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1. Plugging Taxonomic Similarity in First-Order Logic Horn Clauses Comparison

Author

Ferilli, S., Biba, M., Di Mauro, N., Basile, T. M. A., Esposito, F., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Goebel, Randy, editor, Siekmann, Jörg, editor, Wahlster, Wolfgang, editor, Serra, Roberto, editor, and Cucchiara, Rita, editor

Published
2009
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4. Automatic Topics Identification for Reviewer Assignment

Author

Ferilli, S., Di Mauro, N., Basile, T. M. A., Esposito, F., Biba, M., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Carbonell, Jaime G., editor, Siekmann, Jörg, editor, Ali, Moonis, editor, and Dapoigny, Richard, editor

Published
2006
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12. MANENT: An infrastructure for integrating, structuring and searching digital libraries

Author

Biba, M, Xhafa, F, Locoro, A, Grignani, D, Mascardi, V, LOCORO, ANGELA, Mascardi, V., Biba, M, Xhafa, F, Locoro, A, Grignani, D, Mascardi, V, LOCORO, ANGELA, and Mascardi, V.

Abstract

Digital Libraries represent the commitment of research communities to preserve authoritative and well structured sources of knowledge, and to share archival organisations, methods and resources thanks to systems relying on standard metadata formats. This chapter describes some natural language processing techniques exploited for automatically extracting structural information from documents stored in Digital Libraries, based on the exposed metadata. The most prominent results achieved in this area are surveyed and discussed. As an example of an infrastructure for integrating, structuring and searching Digital Libraries based on natural language processing and semantic web techniques, we discuss the MANENT system. MANENT is a working prototype offering services of Digital Library content management and record classification and retrieval. It is hosted on a server at the Computer Science Department of Genova University and, starting from 2011, it will become publicly available. 475,000 records drawn from 138 repositories that all over the world expose OAI-PMH services have been downloaded, stored, and their automatic classification is under way. © 2011 Springer-Verlag Berlin Heidelberg.

