183 results on '"Poitevin, P"'
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2. ExaFEL: extreme-scale real-time data processing for X-ray free electron laser science
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Johannes P. Blaschke, Robert Bolotovsky, Aaron S. Brewster, Jeffrey Donatelli, Antoine DuJardin, Wu-chun Feng, Vidya Ganapati, Wilko Kroeger, Derek Mendez, Peter McCorquodale, Seema Mirchandaney, Christopher P. O'Grady, Daniel W. Paley, Amedeo Perazzo, Frederic P. Poitevin, Billy K. Poon, Vinay B. Ramakrishnaiah, Nicholas K. Sauter, Niteya Shah, Elliott Slaughter, Christine Sweeney, Daniel Tchoń, Monarin Uervirojnangkoorn, Felix Wittwer, Michael E. Wall, Chun Hong Yoon, and Iris D. Young
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exascale ,Single Particle Imaging ,Serial Femtosecond Crystallography ,hardware acceleration ,data-intensive ,interfacility ,Computer software ,QA76.75-76.765 - Abstract
ExaFEL is an HPC-capable X-ray Free Electron Laser (XFEL) data analysis software suite for both Serial Femtosecond Crystallography (SFX) and Single Particle Imaging (SPI) developed in collaboration with the Linac Coherent Lightsource (LCLS), Lawrence Berkeley National Laboratory (LBNL) and Los Alamos National Laboratory. ExaFEL supports real-time data analysis via a cross-facility workflow spanning LCLS and HPC centers such as NERSC and OLCF. Our work therefore constitutes initial path-finding for the US Department of Energy's (DOE) Integrated Research Infrastructure (IRI) program. We present the ExaFEL team's 7 years of experience in developing real-time XFEL data analysis software for the DOE's exascale supercomputers. We present our experiences and lessons learned with the Perlmutter and Frontier supercomputers. Furthermore we outline essential data center services (and the implications for institutional policy) required for real-time data analysis. Finally we summarize our software and performance engineering approaches and our experiences with NERSC's Perlmutter and OLCF's Frontier systems. This work is intended to be a practical blueprint for similar efforts in integrating exascale compute resources into other cross-facility workflows.
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- 2024
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3. Consenso mexicano de cáncer mamario. Cuidados multidisciplinarios en cáncer de mama
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Enrique Soto-Pérez-de-Celis, Dione Aguilar-y-Méndez, Silvia R. Allende-Pérez, Rosa Ma. Álvarez-Gómez, Verónica Cedillo-Compeán, Ma. Teresa de J. Cervantes-Díaz, Mariana Chávez-MacGregor, Mabelid Mabiani-Céspedes, Edith A. Monreal-Carrillo, Ma. Paulina Núñez-Martínez, Guadalupe E. Paredes-Rivera, Edith Rojas-Castillo, Sofía Saba-Cohén, Isabelle A. Timeus-Salvato, Emma L. Verastegui-Avilés, Silvia Vidal-Millán, Talia Wegman-Ostrosky, Claudia Arce-Salinas, Juan E. Bargalló-Rocha, Verónica Bautista-Piña, Guadalupe Cervantes-Sánchez, Christian H. Flores-Balcázar, Ma. del Carmen Lara-Tamburrino, Ana Lluch-Hernández, Antonio Maffuz-Aziz, Víctor M. Pérez-Sánchez, Adela Poitevin-Chacón, Efraín Salas-González, Laura Torrecillas-Torres, Vicente Valero-Castillo, Yolanda Villaseñor-Navarro, and Jesús Cárdenas-Sánchez
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Cáncer de mama. Cuidados multidisciplinarios. Consenso. ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
El cáncer mamario impacta en diversas esferas de la vida del paciente y su entorno familiar y social. Se trata de una enfermedad compleja que requiere un abordaje multidisciplinario tanto para el diagnóstico como para el tratamiento, así como en lo relativo al manejo de la toxicidad mediata y tardía del tratamiento sistémico y la radioterapia y también los aspectos psicológicos. Los cuidados paliativos y el manejo del dolor se incorporan cada vez más tempranamente al tratamiento en beneficio de los pacientes. Actualmente se ha incorporado a los genetistas a este abordaje multidisciplinario debido a los avances en genotipificación y terapias dirigidas. La difusión de este consenso contribuye a la actualización y homogeneidad de criterios de manejo del cáncer mamario y el objetivo de este artículo es el presentar la actualización en el manejo multidisciplinario del cáncer de mama.
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- 2024
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4. Towards interpretable Cryo-EM: disentangling latent spaces of molecular conformations
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David A. Klindt, Aapo Hyvärinen, Axel Levy, Nina Miolane, and Frédéric Poitevin
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cryo-EM ,machine learning ,ICA ,AI for science ,disentanglement ,physics-based models ,Biology (General) ,QH301-705.5 - Abstract
Molecules are essential building blocks of life and their different conformations (i.e., shapes) crucially determine the functional role that they play in living organisms. Cryogenic Electron Microscopy (cryo-EM) allows for acquisition of large image datasets of individual molecules. Recent advances in computational cryo-EM have made it possible to learn latent variable models of conformation landscapes. However, interpreting these latent spaces remains a challenge as their individual dimensions are often arbitrary. The key message of our work is that this interpretation challenge can be viewed as an Independent Component Analysis (ICA) problem where we seek models that have the property of identifiability. That means, they have an essentially unique solution, representing a conformational latent space that separates the different degrees of freedom a molecule is equipped with in nature. Thus, we aim to advance the computational field of cryo-EM beyond visualizations as we connect it with the theoretical framework of (nonlinear) ICA and discuss the need for identifiable models, improved metrics, and benchmarks. Moving forward, we propose future directions for enhancing the disentanglement of latent spaces in cryo-EM, refining evaluation metrics and exploring techniques that leverage physics-based decoders of biomolecular systems. Moreover, we discuss how future technological developments in time-resolved single particle imaging may enable the application of nonlinear ICA models that can discover the true conformation changes of molecules in nature. The pursuit of interpretable conformational latent spaces will empower researchers to unravel complex biological processes and facilitate targeted interventions. This has significant implications for drug discovery and structural biology more broadly. More generally, latent variable models are deployed widely across many scientific disciplines. Thus, the argument we present in this work has much broader applications in AI for science if we want to move from impressive nonlinear neural network models to mathematically grounded methods that can help us learn something new about nature.
