen, H. Hamdaoui, M. Ha Minh, K. Hanson, J. Hardin, A. A. Harnisch, P. Hatch, A. Haungs, K. Helbing, J. Hellrung, F. Henningsen, L. Heuermann, N. Heyer, S. Hickford, A. Hidvegi, C. Hill, G. C. Hill, K. D. Hoffman, S. Hori, K. Hoshina, W. Hou, T. Huber, K. Hultqvist, M. Hünnefeld, R. Hussain, K. Hymon, S. In, A. Ishihara, M. Jacquart, O. Janik, M. Jansson, G. S. Japaridze, M. Jeong, M. Jin, B. J. P. Jones, N. Kamp, D. Kang, W. Kang, X. Kang, A. Kappes, D. Kappesser, L. Kardum, T. Karg, M. Karl, A. Karle, A. Katil, U. Katz, M. Kauer, J. L. Kelley, A. Khatee Zathul, A. Kheirandish, J. Kiryluk, S. R. Klein, A. Kochocki, R. Koirala, H. Kolanoski, T. Kontrimas, L. Köpke, C. Kopper, D. J. Koskinen, P. Koundal, M. Kovacevich, M. Kowalski, T. Kozynets, J. Krishnamoorthi, K. Kruiswijk, E. Krupczak, A. Kumar, E. Kun, N. Kurahashi, N. Lad, C. Lagunas Gualda, M. Lamoureux, M. J. Larson, S. Latseva, F. Lauber, J. P. Lazar, J. W. Lee, K. Leonard DeHolton, A. Leszczyńska, M. Lincetto, Q. R. Liu, M. Liubarska, E. Lohfink, C. Love, C. J. Lozano Mariscal, L. Lu, F. Lucarelli, W. Luszczak, Y. Lyu, J. Madsen, K. B. M. Mahn, Y. Makino, E. Manao, S. Mancina, W. Marie Sainte, I. C. Mariş, S. Marka, Z. Marka, M. Marsee, I. Martinez-Soler, R. Maruyama, F. Mayhew, T. McElroy, F. McNally, J. V. Mead, K. Meagher, S. Mechbal, A. Medina, M. Meier, Y. Merckx, L. Merten, J. Micallef, J. Mitchell, T. Montaruli, R. W. Moore, Y. Morii, R. Morse, M. Moulai, T. Mukherjee, R. Naab, R. Nagai, M. Nakos, U. Naumann, J. Necker, A. Negi, M. Neumann, H. Niederhausen, M. U. Nisa, A. Noell, A. Novikov, S. C. Nowicki, A. Obertacke Pollmann, V. O’Dell, M. Oehler, B. Oeyen, A. Olivas, R. Orsoe, J. Osborn, E. O’Sullivan, H. Pandya, N. Park, G. K. Parker, E. N. Paudel, L. Paul, C. Pérez de los Heros, J. Peterson, S. Philippen, A. Pizzuto, M. Plum, A. Pontén, Y. Popovych, M. Prado Rodriguez, B. Pries, R. Procter-Murphy, G. T. Przybylski, C. Raab, J. Rack-Helleis, K. Rawlins, Z. Rechav, A. Rehman, P. Reichherzer, G. Renzi, E. Resconi, S. Reusch, W. Rhode, B. Riedel, A. Rifaie, E. J. Roberts, S. Robertson, S. Rodan, G. Roellinghoff, M. Rongen, C. Rott, T. Ruhe, L. Ruohan, D. Ryckbosch, I. Safa, J. Saffer, D. Salazar-Gallegos, P. Sampathkumar, S. E. Sanchez Herrera, A. Sandrock, M. Santander, S. Sarkar, J. Savelberg, P. Savina, M. Schaufel, H. Schieler, S. Schindler, L. Schlickmann, B. Schlüter, F. Schlüter, N. Schmeisser, T. Schmidt, J. Schneider, F. G. Schröder, L. Schumacher, G. Schwefer, S. Sclafani, D. Seckel, M. Seikh, S. Seunarine, R. Shah, S. Shefali, N. Shimizu, M. Silva, B. Skrzypek, B. Smithers, R. Snihur, J. Soedingrekso, A. Søgaard, D. Soldin, P. Soldin, G. Sommani, C. Spannfellner, G. M. Spiczak, C. Spiering, M. Stamatikos, T. Stanev, T. Stezelberger, T. Stürwald, T. Stuttard, G. W. Sullivan, I. Taboada, S. Ter-Antonyan, M. Thiesmeyer, W. G. Thompson, J. Thwaites, S. Tilav, K. Tollefson, C. Tönnis, S. Toscano, D. Tosi, A. Trettin, C. F. Tung, R. Turcotte, J. P. Twagirayezu, M. A. Unland Elorrieta, A. K. Upadhyay, K. Upshaw, A. Vaidyanathan, N. Valtonen-Mattila, J. Vandenbroucke, N. van Eijndhoven, D. Vannerom, J. van Santen, J. Vara, J. Veitch-Michaelis, M. Venugopal, M. Vereecken, S. Verpoest, D. Veske, A. Vijai, C. Walck, C. Weaver, P. Weigel, A. Weindl, J. Weldert, A. Y. Wen, C. Wendt, J. Werthebach, M. Weyrauch, N. Whitehorn, C. H. Wiebusch, D. R. Williams, L. Witthaus, A. Wolf, M. Wolf, G. Wrede, X. W. Xu, J. P. Yanez, E. Yildizci, S. Yoshida, R. Young, S. Yu, T. Yuan, Z. Zhang, P. Zhelnin, P. Zilberman, M. Zimmerman, and IceCube Collaboration

Subjects
High energy astrophysics, Active galactic nuclei, Neutrino astronomy, Transient sources, Blazars, Astrophysics, QB460-466
Abstract

IceCube alert events are neutrinos with a moderate-to-high probability of having astrophysical origin. In this study, we analyze 11 yr of IceCube data and investigate 122 alert events and a selection of high-energy tracks detected between 2009 and the end of 2021. This high-energy event selection (alert events + high-energy tracks) has an average probability of ≥0.5 of being of astrophysical origin. We search for additional continuous and transient neutrino emission within the high-energy events’ error regions. We find no evidence for significant continuous neutrino emission from any of the alert event directions. The only locally significant neutrino emission is the transient emission associated with the blazar TXS 0506+056, with a local significance of 3 σ , which confirms previous IceCube studies. When correcting for 122 test positions, the global p -value is 0.156 and compatible with the background hypothesis. We constrain the total continuous flux emitted from all 122 test positions at 100 TeV to be below 1.2 × 10 ^−15 (TeV cm ^2 s) ^−1 at 90% confidence assuming an E ^−2 spectrum. This corresponds to 4.5% of IceCube’s astrophysical diffuse flux. Overall, we find no indication that alert events in general are linked to lower-energetic continuous or transient neutrino emission.

Published
2024
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8. All-sky Search for Transient Astrophysical Neutrino Emission with 10 Years of IceCube Cascade Events