Published
2011

13. EMBRYOLOGY

Author

Furia, G. U., primary, Kostelijk, E. H., additional, Vergouw, C. G., additional, Lee, H., additional, Lee, S., additional, Park, D., additional, Kang, H., additional, Lim, C., additional, Yang, K., additional, Park, Y., additional, Shin, M., additional, Beyhan, Z., additional, Fisch, J. D., additional, Sher, G., additional, Keskintepe, L., additional, VerMilyea, M. D., additional, Anthony, J. T., additional, Graham, J. R., additional, Tucker, M. J., additional, Freour, T., additional, Lattes, S., additional, Lammers, J., additional, Mansour, W., additional, Jean, M., additional, Barriere, P., additional, El Danasouri, I., additional, Gagsteiger, F., additional, Rinaldi, L., additional, Selman, H., additional, Antonova, I., additional, Milachich, T., additional, Valkova, L., additional, Shterev, A., additional, Barcroft, J., additional, Dayoub, N., additional, Thong, J., additional, Abdel Reda, H., additional, Khalaf, Y., additional, El Touky, T., additional, Cabry, R., additional, Brzakowski, R., additional, Lourdel, E., additional, Brasseur, F., additional, Copin, H., additional, Merviel, P., additional, Yamada, M., additional, Takanashi, K., additional, Hamatani, T., additional, Akutsu, H., additional, Fukunaga, T., additional, Inoue, O., additional, Ogawa, S., additional, Sugawara, K., additional, Okumura, N., additional, Chikazawa, N., additional, Kuji, N., additional, Umezawa, A., additional, Tomita, M., additional, Yoshimura, Y., additional, Van der Jeught, M., additional, Ghimire, S., additional, O'Leary, T., additional, Lierman, S., additional, Deforce, D., additional, Chuva de Sousa Lopes, S., additional, Heindryckx, B., additional, De Sutter, P., additional, Herrero, J., additional, Tejera, A., additional, De los Santos, M. J., additional, Castello, D., additional, Romero, J. L., additional, Meseguer, M., additional, Leperlier, F., additional, Mirallie, S., additional, Schats, R., additional, Al-Nofal, M., additional, Lens, J. W., additional, Rooth, H., additional, Hompes, P. G., additional, Lambalk, C. B., additional, Hreinsson, J., additional, Karlstrom, P. O., additional, Wanggren, K., additional, Lundqvist, M., additional, Vahabi, Z., additional, Eftekhari-Yazdi, P., additional, Dalman, A., additional, Ebrahimi, B., additional, Daneshzadeh, M. T., additional, Rajabpour Niknam, M., additional, Choi, E. G., additional, Rho, Y. H., additional, Oh, D. S., additional, Park, L. S., additional, Cheon, H. S., additional, Lee, C. S., additional, Kong, I. K., additional, Lee, S. C., additional, Liebenthron, J., additional, Montag, M., additional, Koster, M., additional, Toth, B., additional, Reinsberg, J., additional, van der Ven, H., additional, Strowitzki, T., additional, Morita, H., additional, Hirosawa, T., additional, Watanabe, S., additional, Wada, T., additional, Kamihata, M., additional, Kuwahata, A., additional, Ochi, M., additional, Horiuchi, T., additional, Fatemeh, H., additional, Karimian, L., additional, Fazel, M., additional, Fouladi, H., additional, Johansson, L., additional, Ruttanajit, T., additional, Chanchamroen, S., additional, Sopaboon, P., additional, Seweewanlop, S., additional, Sawakwongpra, K., additional, Jindasri, P., additional, Jantanalapruek, T., additional, Charoonchip, K., additional, Vajta, G., additional, Quangkananurug, W., additional, Yi, G., additional, Jo, J. W., additional, Jee, B. C., additional, Suh, C. S., additional, Kim, S. H., additional, Zhang, Y., additional, Zhao, H. J., additional, Cui, Y. G., additional, Gao, C., additional, Gao, L. L., additional, Liu, J. Y., additional, Sozen, E., additional, Buluc, B., additional, Vicdan, K., additional, Akarsu, C., additional, Tuncay, G., additional, Hambiliki, F., additional, Bungum, M., additional, Agapitou, K., additional, Makrakis, E., additional, Liarmakopoulou, S., additional, Anagnostopoulou, C., additional, Moustakarias, T., additional, Giannaris, D., additional, Wang, J., additional, Andonov, M., additional, Linara, E., additional, Charleson, C., additional, Ahuja, K. K., additional, Ozsoy, S., additional, Morris, M. B., additional, Day, M. L., additional, Cobo, A., additional, Viloria, T., additional, Campos, P., additional, Vallejo, B., additional, Remohi, J., additional, Roldan, M., additional, Perez-Cano, I., additional, Cruz, M., additional, Martinez, M., additional, Gadea, B., additional, Munoz, M., additional, Garrido, N., additional, Mesut, N., additional, Ciray, H. N., additional, Mesut, A., additional, Isler, A., additional, Bahceci, M., additional, Fortuno, S., additional, Legidos, V., additional, Muela, L., additional, Galindo, N., additional, Gunasheela, S., additional, Gunasheela, D., additional, Ueno, S., additional, Uchiyama, K., additional, Kondo, M., additional, Ito, M., additional, Kato, K., additional, Takehara, Y., additional, Kato, O., additional, Edgar, D. H., additional, Krapez, J. A., additional, Bacer