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1. On isometries of spectral triples associated to $AF$-algebras and crossed products

Author

Bassi, J. and Conti, R.

Subjects
Mathematics - Operator Algebras, Primary: 46L05, 58B34, Secondary: 46L40
Abstract

We examine the structure of two possible candidates of isometry groups for the spectral triples on $AF$-algebras introduced by Christensen and Ivan. In particular, we completely determine the isometry group introduced by Park, and observe that these groups coincide in the case of the Cantor set. We also show that the construction of spectral triples on crossed products given by Hawkins, Skalski, White and Zacharias, is suitable for the purpose of lifting isometries., Comment: 17 pages. We corrected the formula for the group structure of isometries in the case of the Cantor set (Proposition 3.12 and Postface). Accepted for publication in J. Noncommut. Geom

Published
2023

3. A Mixing Property for the Action of SL(3,ℤ) × SL(3,ℤ) on the Stone–Čech Boundary of SL(3,ℤ).

Author

Bassi, J and Rădulescu, F

Subjects
*MATRIX multiplications, *RADON
Abstract

By analogy with the construction of the Furstenberg boundary, the Stone–Čech boundary of |$\textrm {SL}(3,\mathbb {Z})$| is a fibered space over products of projective matrices. The proximal behaviour on this space is exploited to show that the preimages of certain sequences have accumulation points that belong to specific regions, defined in terms of flags. We show that the |$\textrm {SL}(3,\mathbb {Z})\times \textrm {SL}(3,\mathbb {Z})$| -quasi-invariant Radon measures supported on these regions are tempered. Thus, every quasi-invariant Radon boundary measure for |$\textrm {SL}(3,\mathbb {Z})$| is an orthogonal sum of a tempered measure and a measure having matrix coefficients belonging to a certain ideal |$c^{\prime}_0 ((\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$|⁠ , slightly larger than |$c_0 ((\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$|⁠. Hence, the left–right representation of |$C^*(\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$| in the Calkin algebra of |$\textrm {SL}(3,\mathbb {Z})$| factors through |$C^*_{c^{\prime}_0} (\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$| and the centralizer of every infinite subgroup of |$\textrm {SL}(3,\mathbb {Z})$| is amenable. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
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9. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Author

Collier, D. A., De Marco, A., Ferreira, I. A. T. M., Meng, B., Datir, R. P., Walls, A. C., Kemp, S. A., Bassi, J., Pinto, D., Silacci-Fregni, C., Bianchi, S., Tortorici, M. A., Bowen, J., Culap, K., Jaconi, S., Cameroni, E., Snell, G., Pizzuto, M. S., Pellanda, A. F., Garzoni, C., Riva, A., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Mccoy, L. E., Smith, K. G. C., Bradley, J. R., Temperton, N., Ceron-Gutierrez, L., Barcenas-Morales, G., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Torok, M. E., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., Hosmillo, M., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Betteridge, E., Farr, B. W., Goodwin, S., Quail, M. A., Scott, C., Shirley, L., Thurston, S. A. J., Rajan, D., Bronner, I. F., Aigrain, L., Redshaw, N. M., Lensing, S. V., Mccarthy, S., Makunin, A., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Bonfield, J., Puethe, C., Whitwham, A., Liddle, J., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Abnizova, I., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Quail, M., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Seekings, P., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Van, P. J., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Widaa, S., Williams, M., Wilson, M., Wright, S., Harvey, W., Virgin, H. W., Lanzavecchia, A., Piccoli, L., Doffinger, R., Wills, M., Veesler, D., Corti, D., and Gupta, R. K.

Subjects
0301 basic medicine, Male, Models, Molecular, Passive, Antibodies, Viral, Neutralization, 0302 clinical medicine, Models, Monoclonal, 80 and over, Viral, Neutralizing antibody, Neutralizing, Aged, 80 and over, Vaccines, Vaccines, Synthetic, Multidisciplinary, biology, Antibodies, Monoclonal, C500, Middle Aged, C700, Spike Glycoprotein, Vaccination, Spike Glycoprotein, Coronavirus, Female, Angiotensin-Converting Enzyme 2, Antibody, Aged, Antibodies, Neutralizing, COVID-19, COVID-19 Vaccines, HEK293 Cells, Humans, Immune Evasion, Immunization, Passive, Mutation, Neutralization Tests, SARS-CoV-2, medicine.drug_class, B100, Monoclonal antibody, Antibodies, Virus, 03 medical and health sciences, Immune system, medicine, COVID-19 Serotherapy, QR355, Synthetic, Molecular, Virology, Coronavirus, 030104 developmental biology, Immunization, biology.protein, 030217 neurology & neurosurgery
Abstract

