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4. Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness

Author

Chiara Battistini, Hilary A. Kenny, Melissa Zambuto, Valentina Nieddu, Valentina Melocchi, Alessandra Decio, Pietro Lo Riso, Carlo Emanuele Villa, Alessia Gatto, Mariacristina Ghioni, Francesca M. Porta, Giuseppe Testa, Raffaella Giavazzi, Nicoletta Colombo, Fabrizio Bianchi, Ernst Lengyel, and Ugo Cavallaro

Subjects
Cytology, QH573-671
Abstract

Abstract In ovarian tumors, the omental microenvironment profoundly influences the behavior of cancer cells and sustains the acquisition of stem-like traits, with major impacts on tumor aggressiveness and relapse. Here, we leverage a patient-derived platform of organotypic cultures to study the crosstalk between the tumor microenvironment and ovarian cancer stem cells. We discovered that the pro-tumorigenic transcription factor FOXM1 is specifically induced by the microenvironment in ovarian cancer stem cells, through activation of FAK/YAP signaling. The microenvironment-induced FOXM1 sustains stemness, and its inactivation reduces cancer stem cells survival in the omental niche and enhances their response to the PARP inhibitor Olaparib. By unveiling the novel role of FOXM1 in ovarian cancer stemness, our findings highlight patient-derived organotypic co-cultures as a powerful tool to capture clinically relevant mechanisms of the microenvironment/cancer stem cells crosstalk, contributing to the identification of tumor vulnerabilities.

Published
2024
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5. Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness

Author

Battistini, Chiara, Kenny, Hilary A., Zambuto, Melissa, Nieddu, Valentina, Melocchi, Valentina, Decio, Alessandra, Lo Riso, Pietro, Villa, Carlo Emanuele, Gatto, Alessia, Ghioni, Mariacristina, Porta, Francesca M., Testa, Giuseppe, Giavazzi, Raffaella, Colombo, Nicoletta, Bianchi, Fabrizio, Lengyel, Ernst, and Cavallaro, Ugo

Published
2024
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7. Cardiovascular Outcomes in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study)