Author

R. Abbasi, M. Ackermann, J. Adams, S. K. Agarwalla, J. A. Aguilar, M. Ahlers, J. M. Alameddine, N. M. Amin, K. Andeen, G. Anton, C. Argüelles, Y. Ashida, S. Athanasiadou, L. Ausborm, S. N. Axani, X. Bai, A. Balagopal V., M. Baricevic, S. W. Barwick, V. Basu, R. Bay, J. J. Beatty, J. Becker Tjus, J. Beise, C. Bellenghi, C. Benning, S. BenZvi, D. Berley, E. Bernardini, D. Z. Besson, E. Blaufuss, S. Blot, F. Bontempo, J. Y. Book, C. Boscolo Meneguolo, S. Böser, O. Botner, J. Böttcher, J. Braun, B. Brinson, J. Brostean-Kaiser, L. Brusa, R. T. Burley, R. S. Busse, D. Butterfield, M. A. Campana, K. Carloni, E. G. Carnie-Bronca, S. Chattopadhyay, N. Chau, C. Chen, Z. Chen, D. Chirkin, S. Choi, B. A. Clark, A. Coleman, G. H. Collin, A. Connolly, J. M. Conrad, P. Coppin, P. Correa, D. F. Cowen, P. Dave, C. De Clercq, J. J. DeLaunay, D. Delgado, S. Deng, K. Deoskar, A. Desai, P. Desiati, K. D. de Vries, G. de Wasseige, T. DeYoung, A. Diaz, J. C. Díaz-Vélez, M. Dittmer, A. Domi, H. Dujmovic, M. A. DuVernois, T. Ehrhardt, A. Eimer, P. Eller, E. Ellinger, S. El Mentawi, D. Elsässer, R. Engel, H. Erpenbeck, J. Evans, P. A. Evenson, K. L. Fan, K. Fang, K. Farrag, A. R. Fazely, A. Fedynitch, N. Feigl, S. Fiedlschuster, C. Finley, L. Fischer, D. Fox, A. Franckowiak, P. Fürst, J. Gallagher, E. Ganster, A. Garcia, L. Gerhardt, A. Ghadimi, C. Glaser, T. Glauch, T. Glüsenkamp, J. G. Gonzalez, D. Grant, S. J. Gray, O. Gries, S. Griffin, S. Griswold, K. M. Groth, C. Günther, P. Gutjahr, C. Ha, C. Haack, A. Hallgren, R. Halliday, L. Halve, F. Halzen, H. Hamdaoui, M. Ha Minh, M. Handt, K. Hanson, J. Hardin, A. A. Harnisch, P. Hatch, A. Haungs, J. Häußler, K. Helbing, J. Hellrung, J. Hermannsgabner, L. Heuermann, N. Heyer, S. Hickford, A. Hidvegi, C. Hill, G. C. Hill, K. D. Hoffman, S. Hori, K. Hoshina, W. Hou, T. Huber, K. Hultqvist, M. Hünnefeld, R. Hussain, K. Hymon, S. In, A. Ishihara, M. Jacquart, O. Janik, M. Jansson, G. S. Japaridze, M. Jeong, M. Jin, B. J. P. Jones, N. Kamp, D. Kang, W. Kang, X. Kang, A. Kappes, D. Kappesser, L. Kardum, T. Karg, M. Karl, A. Karle, A. Katil, U. Katz, M. Kauer, J. L. Kelley, A. Khatee Zathul, A. Kheirandish, J. Kiryluk, S. R. Klein, A. Kochocki, R. Koirala, H. Kolanoski, T. Kontrimas, L. Köpke, C. Kopper, D. J. Koskinen, P. Koundal, M. Kovacevich, M. Kowalski, T. Kozynets, J. Krishnamoorthi, K. Kruiswijk, E. Krupczak, A. Kumar, E. Kun, N. Kurahashi, N. Lad, C. Lagunas Gualda, M. Lamoureux, M. J. Larson, S. Latseva, F. Lauber, J. P. Lazar, J. W. Lee, K. Leonard DeHolton, A. Leszczyńska, M. Lincetto, Y. Liu, M. Liubarska, E. Lohfink, C. Love, C. J. Lozano Mariscal, L. Lu, F. Lucarelli, W. Luszczak, Y. Lyu, J. Madsen, E. Magnus, K. B. M. Mahn, Y. Makino, E. Manao, S. Mancina, W. Marie Sainte, I. C. Mariş, S. Marka, Z. Marka, M. Marsee, I. Martinez-Soler, R. Maruyama, F. Mayhew, T. McElroy, F. McNally, J. V. Mead, K. Meagher, S. Mechbal, A. Medina, M. Meier, Y. Merckx, L. Merten, J. Micallef, J. Mitchell, T. Montaruli, R. W. Moore, Y. Morii, R. Morse, M. Moulai, T. Mukherjee, R. Naab, R. Nagai, M. Nakos, U. Naumann, J. Necker, A. Negi, M. Neumann, H. Niederhausen, M. U. Nisa, A. Noell, A. Novikov, S. C. Nowicki, A. Obertacke Pollmann, V. O’Dell, B. Oeyen, A. Olivas, R. Orsoe, J. Osborn, E. O’Sullivan, H. Pandya, N. Park, G. K. Parker, E. N. Paudel, L. Paul, C. Pérez de los Heros, J. Peterson, S. Philippen, A. Pizzuto, M. Plum, A. Pontén, Y. Popovych, M. Prado Rodriguez, B. Pries, R. Procter-Murphy, G. T. Przybylski, C. Raab, J. Rack-Helleis, K. Rawlins, Z. Rechav, A. Rehman, P. Reichherzer, E. Resconi, S. Reusch, W. Rhode, B. Riedel, A. Rifaie, E. J. Roberts, S. Robertson, S. Rodan, G. Roellinghoff, M. Rongen, A. Rosted, C. Rott, T. Ruhe, L. Ruohan, D. Ryckbosch, I. Safa, J. Saffer, D. Salazar-Gallegos, P. Sampathkumar, S. E. Sanchez Herrera, A. Sandrock, M. Santander, S. Sarkar, J. Savelberg, P. Savina, M. Schaufel, H. Schieler, S. Schindler, L. Schlickmann, B. Schlüter, F. Schlüter, N. Schmeisser, T. Schmidt, J. Schneider, F. G. Schröder, L. Schumacher, S. Sclafani, D. Seckel, M. Seikh, S. Seunarine, R. Shah, S. Shefali, N. Shimizu, M. Silva, B. Skrzypek, B. Smithers, R. Snihur, J. Soedingrekso, A. Søgaard, D. Soldin, P. Soldin, G. Sommani, C. Spannfellner, G. M. Spiczak, C. Spiering, M. Stamatikos, T. Stanev, T. Stezelberger, T. Stürwald, T. Stuttard, G. W. Sullivan, I. Taboada, S. Ter-Antonyan, M. Thiesmeyer, W. G. Thompson, J. Thwaites, S. Tilav, K. Tollefson, C. Tönnis, S. Toscano, D. Tosi, A. Trettin, C. F. Tung, R. Turcotte, J. P. Twagirayezu, M. A. Unland Elorrieta, A. K. Upadhyay, K. Upshaw, A. Vaidyanathan, N. Valtonen-Mattila, J. Vandenbroucke, N. van Eijndhoven, D. Vannerom, J. van Santen, J. Vara, J. Veitch-Michaelis, M. Venugopal, M. Vereecken, S. Verpoest, D. Veske, A. Vijai, C. Walck, Y. Wang, C. Weaver, P. Weigel, A. Weindl, J. Weldert, A. Y. Wen, C. Wendt, J. Werthebach, M. Weyrauch, N. Whitehorn, C. H. Wiebusch, D. R. Williams, L. Witthaus, A. Wolf, M. Wolf, G. Wrede, X. W. Xu, J. P. Yanez, E. Yildizci, S. Yoshida, R. Young, S. Yu, T. Yuan, Z. Zhang, P. Zhelnin, P. Zilberman, M. Zimmerman, and IceCube Collaboration

Subjects
Neutrino astronomy, High energy astrophysics, Transient sources, Astrophysics, QB460-466
Abstract

Neutrino flares in the sky are searched for in data collected by IceCube between 2011 and 2021 May. This data set contains cascade-like events originating from charged-current electron neutrino and tau neutrino interactions and all-flavor neutral-current interactions. IceCube’s previous all-sky searches for neutrino flares used data sets consisting of track-like events originating from charged-current muon neutrino interactions. The cascade data set is statistically independent of the track data sets, and while inferior in angular resolution, the low-background nature makes it competitive and complementary to previous searches. No statistically significant flare of neutrino emission was observed in an all-sky scan. Upper limits are calculated on neutrino flares of varying duration from 1 hr to 100 days. Furthermore, constraints on the contribution of these flares to the diffuse astrophysical neutrino flux are presented, showing that multiple unresolved transient sources may contribute to the diffuse astrophysical neutrino flux.

Published
2024
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9. Search for 10–1000 GeV Neutrinos from Gamma-Ray Bursts with IceCube

Author

R. Abbasi, M. Ackermann, J. Adams, S. K. Agarwalla, J. A. Aguilar, M. Ahlers, J. M. Alameddine, N. M. Amin, K. Andeen, G. Anton, C. Argüelles, Y. Ashida, S. Athanasiadou, L. Ausborm, S. N. Axani, X. Bai, A. Balagopal V., M. Baricevic, S. W. Barwick, V. Basu, R. Bay, J. J. Beatty, J. Becker Tjus, J. Beise, C. Bellenghi, C. Benning, S. BenZvi, D. Berley, E. Bernardini, D. Z. Besson, E. Blaufuss, S. Blot, F. Bontempo, J. Y. Book, C. Boscolo Meneguolo, S. Böser, O. Botner, J. Böttcher, J. Braun, B. Brinson, J. Brostean-Kaiser, L. Brusa, R. T. Burley, R. S. Busse, D. Butterfield, M. A. Campana, K. Carloni, E. G. Carnie-Bronca, S. Chattopadhyay, N. Chau, C. Chen, Z. Chen, D. Chirkin, S. Choi, B. A. Clark, A. Coleman, G. H. Collin, A. Connolly, J. M. Conrad, P. Coppin, P. Correa, D. F. Cowen, P. Dave, C. De Clercq, J. J. DeLaunay, D. Delgado, S. Deng, K. Deoskar, A. Desai, P. Desiati, K. D. de Vries, G. de Wasseige, T. DeYoung, A. Diaz, J. C. Díaz-Vélez, M. Dittmer, A. Domi, H. Dujmovic, M. A. DuVernois, T. Ehrhardt, A. Eimer, P. Eller, E. Ellinger, S. El Mentawi, D. Elsässer, R. Engel, H. Erpenbeck, J. Evans, P. A. Evenson, K. L. Fan, K. Fang, K. Farrag, A. R. Fazely, A. Fedynitch, N. Feigl, S. Fiedlschuster, C. Finley, L. Fischer, D. Fox, A. Franckowiak, P. Fürst, J. Gallagher, E. Ganster, A. Garcia, L. Gerhardt, A. Ghadimi, C. Glaser, T. Glauch, T. Glüsenkamp, J. G. Gonzalez, D. Grant, S. J. Gray, O. Gries, S. Griffin, S. Griswold, K. M. Groth, C. Günther, P. Gutjahr, C. Ha, C. Haack, A. Hallgren, R. Halliday, L. Halve, F. Halzen, H. Hamdaoui, M. Ha Minh, M. Handt, K. Hanson, J. Hardin, A. A. Harnisch, P. Hatch, A. Haungs, J. Häußler, K. Helbing, J. Hellrung, J. Hermannsgabner, L. Heuermann, N. Heyer, S. Hickford, A. Hidvegi, C. Hill, G. C. Hill, K. D. Hoffman, S. Hori, K. Hoshina, W. Hou, T. Huber, K. Hultqvist, M. Hünnefeld, R. Hussain, K. Hymon, S. In, A. Ishihara, M. Jacquart, O. Janik, M. Jansson, G. S. Japaridze, M. Jeong, M. Jin, B. J. P. Jones, N. Kamp, D. Kang, W. Kang, X. Kang, A. Kappes, D. Kappesser, L. Kardum, T. Karg, M. Karl, A. Karle, A. Katil, U. Katz, M. Kauer, J. L. Kelley, A. Khatee Zathul, A. Kheirandish, J. Kiryluk, S. R. Klein, A. Kochocki, R. Koirala, H. Kolanoski, T. Kontrimas, L. Köpke, C. Kopper, D. J. Koskinen, P. Koundal, M. Kovacevich, M. Kowalski, T. Kozynets, J. Krishnamoorthi, K. Kruiswijk, E. Krupczak, A. Kumar, E. Kun, N. Kurahashi, N. Lad, C. Lagunas Gualda, M. Lamoureux, M. J. Larson, S. Latseva, F. Lauber, J. P. Lazar, J. W. Lee, K. Leonard DeHolton, A. Leszczyńska, M. Lincetto, Y. Liu, M. Liubarska, E. Lohfink, C. Love, C. J. Lozano Mariscal, L. Lu, F. Lucarelli, W. Luszczak, Y. Lyu, J. Madsen, E. Magnus, K. B. M. Mahn, Y. Makino, E. Manao, S. Mancina, W. Marie Sainte, I. C. Mariş, S. Marka, Z. Marka, M. Marsee, I. Martinez-Soler, R. Maruyama, F. Mayhew, T. McElroy, F. McNally, J. V. Mead, K. Meagher, S. Mechbal, A. Medina, M. Meier, Y. Merckx, L. Merten, J. Micallef, J. Mitchell, T. Montaruli, R. W. Moore, Y. Morii, R. Morse, M. Moulai, T. Mukherjee, R. Naab, R. Nagai, M. Nakos, U. Naumann, J. Necker, A. Negi, M. Neumann, H. Niederhausen, M. U. Nisa, A. Noell, A. Novikov, S. C. Nowicki, A. Obertacke Pollmann, V. O’Dell, B. Oeyen, A. Olivas, R. Orsoe, J. Osborn, E. O’Sullivan, H. Pandya, N. Park, G. K. Parker, E. N. Paudel, L. Paul, C. Pérez de los Heros, J. Peterson, S. Philippen, A. Pizzuto, M. Plum, A. Pontén, Y. Popovych, M. Prado Rodriguez, B. Pries, R. Procter-Murphy, G. T. Przybylski, C. Raab, J. Rack-Helleis, K. Rawlins, Z. Rechav, A. Rehman, P. Reichherzer, E. Resconi, S. Reusch, W. Rhode, B. Riedel, A. Rifaie, E. J. Roberts, S. Robertson, S. Rodan, G. Roellinghoff, M. Rongen, A. Rosted, C. Rott, T. Ruhe, L. Ruohan, D. Ryckbosch, I. Safa, J. Saffer, D. Salazar-Gallegos, P. Sampathkumar, S. E. Sanchez Herrera, A. Sandrock, M. Santander, S. Sarkar, J. Savelberg, P. Savina, M. Schaufel, H. Schieler, S. Schindler, L. Schlickmann, B. Schlüter, F. Schlüter, N. Schmeisser, T. Schmidt, J. Schneider, F. G. Schröder, L. Schumacher, S. Sclafani, D. Seckel, M. Seikh, S. Seunarine, R. Shah, S. Shefali, N. Shimizu, C. Silva, M. Silva, B. Skrzypek, B. Smithers, R. Snihur, J. Soedingrekso, A. Søgaard, D. Soldin, P. Soldin, G. Sommani, C. Spannfellner, G. M. Spiczak, C. Spiering, M. Stamatikos, T. Stanev, T. Stezelberger, T. Stürwald, T. Stuttard, G. W. Sullivan, I. Taboada, S. Ter-Antonyan, M. Thiesmeyer, W. G. Thompson, J. Thwaites, S. Tilav, K. Tollefson, C. Tönnis, S. Toscano, D. Tosi, A. Trettin, C. F. Tung, R. Turcotte, J. P. Twagirayezu, M. A. Unland Elorrieta, A. K. Upadhyay, K. Upshaw, A. Vaidyanathan, N. Valtonen-Mattila, J. Vandenbroucke, N. van Eijndhoven, D. Vannerom, J. van Santen, J. Vara, J. Veitch-Michaelis, M. Venugopal, M. Vereecken, S. Verpoest, D. Veske, A. Vijai, C. Walck, Y. Wang, C. Weaver, P. Weigel, A. Weindl, J. Weldert, A. Y. Wen, C. Wendt, J. Werthebach, M. Weyrauch, N. Whitehorn, C. H. Wiebusch, D. R. Williams, L. Witthaus, A. Wolf, M. Wolf, G. Wrede, X. W. Xu, J. P. Yanez, E. Yildizci, S. Yoshida, R. Young, S. Yu, T. Yuan, Z. Zhang, P. Zhelnin, P. Zilberman, M. Zimmerman, and IceCube Collaboration

