Angiopreventive Efficacy of Pure Flavonolignans from Milk Thistle Extract against Prostate Cancer: Targeting VEGF-VEGFR Signaling

The role of neo-angiogenesis in prostate cancer (PCA) growth and metastasis is well established, but the development of effective and non-toxic pharmacological inhibitors of angiogenesis remains an unaccomplished goal. In this regard, targeting aberrant angiogenesis through non-toxic phytochemicals could be an attractive angiopreventive strategy against PCA. The rationale of the present study was to compare the anti-angiogenic potential of four pure diastereoisomeric flavonolignans, namely silybin A, silybin B, isosilybin A and isosilybin B, which we established previously as biologically active constituents in Milk Thistle extract. Results showed that oral feeding of these flavonolignans (50 and 100 mg/kg body weight) effectively inhibit the growth of advanced human PCA DU145 xenografts. Immunohistochemical analyses revealed that these flavonolignans inhibit tumor angiogenesis biomarkers (CD31 and nestin) and signaling molecules regulating angiogenesis (VEGF, VEGFR1, VEGFR2, phospho-Akt and HIF-1α) without adversely affecting the vessel-count in normal tissues (liver, lung, and kidney) of tumor bearing mice. These flavonolignans also inhibited the microvessel sprouting from mouse dorsal aortas ex vivo, and the VEGF-induced cell proliferation, capillary-like tube formation and invasiveness of human umbilical vein endothelial cells (HUVEC) in vitro. Further studies in HUVEC showed that these diastereoisomers target cell cycle, apoptosis and VEGF-induced signaling cascade. Three dimensional growth assay as well as co-culture invasion and in vitro angiogenesis studies (with HUVEC and DU145 cells) suggested the differential effectiveness of the diastereoisomers toward PCA and endothelial cells. Overall, these studies elucidated the comparative anti-angiogenic efficacy of pure flavonolignans from Milk Thistle and suggest their usefulness in PCA angioprevention

Tomato (Solanum lycopersicum L.) seed : a review on bioactives and biomedical activities

The processing of tomato fruit into puree, juices, ketchup, sauces, and dried powders generates a significant amount of waste in the form of tomato pomace, which includes seeds and skin. Tomato processing by-products, particularly seeds, are reservoirs of health-promoting macromolecules, such as proteins (bioactive peptides), carotenoids (lycopene), polysaccharides (pectin), phytochemicals (flavonoids), and vitamins (α-tocopherol). Health-promoting properties make these bioactive components suitable candidates for the development of novel food and nutraceutical products. This review comprehensively demonstrates the bioactive compounds of tomato seeds along with diverse biomedical activities of tomato seed extract (TSE) for treating cardiovascular ailments, neurological disorders, and act as antioxidant, anticancer, and antimicrobial agent. Utilization of bioactive components can improve the economic feasibility of the tomato processing industry and may help to reduce the environmental pollution generated by tomato by-products

Valorization potential of tomato (Solanum lycopersicum L.) seed : nutraceutical quality, food properties, safety aspects, and application as a health-promoting ingredient in foods

The tomato is a member of the Solanaceae family and is a crop that is widely cultivated around the world due to its sweet, sour, salty, juicy, and nutritious berries. The processing of tomatoes generates a significant amount of waste in the form of tomato pomace, which includes seeds and skin. Tomato seeds are reservoirs of various nutrients, such as proteins, carbohydrates, lipids, minerals, and vitamins. These components make tomato seeds an important ingredient for application in food matrices. This review discusses the functional food properties of tomato seeds and their scope of utilization as major ingredients in the functional food industry. In addition, this review describes the development of tomato seeds as a potential nutritional and nutraceutical ingredient, along with recent updates on research conducted worldwide. This is the first review that demonstrates the nutritional profile of tomato seeds along with its diverse functional food properties and application as a functional food ingredient

Bilateral multifocal Warthin's tumors in upper neck lymph nodes. report of a case and brief review of the literature

Cystadenolymphomas (Warthin's tumors) are the second most frequent lesions of the parotid gland. Due to their benign clinical behavior, the low rates of recurrence and malignant transformation they were classified as tumor-like lesions. In addition, a polyclonal growth of the epithelial components of the tumor could be detected. Warthin's tumors occur bilateral in 7-10%, whereas a multifocal appearance is extremely rare. Even if the pathogenesis is still unclear a heterotopia of salivary tissue during embryogenesis is the most likely explanation for the origin of these tumors in the upper neck and periparotideal region. Here we present a rare case of bilateral, multifocal, extraglandular Warthin's tumors in lymph nodes of the upper neck and give a brief review of the literature. If a primary malignancy can be excluded by a careful staging procedure prior to the operation an isolated excision of the lesions of the neck is the adequate treatment

Triphala inhibits both in vitro and in vivo xenograft growth of pancreatic tumor cells by inducing apoptosis