Author

Green, Jennifer B., Everett, Brendan M., Ghosh, Alokananda, Younes, Naji, Krause-Steinrauf, Heidi, Barzilay, Joshua, Desouza, Cyrus, Inzucchi, Silvio E., Pokharel, Yashashwi, Schade, David, Scrymgeour, Alexandra, Tan, Meng H., Utzschneider, Kristina M., Mudaliar, Sunder, Crandall, J.P., McKee, M.D., Behringer-Massera, S., Brown-Friday, J., Xhori, E., Ballentine-Cargill, K., Duran, S., Estrella, H., Gonzalez de la Torre, S., Lukin, J., Phillips, L.S., Burgess, E., Olson, D., Rhee, M., Wilson, P., Raines, T.S., Boers, J., Costello, J., Maher-Albertelli, M., Mungara, R., Savoye, L., White, C.A., Gullett, C., Holloway, L., Morehead, F., Person, S., Sibymon, M., Tanukonda, S., Adams, C., Ross, A., Balasubramanyam, A., Gaba, R., Gonzalez Hattery, E., Ideozu, A., Jimenez, J., Montes, G., Wright, C., Hollander, P., Roe, E., Jackson, A., Smiley, A., Burt, P., Estrada, L., Chionh, K., Ismail-Beigi, F., Falck-Ytter, C., Sayyed Kassem, L., Sood, A., Tiktin, M., Kulow, T., Newman, C., Stancil, K.A., Cramer, B., Iacoboni, J., Kononets, M.V., Sanders, C., Tucker, L., Werner, A., Maxwell, A., McPhee, G., Patel, C., Colosimo, L., Krol, A., Goland, R., Pring, J., Alfano, L., Kringas, P., Hausheer, C., Tejada, J., Gumpel, K., Kirpitch, A., Schneier, H., AbouAssi, H., Chatterjee, R., Feinglos, M.N., English Jones, J., Khan, S.A., Kimpel, J.B., Zimmer, R.P., Furst, M., Satterwhite, B.M., Thacker, C.R., Evans Kreider, K., Mariash, C.N., Mather, K.J., Ismail, H.M., Lteif, A., Mullen, M., Hamilton, T., Patel, N., Riera, G., Jackson, M., Pirics, V., Aguillar, D., Howard, D., Hurt, S., Bergenstal, R., Carlson, A., Martens, T., Johnson, M., Hill, R., Hyatt, J., Jensen, C., Madden, M., Martin, D., Willis, H., Konerza, W., Yang, S., Kleeberger, K., Passi, R., Fortmann, S., Herson, M., Mularski, K., Glauber, H., Prihoda, J., Ash, B., Carlson, C., Ramey, P.A., Schield, E., Torgrimson-Ojerio, B., Arnold, K., Kauffman, B., Panos, E., Sahnow, S., Bays, K., Berame, K., Cook, J., Ghioni, D., Gluth, J., Schell, K., Criscola, J., Friason, C., Jones, S., Nazarov, S., Rassouli, N., Puttnam, R., Ojoawo, B., Nelson, R., Curtis, M., Hollis, B., Sanders-Jones, C., Stokes, K., El-Haqq, Z., Kolli, A., Tran, T., Wexler, D., Larkin, M.E., Meigs, J., Chambers, B., Dushkin, A., Rocchio, G., Yepes, M., Steiner, B., Dulin, H., Cayford, M., Chu, K., DeManbey, A., Hillard, M., Martin, K., Thangthaeng, N., Gurry, L., Kochis, R., Raymond, E., Ripley, V., Stevens, C., Park, J., Aroda, V., Ghazi, A., Magee, M., Ressing, A., Loveland, A., Hamm, M., Hurtado, M., Kuhn, A., Leger, J., Manandhar, L., Mwicigi, F., Sanchez, O., Young, T., Garg, R., Lagari-Libhaber, V., Florez, H.J., Valencia, W.M., Marks, J., Casula, S., Oropesa-Gonzalez, L., Hue, L., Cuadot, A., Nieto-Martinez, R., Riccio Veliz, A.K., Gutt, M., Kendal, Y.J., Veciana, B., Ahmann, A., Aby-Daniel, D., Joarder, F., Morimoto, V., Sprague, C., Yamashita, D., Cady, N., Rivera-Eschright, N., Kirchhoff, P., Morales Gomez, B., Adducci, J., Goncharova, A., Hox, S.H., Petrovitch, H., Matwichyna, M., Jenkins, V., Broadwater, L., Ishii, R.R., Bermudez, N.O., Hsia, D.S., Cefalu, W.T., Greenway, F.L., Waguespack, C., King, E., Fry, G., Dragg, A., Gildersleeve, B., Arceneaux, J., Haynes, N., Thomassie, A., Pavlionis, M., Bourgeois, B., Hazlett, C., Henry, R., Boeder, S., Pettus, J., Diaz, E., Garcia-Acosta, D., Maggs, S., DeLue, C., Stallings, A., Castro, E., Hernandez, S., Krakoff, J., Curtis, J.M., Killean, T., Khalid, M., Joshevama, E., Diaz, E., Martin, D., Tsingine, K., Karshner, T., Albu, J., Pi-Sunyer, F.X., Frances, S., Maggio, C., Ellis, E., Bastawrose, J., Gong, X., Banerji, M.A., August, P., Lee, M., Lorber, D., Brown, N.M., Josephson, D.H., Thomas, L.L., Tsovian, M., Cherian, A., Jacobson, M.H., Mishko, M.M., Kirkman, M.S., Buse, J.B., Diner, J., Dostou, J., Machineni, S., Young, L., Bergamo, K., Goley, A., Kerr, J., Largay, J.F., Guarda, S., Cuffee, J., Culmer, D., Fraser, R., Almeida, H., Coffer, S., Debnam, E., Kiker, L., Morton, S., Josey, K., Fuller, G., Garvey, W.T., Cherrington, A.L., Dyer, D., Lawson, M.C.R., Griffith, O., Agne, A., McCullars, S., Cohen, R.M., Craig, J., Rogge, M.C., Burton, K., Kersey, K., Wilson, C., Lipp, S., Vonder Meulen, M.B., Adkins, C., Onadeko, T., Rasouli, N., Baker, C., Schroeder, E., Razzaghi, M., Lyon, C., Penaloza, R., Underkofler, C., Lorch, R., Douglass, S., Steiner, S., Sivitz, W.I., Cline, E., Knosp, L.K., McConnell, J., Lowe, T., Herman, W.H., Pop-Busui, R., Martin, C., Waltje, A., Katona, A., Goodhall, L., Eggleston, R., Kuo, S., Bojescu, S., Bule, S., Kessler, N., LaSalle, E., Whitley, K., Seaquist, E.R., Bantle, A., Harindhanavudhi, T., Kumar, A., Redmon, B., Bantle, J., Coe, M., Mech, M., Taddese, A., Lesne, L., Smith, S., Kuechenmeister, L., Shivaswamy, V., Burbach, S., Rodriguez, M.G., Seipel, K., Alfred, A., Morales, A.L., Eggert, J., Lord, G., Taylor, W., Tillson, R., Adolphe, A., Burge, M., Duran-Valdez, E., Martinez, J., Bancroft, A., Kunkel, S., Ali Jamaleddin Ahmad, F., Hernandez McGinnis, D., Pucchetti, B., Scripsick, E., Zamorano, A., DeFronzo, R.A., Cersosimo, E., Abdul-Ghani, M., Triplitt, C., Juarez, D., Mullen, M., Garza, R.I., Verastiqui, H., Wright, K., Puckett, C., Raskin, P., Rhee, C., Abraham, S., Jordan, L.F., Sao, S., Morton, L., Smith, O., Osornio Walker, L., Schnurr-Breen, L., Ayala, R., Kreymer, R.B., Sturgess, D., Kahn, S.E., Alarcon-Casas Wright, L., Boyko, E.J., Tsai, E.C., Trence, D.L., Trikudanathan, S., Fattaleh, B.N., Montgomery, B.K., Atkinson, K.M., Kozedub, A., Concepcion, T., Moak, C., Prikhodko, N., Rhothisen, S., Elasy, T.A., Martin, S., Shackelford, L., Goidel, R., Hinkle, N., Lovell, C., Myers, J., Lipps Hogan, J., McGill, J.B., Salam, M., Schweiger, T., Kissel, S., Recklein, C., Clifton, M.J., Tamborlane, W., Camp, A., Gulanski, B., Pham, K., Alguard, M., Gatcomb, P., Lessard, K., Perez, M., Iannone, L., Magenheimer, E., Montosa, A., Cefalu, W.T., Fradkin, J., Burch, H.B., Bremer, A.A., Nathan, D.M., Lachin, J.M., Buse, J.B., Kahn, S.E., Larkin, M.E., Tiktin, M., Wexler, D., Burch, H.B., Bremer, A.A., Lachin, J.M., Bebu, I., Butera, N., Buys, C.J., Fagan, A., Gao, Y., Gramzinski, M.R., Hall, S.D., Kazemi, E., Legowski, E., Liu, H., Suratt, C., Tripputi, M., Arey, A., Backman, M., Bethepu, J., Lund, C., Mangat Dhaliwal, P., McGee, P., Mesimer, E., Ngo, L., Steffes, M., Seegmiller, J., Saenger, A., Arends, V., Gabrielson, D., Conner, T., Warren, S., Day, J., Huminik, J., Soliman, E.Z., Zhang, Z.M., Campbell, C., Hu, J., Keasler, L., Hensley, S., Li, Y., Herman, W.H., Kuo, S., Martin, C., Waltje, A., Mihalcea, R., Min, D.J., Perez-Rosas, V., Prosser, L., Resnicow, K., Ye, W., Shao, H., Zhang, P., Luchsinger, J., Sanchez, D., Assuras, S., Groessl, E., Sakha, F., Chong, H., Hillery, N., Abdouch, I., Bahtiyar, G., Brantley, P., Broyles, F.E., Canaris, G., Copeland, P., Craine, J.J., Fein, W.L., Gliwa, A., Hope, L., Lee, M.S., Meiners, R., Meiners, V., O’Neal, H., Park, J.E., Sacerdote, A., Sledge Jr, E., Soni, L., Steppel-Reznik, J., and Turchin, A.

Published
2024
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12. Recent advances and future perspectives of single-photon avalanche diodes for quantum photonics applications

Author

Ceccarelli, Francesco, Acconcia, Giulia, Gulinatti, Angelo, Ghioni, Massimo, Rech, Ivan, and Osellame, Roberto

Subjects
Physics - Instrumentation and Detectors, Physics - Applied Physics, Physics - Optics, Quantum Physics
Abstract

Photonic quantum technologies promise a revolution of the world of information processing, from simulation and computing to communication and sensing, thanks to the many advantages of exploiting single photons as quantum information carriers. In this scenario, single-photon detectors play a key role. On the one hand, superconducting nanowire single-photon detectors (SNSPDs) are able to provide remarkable performance on a broad spectral range, but their applicability is often limited by the need of cryogenic operating temperatures. On the other hand, single-photon avalanche diodes (SPADs) overcome the intrinsic limitations of SNSPDs by providing a valid alternative at room temperature or slightly below. In this paper, we review the fundamental principles of the SPAD operation and we provide a thorough discussion of the recent progress made in this field, comparing the performance of these devices with the requirements of the quantum photonics applications. In the end, we conclude with our vision of the future by summarizing prospects and unbeaten paths that can open new perspectives in the field of photonic quantum information processing.

