397 results on '"Alvarez, K"'
Search Results
2. Titanium Dioxide-Decorated and Silanized Electrospun Recycled Polyethylene Terephthalate (PET) Fibers for Filtration.
- Author
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Macaraig, L, Zingapan, J, Alvarez, K V N, and Enriquez, E P
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- 2024
- Full Text
- View/download PDF
3. Cellular activation pathway of bemnifosbuvir (AT-527), a drug candidate against SARS-CoV-2 infections
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Chazot, A., primary, Zimberger, C., additional, Feracci, M., additional, Hernandez, S., additional, Falcou, C., additional, Moussa, A., additional, Good, S., additional, Sommadossi, J.-P., additional, Ferron, F., additional, Alvarez, K., additional, and Canard, B., additional
- Published
- 2023
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- View/download PDF
4. Mental health, migration stressors and suicidal ideation among Latino immigrants in Spain and the United States
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Fortuna, L.R., Álvarez, K., Ramos Ortiz, Z., Wang, Y., Mozo Alegría, X., Cook, B.L., and Alegría, M.
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- 2016
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5. Experience in a Public Hospital with patients older than 60 years after breast cancer surgery, admitted to a Hospital Home Care Unit for physiotherapy for rehabilitation
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Calderon, O., primary, Poblete, C., additional, Alvarez, K., additional, and Freire, F., additional
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- 2022
- Full Text
- View/download PDF
6. Cd4+ T cell phenotypes, autoantibodies and transcriptional signatures overlap between myocarditis, ischemic and nonischemic heart failure, suggesting shared inflammatory pathogenic mechanisms
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Sandel, C, primary, Myers, J, additional, Alvarez, K, additional, Stavrakis, S, additional, Gaffney, P, additional, and Cunningham, M, additional
- Published
- 2022
- Full Text
- View/download PDF
7. 21390. TRATAMIENTO FIBRINOLÍTICO EN LA OCLUSIÓN DE ARTERIA CENTRAL DE LA RETINA. EXPERIENCIA CLÍNICA INICIAL EN UNA UNIDAD DE ICTUS
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Núñez Manjarres, G., Madina Korta, I., Irigoyen Laborra, C., Albajar, I., Álvarez, K., Ayuso García, D., Escobar Padilla, C., Lijeron Farel, S., Martínez Zabaleta, M., and de la Riva, P.
- Published
- 2024
- Full Text
- View/download PDF
8. Crystal structure of the N-terminal endonuclease domain of La Crosse virus L-protein bound to compound Baloxavir
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Feracci, M., primary, Hernandez, S., additional, Vincentelli, R., additional, Ferron, F., additional, Reguera, J., additional, Canard, B., additional, and Alvarez, K., additional
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- 2022
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9. CHRONIC THROMBOEMBOLIC DISEASE AFTER ACUTE PULMONARY EMBOLISM RELATED TO SARS-CoV-2
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Caguana Vélez, O A, primary, Khilzi Alvarez, K H, additional, Rodríguez-Sevilla, J J, additional, Badenes Bonet, D, additional, Villar Garcia, J, additional, Gonzalez Garcia, J G, additional, Herranz Blasco, A, additional, Admetllo Papiol, M, additional, Rodo Pin, A, additional, Molina Ferragut, L, additional, Zuccarino, F, additional, Balcells Vilarnau, E, additional, Rodriguez Chiaradía, D A, additional, and Vélez, O, additional
- Published
- 2022
- Full Text
- View/download PDF
10. Crystal structure of the N-terminal endonuclease domain of La Crosse virus L-protein bound to compound L-742,001
- Author
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Feracci, M., primary, Hernandez, S., additional, Vincentelli, R., additional, Ferron, F., additional, Reguera, J., additional, Canard, B., additional, and Alvarez, K., additional
- Published
- 2022
- Full Text
- View/download PDF
11. Blood miR-144-3p: a novel diagnostic and therapeutic tool for depression
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van der Zee, Y.Y., Eijssen, L.M.T., Mews, P., Ramakrishnan, A., Alvarez, K., Lardner, C.K., Cates, H.M., Walker, D.M., Torres-Berrio, A., Browne, C.J., Cunningham, A., Cathomas, F., Kronman, H., Parise, E.M., de Nijs, L., Shen, L., Murrough, J.W., Rutten, B.P.F., Nestler, E.J., Issler, O., van der Zee, Y.Y., Eijssen, L.M.T., Mews, P., Ramakrishnan, A., Alvarez, K., Lardner, C.K., Cates, H.M., Walker, D.M., Torres-Berrio, A., Browne, C.J., Cunningham, A., Cathomas, F., Kronman, H., Parise, E.M., de Nijs, L., Shen, L., Murrough, J.W., Rutten, B.P.F., Nestler, E.J., and Issler, O.
- Abstract
Major depressive disorder (MDD) is the leading cause of disability worldwide. There is an urgent need for objective biomarkers to diagnose this highly heterogeneous syndrome, assign treatment, and evaluate treatment response and prognosis. MicroRNAs (miRNAs) are short non-coding RNAs, which are detected in body fluids that have emerged as potential biomarkers of many disease conditions. The present study explored the potential use of miRNAs as biomarkers for MDD and its treatment. We profiled the expression levels of circulating blood miRNAs from mice that were collected before and after exposure to chronic social defeat stress (CSDS), an extensively validated mouse model used to study depression, as well as after either repeated imipramine or single-dose ketamine treatment. We observed robust differences in blood miRNA signatures between stress-resilient and stress-susceptible mice after an incubation period, but not immediately after exposure to the stress. Furthermore, ketamine treatment was more effective than imipramine at re-establishing baseline miRNA expression levels, but only in mice that responded behaviorally to the drug. We identified the red blood cell-specific miR-144-3p as a candidate biomarker to aid depression diagnosis and predict ketamine treatment response in stress-susceptible mice and MDD patients. Lastly, we demonstrate that systemic knockdown of miR-144-3p, via subcutaneous administration of a specific antagomir, is sufficient to reduce the depression-related phenotype in stress-susceptible mice. RNA-sequencing analysis of blood after such miR-144-3p knockdown revealed a blunted transcriptional stress signature as well. These findings identify miR-144-3p as a novel target for diagnosis of MDD as well as for antidepressant treatment, and enhance our understanding of epigenetic processes associated with depression.
- Published
- 2022
12. A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase
- Author
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Shannon, A., primary, Fattorini, V., additional, Sama, B., additional, Selisko, B., additional, Feracci, M., additional, Falcou, C., additional, Gauffre, P., additional, El Kazzi, P., additional, Delpal, A., additional, Decroly, E., additional, Alvarez, K., additional, Eydoux, C., additional, Guillemot, J.-C., additional, Moussa, A., additional, Good, S., additional, Colla, P., additional, Lin, K., additional, Sommadossi, J.-P., additional, Zhu, Y.X., additional, Yan, X.D., additional, Shi, H., additional, Ferron, F., additional, and Canard, B., additional
- Published
- 2022
- Full Text
- View/download PDF
13. Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database (Genetics in Medicine, (2020), 22, 1, (15-25), 10.1038/s41436-019-0596-9)
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Dominguez-Valentin M., Sampson J. R., Seppala T. T., ten Broeke S. W., Plazzer J. -P., Nakken S., Engel C., Aretz S., Jenkins M. A., Sunde L., Bernstein I., Capella G., Balaguer F., Thomas H., Evans D. G., Burn J., Greenblatt M., Hovig E., de Vos tot Nederveen Cappel W. H., Sijmons R. H., Bertario L., Tibiletti M. G., Cavestro G. M., Lindblom A., Della Valle A., Lopez-Kostner F., Gluck N., Katz L. H., Heinimann K., Vaccaro C. A., Buttner R., Gorgens H., Holinski-Feder E., Morak M., Holzapfel S., Huneburg R., Knebel Doeberitz M., Loeffler M., Rahner N., Schackert H. K., Steinke-Lange V., Schmiegel W., Vangala D., Pylvanainen K., Renkonen-Sinisalo L., Hopper J. L., Win A. K., Haile R. W., Lindor N. M., Gallinger S., Le Marchand L., Newcomb P. A., Figueiredo J. C., Thibodeau S. N., Wadt K., Therkildsen C., Okkels H., Ketabi Z., Moreira L., Sanchez A., Serra-Burriel M., Pineda M., Navarro M., Blanco I., Green K., Lalloo F., Crosbie E. J., Hill J., Denton O. G., Frayling I. M., Rodland E. A., Vasen H., Mints M., Neffa F., Esperon P., Alvarez K., Kariv R., Rosner G., Pinero T. A., Gonzalez M. L., Kalfayan P., Tjandra D., Winship I. M., Macrae F., Moslein G., Mecklin J. -P., Nielsen M., Moller P., Dominguez-Valentin, M., Sampson, J. R., Seppala, T. T., ten Broeke, S. W., Plazzer, J. -P., Nakken, S., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., Hovig, E., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Bertario, L., Tibiletti, M. G., Cavestro, G. M., Lindblom, A., Della Valle, A., Lopez-Kostner, F., Gluck, N., Katz, L. H., Heinimann, K., Vaccaro, C. A., Buttner, R., Gorgens, H., Holinski-Feder, E., Morak, M., Holzapfel, S., Huneburg, R., Knebel Doeberitz, M., Loeffler, M., Rahner, N., Schackert, H. K., Steinke-Lange, V., Schmiegel, W., Vangala, D., Pylvanainen, K., Renkonen-Sinisalo, L., Hopper, J. L., Win, A. K., Haile, R. W., Lindor, N. M., Gallinger, S., Le Marchand, L., Newcomb, P. A., Figueiredo, J. C., Thibodeau, S. N., Wadt, K., Therkildsen, C., Okkels, H., Ketabi, Z., Moreira, L., Sanchez, A., Serra-Burriel, M., Pineda, M., Navarro, M., Blanco, I., Green, K., Lalloo, F., Crosbie, E. J., Hill, J., Denton, O. G., Frayling, I. M., Rodland, E. A., Vasen, H., Mints, M., Neffa, F., Esperon, P., Alvarez, K., Kariv, R., Rosner, G., Pinero, T. A., Gonzalez, M. L., Kalfayan, P., Tjandra, D., Winship, I. M., Macrae, F., Moslein, G., Mecklin, J. -P., Nielsen, M., and Moller, P.
