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101. In situ detection of protein interactions for recombinant therapeutic enzymes

Author

Samoudi, Mojtaba, Kuo, Chih‐Chung, Robinson, Caressa M, Shams‐Ud‐Doha, Km, Schinn, Song‐Min, Kol, Stefan, Weiss, Linus, Bjorn, Sara Petersen, Voldborg, Bjorn G, Campos, Alexandre Rosa, and Lewis, Nathan E

Subjects
Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Glycosylation, HEK293 Cells, Humans, Protein Folding, Protein Interaction Maps, Protein Processing, Post-Translational, Protein Transport, Recombinant Proteins, BioID, cell engineering, disulfide bond, secretory pathway, therapeutic proteins
Abstract

Despite their therapeutic potential, many protein drugs remain inaccessible to patients since they are difficult to secrete. Each recombinant protein has unique physicochemical properties and requires different machinery for proper folding, assembly, and posttranslational modifications (PTMs). Here we aimed to identify the machinery supporting recombinant protein secretion by measuring the protein-protein interaction (PPI) networks of four different recombinant proteins (SERPINA1, SERPINC1, SERPING1, and SeAP) with various PTMs and structural motifs using the proximity-dependent biotin identification (BioID) method. We identified PPIs associated with specific features of the secreted proteins using a Bayesian statistical model and found proteins involved in protein folding, disulfide bond formation, and N-glycosylation were positively correlated with the corresponding features of the four model proteins. Among others, oxidative folding enzymes showed the strongest association with disulfide bond formation, supporting their critical roles in proper folding and maintaining the ER stability. Knockdown of disulfide-isomerase PDIA4, a measured interactor with significance for SERPINC1 but not SERPINA1, led to the decreased secretion of SERPINC1, which relies on its extensive disulfide bonds, compared to SERPINA1, which has no disulfide bonds. Proximity-dependent labeling successfully identified the transient interactions supporting synthesis of secreted recombinant proteins and refined our understanding of key molecular mechanisms of the secretory pathway during recombinant protein production.

Published
2021

102. Panobinostat Effectively Increases Histone Acetylation and Alters Chromatin Accessibility Landscape in Canine Embryonic Fibroblasts but Does Not Enhance Cellular Reprogramming

Author

Moshref, Maryam, Questa, Maria, Lopez-Cervantes, Veronica, Sears, Thomas K, Greathouse, Rachel L, Crawford, Charles K, and Kol, Amir

Subjects
Veterinary Sciences, Agricultural, Veterinary and Food Sciences, Genetics, Stem Cell Research, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, canine iPSC, embryonic fibroblasts, cellular reprogramming, HDAC inhibitors, ATAC sequencing, Veterinary sciences
Abstract

Robust and reproducible protocols to efficiently reprogram adult canine cells to induced pluripotent stem cells are still elusive. Somatic cell reprogramming requires global chromatin remodeling that is finely orchestrated spatially and temporally. Histone acetylation and deacetylation are key regulators of chromatin condensation, mediated by histone acetyltransferases and histone deacetylases (HDACs), respectively. HDAC inhibitors have been used to increase histone acetylation, chromatin accessibility, and somatic cell reprogramming in human and mice cells. We hypothesized that inhibition of HDACs in canine fibroblasts would increase their reprogramming efficiency by altering the epigenomic landscape and enabling greater chromatin accessibility. We report that a combined treatment of panobinostat (LBH589) and vitamin C effectively inhibits HDAC function and increases histone acetylation in canine embryonic fibroblasts in vitro, with no significant cytotoxic effects. We further determined the effect of this treatment on global chromatin accessibility via Assay for Transposase-Accessible Chromatin using sequencing. Finally, the treatment did not induce any significant increase in cellular reprogramming efficiency. Although our data demonstrate that the unique epigenetic landscape of canine cells does not make them amenable to cellular reprogramming through the proposed treatment, it provides a rationale for a targeted, canine-specific, reprogramming approach by enhancing the expression of transcription factors such as CEBP.

Published
2021

103. The Mucosal Innate Immune Response to Cryptosporidium parvum, a Global One Health Issue.

Author

Crawford, Charles K and Kol, Amir

Subjects
Animals, Cattle, Cryptosporidium, Cryptosporidium parvum, Cryptosporidiosis, Immunity, Innate, One Health, innate immune response, intestinal epithelium, intestinal parasite, Immunization, Infectious Diseases, Foodborne Illness, Biodefense, Biotechnology, Vaccine Related, Prevention, Emerging Infectious Diseases, Digestive Diseases, Aetiology, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Biochemistry and Cell Biology, Microbiology
Abstract

Cryptosporidium parvum is an apicomplexan parasite that infects the intestinal epithelium of humans and livestock animals worldwide. Cryptosporidiosis is a leading cause of diarrheal-related deaths in young children and a major cause of economic loss in cattle operations. The disease is especially dangerous to infants and immunocompromised individuals, for which there is no effective treatment or vaccination. As human-to-human, animal-to-animal and animal-to-human transmission play a role in cryptosporidiosis disease ecology, a holistic 'One Health' approach is required for disease control. Upon infection, the host's innate immune response restricts parasite growth and initiates the adaptive immune response, which is necessary for parasite clearance and recovery. The innate immune response involves a complex communicative interplay between epithelial and specialized innate immune cells. Traditional models have been used to study innate immune responses to C. parvum but cannot fully recapitulate natural host-pathogen interactions. Recent shifts to human and bovine organoid cultures are enabling deeper understanding of host-specific innate immunity response to infection. This review examines recent advances and highlights research gaps in our understanding of the host-specific innate immune response to C. parvum. Furthermore, we discuss evolving research models used in the field and potential developments on the horizon.

Published
2021

104. Cell Therapy in Veterinary Medicine as a Proof-of-Concept for Human Therapies: Perspectives From the North American Veterinary Regenerative Medicine Association.

Author

Arzi, Boaz, Webb, Tracy L, Koch, Thomas G, Volk, Susan W, Betts, Dean H, Watts, Ashlee, Goodrich, Laurie, Kallos, Michael S, and Kol, Amir

Subjects
One Health, clinical trial, companion animals, naturally occurring, stem cell, therapy, Biotechnology, Regenerative Medicine, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 5.9 Resources and infrastructure (treatment development), 5.2 Cellular and gene therapies, Neurological, Good Health and Well Being, Veterinary Sciences
Abstract

In the past decade, the potential to translate scientific discoveries in the area of regenerative therapeutics in veterinary species to novel, effective human therapies has gained interest from the scientific and public domains. Translational research using a One Health approach provides a fundamental link between basic biomedical research and medical clinical practice, with the goal of developing strategies for curing or preventing disease and ameliorating pain and suffering in companion animals and humans alike. Veterinary clinical trials in client-owned companion animals affected with naturally occurring, spontaneous disease can inform human clinical trials and significantly improve their outcomes. Innovative cell therapies are an area of rapid development that can benefit from non-traditional and clinically relevant animal models of disease. This manuscript outlines cell types and therapeutic applications that are currently being investigated in companion animals that are affected by naturally occurring diseases. We further discuss how such investigations impact translational efforts into the human medical field, including a critical evaluation of their benefits and shortcomings. Here, leaders in the field of veterinary regenerative medicine argue that experience gained through the use of cell therapies in companion animals with naturally occurring diseases represent a unique and under-utilized resource that could serve as a critical bridge between laboratory/preclinical models and successful human clinical trials through a One-Health approach.