Published
2020
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13. Custom silicon technology for SPAD-arrays with red-enhanced sensitivity and low timing jitter

Author

Gulinatti, Angelo, Ceccarelli, Francesco, Ghioni, Massimo, and Rech, Ivan

Subjects
Physics - Instrumentation and Detectors
Abstract

Single-photon detection is an invaluable tool for many applications ranging from basic research to consumer electronics. In this respect, the Single Photon Avalanche Diode (SPAD) plays a key role in enabling a broad diffusion of these techniques thanks to its remarkable performance, room-temperature operation, and scalability. In this paper we present a silicon technology that allows the fabrication of SPAD-arrays with an unprecedented combination of low timing jitter (95 ps FWHM) and high detection efficiency at red and near infrared wavelengths (peak of 70% at 650 nm, 45% at 800 nm). We discuss the device structure, the fabrication process, and we present a thorough experimental characterization of the fabricated detectors. We think that these long-awaited results can pave the way to new exciting developments in many fields, ranging from quantum optics to single molecule spectroscopy

Published
2020
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15. Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness

Author

Battistini, C, Kenny, H, Zambuto, M, Nieddu, V, Melocchi, V, Decio, A, Lo Riso, P, Villa, C, Gatto, A, Ghioni, M, Porta, F, Testa, G, Giavazzi, R, Colombo, N, Bianchi, F, Lengyel, E, Cavallaro, U, Battistini C., Kenny H. A., Zambuto M., Nieddu V., Melocchi V., Decio A., Lo Riso P., Villa C. E., Gatto A., Ghioni M., Porta F. M., Testa G., Giavazzi R., Colombo N., Bianchi F., Lengyel E., Cavallaro U., Battistini, C, Kenny, H, Zambuto, M, Nieddu, V, Melocchi, V, Decio, A, Lo Riso, P, Villa, C, Gatto, A, Ghioni, M, Porta, F, Testa, G, Giavazzi, R, Colombo, N, Bianchi, F, Lengyel, E, Cavallaro, U, Battistini C., Kenny H. A., Zambuto M., Nieddu V., Melocchi V., Decio A., Lo Riso P., Villa C. E., Gatto A., Ghioni M., Porta F. M., Testa G., Giavazzi R., Colombo N., Bianchi F., Lengyel E., and Cavallaro U.

Abstract

In ovarian tumors, the omental microenvironment profoundly influences the behavior of cancer cells and sustains the acquisition of stem-like traits, with major impacts on tumor aggressiveness and relapse. Here, we leverage a patient-derived platform of organotypic cultures to study the crosstalk between the tumor microenvironment and ovarian cancer stem cells. We discovered that the pro-tumorigenic transcription factor FOXM1 is specifically induced by the microenvironment in ovarian cancer stem cells, through activation of FAK/YAP signaling. The microenvironment-induced FOXM1 sustains stemness, and its inactivation reduces cancer stem cells survival in the omental niche and enhances their response to the PARP inhibitor Olaparib. By unveiling the novel role of FOXM1 in ovarian cancer stemness, our findings highlight patient-derived organotypic co-cultures as a powerful tool to capture clinically relevant mechanisms of the microenvironment/cancer stem cells crosstalk, contributing to the identification of tumor vulnerabilities.

Published
2024

19. The Somigliana’s Double Dislocation Method for the Calculation of the Live Loads Collapse Multiplier of Masonry Arch Bridges

Author

Stagnitto, Giuseppe, Siccardi, Roberto, Ghioni, Massimiliano, di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Pellegrino, Carlo, editor, Faleschini, Flora, editor, Zanini, Mariano Angelo, editor, Matos, José C., editor, Casas, Joan R., editor, and Strauss, Alfred, editor

Published
2022
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20. Optical crosstalk in SPAD arrays for high-throughput single-molecule fluorescence spectroscopy

Author

Ingargiola, Antonino, Segal, Maya, Gulinatti, Angelo, Rech, Ivan, Labanca, Ivan, Maccagnani, Piera, Ghioni, Massimo, Weiss, Shimon, and Michalet, Xavier

Subjects
Nuclear and Plasma Physics, Physical Sciences, Biotechnology, SPAD array, Optical crosstalk, Single-molecule, Fluorescence, Spectroscopy, Astronomical and Space Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Other Physical Sciences, Nuclear & Particles Physics, Nuclear and plasma physics
Abstract

Single-molecule fluorescence spectroscopy (SMFS), based on the detection of individual molecules freely diffusing through the excitation spot of a confocal microscope, has allowed unprecedented insights into biological processes at the molecular level, but suffers from limited throughput. We have recently introduced a multispot version of SMFS, which allows achieving high-throughput SMFS by virtue of parallelization, and relies on custom silicon single-photon avalanche diode (SPAD) detector arrays. Here, we examine the premise of this parallelization approach, which is that data acquired from different spots is uncorrelated. In particular, we measure the optical crosstalk characteristics of the two 48-pixel SPAD arrays used in our recent SMFS studies, and demonstrate that it is negligible (crosstalk probability ≤ 1.1 10-3) and undetectable in cross-correlation analysis of actual single-molecule fluorescence data.

Published
2018

21. Higher burden of cardiometabolic and socioeconomic risk factors in women with type 2 diabetes: an analysis of the Glycemic Reduction Approaches in Diabetes (GRADE) baseline cohort