Kermavner, L., additional, Virant-Klun, I., additional, Pinter, B., additional, Tomazevic, T., additional, Vrtacnik-Bokal, E., additional, Lee, S. G., additional, Kang, S. M., additional, Lee, S. W., additional, Jeong, H. J., additional, Lee, Y. C., additional, Lim, J. H., additional, Bochev, I., additional, Kyurkchiev, S., additional, Wilding, M., additional, Coppola, G., additional, Di Matteo, L., additional, Dale, B., additional, Hormann-Kropfl, M., additional, Kastelic, D., additional, Schenk, M., additional, Fourati Ben Mustapha, S., additional, Khrouf, M., additional, Braham, M., additional, Kallel, L., additional, Elloumi, H., additional, Merdassi, G., additional, Chaker, A., additional, Ben Meftah, M., additional, Zhioua, F., additional, Zhioua, A., additional, Kocent, J., additional, Neri, Q. V., additional, Rosenwaks, Z., additional, Palermo, G. D., additional, Best, L., additional, Campbell, A., additional, Fishel, S., additional, Calimlioglu, N., additional, Sahin, G., additional, Akdogan, A., additional, Susamci, T., additional, Bilgin, M., additional, Goker, E. N. T., additional, Tavmergen, E., additional, Cantatore, C., additional, Ding, J., additional, Depalo, R., additional, Smith, G. D., additional, Kasapi, E., additional, Panagiotidis, Y., additional, Papatheodorou, A., additional, Goudakou, M., additional, Pasadaki, T., additional, Nikolettos, N., additional, Asimakopoulos, B., additional, Prapas, Y., additional, Soydan, E., additional, Gulebenzer, G., additional, Karatekelioglu, E., additional, Budak, E., additional, Pehlivan Budak, T., additional, Alegretti, J., additional, Cuzzi, J., additional, Negrao, P. M., additional, Moraes, M. P., additional, Bueno, M. B., additional, Serafini, P., additional, Motta, E. L. A., additional, Elaimi, A., additional, Harper, J. C., additional, Stecher, A., additional, Baborova, P., additional, Wirleitner, B., additional, Schwerda, D., additional, Vanderzwalmen, P., additional, Zech, N. H., additional, Stanic, P., additional, Hlavati, V., additional, Gelo, N., additional, Pavicic-Baldani, D., additional, Sprem-Goldstajn, M., additional, Radakovic, B., additional, Kasum, M., additional, Strelec, M., additional, Simunic, V., additional, Vrcic, H., additional, Khan, I., additional, Urich, M., additional, Abozaid, T., additional, Ullah, K., additional, Abuzeid, M., additional, Fakih, M., additional, Shamma, N., additional, Ayers, J., additional, Ashraf, M., additional, Milik, S., additional, Pirkevi, C., additional, Atayurt, Z., additional, Yazici, S., additional, Yelke, H., additional, Kahraman, S., additional, Dal Canto, M., additional, Coticchio, G., additional, Brambillasca, F., additional, Mignini Renzini, M., additional, Novara, P., additional, Maragno, L., additional, Karagouga, G., additional, De Ponti, E., additional, Fadini, R., additional, Resta, S., additional, Magli, M. C., additional, Cavallini, G., additional, Muzzonigro, F., additional, Ferraretti, A. P., additional, Gianaroli, L., additional, Barberi, M., additional, Orlando, G., additional, Sciajno, R., additional, Serrao, L., additional, Fava, L., additional, Preti, S., additional, Bonu, M. A., additional, Borini, A., additional, Varras, M., additional, Polonifi, A., additional, Mantzourani, M., additional, Mavrogianni, D., additional, Stefanidis, K., additional, Griva, T., additional, Bletsa, R., additional, Dinopoulou, V., additional, Drakakis, P., additional, Loutradis, D., additional, Hickman, C. F. L., additional, Duffy, S., additional, Bowman, N., additional, Gardner, K., additional, Sati, L., additional, Zeiss, C., additional, Demir, R., additional, McGrath, J., additional, Yildiz, S., additional, Unal, S., additional, Kumtepe, Y., additional, Aljaser, F., additional, Hernandez, J., additional, Tomlinson, M., additional, Campbell, B., additional, Fosas, N., additional, Redondo Ania, M., additional, Marina, F., additional, Molfino, F., additional, Martin, P., additional, Perez, N., additional, Carrasco, A., additional, Garcia, N., additional, Gonzalez, S., additional, Marina, S., additional, Scaruffi, P., additional, Stigliani, S., additional, Tonini, G. P., additional, Venturini, P. L., additional, Anserini, P., additional, Guglielmo, M. C., additional, Albertini, D. F., additional, Lain, M., additional, Caliari, I., additional, Oikonomou, Z., additional, Chatzimeletiou, K., additional, Sioga, A., additional, Oikonomou, L., additional, Kolibianakis, E., additional, Tarlatzis, B., additional, Nottola, S. A., additional, Bianchi, V., additional, Lorenzo, C., additional, Maione, M., additional, Macchiarelli, G., additional, Gomez, E., additional, Gil, M. A., additional, Sanchez-Osorio, J., additional, Maside, C., additional, Martinez, M. J., additional, Torres, I., additional, Rodenas, C., additional, Cuello, C., additional, Parrilla, I., additional, Molina, G., additional, Garcia, A., additional, Margineda, J., additional, Navarro, S., additional, Roca, J., additional, Martinez, E. A., additional, Avcil, F., additional, Ozden, H., additional, Candan, Z. N., additional, Uslu, H., additional, Karaman, Y., additional, Gioacchini, G., additional, Giorgini, E., additional, Carnevali, O., additional, Ferraris, P., additional, Vaccari