Subjects
Cosmological neutrinos, Gamma-ray bursts, Astrophysics, QB460-466
Abstract

We present the results of a search for 10–1000 GeV neutrinos from 2268 gamma-ray bursts (GRBs) over 8 yr of IceCube-DeepCore data. This work probes burst physics below the photosphere where electromagnetic radiation cannot escape. Neutrinos of tens of giga electronvolts are predicted in sub-photospheric collision of free-streaming neutrons with bulk-jet protons. In a first analysis, we searched for the most significant neutrino-GRB coincidence using six overlapping time windows centered on the prompt phase of each GRB. In a second analysis, we conducted a search for a group of GRBs, each individually too weak to be detectable, but potentially significant when combined. No evidence of neutrino emission is found for either analysis. The most significant neutrino coincidence is for Fermi-GBM GRB bn 140807500, with a p -value of 0.097 corrected for all trials. The binomial test used to search for a group of GRBs had a p -value of 0.65 after all trial corrections. The binomial test found a group consisting only of GRB bn 140807500 and no additional GRBs. The neutrino limits of this work complement those obtained by IceCube at tera electronvolt to peta electronvolt energies. We compare our findings for the large set of GRBs as well as GRB 221009A to the sub-photospheric neutron-proton collision model and find that GRB 221009A provides the most constraining limit on baryon loading. For a jet Lorentz factor of 300 (800), the baryon loading on GRB 221009A is lower than 3.85 (2.13) at a 90% confidence level.

Published
2024
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10. Erratum: 'Search for 10–1000 GeV Neutrinos from Gamma-Ray Bursts with IceCube' (2024, ApJ, 964, 126)

Author

R. Abbasi, M. Ackermann, J. Adams, S. K. Agarwalla, J. A. Aguilar, M. Ahlers, J. M. Alameddine, N. M. Amin, K. Andeen, G. Anton, C. Argüelles, Y. Ashida, S. Athanasiadou, L. Ausborm, S. N. Axani, X. Bai, A. Balagopal V., M. Baricevic, S. W. Barwick, V. Basu, R. Bay, J. J. Beatty, J. Becker Tjus, J. Beise, C. Bellenghi, C. Benning, S. BenZvi, D. Berley, E. Bernardini, D. Z. Besson, E. Blaufuss, S. Blot, F. Bontempo, J. Y. Book, C. Boscolo Meneguolo, S. Böser, O. Botner, J. Böttcher, J. Braun, B. Brinson, J. Brostean-Kaiser, L. Brusa, R. T. Burley, R. S. Busse, D. Butterfield, M. A. Campana, K. Carloni, E. G. Carnie-Bronca, S. Chattopadhyay, N. Chau, C. Chen, Z. Chen, D. Chirkin, S. Choi, B. A. Clark, A. Coleman, G. H. Collin, A. Connolly, J. M. Conrad, P. Coppin, P. Correa, D. F. Cowen, P. Dave, C. De Clercq, J. J. DeLaunay, D. Delgado, S. Deng, K. Deoskar, A. Desai, P. Desiati, K. D. de Vries, G. de Wasseige, T. DeYoung, A. Diaz, J. C. Díaz-Vélez, M. Dittmer, A. Domi, H. Dujmovic, M. A. DuVernois, T. Ehrhardt, A. Eimer, P. Eller, E. Ellinger, S. El Mentawi, D. Elsässer, R. Engel, H. Erpenbeck, J. Evans, P. A. Evenson, K. L. Fan, K. Fang, K. Farrag, A. R. Fazely, A. Fedynitch, N. Feigl, S. Fiedlschuster, C. Finley, L. Fischer, D. Fox, A. Franckowiak, P. Fürst, J. Gallagher, E. Ganster, A. Garcia, L. Gerhardt, A. Ghadimi, C. Glaser, T. Glauch, T. Glüsenkamp, J. G. Gonzalez, D. Grant, S. J. Gray, O. Gries, S. Griffin, S. Griswold, K. M. Groth, C. Günther, P. Gutjahr, C. Ha, C. Haack, A. Hallgren, R. Halliday, L. Halve, F. Halzen, H. Hamdaoui, M. Ha Minh, M. Handt, K. Hanson, J. Hardin, A. A. Harnisch, P. Hatch, A. Haungs, J. Häußler, K. Helbing, J. Hellrung, J. Hermannsgabner, L. Heuermann, N. Heyer, S. Hickford, A. Hidvegi, C. Hill, G. C. Hill, K. D. Hoffman, S. Hori, K. Hoshina, W. Hou, T. Huber, K. Hultqvist, M. Hünnefeld, R. Hussain, K. Hymon, S. In, A. Ishihara, M. Jacquart, O. Janik, M. Jansson, G. S. Japaridze, M. Jeong, M. Jin, B. J. P. Jones, N. Kamp, D. Kang, W. Kang, X. Kang, A. Kappes, D. Kappesser, L. Kardum, T. Karg, M. Karl, A. Karle, A. Katil, U. Katz, M. Kauer, J. L. Kelley, A. Khatee Zathul, A. Kheirandish, J. Kiryluk, S. R. Klein, A. Kochocki, R. Koirala, H. Kolanoski, T. Kontrimas, L. Köpke, C. Kopper, D. J. Koskinen, P. Koundal, M. Kovacevich, M. Kowalski, T. Kozynets, J. Krishnamoorthi, K. Kruiswijk, E. Krupczak, A. Kumar, E. Kun, N. Kurahashi, N. Lad, C. Lagunas Gualda, M. Lamoureux, M. J. Larson, S. Latseva, F. Lauber, J. P. Lazar, J. W. Lee, K. Leonard DeHolton, A. Leszczyńska, M. Lincetto, Y. Liu, M. Liubarska, E. Lohfink, C. Love, C. J. Lozano Mariscal, L. Lu, F. Lucarelli, W. Luszczak, Y. Lyu, J. Madsen, E. Magnus, K. B. M. Mahn, Y. Makino, E. Manao, S. Mancina, W. Marie Sainte, I. C. Mariş, S. Marka, Z. Marka, M. Marsee, I. Martinez-Soler, R. Maruyama, F. Mayhew, T. McElroy, F. McNally, J. V. Mead, K. Meagher, S. Mechbal, A. Medina, M. Meier, Y. Merckx, L. Merten, J. Micallef, J. Mitchell, T. Montaruli, R. W. Moore, Y. Morii, R. Morse, M. Moulai, T. Mukherjee, R. Naab, R. Nagai, M. Nakos, U. Naumann, J. Necker, A. Negi, M. Neumann, H. Niederhausen, M. U. Nisa, A. Noell, A. Novikov, S. C. Nowicki, A. Obertacke Pollmann, V. O’Dell, B. Oeyen, A. Olivas, R. Orsoe, J. Osborn, E. O’Sullivan, H. Pandya, N. Park, G. K. Parker, E. N. Paudel, L. Paul, C. Pérez de los Heros, J. Peterson, S. Philippen, A. Pizzuto, M. Plum, A. Pontén, Y. Popovych, M. Prado Rodriguez, B. Pries, R. Procter-Murphy, G. T. Przybylski, C. Raab, J. Rack-Helleis, K. Rawlins, Z. Rechav, A. Rehman, P. Reichherzer, E. Resconi, S. Reusch, W. Rhode, B. Riedel, A. Rifaie, E. J. Roberts, S. Robertson, S. Rodan, G. Roellinghoff, M. Rongen, A. Rosted, C. Rott, T. Ruhe, L. Ruohan, D. Ryckbosch, I. Safa, J. Saffer, D. Salazar-Gallegos, P. Sampathkumar, S. E. Sanchez Herrera, A. Sandrock, M. Santander, S. Sarkar, J. Savelberg, P. Savina, M. Schaufel, H. Schieler, S. Schindler, L. Schlickmann, B. Schlüter, F. Schlüter, N. Schmeisser, T. Schmidt, J. Schneider, F. G. Schröder, L. Schumacher, S. Sclafani, D. Seckel, M. Seikh, S. Seunarine, R. Shah, S. Shefali, N. Shimizu, C. Silva, M. Silva, B. Skrzypek, B. Smithers, R. Snihur, J. Soedingrekso, A. Søgaard, D. Soldin, P. Soldin, G. Sommani, C. Spannfellner, G. M. Spiczak, C. Spiering, M. Stamatikos, T. Stanev, T. Stezelberger, T. Stürwald, T. Stuttard, G. W. Sullivan, I. Taboada, S. Ter-Antonyan, M. Thiesmeyer, W. G. Thompson, J. Thwaites, S. Tilav, K. Tollefson, C. Tönnis, S. Toscano, D. Tosi, A. Trettin, C. F. Tung, R. Turcotte, J. P. Twagirayezu, M. A. Unland Elorrieta, A. K. Upadhyay, K. Upshaw, A. Vaidyanathan, N. Valtonen-Mattila, J. Vandenbroucke, N. van Eijndhoven, D. Vannerom, J. van Santen, J. Vara, J. Veitch-Michaelis, M. Venugopal, M. Vereecken, S. Verpoest, D. Veske, A. Vijai, C. Walck, Y. Wang, C. Weaver, P. Weigel, A. Weindl, J. Weldert, A. Y. Wen, C. Wendt, J. Werthebach, M. Weyrauch, N. Whitehorn, C. H. Wiebusch, D. R. Williams, L. Witthaus, A. Wolf, M. Wolf, G. Wrede, X. W. Xu, J. P. Yanez, E. Yildizci, S. Yoshida, R. Young, S. Yu, T. Yuan, Z. Zhang, P. Zhelnin, P. Zilberman, M. Zimmerman, and IceCube Collaboration

