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G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors in humans. Over 800 GPCRs regulate the (patho)biology of every organ, tissue, and cell type. Consequently, GPCRs are the most prominent therapeutic targets in medicine
David Pamies, Jason Ekert, Marie-Gabrielle Zurich, Olivier Frey, Sophie Werner, MONICA PIERGIOVANNI, Benjamin Freedman, Adrian Keong, Darwin Reyes-Hernandez, Hendrik Erfurth, Peter Loskill, Pelin Candarlioglu, Shan Wang, Thomas Hartung, Sandra Coecke, Glyn Stacey, Marcel Leist
Cell culture technology has seen great innovations and progress in the 21st centuryClassical single-cell and monolayer models have been replaced by more complex 3D models (e.g., reaggregates, spheroids, organoids) to improve the predictivity of in vitro
Darwin Reyes-Hernandez, Mandy Esch, Lorna Ewart, Rohollah Nasiri, Anna Herland, Carolina Lucchesi, Kyung Sung, MONICA PIERGIOVANNI, Jelena Vukasinovic, James Shoemaker, Nureddin Ashammakhi
Limitations with cell cultures and experimental animal-based studies have had the scientific and industrial communities searching for new approaches that can provide reliable human models for applications such as drug development, toxicological assessment
Cardiovascular disease (CVD) is the leading cause of death worldwide, casting a substantial economic footprint and burdening the global healthcare system. Historically, pre-clinical CVD modeling and therapeutic screening has been performed using animal
William Valiant, Jon Borman, Kang Cai, Peter Vallone
An essential step in pharmaceutical product development is screening for contamination with adventitious agents, and there is desire to develop highly sensitive assays to detect adventitious viral nucleic acid. This study sought to examine the nucleic acid
Balanced detection based on double beams is widely used to reduce common-mode noises, such as laser intensity fluctuation and irregular wavelength scanning, in absorption spectroscopy. However, employing an additional detector can increase the total system
Milos Drobnjakovic, Boonserm Kulvatunyou, Vijay Srinivasan, Simon P. Frechette
ISO and IEC have jointly initiated, and recently issued, a series of standards (the ISO/IEC 21838 series) for top-level ontologies. These standards have been used by industrial consortia to develop and disseminate standards for mid-level ontologies to ease
Tsega Solomon, Kinlin Chao, Genevieve Gingras, Yves Aubin, William Brad O'Dell, John Marino, Robert Brinson
The monoclonal antibody (mAb) protein class has become a primary therapeutic platform for the production of new life saving drug products. MAbs are comprised of two domains: the antigen-binding fragment (Fab) and crystallizable fragment (Fc). Despite the
Jacqueline Perodeau, Luke Arbogast, Andrew Nieuwkoop
Monoclonal antibodies (mAbs) are an important and growing class of biotherapeutic drug. Methods development for characterization of critical quality attributes, including higher order structure (HOS), of mAbs remains an area of active inquiry. Recently
Tsega Solomon, Frank Delaglio, John Giddens, John Marino, Yihua Bruce Yu, Marc Taraban, Robert Brinson
The clinical efficacy and safety of protein-based drugs such as monoclonal antibodies (mAbs) rely on the integrity of the protein higher order structure (HOS) during product development, manufacturing, storage, and patient administration. As mAb-based
The impact of five representative Hofmeister salts (NaCl, KCl, MgCl2, Na2SO4, and NaSCN) on the thermal stability and aggregation kinetics of a slightly acidic monoclonal antibody (mAb) were investigated under different pH conditions. The thermal stability
Srivalli Telikepalli, Michael J. Carrier, Dean C. Ripple
Visible protein-like particle standards can improve visual inspection and/or appearance testing practices used in the biotechnology industry. It will improve assay performance resulting in better alignment and more standardized training among different