- Abstract
The original version of this Article did not contain details of Dutch Cancer Society (DCS) funding (grant number UL 2017-8223) in the Acknowledgements section. This has now been corrected in both the PDF and HTML versions of the Article.
- Published
- 2020
14. High yield synthesis, purification and characterisation of the RNase L activators 5′-triphosphate 2′–5′-oligoadenylates
- Author
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Morin, B., Rabah, N., Boretto-Soler, J., Tolou, H., Alvarez, K., and Canard, B.
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- 2010
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15. Observation of arenavirus nucleoprotein heptamer assembly
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Papageorgiou, N., Vaitsopoulou, A., Diop, A., Nguyen, T. H. V., Canard, B., Alvarez, K., and Ferron, F.
- Subjects
Arenaviridae ,assembly ,Bunyavirales ,nucleoprotein - Published
- 2021
16. High-frequency power loss mechanisms in ultra-thin amorphous ribbons
- Author
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Masood, A., Baghbaderani, H. A., Alvarez, K. L., Blanco, J. M., Pavlovic, Z., Ström, Valter, Stamenov, P., Mathuna, C. O., McCloskey, P., Masood, A., Baghbaderani, H. A., Alvarez, K. L., Blanco, J. M., Pavlovic, Z., Ström, Valter, Stamenov, P., Mathuna, C. O., and McCloskey, P.
- Abstract
Soft magnetic amorphous materials with ultra-low power loss are highly desirable for high-frequency drive applications. The present work demonstrates the high-frequency power loss performance and underlying loss mechanisms in ultra-thin amorphous alloys. This is achieved by rapid-quenching amorphous alloys of Co-, CoFe- and Fe-rich systems, investigating their amorphous atomic structure, quantifying the saturation magnetostriction constants (λs), imaging magnetic domains at remanent magnetization, analyzing magnetization reversal from various magnetization levels, and finally, investigating the material loss performance over a broad frequency range (f = 50 kHz–2 MHz) at various excitation levels (Bm = 25–100 mT). The ultra-high performance of ultra-thin Co-rich amorphous ribbons, as compared to CoFe- and Fe-rich alloys, was attributed to the significantly low eddy current loss, due to the reduced thickness, and a minimal amount of excess loss, owning to minimal magnetoelastic contributions and magnetization reversal by rotation. The underlying loss mechanisms were analyzed by decomposing material loss into primary components and identifying the magnetization reversal mechanisms using minor hysteresis loops. In the Co-rich amorphous alloys, we suggest that magnetization reversal by rotation dominates, at least at low excitations, while in CoFe- and Fe-rich alloys domain wall displacement prevails and contributes significantly to the excess loss up to the MHz frequency range. Magnetization reversal by rotation in Co-rich alloys could be attributed to the zero/near-zero λs, and eventually low residual stress, leading to a homogeneous magnetic domain structure, as compared to the inhomogeneous “fingerprint-like” complex domains in highly magnetostrictive CoFe-rich alloys., QC 20210319
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- 2021
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- View/download PDF
17. LBSL: Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations
- Author
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Stellingwerff, M.D., Figuccia, S., Bellacchio, E., Alvarez, K., Castiglioni, C., Topaloglu, P., Stutterd, C.A., Erasmus, C.E., Sanchez-Valle, A., Lebon, S., Hughes, S., Schmitt-Mechelke, T., Vasco, G., Chow, G., Rahikkala, E., Dallabona, C., Okuma, C., Aiello, C., Goffrini, P., Abbink, T.E., Bertini, E.S., Knaap, M.S. van der, Stellingwerff, M.D., Figuccia, S., Bellacchio, E., Alvarez, K., Castiglioni, C., Topaloglu, P., Stutterd, C.A., Erasmus, C.E., Sanchez-Valle, A., Lebon, S., Hughes, S., Schmitt-Mechelke, T., Vasco, G., Chow, G., Rahikkala, E., Dallabona, C., Okuma, C., Aiello, C., Goffrini, P., Abbink, T.E., Bertini, E.S., and Knaap, M.S. van der
- Abstract
Contains fulltext : 234042.pdf (Publisher’s version ) (Open Access), OBJECTIVE: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in DARS2, encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). DARS2 variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. We noticed highly unusual MRI presentations in 15 cases diagnosed by WES. We examined these cases to determine whether they represent consistent novel LBSL phenotypes. METHODS: We reviewed clinical features, MRI abnormalities, and gene variants and investigated the variants' impact on mtAspRS structure and mitochondrial function. RESULTS: We found 2 MRI phenotypes: early severe cerebral hypoplasia/atrophy (9 patients, group 1) and white matter abnormalities without long tract involvement (6 patients, group 2). With antenatal onset, microcephaly, and arrested development, group 1 patients were most severely affected. DARS2 variants were severer than for classic LBSL and severer for group 1 than group 2. All missense variants hit mtAspRS regions involved in tRNA(Asp) binding, aspartyl-adenosine-5'-monophosphate binding, and/or homodimerization. Missense variants expressed in the yeast DARS2 ortholog showed severely affected mitochondrial function. CONCLUSIONS: DARS2 variants are associated with highly heterogeneous phenotypes. New MRI presentations are profound cerebral hypoplasia/atrophy and white matter abnormalities without long tract involvement. Our findings have implications for diagnosis and understanding disease mechanisms, pointing at dominant neuronal/axonal involvement in severe cases. In line with this conclusion, activation of biallelic DARS2 null alleles in conditional transgenic mice leads to massive neuronal apoptosis.
- Published
- 2021
18. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study
- Author
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The International Mismatch Repair Consortium, Win, AK, Dowty, JG, Reece, JC, Lee, G, Templeton, AS, Plazzer, JP, Buchanan, DD, Akagi, K, Aksoy, S, Alonso, A, Alvarez, K, Amor, DJ, Ankathil, R, Aretz, S, Arnold, JL, Aronson, M, Austin, R, Backman, AS, Rasmussen, Lene, The International Mismatch Repair Consortium, Win, AK, Dowty, JG, Reece, JC, Lee, G, Templeton, AS, Plazzer, JP, Buchanan, DD, Akagi, K, Aksoy, S, Alonso, A, Alvarez, K, Amor, DJ, Ankathil, R, Aretz, S, Arnold, JL, Aronson, M, Austin, R, Backman, AS, and Rasmussen, Lene
- Published
- 2021
19. LBSL: Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations.
- Author
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Stellingwerff, MD, Figuccia, S, Bellacchio, E, Alvarez, K, Castiglioni, C, Topaloglu, P, Stutterd, CA, Erasmus, CE, Sanchez-Valle, A, Lebon, S, Hughes, S, Schmitt-Mechelke, T, Vasco, G, Chow, G, Rahikkala, E, Dallabona, C, Okuma, C, Aiello, C, Goffrini, P, Abbink, TEM, Bertini, ES, Van der Knaap, MS, Stellingwerff, MD, Figuccia, S, Bellacchio, E, Alvarez, K, Castiglioni, C, Topaloglu, P, Stutterd, CA, Erasmus, CE, Sanchez-Valle, A, Lebon, S, Hughes, S, Schmitt-Mechelke, T, Vasco, G, Chow, G, Rahikkala, E, Dallabona, C, Okuma, C, Aiello, C, Goffrini, P, Abbink, TEM, Bertini, ES, and Van der Knaap, MS
- Abstract
OBJECTIVE: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in DARS2, encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). DARS2 variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. We noticed highly unusual MRI presentations in 15 cases diagnosed by WES. We examined these cases to determine whether they represent consistent novel LBSL phenotypes. METHODS: We reviewed clinical features, MRI abnormalities, and gene variants and investigated the variants' impact on mtAspRS structure and mitochondrial function. RESULTS: We found 2 MRI phenotypes: early severe cerebral hypoplasia/atrophy (9 patients, group 1) and white matter abnormalities without long tract involvement (6 patients, group 2). With antenatal onset, microcephaly, and arrested development, group 1 patients were most severely affected. DARS2 variants were severer than for classic LBSL and severer for group 1 than group 2. All missense variants hit mtAspRS regions involved in tRNAAsp binding, aspartyl-adenosine-5'-monophosphate binding, and/or homodimerization. Missense variants expressed in the yeast DARS2 ortholog showed severely affected mitochondrial function. CONCLUSIONS: DARS2 variants are associated with highly heterogeneous phenotypes. New MRI presentations are profound cerebral hypoplasia/atrophy and white matter abnormalities without long tract involvement. Our findings have implications for diagnosis and understanding disease mechanisms, pointing at dominant neuronal/axonal involvement in severe cases. In line with this conclusion, activation of biallelic DARS2 null alleles in conditional transgenic mice leads to massive neuronal apoptosis.