, L., additional, Choe, S., additional, Tae, J., additional, Kim, C., additional, Lee, J., additional, Hwang, D., additional, Kim, K., additional, Suh, C., additional, Jee, B., additional, Catt, S. L., additional, Sorenson, H., additional, Vela, M., additional, Duric, V., additional, Chen, P., additional, Temple-Smith, P. D., additional, Pangestu, M., additional, Yoshimura, T., additional, Fukunaga, N., additional, Nagai, R., additional, Kitasaka, H., additional, Tamura, F., additional, Hasegawa, N., additional, Kato, M., additional, Nakayama, K., additional, Takeuchi, M., additional, Aoyagi, N., additional, Yasue, K., additional, Watanabe, H., additional, Asano, E., additional, Hashiba, Y., additional, Asada, Y., additional, Iwata, K., additional, Yumoto, K., additional, Mizoguchi, C., additional, Sargent, H., additional, Kai, Y., additional, Ueda, M., additional, Tsuchie, Y., additional, Imajo, A., additional, Iba, Y., additional, Mio, Y., additional, Els-Smit, C. L., additional, Botha, M. H., additional, Sousa, M., additional, Windt-De Beer, M., additional, Kruger, T. F., additional, Muller, N., additional, Magli, C., additional, Corani, G., additional, Giusti, A., additional, Castelletti, E., additional, Gambardella, L., additional, Seshadri, S., additional, Sunkara, S. K., additional, El-Toukhy, T., additional, Kishi, I., additional, Maruyama, T., additional, Ohishi, M., additional, Akiba, Y., additional, Asada, H., additional, Konishi, Y., additional, Nakano, M., additional, Kamei, K., additional, Lee, J. H., additional, Lee, K. H., additional, Park, I. H., additional, Sun, H. G., additional, Kim, S. G., additional, Kim, Y. Y., additional, Choi, E. M., additional, Lee, D. H., additional, Chavez, S. L., additional, Loewke, K. E., additional, Behr, B., additional, Han, J., additional, Moussavi, F., additional, Reijo Pera, R. A., additional, Yokota, H., additional, Yokota, Y., additional, Yokota, M., additional, Sato, S., additional, Nakagawa, M., additional, Sato, M., additional, Anazawa, I., additional, Araki, Y., additional, Knez, K., additional, Pozlep, B., additional, Vermilyea, M. D., additional, Levy, M. J., additional, Carvalho, M., additional, Cordeiro, I., additional, Leal, F., additional, Aguiar, A., additional, Nunes, J., additional, Rodrigues, C., additional, Soares, A. P., additional, Sousa, S., additional, Calhaz-Jorge, C., additional, Braga, D. P. A. F., additional, Setti, A. S., additional, Figueira, R. C. S., additional, Aoki, T., additional, Iaconelli, A., additional, Borges, E., additional, Ozkavukcu, S., additional, Sonmezer, M., additional, Atabekoglu, C., additional, Berker, B., additional, Ozmen, B., additional, Isbacar, S., additional, Ibis, E., additional, Menezes, J., additional, Lalitkumar, P. G. L., additional, Borg, P., additional, Ekwurtzel, E., additional, Nordqvist, S., additional, Vaegter, K., additional, Tristen, C., additional, Sjoblom, P., additional, Azevedo, M. C., additional, Remohi Gimenez, J., additional, Gamiz, P., additional, Albert, C., additional, Ferreira, R. C., additional, Resende, S., additional, Colturato, S. S., additional, Ferrer Buitrago, M., additional, Ferrer Robles, E., additional, Munoz Soriano, P., additional, Ruiz-Jorro, M., additional, Calatayud Lliso, C., additional, Rawe, V. Y., additional, Hanrieder, J., additional, Gulen-Yaldir, F., additional, Bergquist, J., additional, Stavreus-Evers, A., additional, Grunskis, A., additional, Bazarova, A., additional, Dundure, I., additional, Fodina, V., additional, Brikune, J., additional, Lakutins, J., additional, Pribenszky, C., additional, Cornea, M., additional, Reichart, A., additional, Uhereczky, G., additional, Losonczy, E., additional, Ficsor, L., additional, Lang, Z., additional, Ohgi, S., additional, Nakamura, C., additional, Hagiwara, C., additional, Kawashima, M., additional, Yanaihara, A., additional, Jones, G. M., additional, Biba, M., additional, Kokkali, G., additional, Vaxevanoglou, T., additional, Chronopoulou, M., additional, Petroutsou, K., additional, Sfakianoudis, K., additional, Pantos, K., additional, Romano, S., additional, Albricci, L., additional, Stoppa, M., additional, Cerza, C., additional, Sanges, F., additional, Fusco, S., additional, Capalbo, A., additional, Maggiulli, R., additional, Ubaldi, F., additional, Rienzi, L., additional, Ulrick, J., additional, Kilani, S., additional, Chapman, M., additional, Losada, C., additional, Ortega, I., additional, Pacheco, A., additional, Bronet, F., additional, Aguilar, J., additional, Ojeda, M., additional, Taboas, E., additional, Perez, M., additional, Munoz, E., additional, Pellicer, A., additional, Boumela, I., additional, Assou, S., additional, Haouzi, D., additional, Monzo, C., additional, Dechaud, H., additional, Hamamah, S., additional, Nakaoka, Y., additional, Hashimoto, S., additional, Amo, A., additional, Yamagata, K., additional, Nakano, T., additional, Akamatsu, Y., additional, Mezawa, T., additional, Ohnishi, Y., additional, Himeno, T., additional, Inoue, T., additional, Ito, K., additional, and Morimoto, Y., additional