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

Published
2021

10. Broad betacoronavirus neutralization by a stem helix–specific human antibody

Author

Pinto, D, Sauer, MM, Czudnochowski, N, Low, JS, Alejandra Tortorici, M, Housley, MP, Noack, J, Walls, AC, Bowen, JE, Guarino, B, Rosen, LE, di Iulio, J, Jerak, J, Kaiser, H, Islam, S, Jaconi, S, Sprugasci, N, Culap, K, Abdelnabi, R, Foo, C, Coelmont, L, Bartha, I, Bianchi, S, Silacci-Fregni, C, Bassi, J, Marzi, R, Vetti, E, Cassotta, A, Ceschi, A, Ferrari, P, Cippà, PE, Giannini, O, Ceruti, S, Garzoni, C, Riva, A, Benigni, F, Cameroni, E, Piccoli, L, Pizzuto, MS, Smithey, M, Hong, D, Telenti, A, Lempp, FA, Neyts, J, Havenar-Daughton, C, Lanzavecchia, A, Sallusto, F, Snell, G, Virgin, HW, Beltramello, M, Corti, D, Veesler, D, Pinto, D, Sauer, MM, Czudnochowski, N, Low, JS, Alejandra Tortorici, M, Housley, MP, Noack, J, Walls, AC, Bowen, JE, Guarino, B, Rosen, LE, di Iulio, J, Jerak, J, Kaiser, H, Islam, S, Jaconi, S, Sprugasci, N, Culap, K, Abdelnabi, R, Foo, C, Coelmont, L, Bartha, I, Bianchi, S, Silacci-Fregni, C, Bassi, J, Marzi, R, Vetti, E, Cassotta, A, Ceschi, A, Ferrari, P, Cippà, PE, Giannini, O, Ceruti, S, Garzoni, C, Riva, A, Benigni, F, Cameroni, E, Piccoli, L, Pizzuto, MS, Smithey, M, Hong, D, Telenti, A, Lempp, FA, Neyts, J, Havenar-Daughton, C, Lanzavecchia, A, Sallusto, F, Snell, G, Virgin, HW, Beltramello, M, Corti, D, and Veesler, D

Abstract

The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection.

Published
2021

11. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

Author

Thomson, EC, Rosen, LE, Shepherd, JG, Spreafico, R, da Silva Filipe, A, Wojcechowskyj, JA, Davis, C, Piccoli, L, Pascall, DJ, Dillen, J, Lytras, S, Czudnochowski, N, Shah, R, Meury, M, Jesudason, N, De Marco, A, Li, K, Bassi, J, O'Toole, A, Pinto, D, Colquhoun, RM, Culap, K, Jackson, B, Zatta, F, Rambaut, A, Jaconi, S, Sreenu, VB, Nix, J, Zhang, I, Jarrett, RF, Glass, WG, Beltramello, M, Nomikou, K, Pizzuto, M, Tong, L, Cameroni, E, Croll, TI, Johnson, N, Di Iulio, J, Wickenhagen, A, Ceschi, A, Harbison, AM, Mair, D, Ferrari, P, Smollett, K, Sallusto, F, Carmichael, S, Garzoni, C, Nichols, J, Galli, M, Hughes, J, Riva, A, Ho, A, Schiuma, M, Semple, MG, Openshaw, PJM, Fadda, E, Baillie, JK, Chodera, JD, Rihn, SJ, Lycett, SJ, Virgin, HW, Telenti, A, Corti, D, Robertson, DL, Snell, G, Thomson, EC, Rosen, LE, Shepherd, JG, Spreafico, R, da Silva Filipe, A, Wojcechowskyj, JA, Davis, C, Piccoli, L, Pascall, DJ, Dillen, J, Lytras, S, Czudnochowski, N, Shah, R, Meury, M, Jesudason, N, De Marco, A, Li, K, Bassi, J, O'Toole, A, Pinto, D, Colquhoun, RM, Culap, K, Jackson, B, Zatta, F, Rambaut, A, Jaconi, S, Sreenu, VB, Nix, J, Zhang, I, Jarrett, RF, Glass, WG, Beltramello, M, Nomikou, K, Pizzuto, M, Tong, L, Cameroni, E, Croll, TI, Johnson, N, Di Iulio, J, Wickenhagen, A, Ceschi, A, Harbison, AM, Mair, D, Ferrari, P, Smollett, K, Sallusto, F, Carmichael, S, Garzoni, C, Nichols, J, Galli, M, Hughes, J, Riva, A, Ho, A, Schiuma, M, Semple, MG, Openshaw, PJM, Fadda, E, Baillie, JK, Chodera, JD, Rihn, SJ, Lycett, SJ, Virgin, HW, Telenti, A, Corti, D, Robertson, DL, and Snell, G

Abstract

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics. Epidemiological, clinical, molecular, and structural characterization of the N439K mutation in the SARS-CoV-2 spike receptor binding motif demonstrates that it results in similar viral fitness compared to wild-type while conferring resistance against some neutralizing monoclonal antibodies and reducing the activity of some polyclonal antibody responses.