Published
2021

105. Ventilation practices in burn patients—an international prospective observational cohort study

Author

Schultz, Marcus J, Horn, Janneke, Hollmann, Markus W, Preckel, Benedikt, Glas, Gerie J, Colpaert, Kirsten, Malbrain, Manu, Neto, Ary Serpa, Asehnoune, Karim, de Abreu, Marcello Gamma, Martin-Loeches, Ignacio, Pelosi, Paolo, Sjöberg, Folke, Binnekade, Jan M, Cleffken, Berry, Juffermans, Nicole P, Knape, Paul, Loef, Bert G, Mackie, David P, Enkhbaatar, Perenlei, Depetris, Nadia, Perner, Anders, Herrero, Eva, Cachafeiro, Lucia, Jeschke, Marc, Lipman, Jeffrey, Legrand, Matthieu, Horter, Johannes, Lavrentieva, Athina, Glas, Gerie, Kazemi, Alex, Guttormsen, Anne Berit, Huss, Frederik, Kol, Mark, Wong, Helen, Starr, Therese, De Crop, Luc, de Oliveira Filho, Wilson, Silva, João Manoel, Grion, Cintia MC, Jeschke, Marc G, Burnett, Marjorie, Mondrup, Frederik, Ravat, Francois, Fontaine, Mathieu, Asehoune, Karim, Le Floch, Renan, Jeanne, Mathieu, Bacus, Morgane, Chaussard, Maïté, Lehnhardt, Marcus, Mikhail, Bassem Daniel, Gille, Jochen, Sharkey, Aidan, Trommel, Nicole, Reidinga, Auke C, Vieleers, Nadine, Tilsley, Anna, Onarheim, Henning, Bouza, Maria Teresa, Agrifoglio, Alexander, Fredén, Filip, Palmieri, Tina, Painting, Lynda E, and investigators, LAMiNAR

Subjects
Paediatrics, Biomedical and Clinical Sciences, Physical Injury - Accidents and Adverse Effects, Clinical Research, Lung, Respiratory, Mechanical ventilation, Inhalation trauma, Lung-protective, Critical care, LAMiNAR investigators, Clinical sciences, Medical biotechnology, Biomedical engineering
Abstract

BackgroundIt is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28).MethodsThis is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma.ResultsA total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures

Published
2021

107. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Author

Martinez, Amadeu, Leal, Livia, Jorge Pereira, Antonio, de Oliveira Maia, Marcelo, Neto, Josè Aires, Piras, Claudio, Caser, Eliana Bernadete, Moreira, Cora Lavigne, Braga Gusman, Pablo, Dalcomune, Dyanne Moysés, Ribeiro de Carvalho, Alexandre Guilherme, Gondim, Louise Aline Romão, Castelo Branco Reis, Lívia Mariane, da Cunha Ribeiro, Daniel, de Assis Simões, Leonardo, Campos, Rafaela Siqueira, Fernandez Versiani dos Anjos, José Carlos, Bruzzi Carvalho, Frederico, Alves, Rossine Ambrosio, Nunes, Lilian Batista, Réa-Neto, Álvaro, de Oliveira, Mirella Cristine, Tannous, Luana, Cardoso Gomes, Brenno, Rodriguez, Fernando Borges, Abelha, Priscila, Lugarinho, Marcelo E, Japiassu, Andre, de Melo, Hélder Konrad, Lopes, Elton Afonso, Varaschin, Pedro, de Souza Dantas, Vicente Cés, Freitas Knibel, Marcos, Ponte, Micheli, de Azambuja Rodrigues, Pedro Mendes, Costa Filho, Rubens Carmo, Saddy, Felipe, Wanderley Castellões, Théia Forny, Silva, Suzana Alves, Osorio, Luiz Antonio Gomes, Mannarino, Dora, Espinoza, Rodolfo, Righy, Cassia, Soares, Marcio, Salluh, Jorge, Tanaka, Lilian, Aragão, Daniel, Tavares, Maria Eduarda, Kehdi, Maura Goncalves Pereira, Rezende, Valéria Maria Campos, Carbonell, Roberto Carlos Cruz, Teixeira, Cassiano, de Oliveira, Roselaine Pinheiro, Maccari, Juçara Gasparetto, Castro, Priscylla Souza, Berto, Paula, Schwarz, Patricia, Torelly, André Peretti, Lisboa, Thiago, Moraes, Edison, Dal-Pizzol, Felipe, Tomasi Damiani, Cristiane, Ritter, Cristiane, Ferreira, Juliana Carvalho, Teixeira Costa, Ramon, Caruso, Pedro, Amendola, Cristina Prata, de Oliveira, Amanda Maria R R, Silva, Ulysses V A, Sanches, Luciana Coelho, Almeida, Rosana D S, Azevedo, Luciano Cesar, Park, Marcelo, Schettino, Guilherme, Assunção, Murillo Santucci, Silva, Eliezer, Barboza, Carlos Eduardo, Junior, Antonio Paulo Nassar, Marzocchi Tierno, Paulo Fernando G M, Malbouisson, Luis Marcelo, Oliveira, Lucas, Cristovao, Davi, Neto, Manoel Leitão, Rego, Ênio, Fernandes, Fernanda Eugênia, Romano, Marcelo Luz Pereira, Cavalcanti, Alexandre Biasi, de Souza Barros, Dalton, Suzumura, Érica Aranha, Meira, Karla Loureiro, de Oliveira, Gustavo Affonso, Luciano, Paula Menezes, Pacheco, Evelin Drociunas, Mazza, Bruno Franco, Machado, Flavia Ribeiro, Ferreira, Elaine, dos Santos, Ronaldo Batista, Colombo, Alexandra Siqueira, Nogueira, Antonio Carlos, Fernandes, Juliana Baroni, Nóbrega, Raquel Siqueira, do CS Martins, Barbara, Soriano, Francisco, Morsch, Rafaela Deczka, Nunes, Andre Luiz Baptiston, de Almeida, Juliano Pinheiro, Hajjar, Ludhmila, Moulin, Sílvia, Giannini, Fábio Poianas, Baptiston Nunes, Andre Luiz, Rios, Fernando, Van Haren, Frank, Sottiaux, T, Lora, Fredy S, Azevedo, Luciano C, Depuydt, P, Fan, Eddy, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marcos, Silesky, Juan, Cerny, Vladimir, Nielsen, Jonas, Jibaja, Manuel, Pham, Tài, Wrigge, Hermann, Matamis, Dimitrios, Ranero, Jorge Luis, Hashemian, S M, Amin, Pravin, Clarkson, Kevin, Bellani, Giacomo, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Zeggwagh, Amine Ali, Heunks, Leo M, Laake, Jon Henrik, Palo, Jose Emmanuel, do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Lorente, Jose A, Larsson, Anders, Piquilloud, Lise, Abroug, Fekri, McAuley, Daniel F, McNamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Francois, Guy M, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, Insaurralde, Carolina S, Alejandro, Risso V, Daldin, Julio, Vinzio, Mauricio, Fernandez, Ruben O, Cardonnet, Luis P, Bettini, Lisandro R, Bisso, Mariano Carboni, Osman, Emilio M, Setten, Mariano G, Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, Milstein, Cesar, Pozo, Norberto C, Grubissich, Nicolas, Plotnikow, Gustavo A, Vasquez, Daniela N, Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, Pellegrini, Carlos A, Saenz, María G, Estenssoro, Elisa, Brizuela, Matias, Gianinetto, Hernan, Gomez, Pablo E, Cerrato, Valeria I, Bezzi, Marco G, Borello, Silvina A, Loiacono, Flavia A, Fernandez, Adriana M, Knowles, Serena, Reynolds, Claire, Inskip, Deborah M, Miller, Jennene J, Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J, Millar, Rebecca T, Mckenna, Toni E, Bailey, Irene M, Hanlon, Gabrielle C, Aneman, Anders, Lynch, Joan M, Azad, Raman, Neal, John, Woods, Paul W, Roberts, Brigit L, Kol, Mark R, Wong, Helen S, Riss, Katharina C, Staudinger, Thomas, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A, Dive, Alain M, Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Joris, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I, Beraldo, Daniel O, Ampinelli, Adenilton M R, Nassar Jr, Antonio P, Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M, Gonçalves, Claudio H, Antônio, Ana Carolina P, Ascoli, Aline, Biondi, Rodrigo S, Fontenele, Danielle C, Nobrega, Danielle, Sales, Vanessa M, Shindhe, Suresh, Ismail, Dk Maizatul Aiman B Pg Hj, Laffey, John, Beloncle, Francois, Davies, Kyle G, Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C, Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D, Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R, Garcia, Patricio H, Aliaga, Felipe A, Farías, Pamela A, Yumha, Jacob S, Ortiz, Claudia A, Salas, Javier E, Saez, Alejandro A, Vega, Luis D, Labarca, Eduardo F, Martinez, Felipe T, Carreño, Nicolás G, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Ye, Zheng L, Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Wu, Ya Q, Huang, Xiao B, He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X, Qin, Shu H, Zhu, Bao H, Zhao, Jun, Liu, Jian, Li, Bin, Liu, Jing L, Zhou, Fa C, Li, Qiong J, Zhang, Xing Y, Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, Gao, Yuan N, Zhao, Xian Y, Li, Yuan Y, Li, Xiao L, Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Huang, Qing Q, Zhu, Wei H, Hang, Ai Y, Hua, Ma X, Li, Yimin, Xu, Yonghao, Di, Yu D, Ling, Long L, Qin, Tie H, Wang, Shou H, Qin, Junping, Han, Yi, Zhou, Suming, Vargas, Monica P, Silesky Jimenez, Juan I, González Rojas, Manuel A, Solis-Quesada, Jaime E, Ramirez-Alfaro, Christian M, Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Boris G, Llano, Miguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicolas, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicolas, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicolas, Chiche, Jean-Daniel, Daviaud, Fabrice, Pham, Tai, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Denis, Arnal, Jean-Michel, Briquet, Anais, Hraiech, Sami, Papazian, Laurent, Follin, Arnaud, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelos, Dangers, Laurence, Combes, Alain, Au, Siu-Ming, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H, Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L, Besset, Sebastien L, Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J, Phan, Nga T, Berkelmans, Frantz, Badie, Julio C, Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Francis, Declercq, Pierre-Louis M, Rigaud, Jean-Philippe, Duranteau, Jacques, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Ould Zein, Salem, Richecoeur, Jack R, Combaux, Daniele M, Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elise P, Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, Dany, Baboi, Loredana, Guérin, Claude, Lohner, Ralph, Kraßler, Jens, Schäfer, Susanne, Zacharowski, Kai D, Meybohm, Patrick, Reske, Andreas W, Simon, Philipp, Hopf, Hans-Bernd F, Schuetz, Michael, Baltus, Thomas, Papanikolaou, Metaxia N, Papavasilopoulou, Theonymfi G, Zacharas, Giannis A, Ourailogloy, Vasilis, Mouloudi, Eleni K, Massa, Eleni V, Nagy, Eva O, Stamou, Electra E, Kiourtzieva, Ellada V, Oikonomou, Marina A, Avila, Luis E, Cortez, Cesar A, Citalán, Johanna E, Jog, Sameer A, Sable, Safal D, Shah, Bhagyesh, Gurjar, Mohan, Baronia, Arvind K, Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, Ramesh, Venkatapura J, Shenoy, Anitha, Unnikrishnan, Ramesh, Dixit, Subhal B, Rhayakar, Rachana V, Ramakrishnan, Nagarajan, Bhardwaj, Vallish K, Mahto, Heera L, Sagar, Sudha V, Palaniswamy, Vijayanand, Ganesan, Deeban, Mohammadreza Hashemian, Seyed, Jamaati, Hamidreza, Heidari, Farshad, Meaney, Edel A, Nichol, Alistair, Knapman, Karl M, O'Croinin, Donall, Dunne, Eimhin S, Breen, Dorothy M, Clarkson, Kevin P, Jaafar, Rola F, Dwyer, Rory, Amir, Fahd, Ajetunmobi, Olaitan O, O'Muircheartaigh, Aogan C, Black, Colin S, Treanor, Nuala, Collins, Daniel V, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, Rossi, Anna, Antonelli, Massimo M, Montini, Luca M, Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Roberto R, Poli, Michela M, Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Terragni, Pierpaolo, Pattarino, Ilaria, Mojoli, Francesco, Braschi, Antonio, Borotto, Erika E, Cracchiolo, Andrea N, Palma, Daniela M, Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettore R, Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, Iotti, Giorgio A, Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, Maeyama, Hiroki N, Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Olegs, Oss, Peteris, Haddad, Youssef, Liew, Kong Y, Ñamendys-Silva, Silvio A, Jarquin-Badiola, Yves D, Sanchez-Hurtado, Luis A, Gomez-Flores, Saira S, Marin, Maria C, Villagomez, Asisclo J, Lemus, Jordana S, Fierro, Jonathan M, Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flores, Gonzalez, Daniel R, Dector, Dulce M, Estrella, Claudia R, Sanchez-Medina, Jorge R, Ramirez-Gutierrez, Alvaro, George, Fernando G, Aguirre, Janet S, Buensuseso, Juan A, Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M, Schouten, Jeroen A, Rinia, Myra, Raaijmakers, Monique, Van Wezel, Hellen M, Heines, Serge J, Buise, Marc P, Simonis, Fabienne D, Schultz, Marcus J, Goodson, Jennifer C, rowne, Troy S B, Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A, Bailey, Mathew B, Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Danielle J, Andersen, Finn H, Dolva, Merete S, Laake, Jon H, Barratt-Due, Andreas, Noremark, Kim Andre L, Søreide, Eldar, Sjøbø, Brit Å, Guttormsen, Anne B, Yoshido, Hector H Leon, Aguilar, Ronald Zumaran, Oscanoa, Fredy A Montes, Alisasis, Alain U, Robles, Joanne B, Pasanting-Lim, Rossini Abbie B, Tan, Beatriz C, Andruszkiewicz, Pawel, Jakubowska, Karina, Cox, Cristina M, Alvarez, António M, Oliveira, Bruno S, Montanha, Gustavo M, Barros, Nelson C, Pereira, Carlos S, Messias, António M, Monteiro, Jorge M, Araujo, Ana M, Catorze, Nuno T, Marum, Susan M, Bouw, Maria J, Gomes, Rui M, Brito, Vania A, Castro, Silvia, Estilita, Joana M, Barros, Filipa M, Serra, Isabel M, Martinho, Aurelia M, Tomescu, Dana R, Marcu, Alexandra, Bedreag, Ovidiu H, Papurica, Marius, Corneci, Dan E, Negoita, Silvius Ioan, Grigoriev, Evgeny, Gritsan, Alexey I, Gazenkampf, Andrey A, Almekhlafi, Ghaleb, Albarrak, Mohamad M, Mustafa, Ghanem M, Maghrabi, Khalid A, Salahuddin, Nawal, Aisa, Tharwat M, Al Jabbary, Ahmed S, Tabhan, Edgardo, Arabi, Yaseen M, Trinidad, Olivia A, Al Dorzi, Hasan M, Tabhan, Edgardo E, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juan C, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermo M, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruiz-Aguilar, Antonio L, Claraco-Vega, Luis M, Soler, Juan Alfonso, Lorente, Maria del Carmen, Hermosa, Cecilia, Gordo, Federico, Prieto-González, Miryam, López-Messa, Juan B, Perez, Manuel P, Pere, Cesar P, Allue, Raquel