<p>Abstract</p> <p>Background</p> <p>Triphala is commonly used in Ayurvedic medicine to treat variety of diseases; however its mechanism of action remains unexplored. This study elucidates the molecular mechanism of Triphala against human pancreatic cancer in the cellular and in vivo model.</p> <p>Methods</p> <p>Growth-inhibitory effects of Triphala were evaluated in Capan-2, BxPC-3 and HPDE-6 cells by Sulphoradamine-B assay. Apoptosis was determined by cell death assay and western blotting. Triphala was administered orally to nude mice implanted with Capan-2 xenograft. Tumors were analyzed by immunohistochemistry and western blotting.</p> <p>Results</p> <p>Exposure of Capan-2 cells to the aqueous extract of Triphala for 24 h resulted in the significant decrease in the survival of cells in a dose-dependent manner with an IC50 of about 50 μg/ml. Triphala-mediated reduced cell survival correlated with induction of apoptosis, which was associated with reactive oxygen species (ROS) generation. Triphala-induced apoptosis was linked with phosphorylation of p53 at Ser-15 and ERK at Thr-202/Tyr-204 in Capan-2 cells. Above mentioned effects were significantly blocked when the cells were pretreated with an antioxidant N-acetylcysteine (NAC), suggesting the involvement of ROS generation. Pretreatment of cells with pifithrin-α or U0126, specific inhibitors of p53 or MEK-1/2, significantly attenuated Triphala-induced apoptosis. Moreover, NAC or U0126 pretreatment significantly attenuated Triphala-induced p53 transcriptional activity. Similarly, Triphala induced apoptosis in another pancreatic cancer cell line BxPC-3 by activating ERK. On the other hand, Triphala failed to induce apoptosis or activate ERK or p53 in normal human pancreatic ductal epithelial (HPDE-6) cells. Further, oral administration of 50 mg/kg or 100 mg/kg Triphala in PBS, 5 days/week significantly suppressed the growth of Capan-2 pancreatic tumor-xenograft. Reduced tumor-growth in Triphala fed mice was due to increased apoptosis in the tumors cells, which was associated with increased activation of p53 and ERK.</p> <p>Conclusion</p> <p>Our preclinical studies demonstrate that Triphala is effective in inhibiting the growth of human pancreatic cancer cells in both cellular and in vivo model. Our data also suggests that the growth inhibitory effects of Triphala is mediated by the activation of ERK and p53 and shows potential for the treatment and/or prevention of human pancreatic cancer.</p

Asiatic Acid Inhibits Pro-Angiogenic Effects of VEGF and Human Gliomas in Endothelial Cell Culture Models

Malignant gliomas are one of the most devastating and incurable tumors. Sustained excessive angiogenesis by glioma cells is the major reason for their uncontrolled growth and resistance toward conventional therapies resulting in high mortality. Therefore, targeting angiogenesis should be a logical strategy to prevent or control glioma cell growth. Earlier studies have shown that Asiatic Acid (AsA), a pentacyclic triterpenoid, is effective against glioma and other cancer cells; however, its efficacy against angiogenesis remains unknown. In the present study, we examined the anti-angiogenic efficacy of AsA using human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC). Our results showed that AsA (5–20 µM) inhibits HUVEC growth and induces apoptotic cell death by activating caspases (3 and 9) and modulating the expression of apoptosis regulators Bad, survivin and pAkt-ser473. Further, AsA showed a dose-dependent inhibition of HUVEC migration, invasion and capillary tube formation, and disintegrated preformed capillary network. AsA also inhibited the VEGF-stimulated growth and capillary tube formation by HUVEC and HBMEC. Next, we analyzed the angiogenic potential of conditioned media collected from human glioma LN18 and U87-MG cells treated with either DMSO (control conditioned media, CCM) or AsA 20 µM (AsA20 conditioned media, AsA20CM). CCM from glioma cells significantly enhanced the capillary tube formation in both HUVEC and HBMEC, while capillary tube formation in both endothelial cell lines was greatly compromised in the presence of AsA20CM. Consistent with these results, VEGF expression was lesser in AsA20CM compared to CCM, and indeed AsA strongly inhibited VEGF level (both cellular and secreted) in glioma cells. AsA also showed dose-dependent anti-angiogenic efficacy in Matrigel plug assay, and inhibited the glioma cells potential to attract HUVEC/HBMEC. Overall, the present study clearly showed the strong anti-angiogenic potential of AsA and suggests its usefulness against malignant gliomas

Biological influence of Hakai in cancer: a 10-year review

In order to metastasize, cancer cells must first detach from the primary tumor, migrate, invade through tissues, and attach to a second site. Hakai was discovered as an E3 ubiquitin-ligase that mediates the posttranslational downregulation of E-cadherin, a major component of adherens junctions in epithelial cells that is characterized as a potent tumor suppressor and is modulated during various processes including epithelial–mesenchymal transition. Recent data have provided evidences for novel biological functional role of Hakai during tumor progression and other diseases. Here, we will review the knowledge that has been accumulated since Hakai discovery 10 years ago and its implication in human cancer disease. We will highlight the different signaling pathways leading to the influence on Hakai and suggest its potential usefulness as therapeutic target for cancer