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- 2024
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5. Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers
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Anja Seckinger, Sara Majocchi, Valéry Moine, Lise Nouveau, Hoang Ngoc, Bruno Daubeuf, Ulla Ravn, Nicolas Pleche, Sebastien Calloud, Lucile Broyer, Laura Cons, Adeline Lesnier, Laurence Chatel, Anne Papaioannou, Susana Salgado-Pires, Sebastian Krämer, Ines Gockel, Florian Lordick, Krzysztof Masternak, Yves Poitevin, Giovanni Magistrelli, Pauline Malinge, Limin Shang, Sonja Kallendrusch, Klaus Strein, and Dirk Hose
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Bispecific antibody ,CD3 ,CEACAM5 ,Immunotherapy ,T-cell engager ,Solid cancer ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background T-cell retargeting to eliminate CEACAM5-expressing cancer cells via CEACAM5xCD3 bispecific antibodies (BsAbs) showed limited clinical activity so far, mostly due to insufficient T-cell activation, dose-limiting toxicities, and formation of anti-drug antibodies (ADA). Methods We present here the generation and preclinical development of NILK-2301, a BsAb composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format). Results NILK-2301 binds CD3ɛ on T-cells with its lambda light chain arm with an affinity of ≈100 nM, and the CEACAM5 A2 domain on tumor cells by its kappa light chain arm with an affinity of ≈5 nM. FcγR-binding is abrogated by the “LALAPA” mutation (Leu234Ala, Leu235Ala, Pro329Ala). NILK-2301 induced T-cell activation, proliferation, cytokine release, and T-cell dependent cellular cytotoxicity of CEACAM5-positive tumor cell lines (5/5 colorectal, 2/2 gastric, 2/2 lung), e.g., SK-CO-1 (E max = 89%), MKN-45 (E max = 84%), and H2122 (E max = 97%), with EC50 ranging from 0.02 to 0.14 nM. NILK-2301 binds neither to CEACAM5-negative or primary colon epithelial cells nor to other CEACAM family members. NILK-2301 alone or in combination with checkpoint inhibition showed activity in organotypic tumor tissue slices and colorectal cancer organoid models. In vivo, NILK-2301 at 10 mg/kg significantly delayed tumor progression in colon- and a pancreatic adenocarcinoma model. Single-dose pharmacokinetics (PK) and tolerability in cynomolgus monkeys at 0.5 or 10 mg/kg intravenously or 20 mg subcutaneously showed dose-proportional PK, bioavailability ≈100%, and a projected half-life in humans of 13.1 days. NILK-2301 was well-tolerated. Data were confirmed in human FcRn TG32 mice. Conclusions In summary, NILK-2301 combines promising preclinical activity and safety with lower probability of ADA-generation due to its format compared to other molecules and is scheduled to enter clinical testing at the end of 2023.
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- 2023
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6. Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers
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Seckinger, Anja, Majocchi, Sara, Moine, Valéry, Nouveau, Lise, Ngoc, Hoang, Daubeuf, Bruno, Ravn, Ulla, Pleche, Nicolas, Calloud, Sebastien, Broyer, Lucile, Cons, Laura, Lesnier, Adeline, Chatel, Laurence, Papaioannou, Anne, Salgado-Pires, Susana, Krämer, Sebastian, Gockel, Ines, Lordick, Florian, Masternak, Krzysztof, Poitevin, Yves, Magistrelli, Giovanni, Malinge, Pauline, Shang, Limin, Kallendrusch, Sonja, Strein, Klaus, and Hose, Dirk
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- 2023
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7. Structural insights into functional properties of the oxidized form of cytochrome c oxidase
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Ishigami, Izumi, Sierra, Raymond G., Su, Zhen, Peck, Ariana, Wang, Cong, Poitevin, Frederic, Lisova, Stella, Hayes, Brandon, Moss, III, Frank R., Boutet, Sébastien, Sublett, Robert E., Yoon, Chun Hong, Yeh, Syun-Ru, and Rousseau, Denis L.
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- 2023
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8. Anomalous electronic transport in high-mobility Corbino rings
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Vijayakrishnan, Sujatha, Poitevin, F., Yu, Oulin, Berkson-Korenberg, Z., Petrescu, M., Lilly, M. P., Szkopek, T., Agarwal, Kartiek, West, K. W., Pfeiffer, L. N., and Gervais, G.
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- 2023
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9. Consenso mexicano de cáncer mamario. Manejo del cáncer de mama avanzado
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Guadalupe Cervantes-Sánchez, Tania Hernández-Barragán, Fernando Aldaco-Sarvide, Claudia Arce-Salinas, Juan E. Bargalló-Rocha, Verónica Bautista-Piña, Mariana Chávez-MacGregor, Georgina Garnica-Jaliffe, Christian H. Flores-Balcázar, Ma. del Carmen Lara-Tamburrino, Ana Lluch-Hernández, Antonio Maffuz-Aziz, Perla Pérez, Víctor M. Pérez-Sánchez, Adela Poitevin-Chacón, Efraín Salas-González, Enrique Soto-Pérez-de-Celis, Laura Torrecillas-Torres, Vicente Valero-Castillo, Yolanda Villaseñor-Navarro, and Jesús Cárdenas-Sánchez
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Cáncer de mama. Metástasis. Consenso. ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
El cáncer de mama es la neoplasia más frecuente y con mayor mortalidad en mujeres en todo el mundo. La décima actualización del Consenso Mexicano Sobre Diagnóstico y Tratamiento del Cáncer Mamario (2023) es publicada por sus autores en diferentes artículos. El presente artículo incluye el manejo de cáncer de mama avanzado, el tratamiento sistémico adyuvante, el papel de la cirugía y la radioterapia en enfermedad metastásica y el seguimiento posterior al tratamiento con intención curativa. La difusión de este consenso contribuye a la actualización y homogeneidad de criterios de manejo del cáncer mamario en etapas avanzadas.
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- 2024
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10. Targeting CEACAM5-positive solid tumors using NILK-2401, a novel CEACAM5xCD47 κλ bispecific antibody
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Anja Seckinger, Vanessa Buatois, Valéry Moine, Bruno Daubeuf, Françoise Richard, Laurence Chatel, Alizée Viandier, Nicolas Bosson, Emeline Rousset, Krzysztof Masternak, Susana Salgado-Pires, Claudia Batista, Christelle Mougin, Flora Juan-Bégeot, Yves Poitevin, and Dirk Hose
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bispecific antibody ,CD47 ,CEACAM5 ,immunotherapy ,solid cancer ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundBlocking the CD47 “don’t eat me”-signal on tumor cells with monoclonal antibodies or fusion proteins has shown limited clinical activity in hematologic malignancies and solid tumors thus far. Main side effects are associated with non-tumor targeted binding to CD47 particularly on blood cells.MethodsWe present here the generation and preclinical development of NILK-2401, a CEACAM5×CD47 bispecific antibody (BsAb) composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format).ResultsNILK-2401 is a fully human BsAb binding the CEACAM5 N-terminal domain on tumor cells by its lambda light chain arm with an affinity of ≈4 nM and CD47 with its kappa chain arm with an intendedly low affinity of ≈500 nM to enabling tumor-specific blockade of the CD47-SIRPα interaction. For increased activity, NILK-2401 features a functional IgG1 Fc-part. NILK-2401 eliminates CEACAM5-positive tumor cell lines (3/3 colorectal, 2/2 gastric, 2/2 lung) with EC50 for antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity ranging from 0.38 to 25.84 nM and 0.04 to 0.25 nM, respectively. NILK-2401 binds neither CD47-positive/CEACAM5-negative cell lines nor primary epithelial cells. No erythrophagocytosis or platelet activation is observed. Quantification of the pre-existing NILK-2401-reactive T-cell repertoire in the blood of 14 healthy donors with diverse HLA molecules shows a low immunogenic potential. In vivo, NILK-2401 significantly delayed tumor growth in a NOD-SCID colon cancer model and a syngeneic mouse model using human CD47/human SIRPα transgenic mice and prolonged survival. In cynomolgus monkeys, single doses of 0.5 and 20 mg/kg were well tolerated; PK linked to anti-CD47 and Fc-binding seemed to be more than dose-proportional for Cmax and AUC0-inf. Data were validated in human FcRn TG32 mice. Combination of a CEACAM5-targeting T-cell engager (NILK-2301) with NILK-2401 can either boost NILK-2301 activity (Emax) up to 2.5-fold or allows reaching equal NILK-2301 activity at >600-fold (LS174T) to >3,000-fold (MKN-45) lower doses.ConclusionNILK-2401 combines promising preclinical activity with limited potential side effects due to the tumor-targeted blockade of CD47 and low immunogenicity and is planned to enter clinical testing.