Montoiro, Roche-Campo, Ferran, Ibañez-Santacruz, Marcos, Temprano, Susana, Pintado, Maria C, De Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesias, Jurado, Mª Teresa, Arizmendi, Alfons, Piacentini, Enrique A, Franco, Nieves, Honrubia, Teresa, Perez Cheng, Meisy, Perez Losada, Elena, Blanco, Javier, Yuste, Luis J, Carbayo-Gorriz, Cecilia, Cazorla-Barranquero, Francisca G, Alonso, Javier G, Alda, Rosa S, Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Marcos, Diego Pastor, Montero, Laura Alvarez, Para, Luis Herrera, Sanchez, Roberto Jimenez, Blasco Navalpotro, Miguel Angel, Abad, Ricardo Diaz, Montiel González, Raquel, Toribio, Dácil Parrilla, Castro, Alejandro G, Artiga, Maria Jose D, Penuelas, Oscar, Roser, Tomas P, Olga, Moreno F, Curto, Elena Gallego, Sánchez, Rocío Manzano, Imma, Vallverdu P, Elisabet, Garcia M, Claverias, Laura, Magret, Monica, Pellicer, Ana M, Rodriguez, Lucia L, Sánchez-Ballesteros, Jesús, González-Salamanca, Ángela, Jimenez, Antonio G, Huerta, Francisco P, Diaz, Juan Carlos J Sotillo, Lopez, Esther Bermejo, Moya, David D Llinares, Alfonso, Alec A Tallet, Eugenio Luis, Palazon Sanchez, Cesar, Palazon Sanchez, Rafael, Sánchez I, Virgilio, Corcoles G, Recio, Noelia N, Adamsson, Richard O, Rylander, Christian C, Holzgraefe, Bernhard, Broman, Lars M, Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Hans, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lars, Helleberg, Johan, Eriksson, Karin E, Glietsch, Rita, Larsson, Niklas, Nygren, Ingela, Nunes, Silvia L, Morin, Anna-Karin, Kander, Thomas, Adolfsson, Anne, Zender, Hervé O, Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Ben Souissi, Asma, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onat O, Derman, Suleyman S, Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, McAuley, Danny, Steinberg, Jack, Hopkins, Phil, Mellis, Clare, Stansil, Frank, Kakar, Vivek, Hadfield, Dan, Brown, Christine, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K, Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S, Fawkes, Danielle A, Watt, Philip, Twohey, Linda, Thomas, Rajeev R Jha Matthew, Morton, Alex, Kadaba, Varsha, Smith, Mark J, Hormis, Anil P, Kannan, Santhana G, Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolcs, Nutt, Christopher, Oneill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopher J, Ellis, Helen E, Mckechnie, Stuart, Hutton, Paula J, Di Tomasso, Nora N, Vitale, Michela N, Griffin, Ruth O, Dean, Michael N, Cranshaw, Julius H, Willett, Emma L, Ioannou, Nicholas, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieter D, Williams, Alexandra J, Boyd, Owen, De Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simon K, Wenham, Tim, Szakmany, Tamas, Toth-Tarsoly, Piroska, Mccalman, Katie H, Alexander, Peter, Stephenson, Lorraine, Collyer, Thomas, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M, Sim, Malcolm, Wrathall, David W, Irvine, Donald A, Zantua, Kim S, Adams, John C, Burtenshaw, Andrew J, Sellors, Gareth P, Welters, Ingeborg D, Williams, Karen E, Hessell, Robert J, Oldroyd, Matthew G, Battle, Ceri E, Pillai, Suresh, Kajtor, Istvan, Sivashanmugave, Mageswaran, Okane, Sinead C, Donnelly, Adrian, Frigyik, Aniko D, Careless, Jon P, May, Martin M, Stewart, Richard, Trinder, T John, Hagan, Samantha J, Wise, Matt P, Cole, Jade M, MacFie, Caroline C, Dowling, Anna T, Nin, Nicolás, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C, Santos, Cristina, França, Ana G, Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Banner-Goodspeed, Valerie M, Beitler, Jeremy R, Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Lee, Jarone, Mesar, Tomaz, Shinn Iii, John O, Gomaa, Dina, Tainter, Christopher, Cowley, R Adams, Yeatts, Dale J, Warren, Jessica, Lanspa, Michael J, Miller, Russel R, Grissom, Colin K, Brown, Samuel M, Bauer, Philippe R, Gosselin, Ryan J, Kitch, Barrett T, Cohen, Jason E, Beegle, Scott H, Gueret, Renaud M, Tulaimat, Aiman, Choudry, Shazia, Stigler, William, Batra, Hitesh, Huff, Nidhi G, Lamb, Keith D, Oetting, Trevor W, Mohr, Nicholas M, Judy, Claine, Saito, Shigeki, Kheir, Fayez M, Schlichting, Adam B, Delsing, Angela, Elmasri, Mary, Crouch, Daniel R, Ismail, Dina, Blakeman, Thomas C, Dreyer, Kyle R, Baron, Rebecca M, Grijalba, Carolina Quintana, Hou, Peter C, Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L, Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Rodgers, Helen, Dixon, Barry, Smith, Roger, Kol, Mark, Wong, Helen, Schmid, Werner, Hermans, Greet, Bourgeois, Marc, Anquez, Nathalie, Decruyenaere, Johan, DeCrop, Luc, Neto, Ary Serpa, Souza dos Santos, Rafaella, Beraldo, Daniel, dos Santos, Moreno Calcagnotto, Pellegrini, Jose Augusto Santos, Oliveira, Vanessa, Munhoz, Carlos, Peçanha, Ana Carolina, da Silva Ramos, Fernando José, Maia, Israel, Bahl, Marina, Biondi, Rodrigo, Prado, Daniel, Pinto, Sérgio Felix, Salgado, Jean, Falcão, Luis Fernando, Macruz, Tiago, Ruas, Kessia, Mecatti, Giovana Colozza, Caser, Eliane Bernadete, Gava, Isabela Ambrósio, Carreño, Nicolás, Morales, Mauricio, Avendaño, Rossana, Aguirre, Stefania, Sribar, Andrej, Klaric, Vlasta, Skilijic, Sonja, Dvorscak, Matea Bogdanovic, Krkusek, Marijana, Jurjevic, Matija, Karanovic, Nenad, Simurina, Tatjana, Stourac, Petr, Kratochvil, Milan, Schlegel, Christian, Treschan, Tanja A, Schaefer, Maximilian, Aytulun, Akut, Kienbaum, Peter, Jaafar, Rola, Collins, Daniel, Plant, Robert, Melchionda, Giuseppe, Di Lauro, Eduardo, Russotto, Vincenzo, Caione, Raffaele, Mestria, Donatella, Volta, Carlo Alberto, Seghelini, Elisa, Sales, Gabriele, D'Antini, Davide, Severgnini, Paolo, Bacuzzi, Alessandro, Peluso, Lorenzo, Verrastro, Pasquale, Raimondo, Pasquale, Gecaj-Gashi, Agreta, Tuinman, Pieter Roel, Alberts, Erna, van den Hul, Ingrid, Kuiper, Michael, de Wilde, Robert BP, Koopmans, Matty, Kose, Isil, Zincircioglu, Çiler, Dogan, Nazim, Aydin, Demet, Denker, Ahmet Sukru, Buyukkocak, Unase, Akgun, Nur, Turan, Güldem, Senturk, Evren, Demirtürk, Zerrin, Özcan, Perihan Ergin, Ekinci, Osman, Saylan, Sedat, Eren, Gulay, Ulger, Fatma, Dilek, Ahmet, Ulusoy, Hulya, Goktas, Ugur, Soyoral, Lokman, Toman, Huseyin, Orak, Yavuz, Kahveci, Feda, Mills, Gary H, Pinder, Angela, Walker, Rachel, Harrison, Jonathan, Snell, Jane, Pearson, Rachel, Sharman, Michael, Kaloo, Claire, Bynorth, Natalie, Matthews, Kelly, Hughes, Chloe, Rose, Alastair, Simeson, Karen, Niska, Lotta, Huneke, Nathan, Adderly, Jane, Padilla-Harris, Cheryl, Oliver, Rebecca, Brohi, Farooq, Wilson, Natalie, Talbot, Helen, Wilson, Deborah, Smith, Deborah, Dark, Paulo, Evans, Tracey, Fisher, Nicola, Montgomery, Jane, Fitzell, Pauline, Muench, Christoph, Hugill, Keith, Cirstea, Emanuel, Bentley, Andrew, Lynch, Katie, White, Ian, Cooper, Jonathan, Brazier, Melinda, Devile, Michael, Parris, Michael, Gill, Pardeep, Patel, Tasmin, Criswell, John, Trodd, Dawn, Griffin, Denise, Martin, Jane, Wreybrown, Caroline, Bewley, Jeremy, Sweet, Katie, Grimmer, Lisa, Kozlowski, Marta, James, Shanaz, Limb, James, Cowton, Amanda, Rogerson, David, Downes, Charlotte, Melbourne, Susan, Humphries, Ryan, Pulletz, Mark, Moreton, Sarah, Janes, Stephanie, Corner, Andrew, Linnett, Vanessa, Ritzema, Jenny, Watters, Malcolm, Windebank, Steve, Chenna, Shailaja, Howard-Griffin, Richard, Turner, Kate, Suresh, Sheeba, Blaylock, Heather, Bell, Stephanie, Blenk, Karl, Everett, Lynn, Hadfield, Daniel, Harris, Clair, Chan, Alexandre, Birch, Sian, Pegg, Claire, Plowright, Catherine, Cooper, Lucy, Hatton, Tom, McCullagh, Iain, Wright, Stephen, Scott, Carmen, Boyd, Christine, Holliday, Mark, Poultney, Una, Crowther, Hannah, Thornthwaite, Sarah, Hollister, Nigel, Hunt, Jane, Skinner, Amanda, Matsa, Ramprasad, Salt, Ruth, Matthews, Claire, Venner, Nicola, Barcraft-Barnes, Helena, Tbaily, Lee, Pogson, David, Mouland, Johanna, Rose, Steve, Lamb, Nicola, Tarmey, Nicholas, Knighton, John, Giles, Julian, Weller, Debbie, Reed, Isabelle, Hormis, Anil, Pearson, Sallyane, Harris, Meredith, Howe, Joanne, Paddle, Jonathan, Burt, Karen, Welters, Ingeborg, Walker, Anna, Youds, Laura, Hendry, Sam, Shaw, David, Williams, Karen, Hollands, Robin, Carnahan, Mandy, Stickley, Johanna, Miller, Claire, Donaldson, Denise, Tonks, Louise, Creagh-Brown, Ben, Hull, Daniel, Ortiz-Ruiz, Laura, Gopal, Shammer, Metherell, Stella, Spencer, Hazel, Frey, Christian, Brown, Carly, Clifford, Gayle, Leaver, Susannah, Ryan, Christine, Mellinghoff, Johannes Mellinghoff, Prudden, Sarah Prudden, Green, Helen Green, Roy, Alistair Roy, Furneval, Julie Furneval, Bell, Adam Bell, Lakhani, Sandeep Lakhani, Fasting, Lousie Fasting, Murray, Lorna Murray, Preller, Kobus, McInerney, Amy, Beavis, Sarah, Whileman, Amanda, Toms, Julie, Glenn, Sue, Ramali, Mohamed, Ghosh, Alison, Bullock, Clare, Barrell, Lisa, Young, Eoin, Robertson, Helen, Faulkner, Maria, MacNaughton, Peter, Tyson, Susan, Pulak, Paul, Sewell, Terri-Ann, Smalley, Christopher, Jacob, Reni, Alzugaray, Pedro, Vidal Melo, Marcos F, Joyce, Kristen, Needleman, Joseph, Ahsan, Areef, Faiz, Abul, Alam, AKM Shamsul, Khatoon, Syeda Nafisa, Nath, Ranjan Kumer, Rahman Chowdhury, Mohammed Abdur, Banik, Debabrata, Mondol, Montosh Kumar, Bhuiyan, Sakibur Rahman, Nazneed, Suraiya, Sultana, Rozina, Hamid, Tarikul, Hossain, Mozaffer, Reza, Syed Tariq, Asaduzzaman, Muhammad, Salim, Mohammad, Mostafa Kamal, Abu Hena, Taher, Sheikh Mohammed, Taohid, Taohidul Majid, Karmaker, Pranab, Roy, Sabyasachi, Das, Shantanu, Sarkar, Sohel Ahmed, Dutta, Monju Lal, Roy, Poulomi, Iyer, Shivakumar, Krishna, Bhuvana, Sampath, Sriram, Pattnaik, Rajyabardhan, Kasi, Chinni Krishna, Shah, Jignesh, Dongre, Anand, Reza Hashemian, Seyed Mohammad, Nooraei, Navid, Raessi Estabragh, Reza, Malekmohammad, Majid, Khoundabi, Batoul, Mobasher, Maziar, Mohd Yunos, Nor'azim, Kassim, Mahazir, Voon, Chern Min, Das, Stanis Sutharsa, Azauddin, Siti Nur Suhaila, Dorasamy, Dharshinie, Tai, Li Ling, Mat Nor, Mohd Basri, Zarudin, Nurhafizah, Hasan, Mohd Shahnaz, Jamaluddin, Mohamad Fadhil Hadi, Othman Jailani, Mohamad Irfan, Kayashta, Gyan, Adhikari, Aaradhana, Pangeni, Raju, Hashmi, Madiha, Joseph, Sonia, Akhtar, Aftab, Qadeer, Aayesha, Memon, Iqbal, Ali, Syed Muneeb, Idrees, Farah, Kamal, Saima, Hanif, Sadaf, Rehman, Atta Ur, Taqi, Arshad, Hussain, Tanveer, Farooq, Ahmed, Khaskheli, Saleh, Hayat, Muhammad, Indraratna, Kanishka, Beane, Abigail, Haniffa, Rashan, Samaranayake, Upeka, Mathanalagan, Sathiyamoorthy, Gunaratne, Asoka, Mithraratne, Nimangee, Thilakasiri, Kaushila, Pilimatalawwe, Chamila, Dilhani, Y A Hasitha, Fernando, Marie, Ranatunge, Kumudini, Samarasinghe, Loranthi, Vaas, Manori, Edirisooriya, Manoj, Sigera, Chathurani, Arumoli, Janaki, De Silva, Kesharie, Kudavidanage, Bimal, Pinto, Visanthi, Dissanayake, Lakshman, Chittawatanarat, Kaweesak, Kongpolprom, Napplika, Silachamroon, Udomsak, Pornsuriyasak, Prapaporn, Petnak, Tananchai, Singhatas, Pongsasit, Tangsujaritvijit, Viratch, Rungruanghiranya, Suthat, Piriyapatsom, Annop, Juntaping, Kanokkarn, Trongtrakul, Konlawij, Thungtitigul, Poungrat, Tajarernmuang, Pattraporn, Chatmongkolchart, Sunisa, Bhurayanontachai, Rungsun, Akaraborworn, Osaree, Navasakulpong, Asma, Surasit, Karjbundid, Thwaites, Louise, Nadjm, Behzad, Vu Quoc, Dat, Nguyen Thi Thanh, Ha, Nguyen Van, Kinh, Duong Bich, Thuy, Lam Minh, Yen, Pisani, Luigi, Algera, Anna Geke, Azevedo, Luciano, Paulus, Frederique, de Abreu, Marcelo Gama, Pelosi, Paolo, Dondorp, Arjen M, and Laffey, John G