Denis E. Bergeron, Jeffrey T. Cessna, Ryan P. Fitzgerald, Lizbeth Laureano-Perez, Leticia Pibida, Brian E. Zimmerman
An activity standard for 212Pb in equilibrium with its progeny was realized, based on triple-to-double coincidence ratio (TDCR) liquid scintillation (LS) counting. A Monte Carlo-based approach to estimating uncertainties due to nuclear decay data
Camille Lombard-Banek, Kerstin Pohl, Edward Kwee, John T. Elliott, John E. Schiel
Mass Spectrometry (MS)-based proteomic measurements are uniquely poised to impact the development of cell and gene therapies. With the adoption of rigorous instrumental performance controls (PQs), large-scale proteomics can move from a research to a
Richard E. Cavicchi, Laura Philips, Fook Cheong, David Ruffner, Priya Kasimbeg, Wyatt N. Vreeland
Quantifying the heterogeneous nature of protein aggregates is important to understanding the impact aggregates may have on the performance of antibody therapeutics. The spatially averaged density p of aggregates, defined as the total mass, including water
Kyle Anderson, Kerry Scott, Christina Bergonzo, Ioannis Karageorgos, Elyssia Gallagher, Venkata Tayi, Michael Butler, Jeffrey W. Hudgens
Previous reports present different models for the stabilization of the Fc—FcγRI immune complex. Although accord exists on the importance of L235 in IgG1 and some hydrophobic contacts for complex stabilization, discord exists regarding the existence of
Genome-enabled technologies have supported a dramatic increase in our ability to study microbial communities in environments and hosts. Taking stock of previously funded microbiome research can help to identify common themes, under-represented areas and
Qian Dong, Xinjian Yan, Yuxue Liang, Sanford Markey, Sergey L. Sheetlin, Concepcion Remoroza, William E. Wallace, Stephen Stein
This work presents methods for identifying and then creating a mass spectral library for disulfide-linked peptides originating from the NISTmAb. Analysis involved both partially- reduced and non-reduced proteins under neutral and weakly basic conditions
Korth Elliott, Frank Delaglio, Mats Wikstrom, John Marino, Luke Arbogast
The one-dimensional (1D) diffusion edited proton NMR method, Protein Fingerprint by Lineshape Enhancement (PROFILE) has been demonstrated to be suitable for higher order structure (HOS) characterization of protein therapeutics including monoclonal
A series of novel 1,3-oxazole sulfonamides were constructed and screened for their potential to inhibit cancer cell growth. These compounds were evaluated against the full NCI-60 human tumor cell lines; with the majority exhibiting promising overall growth
Argon cluster ions have enabled molecular depth profiling to unprecedented depths, with minimal loss of chemical information or changes in sputter rate. However, for deep depth profiles of organic films using the gas cluster ion source (> 10 µm of
A. D. Tollefson, C. M. Smith, M. H. Carpenter, M. P. Croce, M. E. Fassbender, K. D. John, K. E. Koehler, L. M. Lilley, E. M. O'Brien, Daniel Schmidt, B. W. Stein, Joel Ullom, M. D. Yoho, D. J. Mercer
225Ac is a valuable medical isotope for targeted alpha therapy, but 227Ac is an undesirable byproduct of an accelerator-based synthesis method under investigation. Sufficient detector sensitivity is critical for quantifying the trace impurity of 227Ac
Johnathan D. Guest, Ruixue Wang, Khadija Elkholy, Andrezza Chagas, Kinlin L. Chao, Thomas Cleveland, Young C. Kim, Zhen-Yong Keck, Alexander Marin, Roy Mariuzza, Alexander K. Andrianov, Eric A. Toth, Steven Foung, Brian Pierce, Thomas R. Fuerst
Hepatitis C virus (HCV) is a major worldwide health burden, and a preventive vaccine is needed for global control or eradication of this virus. A substantial hurdle to an effective HCV vaccine is the high variability of the virus, leading to immune escape
Fractography is a powerful but underutilized tool for the analysis of fractured glasses and ceramics, for fractures in the laboratory and for component failures in service. Fractography can identify the cause of failure and can even provide quantitative