Published
2021

14. Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology

Author

Piccoli, L, Park, YJ, Tortorici, MA, Czudnochowski, N, Walls, AC, Beltramello, M, Silacci-Fregni, C, Pinto, D, Rosen, LE, Bowen, JE, Acton, OJ, Jaconi, S, Guarino, B, Minola, A, Zatta, F, Sprugasci, N, Bassi, J, Peter, A, De Marco, A, Nix, JC, Mele, F, Jovic, S, Rodriguez, BF, Gupta, SV, Jin, F, Piumatti, G, Lo Presti, G, Pellanda, AF, Biggiogero, M, Tarkowski, M, Pizzuto, MS, Cameroni, E, Havenar-Daughton, C, Smithey, M, Hong, D, Lepori, V, Albanese, E, Ceschi, A, Bernasconi, E, Elzi, L, Ferrari, P, Garzoni, C, Riva, A, Snell, G, Sallusto, F, Fink, K, Virgin, HW, Lanzavecchia, A, Corti, D, Veesler, D, Piccoli, L, Park, YJ, Tortorici, MA, Czudnochowski, N, Walls, AC, Beltramello, M, Silacci-Fregni, C, Pinto, D, Rosen, LE, Bowen, JE, Acton, OJ, Jaconi, S, Guarino, B, Minola, A, Zatta, F, Sprugasci, N, Bassi, J, Peter, A, De Marco, A, Nix, JC, Mele, F, Jovic, S, Rodriguez, BF, Gupta, SV, Jin, F, Piumatti, G, Lo Presti, G, Pellanda, AF, Biggiogero, M, Tarkowski, M, Pizzuto, MS, Cameroni, E, Havenar-Daughton, C, Smithey, M, Hong, D, Lepori, V, Albanese, E, Ceschi, A, Bernasconi, E, Elzi, L, Ferrari, P, Garzoni, C, Riva, A, Snell, G, Sallusto, F, Fink, K, Virgin, HW, Lanzavecchia, A, Corti, D, and Veesler, D

Abstract

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.

Published
2020

20. Coronal Mass Ejections and Coronal Structures

Author

Hildner, E., Bassi, J., Bougeret, J. L., Duncan, R. A., Gary, D. E., Gergely, T. E., Harrison, R. A., Howard, R. A., Illing, R. M. E., Jackson, B. V., Kahler, S. W., Kopp, R., Low, B. C., Lantos, P., Phillips, K. J. H., Poletto, G., Sheeley, N. R., Jr., Stewart, R. T., Svestka, Z., Waggett, P. W., Wu, S. T., Kundu, M. R., editor, Woodgate, B., editor, and Schmahl, E. J., editor

Published
1989
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22. Analysis of the results of ipsilateral hip and shaft femur fractures treated with reconstruction nail

Author

Garg Rajnish, Bassi J, and Yamin M

Subjects
musculoskeletal diseases, lcsh:RD701-811, lcsh:Orthopedic surgery, Ipsilateral hip and femur fractures, Reconstruction nail
Abstract

Background : Ipsilateral fractures of hip and shaft femur are a complex problem. High rate of complications are inherent with this injury. To choose from wide variety operative techniques and hardware available makes a life further difficult for an average orthopedic surgeon. Method : We present a series of 25 cases with ipsilateral hip and shaft femur fractures treated by intramedullary reconstruction nail. Intraoperative complications and postoperative results were critically analyzed. Results : Difficulty in reduction was observed in thirteen patients, improper placement of cervical screws in eleven patients and there was postoperative distraction present at fracture site in seven patients. Seven patients had malunion at hip and three at shaft femur. Nonunion was present in three patients with fracture shaft femur and one patient with fracture neck of femur requiring secondary surgical procedures. Conclusion : Though reconstruction nail is a good option for undisplaced or minimally displaced fractures at hip. In patients with marked displacement and comminution at fracture site its results are good only in experienced hands and needs further evaluation. Experience of the surgeon in managing these kinds of complex injuries cannot be over emphasized.