Published
2022
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108. What is your diagnosis? Peritoneal effusion in a 7‐year‐old dog

Author

Alonso, Flavio H, Roy, Melissa A, and Kol, Amir

Subjects
Veterinary Sciences, Agricultural, Veterinary and Food Sciences, Animals, Ascitic Fluid, Dog Diseases, Dogs, Peritoneal Neoplasms, gelatinous ascites, mucin, mucinous adenocarcinoma, windrowing, Zoology, Veterinary sciences
Published
2020

109. Loss of sympathetic innervation to islets of Langerhans in canine diabetes and pancreatitis is not associated with insulitis.

Author

Gilor, Chen, Pires, Jully, Greathouse, Rachel, Horn, Rebecca, Huising, Mark O, Marks, Stanley L, Murphy, Brian, and Kol, Amir

Abstract

Canine diabetes mellitus (DM) affects 0.6% of the canine population and yet, its etiology is poorly understood. Most affected dogs are diagnosed as adults and are insulin-dependent. We compared pan-leukocyte and sympathetic innervation markers in pancreatic islets of adult dogs with spontaneous DM (sDM), spontaneous pancreatitis (sPanc), both (sDMPanc), toxin-induced DM (iDM) and controls. We found evidence of decreased islet sympathetic innervation but no significant infiltration of islets with leukocytes in all disease groups. We show that loss of sympathetic innervation is ongoing in canine DM and does not necessarily precede it. We further found selective loss of islet-associated beta cells in dogs with sDM and sDMPanc, suggesting that collateral damage from inflammation in the exocrine pancreas is not a likely cause of DM in these dogs. The cause of this selective loss of beta cells needs to be further elucidated but overall, our findings are not supportive of an autoimmune process as a cause of sDM in adult dogs. The loss of sympathetic innervation in sPanc in dogs that do not suffer from DM links the disease in the exocrine pancreas to a pathological process in the endocrine pancreas, suggesting pancreatitis might be a potential precursor to DM.

Published
2020

114. Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials

Author

Brian G. Murphy, Diego Castillo, N E Neely, Amir Kol, Terza Brostoff, Chris K. Grant, and Krystle L. Reagan

Subjects
cat, FIP, feline coronavirus, antiviral compound, serology, Microbiology, QR1-502
Abstract

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR “serotyped” (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

Published
2024
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115. Effectiveness of Ultrasound-guided versus Anatomical Landmark-guided Genicular Nerve Block to Treat Chronic Knee Osteoarthritis: A Retrospective Cohort Study

Author

Sarbhjit Singh, Sarbhan Singh, Maniventhan Nachimuthu, Ahmad Fauzey Kassim, Avreena Kaur Bhullar, Rajkumar Veerakumaran, Goh Ni Kol, and Nurul Azreen Mohd Roslan

Subjects
osteoarthritis of knee, pain management, nerve block, ultrasound, anatomical landmark, malaysia, Medicine
Abstract

Objectives: There is limited data on the relative effectiveness of different techniques used for administering genicular nerve block (GNB) for pain management of chronic knee osteoarthritis (OA) in the Malaysian population. This study aims to determine and compare the effectiveness of GNB administered using two pain management techniques—anatomical landmark-guided (ALG) and ultrasound-guided (USG)—for chronic knee OA in this population. Methods: This retrospective cohort study included 40 patients with chronic knee OA who received GNB, 20 of whom underwent treatment with the USG technique and the other 20 with the ALG technique. Pain, stiffness, and functional limitation scores were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index Questionnaire (WOMAC) and Numeric Rating Scale (NRS-11) at baseline and post-treatment day one, three weeks, and six weeks. Results: Both groups reported a significant reduction in WOMAC and NRS-11 scores as per their feedback on day one, three weeks, and six weeks post-treatment. Greater reductions in WOMAC and NRS-11 scores were reported by patients who received GNB via USG than by ALG technique, the difference achieving statistical significance at six weeks after treatment (p =0.026). Conclusions: GNB administration using USG and ALG techniques are both effective in significantly reducing pain, stiffness, and functional limitation in patients suffering from chronic knee OA. Among the two techniques, USG appears to be more effective. Nevertheless, GNB guided by ALG continues to be a viable treatment modality, especially in healthcare settings with limited to no USG facilities.