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- 2024
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11. Latin American Consensus on the Treatment of Head and Neck Cancer
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Leandro Luongo Matos, Luiz Paulo Kowalski, Aline Lauda Freitas Chaves, Thiago Bueno de Oliveira, Gustavo Nader Marta, Maria Paula Curado, Gilberto de Castro Junior, Terence P. Farias, Gustavo Sarria Bardales, Mario Avila Cabrera, Renato de Castro Capuzzo, Genival Barbosa de Carvalho, Claudio Roberto Cernea, Rogério Aparecido Dedivitis, Fernando Luiz Dias, Andrés Munyo Estefan, Agustin Horacio Falco, Gustavo Alberto Ferraris, Alejandro Gonzalez-Motta, Andre Guimarães Gouveia, Alexandre Arthur Jacinto, Marco Aurelio Vamondes Kulcsar, Ana Kober Leite, Renan Bezerra Lira, Milena Perez Mak, Pedro De Marchi, Evandro Sobroza de Mello, Fátima Cristina Mendes de Matos, Pablo H. Montero, Eduardo Dias de Moraes, Fabio Ynoe de Moraes, Diego Chaves Rezende Morais, Fernando Miguel Poenitz, Adela Poitevin, Hernán Ortiz Riveros, Álvaro Sanabria, Miguel Ticona-Castro, José Guilherme Vartanian, Gustavo Viani, Eugenio F. Vines, William Nassib William Junior, David Conway, Shama Virani, and Paul Brennan
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery—oral cavity, Clinical oncology—oral cavity, Head and neck surgery—oropharynx, Clinical oncology—oropharynx, Head and neck surgery—larynx, Head and neck surgery—larynx/hypopharynx, Clinical oncology—larynx/hypopharynx, Clinical oncology—recurrent and metastatic head and neck cancer, Head and neck surgery—reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.
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- 2024
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12. Structural insights into functional properties of the oxidized form of cytochrome c oxidase
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Izumi Ishigami, Raymond G. Sierra, Zhen Su, Ariana Peck, Cong Wang, Frederic Poitevin, Stella Lisova, Brandon Hayes, Frank R. Moss, Sébastien Boutet, Robert E. Sublett, Chun Hong Yoon, Syun-Ru Yeh, and Denis L. Rousseau
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Science - Abstract
Abstract Cytochrome c oxidase (CcO) is an essential enzyme in mitochondrial and bacterial respiration. It catalyzes the four-electron reduction of molecular oxygen to water and harnesses the chemical energy to translocate four protons across biological membranes. The turnover of the CcO reaction involves an oxidative phase, in which the reduced enzyme (R) is oxidized to the metastable OH state, and a reductive phase, in which OH is reduced back to the R state. During each phase, two protons are translocated across the membrane. However, if OH is allowed to relax to the resting oxidized state (O), a redox equivalent to OH, its subsequent reduction to R is incapable of driving proton translocation. Here, with resonance Raman spectroscopy and serial femtosecond X-ray crystallography (SFX), we show that the heme a 3 iron and CuB in the active site of the O state, like those in the OH state, are coordinated by a hydroxide ion and a water molecule, respectively. However, Y244, critical for the oxygen reduction chemistry, is in the neutral protonated form, which distinguishes O from OH, where Y244 is in the deprotonated tyrosinate form. These structural characteristics of O provide insights into the proton translocation mechanism of CcO.
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- 2023
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13. Antifungal activity of essential oils and their combinations against storage fungi
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Zimmermann, Rubens Candido, Poitevin, Carolina Gracia, da Luz, Thaisa Siqueira, Mazarotto, Edson José, Furuie, Jason Lee, Martins, Carlos Eduardo Nogueira, do Amaral, Wanderlei, Cipriano, Roger Raupp, da Rosa, Joatan Machado, Pimentel, Ida Chapaval, and Zawadneak, Maria A. C.
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- 2023
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14. Anomalous electronic transport in high-mobility Corbino rings
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Sujatha Vijayakrishnan, F. Poitevin, Oulin Yu, Z. Berkson-Korenberg, M. Petrescu, M. P. Lilly, T. Szkopek, Kartiek Agarwal, K. W. West, L. N. Pfeiffer, and G. Gervais
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Science - Abstract
Abstract We report low-temperature electronic transport measurements performed in two multi-terminal Corbino samples formed in GaAs/Al-GaAs two-dimensional electron gases (2DEG) with both ultra-high electron mobility ( ≳ 20 × 106 cm2/ Vs) and with distinct electron density of 1.7 and 3.6 × 1011 cm−2. In both Corbino samples, a non-monotonic behavior is observed in the temperature dependence of the resistance below 1 K. Surprisingly, a sharp decrease in resistance is observed with increasing temperature in the sample with lower electron density, whereas an opposite behavior is observed in the sample with higher density. To investigate further, transport measurements were performed in large van der Pauw samples having identical heterostructures, and as expected they exhibit resistivity that is monotonic with temperature. Finally, we discuss the results in terms of various lengthscales leading to ballistic and hydrodynamic electronic transport, as well as a possible Gurzhi effect.
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- 2023
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15. Consenso mexicano de cáncer mamario. Manejo del cáncer de mama temprano
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Juan E. Bargalló-Rocha, Sergio Aguilar-Villanueva, Carolina Ahumada-Pámanes, Claudia Arce-Salinas, Alethia Álvarez-Cano, Isaac Baley-Spindel, Verónica Bautista-Piña, Guadalupe Cervantes-Sánchez, Mariana Chávez-MacGregor, Nererida Esparza-Arias, Johnatan Figueroa-Padilla, Christian H. Flores-Balcázar, Sonia Ma. Flores-Moreno, Antonio Maffuz-Aziz, Federico Maldonado-Magos, Ma. del Carmen Lara-Tamburrino, Ana Lluch-Hernández, Sarina Navarro-Santiesteban, Víctor M. Pérez-Sánchez, Adela Poitevin-Chacón, Eva Ruvalcaba-Limón, Efraín Salas-González, Amelia Sarricolea-Puch, Enrique Soto-Pérez-de-Celis, Laura Torrecillas-Torres, Vicente Valero-Castillo, Yolanda Villaseñor-Navarro, and Jesús Cárdenas-Sánchez
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Cáncer de mama. Estadios tempranos. Consenso. ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
El cáncer mamario en estadios tempranos tiene un manejo local (quirúrgico y radioterapia) y sistémico específico. Este tipo de cáncer incluye el carcinoma ductal in situ y los cánceres de mama en estadios I, IIA, IIB y IIIA. Esta décima actualización del Consenso Mexicano de Cáncer Mamario abordó el manejo de los estadios tempranos. La difusión de este consenso contribuye a la actualización y homogeneidad de criterios de manejo del cáncer mamario y el objetivo de este artículo es presentar la actualización en el manejo multidisciplinario del cáncer de mama.