Published
2012
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29. Similarity-Guided Clause Generalization.

Author

Carbonell, Jaime G., Siekmann, Jörg, Basili, Roberto, Pazienza, Maria Teresa, Ferilli, S., Basile, T. M. A., Di Mauro, N., Biba, M., and Esposito, F.

Abstract

Few works are available in the literature to define similarity criteria between First-Order Logic formulæ, where the presence of relations causes various portions of one description to be possibly mapped in different ways onto another description, which poses serious computational problems. Hence, the need for a set of general criteria that are able to support the comparison between formulæ. This could have many applications; this paper tackles the case of two descriptions (e.g., a definition and an observation) to be generalized, where the similarity criteria could help in focussing on the subparts of the descriptions that are more similar and hence more likely to correspond to each other, based only on their syntactic structure. Experiments on real-world datasets prove the effectiveness of the proposal, and the efficiency of the corresponding implementation in a generalization procedure. [ABSTRACT FROM AUTHOR]

Published
2007
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31. Loss of chromatic sensitivity in AMD and diabetes: a comparative study.

Author

O'Neill-Biba, M., Sivaprasad, S., Rodriguez-Carmona, M., Wolf, J. E., and Barbur, J. L.

Subjects
*DIABETES, *COMPARATIVE studies, *PHOTORECEPTORS, *RETINAL degeneration, *VISUAL perception
Abstract

Background: Abnormalities in rod and cone photoreceptor morphology have been reported in normal aging retinas in the absence of known pathology and have been taken as an indicator of susceptibility to retinal disease. Some loss of visual performance may therefore precede retinal structural changes that can be detected reliably using conventional fundus imaging techniques. Red/green (RG) and yellow/blue (YB) colour discrimination thresholds are sensitive measures of normal retinal function and poor YB discrimination is often taken as an indicator of retinal disease, though it is generally acknowledged that RG loss is also present in most cases of acquired deficiency. Although structural changes in age-related macular degeneration (AMD) and diabetes share some similarities, significant differences remain and this may result in different patterns of RG and YB loss. Aim: The aim of this study was to quantify and compare the severity of RG and YB loss of chromatic sensitivity in patients with AMD and diabetes. Methods: Patients with varying severity of AMD and diabetes and normal subjects of similar age were recruited for the study. RG and YB colour detection thresholds were measured in the two groups of patients and the control group, using the Colour Assessment and Diagnosis (CAD) test. Results: Each AMD subject investigated showed significant, but unequal loss of YB and RG chromatic sensitivity, with YB discrimination showing the greatest loss. Diabetic subjects also exhibited reduced chromatic sensitivity, but with almost equal and highly correlated RG and YB thresholds ( R2 = 0.99). The severity of colour vision loss measured with the CAD test also correlates well with a clinical classification index of disease progression in AMD, and with the level of hyperglycaemic control in diabetes. Conclusions: These findings suggest that accurate measurements of RG and YB colour thresholds can provide a sensitive measure of functional change in diseases of the retina with patterns of loss that differ significantly in AMD and diabetes. [ABSTRACT FROM AUTHOR]

Published
2010
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32. Adsorbent Screening for Metal Impurity Removal in Pharmaceutical Process Research

Author

Welch, C. J., Albaneze-Walker, J., Leonard, W. R., Biba, M., DaSilva, J., Henderson, D., Laing, B., Mathre, D. J., Spencer, S., Bu, X., and Wang, T.

Abstract

A microtube screening approach affords simple and convenient assessment of the selective adsorption of metal impurities by a variety of different process adsorbents. This approach is helpful in identifying rapid solutions to metal impurity problems in pharmaceutical process research. Several examples illustrating the utility of the approach are presented.