Published
2006

23. Determinación de la Dimensión Vertical Oclusal en desdentados totales: comparación de métodos convencionales con el craneómetro de Knebelman

Author

Quiroga Del Pozo, R, Riquelme Belmar, R, Sierra Fuentes, M, Del Pozo Bassi, J, and Quiroga Aravena, R

Subjects
Knebelman craneometer, cranéometro de Knebelman, Vertical Dimension, Dimensión Vertical
Abstract

Objetivo: Se realizó una investigación cuyo propósito fue comparar la DVO determinada mediante métodos convencionales y la determinada por el craneómetro de Knebelman en el mismo paciente. Método: Se consideró como metodología convencional la DVO medida estando el paciente con sus prótesis en máxima intercuspidación. El estudio se realizo en una muestra de 45 individuos desdentados totales y parciales sin referencia oclusiva, rehabilitados con prótesis removible en la en la Clínica Integral del Adulto I y II. Los resultados fueron analizados empleando el test t pareado expresado en mm. de la DVO determinada con cada metodología. Resultado: Se encontraron diferencias significativas entre ambas mediciones y se empleó el test Chi-Cuadrado para analizar la influencia en la magnitud de la DVO observada cuando se emplea una o más referencias en su determinación, donde no se encontraron diferencias significativas. El rango de diferencias entre ambas metodologías de determinación en promedio fue de 2.93 mm considerado no relevante desde el punto de vista clínico. Conclusión: En este contexto el craneómetro de Knebelman puede ser un valioso instrumento que permita simplificar la determinación de la DVO en pacientes desdentados. Objective: The purpose of this investigation was to compare the OVD obtained with the conventional methods and the one that is obtained with the Knebelman craniometric system in the same patient. Methods: The OVD considered as "conventional" was the one obtained with the patient using his/her dental prosthesis in maximum intercuspidation. This study was made using a sample of 45 edentulous and partially edentulous subjects, all treated with full removable denture and RPD in "Odontologia Integral del Adulto I & II". The results were analyzed using pair comparison system for the different OVD obtained with both methods (all expressed in millimeters). Results: Significant differences were found between both methods. The Chi-Square test to analyze de influence in the OVD when one or more references are used, didn´t show any significant differences. The average discrepancy between the two methods was 2.93 mm, which is considered as not clinically significant. Conclusion: In this context the Knebelman craneometer can be considered as an important instrument to simplify the determination of the OVD in edentulous patients.

Published
2012

24. Adaptación del Sistema Espiga Muñón en Relación a la Preparación del Conducto

Author

Quiroga Del Pozo, J, Ruz Espinoza, P, Sierra Fuentes, M, Del Pozo Bassi, J, and Quiroga Aravena, R

Subjects
Cast post and core, Perno muñón colado, adaptación, ajuste, fit
Abstract

Se realizó un estudio in vitro que tuvo por objetivo medir el grado de adaptación del sistema espiga muñón, debido a que es uno de los factores fundamentales para lograr un buen anclaje de estos artificios, medido a nivel del núcleo de éste con respecto a los planos radiculares y de la espiga a las paredes del conducto, cuando es conformado con fresas Peeso y cuando es conformado usando fresas Peeso terminando con fresas del sistema Mooser. Seleccionamos 40 dientes que se dividieron al azar en dos grupos de 20, denominados P y M, respectivamente. Se confeccionó en cada muestra, previamente tratado su conducto mediante método indirecto, un perno muñón colado que fue probado en la preparación donde se midió el ajuste del muñón propiamente tal, después de logrado el asentamiento adecuado mediante desgastes en las interferencias de la espiga fueron cementados, posteriormente se realizaron dos cortes transversales a todo el espesor de la raíz a diferentes alturas, donde se midió la interfase entre la espiga y las paredes del conducto (adaptación). Los resultados fueron analizados utilizando los test de Mann-Whitney, Tukey y test T pareado, con software Systat versión 11, encontrándose que la mejor adaptación se observa en las muestras del grupo M en los dos sitios observados, comparadas con las del grupo P Estas diferencias son estadísticamente significativas. We carried out a research aumed to determine the adaptation of the system called cast post and core, because it's one of the main factors to achieve a good adaptation of these devices measured from the core of this device to radicular plan, and from the post to the canal protesic's surface, when this one was prepared with Peeso's burs, and when was also prepared starting with Peeso's burs but finishing with Mooser system's burs. For that objective, we selected 40 teeth that were divided randomly into two groups of 20, called P and M respectively. A cast post and core was made in each sample through indirect method, previously treated the protesic canal. The cast post and core was tested in the preparation where the fit of the core was measured. Once achieved the proper settlement through the wearing out of the post's interferences and once the cast post and core was cemented, we made two cross cuttings to the thickness of the root at two differents levels, where the interface between the post and canal protesic's surface was measured (adaptation). The results were analyzed using the Mann-Whithny test, Tukey and paired T test, with Systast software version 11, having found that the best adaptation was observed in the samples of group M at the two points analyzed, compared to group P. These differences are statistically significant.