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- 2024
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16. Physicians’ attitudes and perceived barriers to adherence to the national breast cancer clinical practice guidelines in Mexico: a survey study
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Martinez-Cannon, Bertha Alejandra, Soto-Perez-de-Celis, Enrique, Erazo Valle-Solis, Aura, Arce-Salinas, Claudia, Bargallo-Rocha, Enrique, Bautista-Piña, Veronica, Cervantes-Sanchez, Guadalupe, Flores-Balcázar, Christian Haydeé, Lara Tamburrino, Maria del Carmen, Lluch, Ana, Maffuz-Aziz, Antonio, Pérez-Sánchez, Victor Manuel, Poitevin-Chacón, Adela, Salas-González, Efraín, Torrecillas Torres, Laura, Valero, Vicente, Villaseñor-Navarro, Yolanda, and Cárdenas-Sánchez, Jesús
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- 2023
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17. Anestesia local con epinefrina, sin manguito hemostático, para la liberación del túnel carpiano. Estudio comparativo de dos variantes técnicas en 89 casos
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Luciano Poitevin and María Solange Ferraguti
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mano ,síndrome del túnel carpiano ,anestesia local ,epinefrina. ,Orthopedic surgery ,RD701-811 - Abstract
Objetivo: Evaluar la eficacia intra- y posoperatoria, y la comodidad para el paciente de dos variantes de la anestesia en dos grupos con síndrome del túnel carpiano. Materiales y Métodos: Estudio descriptivo, comparativo, retrospectivo, observacional mediante un cuestionario telefónico de 12 ítems sobre la anestesia local sin manguito. Se incorporó a pacientes con síndrome del túnel carpiano operados entre 2008 y 2019, mediante un miniabordaje abierto. Se dividió en: grupo 1: lidocaína al 2% más bupivacaína al 0,5% más epinefrina 1:200.000 más sedación ligera (n = 32) y grupo 2: lidocaína al 2% más epinefrina 1:200.000 (n = 57). Resultados: Se evaluó a 89 pacientes (media de edad 66.9 años). Todos se mostraron satisfechos, confirmaron que volverían a elegir este procedimiento. No hubo diferencias significativas en la comodidad o el posible desarrollo de síntomas intra- o posoperatorios entre ambos grupos. La permanencia posoperatoria fue de 1-3 h, sin hospitalización. El sangrado fue mínimo. Conclusiones: La liberación del túnel carpiano bajo anestesia local más epinefrina, sin manguito hemostático, resultó segura y sin complicaciones. Los pacientes no refirieron dolor local intraoperatorio ni posoperatorio inmediato, ni en el sitio del torniquete. La permanencia en el centro asistencial fue breve. La estancia corta y la menor cantidad de elementos empleados (anestésicos, manguito) implican una reducción de los costos del procedimiento. Si bien es recomendable la presencia de un anestesiólogo, puede llegar a realizarse en ámbitos adecuados sin él. No se recomienda su empleo sin estudios prequirúrgicos ni fuera del quirófano. Nivel de Evidencia: III
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- 2022
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18. Usos y aplicaciones actuales de la radioterapia corporal estereotáctica
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Rubí Ramos-Prudencio, Francisco Lozano-Ruiz, Alejandro Rodríguez-Laguna, and Ma. Adela Poitevin-Chacón
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Oligometástasis. Radiocirugía. Radiocirugía corporal estereotáctica. ,Public aspects of medicine ,RA1-1270 ,Internal medicine ,RC31-1245 - Abstract
La radioterapia corporal estereotáctica es una modalidad que con alta precisión administra dosis alta de radiación a un objetivo tumoral bien definido, en una o en pocas fracciones, y reduce significativamente la dosis que reciben los tejidos sanos circundantes. Está indicada en cáncer primario de pulmón de células no pequeñas en estadios tempranos (T1 y T2) no operable, metástasis pulmonares con un tumor primario controlado, tumores prostáticos y enfermedad oligometastásica. A pesar de la falta de estudios a largo plazo o fase III, los resultados de su eficacia en el control local es superior a 90 %, con toxicidad similar a la reportada con fraccionamientos convencionales de radioterapia. Este artículo describe la tecnología y la técnica de radioterapia corporal estereotáctica, con las aplicaciones clínicas, indicaciones y limitaciones de esta modalidad terapéutica.
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- 2023
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19. Analysis of the Pediatric Radiotherapy Landscape in Mexico and a Subsequent Educational e-Contouring Intervention
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Raymond B. Mailhot Vega, Beatriz E. Garcia Robles, Christopher G. Morris, Kara Buss, Ulises Mejia, Adela Poitevin, Maria Fatima Chilaca Rosas, Heynar Perez Villanueva, Jesus Armando Felix Leyva, Daniel J. Indelicato, and Dolores De la Mata
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PURPOSEMexico and Central America have the highest childhood cancer incidence in the West. Pediatric-specific oncology knowledge contributes to the disparity. We sought to (1) determine the self-identified treatment patterns and needs of Mexican pediatric radiation oncologists and (2) pilot a workshop to improve contouring accuracy.MATERIALS AND METHODSPartnering with local experts and the Sociedad Mexicana de Radioterapeutas (SOMERA), a 35-question survey was designed to ascertain pediatric radiotherapy capacity and distributed through the SOMERA listserv. The most challenging malignancies were selected for workshop. Participants received precontouring and postcontouring homework to assess improvement per the Dice metric. The Wilcoxon sign-rank test was used for comparative statistics.RESULTSNinety-four radiation oncologists attempted and 79 completed the survey. Forty-four (76%) felt comfortable treating a pediatric patient, and 36 (62%) were familiar with national protocols for pediatric treatment. Most had access to nutrition, rehabilitation, endocrinology, and anesthesia; 14% had access to fertility services and 27% to neurocognitive support; 11% noted no support, and only one respondent had child-life support. The postsurvey contouring workshop was conducted for high-grade glioma, medulloblastoma, and Hodgkin lymphoma. Significant improvements were seen in all target volumes.CONCLUSIONWe present the first national survey of Mexico's pediatric radiotherapy capacity and Latin American e-contouring educational intervention with preworkshop and postworkshop Dice metrics, noting statistically significant improvement in all target volumes. Participation improved compared with prior experience through SOMERA partnership and Continuing Medical Education incentivization.
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- 2023
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20. Massive Scale Data Analytics at LCLS-II
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Thayer Jana, Chen Zhantao, Claus Richard, Damiani Daniel, Ford Christopher, Dubrovin Mikhail, Elmir Victor, Kroeger Wilko, Li Xiang, Marchesini Stefano, Mariani Valerio, Melcchiori Riccardo, Nelson Silke, Peck Ariana, Perazzo Amedeo, Poitevin Frederic, O’Grady Christopher Paul, Otero Julieth, Quijano Omar, Shankar Murali, Uervirojnangkoorn Monarin, Veraldi Riccardo, Weaver Matthew, Weninger Clemens, Yamajala Seshu, Wang Cong, and Yoon Chun Hong
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Physics ,QC1-999 - Abstract
The increasing volumes of data produced at light sources such as the Linac Coherent Light Source (LCLS) enable the direct observation of materials and molecular assemblies at the length and timescales of molecular and atomic motion. This exponential increase in the scale and speed of data production is prohibitive to traditional analysis workflows that rely on scientists tuning parameters during live experiments to adapt data collection and analysis. User facilities will increasingly rely on the automated delivery of actionable information in real time for rapid experiment adaptation which presents a considerable challenge for data acquisition, data processing, data management, and workflow orchestration. In addition, the desire from researchers to accelerate science requires rapid analysis, dynamic integration of experiment and theory, the ability to visualize results in near real-time, and the introduction of ML and AI techniques. We present the LCLS-II Data System architecture which is designed to address these challenges via an adaptable data reduction pipeline (DRP) to reduce data volume on-thefly, online monitoring analysis software for real-time data visualization and experiment feedback, and the ability to scale to computing needs by utilizing local and remote compute resources, such as the ASCR Leadership Class Facilities, to enable quasi-real-time data analysis in minutes. We discuss the overall challenges facing LCLS, our ongoing work to develop a system responsive to these challenges, and our vision for future developments.