Published
2005

42. MANENT: An infrastructure for integrating, structuring and searching digital libraries

Author

Angela Locoro, Viviana Mascardi, Daniele Grignani, Biba, M, Xhafa, F, Locoro, A, Grignani, D, and Mascardi, V

Subjects
Word-sense disambiguation, Digital libraries, business.industry, Computer science, Digital library, Structuring, World Wide Web, Metadata, Semantic similarity, Artificial Intelligence, business, Semantic Web, Content management, Metadata record
Abstract

Digital Libraries represent the commitment of research communities to preserve authoritative and well structured sources of knowledge, and to share archival organisations, methods and resources thanks to systems relying on standard metadata formats. This chapter describes some natural language processing techniques exploited for automatically extracting structural information from documents stored in Digital Libraries, based on the exposed metadata. The most prominent results achieved in this area are surveyed and discussed. As an example of an infrastructure for integrating, structuring and searching Digital Libraries based on natural language processing and semantic web techniques, we discuss the MANENT system. MANENT is a working prototype offering services of Digital Library content management and record classification and retrieval. It is hosted on a server at the Computer Science Department of Genova University and, starting from 2011, it will become publicly available. 475,000 records drawn from 138 repositories that all over the world expose OAI-PMH services have been downloaded, stored, and their automatic classification is under way. © 2011 Springer-Verlag Berlin Heidelberg.

Published
2011

43. Synthesis of a Complex and Highly Potent PCSK9 Inhibitor.

Author

Kuethe JT, Lee J, Thaisrivongs D, Yasuda N, Pollack SR, Leone J, DaSilva J, Biba M, Tsay FR, Regalado EL, Qi J, Li H, Poggetto GD, and Cohen R

Subjects
Proprotein Convertase 9
Abstract

The solution-based gram-scale synthesis of complex and highly potent proprotein convertase subtilisin-like/kexin type 9 (PCSK9) inhibitor 1 is presented. Construction of Northern fragment 2 , followed by stepwise installation of Eastern 3 , Southern 4 , and Western 5 fragments, provided macrocyclic precursor 19 . This intermediate was cross-linked via an intramolecular azide-alkyne click reaction, which preceded macrolactamization to afford the core framework of compound 1 . Finally, coupling with poly(ethylene glycol) side-chain-based 6 gave the PCSK9 inhibitor 1 .

Published
2023
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44. Will treating progressive myopia overwhelm the eye care workforce? A workforce modelling study.

Author

Lingham G, Loughman J, Kuzmenko S, Biba M, and Flitcroft DI

Subjects
Adolescent, Disease Progression, Forecasting, Humans, Prevalence, Refraction, Ocular, Workforce, Myopia, Degenerative
Abstract

Purpose: Treatments for myopia progression are now available, but implementing these into clinical practice will place a burden on the eye care workforce. This study estimated the full-time equivalent (FTE) workforce required to implement myopia control treatments in the UK and Ireland., Methods: To estimate the number of 6- to 21-year-olds with myopia, two models utilising separate data sources were developed. The examination-based model used: (1) the number of primary care eye examinations conducted annually and (2) the proportion of these that are for myopic young people. The prevalence-based model used epidemiological data on the age-specific prevalence of myopia. The proportion of myopic young people progressing ≥0.25 dioptres (D)/year or ≥0.50 D/year was obtained from Irish electronic health records and the recommended review schedule from clinical management guidelines., Results: Using the examination and prevalence models, respectively, the estimated number of young people with myopia was 2,469,943 and 2,235,713. The extra workforce required to provide comprehensive myopia management for this target population was estimated at 226-317 FTE at the 0.50 D/year threshold and 433-630 FTE at the 0.25 D/year threshold. Extra visits required for myopia control treatment represented approximately 2.6% of current primary eye care examinations versus 13.6% of hospital examinations., Conclusions: Implementing new myopia control treatments in primary care settings over the medium-term is unlikely to overwhelm the eye care workforce completely. Further increases to workforce, upskilling of current workforce and tools to reduce chair time will help to ensure sustainability of the eye care workforce into the future., (© 2022 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Published
2022
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45. Identification and quantitation of isomeric pneumococcal polysaccharides by partial chemical degradation followed by mass spectrometry.