Author

C Wright, C Sanders, C Wilson, L Tucker, S Jones, S Douglass, C Patel, A Kumar, S Smith, A Ghosh, C Adams, R Hill, D Martin, J Hu, M Lee, N Patel, O Smith, J Cook, J Day, M Jackson, G Riera, P McGee, J Park, J Jiménez, S Yang, A Carlson, C Martin, H Liu, Y Li, A Krol, K Wright, S Golden, A Sood, J Martinez, D Sanchez, K Burton, Y Gao, S Martin, O Sanchez, C DeSouza, M Johnson, L Estrada, A Jackson, J Higgins, K Martin, J Craig, A Kuhn, L Ngo, Deborah J Wexler, R Chatterjee, E Walker, J Kerr, W Taylor, J Lim, M Perez, R Henry, Vanita R Aroda, R Fraser, Cyrus Desouza, E King, C Campbell, J González, E Diaz, P Zhang, J Marks, S Abraham, A Ross, M Khalid, T Young, J Myers, J Barzilay, B Chambers, G Montes, C Jensen, J McConnell, R Nelson, L Prosser, S Morton, M Curtis, P Wilson, L Young, M Fürst, S Warren, C Newman, S Kuo, N Rasouli, A Werner, L Morton, A Ghazi, M Salam, F Ismail-Beigi, P Kringas, C Baker, E Ellis, A Cherian, L Holloway, M Madden, B Hollis, G Fuller, B Steiner, K Stokes, R Ayala, T Lowe, K Chu, S Durán, D Dyer, A Alfred, J Leger, Nicole M Butera, T Hamilton, J Costello, E Burgess, R Garg, A Maxwell, C Stevens, W Ye, T Tran, L Fischer, M Hurtado, H Schneier, C Lund, R Lorch, M Mullen, J Bantle, K Arnold, D Wexler, A TURCHIN, MS Lee, D Howard, J Tejada, S Hernandez, Tasma Harindhanavudhi, E Schroeder, K Pham, S Kunkel, A Fagan, G Lord, H CHONG, A Smiley, E Debnam, H Petrovitch, M Bäckman, B Kauffman, V Jenkins, B Cramer, JP Crandall, MD McKee, S Behringer-Massera, J Brown-Friday, E Xhori, K Ballentine-Cargill, H Estrella, S Gonzalez de la torre, J Lukin, LS Phillips, D Olson, M Rhee, TS Raines, J Boers, C Gullett, M Maher-Albertelli, R Mungara, L Savoye, CA White, F Morehead, S Person, M Sibymon, S Tanukonda, A Balasubramanyam, R Gaba, P Hollander, E Roe, P Burt, K Chionh, C Falck-Ytter, L Sayyed Kassem, M Tiktin, T Kulow, KA Stancil, J Iacoboni, MV Kononets, L Colosimo, R Goland, J Pring, L Alfano, C Hausheer, K Gumpel, A Kirpitch, JB Green, H AbouAssi, MN Feinglos, J English Jones, RP Zimmer, BM Satterwhite, K Evans Kreider, CR Thacker, CN Mariash, KJ Mather, A Lteif, V Pirics, D Aguillar, S Hurt, R Bergenstal, T Martens, J Hyatt, H Willis, W Konerza, K Kleeberger, R Passi, S Fortmann, M Herson, K Mularski, H Glauber, J Prihoda, B Ash, C Carlson, PA Ramey, E Schield, B Torgrimson-Ojerio, E Panos, S Sahnow, K Bays, K Berame, D Ghioni, J Gluth, K Schell, J Criscola, C Friason, S Nazarov, N Rassouli, R Puttnam, B Ojoawo, C Sanders-Jones, Z El-Haqq, A Kolli, J Meigs, A Dushkin, G Rocchio, M Yepes, H Dulin, M Cayford, A DeManbey, M Hillard, N Thangthaeng, L Gurry, R Kochis, E Raymond, V Ripley, V Aroda, A Loveland, M Hamm, HJ Florez, WM Valencia, S Casula, L Oropesa-Gonzalez, L Hue, AK Riccio Veliz, R Nieto-Martinez, M Gutt, A Ahmann, D Aby-Daniel, F Joarder, V Morimoto, C Sprague, D Yamashita, N Cady, N Rivera-Eschright, P Kirchhoff, B Morales Gomez, J Adducci, A Goncharova, SH Hox, M Matwichyna, NO Bermudez, L Broadwater, RR Ishii, DS Hsia, WT Cefalu, FL Greenway, C Waguespack, N Haynes, A Thomassie, B Bourgeois, C Hazlett, S Mudaliar, S Boeder, J Pettus, D Garcia-Acosta, S Maggs, C DeLue, E Castro, J Krakoff, JM Curtis, T Killean, E Joshevama, K Tsingine, T Karshner, J Albu, FX Pi-Sunyer, S Frances, C Maggio, J Bastawrose, X Gong, MA Banerji, D Lorber, NM Brown, DH Josephson, LL Thomas, M Tsovian, MH Jacobson, MM Mishko, MS Kirkman, JB Buse, J Dostou, K Bergamo, A Goley, JF Largay, S Guarda, J Cuffee, D Culmer, H Almeida, S Coffer, L Kiker, K Josey, WT Garvey, A Agne, S McCullars, RM Cohen, MC Rogge, K Kersey, S Lipp, MB Vonder Meulen, C Underkofler, S Steiner, E Cline, WH Herman, R Pop-Busui, MH Tan, A Waltje, A Katona, L Goodhall, R Eggleston, K Whitley, S Bule, N Kessler, E LaSalle, ER Seaquist, A Bantle, T Harindhanavudhi, B Redmon, M Coe, M Mech, A Taddese, L Lesne, L Kuechenmeister, V Shivaswamy, AL Morales, K Seipel, J Eggert, R Tillson, DS Schade, A Adolphe, M Burge, E Duran-Valdez, P August, MG Rodriguez, O Griffith, A Naik, Barbara I Gulanski, Heidi Krause-Steinrauf, Judith H Lichtman, Jennifer B Green, Colleen E Suratt, Hiba AbouAssi, Andrew J Ahmann, E Gonzalez Hattery, A Ideozu, G McPhee, SA Khan, JB Kimpel, HM Ismail, ME Larkin, M Magee, A Ressing, L Manandhar, F Mwicigi, V Lagari-Libhaber, A Cuadot, YJ Kendal, B Veciana, G Fry, A Dragg, B Gildersleeve, J Arceneaux, M Pavlionis, A Stallings, S Machineni, AL Cherrington, MCR Lawson, C Adkins, T Onadeko, M Razzaghi, C Lyon, R Penaloza, WI Sivitz, LK Knosp, S Bojescu, S Burbach, A Bancroft, FA Jamaleddin Ahmad, D Hernandez McGinnis, B Pucchetti, E Scripsick, A Zamorano, RA DeFronzo, E Cersosimo, M Abdul-Ghani, C Triplitt, D Juarez, RI Garza, H Verastiqui, C Puckett, P Raskin, C Rhee, LF Jordan, S Sao, L Osornio Walker, L Schnurr-Breen, RB Kreymer, D Sturgess, KM Utzschneider, SE Kahn, L Alarcon-Casas Wright, EJ Boyko, EC Tsai, DL Trence, S Trikudanathan, BN Fattaleh, BK Montgomery, KM Atkinson, A Kozedub, T Concepcion, C Moak, N Prikhodko, S Rhothisen, TA Elasy, L Shackelford, R Goidel, N Hinkle, C Lovell, J Lipps Hogan, JB McGill, T Schweiger, S Kissel, C Recklein, MJ Clifton, W Tamborlane, A Camp, B Gulanski, SE Inzucchi, M Alguard, P Gatcomb, K Lessard, L Iannone, A Montosa, E Magenheimer, J Fradkin, HB Burch, AA Bremer, DM Nathan, JM Lachin, H Krause-Steinrauf, N Younes, I Bebu, N Butera, CJ Buys, MR Gramzinski, SD Hall, E Kazemi, E Legowski, C Suratt, M Tripputi, A Arey, J Bethepu, P Mangat Dhaliwal, E Mesimer, M Steffes, J Seegmiller, A Saenger, V Arends, D Gabrielson, T Conner, J Huminik, A Scrymgeour, EZ Soliman, Y Pokharel, ZM Zhang, L Keasler, S Hensley, R Mihalcea, DJ Min, V Perez-Rosas, K Resnicow, H Shao, J Luchsinger, S Assuras, E Groessl, F Sakha, N Hillery, BM Everett, I Abdouch, G Bahtiyar, P Brantley, FE Broyles, G Canaris, P Copeland, JJ Craine, WL Fein, A Gliwa, L Hope, R Meiners, V Meiners, H O’Neal, JE Park, A Sacerdote, E Sledge, L Soni, J Steppel-Reznik, B Brooks-Worrell, CS Hampe, JP Palmer, A Shojaie, L Doner Lotenberg, JM Gallivan, and DM Tuncer