Subjects
Astrophysics, QB460-466
Published
2024
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11. Probing the Connection between IceCube Neutrinos and MOJAVE AGN

Author

R. Abbasi, M. Ackermann, J. Adams, S. K. Agarwalla, J. A. Aguilar, M. Ahlers, J. M. Alameddine, N. M. Amin, K. Andeen, C. Argüelles, Y. Ashida, S. Athanasiadou, L. Ausborm, S. N. Axani, X. Bai, A. Balagopal V., M. Baricevic, S. W. Barwick, S. Bash, V. Basu, R. Bay, J. J. Beatty, J. Becker Tjus, J. Beise, C. Bellenghi, C. Benning, S. BenZvi, D. Berley, E. Bernardini, D. Z. Besson, E. Blaufuss, L. Bloom, S. Blot, F. Bontempo, J. Y. Book Motzkin, C. Boscolo Meneguolo, S. Böser, O. Botner, J. Böttcher, J. Braun, B. Brinson, J. Brostean-Kaiser, L. Brusa, R. T. Burley, D. Butterfield, M. A. Campana, I. Caracas, K. Carloni, J. Carpio, S. Chattopadhyay, N. Chau, Z. Chen, D. Chirkin, S. Choi, B. A. Clark, A. Coleman, G. H. Collin, A. Connolly, J. M. Conrad, R. Corley, D. F. Cowen, P. Dave, C. De Clercq, J. J. DeLaunay, D. Delgado, S. Deng, A. Desai, P. Desiati, K. D. de Vries, G. de Wasseige, T. DeYoung, A. Diaz, J. C. Díaz-Vélez, P. Dierichs, M. Dittmer, A. Domi, L. Draper, H. Dujmovic, D. Durnford, K. Dutta, M. A. DuVernois, T. Ehrhardt, L. Eidenschink, A. Eimer, P. Eller, E. Ellinger, S. El Mentawi, D. Elsässer, R. Engel, H. Erpenbeck, J. Evans, P. A. Evenson, K. L. Fan, K. Fang, K. Farrag, A. R. Fazely, A. Fedynitch, N. Feigl, S. Fiedlschuster, C. Finley, L. Fischer, D. Fox, A. Franckowiak, S. Fukami, P. Fürst, J. Gallagher, E. Ganster, A. Garcia, M. Garcia, G. Garg, E. Genton, L. Gerhardt, A. Ghadimi, C. Girard-Carillo, C. Glaser, T. Glüsenkamp, J. G. Gonzalez, S. Goswami, A. Granados, D. Grant, S. J. Gray, O. Gries, S. Griffin, S. Griswold, K. M. Groth, D. Guevel, C. Günther, P. Gutjahr, C. Ha, C. Haack, A. Hallgren, L. Halve, F. Halzen, H. Hamdaoui, M. Ha Minh, M. Handt, K. Hanson, J. Hardin, A. A. Harnisch, P. Hatch, A. Haungs, J. Häußler, K. Helbing, J. Hellrung, J. Hermannsgabner, L. Heuermann, N. Heyer, S. Hickford, A. Hidvegi, C. Hill, G. C. Hill, K. D. Hoffman, S. Hori, K. Hoshina, M. Hostert, W. Hou, T. Huber, K. Hultqvist, M. Hünnefeld, R. Hussain, K. Hymon, A. Ishihara, W. Iwakiri, M. Jacquart, S. Jain, O. Janik, M. Jansson, G. S. Japaridze, M. Jeong, M. Jin, B. J. P. Jones, N. Kamp, D. Kang, W. Kang, X. Kang, A. Kappes, D. Kappesser, L. Kardum, T. Karg, M. Karl, A. Karle, A. Katil, U. Katz, M. Kauer, J. L. Kelley, M. Khanal, A. Khatee Zathul, A. Kheirandish, J. Kiryluk, S. R. Klein, A. Kochocki, R. Koirala, H. Kolanoski, T. Kontrimas, L. Köpke, C. Kopper, D. J. Koskinen, P. Koundal, M. Kovacevich, M. Kowalski, T. Kozynets, J. Krishnamoorthi, K. Kruiswijk, E. Krupczak, A. Kumar, E. Kun, N. Kurahashi, N. Lad, C. Lagunas Gualda, M. Lamoureux, M. J. Larson, S. Latseva, F. Lauber, J. P. Lazar, J. W. Lee, K. Leonard DeHolton, A. Leszczyńska, J. Liao, M. Lincetto, Y. T. Liu, M. Liubarska, C. Love, L. Lu, F. Lucarelli, W. Luszczak, Y. Lyu, J. Madsen, E. Magnus, K. B. M. Mahn, Y. Makino, E. Manao, S. Mancina, W. Marie Sainte, I. C. Mariş, S. Marka, Z. Marka, M. Marsee, I. Martinez-Soler, R. Maruyama, F. Mayhew, F. McNally, J. V. Mead, K. Meagher, S. Mechbal, A. Medina, M. Meier, Y. Merckx, L. Merten, J. Micallef, J. Mitchell, T. Montaruli, R. W. Moore, Y. Morii, R. Morse, M. Moulai, T. Mukherjee, R. Naab, R. Nagai, M. Nakos, U. Naumann, J. Necker, A. Negi, L. Neste, M. Neumann, H. Niederhausen, M. U. Nisa, K. Noda, A. Noell, A. Novikov, A. Obertacke Pollmann, V. O’Dell, B. Oeyen, A. Olivas, R. Orsoe, J. Osborn, E. O’Sullivan, V. Palusova, H. Pandya, N. Park, G. K. Parker, E. N. Paudel, L. Paul, C. Pérez de los Heros, T. Pernice, J. Peterson, A. Pizzuto, M. Plum, A. Pontén, Y. Popovych, M. Prado Rodriguez, B. Pries, R. Procter-Murphy, G. T. Przybylski, C. Raab, J. Rack-Helleis, M. Ravn, K. Rawlins, Z. Rechav, A. Rehman, P. Reichherzer, E. Resconi, S. Reusch, W. Rhode, B. Riedel, A. Rifaie, E. J. Roberts, S. Robertson, S. Rodan, G. Roellinghoff, M. Rongen, A. Rosted, C. Rott, T. Ruhe, L. Ruohan, D. Ryckbosch, I. Safa, J. Saffer, D. Salazar-Gallegos, P. Sampathkumar, A. Sandrock, M. Santander, S. Sarkar, J. Savelberg, P. Savina, P. Schaile, M. Schaufel, H. Schieler, S. Schindler, L. Schlickmann, B. Schlüter, F. Schlüter, N. Schmeisser, T. Schmidt, J. Schneider, F. G. Schröder, L. Schumacher, S. Sclafani, D. Seckel, M. Seikh, M. Seo, S. Seunarine, P. Sevle Myhr, R. Shah, S. Shefali, N. Shimizu, M. Silva, B. Skrzypek, B. Smithers, R. Snihur, J. Soedingrekso, A. Søgaard, D. Soldin, P. Soldin, G. Sommani, C. Spannfellner, G. M. Spiczak, C. Spiering, M. Stamatikos, T. Stanev, T. Stezelberger, T. Stürwald, T. Stuttard, G. W. Sullivan, I. Taboada, S. Ter-Antonyan, A. Terliuk, M. Thiesmeyer, W. G. Thompson, J. Thwaites, S. Tilav, K. Tollefson, C. Tönnis, S. Toscano, D. Tosi, A. Trettin, R. Turcotte, J. P. Twagirayezu, M. A. Unland Elorrieta, A. K. Upadhyay, K. Upshaw, A. Vaidyanathan, N. Valtonen-Mattila, J. Vandenbroucke, N. van Eijndhoven, D. Vannerom, J. van Santen, J. Vara, F. Varsi, J. Veitch-Michaelis, M. Venugopal, M. Vereecken, S. Vergara Carrasco, S. Verpoest, D. Veske, A. Vijai, C. Walck, A. Wang, C. Weaver, P. Weigel, A. Weindl, J. Weldert, A. Y. Wen, C. Wendt, J. Werthebach, M. Weyrauch, N. Whitehorn, C. H. Wiebusch, D. R. Williams, L. Witthaus, A. Wolf, M. Wolf, G. Wrede, X. W. Xu, J. P. Yanez, E. Yildizci, S. Yoshida, R. Young, S. Yu, T. Yuan, Z. Zhang, P. Zhelnin, P. Zilberman, and M. Zimmerman