Search of the early O3 LIGO data for continuous gravitational waves from the Cassiopeia A and Vela Jr. supernova remnants

partially_open1412sìWe present directed searches for continuous gravitational waves from the neutron stars in the Cassiopeia A (Cas A) and Vela Jr. supernova remnants. We carry out the searches in the LIGO detector data from the first six months of the third Advanced LIGO and Virgo observing run using the weave semicoherent method, which sums matched-filter detection-statistic values over many time segments spanning the observation period. No gravitational wave signal is detected in the search band of 20–976 Hz for assumed source ages greater than 300 years for Cas A and greater than 700 years for Vela Jr. Estimates from simulated continuous wave signals indicate we achieve the most sensitive results to date across the explored parameter space volume, probing to strain magnitudes as low as ∼6.3×10^−26 for Cas A and ∼5.6×10^−26 for Vela Jr. at frequencies near 166 Hz at 95% efficiency.openAbbott, R.; Abbott, T. D.; Acernese, F.; Ackley, K.; Adams, C.; Adhikari, N.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agarwal, D.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Albanesi, S.; Allocca, A.; Altin, P. A.; Amato, A.; Anand, C.; Anand, S.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Andrade, T.; Andres, N.; Andrić, T.; Angelova, S. V.; Ansoldi, S.; Antelis, J. M.; Antier, S.; Appert, S.; Arai, K.; Araya, M. C.; Areeda, J. S.; Arène, M.; Arnaud, N.; Aronson, S. M.; Arun, K. G.; Asali, Y.; Ashton, G.; Assiduo, M.; Aston, S. M.; Astone, P.; Aubin, F.; Austin, C.; Babak, S.; Badaracco, F.; Bader, M. K. M.; Badger, C.; Bae, S.; Baer, A. M.; Bagnasco, S.; Bai, Y.; Baird, J.; Ball, M.; Ballardin, G.; Ballmer, S. W.; Balsamo, A.; Baltus, G.; Banagiri, S.; Bankar, D.; Barayoga, J. C.; Barbieri, C.; Barish, B. C.; Barker, D.; Barneo, P.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Bawaj, M.; Bayley, J. C.; Baylor, A. C.; Bazzan, M.; Bécsy, B.; Bedakihale, V. M.; Bejger, M.; Belahcene, I.; Benedetto, V.; Beniwal, D.; Bennett, T. F.; Bentley, J. D.; BenYaala, M.; Bergamin, F.; Berger, B. K.; Bernuzzi, S.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Beveridge, D.; Bhandare, R.; Bhardwaj, U.; Bhattacharjee, D.; Bhaumik, S.; Bilenko, I. A.; Billingsley, G.; Bini, S.; Birney, R.; Birnholtz, O.; Biscans, S.; Bischi, M.; Biscoveanu, S.; Bisht, A.; Biswas, B.; Bitossi, M.; Bizouard, M.-A.; Blackburn, J. K.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bobba, F.; Bode, N.; Boer, M.; Bogaert, G.; Boldrini, M.; Bonavena, L. D.; Bondu, F.; Bonilla, E.; Bonnand, R.; Booker, P.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, N.; Bose, S.; Bossilkov, V.; Boudart, V.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Bramley, A.; Branch, A.; Branchesi, M.; Brau, J. E.; Breschi, M.; Briant, T.; Briggs, J. H.; Brillet, A.; Brinkmann, M.; Brockill, P.; Brooks, A. F.; Brooks, J.; Brown, D. D.; Brunett, S.; Bruno, G.; Bruntz, R.; Bryant, J.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buscicchio, R.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Bustillo, J. Calderón; Callaghan, J. D.; Callister, T. A.; Calloni, E.; Cameron, J.; Camp, J. B.; Canepa, M.; Canevarolo, S.; Cannavacciuolo, M.; Cannon, K. C.; Cao, H.; Capote, E.; Carapella, G.; Carbognani, F.; Carlin, J. B.; Carney, M. F.; Carpinelli, M.; Carrillo, G.; Carullo, G.; Carver, T. L.; Diaz, J. Casanueva; Casentini, C.; Castaldi, G.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Ceasar, M.; Cella, G.; Cerdá-Durán, P.; Cesarini, E.; Chaibi, W.; Chakravarti, K.; Subrahmanya, S. Chalathadka; Champion, E.; Chan, C.-H.; Chan, C.; Chan, C. L.; Chan, K.; Chandra, K.; Chanial, P.; Chao, S.; Charlton, P.; Chase, E. A.; Chassande-Mottin, E.; Chatterjee, C.; Chatterjee, Debarati; Chatterjee, Deep; Chaturvedi, M.; Chaty, S.; Chen, H. Y.; Chen, J.; Chen, X.; Chen, Y.; Chen, Z.; Cheng, H.; Cheong, C. K.; Cheung, H. Y.; Chia, H. Y.; Chiadini, F.; Chiarini, G.; Chierici, R.; Chincarini, A.; Chiofalo, M. L.; Chiummo, A.; Cho, G.; Cho, H. S.; Choudhary, R. K.; Choudhary, S.; Christensen, N.; Chu, Q.; Chua, S.; Chung, K. W.; Ciani, G.; Ciecielag, P.; Cieślar, M.; Cifaldi, M.; Ciobanu, A. A.; Ciolfi, R.; Cipriano, F.; Cirone, A.; Clara, F.; Clark, E. N.; Clark, J. A.; Clarke, L.; Clearwater, P.; Clesse, S.; Cleva, F.; Coccia, E.; Codazzo, E.; Cohadon, P.