- Published
- 2021
20. Uptake of hysterectomy and bilateral salpingooophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report
- Author
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Seppala, TT, Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Vida, JB, Kariv, R, Rosner, G, Pinero, TA, Pavicic, W, Kalfayan, P, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Redler, S, Weitz, J, Pylvaenaeinen, K, Renkonen-Sinisalo, L, Lepisto, A, Hopper, JL, Win, AK, Lindor, NM, Gallinger, S, Marchand, LL, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Wadt, KAW, Mourits, MJE, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Rokkones, E, Sampson, JR, Evans, DG, Moller, P, Seppala, TT, Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Vida, JB, Kariv, R, Rosner, G, Pinero, TA, Pavicic, W, Kalfayan, P, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Redler, S, Weitz, J, Pylvaenaeinen, K, Renkonen-Sinisalo, L, Lepisto, A, Hopper, JL, Win, AK, Lindor, NM, Gallinger, S, Marchand, LL, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Wadt, KAW, Mourits, MJE, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Rokkones, E, Sampson, JR, Evans, DG, and Moller, P
- Abstract
PURPOSE: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years. RESULTS: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery. CONCLUSION: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene- and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syndrome to improve outcomes.
- Published
- 2021
21. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report
- Author
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Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Nakken, S, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Brunet Vidal, J, Kariv, R, Rosner, G, Alejandra Pinero, T, Laura Gonzalez, M, Kalfayan, P, Ryan, N, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Auranen, A, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Okkels, H, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Sampson, JR, Evans, DG, Seppala, TT, Moller, P, Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Nakken, S, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Brunet Vidal, J, Kariv, R, Rosner, G, Alejandra Pinero, T, Laura Gonzalez, M, Kalfayan, P, Ryan, N, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Auranen, A, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Okkels, H, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Sampson, JR, Evans, DG, Seppala, TT, and Moller, P
- Abstract
PURPOSE: To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. RESULTS: Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. CONCLUSION: Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.
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- 2021
22. No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
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Dominguez-Valentin, M, Plazzer, J-P, Sampson, JR, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Macrae, F, Winship, IM, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Cappel, WHDVTN, Sijmons, RH, Nielsen, M, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Alvarez, K, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Nakken, S, Hovig, E, Green, K, Lalloo, F, Hill, J, Vasen, HFA, Perne, C, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Steinke-Lange, V, Schmiegel, W, Vangala, D, Crosbie, EJ, Pineda, M, Navarro, M, Brunet, J, Moreira, L, Sanchez, A, Serra-Burriel, M, Mints, M, Kariv, R, Rosner, G, Pinero, TA, Pavicic, WH, Kalfayan, P, ten Broeke, SW, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Hopper, JL, Win, AK, Buchanan, DD, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Hansen, TVO, Lindberg, L, Rodland, EA, Neffa, F, Esperon, P, Tjandra, D, Moslein, G, Seppala, TT, Moller, P, Dominguez-Valentin, M, Plazzer, J-P, Sampson, JR, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Macrae, F, Winship, IM, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Cappel, WHDVTN, Sijmons, RH, Nielsen, M, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Alvarez, K, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Nakken, S, Hovig, E, Green, K, Lalloo, F, Hill, J, Vasen, HFA, Perne, C, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Steinke-Lange, V, Schmiegel, W, Vangala, D, Crosbie, EJ, Pineda, M, Navarro, M, Brunet, J, Moreira, L, Sanchez, A, Serra-Burriel, M, Mints, M, Kariv, R, Rosner, G, Pinero, TA, Pavicic, WH, Kalfayan, P, ten Broeke, SW, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Hopper, JL, Win, AK, Buchanan, DD, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Hansen, TVO, Lindberg, L, Rodland, EA, Neffa, F, Esperon, P, Tjandra, D, Moslein, G, Seppala, TT, and Moller, P
- Abstract
BACKGROUND: Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. OBJECTIVE: To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. METHODS: Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. RESULTS: Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. CONCLUSION: Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
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- 2021
23. LBSL case series and DARS2 variant analysis in early severe forms with unexpected presentations
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Stellingwerff, M. D. (Menno D.), Figuccia, S. (Sonia), Bellacchio, E. (Emanuele), Alvarez, K. (Karin), Castiglioni, C. (Claudia), Topaloglu, P. (Pinar), Stutterd, C. A. (Chloe A.), Erasmus, C. E. (Corrie E.), Sanchez‐Valle, A. (Amarilis), Lebon, S. (Sebastien), Hughes, S. (Sarah), Schmitt-Mechelke, T. (Thomas), Vasco, G. (Gessica), Chow, G. (Gabriel), Rahikkala, E. (Elisa), Dallabona, C. (Cristina), Okuma, C. (Cecilia), Aiello, C. (Chiara), Goffrini, P. (Paola), Abbink, T. E. (Truus E.M.), Bertini, E. S. (Enrico S.), Van der Knaap, M. S. (Marjo S.), Stellingwerff, M. D. (Menno D.), Figuccia, S. (Sonia), Bellacchio, E. (Emanuele), Alvarez, K. (Karin), Castiglioni, C. (Claudia), Topaloglu, P. (Pinar), Stutterd, C. A. (Chloe A.), Erasmus, C. E. (Corrie E.), Sanchez‐Valle, A. (Amarilis), Lebon, S. (Sebastien), Hughes, S. (Sarah), Schmitt-Mechelke, T. (Thomas), Vasco, G. (Gessica), Chow, G. (Gabriel), Rahikkala, E. (Elisa), Dallabona, C. (Cristina), Okuma, C. (Cecilia), Aiello, C. (Chiara), Goffrini, P. (Paola), Abbink, T. E. (Truus E.M.), Bertini, E. S. (Enrico S.), and Van der Knaap, M. S. (Marjo S.)
- Abstract
Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in DARS2, encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). DARS2 variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. We noticed highly unusual MRI presentations in 15 cases diagnosed by WES. We examined these cases to determine whether they represent consistent novel LBSL phenotypes. Methods: We reviewed clinical features, MRI abnormalities, and gene variants and investigated the variants’ impact on mtAspRS structure and mitochondrial function. Results: We found 2 MRI phenotypes: early severe cerebral hypoplasia/atrophy (9 patients, group 1) and white matter abnormalities without long tract involvement (6 patients, group 2). With antenatal onset, microcephaly, and arrested development, group 1 patients were most severely affected. DARS2 variants were severer than for classic LBSL and severer for group 1 than group 2. All missense variants hit mtAspRS regions involved in tRNAAsp binding, aspartyl-adenosine-59-monophosphate binding, and/or homodimerization. Missense variants expressed in the yeast DARS2 ortholog showed severely affected mitochondrial function. Conclusions: DARS2 variants are associated with highly heterogeneous phenotypes. New MRI presentations are profound cerebral hypoplasia/atrophy and white matter abnormalities without long tract involvement. Our findings have implications for diagnosis and understanding disease mechanisms, pointing at dominant neuronal/axonal involvement in severe cases. In line with this conclusion, activation of biallelic DARS2 null alleles in conditional transgenic mice leads to massive neuronal apoptosis.
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- 2021
24. Analysis in the Prospective Lynch Syndrome Database identifies sarcoma as part of the Lynch syndrome tumor spectrum
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Dominguez-Valentin M., Sampson J. R., Moller P., Seppala T. T., Plazzer J. -P., Nakken S., Engel C., Aretz S., Jenkins M. A., Sunde L., Bernstein I., Capella G., Balaguer F., Thomas H., Evans D. G., Burn J., Greenblatt M., Hovig E., Nielsen M., de Vos tot Nederveen Cappel W. H., Sijmons R. H., Bertario L., Tibiletti M. G., Cavestro G. M., Lindblom A., Valle A. D., Lopez-Kostner F., Gluck N., Katz L. H., Heinimann K., Vaccaro C. A., Buttner R., Gorgens H., Holinski-Feder E., Morak M., Holzapfel S., Huneburg R., von Knebel Doeberitz M., Loeffler M., Rahner N., Weitz J., Steinke-Lange V., ten Broeke S. W., Schmiegel W., Vangala D., Pylvanainen K., Renkonen-Sinisalo L., Hopper J. L., Win A. K., Haile R. W., Lindor N. M., Gallinger S., Le Marchand L., Newcomb P. A., Figueiredo J. C., Thibodeau S. N., Jensen L. H., Madsen M. B., Kroldrup L., Nilbert M., Moreira L., Sanchez A., Serra-Burriel M., Pineda M., Navarro M., Vidal J. B., Blanco I., Green K., Lalloo F., Crosbie E. J., Hill J., Denton O. G., Rodland E. A., Vasen H., Mints M., Neffa F., Esperon P., Alvarez K., Kariv R., Rosner G., Pinero T. A., Gonzalez M. L., Kalfayan P., Tjandra D., Winship I. M., Macrae F., Moslein G., Mecklin J. -P., Dominguez-Valentin, M., Sampson, J. R., Moller, P., Seppala, T. T., Plazzer, J. -P., Nakken, S., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., Hovig, E., Nielsen, M., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Bertario, L., Tibiletti, M. G., Cavestro, G. M., Lindblom, A., Valle, A. D., Lopez-Kostner, F., Gluck, N., Katz, L. H., Heinimann, K., Vaccaro, C. A., Buttner, R., Gorgens, H., Holinski-Feder, E., Morak, M., Holzapfel, S., Huneburg, R., von Knebel Doeberitz, M., Loeffler, M., Rahner, N., Weitz, J., Steinke-Lange, V., ten Broeke, S. W., Schmiegel, W., Vangala, D., Pylvanainen, K., Renkonen-Sinisalo, L., Hopper, J. L., Win, A. K., Haile, R. W., Lindor, N. M., Gallinger, S., Le Marchand, L., Newcomb, P. A., Figueiredo, J. C., Thibodeau, S. N., Jensen, L. H., Madsen, M. B., Kroldrup, L., Nilbert, M., Moreira, L., Sanchez, A., Serra-Burriel, M., Pineda, M., Navarro, M., Vidal, J. B., Blanco, I., Green, K., Lalloo, F., Crosbie, E. J., Hill, J., Denton, O. G., Rodland, E. A., Vasen, H., Mints, M., Neffa, F., Esperon, P., Alvarez, K., Kariv, R., Rosner, G., Pinero, T. A., Gonzalez, M. L., Kalfayan, P., Tjandra, D., Winship, I. M., Macrae, F., Moslein, G., and Mecklin, J. -P.