Subjects
Neutrino astronomy, High energy astrophysics, Radio astronomy, Astrophysics, QB460-466
Abstract

Active galactic nuclei (AGN) are prime candidate sources of the high-energy, astrophysical neutrinos detected by IceCube. This is demonstrated by the real-time multimessenger detection of the blazar TXS 0506+056 and the recent evidence of neutrino emission from NGC 1068 from a separate time-averaged study. However, the production mechanism of the astrophysical neutrinos in AGN is not well established, which can be resolved via correlation studies with photon observations. For neutrinos produced due to photohadronic interactions in AGN, in addition to a correlation of neutrinos with high-energy photons, there would also be a correlation of neutrinos with photons emitted at radio wavelengths. In this work, we perform an in-depth stacking study of the correlation between 15 GHz radio observations of AGN reported in the MOJAVE XV catalog, and 10 yr of neutrino data from IceCube. We also use a time-dependent approach, which improves the statistical power of the stacking analysis. No significant correlation was found for both analyses, and upper limits are reported. When compared to the IceCube diffuse flux, at 100 TeV and for a spectral index of 2.5, the upper limits derived are ∼3% and ∼9% for the time-averaged and time-dependent cases, respectively.

Published
2024
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12. High-throughput somatic mutation profiling in pulmonary sarcomatoid carcinomas using the LungCarta™ Panel: exploring therapeutic targets

Author

F. Thivolet-Bejui, D. Moro-Sibilot, T. Vieira, Raphaël Saffroy, Julien Mazieres, Sylvie Lantuejoul, Virginie Poulot, Nicolas Girard, Vincent Fallet, Isabelle Rouquette, Jacques Cadranel, Marie Wislez, Antoinette Lemoine, Mony Ung, Martine Antoine, and L. Schlick

Subjects
Neuroblastoma RAS viral oncogene homolog, Adult, Male, Mutation rate, Lung Neoplasms, STK11, Protein Serine-Threonine Kinases, medicine.disease_cause, Genetic analysis, GTP Phosphohydrolases, Cohort Studies, Proto-Oncogene Proteins p21(ras), Germline mutation, AMP-Activated Protein Kinase Kinases, Carcinosarcoma, Carcinoma, Non-Small-Cell Lung, Biopsy, medicine, Humans, Receptor, Notch1, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Lung Sarcomatoid Carcinoma, Carcinoma, High-Throughput Nucleotide Sequencing, Membrane Proteins, Nuclear Proteins, Carcinoma, Giant Cell, Hematology, Middle Aged, ErbB Receptors, Oncology, Mutation, Cancer research, Female, KRAS, Tumor Suppressor Protein p53, business, Transcription Factors
Abstract

Background Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology. Patients and methods We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes. Results In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold. Conclusion Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials.

Published
2015

13. Facteurs associés à l’expression de PD-L1 dans les carcinomes sarcomatoïdes

Author

Virginie Poulot, Nathalie Rabbe, A. Rodenas, Marie Wislez, Jacques Cadranel, T. Vieira, Armelle Lavolé, L. Schlick, and Martine Antoine

Subjects
Pulmonary and Respiratory Medicine, business.industry, Medicine, business, Molecular biology
Abstract

Introduction Les carcinomes sarcomatoides (CS) sont des tumeurs de mauvais pronostic et chimio-resistantes. Les therapies ciblant l’axe PD-1/PD-L1 offrent une nouvelle piste de traitement ; caracteriser l’infiltrat inflammatoire intratumoral et mesurer l’expression de l’axe PD-1/PD-L1 sur ces tumeurs permettraient d’apprehender l’efficacite de ces traitements. Methodes De 1997 a 2013, tous les patients operes d’un CS ont ete colliges. L’infiltrat inflammatoire et l’expression de PD-L1 ont ete etudies par etude en IHC : CD3 (clone SP7), CD4 (clone 1F6), CD8 (clone C8/144b), CD20 (clone L26), CD163 (clone 10D6), MPO (clone 59A5), PD-L1 (clone 5H1). Resultats Soixante-quinze patients etaient inclus. L’infiltrat inflammatoire etait compose de lymphocytes T CD3+ (mediane 23 % [17–30] de la surface tumorale) de T CD8+ (9 % [7–12]) de T CD4+ (10 % [5–14]), de B CD20+ (3,5 % [1–8]), de macrophages CD163+ (23 % [17–30]), ainsi que de neutrophiles MPO+ (5,5 % [2–11]). Quarante tumeurs (53 %) exprimaient PD-L1. L’expression tumorale de PD-L1 etait associee a l’extension vasculaire sanguine, l’expression de TTF1 et l’absence d’expression tumorale de P63 et la presence d’une mutation de KRAS. L’expression tumorale de PD-L1 etait associee a une infiltration plus importante de lymphocytes CD8+ et de macrophages. L’expression de PD-L1 n’etait pas un facteur pronostique de survie. Conclusion Les inhibiteurs de PD-1/PD-L1 pourraient etre une piste therapeutique des CS du fait du degre d’infiltration lymphocytaire et de l’expression de PD-L1 dans ces tumeurs.

Published
2015
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14. L’activation de la voie Sonic Hedgehog est associée à la résistance à la chimiothérapie à base de sels de platine dans le cancer bronchique non à petites cellules

Author

Marie Wislez, Nathalie Rabbe, T. Vieira, L. Schlick, N. Rozensztajn, E. Giroux Leprieur, Martine Antoine, and Jacques Cadranel

Subjects
Pulmonary and Respiratory Medicine, Gynecology, medicine.medical_specialty, business.industry, medicine, business
Abstract

Introduction La chimioresistance est un defi majeur dans la prise en charge des patients avec un cancer bronchique non a petites cellules (CBNPC) de stade avance. La voie Sonic Hedgehog (Shh), mise en jeu lors du developpement, est reactivee dans le CBNPC. Nous avons cherche dans cette etude un lien entre l’activation de la voie Shh et la chimioresistance. Methodes A partir d’une cohorte de 178 patients avec CBNPC de stade avance traites entre 2003 et 2006 par chimiotherapie a base de platine en 1 re ligne, nous avons retenus les patients avec un prelevement chirurgical diagnostique ( n = 36). L’activation de la voie Shh a ete etudiee par l’expression de Gli1 et Gli2 en immuno-histochimie (score quantitatif). Nous avons aussi utilise des lignees cellulaires de CBNPC (H322 et A549) et des cultures primaires issues de patients ayant un carcinome sarcomatoide ( n = 4). Nous les avons traitees par du cisplatine, du vismodegib (inhibiteur de la voie Shh) et par la combinaison des 2 medicaments, et cherche un effet potentialisateur du vismodegib sur l’inhibition de la proliferation cellulaire. Resultats Sur les 36 patients, 12 etaient refractaires a la chimiotherapie (33,3 %) et 24 controles. L’expression de Gli1 n’etait pas differente entre les patients refractaires et les controles ( p = 0,35). L’expression de Gli2 etait plus souvent positive chez les patients refractaires que les controles (41,7 % versus 8,3 %, p = 0,02). La mediane de survie sans progression (SSP) etait de 2,1 mois en cas de score positif, versus 6,7 mois en cas de score negatif ( p = 0,03), et celle de survie globale etait de 8 mois en cas de score positif, versus 18 mois en cas de score negatif ( p = 0,002). Le score Gli2 etait independamment correle a la SSP et la survie globale en analyse multivariee. Les lignees cellulaires de carcinome sarcomatoide etaient les plus resistantes au cisplatine. L’association vismodegib et cisplatine avait un effet synergique sur les lignees les plus resistantes au cisplatine. Conclusion Cette etude confirme le role de la voie Shh dans la resistance a la chimiotherapie a base de sel de platine dans le CBNPC.