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- 2024
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21. Influenza A, like Omicron SARS-CoV-2, Is Similarly Detected in Saliva or Nasopharyngeal Samples via RT-qPCR
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Hellen Abreu, Carla Adriane Royer, Carolina Gracia Poitevin, Ana Flávia Kohler, Ana Carolina Rodrigues, Sonia Mara Raboni, Meri Bordignon Nogueira, Pedro Henrique Cardoso, Monica Barcellos Arruda, Patrícia Alvarez da Silva Baptista, Ana Claudia Bonatto, Daniela Fiori Gradia, Douglas Adamoski, Emanuel Maltempi de Souza, and Jaqueline Carvalho de Oliveira
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virus detection ,diagnostic techniques and procedures ,surveillance ,flu ,COVID-19 ,Microbiology ,QR1-502 - Abstract
After the Coronavirus pandemic, the importance of virus surveillance was highlighted, reinforcing the constant necessity of discussing and updating the methods for collection and diagnoses, including for other respiratory viruses. Although the nasopharyngeal swab is the gold-standard sample for detecting and genotyping SARS-CoV-2 and Influenza viruses, its collection is uncomfortable and requires specialized teams, which can be costly. During the pandemic, non-invasive saliva samples proved to be a suitable alternative for SARS-CoV-2 diagnosis, but for Influenza virus the use of this sample source is not recognized yet. In addition, most SARS-CoV-2 comparisons were conducted before the Omicron variant emerged. Here, we aimed to compare Influenza A and Omicron RT-qPCR analysis of nasopharyngeal swabs and saliva self-collection in paired samples from 663 individuals. We found that both nasopharyngeal swab and saliva collection are efficient for the diagnosis of Omicron (including sub-lineages) and for Influenza A, with high sensitivity and accuracy (>90%). The kappa index is 0.938 for Influenza A and 0.905 for SARS-CoV-2. These results showed excellent agreement between the two samples reinforcing saliva samples as a reliable source for detecting Omicron and highlighting saliva as a valid sample source for Influenza detection, considering this cheaper and more comfortable alternative.
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- 2023
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22. Streptomyces spp. Isolated from Marine and Caatinga Biomes in Brazil for the Biological Control of Duponchelia fovealis
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Porsani, Mariana Vieira, Poitevin, Carolina Gracia, Tralamazza, Sabina Moser, de Souza, Mireli Trombin, de Souza, Michele Trombin, da Silva, Éder David Borges, Zawadneak, Maria Aparecida Cassilha, Pimentel, Ida Chapaval, and de Melo, Itamar Soares
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- 2022
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23. Cooperative allostery and structural dynamics of streptavidin at cryogenic- and ambient-temperature
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Ayan, Esra, Yuksel, Busra, Destan, Ebru, Ertem, Fatma Betul, Yildirim, Gunseli, Eren, Meryem, Yefanov, Oleksandr M., Barty, Anton, Tolstikova, Alexandra, Ketawala, Gihan K., Botha, Sabine, Dao, E. Han, Hayes, Brandon, Liang, Mengning, Seaberg, Matthew H., Hunter, Mark S., Batyuk, Alexander, Mariani, Valerio, Su, Zhen, Poitevin, Frederic, Yoon, Chun Hong, Kupitz, Christopher, Cohen, Aina, Doukov, Tzanko, Sierra, Raymond G., Dağ, Çağdaş, and DeMirci, Hasan
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- 2022
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24. Scientific guidelines for preclinical research on potentised preparations manufactured according to current pharmacopoeias—the PrePoP guidelines.
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Tournier, Alexander L., Bonamin, Leoni V., Buchheim-Schmidt, Susann, Cartwright, Steven, Dombrowsky, Christoph, Doesburg, Paul, Holandino, Carla, Kokornaczyk, Maria Olga, van de Kraats, Everine B., López-Carvallo, Jesús Antonio, Nandy, Papiya, Mazón-Suástegui, José Manuel, Mirzajani, Fateme, Poitevin, Bernard, Scherr, Claudia, Thieves, Karin, Würtenberger, Sandra, and Baumgartner, Stephan
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- 2024
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25. Chemical crystallography by serial femtosecond X-ray diffraction
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Schriber, Elyse A., Paley, Daniel W., Bolotovsky, Robert, Rosenberg, Daniel J., Sierra, Raymond G., Aquila, Andrew, Mendez, Derek, Poitevin, Frédéric, Blaschke, Johannes P., Bhowmick, Asmit, Kelly, Ryan P., Hunter, Mark, Hayes, Brandon, Popple, Derek C., Yeung, Matthew, Pareja-Rivera, Carina, Lisova, Stella, Tono, Kensuke, Sugahara, Michihiro, Owada, Shigeki, Kuykendall, Tevye, Yao, Kaiyuan, Schuck, P. James, Solis-Ibarra, Diego, Sauter, Nicholas K., Brewster, Aaron S., and Hohman, J. Nathan
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- 2022
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26. Application of transport-based metric for continuous interpolation between cryo-EM density maps
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Arthur Ecoffet, Geoffrey Woollard, Artem Kushner, Frédéric Poitevin, and Khanh Dao Duc
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optimal transport ,interpolation ,3d shapes ,cryo-em ,conformational heterogeneity ,Mathematics ,QA1-939 - Abstract
Cryogenic electron microscopy (cryo-EM) has become widely used for the past few years in structural biology, to collect single images of macromolecules "frozen in time". As this technique facilitates the identification of multiple conformational states adopted by the same molecule, a direct product of it is a set of 3D volumes, also called EM maps. To gain more insights on the possible mechanisms that govern transitions between different states, and hence the mode of action of a molecule, we recently introduced a bioinformatic tool that interpolates and generates morphing trajectories joining two given EM maps. This tool is based on recent advances made in optimal transport, that allow efficient evaluation of Wasserstein barycenters of 3D shapes. As the overall performance of the method depends on various key parameters, including the sensitivity of the regularization parameter, we performed various numerical experiments to demonstrate how MorphOT can be applied in different contexts and settings. Finally, we discuss current limitations and further potential connections between other optimal transport theories and the conformational heterogeneity problem inherent with cryo-EM data.
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- 2022
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27. Cooperative allostery and structural dynamics of streptavidin at cryogenic- and ambient-temperature
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Esra Ayan, Busra Yuksel, Ebru Destan, Fatma Betul Ertem, Gunseli Yildirim, Meryem Eren, Oleksandr M. Yefanov, Anton Barty, Alexandra Tolstikova, Gihan K. Ketawala, Sabine Botha, E. Han Dao, Brandon Hayes, Mengning Liang, Matthew H. Seaberg, Mark S. Hunter, Alexander Batyuk, Valerio Mariani, Zhen Su, Frederic Poitevin, Chun Hong Yoon, Christopher Kupitz, Aina Cohen, Tzanko Doukov, Raymond G. Sierra, Çağdaş Dağ, and Hasan DeMirci
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Biology (General) ,QH301-705.5 - Abstract
Ayan et al. report two structures of the protein streptavidin - one at ambient temperature determined using serial femtosecond crystallography and a second one determined at cryogenic temperature. These results provide insights into the structural dynamics of apo streptavidin and reveal a cooperative allostery between monomers for binding to biotin, and the findings are supported by GNM analysis.
