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PanDDA Inspect was used to sequentially assess each event in Coot 35 , and ligands were added to the TRF1 TRFH model if density could be confidently assigned in real space

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Reactions without the phi 29 polymerase enzyme were included as a negative control

Abbreviations AE: Adverse events AUC: Area under the plasma concentration time curve BID: Twice daily CI: Confidence interval CL: Clearance C max : Maximum observed plasma concentration COPD: Chronic obstructive pulmonary disease CS: Closed system CV%: Coefficient of variation DPI: Dry powder inhaler F: Fraction bioavailable FEV 1 : Forced expiratory volume in 1 s FVC: Forced vital capacity GLY: Glycopyrronium bromide GOLD: Global Initiative for Chronic Obstructive Lung Disease ICS: Inhaled corticosteroid IV: Intravenous LAMA: Long-acting muscarinic antagonist LS: Least squares PK: Pharmacokinetics pMDI: Pressurized metered dose inhaler SAE: Serious adverse event SD: Standard deviation t : Elimination half-life t max : Time to reach maximum plasma concentration V ss : Volume of distribution at steady state V z : Volume of distribution References Decramer M, Janssens W, Miravitlles M

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Critical evaluation of cryo-techniques for transmission electron microscopy: preparation of biological samples