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

Published
2023
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22. Human Papillomavirus Genotype Richness and the Biodiversity of Squamous and Glandular Cervical Dysplasias: A Cross-Sectional Study

Author

Elisa Gozzini, Davide Radice, Fabio Bottari, Sara Boveri, Maria Elena Guerrieri, Eleonora Petra Preti, Noemi Spolti, Mariacristina Ghioni, Federico Ferrari, and Anna Daniela Iacobone

Subjects
human papillomavirus (HPV), multiple infections, HPV genotype richness, biodiversity, cervical dysplasia, squamous lesions, Medicine
Abstract

The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of precancerous lesions. We conducted a cross-sectional analysis involving 469 women who attended the Colposcopy Unit at the European Institute of Oncology in Milan, Italy, from December 2006 to December 2014. HPV type richness was measured as the number of different genotypes per patient. We calculated the associations between richness and age, as well as histologic grade, along with Simpson’s biodiversity index for cervical dysplasias. We observed significant inverse relationships between the richness of high-risk (HR) genotypes and both age (p = 0.007) and histologic grade (p < 0.001). Furthermore, as the histologic grade increased, the mean biodiversity index of cervical dysplasias decreased, with exceptions noted in cases of normal histology and adenocarcinoma in situ. Different histologic grades formed five clusters with distinct mean ages and mean biodiversity indices. These findings suggest that HPV genotype richness and the biodiversity of cervical dysplasias may play a crucial role in predicting the risk of high-grade cervical lesions, enabling personalized management of precancers.

Published
2023
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25. 48-spot single-molecule FRET setup with periodic acceptor excitation

Author

Ingargiola, Antonino, Segal, Maya, Gulinatti, Angelo, Rech, Ivan, Labanca, Ivan, Maccagnani, Piera, Ghioni, Massimo, Weiss, Shimon, and Michalet, Xavier

Subjects
Physical Sciences, Chemical Sciences, Physical Chemistry, Genetics, DNA, Fluorescence Resonance Energy Transfer, Fluorescent Dyes, Kinetics, Time Factors, Engineering, Chemical Physics, Chemical sciences, Physical sciences
Abstract

Single-molecule Förster resonance energy transfer (smFRET) allows measuring distances between donor and acceptor fluorophores on the 3-10 nm range. Solution-based smFRET allows measurement of binding-unbinding events or conformational changes of dye-labeled biomolecules without ensemble averaging and free from surface perturbations. When employing dual (or multi) laser excitation, smFRET allows resolving the number of fluorescent labels on each molecule, greatly enhancing the ability to study heterogeneous samples. A major drawback to solution-based smFRET is the low throughput, which renders repetitive measurements expensive and hinders the ability to study kinetic phenomena in real-time. Here we demonstrate a high-throughput smFRET system that multiplexes acquisition by using 48 excitation spots and two 48-pixel single-photon avalanche diode array detectors. The system employs two excitation lasers allowing separation of species with one or two active fluorophores. The performance of the system is demonstrated on a set of doubly labeled double-stranded DNA oligonucleotides with different distances between donor and acceptor dyes along the DNA duplex. We show that the acquisition time for accurate subpopulation identification is reduced from several minutes to seconds, opening the way to high-throughput screening applications and real-time kinetics studies of enzymatic reactions such as DNA transcription by bacterial RNA polymerase.

Published
2018

28. Optical crosstalk in SPAD arrays for high-throughput single-molecule fluorescence spectroscopy

Author

Ingargiola, Antonino, Segal, Maya, Gulinatti, Angelo, Rech, Ivan, Labanca, Ivan, Maccagnani, Piera, Ghioni, Massimo, Weiss, Shimon, and Michalet, Xavier

Abstract

Single-molecule fluorescence spectroscopy (SMFS), based on the detection of individual molecules freely diffusing through the excitation spot of a confocal microscope, has allowed unprecedented insights into biological processes at the molecular level, but suffers from limited throughput. We have recently introduced a multispot version of SMFS, which allows achieving high-throughput SMFS by virtue of parallelization, and relies on custom silicon single-photon avalanche diode (SPAD) detector arrays. Here, we examine the premise of this parallelization approach, which is that data acquired from different spots is uncorrelated. In particular, we measure the optical crosstalk characteristics of the two 48-SPAD arrays used in our recent SMFS studies, and demonstrate that it is negligible (crosstalk probability ≤ 1.1 10 −3 ) and is undetectable in cross-correlation analysis of actual single-molecule fluorescence data.

Published
2017

29. 48-spot single-molecule FRET setup with periodic acceptor excitation

Author

Ingargiola, Antonino, Segal, Maya, Gulinatti, Angelo, Rech, Ivan, Labanca, Ivan, Maccagnani, Piera, Ghioni, Massimo, Weiss, Shimon, and Michalet, Xavier

Subjects
Genetics
Abstract

Single-molecule FRET (smFRET) allows measuring distances between donor and acceptor fluorophores on the 3-10 nm range. Solution-based smFRET allows measurement of binding-unbinding events or conformational changes of dye-labeled biomolecules without ensemble averaging and free from surface perturbations. When employing dual (or multi) laser exci-tation, smFRET allows resolving the number of fluorescent labels on each molecule, greatly enhancing the ability to study heterogeneous samples. A major drawback to solution-based smFRET is the low throughput, which renders repetitive measurements expensive and hin-ders the ability to study kinetic phenomena in real-time. Here we demonstrate a high-throughput smFRET system which multiplexes acquisition by using 48 excitation spots and two 48-pixel SPAD array detectors. The system employs two excitation lasers allowing separation of species with one or two active fluorophores. The performance of the system is demonstrated on a set of doubly-labeled double-stranded DNA oligonucleotides with different distances between donor and acceptor dyes along the DNA duplex. We show that the acquisition time for accurate subpopulation identification is reduced from several minutes to seconds, opening the way to high-throughput screening applications and real-time kinetics studies of enzymatic reactions such as DNA transcription by bacterial RNA polymerase.