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Male ,Adult ,Oncology ,Cancer Research ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,sarcoma ,Databases, Factual ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Sarcoma/diagnosis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Aged ,business.industry ,Sarcoma ,Syndrome ,Middle Aged ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Lynch syndrome ,MSH2 ,030220 oncology & carcinogenesis ,Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis ,Female ,030211 gastroenterology & hepatology ,business - Published
- 2020
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25. Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database (vol 22, pg 15, 2020)
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Dominguez-Valentin, M, Sampson, JR, Seppala, TT, ten Broeke, SW, Plazzer, J-P, Nakken, S, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Hovig, E, de Vos tot Nederveen Cappel, WH, Sijmons, RH, Bertario, L, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Gluck, N, Katz, LH, Heinimann, K, Vaccaro, CA, Buttner, R, Gorgens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Huneburg, R, Knebel Doeberitz, MV, Loeffler, M, Rahner, N, Schackert, HK, Steinke-Lange, V, Schmiegel, W, Vangala, D, Pylvanainen, K, Renkonen-Sinisalo, L, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Wadt, K, Therkildsen, C, Okkels, H, Ketabi, Z, Moreira, L, Sanchez, A, Serra-Burriel, M, Pineda, M, Navarro, M, Blanco, I, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Denton, OG, Frayling, IM, Rodland, EA, Vasen, H, Mints, M, Neffa, F, Esperon, P, Alvarez, K, Kariv, R, Rosner, G, Pinero, TA, Gonzalez, ML, Kalfayan, P, Tjandra, D, Winship, IM, Macrae, F, Moslein, G, Mecklin, J-P, Nielsen, M, Moller, P, Dominguez-Valentin, M, Sampson, JR, Seppala, TT, ten Broeke, SW, Plazzer, J-P, Nakken, S, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Hovig, E, de Vos tot Nederveen Cappel, WH, Sijmons, RH, Bertario, L, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Gluck, N, Katz, LH, Heinimann, K, Vaccaro, CA, Buttner, R, Gorgens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Huneburg, R, Knebel Doeberitz, MV, Loeffler, M, Rahner, N, Schackert, HK, Steinke-Lange, V, Schmiegel, W, Vangala, D, Pylvanainen, K, Renkonen-Sinisalo, L, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Wadt, K, Therkildsen, C, Okkels, H, Ketabi, Z, Moreira, L, Sanchez, A, Serra-Burriel, M, Pineda, M, Navarro, M, Blanco, I, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Denton, OG, Frayling, IM, Rodland, EA, Vasen, H, Mints, M, Neffa, F, Esperon, P, Alvarez, K, Kariv, R, Rosner, G, Pinero, TA, Gonzalez, ML, Kalfayan, P, Tjandra, D, Winship, IM, Macrae, F, Moslein, G, Mecklin, J-P, Nielsen, M, and Moller, P
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
26. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
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Dominguez-Valentin, M, Sampson, JR, Seppala, TT, ten Broeke, SW, Plazzer, J-P, Nakken, S, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Hovig, E, de Vos Tot Nederveen Cappel, WH, Sijmons, RH, Bertario, L, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Gluck, N, Katz, LH, Heinimann, K, Vaccaro, CA, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Schackert, HK, Steinke-Lange, V, Schmiegel, W, Vangala, D, Pylvanainen, K, Renkonen-Sinisalo, L, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Wadt, K, Therkildsen, C, Okkels, H, Ketabi, Z, Moreira, L, Sanchez, A, Serra-Burriel, M, Pineda, M, Navarro, M, Blanco, I, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Denton, OG, Frayling, IM, Rodland, EA, Vasen, H, Mints, M, Neffa, F, Esperon, P, Alvarez, K, Kariv, R, Rosner, G, Pinero, TA, Gonzalez, ML, Kalfayan, P, Tjandra, D, Winship, IM, Macrae, F, Moeslein, G, Mecklin, J-P, Nielsen, M, Moller, P, Dominguez-Valentin, M, Sampson, JR, Seppala, TT, ten Broeke, SW, Plazzer, J-P, Nakken, S, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Hovig, E, de Vos Tot Nederveen Cappel, WH, Sijmons, RH, Bertario, L, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Gluck, N, Katz, LH, Heinimann, K, Vaccaro, CA, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Schackert, HK, Steinke-Lange, V, Schmiegel, W, Vangala, D, Pylvanainen, K, Renkonen-Sinisalo, L, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Wadt, K, Therkildsen, C, Okkels, H, Ketabi, Z, Moreira, L, Sanchez, A, Serra-Burriel, M, Pineda, M, Navarro, M, Blanco, I, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Denton, OG, Frayling, IM, Rodland, EA, Vasen, H, Mints, M, Neffa, F, Esperon, P, Alvarez, K, Kariv, R, Rosner, G, Pinero, TA, Gonzalez, ML, Kalfayan, P, Tjandra, D, Winship, IM, Macrae, F, Moeslein, G, Mecklin, J-P, Nielsen, M, and Moller, P
- Abstract
PURPOSE: Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. METHODS: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. RESULTS: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. CONCLUSION: Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.
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- 2020
27. Peer Review #3 of "Psychometric properties of the Multi-group Ethnic Identity Measure (MEIM) in a sample of Iranian young adults (v0.1)"
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Alvarez, K, additional
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- 2021
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28. Large deletions and splicing-site mutations in the STK11 gene in Peutz-Jeghers Chilean families
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Orellana, P., López-Köstner, F., Heine, C., Suazo, C., Pinto, E., Church, J., Carvallo, P., and Alvarez, K.
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- 2013
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29. Physical and mechanical properties evaluation of Acropora palmata coralline species for bone substitution applications
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Alvarez, K., Camero, S., Alarcón, M. E., Rivas, A., and González, G.
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- 2002
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30. Notch Signalling Regulates Cytokine Production by CD8+ and CD4+ T Cells
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Sauma, D., Ramirez, A., Alvarez, K., Rosemblatt, M., and Bono, M. R.
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- 2012
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31. The evolution of star formation in QSOs according to WISE
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Cutiva-Alvarez, K. A., primary, Coziol, R., additional, Torres-Papaqui, J. P., additional, Andernach, H., additional, and Robleto-Orús, A. C., additional
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- 2020
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32. A MUSE study of NGC 7469: Spatially resolved star-formation and AGN-driven outflows
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Robleto-Orús, A. C., primary, Torres-Papaqui, J. P., additional, Longinotti, A. L., additional, Ortega-Minakata, R. A., additional, Sánchez, S. F., additional, Ascasibar, Y., additional, Bellocchi, E., additional, Galbany, L., additional, Chow-Martínez, M., additional, Trejo-Alonso, J. J., additional, Morales-Vargas, A., additional, Romero-Cruz, F. J., additional, Cutiva-Alvarez, K. A., additional, and Coziol, R., additional
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- 2020
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33. Usefulness of immunohistochemistry and microsatellite instability in families with suspected Lynch syndrome: F07
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Orellana, P., Wielandt, A. M., Alvarez, K., Pinto, E., Hurtado, C., Zarate, A. J., Suazo, C., Garmendia, A., Contreras, L., Kronberg, U., Church, J., Carvallo, P., and Lopez-Kostner, F.
- Published
- 2010
34. Multi-Spectral and Fluorescence Imaging in Prevention of Overdose of Herbicides: The Case of Maize
- Author
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Jeremie T. Zoueu, Alvarez K. Taky, Adama P. Soro, and Anicet K. Kouakou
- Subjects
Fluorescence-lifetime imaging microscopy ,Wavelength ,Materials science ,Scattering ,Energy absorbing ,Analytical chemistry ,Multi spectral ,Context (language use) ,Fluorescence ,Spectral line - Abstract
Evaluation of the impact of herbicides on maize was done through multi- spectral and multi-modal imaging and multi-spectral fluorescence imaging combined with statistical methods. Spectra containing 13 wavelengths ranging from 375 nm to 940 nm were derived from multi-spectral images in transmission, reflection and scattering mode and fluorescence images obtained using high-pass filters (F450 nm, F500 nm, F550 nm, F600 nm, F650 nm) on control maize samples and maize samples treated with Herbextra herbicide were used. The appearance of the spectra allowed us to characterize the effect of the herbicide on the maize pigment concentration. The fluorescence images allowed us to track the fate of absorbed energy and through PLS-DA and SVM-DA to discriminate the two leaf categories with very low error rates for the test, i.e. 4.9% and 2% respectively. The results of this technique can be used in the context of precision agriculture.