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- 2022
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28. Detection and characterization of small-sized microplastics (≥ 5 µm) in milk products
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Paulo A. Da Costa Filho, Daniel Andrey, Bjorn Eriksen, Rafael P. Peixoto, Benoit M. Carreres, Mark E. Ambühl, Josep B. Descarrega, Stephane Dubascoux, Pascal Zbinden, Alexandre Panchaud, and Eric Poitevin
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Medicine ,Science - Abstract
Abstract Microplastics (MPs) have gained a high degree of public interest since they are associated with the global release of plastics into the environment. Various studies have confirmed the presence of MPs throughout the food chain. However, information on the ingestion of MPs via the consumption of many commonly consumed foods like dairy products are scarce due to the lack of studies investigating the “contamination” of this food group by MPs. This lack of occurrence data is mainly due to the absence of robust analytical methods capable of reliably quantifying MPs with size
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- 2021
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29. Cross-Sectional International Survey to Determine the Educational Interests of Spanish-Speaking Latin American Radiation Oncologists
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Raymond B. Mailhot Vega, Dolores De La Mata, Beatriz Amendola, Benjamin Li, Adela Poitevin, Gustavo Sarria, Sebastian Sole, David J. Sher, and Patricia Hardenbergh
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PURPOSEWith the existing oncology disparities in Latin America, physician expertise has been cited as a possible contributor to inferior oncologic outcomes in some cancers. As two-dimensional radiotherapy rapidly evolved to intensity-modulated radiation therapy in Latin America, adequate contouring education is an actionable target to improving physician knowledge and clinical outcomes. Yet, topics of interest to Latin American radiation oncologists are underreported. We assessed Latin American interest in a virtual platform for case discussion and identified the educational topics of most interest to them.MATERIALS AND METHODSA Spanish-language online survey was designed by a team of Latin American educators. The questions assessed professional nationality, desire for an online educational platform for case presentation, career length, and topics of interest. Educational topics included head and neck (H&N), CNS, GI, lung, gynecologic, breast, and pediatric cancers, lymphoma, sarcoma, stereotactic body radiotherapy (SBRT), brachytherapy, and medical physics.RESULTSOne hundred thirty-three surveys were included for analysis. Overall, 127 respondents (98%) affirmed interest in participating in a virtual platform for case discussion and treatment advances. The most popular educational themes were H&N cancers (24%), SBRT (14%), and CNS cancers (13%). Of countries with > 10 respondents, the most popular educational topic remained H&N cancers for Argentina, Chile, and Mexico, but the most popular topic among Peruvian respondents was CNS cancer (27%).CONCLUSIONWith international collaboration and a large sample size, we present the first survey results describing Latin American radiation oncology educational interests. Participants were overwhelmingly interested in a virtual platform, and most were specifically interested in H&N cancer education. These results can be used for focused didactic preparation in Latin America. Future efforts should expand on improving representation and outreach among Central American radiation oncologists.
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- 2021
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30. Electrically stimulated droplet injector for reduced sample consumption in serial crystallography
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Mukul Sonker, Diandra Doppler, Ana Egatz-Gomez, Sahba Zaare, Mohammad T. Rabbani, Abhik Manna, Jorvani Cruz Villarreal, Garrett Nelson, Gihan K. Ketawala, Konstantinos Karpos, Roberto C. Alvarez, Reza Nazari, Darren Thifault, Rebecca Jernigan, Dominik Oberthür, Huijong Han, Raymond Sierra, Mark S. Hunter, Alexander Batyuk, Christopher J. Kupitz, Robert E. Sublett, Frederic Poitevin, Stella Lisova, Valerio Mariani, Alexandra Tolstikova, Sebastien Boutet, Marc Messerschmidt, J. Domingo Meza-Aguilar, Raimund Fromme, Jose M. Martin-Garcia, Sabine Botha, Petra Fromme, Thomas D. Grant, Richard A. Kirian, and Alexandra Ros
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Physics ,QC1-999 ,Biology (General) ,QH301-705.5 - Abstract
With advances in X-ray free-electron lasers (XFELs), serial femtosecond crystallography (SFX) has enabled the static and dynamic structure determination for challenging proteins such as membrane protein complexes. In SFX with XFELs, the crystals are typically destroyed after interacting with a single XFEL pulse. Therefore, thousands of new crystals must be sequentially introduced into the X-ray beam to collect full data sets. Because of the serial nature of any SFX experiment, up to 99% of the sample delivered to the X-ray beam during its “off-time” between X-ray pulses is wasted due to the intrinsic pulsed nature of all current XFELs. To solve this major problem of large and often limiting sample consumption, we report on improvements of a revolutionary sample-saving method that is compatible with all current XFELs. We previously reported 3D-printed injection devices coupled with gas dynamic virtual nozzles (GDVNs) capable of generating samples containing droplets segmented by an immiscible oil phase for jetting crystal-laden droplets into the path of an XFEL. Here, we have further improved the device design by including metal electrodes inducing electrowetting effects for improved control over droplet generation frequency to stimulate the droplet release to matching the XFEL repetition rate by employing an electrical feedback mechanism. We report the improvements in this electrically triggered segmented flow approach for sample conservation in comparison with a continuous GDVN injection using the microcrystals of lysozyme and 3-deoxy-D-manno-octulosonate 8-phosphate synthase and report the segmented flow approach for sample injection applied at the Macromolecular Femtosecond Crystallography instrument at the Linear Coherent Light Source for the first time.
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- 2022
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31. A note on representations of Orlicz lattices
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Poitevin, Pedro
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- 2021
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32. A pilot study of procoagulant platelet extracellular vesicles and P-selectin increase during induction treatment in acute lymphoblastic leukaemia paediatric patients: two new biomarkers of thrombogenic risk?
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Pluchart, Claire, Barbe, Coralie, Poitevin, Gael, Audonnet, Sandra, and Nguyen, Philippe
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- 2021
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33. Protocol for structure determination of SARS-CoV-2 main protease at near-physiological-temperature by serial femtosecond crystallography
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Fatma Betul Ertem, Omur Guven, Cengizhan Buyukdag, Oktay Gocenler, Esra Ayan, Busra Yuksel, Mehmet Gul, Gozde Usta, Barıs Cakılkaya, J. Austin Johnson, E. Han Dao, Zhen Su, Frederic Poitevin, Chun Hong Yoon, Christopher Kupitz, Brandon Hayes, Mengning Liang, Mark S. Hunter, Alexander Batyuk, Raymond G. Sierra, Gihan Ketawala, Sabine Botha, Çağdaş Dağ, and Hasan DeMirci
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Protein Biochemistry ,Protein expression and purification ,Structural Biology ,X-ray Crystallography ,Science (General) ,Q1-390 - Abstract
Summary: The SARS-CoV-2 main protease of (Mpro) is an important target for SARS-CoV-2 related drug repurposing and development studies. Here, we describe the steps for structural characterization of SARS-CoV-2 Mpro, starting from plasmid preparation and protein purification. We detail the steps for crystallization using the sitting drop, microbatch (under oil) approach. Finally, we cover data collection and structure determination using serial femtosecond crystallography.For complete details on the use and execution of this protocol, please refer to Durdagi et al. (2021).
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- 2022
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34. Pathogenic Fusarium species complexes associated to seeds of indigenous Brazilian forest tree Aspidosperma polyneuron
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Mazarotto, E. J., Poitevin, C. G., do Carmo, A. L. M., dos Santos, A. F., Tralamazza, S. M., and Pimentel, I. C.
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- 2020
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35. Sera From Patients With Minimal Change Disease Increase Endothelial Permeability to Sodium
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Florence Daviet, Muriel G. Blin, Karim Fallague, Richard Bachelier, Manon Laforêt, Manon Carré, Stéphane Poitevin, Françoise Dignat-George, Marcel Blot-Chabaud, Nathalie Bardin, Stéphane Burtey, Noémie Jourde-Chiche, and Aurélie S. Leroyer
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Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2020
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36. Detection and characterization of small-sized microplastics (≥ 5 µm) in milk products
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Da Costa Filho, Paulo A., Andrey, Daniel, Eriksen, Bjorn, Peixoto, Rafael P., Carreres, Benoit M., Ambühl, Mark E., Descarrega, Josep B., Dubascoux, Stephane, Zbinden, Pascal, Panchaud, Alexandre, and Poitevin, Eric
- Published
- 2021
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37. Uncovering hidden urban bounty: A case study of Hidden Harvest
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Chloé Poitevin DesRivières
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gleaning ,social enterprise ,localized food systems ,diverse economies ,social economies ,Nutrition. Foods and food supply ,TX341-641 ,Social Sciences - Abstract
Urban food systems primarily rely on foods grown in rural spaces, and often face challenges in creating spaces to grow fresh, healthful and affordable food in cities. Urban food harvest organizations aim to overcome these challenges by locating and harvesting food that already exists in cities on the numerous fruit- and nut-bearing trees located on public and private lands. Hidden Harvest is a leading initiative for urban fruit and nut harvesting in Canada, and unique in its for-profit social enterprise model. The organization aims to legitimize and support the practice of harvesting fruits and nuts in urban areas, and provides a means to increase access to—and availability of—fresh, healthful foods hyper-locally in Ottawa, as people harvest from their own (or nearby) neighborhoods. This field report examines the challenges and opportunities faced by Hidden Harvest in attempting to link multiple social, environmental and economic goals relating to food sovereignty, social justice and ecological sustainability. In particular, the organization seeks to establish a self-sustaining business model through innovative solutions and the development of networks with local food processes, food organizations and businesses, which enables Hidden Harvest to grow and develop distinct ties and relationships in Ottawa. This case study reveals how organizations such as Hidden Harvest use food to enhance and tie together local economies, knowledge, food security and community well-being.