Published
2010

27. Leptin Mediates the Increase in Blood Pressure Associated with Obesity

Author

Simonds, SE, Pryor, JT, Ravussin, E, Greenway, FL, Dileone, R, Allen, AM, Bassi, J, Elmquist, JK, Keogh, JM, Henning, E, Myers, MG, Licinio, J, Brown, RD, Enriori, PJ, O'Rahilly, S, Sternson, SM, Grove, KL, Spanswick, DC, Farooqi, IS, Cowley, MA, Simonds, SE, Pryor, JT, Ravussin, E, Greenway, FL, Dileone, R, Allen, AM, Bassi, J, Elmquist, JK, Keogh, JM, Henning, E, Myers, MG, Licinio, J, Brown, RD, Enriori, PJ, O'Rahilly, S, Sternson, SM, Grove, KL, Spanswick, DC, Farooqi, IS, and Cowley, MA

Abstract

Obesity is associated with increased blood pressure (BP), which in turn increases the risk of cardiovascular diseases. We found that the increase in leptin levels seen in diet-induced obesity (DIO) drives an increase in BP in rodents, an effect that was not seen in animals deficient in leptin or leptin receptors (LepR). Furthermore, humans with loss-of-function mutations in leptin and the LepR have low BP despite severe obesity. Leptin's effects on BP are mediated by neuronal circuits in the dorsomedial hypothalamus (DMH), as blocking leptin with a specific antibody, antagonist, or inhibition of the activity of LepR-expressing neurons in the DMH caused a rapid reduction of BP in DIO mice, independent of changes in weight. Re-expression of LepRs in the DMH of DIO LepR-deficient mice caused an increase in BP. These studies demonstrate that leptin couples changes in weight to changes in BP in mammalian species.

Published
2014

28. Coronal Mass Ejections and Coronal Structures

Author

Hildner, E., primary, Bassi, J., additional, Bougeret, J. L., additional, Duncan, R. A., additional, Gary, D. E., additional, Gergely, T. E., additional, Harrison, R. A., additional, Howard, R. A., additional, Illing, R. M. E., additional, Jackson, B. V., additional, Kahler, S. W., additional, Kopp, R., additional, Low, B. C., additional, Lantos, P., additional, Phillips, K. J. H., additional, Poletto, G., additional, Sheeley, N. R., additional, Stewart, R. T., additional, Svestka, Z., additional, Waggett, P. W., additional, and Wu, S. T., additional

Published
1989
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36. Coronal mass ejections and coronal structures

Author

Hildner, E, Bassi, J, Bougeret, J. L, Duncan, R. A, Gary, D. E, Gergely, T. E, Harrison, R. A, Howard, R. A, Illing, R. M. E, and Jackson, B. V

Subjects
Solar Physics
Abstract

Research on coronal mass ejections (CMF) took a variety of forms, both observational and theoretical. On the observational side there were: case studies of individual events, in which it was attempted to provide the most complete descriptions possible, using correlative observations in diverse wavelengths; statistical studies of the properties CMEs and their associated activity; observations which may tell us about the initiation of mass ejections; interplanetary observations of associated shocks and energetic particles even observations of CMEs traversing interplanetary space; and the beautiful synoptic charts which show to what degree mass ejections affect the background corona and how rapidly (if at all) the corona recovers its pre-disturbance form. These efforts are described in capsule form with an emphasis on presenting pictures, graphs, and tables so that the reader can form a personal appreciation of the work and its results.

Published
1986

37. Low latitude middle atmosphere ionization studies

Author

Bassi, J. P

Subjects
Geophysics
Abstract

Low latitude middle atmosphere ionization was studied with data obtained from three blunt conductivity probes and one Gerdien condenser. An investigation was conducted into the effects of various ionization sources in the 40 to 65 Km altitude range. An observed enhancement of positive ion conductivity taking place during the night can be explained by an atmsopheric effect, with cosmic rays being the only source of ionization only if the ion-ion recombination coefficient (alpha sub i) is small(10 to the -7 power cu cm/s) and varies greatly with altitude. More generally accepted values of alpha sub i ( approximately equal to 3x10 to the -7 power cu cm/s) require an additional source of ionization peaking at about 65 Km, and corresponding approximately to the integrated effect of an X-ray flux measured on a rocket flown in conjunction with the ionization measurements. The reasonable assumption of an alpha sub i which does not vary with altitude in the 50-70 Km range implies an even greater value alpha sub i and a more intense and harder X-ray spectrum.