- Published
- 2017
- Full Text
- View/download PDF
35. High-yield production of short GpppA- and 7MeGpppA-capped RNAs and HPLC-monitoring of methyltransfer reactions at the guanine-N7 and adenosine-2′O positions
- Author
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Peyrane, F., Selisko, B., Decroly, E., Vasseur, J. J., Benarroch, D., Canard, B., and Alvarez, K.
- Published
- 2007
36. PERIPHERAL BLOOD PROGENITOR CELL MOBILIZATION AND COLLECTION IN 23 PATIENTS WITH SYSTEMIC MULTIPLE SCLEROSIS: P-535
- Author
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Ribeiro, A., Sakashita, A. M.K., Alvarez, K. C.A., Hamerschlak, N., Kutner, J. M., Cipolletta, A. N., and Pereira, R. A.A.
- Published
- 2006
37. SIOG2022-0199 - Experience in a Public Hospital with patients older than 60 years after breast cancer surgery, admitted to a Hospital Home Care Unit for physiotherapy for rehabilitation
- Author
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Calderon, O., Poblete, C., Alvarez, K., and Freire, F.
- Published
- 2022
- Full Text
- View/download PDF
38. Flow Cytometric Measurement of Apoptosis and Necrosis in CD34+ Cells in Cryopreserved Peripheral Blood and Cord Blood Samples
- Author
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Ribeiro, A A, Alvarez, K A, Bendit, I, Carmo, A O, Ioguy, S S, and Kutner, J M
- Published
- 2003
39. Developing multimodal intelligent affective interfaces for tele-home health care
- Author
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Lisetti, C., Nasoz, F., LeRouge, C., Ozyer, O., and Alvarez, K.
- Published
- 2003
- Full Text
- View/download PDF
40. A numerical model of the behavior of the resistance to compression in prisms of solid masonry
- Author
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Afanador García, N, primary, Farelo Alvarez, K A, additional, and Calderon, F, additional
- Published
- 2019
- Full Text
- View/download PDF
41. P6288Autoantibodies in heart failure associate with disease severity and differentially expressed genes in apoptotic, fibrotic, and hypoxia pathways in cardiomyocytes
- Author
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Myers, J, primary, Sandel, C, additional, Alvarez, K, additional, Garman, L, additional, White, K, additional, Wiley, G, additional, Montgomery, C G, additional, Gaffney, P, additional, Stavrakis, S, additional, Cooper, L T, additional, and Cunningham, M W, additional
- Published
- 2019
- Full Text
- View/download PDF
42. PS1467 EARLY RESULTS OF A PHASE II STUDY OF COMBINED RUXOLITINIB AND THALIDOMIDE IN PATIENTS WITH MYELOFIBROSIS
- Author
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Rampal, R., primary, Verstovsek, S., additional, Devlin, S., additional, Stein, E., additional, Kadia, T., additional, Mauro, M., additional, Naveen, P., additional, Montalban-Bravo, G., additional, King, A., additional, Alvarez, K., additional, Ard, N., additional, Goodman, T., additional, Taylor, B., additional, and Bose, P., additional
- Published
- 2019
- Full Text
- View/download PDF
43. EGF-based vaccine: Recent immunological results in advanced lung cancer and non-invasive bladder cancer patients
- Author
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Mazorra, Z., primary, Saavedra, D., additional, Popa, X., additional, Martínez, L., additional, Fuentes, K., additional, Huerta, V., additional, Alvarez, K., additional, Viada, C., additional, Neninger, E., additional, Ibañez, E., additional, Rodríguez, C., additional, Hernández, M., additional, González, Z., additional, González, A., additional, García, B., additional, and Crombet, T., additional
- Published
- 2019
- Full Text
- View/download PDF
44. Paying it forward: How helping others can reduce the psychological threat of receiving help
- Author
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Alvarez, K., van Leeuwen, E., and Social & Organizational Psychology
- Abstract
This paper shows that receiving help could be psychologically harmful for recipients, and passing on help to others after receiving help (“helping forward”) is a good strategy to improve and restore help recipients' self-competence. Participants (N = 87) received autonomy- or dependency-oriented help and anticipated helping forward or not. Compared to receiving autonomy-oriented help, receiving dependency-oriented help negatively affected participants' self-competence and their evaluation of the helper. Anticipation of future helping increased the liking for and evaluation of the helper. After paying help forward, participants felt more self-competent than before helping, and this effect was more pronounced among former recipients of dependency-oriented help. These results show that helping forward can negate the psychological threat associated with receiving help.
- Published
- 2015
- Full Text
- View/download PDF
45. Risk factors and mortality rate in Covid-19 critically ill patients in Mexico
- Author
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Bejarano, M., Ramos, C.O., Rosas, E.A., Madera, C.E., Rascón, R., Balderas, C., Cabrera, Á., Rocha, U., Fuchs, V., Sánchez, A., Bermeo, E., Guzmán, R., Álvarez, K., Gallardo, A., Hernández, E., Sierra, M., and Acosta, G.
- Published
- 2021
- Full Text
- View/download PDF
46. Search for gravitational waves from Scorpius X-1 in the first Advanced LIGO observing run with a hidden Markov model
- Author
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Abbott, and Abbott, B. P., and Abbott, R., and Acernese, D., and Ackley, F., and Adams, K., and Adams, C., and Addesso, T., and Adhikari, P., and Adya, R. X., and Affeldt, V. B., and Afrough, C., and Agarwal, M., and Agatsuma, B., and Aggarwal, K., and Aguiar, N., and Aiello, O. D., and Ain, L., and Ajith, A., and Allen, P., and Allen, B., and Allocca, G., and Almoubayyed, A., and Altin, H., and Amato, P. A., and Ananyeva, A., and Anderson, A., and Anderson, S. B., and Antier, W. G., and Appert, S., and Arai, S., and Araya, K., and Areeda, M. C., and Arnaud, J. S., and Arun, N., and Ascenzi, K. G., and Ashton, S., and Ast, G., and Aston, M., and Astone, S. M., and Aufmuth, P., and Aulbert, P., and AultONeal, C., and Avila-Alvarez, K., and Babak, A., and Bacon, S., and Bader, P., and Bae, M. K. M., and Baker, S., and Baldaccini, P. T., and Ballardin, F., and Ballmer, G., and Banagiri, S. W., and Barayoga, S., and Barclay, J. C., and Barish, S. E., and Barker, B. C., and Barone, D., and Barr, F., and Barsotti, B., and Barsuglia, L., and Barta, M., and Bartlett, D., and Bartos, J., and Bassiri, I., and Basti, R., and Batch, A., and Baune, J. C., and Bawaj, C., and Bazzan, M., and Becsy, M., and Beer, B., and Bejger, C., and Belahcene, M., and Bell, I., and Berger, A. S., and Bergmann, B. K., and Berry, G., and Bersanetti, C. P. L., and Bertolini, D., and Etienne, A., and Betzwieser, Z. B., and Bhagwat, J., and Bhandare, S., and Bilenko, R., and Billingsley, I. A., and Billman, G., and Birch, C. R., and Birney, J., and Birnholtz, R., and Biscans, O., and Bisht, S., and Bitossi, A., and Biwer, M., and Bizouard, C., and Blackburn, M. A., and Blackman, J. K., and Blair, J., and Blari, C. D., and Blair, D. G., and Bloemen, R. M., and Bock, S., and Bode, O., and Boer, N., and Bogaert, M., and Bohe, G., and Bondu, A., and Bonnand, F., and Boom, R., and Bork, B. A., and Boschi, R., and Bose, V., and Bouffanais, S., and Bozzi, Y., and Bradaschia, A., and Brady, C., and Braginsky, P. R., and Branchesi, V. B., and Brau, M., and Briant, J. E., and Brillet, T., and Brinkmann, A., and Brisson, M., and Brockill, V., and Broida, P., and Brooks, J. E., and Brown, A. F., and Brown, D. A., and Brown, D. D., and Brunett, N. M., and Buchanan, S., and Buikema, C. C., and Bulik, A., and Bulten, T., and Buonanno, H. J., and Buskulic, A., and Buy, D., and Byer, C., and Cabero, R. L., and Cadonati, M., and Cagnoli, L., and Cahillane, G., and Bustillo, C., Calderon and Callister, J., and Calloni, T. A., and Camp, E., and Canepa, J. B., and Canizares, M., and Cannon, P., and