-F.; Cohen, D. E.; Cohen, L.; Colleoni, M.; Collette, C. G.; Colombo, A.; Colpi, M.; Compton, C. M.; Constancio, M.; Conti, L.; Cooper, S. J.; Corban, P.; Corbitt, T. R.; Cordero-Carrión, I.; Corezzi, S.; Corley, K. R.; Cornish, N.; Corre, D.; Corsi, A.; Cortese, S.; Costa, C. A.; Cotesta, R.; Coughlin, M. W.; Coulon, J.-P.; Countryman, S. T.; Cousins, B.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Creighton, J. D. E.; Creighton, T. D.; Criswell, A. W.; Croquette, M.; Crowder, S. G.; Cudell, J. R.; Cullen, T. J.; Cumming, A.; Cummings, R.; Cunningham, L.; Cuoco, E.; Curyło, M.; Dabadie, P.; Canton, T. Dal; Dall’Osso, S.; Dálya, G.; Dana, A.; DaneshgaranBajastani, L. M.; D’Angelo, B.; Danilishin, S.; D’Antonio, S.; Danzmann, K.; Darsow-Fromm, C.; Dasgupta, A.; Datrier, L. E. H.; Datta, S.; Dattilo, V.; Dave, I.; Davier, M.; Davies, G. S.; Davis, D.; Davis, M. C.; Daw, E. J.; Dean, R.; DeBra, D.; Deenadayalan, M.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Favero, V.; De Lillo, F.; De Lillo, N.; Del Pozzo, W.; DeMarchi, L. M.; De Matteis, F.; D’Emilio, V.; Demos, N.; Dent, T.; Depasse, A.; De Pietri, R.; De Rosa, R.; De Rossi, C.; DeSalvo, R.; De Simone, R.; Dhurandhar, S.; Díaz, M. C.; Diaz-Ortiz, M.; Didio, N. A.; Dietrich, T.; Di Fiore, L.; Di Fronzo, C.; Di Giorgio, C.; Di Giovanni, F.; Di Giovanni, M.; Di Girolamo, T.; Di Lieto, A.; Ding, B.; Di Pace, S.; Di Palma, I.; Di Renzo, F.; Divakarla, A. K.; Dmitriev, A.; Doctor, Z.; D’Onofrio, L.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Drago, M.; Driggers, J. C.; Drori, Y.; Ducoin, J.-G.; Dupej, P.; Durante, O.; D’Urso, D.; Duverne, P.-A.; Dwyer, S. E.; Eassa, C.; Easter, P. J.; Ebersold, M.; Eckhardt, T.; Eddolls, G.; Edelman, B.; Edo, T. B.; Edy, O.; Effler, A.; Eichholz, J.; Eikenberry, S. S.; Eisenmann, M.; Eisenstein, R. A.; Ejlli, A.; Engelby, E.; Errico, L.; Essick, R. C.; Estellés, H.; Estevez, D.; Etienne, Z.; Etzel, T.; Evans, M.; Evans, T. M.; Ewing, B. E.; Fafone, V.; Fair, H.; Fairhurst, S.; Farah, A. M.; Farinon, S.; Farr, B.; Farr, W. M.; Farrow, N. W.; Fauchon-Jones, E. J.; Favaro, G.; Favata, M.; Fays, M.; Fazio, M.; Feicht, J.; Fejer, M. M.; Fenyvesi, E.; Ferguson, D. L.; Fernandez-Galiana, A.; Ferrante, I.; Ferreira, T. A.; Fidecaro, F.; Figura, P.; Fiori, I.; Fishbach, M.; Fisher, R. P.; Fittipaldi, R.; Fiumara, V.; Flaminio, R.; Floden, E.; Fong, H.; Font, J. A.; Fornal, B.; Forsyth, P. W. F.; Franke, A.; Frasca, S.; Frasconi, F.; Frederick, C.; Freed, J. P.; Frei, Z.; Freise, A.; Frey, R.; Fritschel, P.; Frolov, V. V.; Fronzé, G. G.; Fulda, P.; Fyffe, M.; Gabbard, H. A.; Gadre, B. U.; Gair, J. R.; Gais, J.; Galaudage, S.; Gamba, R.; Ganapathy, D.; Ganguly, A.; Gaonkar, S. G.; Garaventa, B.; García-Núñez, C.; García-Quirós, C.; Garufi, F.; Gateley, B.; Gaudio, S.; Gayathri, V.; Gemme, G.; Gennai, A.; George, J.; Gerberding, O.; Gergely, L.; Gewecke, P.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, Shaon; Ghosh, Shrobana; Giacomazzo, B.; Giacoppo, L.; Giaime, J. A.; Giardina, K. D.; Gibson, D. R.; Gier, C.; Giesler, M.; Giri, P.; Gissi, F.; Glanzer, J.; Gleckl, A. E.; Godwin, P.; Goetz, E.; Goetz, R.; Gohlke, N.; Goncharov, B.; González, G.; Gopakumar, A.; Gosselin, M.; Gouaty, R.; Gould, D. W.; Grace, B.; Grado, A.; Granata, M.; Granata, V.; Grant, A.; Gras, S.; Grassia, P.; Gray, C.; Gray, R.; Greco, G.; Green, A. C.; Green, R.; Gretarsson, A. M.; Gretarsson, E. M.; Griffith, D.; Griffiths, W.; Griggs, H. L.; Grignani, G.; Grimaldi, A.; Grimm, S. J.; Grote, H.; Grunewald, S.; Gruning, P.; Guerra, D.; Guidi, Gianluca; Guimaraes, A. R.; Guixé, G.; Gulati, H. K.; Guo, H.-K.; Guo, Y.; Gupta, Anchal; Gupta, Anuradha; Gupta, P.; Gustafson, E. K.; Gustafson, R.; Guzman, F.; Haegel, L.; Halim, O.; Hall, E. D.; Hamilton, E. Z.; Hammond, G.; Haney, M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hannuksela, O.; Hansen, H.; Hansen, T. J.; Hanson, J.; Harder, T.; Hardwick, T.; Haris, K.; Harms, J.; Harry, G. M.; Harry, I. W.; Hartwig, D.; Haskell, B.; Hasskew, R. K.; Haster, C.-J.; Haughian, K.; Hayes, F. J.; Healy, J.; Heidmann, A.; Heidt, A.; Heintze, M. C.; Heinze, J.; Heinzel, J.; Heitmann, H.; Hellman, F.; Hello, P.; Helmling-Cornell, A. F.