Published
2017

30. 16ch time-resolved single-molecule spectroscopy using line excitation

Author

Ingargiola, Antonino, Peronio, Pietro, Lerner, Eitan, Gulinatti, Angelo, Rech, Ivan, Ghioni, Massimo, Weiss, Shimon, and Michalet, Xavier

Subjects
Atomic, Molecular and Optical Physics, Physical Sciences, single-molecule, fluorescence, high-throughput, TCSPC, SPAD array, Communications engineering, Electronics, sensors and digital hardware, Atomic, molecular and optical physics
Abstract

Single-molecule spectroscopy on freely-diffusing molecules allows detecting conformational changes of biomolecules without perturbation from surface immobilization. Resolving fluorescence lifetimes increases the sensitivity in detecting conformational changes and overcomes artifacts common in intensity-based measurements. Common to all freely-diffusing techniques, however, are the long acquisition times. We report a time-resolved multispot system employing a 16-channel SPAD array and TCSPC electronics, which overcomes the throughput issue. Excitation is obtained by shaping a 532 nm pulsed laser into a line, matching the linear SPAD array geometry. We show that the line-excitation is a robust and cost-effective approach to implement multispot systems based on linear detector arrays.

Published
2017

31. Multispot single-molecule FRET: High-throughput analysis of freely diffusing molecules

Author

Ingargiola, Antonino, Lerner, Eitan, Chung, SangYoon, Panzeri, Francesco, Gulinatti, Angelo, Rech, Ivan, Ghioni, Massimo, Weiss, Shimon, and Michalet, Xavier

Subjects
Analytical Chemistry, Chemical Sciences, Physical Sciences, Genetics, DNA, DNA-Directed RNA Polymerases, Diffusion, Equipment Design, Escherichia coli, High-Throughput Screening Assays, Kinetics, Lasers, Microscopy, Microscopy, Confocal, Promoter Regions, Genetic, Spectrometry, Fluorescence, Transcription, Genetic, General Science & Technology
Abstract

We describe an 8-spot confocal setup for high-throughput smFRET assays and illustrate its performance with two characteristic experiments. First, measurements on a series of freely diffusing doubly-labeled dsDNA samples allow us to demonstrate that data acquired in multiple spots in parallel can be properly corrected and result in measured sample characteristics consistent with those obtained with a standard single-spot setup. We then take advantage of the higher throughput provided by parallel acquisition to address an outstanding question about the kinetics of the initial steps of bacterial RNA transcription. Our real-time kinetic analysis of promoter escape by bacterial RNA polymerase confirms results obtained by a more indirect route, shedding additional light on the initial steps of transcription. Finally, we discuss the advantages of our multispot setup, while pointing potential limitations of the current single laser excitation design, as well as analysis challenges and their solutions.

Published
2017

32. 16-Ch Time-resolved Single-Molecule Spectroscopy Using Line Excitation.

Author

Ingargiola, Antonino, Peronio, Pietro, Lerner, Eitan, Gulinatti, Angelo, Rech, Ivan, Ghioni, Massimo, Weiss, Shimon, and Michalet, Xavier

Subjects
SPAD array, TCSPC, fluorescence, high-throughput, single-molecule, Bioengineering
Abstract

Single-molecule spectroscopy on freely-diffusing molecules allows detecting conformational changes of biomolecules without perturbation from surface immobilization. Resolving fluorescence lifetimes increases the sensitivity in detecting conformational changes and overcomes artifacts common in intensity-based measurements. Common to all freely-diffusing techniques, however, are the long acquisition times. We report a time-resolved multispot system employing a 16-channel SPAD array and TCSPC electronics, which overcomes the throughput issue. Excitation is obtained by shaping a 532 nm pulsed laser into a line, matching the linear SPAD array geometry. We show that the line-excitation is a robust and cost-effective approach to implement multispot systems based on linear detector arrays.

Published
2017

33. Hybrid Resonant Switched Tank Converters for High Step-Down Voltage Conversion

Author

Dago, Alessandro, Balutto, Mattia, Saggini, Stefano, Leoncini, Mauro, Levantino, Salvatore, and Ghioni, Massimo

Abstract

In this article, we propose a new family of modular hybrid resonant switched tank converters (HRSTC) to perform high fixed-ratio 48 V-to-intermediate bus voltage down-conversion in data center applications. These topologies exploit a modular approach to address the challenge of achieving compact and efficient high voltage conversion ratio in a configurable way. The HRSTC leverages the use of a multitapped autotransformer (MTA) to enhance the conversion ratio of the switched-capacitor converter structure. In addition, using the residual energy of the MTA leakage and magnetizing inductances, quasi-zero current switching and zero voltage switching commutation is achieved. After introducing, deriving, and analyzing the HRSTC structures, we present a prototype converter for 48-to-3.4 V nominal voltage conversion at 260 A maximum output current. The developed prototype achieves a peak efficiency of 96.6 % and a power density of 920 W/inch3. This prototype validates the expected operation and performance of the HRSTC.

Published
2024
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37. Multispot single-molecule FRET: high-throughput analysis of freely diffusing molecules

Author

Ingargiola, A, Lerner, E, Chung, S, Panzeri, F, Gulinatti, A, Rech, I, Ghioni, M, Weiss, S, and Michalet, X

Subjects
Genetics
Abstract

We describe an 8-spot confocal setup for high-throughput smFRET assays and illustrate its performance with two characteristic experiments. First, measurements on a series of freely diffusing doubly-labeled dsDNA samples allow us to demonstrate that data acquired in multiple spots in parallel can be properly corrected and result in measured sample characteristics identical to those obtained with a standard single-spot setup. We then take advantage of the higher throughput provided by parallel acquisition to address an outstanding question about the kinetics of the initial steps of bacterial RNA transcription. Our real-time kinetic analysis of promoter escape by bacterial RNA polymerase confirms results obtained by a more indirect route, shedding additional light on the initial steps of transcription. Finally, we discuss the advantages of our multispot setup, while pointing potential limitations of the current single laser excitation design, as well as analysis challenges and their solutions.