Published
2023
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116. Triangle diagram, Distance Geometry and Symmetries of Feynman Integrals

Author

Kol, Barak and Mazumdar, Subhajit

Subjects
High Energy Physics - Theory
Abstract

We study the most general triangle diagram through the Symmetries of Feynman Integrals (SFI) approach. The SFI equation system is obtained and presented in a simple basis. The system is solved providing a novel derivation of an essentially known expression. We stress a description of the underlying geometry in terms of the Distance Geometry of a tetrahedron discussed by Davydychev-Delbourgo [1], a tetrahedron which is the dual on-shell diagram. In addition, the singular locus is identified and the diagram's value on the locus's two components is expressed as a linear combination of descendant bubble diagrams. The massless triangle and the associated magic connection are revisited., Comment: 29 pages, JHEP published version

Published
2019
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117. Convex Set Disjointness, Distributed Learning of Halfspaces, and LP Feasibility

Author

Braverman, Mark, Kol, Gillat, Moran, Shay, and Saxena, Raghuvansh R.

Subjects
Computer Science - Data Structures and Algorithms, Computer Science - Computational Complexity, Computer Science - Computational Geometry, Computer Science - Discrete Mathematics, Computer Science - Machine Learning
Abstract

We study the Convex Set Disjointness (CSD) problem, where two players have input sets taken from an arbitrary fixed domain~$U\subseteq \mathbb{R}^d$ of size $\lvert U\rvert = n$. Their mutual goal is to decide using minimum communication whether the convex hulls of their sets intersect (equivalently, whether their sets can be separated by a hyperplane). Different forms of this problem naturally arise in distributed learning and optimization: it is equivalent to {\em Distributed Linear Program (LP) Feasibility} -- a basic task in distributed optimization, and it is tightly linked to {\it Distributed Learning of Halfdpaces in $\mathbb{R}^d$}. In {communication complexity theory}, CSD can be viewed as a geometric interpolation between the classical problems of {Set Disjointness} (when~$d\geq n-1$) and {Greater-Than} (when $d=1$). We establish a nearly tight bound of $\tilde \Theta(d\log n)$ on the communication complexity of learning halfspaces in $\mathbb{R}^d$. For Convex Set Disjointness (and the equivalent task of distributed LP feasibility) we derive upper and lower bounds of $\tilde O(d^2\log n)$ and~$\Omega(d\log n)$. These results improve upon several previous works in distributed learning and optimization. Unlike typical works in communication complexity, the main technical contribution of this work lies in the upper bounds. In particular, our protocols are based on a {\it Container Lemma for Halfspaces} and on two variants of {\it Carath\'eodory's Theorem}, which may be of independent interest. These geometric statements are used by our protocols to provide a compressed summary of the players' input., Comment: 37 pages, 8 figures

Published
2019

118. Properties of Dual Supertranslation Charges in Asymptotically Flat Spacetimes

Author

Kol, Uri and Porrati, Massimo

Subjects
High Energy Physics - Theory, General Relativity and Quantum Cosmology
Abstract

We study several properties of some new charges of asymptotically flat spacetimes. These dual supertranslation charges are akin to the magnetic large $U(1)$ charges in QED. In this paper we find the symmetries associated with these charges and show that the global dual supertranslation charge is topological because it is invariant under globally defined, smooth variations of the asymptotic metric. We also exhibit spacetimes where the charge does not vanish and we find dynamical processes that interpolate between regions with different values of these charges., Comment: 39 pages, 6 figures. v2: typos corrected, published in PRD

Published
2019
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119. Diabetes mellitus, glycaemic control, and severe COVID-19 in the Australian critical care setting: A nested cohort study

Author

Visser, Adam, Mattke, Adrian, Regli, Adrian, Rashid, Alan, Tabah, Alexis, Walker, Alison, Cheng, Allen, Corley, Amanda, Udy, Andrew, Ramnani, Anil, Eidan, Anthony, DeKeulenaer, Bart, Reddi, Benjamin, Richards, Brent, Knott, Cameron, Moore, Cara, Delzoppo, Carmel, Boschert, Catherine, Tacon, Catherine, French, Craig, Austin, Danielle, Brewster, David, Cooper, David, Crosbie, David, Hawkins, David, Jessen, Edda, Martinez, Eduardo, Fysh, Edward, Litton, Edward, Oberender, Felix, McGain, Forbes, Salt, Gavin, Eastwood, Glenn, Taori, Gopal, White, Hayden, Buscher, Hergen, Seppelt, Ian, Leditschke, Isabel Anne, Young, Janelle, Lavana, Jayshree, Cohen, Jeremy, Lugsdin, Jessica, Botha, John, Santamaria, John, Barrett, Jonathan, Singh, Kasha, Laupland, Kevin, El-Khawas, Khaled, Estensen, Kristine, Deshpande, Kush, White, Kyle, Fitzpatrick, Leigh, Campbell, Lewis, Ramanan, Mahesh, Saxena, Manoj, Kainer, Marion, Kol, Mark, Page, Mark, Plummer, Mark, Sterba, Martin, Anstey, Matthew, Brain, Matthew, Maiden, Matthew, Kilminster, Myrene, Hammond, Naomi, Bhadange, Neeraj, Humphreys, Nicole, Jain, Paras, Azzi, Paul, Secombe, Paul, Lister, Paula, Chan, Peter, McCanny, Peter, Britton, Phillip, Janin, Pierre, Krishnamurthy, Ravi, Sonawane, Ravikiran, Tiruvoipati, Ravindranath, Totaro, Richard, Bellomo, Rinaldo, Sanghavi, Ritesh, Bates, Samantha, Peake, Sandra, Bihari, Shailesh, George, Shane, Erickson, Simon, Webb, Steve, Arora, Subhash, Ganu, Subodh, Rozen, Thomas, McKenna, Toni, Kadam, Umesh, Nayyar, Vineet, Choy, Wei Han, Albassam, Wisam, Plummer, Mark P., Rait, Louise, Finnis, Mark E., French, Craig J., Douglas, James, Bhurani, Mansi, Broadley, Tessa, Trapani, Tony, Deane, Adam M., Udy, Andrew A., and Burrell, Aidan J.C.

Published
2023
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122. Multiplex secretome engineering enhances recombinant protein production and purity.

Author

Kol, Stefan, Ley, Daniel, Wulff, Tune, Decker, Marianne, Arnsdorf, Johnny, Schoffelen, Sanne, Hansen, Anders Holmgaard, Jensen, Tanja Lyholm, Gutierrez, Jahir M, Chiang, Austin WT, Masson, Helen O, Palsson, Bernhard O, Voldborg, Bjørn G, Pedersen, Lasse Ebdrup, Kildegaard, Helene Faustrup, Lee, Gyun Min, and Lewis, Nathan E

Subjects
CHO Cells, Animals, Cricetulus, Recombinant Proteins, Biological Products, Antibodies, Monoclonal, Chromatography, Gene Knockout Techniques, Synthetic Biology, High-Throughput Nucleotide Sequencing, Metabolic Engineering, Rituximab
Abstract

Host cell proteins (HCPs) are process-related impurities generated during biotherapeutic protein production. HCPs can be problematic if they pose a significant metabolic demand, degrade product quality, or contaminate the final product. Here, we present an effort to create a "clean" Chinese hamster ovary (CHO) cell by disrupting multiple genes to eliminate HCPs. Using a model of CHO cell protein secretion, we predict that the elimination of unnecessary HCPs could have a non-negligible impact on protein production. We analyze the HCP content of 6-protein, 11-protein, and 14-protein knockout clones. These cell lines exhibit a substantial reduction in total HCP content (40%-70%). We also observe higher productivity and improved growth characteristics in specific clones. The reduced HCP content facilitates purification of a monoclonal antibody. Thus, substantial improvements can be made in protein titer and purity through large-scale HCP deletion, providing an avenue to increased quality and affordability of high-value biopharmaceuticals.