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennes, E.; Hennig, J.; Hennig, M. H.; Hernandez, A. G.; Vivanco, F. Hernandez; Heurs, M.; Hild, S.; Hill, P.; Hines, A. S.; Hochheim, S.; Hofman, D.; Hohmann, J. N.; Holcomb, D. G.; Holland, N. A.; Hollows, I. J.; Holmes, Z. J.; Holt, K.; Holz, D. E.; Hopkins, P.; Hough, J.; Hourihane, S.; Howell, E. J.; Hoy, C. G.; Hoyland, D.; Hreibi, A.; Hsu, Y.; Huang, Y.; Hübner, M. T.; Huddart, A. D.; Hughey, B.; Hui, V.; Husa, S.; Huttner, S. H.; Huxford, R.; Huynh-Dinh, T.; Idzkowski, B.; Iess, A.; Ingram, C.; Isi, M.; Isleif, K.; Iyer, B. R.; JaberianHamedan, V.; Jacqmin, T.; Jadhav, S. J.; Jadhav, S. P.; James, A. L.; Jan, A. Z.; Jani, K.; Janquart, J.; Janssens, K.; Janthalur, N. N.; Jaranowski, P.; Jariwala, D.; Jaume, R.; Jenkins, A. C.; Jenner, K.; Jeunon, M.; Jia, W.; Johns, G. R.; Jones, A. W.; Jones, D. I.; Jones, J. D.; Jones, P.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Juste, V.; Kalaghatgi, C. V.; Kalogera, V.; Kamai, B.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kao, Y.; Kapadia, S. J.; Kapasi, D. P.; Karat, S.; Karathanasis, C.; Karki, S.; Kashyap, R.; Kasprzack, M.; Kastaun, W.; Katsanevas, S.; Katsavounidis, E.; Katzman, W.; Kaur, T.; Kawabe, K.; Kéfélian, F.; Keitel, D.; Key, J. S.; Khadka, S.; Khalili, F. Y.; Khan, S.; Khazanov, E. A.; Khetan, N.; Khursheed, M.; Kijbunchoo, N.; Kim, C.; Kim, J. C.; Kim, K.; Kim, W. S.; Kim, Y.-M.; Kimball, C.; Kinley-Hanlon, M.; Kirchhoff, R.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Knee, A. M.; Knowles, T. D.; Knyazev, E.; Koch, P.; Koekoek, G.; Koley, S.; Kolitsidou, P.; Kolstein, M.; Komori, K.; Kondrashov, V.; Kontos, A.; Koper, N.; Korobko, M.; Kovalam, M.; Kozak, D. B.; Kringel, V.; Krishnendu, N. V.; Królak, A.; Kuehn, G.; Kuei, F.; Kuijer, P.; Kumar, A.; Kumar, P.; Kumar, Rahul; Kumar, Rakesh; Kuns, K.; Kuwahara, S.; Lagabbe, P.; Laghi, D.; Lalande, E.; Lam, T. L.; Lamberts, A.; Landry, M.; Lane, B. B.; Lang, R. N.; Lange, J.; Lantz, B.; La Rosa, I.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lecoeuche, Y. K.; Lee, H. M.; Lee, H. W.; Lee, J.; Lee, K.; Lehmann, J.; Lemaître, A.; Leroy, N.; Letendre, N.; Levesque, C.; Levin, Y.; Leviton, J. N.; Leyde, K.; Li, A. K. Y.; Li, B.; Li, J.; Li, T. G. F.; Li, X.; Linde, F.; Linker, S. D.; Linley, J. N.; Littenberg, T. B.; Liu, J.; Liu, K.; Liu, X.; Llamas, F.; Llorens-Monteagudo, M.; Lo, R. K. L.; Lockwood, A.; London, L. T.; Longo, A.; Lopez, D.; Portilla, M. Lopez; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lott, T. P.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lucaccioni, J. F.; Lück, H.; Lumaca, D.; Lundgren, A. P.; Lynam, J. E.; Macas, R.; MacInnis, M.; Macleod, D. M.; MacMillan, I. A. O.; Macquet, A.; Hernandez, I. Magaña; Magazzù, C.; Magee, R. M.; Maggiore, R.; Magnozzi, M.; Mahesh, S.; Majorana, E.; Makarem, C.; Maksimovic, I.; Maliakal, S.; Malik, A.; Man, N.; Mandic, V.; Mangano, V.; Mango, J. L.; Mansell, G. L.; Manske, M.; Mantovani, M.; Mapelli, M.; Marchesoni, F.; Marion, F.; Mark, Z.; Márka, S.; Márka, Z.; Markakis, C.; Markosyan, A. S.; Markowitz, A.; Maros, E.; Marquina, A.; Marsat, S.; Martelli, F.; Martin, I. W.; Martin, R. M.; Martinez, M.; Martinez, V. A.; Martinez, V.; Martinovic, K.; Martynov, D. V.; Marx, E. J.; Masalehdan, H.; Mason, K.; Massera, E.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matas, A.; Mateu-Lucena, M.; Matichard, F.; Matiushechkina, M.; Mavalvala, N.; McCann, J. J.; McCarthy, R.; McClelland, D. E.; McClincy, P. K.; McCormick, S.; McCuller, L.; McGhee, G. I.; McGuire, S. C.; McIsaac, C.; McIver, J.; McRae, T.; McWilliams, S. T.; Meacher, D.; Mehmet, M.; Mehta, A. K.; Meijer, Q.; Melatos, A.; Melchor, D. A.; Mendell, G.; Menendez-Vazquez, A.; Menoni, C. S.; Mercer, R. A.; Mereni, L.; Merfeld, K.; Merilh, E. L.; Merritt, J. D.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Meyers, P. M.; Meylahn, F.; Mhaske, A.; Miani, A.; Miao, H.; Michaloliakos, I.; Michel, C.; Middleton, H.; Milano, L.; Miller, A.; Miller, A. L.; Miller, B.; Millhouse, M.; Mills, J. C.; Milotti, E.; Minazzoli, O.; Minenkov, Y.; Mir, Ll. M.; Miravet-Tenés, M.; Mishra, C.; Mishra, T.; Mistry, T.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Mo, Geoffrey; Moguel, E.; Mogushi, K.; Mohapatra, S. R. P.; Mohite, S. R.; Molina, I.; Molina-Ruiz, M.; Mondin, M.; Montani, M.; Moore, C. J.; Moraru, D.; Morawski, F.; More, A.; Moreno, C.; Moreno, G.; Morisaki, S.; Mours, B.; Mow-Lowry, C. M.; Mozzon, S.; Muciaccia, F.