Published
1976

38. Regulation of angiotensinogen by angiotensin II in mouse primary astrocyte cultures.

Author

O'Callaghan, E. L., Bassi, J. K., Porrello, E. R., Delbridge, L. M. D., Thomas, W. G., and Allen, A. M.

Subjects
*RENIN-angiotensin system, *HOMEOSTASIS, *LIVER cells, *GENE expression, *G proteins, *CEREBROSPINAL fluid
Abstract

J. Neurochem. (2011) 119, 18-26. Abstract Astrocytes are the major source of angiotensinogen in the brain and play an important role in the brain renin-angiotensin system. Regulating brain angiotensinogen production alters blood pressure and fluid and electrolyte homeostasis. In turn, several physiological and pathological manipulations alter expression of angiotensinogen in brain. Surprisingly, little is known about the factors that regulate astrocytic expression of angiotensinogen. There is evidence that angiotensinogen production in both hepatocytes and cardiac myocytes can be positively regulated via the angiotensin type 1 receptor, but this effect has not yet been studied in astrocytes. Therefore, the aim of this project was to establish whether angiotensin II modulates angiotensinogen production in brain astrocytes. Primary astrocyte cultures, prepared from neonatal C57Bl6 mice, expressed angiotensinogen measured by immunocytochemistry and real-time PCR. Using a variety of approaches we were unable to identify angiotensin receptors on cultured astrocytes. Exposure of cultured astrocytes to angiotensin II also did not affect angiotensinogen expression. When astrocyte cultures were transduced with the angiotensin type 1A receptor, using adenoviral vectors, angiotensin II induced a robust down-regulation (91.4% ± 1.8%, p < 0.01, n = 4) of angiotensinogen gene expression. We conclude that receptors for angiotensin II are present in extremely low levels in astrocytes, and that this concurs with available data in vivo. The signaling pathways activated by the angiotensin type 1A receptor are negatively coupled to angiotensinogen expression and represent a powerful pathway for decreasing expression of this protein, potentially via signaling pathways coupled to Gαq/11. [ABSTRACT FROM AUTHOR]

Published
2011
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39. Central Neural Regulation of Cardiovascular Function by Angiotensin: A Focus on the Rostral Ventrolateral Medulla.

Author

Allen, Andrew M., O'Callaghan, E. L., Chen, D., and Bassi, J. K.

Subjects
ANGIOTENSIN II, BRAIN, ELECTROLYTES, EFFERENT pathways, CARDIOVASCULAR system, BLOOD pressure
Abstract

Angiotensin II acts through specific receptors to alter several brain functions including fluid and electrolyte control, neuroendocrine function and autonomic efferent activity. This review discusses one brain site, the rostral ventrolateral medulla, where the actions of angiotensin II have been intensively studied. The rostral ventrolateral medulla plays a critical role in the generation and regulation of sympathetic activity to the cardiovascular system and hence is important for blood pressure control. Current evidence indicates that angiotensin II activates neurons in the rostral ventrolateral medulla via the AT1A receptor. In some models of cardiovascular disease, blockade of AT1 receptors in the rostral ventrolateral medulla reduces sympathetic nerve activity and blood pressure suggesting that overactivity of the angiotensin system in this nucleus may play a role in the maintenance of high blood pressure. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2009
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42. SHORT NOTES.

Author

Allan, D. G., Tarboton, W. R., Filmer, R. J., Bassi, J., Cyrus, Digby, Marx, Jan T, Stoltz, L. P., Ward, David, Komen, Joris, Martin, A. P., and Martin, J. A.

Published
1988
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43. L'évacuation des blessés au moyen des téléphériques dans la guerre de montagne.

Author

Bassi, J.

Abstract

L'évacuation des blessés, partiqulièrement dans la zone comprise entre la ligne de combat et les hôpitaux de camp de corps d'armée (zone de première évacuation), atteignit, dans le premier conflit, une importance et une gravité nouvelles et imprévues, de sorte que, les premiers temps, les services sanitaires des diverses armées belligérantes se trouvèrent plus ou moins bien préparés. [ABSTRACT FROM PUBLISHER]

Published
1933
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45. Mice with selective angiotensin type 1A receptor deletion from catecholaminergic neurons show altered angiotensin II-dependent hypertension.

Author

Allen, A. M., Jancovski, N., Bassi, J. K., Connelly, A. A., Brandi, J., Stevens, E. A., and Head, G. A.