Published
2020

123. Evolution-guided engineering of small-molecule biosensors

Author

Snoek, Tim, Chaberski, Evan K, Ambri, Francesca, Kol, Stefan, Bjørn, Sara P, Pang, Bo, Barajas, Jesus F, Welner, Ditte H, Jensen, Michael K, and Keasling, Jay D

Subjects
Biochemistry and Cell Biology, Biological Sciences, Chemical Sciences, Industrial Biotechnology, Biotechnology, Bioengineering, Generic health relevance, Biosensing Techniques, DNA, DNA-Binding Proteins, Directed Molecular Evolution, Escherichia coli, Gene Library, Genes, Reporter, Genetic Engineering, Green Fluorescent Proteins, Ligands, Models, Molecular, Mutagenesis, Protein Domains, Protein Structure, Secondary, Saccharomyces cerevisiae, Sorbic Acid, Transcription Factors, Environmental Sciences, Information and Computing Sciences, Developmental Biology, Biological sciences, Chemical sciences, Environmental sciences
Abstract

Allosteric transcription factors (aTFs) have proven widely applicable for biotechnology and synthetic biology as ligand-specific biosensors enabling real-time monitoring, selection and regulation of cellular metabolism. However, both the biosensor specificity and the correlation between ligand concentration and biosensor output signal, also known as the transfer function, often needs to be optimized before meeting application needs. Here, we present a versatile and high-throughput method to evolve prokaryotic aTF specificity and transfer functions in a eukaryote chassis, namely baker's yeast Saccharomyces cerevisiae. From a single round of mutagenesis of the effector-binding domain (EBD) coupled with various toggled selection regimes, we robustly select aTF variants of the cis,cis-muconic acid-inducible transcription factor BenM evolved for change in ligand specificity, increased dynamic output range, shifts in operational range, and a complete inversion-of-function from activation to repression. Importantly, by targeting only the EBD, the evolved biosensors display DNA-binding affinities similar to BenM, and are functional when ported back into a prokaryotic chassis. The developed platform technology thus leverages aTF evolvability for the development of new host-agnostic biosensors with user-defined small-molecule specificities and transfer functions.

Published
2020

124. Immunopathogenesis of canine chronic ulcerative stomatitis.

Author

Anderson, JG, Kol, A, Bizikova, P, Stapelton, BP, Ford, K, Villarreal, A, Jimenez, RJ, Vasilatis, D, and Murphy, BG

Subjects
Mouth Mucosa, Leukocytes, Animals, Dogs, Gingivitis, Necrotizing Ulcerative, Periodontal Diseases, Dog Diseases, Chronic Disease, Inflammation, Diagnosis, Differential, Fluorescent Antibody Technique, Direct, General Science & Technology
Abstract

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis.

Published
2020

126. Effects of Manufacturing Conditions on the Properties of Boric Acid/Melamine-Urea-Formaldehyde Microcapsules Prepared By in situ Polymerization: Its Inhibition Behavior on Wood Destroying Fungi

Author

Sema Aysal Keskin and Hamiyet Sahin Kol

Subjects
microencapsulation, inhibition, decay, fungi, boric acid, Biotechnology, TP248.13-248.65
Abstract

Water-soluble boric acid (BA) was microencapsulated by in situ polymerization with a melamine-urea formaldehyde shell. The effects of core-shell ratio, time, and temperature on the microcapsule characteristics were investigated. The microencapsulated BA was tested for its effectiveness against wood-destroying fungi. The results showed that the core:shell ratio affected the individuality of the microcapsules (MCs), and the most individual microcapsules were those with the 1:1 core:shell ratio. The microencapsulation temperature at the 1:1 core:shell ratio affected the surface porosity and size spectrum of MCs. The surface was porous, and the size spectrum was narrow at 50 °C. The microencapsulation reaction time at the 1:1 core-shell ratio did not have a considerable effect on the MC size. Although the MC size spectrum varied in the studied parameters (core: shell ratio, temperature, time), the average MC sizes were large enough to pass through the bordered pits of the softwood cell wall. Slow boron release was obtained by optimizing the MC preparation parameters. The optimum microencapsulation parameters for slow release of BA were the 1:1 core:shell ratio, 50 °C, and time of 120 min. The capsules produced at optimum microencapsulation parameters were biologically active against the fungus Coniophora puteana and leaching resistance was improved.

Published
2022

130. Reduced penetrance of an eastern French mutation in ATL1 autosomal-dominant inheritance (SPG3A): extended phenotypic spectrum coupled with brain 18F-FDG PET

Author

Hocquel, Armand, Ravel, Jean-Marie, Lambert, Laetitia, Bonnet, Céline, Banneau, Guillaume, Kol, Bophara, Tissier, Laurène, Hopes, Lucie, Meyer, Mylène, Dillier, Céline, Michaud, Maud, Lardin, Arnaud, Kaminsky, Anne-Laure, Schmitt, Emmanuelle, Liao, Liang, Zhu, François, Myriam, Bronner, Bossenmeyer-Pourié, Carine, Verger, Antoine, and Renaud, Mathilde

Published
2022
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133. Interactive Coding with Small Memory

Author

Efremenko, Klim, primary, Haeupler, Bernhard, additional, Kalai, Yael Tauman, additional, Kol, Gillat, additional, Resch, Nicolas, additional, and Saxena, Raghuvansh R., additional

Published
2023
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141. A Location-Inventory Model for Casualty Response Planning in Crisis Situations

Author

Behnam Vahdani and Fatemeh Farzaneh Kol Tappeh

Subjects
relief supply chain, location, inventory, meta-heuristic algorithm, Management. Industrial management, HD28-70
Abstract

When it comes to providing aid to the victims of natural and unnatural disasters, the main goal of a relief chain is to provide the items needed by the victims such as water and food, medicine, shelter and other necessities to reduce the number of deaths caused by reduce the occurrence of disasters as much as possible; therefore, designing, developing and implementing a relief chain can play an important role in finding a suitable answer. The most obvious differences in dealing with the relief supply chain are the unpredictability of demand in terms of time, place, type, scale and volume. Other reasons such chains are the sudden occurrence of a large amount of demand and a very short opportunity to provide a large amount of goods, lack of resources including goods, relief forces, appropriate technology, transportation capacity, the need to provide timely and sufficient supplies after the accident, and the risks in the relief environment. In the present research, a mathematical model for the location-inventory problem for planning response to casualties is presented; also, due to the NP-hard nature of the problem considered, meta-heuristic algorithms were used to solve it.

Published
2022
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142. Inflammatory cytokines directly disrupt the bovine intestinal epithelial barrier

Author

Charles K. Crawford, Veronica Lopez Cervantes, Mary L. Quilici, Aníbal G. Armién, María Questa, Muhammad S. Matloob, Leon D. Huynh, Aeelin Beltran, Sophie J. Karchemskiy, Katti R. Crakes, and Amir Kol

Subjects
Medicine, Science
Abstract

Abstract The small intestinal mucosa constitutes a physical barrier separating the gut lumen from sterile internal tissues. Junctional complexes between cells regulate transport across the barrier, preventing water loss and the entry of noxious molecules or pathogens. Inflammatory diseases in cattle disrupt this barrier; nonetheless, mechanisms of barrier disruption in cattle are poorly understood. We investigated the direct effects of three inflammatory cytokines, TNFα, IFNγ, and IL-18, on the bovine intestinal barrier utilizing intestinal organoids. Flux of fluorescein isothiocyanate (FITC)-labeled dextran was used to investigate barrier permeability. Immunocytochemistry and transmission electron microscopy were used to investigate junctional morphology, specifically tortuosity and length/width, respectively. Immunocytochemistry and flow cytometry was used to investigate cellular turnover via proliferation and apoptosis. Our study shows that 24-h cytokine treatment with TNFα or IFNγ significantly increased dextran permeability and tight junctional tortuosity, and reduced cellular proliferation. TNFα reduced the percentage of G2/M phase cells, and IFNγ treatment increased cell apoptotic rate. IL-18 did not directly induce significant changes to barrier permeability or cellular turnover. Our study concludes that the inflammatory cytokines, TNFα and IFNγ, directly induce intestinal epithelial barrier dysfunction and alter the tight junctional morphology and rate of cellular turnover in bovine intestinal epithelial cells.