Published
2015
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15. Aérosolthérapie anti-VEGF dans les adénocarcinomes pulmonaires primitifs mutés pour K-ras

Author

Etienne Lemarié, Laurent Guilleminault, Françoise Rédini, Virginie Hervé, Michael Duruisseaux, Nathalie Rabbe, Nathalie Heuzé-Vourc'h, Marie Wislez, Delphine Fouquenet, Nicolas Azzopardi, Jérôme Montharu, Gilles Paintaud, L. Schlick, F. Paul, and Jacques Cadranel

Subjects
Pulmonary and Respiratory Medicine, business.industry, Medicine, business, Molecular biology
Abstract

Introduction Parmi les cancers bronchopulmonaires non a petites cellules, 10 a 30 % sont porteurs d’une mutation au niveau du gene RAS, qui semble responsable de resistance a certains traitements et a la chimiotherapie. Une des alternatives therapeutiques est de cibler le vascular endothelial growth factor (VEGF), mediateur de l’angiogenese favorisant la croissance tumorale. Sa neutralisation par un anticorps monoclonal (AcM) administre par voie intraveineuse (IV) a demontre son efficacite, mais ses effets secondaires limitent son utilisation. Nous avons donc etudie l’administration d’un AcM anti-VEGF, le G6-31, par voie pulmonaire, dans un modele murin d’adenocarcinome pulmonaire primitif mute pour K-ras (K-rasLA1). Methodes Le G6-31 a ete fourni par Genentech (MTA OR-209 778). Une experience a ete menee sur des souris saines afin d’evaluer la tolerance du G6-31 administre par voie aerosol, a 10 mg/kg, 1 fois/semaine (sem), pendant 4 sem. L’efficacite anti-tumorale du G6-31 a ensuite ete evaluee sur des souris K-rasLA1 (injection par voie intraperitoneale ou aerosol a 2,5 ou 10 mg/kg, 1 fois/sem, pendant 4 sem). Les nodules ont ete denombres, les proteines extraites pour analyser les voies de signalisation et un poumon fixe pour les analyses histologiques. Enfin, pour realiser une analyse pharmacocinetique, le G6-31 a ete injecte a 10 mg/kg, par voie IV ou aerosol, et des prelevements sanguins ont ete effectues pour quantifier le G6-31 par Elisa. Resultats L’administration pulmonaire du G6-31, des 2,5 mg/kg, a diminue significativement le nombre de tumeurs. Le G6-31 induit l’inhibition du VEGFR2, impactant sur la croissance des vaisseaux sanguins et la proliferation tumorale. De plus, le G6-31 administre par voie aerosol a montre un faible passage dans le sang, ce qui permettrait de reduire ses effets secondaires. Conclusion Nos resultats montrent ainsi la pertinence de l’administration d’AcM anti-angiogenique par voie aerosol pour traiter les adenocarcinomes pulmonaires mutes pour K-ras.

Published
2015
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17. Search for Correlations of High-energy Neutrinos Detected in IceCube with Radio-bright AGN and Gamma-Ray Emission from Blazars

Author

R. Abbasi, M. Ackermann, J. Adams, S. K. Agarwalla, J. A. Aguilar, M. Ahlers, J. M. Alameddine, N. M. Amin, K. Andeen, G. Anton, C. Argüelles, Y. Ashida, S. Athanasiadou, S. N. Axani, X. Bai, A. Balagopal V., M. Baricevic, S. W. Barwick, V. Basu, R. Bay, J. J. Beatty, K.-H. Becker, J. Becker Tjus, J. Beise, C. Bellenghi, C. Benning, S. BenZvi, D. Berley, E. Bernardini, D. Z. Besson, G. Binder, E. Blaufuss, S. Blot, F. Bontempo, J. Y. Book, C. Boscolo Meneguolo, S. Böser, O. Botner, J. Böttcher, E. Bourbeau, J. Braun, B. Brinson, J. Brostean-Kaiser, R. T. Burley, R. S. Busse, D. Butterfield, M. A. Campana, K. Carloni, E. G. Carnie-Bronca, S. Chattopadhyay, N. Chau, C. Chen, Z. Chen, D. Chirkin, S. Choi, B. A. Clark, L. Classen, A. Coleman, G. H. Collin, A. Connolly, J. M. Conrad, P. Coppin, P. Correa, S. Countryman, D. F. Cowen, P. Dave, C. De Clercq, J. J. DeLaunay, D. Delgado, H. Dembinski, S. Deng, K. Deoskar, A. Desai, P. Desiati, K. D. de Vries, G. de Wasseige, T. DeYoung, A. Diaz, J. C. Díaz-Vélez, M. Dittmer, A. Domi, H. Dujmovic, M. A. DuVernois, T. Ehrhardt, P. Eller, S. El Mentawi, R. Engel, H. Erpenbeck, J. Evans, P. A. Evenson, K. L. Fan, K. Fang, K. Farrag, A. R. Fazely, A. Fedynitch, N. Feigl, S. Fiedlschuster, C. Finley, L. Fischer, D. Fox, A. Franckowiak, E. Friedman, A. Fritz, P. Fürst, T. K. Gaisser, J. Gallagher, E. Ganster, A. Garcia, L. Gerhardt, A. Ghadimi, C. Glaser, T. Glauch, T. Glüsenkamp, N. Goehlke, J. G. Gonzalez, S. Goswami, D. Grant, S. J. Gray, O. Gries, S. Griffin, S. Griswold, C. Günther, P. Gutjahr, C. Haack, A. Hallgren, R. Halliday, L. Halve, F. Halzen, H. Hamdaoui, M. Ha Minh, K. Hanson, J. Hardin, A. A. Harnisch, P. Hatch, A. Haungs, K. Helbing, J. Hellrung, F. Henningsen, L. Heuermann, N. Heyer, S. Hickford, A. Hidvegi, C. Hill, G. C. Hill, K. D. Hoffman, S. Hori, K. Hoshina, W. Hou, T. Huber, K. Hultqvist, M. Hünnefeld, R. Hussain, K. Hymon, S. In, A. Ishihara, M. Jacquart, O. Janik, M. Jansson, G. S. Japaridze, K. Jayakumar, M. Jeong, M. Jin, B. J. P. Jones, D. Kang, W. Kang, X. Kang, A. Kappes, D. Kappesser, L. Kardum, T. Karg, M. Karl, A. Karle, U. Katz, M. Kauer, J. L. Kelley, A. Khatee Zathul, A. Kheirandish, J. Kiryluk, S. R. Klein, A. Kochocki, R. Koirala, H. Kolanoski, T. Kontrimas, L. Köpke, C. Kopper, D. J. Koskinen, P. Koundal, M. Kovacevich, M. Kowalski, T. Kozynets, K. Kruiswijk, E. Krupczak, A. Kumar, E. Kun, N. Kurahashi, N. Lad, C. Lagunas Gualda, M. Lamoureux, M. J. Larson, S. Latseva, F. Lauber, J. P. Lazar, J. W. Lee, K. Leonard DeHolton, A. Leszczyńska, M. Lincetto, Q. R. Liu, M. Liubarska, E. Lohfink, C. Love, C. J. Lozano Mariscal, L. Lu, F. Lucarelli, A. Ludwig, W. Luszczak, Y. Lyu, J. Madsen, K. B. M. Mahn, Y. Makino, E. Manao, S. Mancina, W. Marie Sainte, I. C. Mariş, S. Marka, Z. Marka, M. Marsee, I. Martinez-Soler, R. Maruyama, F. Mayhew, T. McElroy, F. McNally, J. V. Mead, K. Meagher, S. Mechbal, A. Medina, M. Meier, Y. Merckx, L. Merten, J. Micallef, T. Montaruli, R. W. Moore, Y. Morii, R. Morse, M. Moulai, T. Mukherjee, R. Naab, R. Nagai, M. Nakos, U. Naumann, J. Necker, M. Neumann, H. Niederhausen, M. U. Nisa, A. Noell, S. C. Nowicki, A. Obertacke Pollmann, V. O’Dell, M. Oehler, B. Oeyen, A. Olivas, R. Orsoe, J. Osborn, E. O’Sullivan, H. Pandya, N. Park, G. K. Parker, E. N. Paudel, L. Paul, C. Pérez de los Heros, J. Peterson, S. Philippen, S. Pieper, A. Pizzuto, M. Plum, A. Pontén, Y. Popovych, M. Prado Rodriguez, B. Pries, R. Procter-Murphy, G. T. Przybylski, J. Rack-Helleis, K. Rawlins, Z. Rechav, A. Rehman, P. Reichherzer, G. Renzi, E. Resconi, S. Reusch, W. Rhode, M. Richman, B. Riedel, A. Rifaie, E. J. Roberts, S. Robertson, S. Rodan, G. Roellinghoff, M. Rongen, C. Rott, T. Ruhe, L. Ruohan, D. Ryckbosch, I. Safa, J. Saffer, D. Salazar-Gallegos, P. Sampathkumar, S. E. Sanchez Herrera, A. Sandrock, M. Santander, S. Sarkar, J. Savelberg, P. Savina, M. Schaufel, H. Schieler, S. Schindler, L. Schlickmann, B. Schlüter, F. Schlüter, T. Schmidt, J. Schneider, F. G. Schröder, L. Schumacher, G. Schwefer, S. Sclafani, D. Seckel, M. Seikh, S. Seunarine, R. Shah, A. Sharma, S. Shefali, N. Shimizu, M. Silva, B. Skrzypek, B. Smithers, R. Snihur, J. Soedingrekso, A. Søgaard, D. Soldin, P. Soldin, G. Sommani, C. Spannfellner, G. M. Spiczak, C. Spiering, M. Stamatikos, T. Stanev, T. Stezelberger, T. Stürwald, T. Stuttard, G. W. Sullivan, I. Taboada, S. Ter-Antonyan, M. Thiesmeyer, W. G. Thompson, J. Thwaites, S. Tilav, K. Tollefson, C. Tönnis, S. Toscano, D. Tosi, A. Trettin, C. F. Tung, R. Turcotte, J. P. Twagirayezu, B. Ty, M. A. Unland Elorrieta, A. K. Upadhyay, K. Upshaw, N. Valtonen-Mattila, J. Vandenbroucke, N. van Eijndhoven, D. Vannerom, J. van Santen, J. Vara, J. Veitch-Michaelis, M. Venugopal, M. Vereecken, S. Verpoest, D. Veske, C. Walck, T. B. Watson, C. Weaver, P. Weigel, A. Weindl, J. Weldert, C. Wendt, J. Werthebach, M. Weyrauch, N. Whitehorn, C. H. Wiebusch, N. Willey, D. R. Williams, A. Wolf, M. Wolf, G. Wrede, X. W. Xu, J. P. Yanez, E. Yildizci, S. Yoshida, R. Young, F. Yu, S. Yu, T. Yuan, Z. Zhang, P. Zhelnin, and IceCube Collaboration

Subjects
Neutrino astronomy, Gamma-ray sources, Radio active galactic nuclei, Astrophysics, QB460-466
Abstract

The IceCube Neutrino Observatory sends realtime neutrino alerts with a high probability of being astrophysical in origin. We present a new method to correlate these events and possible candidate sources using 2089 blazars from the Fermi-LAT 4LAC-DR2 catalog and with 3413 active galactic nuclei (AGNs) from the Radio Fundamental Catalog. No statistically significant neutrino emission was found in any of the catalog searches. The result suggests that a small fraction,

Published
2023
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18. Search for Extended Sources of Neutrino Emission in the Galactic Plane with IceCube