Author

Manheim J, Lin M, Kong J, Biba M, and Zhuang P

Subjects
Ions, Isomerism, Mass Spectrometry methods, Oligosaccharides chemistry, Pneumococcal Vaccines
Abstract

Quantitation of isomeric pneumococcal polysaccharides in vaccines is a challenging task due to mixture complexity, their low quantities, and identical monosaccharide compositions. Differentiation and quantitation of isomeric pneumococcal polysaccharides were investigated here based on a partial chemical degradation mass spectrometry approach to generate an oligosaccharide marker for one isomer, and not the other. Mild base conditions were successful at generating unique ions for the isomers with the weakest glycosidic bonds, while strong base and acid conditions were successful at generating unique ions for the more stable isomers. Linear relationships between the ion abundance of the oligosaccharide marker and the starting pneumococcal polysaccharides concentration were established for all isomers. Furthermore, precision measurements for each method were below 12% demonstrating good robustness. Therefore, partial chemical degradation followed by mass spectrometry was successful at differentiating and quantifying isomeric pneumococcal polysaccharides and may be adopted for other bacterial types., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
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46. A kinase-cGAS cascade to synthesize a therapeutic STING activator.

Author

McIntosh JA, Liu Z, Andresen BM, Marzijarani NS, Moore JC, Marshall NM, Borra-Garske M, Obligacion JV, Fier PS, Peng F, Forstater JH, Winston MS, An C, Chang W, Lim J, Huffman MA, Miller SP, Tsay FR, Altman MD, Lesburg CA, Steinhuebel D, Trotter BW, Cumming JN, Northrup A, Bu X, Mann BF, Biba M, Hiraga K, Murphy GS, Kolev JN, Makarewicz A, Pan W, Farasat I, Bade RS, Stone K, Duan D, Alvizo O, Adpressa D, Guetschow E, Hoyt E, Regalado EL, Castro S, Rivera N, Smith JP, Wang F, Crespo A, Verma D, Axnanda S, Dance ZEX, Devine PN, Tschaen D, Canada KA, Bulger PG, Sherry BD, Truppo MD, Ruck RT, Campeau LC, Bennett DJ, Humphrey GR, Campos KR, and Maddess ML

Subjects
Adenosine, Animals, Interferons, Membrane Proteins genetics, Membrane Proteins metabolism, Signal Transduction, Guanosine, Nucleotidyltransferases metabolism
Abstract

The introduction of molecular complexity in an atom- and step-efficient manner remains an outstanding goal in modern synthetic chemistry. Artificial biosynthetic pathways are uniquely able to address this challenge by using enzymes to carry out multiple synthetic steps simultaneously or in a one-pot sequence 1-3 . Conducting biosynthesis ex vivo further broadens its applicability by avoiding cross-talk with cellular metabolism and enabling the redesign of key biosynthetic pathways through the use of non-natural cofactors and synthetic reagents 4,5 . Here we describe the discovery and construction of an enzymatic cascade to MK-1454, a highly potent stimulator of interferon genes (STING) activator under study as an immuno-oncology therapeutic 6,7 (ClinicalTrials.gov study NCT04220866 ). From two non-natural nucleotide monothiophosphates, MK-1454 is assembled diastereoselectively in a one-pot cascade, in which two thiotriphosphate nucleotides are simultaneously generated biocatalytically, followed by coupling and cyclization catalysed by an engineered animal cyclic guanosine-adenosine synthase (cGAS). For the thiotriphosphate synthesis, three kinase enzymes were engineered to develop a non-natural cofactor recycling system in which one thiotriphosphate serves as a cofactor in its own synthesis. This study demonstrates the substantial capacity that currently exists to use biosynthetic approaches to discover and manufacture complex, non-natural molecules., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2022
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47. Development of ProTx-II Analogues as Highly Selective Peptide Blockers of Na v 1.7 for the Treatment of Pain.

Author

Adams GL, Pall PS, Grauer SM, Zhou X, Ballard JE, Vavrek M, Kraus RL, Morissette P, Li N, Colarusso S, Bianchi E, Palani A, Klein R, John CT, Wang D, Tudor M, Nolting AF, Biba M, Nowak T, Makarov AA, Reibarkh M, Buevich AV, Zhong W, Regalado EL, Wang X, Gao Q, Shahripour A, Zhu Y, de Simone D, Frattarelli T, Pasquini NM, Magotti P, Iaccarino R, Li Y, Solly K, Lee KJ, Wang W, Chen F, Zeng H, Wang J, Regan H, Amin RP, Regan CP, Burgey CS, Henze DA, Sun C, and Tellers DM

Subjects
Animals, Cell Degranulation drug effects, Cystine chemistry, Drug Design, Hot Temperature, Mast Cells drug effects, Models, Molecular, Pain Measurement drug effects, Rats, Spider Venoms pharmacology, NAV1.7 Voltage-Gated Sodium Channel drug effects, Pain drug therapy, Sodium Channel Blockers chemical synthesis, Sodium Channel Blockers pharmacology, Spider Venoms chemical synthesis
Abstract

Inhibitor cystine knot peptides, derived from venom, have evolved to block ion channel function but are often toxic when dosed at pharmacologically relevant levels in vivo . The article describes the design of analogues of ProTx-II that safely display systemic in vivo blocking of Na v 1.7, resulting in a latency of response to thermal stimuli in rodents. The new designs achieve a better in vivo profile by improving ion channel selectivity and limiting the ability of the peptides to cause mast cell degranulation. The design rationale, structural modeling, in vitro profiles, and rat tail flick outcomes are disclosed and discussed.