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, Soma; Mukherjee, Subroto; Mukherjee, Suvodip; Mukund, N.; Mullavey, A.; Munch, J.; Muñiz, E. A.; Murray, P. G.; Musenich, R.; Muusse, S.; Nadji, S. L.; Nagar, A.; Napolano, V.; Nardecchia, I.; Naticchioni, L.; Nayak, B.; Nayak, R. K.; Neil, B. F.; Neilson, J.; Nelemans, G.; Nelson, T. J. N.; Nery, M.; Neubauer, P.; Neunzert, A.; Ng, K. Y.; Ng, S. W. S.; Nguyen, C.; Nguyen, P.; Nguyen, T.; Nichols, S. A.; Nissanke, S.; Nitoglia, E.; Nocera, F.; Norman, M.; North, C.; Nuttall, L. K.; Oberling, J.; O’Brien, B. D.; O’Dell, J.; Oelker, E.; Oganesyan, G.; Oh, J. J.; Oh, S. H.; Ohme, F.; Ohta, H.; Okada, M. A.; Olivetto, C.; Oram, R.; O’Reilly, B.; Ormiston, R. G.; Ormsby, N. D.; Ortega, L. F.; O’Shaughnessy, R.; O’Shea, E.; Ossokine, S.; Osthelder, C.; Ottaway, D. J.; Overmier, H.; Pace, A. E.; Pagano, G.; Page, M. A.; Pagliaroli, G.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pan, H.; Panda, P. K.; Pang, P. T. H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Panther, F. H.; Paoletti, F.; Paoli, A.; Paolone, A.; Park, H.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patel, M.; Pathak, M.; Patricelli, B.; Patron, A. S.; Paul, S.; Payne, E.; Pedraza, M.; Pegoraro, M.; Pele, A.; Penn, S.; Perego, A.; Pereira, A.; Pereira, T.; Perez, C. J.; Périgois, C.; Perkins, C. C.; Perreca, A.; Perriès, S.; Petermann, J.; Petterson, D.; Pfeiffer, H. P.; Pham, K. A.; Phukon, K. S.; Piccinni, O. J.; Pichot, M.; Piendibene, M.; Piergiovanni, F.; Pierini, L.; Pierro, V.; Pillant, G.; Pillas, M.; Pilo, F.; Pinard, L.; Pinto, I. M.; Pinto, M.; Piotrzkowski, K.; Pirello, M.; Pitkin, M. D.; Placidi, E.; Planas, L.; Plastino, W.; Pluchar, C.; Poggiani, R.; Polini, E.; Pong, D. Y. T.; Ponrathnam, S.; Popolizio, P.; Porter, E. K.; Poulton, R.; Powell, J.; Pracchia, M.; Pradier, T.; Prajapati, A. K.; Prasai, K.; Prasanna, R.; Pratten, G.; Principe, M.; Prodi, G. A.; Prokhorov, L.; Prosposito, P.; Prudenzi, L.; Puecher, A.; Punturo, M.; Puosi, F.; Puppo, P.; Pürrer, M.; Qi, H.; Quetschke, V.; Quitzow-James, R.; Raab, F. J.; Raaijmakers, G.; Radkins, H.; Radulesco, N.; Raffai, P.; Rail, S. X.; Raja, S.; Rajan, C.; Ramirez, K. E.; Ramirez, T. D.; Ramos-Buades, A.; Rana, J.; Rapagnani, P.; Rapol, U. D.; Ray, A.; Raymond, V.; Raza, N.; Razzano, M.; Read, J.; Rees, L. A.; Regimbau, T.; Rei, L.; Reid, S.; Reid, S. W.; Reitze, D. H.; Relton, P.; Renzini, A.; Rettegno, P.; Rezac, M.; Ricci, F.; Richards, D.; Richardson, J. W.; Richardson, L.; Riemenschneider, G.; Riles, K.; Rinaldi, S.; Rink, K.; Rizzo, M.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rodriguez, S.; Rolland, L.; Rollins, J. G.; Romanelli, M.; Romano, R.; Romel, C. L.; Romero-Rodríguez, A.; Romero-Shaw, I. M.; Romie, J. H.; Ronchini, S.; Rosa, L.; Rose, C. A.; Rosińska, D.; Ross, M. P.; Rowan, S.; Rowlinson, S. J.; Roy, S.; Roy, Santosh; Roy, Soumen; Rozza, D.; Ruggi, P.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadiq, J.; Sakellariadou, M.; Salafia, O. S.; Salconi, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sanchez, E. J.; Sanchez, J. H.; Sanchez, L. E.; Sanchis-Gual, N.; Sanders, J. R.; Sanuy, A.; Saravanan, T. R.; Sarin, N.; Sassolas, B.; Satari, H.; Sathyaprakash, B. S.; Sauter, O.; Savage, R. L.; Sawant, D.; Sawant, H. L.; Sayah, S.; Schaetzl, D.; Scheel, M.; Scheuer, J.; Schiworski, M.; Schmidt, P.; Schmidt, S.; Schnabel, R.; Schneewind, M.; Schofield, R. M. S.; Schönbeck, A.; Schulte, B. W.; Schutz, B. F.; Schwartz, E.; Scott, J.; Scott, S. M.; Seglar-Arroyo, M.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Seo, E. G.; Sequino, V.; Sergeev, A.; Setyawati, Y.; Shaffer, T.; Shahriar, M. S.; Shams, B.; Sharma, A.; Sharma, P.; Shawhan, P.; Shcheblanov, N. S.; Shikauchi, M.; Shoemaker, D. H.; Shoemaker, D. M.; ShyamSundar, S.; Sieniawska, M.; Sigg, D.; Singer, L. P.; Singh, D.; Singh, N.; Singha, A.; Sintes, A. M.; Sipala, V.; Skliris, V.; Slagmolen, B. J. J.; Slaven-Blair, T. J.; Smetana, J.; Smith, J. R.; Smith, R. J. E.; Soldateschi, J.; Somala, S. N.; Son, E. J.; Soni, K.; Soni, S.; Sordini, V.; Sorrentino, F.; Sorrentino, N.; Soulard, R.; Souradeep, T.; Sowell, E.; Spagnuolo, V.; Spencer, A. P.; Spera, M.; Srinivasan, R.; Srivastava, A. K.; Srivastava, V.; Staats, K.; Stachie, C.; Steer, D. A.; Steinlechner, J.; Steinlechner, S.; Stops, D. J.; Stover, M.; Strain, K. A.; Strang, L. C.; Stratta, G.; Strunk, A.; Sturani, R.; Stuver, A. L.; Sudhagar, S.; Sudhir, V.; Suh, H. G.; Summerscales, T. Z.; Sun, H.; Sun, L.; Sunil, S.; Sur, A.; Suresh, J.; Sutton, P. J.; Swinkels, B. L.; Szczepańczyk, M. J.; Szewczyk, P.; Tacca, M.; Tait, S. C.; Talbot, C. J.; Talbot, C.; Tanasijczuk, A. J.; Tanner, D. B.; Tao, D.; Tao, L.; Martín, E. N. Tapia