Author

R. Abbasi, M. Ackermann, J. Adams, S. K. Agarwalla, J. A. Aguilar, M. Ahlers, J. M. Alameddine, N. M. Amin, K. Andeen, G. Anton, C. Argüelles, Y. Ashida, S. Athanasiadou, S. N. Axani, X. Bai, A. Balagopal V., M. Baricevic, S. W. Barwick, V. Basu, R. Bay, J. J. Beatty, J. Becker Tjus, J. Beise, C. Bellenghi, C. Benning, S. BenZvi, D. Berley, E. Bernardini, D. Z. Besson, E. Blaufuss, S. Blot, F. Bontempo, J. Y. Book, C. Boscolo Meneguolo, S. Böser, O. Botner, J. Böttcher, E. Bourbeau, J. Braun, B. Brinson, J. Brostean-Kaiser, R. T. Burley, R. S. Busse, D. Butterfield, M. A. Campana, K. Carloni, E. G. Carnie-Bronca, S. Chattopadhyay, N. Chau, C. Chen, Z. Chen, D. Chirkin, S. Choi, B. A. Clark, L. Classen, A. Coleman, G. H. Collin, A. Connolly, J. M. Conrad, P. Coppin, P. Correa, D. F. Cowen, P. Dave, C. De Clercq, J. J. DeLaunay, D. Delgado, S. Deng, K. Deoskar, A. Desai, P. Desiati, K. D. de Vries, G. de Wasseige, T. DeYoung, A. Diaz, J. C. Díaz-Vélez, M. Dittmer, A. Domi, H. Dujmovic, M. A. DuVernois, T. Ehrhardt, P. Eller, E. Ellinger, S. El Mentawi, D. Elsässer, R. Engel, H. Erpenbeck, J. Evans, P. A. Evenson, K. L. Fan, K. Fang, K. Farrag, A. R. Fazely, A. Fedynitch, N. Feigl, S. Fiedlschuster, C. Finley, L. Fischer, D. Fox, A. Franckowiak, A. Fritz, P. Fürst, J. Gallagher, E. Ganster, A. Garcia, L. Gerhardt, A. Ghadimi, C. Glaser, T. Glauch, T. Glüsenkamp, N. Goehlke, J. G. Gonzalez, S. Goswami, D. Grant, S. J. Gray, O. Gries, S. Griffin, S. Griswold, K. M. Groth, C. Günther, P. Gutjahr, C. Haack, A. Hallgren, R. Halliday, L. Halve, F. Halzen, H. Hamdaoui, M. Ha Minh, K. Hanson, J. Hardin, A. A. Harnisch, P. Hatch, A. Haungs, K. Helbing, J. Hellrung, F. Henningsen, L. Heuermann, N. Heyer, S. Hickford, A. Hidvegi, C. Hill, G. C. Hill, K. D. Hoffman, S. Hori, K. Hoshina, W. Hou, T. Huber, K. Hultqvist, M. Hünnefeld, R. Hussain, K. Hymon, S. In, A. Ishihara, M. Jacquart, O. Janik, M. Jansson, G. S. Japaridze, M. Jeong, M. Jin, B. J. P. Jones, D. Kang, W. Kang, X. Kang, A. Kappes, D. Kappesser, L. Kardum, T. Karg, M. Karl, A. Karle, U. Katz, M. Kauer, J. L. Kelley, A. Khatee Zathul, A. Kheirandish, J. Kiryluk, S. R. Klein, A. Kochocki, R. Koirala, H. Kolanoski, T. Kontrimas, L. Köpke, C. Kopper, D. J. Koskinen, P. Koundal, M. Kovacevich, M. Kowalski, T. Kozynets, J. Krishnamoorthi, K. Kruiswijk, E. Krupczak, A. Kumar, E. Kun, N. Kurahashi, N. Lad, C. Lagunas Gualda, M. Lamoureux, M. J. Larson, S. Latseva, F. Lauber, J. P. Lazar, J. W. Lee, K. Leonard DeHolton, A. Leszczyńska, M. Lincetto, Q. R. Liu, M. Liubarska, E. Lohfink, C. Love, C. J. Lozano Mariscal, L. Lu, F. Lucarelli, W. Luszczak, Y. Lyu, J. Madsen, K. B. M. Mahn, Y. Makino, E. Manao, S. Mancina, W. Marie Sainte, I. C. Mariş, S. Marka, Z. Marka, M. Marsee, I. Martinez-Soler, R. Maruyama, F. Mayhew, T. McElroy, F. McNally, J. V. Mead, K. Meagher, S. Mechbal, A. Medina, M. Meier, Y. Merckx, L. Merten, J. Micallef, J. Mitchell, T. Montaruli, R. W. Moore, Y. Morii, R. Morse, M. Moulai, T. Mukherjee, R. Naab, R. Nagai, M. Nakos, U. Naumann, J. Necker, A. Negi, M. Neumann, H. Niederhausen, M. U. Nisa, A. Noell, A. Novikov, S. C. Nowicki, A. Obertacke Pollmann, V. O’Dell, M. Oehler, B. Oeyen, A. Olivas, R. Orsoe, J. Osborn, E. O’Sullivan, H. Pandya, N. Park, G. K. Parker, E. N. Paudel, L. Paul, C. Pérez de los Heros, J. Peterson, S. Philippen, A. Pizzuto, M. Plum, A. Pontén, Y. Popovych, M. Prado Rodriguez, B. Pries, R. Procter-Murphy, G. T. Przybylski, C. Raab, J. Rack-Helleis, K. Rawlins, Z. Rechav, A. Rehman, P. Reichherzer, G. Renzi, E. Resconi, S. Reusch, W. Rhode, B. Riedel, A. Rifaie, E. J. Roberts, S. Robertson, S. Rodan, G. Roellinghoff, M. Rongen, C. Rott, T. Ruhe, L. Ruohan, D. Ryckbosch, D. Rysewyk, I. Safa, J. Saffer, D. Salazar-Gallegos, P. Sampathkumar, S. E. Sanchez Herrera, A. Sandrock, M. Santander, S. Sarkar, J. Savelberg, P. Savina, M. Schaufel, H. Schieler, S. Schindler, L. Schlickmann, B. Schlüter, F. Schlüter, N. Schmeisser, T. Schmidt, J. Schneider, F. G. Schröder, L. Schumacher, G. Schwefer, S. Sclafani, D. Seckel, M. Seikh, S. Seunarine, R. Shah, A. Sharma, S. Shefali, N. Shimizu, M. Silva, B. Skrzypek, B. Smithers, R. Snihur, J. Soedingrekso, A. Søgaard, D. Soldin, P. Soldin, G. Sommani, C. Spannfellner, G. M. Spiczak, C. Spiering, M. Stamatikos, T. Stanev, T. Stezelberger, T. Stürwald, T. Stuttard, G. W. Sullivan, I. Taboada, S. Ter-Antonyan, M. Thiesmeyer, W. G. Thompson, J. Thwaites, S. Tilav, K. Tollefson, C. Tönnis, S. Toscano, D. Tosi, A. Trettin, C. F. Tung, R. Turcotte, J. P. Twagirayezu, B. Ty, M. A. Unland Elorrieta, A. K. Upadhyay, K. Upshaw, N. Valtonen-Mattila, J. Vandenbroucke, N. van Eijndhoven, D. Vannerom, J. van Santen, J. Vara, J. Veitch-Michaelis, M. Venugopal, M. Vereecken, S. Verpoest, D. Veske, A. Vijai, C. Walck, C. Weaver, P. Weigel, A. Weindl, J. Weldert, C. Wendt, J. Werthebach, M. Weyrauch, N. Whitehorn, C. H. Wiebusch, N. Willey, D. R. Williams, A. Wolf, M. Wolf, G. Wrede, X. W. Xu, J. P. Yanez, E. Yildizci, S. Yoshida, R. Young, F. Yu, S. Yu, T. Yuan, Z. Zhang, P. Zhelnin, M. Zimmerman, and IceCube Collaboration

Subjects
Neutrino astronomy, Astrophysics, QB460-466
Abstract

The Galactic plane, harboring a diffuse neutrino flux, is a particularly interesting target in which to study potential cosmic-ray acceleration sites. Recent gamma-ray observations by HAWC and LHAASO have presented evidence for multiple Galactic sources that exhibit a spatially extended morphology and have energy spectra continuing beyond 100 TeV. A fraction of such emission could be produced by interactions of accelerated hadronic cosmic rays, resulting in an excess of high-energy neutrinos clustered near these regions. Using 10 years of IceCube data comprising track-like events that originate from charged-current muon neutrino interactions, we perform a dedicated search for extended neutrino sources in the Galaxy. We find no evidence for time-integrated neutrino emission from the potential extended sources studied in the Galactic plane. The most significant location, at 2.6 σ post-trials, is a 1.°7 sized region coincident with the unidentified TeV gamma-ray source 3HWC J1951+266. We provide strong constraints on hadronic emission from several regions in the galaxy.

Published
2023
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20. Soybean and Sunflower Oil Performance in a Diesel Engine

Author

M. L. Schlick, J. L. Schinstock, and M. A. Hanna

Subjects
Diesel fuel, food.ingredient, food, Waste management, Winter diesel fuel, Sunflower oil, Environmental science, Fuel oil, Combustion chamber, Diesel engine, Agricultural and Biological Sciences (miscellaneous), Soybean oil, Heat engine
Abstract

THE performance of a direct injection diesel engine operating on mechanically expelled-unrefined soybean oil and sunflower oil blended with number 2 diesel fuel on a 25:75 v/v basis was evaluated. The power remained constant throughout 200 h of operation. Excessive carbon deposits on all combustion chamber parts precludes the use of these fuel blends, at least in this engine and under the specified EMA operating conditions.

Published
1988
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21. Evidence for NR2F2/COUP-TFII involvement in human testis development.