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- 2019
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38. 265 CD47xPD-L1 bispecific antibodies for cancer therapy
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Walter Ferlin, Stéphanie Hugues, Xavier Chauchet, Elise Pernarrieta, Nicolas Bosson, Sébastien Calloud, Louis Hellequin, Margaux Legrand, Alizée Viandier, Françoise Richard, Laura Cons, Pauline Malinge, Tereza Bautzova, Jérémie Bourguignon, Guillemette Pontini, Mengzhu Sun, Ulla Ravn, Valéry Moine, Yves Poitevin, Nicolas Fischer, Limin Shang, and Krzysztof Masternak
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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39. [Untitled]
- Author
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Adela Poitevin-Chacón
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
40. Reproducibility of protein x-ray diffuse scattering and potential utility for modeling atomic displacement parameters
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Zhen Su, Medhanjali Dasgupta, Frédéric Poitevin, Irimpan I. Mathews, Henry van den Bedem, Michael E. Wall, Chun Hong Yoon, and Mark A. Wilson
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Crystallography ,QD901-999 - Abstract
Protein structure and dynamics can be probed using x-ray crystallography. Whereas the Bragg peaks are only sensitive to the average unit-cell electron density, the signal between the Bragg peaks—diffuse scattering—is sensitive to spatial correlations in electron-density variations. Although diffuse scattering contains valuable information about protein dynamics, the diffuse signal is more difficult to isolate from the background compared to the Bragg signal, and the reproducibility of diffuse signal is not yet well understood. We present a systematic study of the reproducibility of diffuse scattering from isocyanide hydratase in three different protein forms. Both replicate diffuse datasets and datasets obtained from different mutants were similar in pairwise comparisons (Pearson correlation coefficient ≥0.8). The data were processed in a manner inspired by previously published methods using custom software with modular design, enabling us to perform an analysis of various data processing choices to determine how to obtain the highest quality data as assessed using unbiased measures of symmetry and reproducibility. The diffuse data were then used to characterize atomic mobility using a liquid-like motions (LLM) model. This characterization was able to discriminate between distinct anisotropic atomic displacement parameter (ADP) models arising from different anisotropic scaling choices that agreed comparably with the Bragg data. Our results emphasize the importance of data reproducibility as a model-free measure of diffuse data quality, illustrate the ability of LLM analysis of diffuse scattering to select among alternative ADP models, and offer insights into the design of successful diffuse scattering experiments.
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- 2021
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41. In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia
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Rida Al-Rifai, Philippe Nguyen, Nicole Bouland, Christine Terryn, Lukshe Kanagaratnam, Gaël Poitevin, Caroline François, Catherine Boisson-Vidal, Marie-Antoinette Sevestre, and Claire Tournois
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Angiogenesis ,Cell therapy ,Critical limb ischemia ,Mesenchymal stem cells ,Medicine - Abstract
Abstract Background Cell therapy has been proposed for patients with critical limb ischemia (CLI). Autologous bone marrow derived cells (BMCs) have been mostly used, mesenchymal stem cells (MSCs) being an alternative. The aim of this study was to characterize two types of MSCs and evaluate their efficacy. Methods MSCs were obtained from CLI-patients BMCs. Stimulated- (S-) MSCs were cultured in endothelial growth medium. Cells were characterized by the expression of cell surface markers, the relative expression of 6 genes, the secretion of 10 cytokines and the ability to form vessel-like structures. The cell proangiogenic properties was analysed in vivo, in a hindlimb ischemia model. Perfusion of lower limbs and functional tests were assessed for 28 days after cell infusion. Muscle histological analysis (neoangiogenesis, arteriogenesis and muscle repair) was performed. Results S-MSCs can be obtained from CLI-patients BMCs. They do not express endothelial specific markers but can be distinguished from MSCs by their secretome. S-MSCs have the ability to form tube-like structures and, in vivo, to induce blood flow recovery. No amputation was observed in S-MSCs treated mice. Functional tests showed improvement in treated groups with a superiority of MSCs and S-MSCs. In muscles, CD31+ and αSMA+ labelling were the highest in S-MSCs treated mice. S-MSCs induced the highest muscle repair. Conclusions S-MSCs exert angiogenic potential probably mediated by a paracrine mechanism. Their administration is associated with flow recovery, limb salvage and muscle repair. The secretome from S-MSCs or secretome-derived products may have a strong potential in vessel regeneration and muscle repair. Trial registration NCT00533104
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- 2019
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42. A behavioral economic risk aversion experiment in the context of the COVID-19 pandemic.
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Bruno Kluwe-Schiavon, Thiago Wendt Viola, Lucas Poitevin Bandinelli, Sayra Catalina Coral Castro, Christian Haag Kristensen, Jaderson Costa da Costa, and Rodrigo Grassi-Oliveira
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Medicine ,Science - Abstract
We investigated what degree of risk of infection with COVID-19 is necessary so that people intend to stay home, even when doing so means losing their salary. We conducted an online survey across Brazil during the initial outbreak, in which 8,345 participants answered a questionnaire designed to identify the maximum tolerated risk (k') necessary for them to disregard social distancing recommendations and guarantee their salaries. Generalized linear mixed models, path analysis structural equation, and conditional interference classification tree were performed to further understand how sociodemographic factors impact k' and to establish a predictive model for the risk behavior of leaving home during the pandemic. We found that, on average, people tolerate 38% risk of infection to leave home and earn a full salary, but this number decreased to 13% when the individual risk perception of becoming ill from severe acute respiratory syndrome coronavirus-2 is considered. Furthermore, participants who have a medium-to-high household income and who are older than 35 years are more likely to be part of the risk-taking group who leave home regardless of the potential COVID-19 infection level; while participants over 45 years old and with good financial health are more likely to be part of the risk-averse group, who stay home at the expense of any salary offered. Our findings add to the political and public debate concerning lockdown strategies by showing that, contrary to supposition, people with low socioeconomic status are not more likely to ignore social distancing recommendations due to personal economic matters.
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- 2021
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43. Tryptophan Metabolites Regulate Neuropentraxin 1 Expression in Endothelial Cells
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Romain Vial, Stéphane Poitevin, Nathalie McKay, Stéphane Burtey, and Claire Cerini
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aryl hydrocarbon receptor ,indolic uremic toxins ,indoxyl sulfate ,indole-3-acetic acid ,neuropentraxin 1 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
In patients with chronic kidney disease (CKD) and in animal models of CKD, the transcription factor Aryl Hydrocabon Receptor (AhR) is overactivated. In addition to the canonical AhR targets constituting the AhR signature, numerous other genes are regulated by this factor. We identified neuronal pentraxin 1 (NPTX1) as a new AhR target. Belonging to the inflammatory protein family, NPTX1 seems of prime interest regarding the inflammatory state observed in CKD. Endothelial cells were exposed to tryptophan-derived toxins, indoxyl sulfate (IS) and indole-3-acetic acid (IAA). The adenine mouse model of CKD was used to analyze NPTX1 expression in the burden of uremia. NPTX1 expression was quantified by RT-PCR and western blot. AhR involvement was analyzed using silencing RNA. We found that IS and IAA upregulated NPTX1 expression in an AhR-dependent way. Furthermore, this effect was not restricted to uremic indolic toxins since the dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) do the same. In CKD mice, NPTX1 expression was increased in the aorta. Therefore, NPTX1 is a new target of AhR and further work is necessary to elucidate its exact role during CKD.