San; Taranto, C.; Tasson, J. D.; Tenorio, R.; Terhune, J. E.; Terkowski, L.; Thirugnanasambandam, M. P.; Thomas, M.; Thomas, P.; Thompson, J. E.; Thondapu, S. R.; Thorne, K. A.; Thrane, E.; Tiwari, Shubhanshu; Tiwari, Srishti; Tiwari, V.; Toivonen, A. M.; Toland, K.; Tolley, A. E.; Tonelli, M.; Torres-Forné, A.; Torrie, C. I.; e Melo, I. Tosta; Töyrä, D.; Trapananti, A.; Travasso, F.; Traylor, G.; Trevor, M.; Tringali, M. C.; Tripathee, A.; Troiano, L.; Trovato, A.; Trozzo, L.; Trudeau, R. J.; Tsai, D. S.; Tsai, D.; Tsang, K. W.; Tse, M.; Tso, R.; Tsukada, L.; Tsuna, D.; Tsutsui, T.; Turbang, K.; Turconi, M.; Ubhi, A. S.; Udall, R. P.; Ueno, K.; Unnikrishnan, C. S.; Urban, A. L.; Utina, A.; Vahlbruch, H.; Vajente, G.; Vajpeyi, A.; Valdes, G.; Valentini, M.; Valsan, V.; van Bakel, N.; van Beuzekom, M.; van den Brand, J. F. J.; Van Den Broeck, C.; Vander-Hyde, D. C.; van der Schaaf, L.; van Heijningen, J. V.; Vanosky, J.; van Remortel, N.; Vardaro, M.; Vargas, A. F.; Varma, V.; Vasúth, M.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venneberg, J.; Venugopalan, G.; Verkindt, D.; Verma, P.; Verma, Y.; Veske, D.; Vetrano, F.; Vicere', Andrea; Vidyant, S.; Viets, A. D.; Vijaykumar, A.; Villa-Ortega, V.; Vinet, J.-Y.; Virtuoso, A.; Vitale, S.; Vo, T.; Vocca, H.; von Reis, E. R. G.; von Wrangel, J. S. A.; Vorvick, C.; Vyatchanin, S. P.; Wade, L. E.; Wade, M.; Wagner, K. J.; Walet, R. C.; Walker, M.; Wallace, G. S.; Wallace, L.; Walsh, S.; Wang, J. Z.; Wang, W. H.; Ward, R. L.; Warner, J.; Was, M.; Washington, N. Y.; Watchi, J.; Weaver, B.; Webster, S. A.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Weldon, G.; Weller, C. M.; Wellmann, F.; Wen, L.; Weßels, P.; Wette, K.; Whelan, J. T.; White, D. D.; Whiting, B. F.; Whittle, C.; Wilken, D.; Williams, D.; Williams, M. J.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wilson, D. J.; Winkler, W.; Wipf, C. C.; Wlodarczyk, T.; Woan, G.; Woehler, J.; Wofford, J. K.; Wong, I. C. F.; Wu, D. S.; Wysocki, D. M.; Xiao, L.; Yamamoto, H.; Yang, F. W.; Yang, L.; Yang, Yang; Yang, Z.; Yap, M. J.; Yeeles, D. W.; Yelikar, A. B.; Ying, M.; Yoo, J.; Yu, Hang; Yu, Haocun; Zadrożny, A.; Zanolin, M.; Zelenova, T.; Zendri, J.-P.; Zevin, M.; Zhang, J.; Zhang, L.; Zhang, T.; Zhang, Y.; Zhao, C.; Zhao, G.; Zhao, Yue; Zhou, R.; Zhou, Z.; Zhu, X. J.; Zimmerman, A. B.; Zucker, M. E.; Zweizig, J.Abbott, R.; Abbott, T.  D.; Acernese, F.; Ackley, K.; Adams, C.; Adhikari, N.; Adhikari, R.  X.; Adya, V.  B.; Affeldt, C.; Agarwal, D.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O.  D.; Aiello, L.; Ain, A.; Ajith, P.; Albanesi, S.; Allocca, A.; Altin, P.  A.; Amato, A.; Anand, C.; Anand, S.; Ananyeva, A.; Anderson, S.  B.; Anderson, W.  G.; Andrade, T.; Andres, N.; Andrić, T.; Angelova, S.  V.; Ansoldi, S.; Antelis, J.  M.; Antier, S.; Appert, S.; Arai, K.; Araya, M.  C.; Areeda, J.  S.; Arène, M.; Arnaud, N.; Aronson, S.  M.; Arun, K.  G.; Asali, Y.; Ashton, G.; Assiduo, M.; Aston, S.  M.; Astone, P.; Aubin, F.; Austin, C.; Babak, S.; Badaracco, F.; Bader, M.  K.  M.; Badger, C.; Bae, S.; Baer, A.  M.; Bagnasco, S.; Bai, Y.; Baird, J.; Ball, M.; Ballardin, G.; Ballmer, S.  W.; Balsamo, A.; Baltus, G.; Banagiri, S.; Bankar, D.; Barayoga, J.  C.; Barbieri, C.; Barish, B.  C.; Barker, D.; Barneo, P.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M.  A.; Bartos, I.; Bassiri, R.; Basti, A.; Bawaj, M.; Bayley, J.  C.; Baylor, A.  C.; Bazzan, M.; Bécsy, B.; Bedakihale, V.  M.; Bejger, M.; Belahcene, I.; Benedetto, V.; Beniwal, D.; Bennett, T.  F.; Bentley, J.  D.; Benyaala, M.; Bergamin, F.; Berger, B.  K.; Bernuzzi, S.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Beveridge, D.; Bhandare, R.; Bhardwaj, U.; Bhattacharjee, D.; Bhaumik, S.; Bilenko, I.  A.; Billingsley, G.; Bini, S.; Birney, R.; Birnholtz, O.; Biscans, S.; Bischi, M.; Biscoveanu, S.; Bisht, A.; Biswas, B.; Bitossi,