Published
2022
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48. Enhanced fluidity liquid chromatography: A guide to scaling up from analytical to preparative separations.

Author

Bennett R, Biba M, Liu J, Haidar Ahmad IA, Hicks MB, and Regalado EL

Subjects
Acetonitriles chemistry, Hydrophobic and Hydrophilic Interactions, Methanol chemistry, Nucleotides chemistry, Proteins chemistry, Water chemistry, Chemistry Techniques, Analytical methods, Chromatography, Supercritical Fluid
Abstract

The evolution of supercritical fluid chromatography (SFC) instrumentation, improved detection capability, and expanded modifier range has led to extending the reach of SFC to the analysis of a broader spectrum of analytes beyond enantioselective separations. However, preparative SFC has yet to see the same technological revitalization, especially in regards to the purification of highly polar analytes. Enhanced fluidity liquid chromatography (EFLC) has been demonstrated as one of the ways to extend the applicable range of SFC instrumentation to highly polar analytes such as proteins, carbohydrates, and nucleotides. Despite recent applications of EFLC for challenging mixtures of hydrophilic metabolites and analogs, its viability in preparative purification, which is of great importance to the pharmaceutical industry, remains unknown. Herein, multiple chromatographic parameters that are critical to achieve feasible EFLC purification methods were investigated, including system pressure as a function of modifier composition (for several MeOH:H 2 O ratios), effect of diluent injection conditions on peak shape, and optimization of mass load with diluent composition. The usage of 50% acetonitrile or methanol diluents provided the most volumetric loading capacity. In the case of sucrose, leveraging higher analyte solubility in water proved to be more favorable than the volumetric loading capacity of diluents with higher organic content. In fact, an 80 mg injection of sucrose was possible on a 2 cm preparative HILIC column with minimal peak shape degradation. The combined information led to the successful demonstration of EFLC for the preparative separation of sugars using readily available MS-directed SFC instrumentation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2019
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49. Beyond optical rotation: what's left is not always right in total synthesis.

Author

Joyce LA, Nawrat CC, Sherer EC, Biba M, Brunskill A, Martin GE, Cohen RD, and Davies IW

Abstract

This work describes the application of vibrational (VCD) and electronic (ECD) circular dichroism spectroscopy to solve the longstanding debate around the absolute configuration of (+)-frondosin B ( 1 ). The absolute configuration of (+)- 1 could confidently be assigned as ( R ) using these spectroscopic techniques. The discrepancy in the optical rotation (OR) values obtained in previous studies can be attributed to an undetected minor impurity ( ca. 7%) that arose unexpectedly in a key step late in the synthesis. Additionally, the conditions used in the final step of the previous reports for demethylation to form the natural product proceeded with significant loss of enantiopurity. The large OR measured for the impurity at its observed level, when compared to the small rotation for the less enantiopure natural product 1 , led to a measured OR value for the synthetic material that had the opposite sign of the natural product.

Published
2017
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50. MISER chiral supercritical fluid chromatography for high throughput analysis of enantiopurity.

Author

Zawatzky K, Biba M, Regalado EL, and Welch CJ

Subjects
Carbon Dioxide chemistry, Chemistry Techniques, Analytical methods, Chromatography, Supercritical Fluid
Abstract

MISER chromatographic analysis (Multiple Injections in a Single Experimental Run) using supercritical fluid chromatography (SFC) with pressurized carbon dioxide-based eluents is well suited to the high throughput analysis of enantiopurity. SFC is currently the preferred method for fast enantiopurity analysis, with analysis times of only a few seconds achievable in some cases. Injector programming using both the Agilent Infinity and Shimadzu Nexera UC instruments permitted MISER SFC experiments to be performed. Several case studies are presented, showcasing the power and versatility of the technique, with 'plate analysis times' (the time required for analysis of enantiopurity of 96 samples) of less than 33-34 min achievable in the best cases., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Published
2016
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