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- 2022
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44. Vincristine induces procoagulant activity of the human lymphoblastic leukemia cell line Jurkat through the release of extracellular vesicles
- Author
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Pluchart, Claire, Poitevin, Gael, Colinart-Thomas, Maud, Guimard, Gregory, Audonnet, Sandra, Terryn, Christine, and Nguyen, Philippe
- Published
- 2019
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45. Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells
- Author
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Addi, Tawfik, Poitevin, Stéphane, McKay, Nathalie, El Mecherfi, Kamel Eddine, Kheroua, Omar, Jourde-Chiche, Noémie, de Macedo, Alix, Gondouin, Bertrand, Cerini, Claire, Brunet, Philippe, Dignat-George, Françoise, Burtey, Stéphane, and Dou, Laetitia
- Published
- 2019
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46. Ciencia, matemáticas y poesía
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Pedro Poitevin
- Subjects
Poesía ,Ciencias Naturales ,Matemáticas ,Estructuralismo ,Law ,Architecture ,NA1-9428 ,Social Sciences - Abstract
Este texto explora las distintas modalidades que manifiesta la relación entre poesía y ciencias matemáticas y naturales. También propone un esquema estructuralista para identificar senderos por los que la poesía de la ciencia puede cultivar armonía y/o tensión con el conocimiento científico.
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- 2020
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47. Assessment of Thrombotic and Bleeding Tendency in Two Mouse Models of Chronic Kidney Disease: Adenine-Diet and 5/6th Nephrectomy
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Camélia Makhloufi, Lydie Crescence, Roxane Darbousset, Nathalie McKay, Ziad A. Massy, Christophe Dubois, Laurence Panicot-Dubois, Stéphane Burtey, and Stéphane Poitevin
- Subjects
tissue factor ,platelets ,hemostasis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The coexistence of bleeding and thrombosis in patients with chronic kidney disease (CKD) is frequent and poorly understood. Mouse models are essential to understand complications of CKD and to develop new therapeutic approaches improving the health of patients. We evaluated the hemostasis in two models of renal insufficiency: adenine-diet and 5/6th nephrectomy (5/6Nx). Compared with 5/6Nx mice, mice fed with 0.25% adenine had more severe renal insufficiency and so higher levels of prothrombotic uremic toxins like indoxyl sulfate. More severe renal inflammation and fibrosis were observed in the adenine group, as demonstrated by histological and reverse transcription quantitative polymerase chain reaction experiments. Liver fibrinogen γ chain expression and level of plasma fibrinogen were increased only in adenine mice. In both CKD mouse models, tissue factor (TF) expression was increased in kidney and aorta extracts. Immunochemistry analysis of kidney sections showed that TF is localized in the vascular walls. Thrombin–antithrombin complexes were significantly increased in plasma from both adenine and 5/6Nx mice. Tail bleeding time increased significantly only in adenine mice, whereas platelet count was not significant altered. Finally, results obtained by intravital microscopy after laser-induced endothelial injury showed impaired platelet function in adenine mice and an increase in fibrin generation in 5/6Nx mice. To summarize, adenine diet causes a more severe renal insufficiency compared with 5/6Nx. The TF upregulation and the hypercoagulable state were observed in both CKD models. Bleeding tendency was observed only in the adenine model of CKD that recapitulates the whole spectrum of hemostasis abnormalities observed in advanced human CKD.
- Published
- 2020
- Full Text
- View/download PDF
48. Intermolecular correlations are necessary to explain diffuse scattering from protein crystals
- Author
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Ariana Peck, Frédéric Poitevin, and Thomas J. Lane
- Subjects
diffuse scattering ,intermolecular correlations ,Crystallography ,QD901-999 - Abstract
Conformational changes drive protein function, including catalysis, allostery and signaling. X-ray diffuse scattering from protein crystals has frequently been cited as a probe of these correlated motions, with significant potential to advance our understanding of biological dynamics. However, recent work has challenged this prevailing view, suggesting instead that diffuse scattering primarily originates from rigid-body motions and could therefore be applied to improve structure determination. To investigate the nature of the disorder giving rise to diffuse scattering, and thus the potential applications of this signal, a diverse repertoire of disorder models was assessed for its ability to reproduce the diffuse signal reconstructed from three protein crystals. This comparison revealed that multiple models of intramolecular conformational dynamics, including ensemble models inferred from the Bragg data, could not explain the signal. Models of rigid-body or short-range liquid-like motions, in which dynamics are confined to the biological unit, showed modest agreement with the diffuse maps, but were unable to reproduce experimental features indicative of long-range correlations. Extending a model of liquid-like motions to include disorder across neighboring proteins in the crystal significantly improved agreement with all three systems and highlighted the contribution of intermolecular correlations to the observed signal. These findings anticipate a need to account for intermolecular disorder in order to advance the interpretation of diffuse scattering to either extract biological motions or aid structural inference.
- Published
- 2018
- Full Text
- View/download PDF
49. Case Study of High-Throughput Drug Screening and Remote Data Collection for SARS-CoV-2 Main Protease by Using Serial Femtosecond X-ray Crystallography
- Author
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Omur Guven, Mehmet Gul, Esra Ayan, J Austin Johnson, Baris Cakilkaya, Gozde Usta, Fatma Betul Ertem, Nurettin Tokay, Busra Yuksel, Oktay Gocenler, Cengizhan Buyukdag, Sabine Botha, Gihan Ketawala, Zhen Su, Brandon Hayes, Frederic Poitevin, Alexander Batyuk, Chun Hong Yoon, Christopher Kupitz, Serdar Durdagi, Raymond G. Sierra, and Hasan DeMirci
- Subjects
SARS-CoV-2 ,main protease ,serial femtosecond crystallography ,high-throughput drug screening ,Crystallography ,QD901-999 - Abstract
Since early 2020, COVID-19 has grown to affect the lives of billions globally. A worldwide investigation has been ongoing for characterizing the virus and also for finding an effective drug and developing vaccines. As time has been of the essence, a crucial part of this research has been drug repurposing; therefore, confirmation of in silico drug screening studies have been carried out for this purpose. Here we demonstrated the possibility of screening a variety of drugs efficiently by leveraging a high data collection rate of 120 images/second with the new low-noise, high dynamic range ePix10k2M Pixel Array Detector installed at the Macromolecular Femtosecond Crystallography (MFX) instrument at the Linac Coherent Light Source (LCLS). The X-ray Free-Electron Laser (XFEL) is used for remote high-throughput data collection for drug repurposing of the main protease (Mpro) of SARS-CoV-2 at ambient temperature with mitigated X-ray radiation damage. We obtained multiple structures soaked with nine drug candidate molecules in two crystal forms. Although our drug binding attempts failed, we successfully established a high-throughput Serial Femtosecond X-ray crystallographic (SFX) data collection protocol.
- Published
- 2021
- Full Text
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50. Nutrient transport suggests an evolutionary basis for charged archaeal surface layer proteins
- Author
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Li, Po-Nan, Herrmann, Jonathan, Tolar, Bradley B., Poitevin, Frédéric, Ramdasi, Rasika, Bargar, John R., Stahl, David A., Jensen, Grant J., Francis, Christopher A., Wakatsuki, Soichi, and van den Bedem, Henry
- Published
- 2018
- Full Text
- View/download PDF
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