Published
2016

38. Expression of tumor-associated antigens in breast cancer subtypes

Author

Giuseppe Curigliano, Vincenzo Bagnardi, Mariacristina Ghioni, Jamila Louahed, Vincent Brichard, Frederic F. Lehmann, Antonio Marra, Dario Trapani, Carmen Criscitiello, and Giuseppe Viale

Subjects
Tumor-associated antigens, Cancer testis antigens, Breast cancer, WT1, PRAME, NY-ESO-1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objectives: Tumor-associated antigens (TAAs) are frequently overexpressed in several cancer types. The aim of this study was to investigate the expression of TAAs in breast cancer. Material and methods: A total of 250 selected invasive breast cancers including 50 estrogen receptor (ER)-positive (Luminal B like), 50 triple-negative (TN), 50 ER-positive lobular type, 50 ER- and progesterone receptor (PgR)-positive (Luminal A like) and 50 cerbB2-positive breast cancers, were assessed for New York esophageal squamous cell carcinoma-1 (NY-ESO-1), Wilms tumor antigen (WT-1) and PReferentially expressed Antigen of MElanoma (PRAME) antigen expression by immunohistochemistry (IHC). Results: A significantly higher expression of cancer testis (CT)-antigens NY-ESO-1 and WT-1 antigen was detected in TN breast cancers compared with ER-positive tumors. NY-ESO-1 overexpression (score 2 + and 3+) assessed by monoclonal and polyclonal antibodies was detected in 9 (18%) TN cancers as compared to 2 (4%) ER-positive tumors (p = 0.002). WT1 over-expression (score 2 + and 3+) was confirmed in 27 (54%) TN tumor samples as compared to 6 (12%) ER-positive (p

Published
2020
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39. Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget’s Disease of the Vulva: A Referral Center Experience

Author

Anna Daniela Iacobone, Maria Elena Guerrieri, Eleonora Petra Preti, Noemi Spolti, Gianluigi Radici, Giulia Peveri, Vincenzo Bagnardi, Giulio Tosti, Angelo Maggioni, Fabio Bottari, Chiara Scacchi, and Mariacristina Ghioni

Subjects
vulvar extramammary Paget’s disease (EMPD), cervico-vaginal involvement, atypical glandular cytology, colposcopic-guided biopsy, Paget cells, Medicine (General), R5-920
Abstract

Cervico-vaginal (CV) localization of extra-mammary Paget’s disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5–8.0%) at 5 years, 6.5% (95% CI: 1.9–15.1%) at 10 years and 14.0% (95% CI: 4.8–27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget’s disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up.

Published
2023
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40. Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget’s Disease of the Vulva: A Referral Center Experience

Author

Iacobone, A, Guerrieri, M, Preti, E, Spolti, N, Radici, G, Peveri, G, Bagnardi, V, Tosti, G, Maggioni, A, Bottari, F, Scacchi, C, Ghioni, M, Iacobone A. D., Guerrieri M. E., Preti E. P., Spolti N., Radici G., Peveri G., Bagnardi V., Tosti G., Maggioni A., Bottari F., Scacchi C., Ghioni M., Iacobone, A, Guerrieri, M, Preti, E, Spolti, N, Radici, G, Peveri, G, Bagnardi, V, Tosti, G, Maggioni, A, Bottari, F, Scacchi, C, Ghioni, M, Iacobone A. D., Guerrieri M. E., Preti E. P., Spolti N., Radici G., Peveri G., Bagnardi V., Tosti G., Maggioni A., Bottari F., Scacchi C., and Ghioni M.

Abstract

Cervico-vaginal (CV) localization of extra-mammary Paget’s disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5–8.0%) at 5 years, 6.5% (95% CI: 1.9–15.1%) at 10 years and 14.0% (95% CI: 4.8–27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget’s disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up.

Published
2023

41. An extremely low-noise heralded single-photon source: a breakthrough for quantum technologies

Author

Brida, G., Degiovanni, I. P., Genovese, M., Piacentini, F., Traina, P., Della Frera, A., Tosi, A., Shehata, A. Bahgat, Scarcella, C., Gulinatti, A., Ghioni, M., Polyakov, S. V., Migdall, A., and Giudice, A.

Subjects
Quantum Physics
Abstract

Low noise single-photon sources are a critical element for quantum technologies. We present a heralded single-photon source with an extremely low level of residual background photons, by implementing low-jitter detectors and electronics and a fast custom-made pulse generator controlling an optical shutter (a LiNbO3 waveguide optical switch) on the output of the source. This source has a second-order autocorrelation g^{(2)}(0)=0.005(7), and an "Output Noise Factor" (defined as the ratio of the number of noise photons to total photons at the source output channel) of 0.25(1)%. These are the best performance characteristics reported to date.

Published
2013
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42. Shape of the OGTT glucose response curve: relationship with β-cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin

Author

C Wright, C Sanders, C Wilson, L Tucker, S Jones, S Douglass, C Patel, A Kumar, S Smith, C Adams, R Hill, D Martin, M Lee, J Cook, M Jackson, G Riera, E González, J Park, S Yang, A Carlson, C Martin, A Krol, A Sood, J Martinez, C DeSouza, M Johnson, L Estrada, A Jackson, K Martin, SA Khan, J Craig, A Kuhn, Deborah J Wexler, R Chatterjee, J Kerr, W Taylor, R Henry, R Fraser, Kieren J Mather, M Larkin, E King, E Diaz, J Marks, A Ross, M Khalid, J Barzilay, B Chambers, G Montes, C Jensen, J McConnell, R Nelson, S Morton, M Curtis, P Wilson, L Young, M Fürst, C Newman, S Kuo, N Rasouli, A Werner, A Ghazi, F Ismail-Beigi, P Kringas, C Baker, E Ellis, Philip Raskin, A Cherian, L Holloway, M Madden, B Hollis, G Fuller, B Steiner, K Stokes, T Lowe, K Chu, S Durán, A Alfred, John M Lachin, T Hamilton, J Costello, E Burgess, R Garg, C Stevens, T Tran, M Hurtado, H Schneier, R Lorch, M Mullen, J Bantle, K Arnold, D Wexler, Neda Rasouli, D Howard, J Tejada, S Hernandez, E Schroeder, S Kunkel, G Lord, A Smiley, E Debnam, H Petrovitch, B Kauffman, V Jenkins, B Cramer, Kristina M Utzschneider, Naji Younes, Joshua I Barzilay, Mary Ann Banerji, Robert M Cohen, Erica V Gonzalez, Faramarz Ismail-Beigi, Steven E Kahn, JP Crandall, MD McKee, S Behringer-Massera, J Brown-Friday, E Xhori, K Ballentine-Cargill, H Estrella, S Gonzalez de la torre, J Lukin, LS Phillips, D Olson, M Rhee, TS Raines, J Boers, C Gullett, M Maher-Albertelli, R Mungara, L Savoye, CA White, F Morehead, S Person, M Sibymon, S Tanukonda, A Balasubramanyam, R Gaba, P Hollander, E Roe, P Burt, K Chionh, C Falck-Ytter, L Sayyed Kassem, M Tiktin, T Kulow, KA Stancil, J Iacoboni, MV Kononets, G McPhee AMaxwell, L Colosimo, R Goland, J Pring, L Alfano, C Hausheer, K Gumpel, A Kirpitch, JB Green, H AbouAssi, MN Feinglos, J English Jones, RP Zimmer, BM Satterwhite, K Evans Kreider, CR Thacker, CN Mariash, KJ Mather, A Lteif, V Pirics, D Aguillar, S Hurt, R Bergenstal, T Martens, J Hyatt, H Willis, W Konerza, K Kleeberger, R Passi, S Fortmann, M Herson, K Mularski, H Glauber, J Prihoda, B Ash, C Carlson, PA Ramey, E Schield, B Torgrimson-Ojerio, E Panos, S Sahnow, K Bays, K Berame, D Ghioni, J Gluth, K Schell, J Criscola, C Friason, S Nazarov, N Rassouli, R Puttnam, B Ojoawo, C Sanders-Jones, Z El-Haqq, A Kolli, J Meigs, A Dushkin, G Rocchio, M Yepes, H Dulin, M Cayford, A DeManbey, M Hillard, N Thangthaeng, L Gurry, R Kochis, E Raymond, V Ripley, V Aroda, Ann Ressing, A Loveland, M Hamm, F Mofor, HJ Florez, WM Valencia, S Casula, L Oropesa-Gonzalez, L Hue, AK Riccio Veliz, R Nieto-Martinez, M Gutt, A Ahmann, D Aby-Daniel, F Joarder, V Morimoto, C Sprague, D Yamashita, N Cady, N Rivera-Eschright, P Kirchhoff, B Morales Gomez, J Adducci, A Goncharova, SH Hox, M Matwichyna, NO Bermudez, L Broadwater, RR Ishii, DS Hsia, WT Cefalu, FL Greenway, C Waguespack, N Haynes, A Thomassie, B Bourgeois, C Hazlett, S Mudaliar, S Boeder, J Pettus, D Garcia-Acosta, S Maggs, C DeLue, E Castro, J Krakoff, JM Curtis, T Killean, E Joshevama, K Tsingine, T Karshner, J Albu, FX Pi-Sunyer, S Frances, C Maggio, J Bastawrose, X Gong, MA Banerji, D Lorber, NM Brown, DH Josephson, LL Thomas, M Tsovian, MH Jacobson, MM Mishko, MS Kirkman, JB Buse, J Dostou, K Bergamo, A Goley, JF Largay, S Guarda, J Cuffee, D Culmer, H Almeida, S Coffer, L Kiker, K Josey, WT Garvey, A Cherrington, D Golson, MC Robertson, A Agne, S McCullars, RM Cohen, MC Rogge, K Kersey, S Lipp, MB Vonder Meulen, C Underkofler, S Steiner, W Sivitz, E Cline, L Knosp, WH Herman, R Pop-Busui, MH Tan, A Waltje, A Katona, L Goodhall, R Eggleston, K Whitley, S Bule, N Kessler, E LaSalle, ER Seaquist, A Bantle, T Harindhanavudhi, B Redmon, M Coe, M Mech, A Taddese, L Lesne, L Kuechenmeister, V Shivaswamy, AL Morales, K Seipel, J Eggert, R Tillson, DS Schade, A Adolphe, M Burge, E Duran-Valdez, P August, MG Rodriguez, JB Kimpel, and O Griffith

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Published
2021
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43. Silicon Photon-Counting Avalanche Diodes for Single-Molecule Fluorescence Spectroscopy

Author

Michalet, Xavier, Ingargiola, Antonino, Colyer, Ryan A, Scalia, Giuseppe, Weiss, Shimon, Maccagnani, Piera, Gulinatti, Angelo, Rech, Ivan, and Ghioni, Massimo

Subjects
Bioengineering, Single-molecule, Fluorescence, FRET, FCS, single-photon avalanche diode, detector array, Single-photon avalanche diode, Optical Physics, Quantum Physics, Electrical and Electronic Engineering, Optoelectronics & Photonics
Abstract

Solution-based single-molecule fluorescence spectroscopy is a powerful experimental tool with applications in cell biology, biochemistry and biophysics. The basic feature of this technique is to excite and collect light from a very small volume and work in a low concentration regime resulting in rare burst-like events corresponding to the transit of a single molecule. Detecting photon bursts is a challenging task: the small number of emitted photons in each burst calls for high detector sensitivity. Bursts are very brief, requiring detectors with fast response time and capable of sustaining high count rates. Finally, many bursts need to be accumulated to achieve proper statistical accuracy, resulting in long measurement time unless parallelization strategies are implemented to speed up data acquisition. In this paper we will show that silicon single-photon avalanche diodes (SPADs) best meet the needs of single-molecule detection. We will review the key SPAD parameters and highlight the issues to be addressed in their design, fabrication and operation. After surveying the state-of-the-art SPAD technologies, we will describe our recent progress towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. The potential of this approach is illustrated with single-molecule Förster resonance energy transfer measurements.

Published
2014

50. Pragmatic Meanings Comprehension in Non-Native Argentinian Spanish Speakers

Author

Agustín Arispe, Brenda Steeb, María Carla Ghioni, Florencia Vera Spinelli, and Nicolás Arellano

Subjects
español como lengua segunda y extranjera, pragmática, actos de habla, cortesía, comprensión, español de argentina, Romanic languages, PC1-5498, Language. Linguistic theory. Comparative grammar, P101-410
Abstract

The objective of this research is to make a comprehensive description of the understanding of pragmatic meanings by speakers of Spanish as a second and foreign language. Our hypothesis is that the performance in the understanding of pragmatic contents improves if these are conveyed through a lexical or contextual item, and not grammatical one, or through a non-directive type of speech. The study is carried out through an online survey to 49 non-native Spanish speakers, which consist of 19 scenes that require a mandatory pragmatic interpretation. The statistically analyzed results confirm that performance in non-directive speech acts is better than in directive ones. However, there are no performance differences according to the level (grammatical, contextual or semantic-lexical) at which the pragmatic contents are conveyed. Furthermore, it is observed that Brazilian Portuguese speakers better understand the pragmatics of utterances as a whole and show less difficulties with directive speech acts. Other variables, such as instruction or residence time, do not contribute significantly to improving performance in understanding these statements.

Published
2020

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