Cao, C., and Cao, H., and Capano, J., and Capocasa, C. D., and Carbognani, E., and Caride, F., and Carney, S., and Diaz, M. F., Casanueva and Casentini, J., and Caudill, C., and Cavaglia, S., and Cavalier, M., and Cavalieri, F., and Cella, R., and Cepeda, G., and Baiardi, C. B., Cerboni and Cerretani, L., and Cesarini, G., and Chamberlin, E., and Chan, S. J., and Chao, M., and Charlton, S., and Chassande-Mottin, P., and Chatterjee, E., and Cheeseboro, D., and Chen, B. D., and Chen, H. Y., and Cheng, Y., and Chincarini, H. -. P., and Chiummo, A., and Chmiel, A., and Cho, T., and Cho, H. S., and Chow, M., and Christensen, J. H., and Chu, N., and Chua, Q., and Chua, A. J. K., and Chung, S., and Chung, A. K. W., and Ciani, S., and Ciolfi, G., and Cirelli, R., and Cirone, C. E., and Clara, A., and Clark, F., and Cleva, J. A., and Cocchieri, F., and Coccia, C., and Cohadon, E., and Colla, P. -. F., and Collette, A., and Cominsky, C. G., and Constancio, R., J. r., and Conti, M., and Cooper, L., and Corban, S. J., and Corbitt, P., and Corley, T. R., and Cornish, K. R., and Corsi, N., and Cortese, A., and Costa, S., and Coughlin, C. A., and Coughlin, M. W., and Coulon, S. B., and Countryman, J. -. P., and Couvares, S. T., and Covas, P., and Cowan, P. B., and Coward, E. E., and Cowart, D. M., and Coyne, M. J., and Coyne, D. C., and Creighton, R., and Creighton, J. D. E., and Cripe, T. D., and Crowder, J., and Cullen, S. G., and Cumming, T. J., and Cunningham, A., and Cuoco, L., and Dal Canton, E., and Danilishin, T., and D'Antonio, S. L., and Danzmann, S., and Dasgupta, K., and Costa, A., Da Silva and Dattilo, C. F., and Dave, V., and Davier, I., and Davies, M., and Davis, G. S., and Daw, D., and Day, E. J., and De, B., and Debra, S., and Deelman, D., and Degallaix, E., and De Laurentis, J., and Deleglise, M., and Del Pozzo, S., and Denker, W., and Dent, T., and Dergachev, T., and De Rosa, V., and DeRosa, R., and DeSalvo, R. T., and Devenson, R., and Devine, J., and Dhurandhar, R. C., and Diaz, S., and Di Fiore, M. C., and Di Giovanni, L., and Di Girolamo, M., and Di Lieto, T., and Di Pace, A., and Di Palma, S., and Di Renzo, I., and Doctor, F., and Dolique, Z., and Donovan, V., and Dooley, F., and Doravari, K. L., and Dorrington, S., and Douglas, I., and Alvarez, R., Dovale and Downes, M., and Drago, T. P., and Drever, M., and Driggers, R. W. P., and Du, J. C., and Ducrot, Z., and Duncan, M., and Dwyer, J., and Edo, S. E., and Edwards, T. B., and Effler, M. C., and Eggenstein, A., and Ehrens, H. -. B., and Eichholz, P., and Eikenberry, J., and Essick, S. S., and Etzel, R. C., and Evans, T., and Evans, M., and Factourovich, T. M., and Fafone, M., and Fair, V., and Fairhurst, H., and Fan, S., and Farinon, X., and Farr, S., and Farr, B., and Fauchon-Jones, W. M., and Favata, E. J., and Fays, M., and Fehrmann, M., and Feicht, H., and Fejer, J., and Fernandez-Galiana, M. M., and Ferrante, A., and Ferreira, I., and Ferrini, E. C., and Fidecaro, F., and Fiori, F., and Fiorucci, I., and Fisher, D., and Flaminio, R. P., and Fletcher, R., and Fong, M., and Forsyth, H., and Forsyth, P. W. F., and Fournier, S. S., and Frasca, J. -. D., and Frasconi, S., and Frei, F., and Freise, Z., and Frey, A., and Frey, R., and Fries, V., and Fritschel, E. M., and Frolov, P., and Fulda, V. V., and Fyffe, P., and Gabbard, M., and Gabel, H., and Gadre, M., and Gaebel, B. U., and Gair, S. M., and Gammaitoni, J. R., and Ganija, L., and Gaonkar, M. R., and Garufi, S. G., and Gaudio, F., and Gaur, S., and Gayathri, G., and Gehrels, V., and Gemme, N., and Genin, G., and Gennai, E., and George, A., and George, D., and Gergely, J., and Germain, L., and Ghonge, V., and Ghosh, S., Abhirup and Ghosh, Archisman and Ghosh, and Giaime, S., and Giardina, J. A., and Giazotto, K. D., and Gill, A., and Glover, K., and Goetz, L., and Goetz, E., and Gomes, R., and Gonzalez, S., and Castro, G., Gonzalez and Gopakumar, J. M., and Gorodetsky, A., and Gossan, M. L., and Gosselin, S. E., and Gouaty, M., and Grado, R., and Graef, A., and Granata, C., and Grant, M., and Gras, A., and Gray, S., and Greco, C., and Green, G., and Groot, A. C., and Grote, P., and Grunewald, H., and Gruning, S., and Guidi, P., and Guo, G. M., and Gupta, X., and Gupta, A., and Gushwa, M. K., and Gustafson, K. E., and Gustafson, E. K., and Hall, R., and Hall, B. R., and Hammond, E. D., and Haney, G., and Hanke, M., and Hanks, M. M., and Hanna, J., and Hannuksela, C., and Hanson, O. A., and Hardwick, J., and Harms, T., and Harry, J., and Harry, G. M., and Hart, I. W., and Haster, M. J., and Haughian, C. -. J., and Healy, K., and Heidmann, J., and Heintze, A., and Heitmann, M. C., and Hello, H., and Hemming, P., and Hendry, G., and Heng, M., and Hennig, I. S., and Henry, J., and Heptonstall, J., and Heurs, A. W., and Hild, M., and Hoak, S., and Hofman, D., and Holt, D., and Holz, K., and Hopkins, D. E., and Horst, P., and Hough, C., and Houston, J., and Howell, E. A., and Hu, E. J., and Huerta, Y. M., and Huet, E. A., and Hughey, D., and Husa, B., and Huttner, S., and Huynh-Dinh, S. H., and Indik, T., and Ingram, N., and Inta, D. R., and Intini, R., and Isa, G., and Isac, H. N., and Isi, J. -. M., and Iyer, M., and Izumi, B. R., and Jacqmin, K., and Jani, T., and Jaranowski, K., and Jawahar, P., and Jimenez-Forteza, S., and Johnson, F., and Jones, W. W., and Jones, D. I., and Jonker, R., and Ju, R. J. G., and Junker, L., and Kalaghatgi, J., and Kalogera, C. V., and Kandhasamy, V., and Kang, S., and Kanner, G., and Karki, J. B., and Karvinen, S., and Kasprzack, K. S., and Katolik, M., and Katsavounidis, M., and Katzman, E., and Kaufer, W., and Kawabe, S., and Kefelian, K., and Keitel, F., and Kemball, D., and Kennedy, A. J., and Kent, R., and Key, C., and Khalili, J. S., and Khan, F. Y., and Khan, I., and Khan, S., and Khazanov, Z., and Kijbunchoo, E. A., and Kim, N., Chunglee and Kim, and Kim, J. C., and Kim, W., and Kim, W. S., and Kimbrell, Y. -. M., and King, S. J., and King, E. J., and Kirchhoff, P. J., and Kissel, R., and Kleybolte, J. S., and Klimenko, L., and Koch, S., and Koehlenbeck, P., and Koley, S. M., and Kondrashov, S., and Kontos, V., and Korobko, A., and Korth, M., and Kowalska, W. Z., and Kozak, I., and Kramer, D. B., and Kringel, C., and Krishnan, V., and Krolak, B., and Kuehn, A., and Kumar, G., and Kumar, P., and Kumar, R., and Kuo, S., and Kutynia, L., and Kwang, A., and Lackey, S., and Lai, B. D., and Landry, K. H., and Lang, M., and Lange, R. N., and Lantz, J., and Lanza, B., and Lartaux-Vollard, R. K., and Lasky, A., and Laxen, P. D., and Lazzarini, M., and Lazzaro, A., and Leaci, C., and Leavey, P., and Lee, S., and Lee, C. H., and Lee, H. K., and Lee, H. M., and Lee, H. W., and Lehmann, K., and Lenon, J., and Leonardi, A., and Leroy, M., and Letendre, N., and Levin, N., and Li, Y., and Libson, T. G. F., and Littenberg, A., and Liu, T. B., and Lockerbie, J., and London, N. A., and Lord, L. T., and Lorenzini, J. E., and Loriette, M., and Lormand, V., and Losurdo, M., and Lough, G., and Lovelace, J. D., and Luck, G., and Lumaca, H., and Lundgren, D., and Lynch, A. 