Subjects
ANGIOTENSIN II, SYMPATHETIC nervous system, SUPEROXIDES
Abstract

Background: Angiotensin II (AngII) acts via several tissues, including the brain to exert its well established roles in the regulation of blood pressure (BP) and fluid and electrolyte regulation. Manipulation of brain AngII can also induce metabolic changes including lean phenotype and increased metabolic rate possibly via modulation of the sympathetic nervous system. These actions are mediated via activation of the AngII type 1A receptor (AT1AR). In addition, chronic low dose infusion of Ang II induces hypertension via activation of the AT1AR. Whilst the involvement of AT1AR in specific cells of the kidney has been demonstrated in AngII-dependent hypertension it is not clear whether other tissues are involved. The present study aimed to investigate whether targeted deletion of AT1ARs from the catecholaminergic cells affects the baseline metabolic parameters and blood pressure (BP) and the response to sustained infusion of AngII. Methods: All experiments were approved by the University of Melbourne Animal Experimentation Ethics Committee in accordance with guidelines of the Australian National Health and Medical Research Council. Mice (C57Bl/6 background) with cell-selective deletion of the AT1AR from catecholaminergic cells were generated by crossing AT1AR floxed (AT1ARfl/fl) mice with mice expressing crerecombinase (Cre) under the control of the tyrosine hydroxylase (TH) promoter. Two different genotypes AT1ARfl/fl;THCre+/- (knockouts) and AT1ARfl/fl;TH-Cre-/- (controls) were used in this study. In vitro autoradiography was performed to confirm the loss of AT1R binding from catecholaminergic cells. All surgical procedures were performed under surgical anesthesia (loss of pedal withdrawal reflex) using either isoflurane delivered by a gas mask (~2% in oxygen) or ketamine/xylacine i.p. (75 mg/kg:10 mg/kg). All animals received a long-acting, non-steroidal anti-inflammatory agent at the start of the surgical procedure (caroprofen 5 mg/kg). Telemetry devices were used to record baseline BP and heart rate (HR). For the metabolic studies, mice were housed individually in metabolic cages with free access to food and water. After 1 day acclimatization 24 hour urine output and food and water intake were recorded. AngII-dependent hypertension was induced by subcutaneous implantation of mini-osmotic pumps designed to infuse Ang II (500 ng/kg/min) for 4 weeks. Results: AT1R binding was completely absent in the adrenal medulla and thoracic sympathetic ganglia of the AT1AR fl/fl;TH-Cre+/- mice. Basal systolic BP and HR were not different between the groups (mean±SEM; 109± 1mmHg vs. 108 ± 2 mmHg and 553± 10 bpm vs. 573 ± 10 bpm). Body weight, water intake, and 24 h urine volumes were also not different between groups. Infusion of Ang II in AT1ARfl/fl;TH-Cre-/- induced a gradual pressor response that was increased above baseline by day 5 of infusion. The maximal change in BP occurred at day 13. After day 17 BP gradually decreased toward baseline. The trajectory of BP increase was less in the AT1A fl/fl;TH Cre+/- mice throughout the infusion with a significant decrease in the maximal response at day 13 of infusion (150± 3 mmHg vs. 133 ± 2 mmHg; P<0.05). The reduced pressor response was associated with reduced fluid and electrolyte retention, reduced activation of the sympathetic nervous system and loss of superoxide formation in key brain cardiovascular nuclei. Conclusions: AT1AR knockout from catecholaminergic cells does not elicit changes in metabolic state, baseline systolic BP or HR but expression of the receptor by these cells is essential for the full development of AngII hypertension. [ABSTRACT FROM AUTHOR]

Published
2013

48. Successful correction of flat-chested kitten syndrome in two littermate kittens.

Author

Fusi J, Bagardi M, Bassi J, Ferrari F, and Veronesi MC

Abstract

Case summary Two 18-day-old domestic shorthair kittens presented with dyspnoea, mild cyanosis, heart murmur, lung pattern, abnormal crawling and a marked dorsoventral flattening of the thorax. Deformity of the thoracic wall without pectus excavatum was diagnosed. Cardboard corsets tailored to each kitten were applied. This gave immediate respiratory relief, easing distress and pain. After 10 days, clinical and radiographic monitoring revealed normalisation of the shape of the chest wall with an improvement in general condition. At 6 months of age, clinical examination showed normal growth and development of both kittens, with a normal thoracic profile and shape also seen on radiographs. Relevance and novel information Data about flat-chested kitten syndrome and its aetiopathogenesis, treatment and outcome are scarce, but there is significant experience among breeders that is shared through online communities. High mortality rates are reported. The use of a cardboard splint appears to be novel in the published literature; in this case report, it proved to be a rapid and easy solution. For this reason, cardboard splints could be considered as a first approach for the clinical management of flat-chested kitten syndrome., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Published
2024
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49. The utility of artificial intelligence in identifying radiological evidence of lung cancer and pulmonary tuberculosis in a high-burden tuberculosis setting.