Published
2022
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143. The Effects of Carotid Endarterectomy Surgery on Cerebral Oxygenation, Randomized Clinical Trial

Author

Gonca KAYA MERT, Onur AVCI, Oğuz GÜNDOĞDU, Cemil İSBİR, İclal ÖZDEMİR KOL, Sinan GÜRSOY, and Kenan KAYGUSUZ

Subjects
carotid endarterectomy, cerebral ischemia, near-infrared spectroscopy, Medicine
Abstract

Purpose: The aim of this study is to assess how NIRS values changed with cross-clamp (CC) duration in carotis endarterectomy (CEA) surgeries. Materials and Methods: The study included 30 patients. Before induction of general anesthesia, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (SpO2), and regional oxygen saturation(rSO2) values were recorded as right and left sides. The same parameters were recorded before the carotid CC, at the 3rd, 5th, and 10th minutes of the carotid CC, and at the 1st and 5th minutes after the cross-clamp removal postoperatively. Results: When the rSO2 values of the study participants were measured at different times, there was a significant difference (p

Published
2022
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145. Methodological approaches to the CO2 emissions estimation in rail transport

Author

Bezdudnaya Anna, Kol Olga, Smirnov Roman, and Treyman Marina

Subjects
transport and logistics sector, rail transport, greenhouse gases, volumes of net carbon dioxide, Environmental sciences, GE1-350
Abstract

Today there is a growing interest in the problems of assessing the impact of greenhouse gases on the environment. Modern methods for estimating the volume of CO2 emissions from cargo transportation processes are inaccurate. The study aims to develop a methodology for calculating and estimating the volume of CO2 emissions generated by rail transport during the transportation of goods and its subsequent validation. Research methods – analysis of Russian and international regulatory documents, scientific and practical methodological approaches to determine the volume of CO2 emissions for rail transport. It is substantiated that the actual methodological approach should consider direct emissions, indirect emissions and specific parameters: carbon intensity and cargo intensity, mass of transported cargo. The result of study is a methodology for calculating the volume of CO2 emissions, considering the specifics of freight transportation on railway transport and accounting for direct and indirect CO2 emissions. An example of calculating the volume of CO2 emissions during the transportation of building materials by rail between St. Petersburg and Murmansk is given. The proposed methodology makes it possible to include the amount of estimated CO2 emissions in the service, which will facilitate the introduction of "green" certificates for customers.

Published
2024
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146. Adult Animal Stem Cell-Derived Organoids in Biomedical Research and the One Health Paradigm

Author

Vojtech Gabriel, Christopher Zdyrski, Dipak K. Sahoo, Abigail Ralston, Hannah Wickham, Agnes Bourgois-Mochel, Basant Ahmed, Maria M. Merodio, Karel Paukner, Pablo Piñeyro, Jamie Kopper, Eric W. Rowe, Jodi D. Smith, David Meyerholz, Amir Kol, Austin Viall, Mohamed Elbadawy, Jonathan P. Mochel, and Karin Allenspach

Subjects
organoid, biomedical, reverse translational research, veterinary medicine, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Preclinical biomedical research is limited by the predictiveness of in vivo and in vitro models. While in vivo models offer the most complex system for experimentation, they are also limited by ethical, financial, and experimental constraints. In vitro models are simplified models that do not offer the same complexity as living animals but do offer financial affordability and more experimental freedom; therefore, they are commonly used. Traditional 2D cell lines cannot fully simulate the complexity of the epithelium of healthy organs and limit scientific progress. The One Health Initiative was established to consolidate human, animal, and environmental health while also tackling complex and multifactorial medical problems. Reverse translational research allows for the sharing of knowledge between clinical research in veterinary and human medicine. Recently, organoid technology has been developed to mimic the original organ’s epithelial microstructure and function more reliably. While human and murine organoids are available, numerous other organoids have been derived from traditional veterinary animals and exotic species in the last decade. With these additional organoid models, species previously excluded from in vitro research are becoming accessible, therefore unlocking potential translational and reverse translational applications of animals with unique adaptations that overcome common problems in veterinary and human medicine.

Published
2024
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147. A multidisciplinary nephrogenetic referral clinic for children and adults—diagnostic achievements and insights

Author

Pode-Shakked, Ben, Ben-Moshe, Yishay, Barel, Ortal, Regev, Lilach C., Kagan, Maayan, Eliyahu, Aviva, Marek-Yagel, Dina, Atias-Varon, Danit, Lahav, Einat, Issler, Naomi, Shlomovitz, Omer, Semo Oz, Rotem, Kol, Nitzan, Mor, Nofar, Bar-Joseph, Ifat, Khavkin, Yulia, Javasky, Elisheva, Beckerman, Pazit, Greenberg, Meidad, Volovelsky, Oded, Borovitz, Yael, Davidovits, Miriam, Haskin, Orly, Alfandary, Hadas, Levi, Shely, Kaidar, Maital, Katzir, Ze’ev, Angel-Korman, Avital, Becker-Cohen, Rachel, Ben-Shalom, Efrat, Leiba, Adi, Mor, Eytan, Dagan, Amit, Pessach, Itai M., Lotan, Danny, Shashar, Moshe, Anikster, Yair, Raas-Rothschild, Annick, Rechavi, Gideon, Dekel, Benjamin, and Vivante, Asaf

Published
2022
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149. The propagator seagull: general evaluation of a two loop diagram

Author

Kol, Barak and Shir, Ruth

Subjects
High Energy Physics - Theory, High Energy Physics - Phenomenology
Abstract

We study a two loop diagram of propagator type with general parameters through the Symmetries of Feynman Integrals (SFI) method. We present the SFI group and equation system, the group invariant in parameter space and a general representation as a line integral over simpler diagrams. We present close form expressions for three sectors, each with three or four energy scales, for any spacetime dimension $d$ as well as the $\epsilon$ expansion. We determine the singular locus and the diagram's value on it., Comment: 33 pages. v3: The published version - includes the $\epsilon$ expansion for the four energy scales sector

Published
2018
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150. Most Permissive Semantics of Boolean Networks

Author

Chatain, Thomas, Haar, Stefan, Kol{č}ák, Juraj, and Paulevé, Loïc

Subjects
Computer Science - Formal Languages and Automata Theory, Computer Science - Logic in Computer Science, Quantitative Biology - Quantitative Methods
Abstract

As shown in (http://dx.doi.org/10.1101/2020.03.22.998377), the usual update modes of Boolean networks (BNs), including synchronous and (generalized) asynchronous, fail to capture behaviors introduced by multivalued refinements. Thus, update modes do not allow a correct abstract reasoning on dynamics of biological systems, as they may lead to reject valid BN models.This technical report lists the main definitions and properties of the most permissive semantics of BNs introduced in http://dx.doi.org/10.1101/2020.03.22.998377. This semantics meets with a correct abstraction of any multivalued refinements, with any update mode. It subsumes all the usual updating modes, while enabling new behaviors achievable by more concrete models. Moreover, it appears that classical dynamical analyzes of reachability and attractors have a simpler computational complexity:- reachability can be assessed in a polynomial number of iterations. The computation of iterations is in NP in the very general case, and is linear when local functions are monotonic, or with some usual representations of functions of BNs (binary decision diagrams, Petri nets, automata networks, etc.). Thus, reachability is in P with locally-monotonic BNs, and P$^{\text{NP}}$ otherwise (instead of being PSPACE-complete with update modes);- deciding wherever a configuration belongs to an attractor is in coNP with locally-monotonic BNs, and coNP$^{\text{coNP}}$ otherwise (instead of PSPACE-complete with update modes).Furthermore, we demonstrate that the semantics completely captures any behavior achievable with any multilevel or ODE refinement of the BN; and the semantics is minimal with respect to this model refinement criteria: to any most permissive trajectory, there exists a multilevel refinement of the BN which can reproduce it.In brief, the most permissive semantics of BNs enables a correct abstract reasoning on dynamics of BNs, with a greater tractability than previously introduced update modes.

Published
2018

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