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J., Laboratoire d'Annecy de Physique des Particules (LAPP/Laboratoire d'Annecy-le-Vieux de Physique des Particules), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire des matériaux avancés (LMA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'Accélérateur Linéaire (LAL), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), AstroParticule et Cosmologie (APC (UMR_7164)), Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Observatoire de la Côte d'Azur (OCA), Centre National de la Recherche Scientifique (CNRS), Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Kastler Brossel (LKB [Collège de France]), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Collège de France (CdF)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire de Lyon (IPNL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), ESPCI ParisTech, LIGO Scientific, VIRGO, Abbott, B. .p., Abbott, R., Abbott, T. .d., Acernese, F., Ackley, K., Adams, C., Adams, T., Addesso, P., Adhikari, R. .x., Adya, V. .b., Affeldt, C., Afrough, M., Agarwal, B., Agatsuma, K., Aggarwal, N., Aguiar, O. .d., Aiello, L., Ain, A., Ajith, P., Allen, B., Allen, G., Allocca, A., Almoubayyed, H., Altin, P. .a., Amato, A., Ananyeva, A., Anderson, S. .b., Anderson, W. .g., Antier, S., Appert, S., Arai, K., Araya, M. .c., Areeda, J. .s., Arnaud, N., Arun, K. .g., Ascenzi, S., Ashton, G., Ast, M., Aston, S. .m., Astone, P., Aufmuth, P., Aulbert, C., Aultoneal, K., Avila Alvarez, A., Babak, S., Bacon, P., Bader, M. .k. .m., Bae, S., Baker, P. .t., Baldaccini, F., Ballardin, G., Ballmer, S. .w., Banagiri, S., Barayoga, J. .c., Barclay, S. .e., Barish, B. .c., Barker, D., Barone, F., Barr, B., Barsotti, L., Barsuglia, M., Barta, D., Bartlett, J., Bartos, I., Bassiri, R., Basti, A., Batch, J. .c., Baune, C., Bawaj, M., Bazzan, M., Bécsy, B., Beer, C., Bejger, M., Belahcene, I., Bell, A. .s., Berger, B. .k., Bergmann, G., Berry, C. .p. .l., Bersanetti, D., Bertolini, A., Etienne, Z. .b., Betzwieser, J., Bhagwat, S., Bhandare, R., Bilenko, I. .a., Billingsley, G., Billman, C. .r., Birch, J., Birney, R., Birnholtz, O., Biscans, S., Bisht, A., Bitossi, M., Biwer, C., Bizouard, M. .a., Blackburn, J. .k., Blackman, J., Blair, C. .d., Blair, D. .g., Blair, R. .m., Bloemen, S., Bock, O., Bode, N., Boer, M., Bogaert, G., Bohe, A., Bondu, F., Bonnand, R., Boom, B. .a., Bork, R., Boschi, V., Bose, S., Bouffanais, Y., Bozzi, A., Bradaschia, C., Brady, P. .r., Braginsky, V. .b., BRANCHESI, MARICA, Brau, J. .e., Briant, T., Brillet, A., Brinkmann, M., Brisson, V., Brockill, P., Broida, J. .e., Brooks, A. .f., Brown, D. .a., Brown, D. .d., Brown, N. .m., Brunett, S., Buchanan, C. .c., Buikema, A., Bulik, T., Bulten, H. .j., Buonanno, A., Buskulic, D., Buy, C., Byer, R. .l., Cabero, M., Cadonati, L., Cagnoli, G., Cahillane, C., Calderón Bustillo, J., Callister, T. .a., Calloni, E., Camp, J. .b., Canepa, M., Canizares, P., Cannon, K. .c., Cao, H., Cao, J., Capano, C. .d., Capocasa, E., Carbognani, F., Caride, S., Carney, M. .f., Casanueva Diaz, J., Casentini, C., Caudill, S., Cavaglià, M., Cavalier, F., Cavalieri, R., Cella, G., Cepeda, C. .b., CERBONI BAIARDI, LORENZO, Cerretani, G., Cesarini, E., Chamberlin, S. .j., Chan, M., Chao, S., Charlton, P., Chassande Mottin, E., Chatterjee, D., Cheeseboro, B. .d., Chen, H. .y., Chen, Y., Cheng, H. 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. j., Zhu, X. . j., Zucker, M. . e., Evans, R. . j., Laboratoire d'Annecy de Physique des Particules (LAPP), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Collège de France (CdF (institution)), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7), The LIGO Scientific Collaboration, The Virgo Collaboration, and (Astro)-Particles Physics
- Subjects
Physics and Astronomy (miscellaneous) ,Astronomy ,X-ray binary ,Gravitational Wave ,Astrophysics ,01 natural sciences ,General Relativity and Quantum Cosmology ,NOISE ,LIGO ,010303 astronomy & astrophysics ,QC ,QB ,Physics ,Scorpius X-1 ,PULSARS ,Polarization (waves) ,Frequency domain ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,[PHYS.GRQC]Physics [physics]/General Relativity and Quantum Cosmology [gr-qc] ,X-ray: binary ,gravitational radiation: polarization ,ACCRETING NEUTRON-STARS ,X-RAY BINARIES ,RADIATION ,EMISSION ,INSTABILITY ,BOUNDS ,Gravitational Waves, Scorpius X-1, O1, Advanced LIGO ,NEUTRON-STARS ,neutron star: spin ,FOS: Physical sciences ,General Relativity and Quantum Cosmology (gr-qc) ,Markov model ,gravitational radiation: direct detection ,O1 ,Pulsar ,statistical analysis ,0103 physical sciences ,Advanced LIGO ,ddc:530 ,Gravitational Waves ,010308 nuclear & particles physics ,Gravitational wave ,gravitational radiation ,530 Physik ,gravitational radiation detector ,Neutron star ,Physics and Astronomy ,gravitational radiation: emission ,Dewey Decimal Classification::500 | Naturwissenschaften::530 | Physik - Abstract
Article is made available in accordance with the publisher's policy. Please refer to the publisher's site for terms of use., Results are presented from a semicoherent search for continuous gravitational waves from the brightest low-mass X-ray binary, Scorpius X-1, using data collected during the first Advanced LIGO observing run. The search combines a frequency domain matched filter (Bessel-weighted F-statistic) with a hidden Markov model to track wandering of the neutron star spin frequency. No evidence of gravitational waves is found in the frequency range 60–650 Hz. Frequentist 95% confidence strain upper limits, h95% 0 ¼ 4.0 × 10−25, 8.3 × 10−25, and 3.0 × 10−25 for electromagnetically restricted source orientation, unknown polarization, and circular polarization, respectively, are reported at 106 Hz. They are ≤ 10 times higher than the theoretical torque-balance limit at 106 Hz.
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- 2017
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47. Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO
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H., Zhao, C., Zhou, M., Zhou, Z., Zhu, X. . j., Zucker, M. . e., Zweizig, J., Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire des matériaux avancés (LMA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'Accélérateur Linéaire (LAL), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et 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Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire de Lyon (IPNL), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), LIGO Scientific, Virgo, Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Collège de France (CdF (institution)), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), (Astro)-Particles Physics, Abbott, B. .p., Abbott, T. .d., Adhikari, R. .x., Adya, V. .b., Aguiar, O. .d., Altin, P. .a., Anderson, S. .b., Anderson, W. .g., Araya, M. .c., Areeda, J. .s., Arun, K. .g., Aston, S. .m., Bader, M. .k. .m., Baker, P. .t., Ballmer, S. .w., Barayoga, J. .c., Barclay, S. .e., Barish, B. .c., Batch, J. .c., Bell, A. .s., Berger, B. .k., Berry, C. .p. .l., Bilenko, I. .a., Billman, C. .r., Bizouard, M. .a., Blackburn, J. .k., Blair, C. .d., Blair, D. .g., Blair, R. .m., Boom, B. .a., Brady, P. .r., Braginsky, V. .b., BRANCHESI, MARICA, Brau, J. .e., Broida, J. .e., Brooks, A. .f., Brown, D. .a., Brown, D. .d., Brown, N. .m., Buchanan, C. .c., Bulten, H. .j., Byer, R. .l., Callister, T. .a., Calloni, E., Camp, J. .b., Cannon, K. .c., Capano, C. .d., Carney, M. .f., Cepeda, C. .b., CERBONI BAIARDI, LORENZO, Chamberlin, S. .j., Cheeseboro, B. .d., Chen, H. .y., Cho, H. .s., Chow, J. .h., Chua, A. .j. .k., Chung, A. .k. .w., Cirelli, C. .e., Clark, J. .a., Collette, C. .g., Cominsky, L. .r., Cooper, S. .j., Corbitt, T. .r., Corley, K. .r., Costa, C. .a., Coughlin, M. .w., Coughlin, S. .b., Countryman, S. .t., Covas, P. .b., Cowan, E. .e., Coward, D. .m., Cowart, M. .j., Coyne, D. .c., Creighton, J. .d. .e., Creighton, T. .d., Crowder, S. .g., Cullen, T. .j., Danilishin, S. .l., Da Silva Costa, C. .f., Davies, G. .s., Daw, E. .j., De Laurentis, M., De Rosa, R., Derosa, R. .t., Devine, R. .c., Díaz, M. .c., Di Girolamo, T., Dooley, K. .l., Downes, T. .p., Drever, R. .w. .p., Driggers, J. .c., Dwyer, S. .e., Edo, T. .b., Edwards, M. .c., Eikenberry, S. .s., Eisenstein, R. .a., Essick, R. .c., Evans, T. .m., Farr, W. .m., Fauchon Jones, E. .j., Fejer, M. .m., Ferreira, E. .c., Fisher, R. .p., Forsyth, P. .w. .f., Forsyth, S. .s., Fries, E. .m., Frolov, V. .v., Gadre, B. .u., Gaebel, S. .m., Gair, J. .r., Ganija, M. .r., Gaonkar, S. .g., Garufi, F., Giaime, J. .a., Giardina, K. .d., Gonzalez Castro, J. .m., Gorodetsky, M. .l., Gossan, S. .e., GRECO, GIUSEPPE, Green, A. .c., GUIDI, GIANLUCA