Author

Nxumalo ZZ, Irusen EM, Allwood BW, Tadepalli M, Bassi J, and Koegelenberg CFN

Subjects
Humans, Female, Male, Middle Aged, Adult, Radiography, Thoracic methods, Aged, Predictive Value of Tests, Software, Tuberculosis, Pulmonary diagnostic imaging, Tuberculosis, Pulmonary diagnosis, Lung Neoplasms diagnostic imaging, Artificial Intelligence, Sensitivity and Specificity
Abstract

Background: Artificial intelligence (AI), using deep learning (DL) systems, can be utilised to detect radiological changes of various pulmonary diseases. Settings with a high burden of tuberculosis (TB) and people living with HIV can potentially benefit from the use of AI to augment resource-constrained healthcare systems., Objective: To assess the utility of qXR software (AI) in detecting radiological changes compatible with lung cancer or pulmonary TB (PTB)., Methods: We performed an observational study in a tertiary institution that serves a population with a high burden of lung cancer and PTB. In total, 382 chest radiographs that had a confirmed diagnosis were assessed: 127 with lung cancer, 144 with PTB and 111 normal. These chest radiographs were de-identified and randomly uploaded by a blinded investigator into qXR software. The output was generated as probability scores from predefined threshold values., Results: The overall sensitivity of the qXR in detecting lung cancer was 84% (95% confidence interval (CI) 80 - 87%), specificity 91% (95% CI 84 - 96%) and positive predictive value of 97% (95% CI 95 - 99%). For PTB, it had a sensitivity of 90% (95% CI 87 - 93%) and specificity of 79% (95% CI 73 - 84%) and negative predictive value of 85% (95% CI 79 - 91%)., Conclusion: The qXR software was sensitive and specific in categorising chest radiographs as consistent with lung cancer or TB, and can potentially aid in the earlier detection and management of these diseases.

Published
2024
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50. Increased breadth and neutralization of antibodies against SARS-CoV-2 variants after infection and vaccination: A serosurveillance study in pediatric patients of Southern Switzerland.

Author

Mazzara C, Bassi J, Silacci-Fregni C, Muoio F, Passini N, Corti D, Simonetti GD, Vanoni F, Kottanattu L, and Piccoli L

Subjects
Humans, Child, Seroepidemiologic Studies, Switzerland epidemiology, Antibodies, Neutralizing, Vaccination, Antibodies, Viral, SARS-CoV-2, COVID-19 epidemiology, COVID-19 prevention & control
Abstract

Little information is available about the nature of the immune response in children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. The aim of this study is to define the seroprevalence and the features of the antibody response in children of Southern Switzerland during the different waves of Coronavirus Disease 2019 (COVID-19) pandemic. By analyzing 756 sera collected from children aged 0 to 16 years admitted to the Institute of Pediatrics of Southern Switzerland during the prepandemic period (before March 2020) and the first four pandemic waves (between March 2020 and June 2022), we investigated binding titers, cross-reactivity, and neutralizing properties of the serum antibodies against SARS-CoV-2 variants. Seroprevalence varied from 6% during the first wave to 14% and 17% during the second and third waves, respectively, peaking at 39% during the fourth wave. The 96 seropositive cases were mostly asymptomatic (42.7%) or showed mild (20.8%) to moderate (32.3%) symptoms. Moderate symptoms and close contact with COVID-19-positive individuals were associated with a higher infection risk (P < 0.001). The antibody response was mainly driven by IgG directed to the receptor-binding domain (RBD) of Wuhan-1 SARS-CoV-2 Spike (S). Children infected in the first three waves produced antibodies with up to 11-fold and 5.5-fold reduction in binding and neutralizing titers, respectively, against different SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, BA.2, and BA.5. Such reductions were less pronounced in children infected during the fourth wave, who showed the highest frequency and titers of neutralizing antibodies against the same variants. Compared to infection, vaccination with a Wuhan-1-based messenger RNA (mRNA) vaccine induced higher and heterogenous levels of antibodies cross-reacting to the different SARS-CoV-2 variants analyzed.   Conclusions: Despite the high burden of COVID-19 in Southern Switzerland, we observed an initial low seroprevalence of SARS-CoV-2 in children, which increased in the later waves. The antibody response was poor in the first three waves and improved in the fourth wave, when children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants. What is Known: • Children were marginally affected by the initial SARS-CoV-2 variants. • The number of infected and hospitalized children increased after the appearance of the Omicron variants. What is New: • Seroprevalence of SARS-CoV-2 in children of Southern Switzerland increased overtime. • Children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants in the fourth wave compared to children infected in the first three waves., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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