Search for subsolar-mass black hole binaries in the second part of Advanced LIGO’s and Advanced Virgo’s third observing run

We describe a search for gravitational waves from compact binaries with at least one component with mass 0.2 M⊙–1.0 M⊙ and mass ratio q ≥ 0.1 in Advanced LIGO and Advanced Virgo data collected between 1 November 2019, 15:00 UTC and 27 March 2020, 17:00 UTC. No signals were detected. The most significant candidate has a false alarm rate of 0.2yr−1 ⁠. We estimate the sensitivity of our search over the entirety of Advanced LIGO’s and Advanced Virgo’s third observing run, and present the most stringent limits to date on the merger rate of binary black holes with at least one subsolar-mass component. We use the upper limits to constrain two fiducial scenarios that could produce subsolar-mass black holes: primordial black holes (PBH) and a model of dissipative dark matter. The PBH model uses recent prescriptions for the merger rate of PBH binaries that include a rate suppression factor to effectively account for PBH early binary disruptions. If the PBHs are monochromatically distributed, we can exclude a dark matter fraction in PBHs fPBH ≳ 0.6 (at 90% confidence) in the probed subsolar-mass range. However, if we allow for broad PBH mass distributions we are unable to rule out fPBH = 1. For the dissipative model, where the dark matter has chemistry that allows a small fraction to cool and collapse into black holes, we find an upper bound fDBH &lt; 10−5 on the fraction of atomic dark matter collapsed into black holes