Author

Wankanit S, Zidoune H, Bignon-Topalovic J, Schlick L, Houzelstein D, Fusée L, Boukri A, Nouri N, McElreavey K, Bashamboo A, and Elzaiat M

Subjects
Humans, Male, Steroidogenic Factor 1 metabolism, Steroidogenic Factor 1 genetics, Mutation, Hypogonadism genetics, Hypogonadism metabolism, COUP Transcription Factor II metabolism, COUP Transcription Factor II genetics, Testis metabolism
Abstract

NR2F2 encodes COUP-TFII, an orphan nuclear receptor required for the development of the steroidogenic lineages of the murine fetal testes and ovaries. Pathogenic variants in human NR2F2 are associated with testis formation in 46,XX individuals, however, the function of COUP-TFII in the human testis is unknown. We report a de novo heterozygous variant in NR2F2 (c.737G > A, p.Arg246His) in a 46,XY under-masculinized boy with primary hypogonadism. The variant, located within the ligand-binding domain, is predicted to be highly damaging. In vitro studies indicated that the mutation does not impact the stability or subcellular localization of the protein. NR5A1, a related nuclear receptor that is a key factor in gonad formation and function, is known to physically interact with COUP-TFII to regulate gene expression. The mutant protein did not affect the physical interaction with NR5A1. However, in-vitro assays demonstrated that the mutant protein significantly loses the inhibitory effect on NR5A1-mediated activation of both the LHB and INSL3 promoters. The data support a role for COUP-TFII in human testis formation. Although mutually antagonistic sets of genes are known to regulate testis and ovarian pathways, we extend the list of genes, that together with NR5A1 and WT1, are associated with both 46,XX and 46,XY DSD., (© 2024. The Author(s).)

Published
2024
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22. A conserved NR5A1-responsive enhancer regulates SRY in testis-determination.

Author

Houzelstein D, Eozenou C, Lagos CF, Elzaiat M, Bignon-Topalovic J, Gonzalez I, Laville V, Schlick L, Wankanit S, Madon P, Kirtane J, Athalye A, Buonocore F, Bigou S, Conway GS, Bohl D, Achermann JC, Bashamboo A, and McElreavey K

Subjects
Animals, Female, Humans, Male, Cell Line, Mammals genetics, Regulatory Sequences, Nucleic Acid, Sertoli Cells metabolism, Sex-Determining Region Y Protein genetics, Steroidogenic Factor 1 genetics, Steroidogenic Factor 1 metabolism, Gonadal Dysgenesis, Testis metabolism
Abstract

The Y-linked SRY gene initiates mammalian testis-determination. However, how the expression of SRY is regulated remains elusive. Here, we demonstrate that a conserved steroidogenic factor-1 (SF-1)/NR5A1 binding enhancer is required for appropriate SRY expression to initiate testis-determination in humans. Comparative sequence analysis of SRY 5' regions in mammals identified an evolutionary conserved SF-1/NR5A1-binding motif within a 250 bp region of open chromatin located 5 kilobases upstream of the SRY transcription start site. Genomic analysis of 46,XY individuals with disrupted testis-determination, including a large multigenerational family, identified unique single-base substitutions of highly conserved residues within the SF-1/NR5A1-binding element. In silico modelling and in vitro assays demonstrate the enhancer properties of the NR5A1 motif. Deletion of this hemizygous element by genome-editing, in a novel in vitro cellular model recapitulating human Sertoli cell formation, resulted in a significant reduction in expression of SRY. Therefore, human NR5A1 acts as a regulatory switch between testis and ovary development by upregulating SRY expression, a role that may predate the eutherian radiation. We show that disruption of an enhancer can phenocopy variants in the coding regions of SRY that cause human testis dysgenesis. Since disease causing variants in enhancers are currently rare, the regulation of gene expression in testis-determination offers a paradigm to define enhancer activity in a key developmental process., (© 2024. The Author(s).)

Published
2024
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23. Serum autoantibodies against α7-nicotinic receptors in subgroups of patients with bipolar disorder or schizophrenia: clinical features and link with peripheral inflammation.

Author

Darrau E, Jacquemet E, Pons S, Schlick L, Zouridakis M, Wu CL, Richard JR, Barau C, Le Corvoisier P, Yolken R, Tamouza R, Leboyer M, and Maskos U

Subjects
Humans, Mice, Animals, alpha7 Nicotinic Acetylcholine Receptor, Inflammation metabolism, Autoantibodies, Bipolar Disorder, Schizophrenia, Receptors, Nicotinic
Abstract

There is growing evidence that autoantibodies (AAbs) against proteins expressed in the brain are playing an important role in neurological and psychiatric disorders. Here, we explore the presence and the role of peripheral AAbs to the α7-nicotinic acetylcholine receptor (nAChR) in inflammatory subgroups of psychiatric patients with bipolar disorder (BD) or schizophrenia (SCZ) and healthy controls. We have identified a continuum of AAb levels in serum when employing a novel ELISA technique, with a significant elevation in patients compared to controls. Using unsupervised two-step clustering to stratify all the subjects according to their immuno-inflammatory background, we delineate one subgroup consisting solely of psychiatric patients with severe symptoms, high inflammatory profile, and significantly increased levels of anti-nAChR AAbs. In this context, we have used monoclonal mouse anti-human α7-nAChR antibodies (α7-nAChR-mAbs) and shown that TNF-α release was enhanced upon LPS stimulation in macrophages pre-incubated with α7-nAChR-mAbs compared to the use of an isotype control. These findings provide a basis for further study of circulating nicotinic AAbs, and the inflammatory profile observed in patients with major mood and psychotic disorders., (© 2024. The Author(s).)

Published
2024
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24. Functional maturation of human iPSC-derived pyramidal neurons in vivo is dependent on proximity with the host tissue.

Author

Raïs C, Gaspar Santos D, Sansone G, Blanchard S, Bourgeois JP, Jagla B, Saudemont B, Schlick L, Pons S, and Maskos U

Abstract

Human induced pluripotent stem cells (hiPSCs) have been used extensively in vitro to model early events in neurodevelopment. Because of a number of shortcomings, previous work has established a potential to use these cells in vivo after transplantation into the mouse brain. Here, we describe a systematic approach for the analysis of transplanted hiPSC-derived neurons and glial cells over time in the mouse brain. Using functional two-photon imaging of GCaMP6f- expressing human neural cells, we define and quantify the embryonic-like features of their spontaneous activity. This is substantiated by detailed electron microscopy (EM) of the graft. We relate this to the synaptic development the neurons undergo up to 7 months in vivo. This system can now be used further for the genetic or experimental manipulation of developing hiPSC-derived cells addressing neurodevelopmental diseases like schizophrenia or Autism Spectrum Disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Raïs, Gaspar Santos, Sansone, Blanchard, Bourgeois, Jagla, Saudemont, Schlick, Pons and Maskos.)

Published
2023
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25. High-throughput somatic mutation profiling in pulmonary sarcomatoid carcinomas using the LungCarta™ Panel: exploring therapeutic targets.

Author

Fallet V, Saffroy R, Girard N, Mazieres J, Lantuejoul S, Vieira T, Rouquette I, Thivolet-Bejui F, Ung M, Poulot V, Schlick L, Moro-Sibilot D, Antoine M, Cadranel J, Lemoine A, and Wislez M

Subjects
AMP-Activated Protein Kinase Kinases, Adult, Aged, Carcinoma genetics, Cohort Studies, ErbB Receptors genetics, Female, GTP Phosphohydrolases genetics, High-Throughput Nucleotide Sequencing, Humans, Male, Membrane Proteins genetics, Middle Aged, Mutation, Nuclear Proteins genetics, Protein Serine-Threonine Kinases genetics, Proto-Oncogene Proteins p21(ras) genetics, Receptor, Notch1 genetics, Retrospective Studies, Transcription Factors genetics, Tumor Suppressor Protein p53 genetics, Carcinoma, Giant Cell genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinosarcoma genetics, Lung Neoplasms genetics
Abstract

Background: Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology., Patients and Methods: We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes., Results: In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold., Conclusion: Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2015
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26. VEGF neutralizing aerosol therapy in primary pulmonary adenocarcinoma with K-ras activating-mutations.

Author

Hervé V, Rabbe N, Guilleminault L, Paul F, Schlick L, Azzopardi N, Duruisseaux M, Fouquenet D, Montharu J, Redini F, Paintaud G, Lemarié E, Cadranel J, Wislez M, and Heuzé-Vourc'h N

Subjects
Adenocarcinoma genetics, Adenocarcinoma metabolism, Aerosols, Animals, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal pharmacokinetics, Antibodies, Neutralizing administration & dosage, Antibodies, Neutralizing immunology, Antibodies, Neutralizing pharmacology, Area Under Curve, Biological Availability, Blotting, Western, Cell Proliferation drug effects, Cells, Cultured, Humans, Immunohistochemistry, Injections, Intraperitoneal, Lung Neoplasms genetics, Lung Neoplasms metabolism, Mice, Inbred C57BL, Mice, Knockout, Mutation, Neovascularization, Pathologic genetics, Neovascularization, Pathologic prevention & control, Proto-Oncogene Proteins p21(ras) genetics, Treatment Outcome, Vascular Endothelial Growth Factor A immunology, Vascular Endothelial Growth Factor Receptor-2 metabolism, Adenocarcinoma drug therapy, Antibodies, Monoclonal pharmacology, Lung Neoplasms drug therapy, Vascular Endothelial Growth Factor A antagonists & inhibitors
Abstract

K-ras mutations promote angiogenesis in lung cancer and contribute to the drug resistance of cancer cells. It is not clear whether K-ras mutated adenocarcinomas are sensitive to anti-angiogenic therapy with monoclonal antibodies (mAbs) that target vascular endothelial growth factor (VEGF). Anti-angiogenic mAbs are usually delivered systemically, but only a small proportion reaches the lung after intravenous injection. We investigated the relevance of a non-invasive pulmonary route for the delivery of anti-VEGF mAbs in the mouse K-ras(LA1) model. We found that pulmonary delivery of these mAbs significantly reduced the number of tumor lesions and inhibited malignant progression. The antitumor effect involves the VEGFR2-dependent inhibition of blood vessel growth, which impairs tumor proliferation. Pharmacokinetic analysis of aerosolized anti-VEGF showed its low rate of passage into the bloodstream, suggesting that this delivery route is associated with reduced systemic side effects. Our findings highlight the value of the aerosol route for administration of anti-angiogenic mAbs in pulmonary adenocarcinoma with K-ras activating-mutations.

Published
2014
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