MARIA, Gupta, M. .k., Gushwa, K. .e., Gustafson, E. .k., Hall, B. .r., Hall, E. .d., Hanke, M. .m., Hannam, M. .d., Hannuksela, O. .a., HARMS, JAN, Harry, G. .m., Harry, I. .w., Hart, M. .j., Heintze, M. .c., Heng, I. .s., Heptonstall, A. .w., Holz, D. .e., Houston, E. .a., Howell, E. .j., Hu, Y. .m., Huerta, E. .a., Huttner, S. .h., Ingram, D. .r., Isa, H. .n., Iyer, B. .r., Johnson, W. .w., Jones, D. .i., Jonker, R. .j. .g., Kalaghatgi, C. .v., Kanner, J. .b., Karvinen, K. .s., Kemball, A. .j., Key, J. .s., Khalili, F. .y., Khazanov, E. .a., Kim, J. .c., Kim, W. .s., Kimbrell, S. .j., King, E. .j., King, P. .j., Kissel, J. .s., Koehlenbeck, S. .m., Korth, W. .z., Kozak, D. .b., Lackey, B. .d., Lai, K. .h., Lang, R. .n., Lanza, R. .k., Lasky, P. .d., Lee, C. .h., Lee, H. .k., Lee, H. .m., Lee, H. .w., Li, T. .g. .f., Littenberg, T. .b., Lockerbie, N. .a., London, L. .t., Lord, J. .e., Lough, J. .d., Lousto, C. .o., Lundgren, A. .p., Macleod, D. .m., Magee, R. .m., Mansell, G. .l., Markosyan, A. .s., MARTELLI, FILIPPO, Martin, I. .w., Martynov, D. .v., Marx, J. .n., Massinger, T. .j., Mcclelland, D. .e., Mcguire, S. .c., Mcmanus, D. .j., Mcwilliams, S. .t., Meadors, G. .d., Mercer, R. .a., Merilh, E. .l., Meyers, P. .m., Mikhailov, E. .e., Milano, L., Miller, A. .l., Miller, B. .b., Mitrofanov, V. .p., Mohapatra, S. .r. .p., MONTANI, MATTEO, Moore, B. .c., Moore, C. .j., Morriss, S. .r., Mow Lowry, C. .m., Muir, A. .w., Muniz, E. .a. .m., Murray, P. .g., Nayak, R. .k., Nelson, T. .j. .n., Newport, J. .m., Ng, K. .k. .y., Nguyen, T. .t., Nielsen, A. .b., Normandin, M. .e. .n., Nuttall, L. .k., Ogin, G. .h., Oh, J. .j., Oh, S. .h., Ortega, L. .f., Ottaway, D. .j., Owen, B. .j., Pace, A. .e., Page, M. .a., Pai, S. .a., Palamos, J. .r., Pang, P. .t. .h., Pant, B. .c., Papa, M. .a., Paris, H. .r., Pearlstone, B. .l., Perez, C. .j., Perri, L. .m., Pfeiffer, H. .p., Piccinni, O. .j., PIERGIOVANNI, FRANCESCO, Pinto, I. .m., Porter, E. .k., Pratt, J. .w. .w., Prodi, G. .a., Prokhorov, L. .g., Quintero, E. .a., Raab, F. .j., Rabeling, D. .s., Ramirez, K. .e., Reitze, D. .h., Reyes, S. .d., Ricker, P. .m., Robertson, N. .a., Rollins, J. .g., Roma, V. .j., Romel, C. .l., Romie, J. .h., Ross, M. .p., Sampson, L. .m., Sanchez, E. .j., Sanders, J. .r., Sathyaprakash, B. .s., Saulson, P. .r., Savage, R. .l., Schofield, R. .m. .s., Schulte, B. .w., Schutz, B. .f., Schwalbe, S. .g., Scott, S. .m., Sengupta, A. .s., Shaddock, D. .a., Shaffer, T. .j., Shah, A. .a., Shahriar, M. .s., Shoemaker, D. .h., Shoemaker, D. .m., Silva, A. .d., Singer, L. .p., Sintes, A. .m., Slagmolen, B. .j. .j., Smith, J. .r., Smith, R. .j. .e., Son, E. .j., Sonnenberg, J. .a., Spencer, A. .p., Srivastava, A. .k., Stephens, B. .c., Strain, K. .a., STRATTA, MARIA GIULIANA, Strigin, S. .e., Stuver, A. .l., Summerscales, T. .z., Sutton, P. .j., Swinkels, B. .l., Szczepańczyk, M. .j., Tanner, D. .b., Taylor, J. .a., Thomas, E. .g., Thorne, K. .a., Thorne, K. .s., Tokmakov, K. .v., Torrie, C. .i., Tringali, M. .c., Tsang, K. .w., Unnikrishnan, C. .s., Urban, A. .l., Usman, S. .a., van den Brand, J. .f. .j., Vander Hyde, D. .c., van Heijningen, J. .v., van Veggel, A. .a., Veitch, P. .j., VETRANO, FLAVIO, VICERE', ANDREA, Viets, A. .d., Vine, D. .j., Voss, D. .v., Vousden, W. .d., Vyatchanin, S. .p., Wade, A. .r., Wade, L. .e., Wang, J. .z., Ward, R. .l., Weinstein, A. .j., Wessel, E. .k., Whelan, J. .t., Whiting, B. .f., Williams, R. .d., Williamson, A. .r., Willis, J. .l., Wimmer, M. .h., Wipf, C. .c., Wong, K. .w. .k., Wright, J. .l., Wu, D. .s., Yancey, C. .c., Yap, M. .j., Zhu, X. .j., and Zucker, M. .e.
- Subjects
Physics and Astronomy (miscellaneous) ,Astronomy ,Gravitational Wave ,Binary number ,Astrophysics ,01 natural sciences ,General Relativity and Quantum Cosmology ,star ,jet ,clusters ,LIGO ,010303 astronomy & astrophysics ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,QC ,97.60.Lf ,QB ,candidate ,Physics ,black hole: spin ,04.25.dg ,04.30.-w ,[PHYS.GRQC]Physics [physics]/General Relativity and Quantum Cosmology [gr-qc] ,mergers ,Angular momentum ,coalescences ,Astrophysics::High Energy Astrophysical Phenomena ,IMBH ,FOS: Physical sciences ,General Relativity and Quantum Cosmology (gr-qc) ,Astrophysics::Cosmology and Extragalactic Astrophysics ,gravitational radiation: direct detection ,angular momentum ,O1 ,Intermediate BH search ,Binary black hole ,0103 physical sciences ,Binary star ,gravitational radiation: burst ,ddc:530 ,Gravitational Waves ,010308 nuclear & particles physics ,Gravitational wave ,gravitational radiation ,black hole: mass ,Gravitational Waves, LIGO, O1, IMBH ,530 Physik ,04.80.Nn ,gravitational radiation detector ,detector: sensitivity ,Physics and Astronomy ,Orders of magnitude (time) ,black hole: binary ,Intermediate-mass black hole ,gravitational radiation: emission ,Dewey Decimal Classification::500 | Naturwissenschaften::530 | Physik ,limits ,gravitational-waves - Abstract
During their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals and GW151226, produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected, therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass $100\,M_\odot$, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than $0.93~\mathrm{Gpc^{-3}\,yr}^{-1}$ in comoving units at the $90\%$ confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits., 8 pages, 2 figures
- Published
- 2017
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- View/download PDF
48. SMA CLINICAL DATA, OUTCOME MEASURES AND REGISTRIES
- Author
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Martínez-Jalile, M., primary, Lozano-Arango, A., additional, Diemer, C., additional, Suárez, B., additional, Alvarez, K., additional, and Castiglioni, C., additional
- Published
- 2018
- Full Text
- View/download PDF
49. Magnetic Properties of Annealed Amorphous Alloys (Fe-rich) Obtained by Gas Atomization Technique
- Author
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Alvarez, K. L., primary, Martin, J. M., additional, Ipatov, M., additional, Dominguez, L., additional, and Gonzalez, J., additional
- Published
- 2018
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- View/download PDF
50. Large deletions and splicing-site mutations in the STK11 gene in Peutz-Jeghers Chilean families
- Author
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Pilar Carvallo, E Pinto, James M. Church, F López-Köstner, C Heine, Orellana P, C Suazo, and Alvarez K
- Subjects
Genetics ,congenital, hereditary, and neonatal diseases and abnormalities ,Point mutation ,STK11 ,Peutz–Jeghers syndrome ,Biology ,medicine.disease ,Molecular biology ,DNA sequencing ,law.invention ,Germline mutation ,law ,Genotype ,medicine ,skin and connective tissue diseases ,Gene ,Genetics (clinical) ,Polymerase chain reaction - Abstract
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by mucocutaneous melanocytic macules, gastrointestinal hamartomatous polyposis and an increased risk of various neoplasms. Germline mutations in the serine/threonine kinase 11 (STK11) gene have been identified as a cause for PJS. The aim of this study was to characterize the genotype of Chilean PJS patients. Mutation screening of 13 patients from eight PJS families was performed using a single strand conformation polymorphism analysis, DNA sequencing and multiplex ligation-dependent probe amplification assay. The breakpoints of the genomic rearrangements were assessed by a long-range polymerase chain reaction and sequencing. The results revealed the existence of seven different pathogenic mutations in STK11 gene in seven unrelated families, including three point mutations and four large genomic deletions. Three of these point mutations (43%, 3/7) may be considered as novel. Our results showed that a germline mutation is present in STK11 in 88% of probands fulfilling the diagnostic criteria of PJS. In this study, the combination of two different experimental approaches in the screening of the STK11 in PJS, led to a higher percentage of mutation detection.
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- 2013
- Full Text
- View/download PDF
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