We report several limitations and failure modes of the recently expanded Layzer model for hydrodynamic instabilities. The failures occur for large initial amplitudes, for stable accelerations, and for spikes in two-fluid systems.
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http://dx.doi.org/10.1103/PhysRevE.78.015303 | DOI Listing |
Proc Natl Acad Sci U S A
July 2024
Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Hemostasis relies on a reaction network of serine proteases and their cofactors to form a blood clot. Coagulation factor IXa (protease) plays an essential role in hemostasis as evident from the bleeding disease associated with its absence. RNA aptamers specifically targeting individual coagulation factors have potential as anticoagulants and as probes of the relationship between structure and function.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2022
Department of Surgery, Duke University Medical Center and Health System, 2301 Erwin Road, Box 3443, Durham, NC 27710, USA.
Extracorporeal membrane oxygenation (ECMO) requires anticoagulation to prevent clotting when the patient's blood contacts the circuit. Unfractionated heparin (UFH) usually prevents clotting but can cause life-threatening bleeding. An anticoagulant that selectively inhibits the contact activation (intrinsic) pathway while sparing the tissue factor (extrinsic) pathway of coagulation might prevent clotting triggered by the circuit while permitting physiologic coagulation at surgical sites.
View Article and Find Full Text PDFMol Ther
July 2019
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:
Endothelial surface and circulating glycoprotein von Willebrand factor (vWF) regulates platelet adhesion and is associated with thrombotic diseases, including ischemic stroke, myocardial infarction, and peripheral vascular disease. Thrombosis, as manifested in these diseases, is the leading cause of disability and death in the western world. Current parenteral antithrombotic and thrombolytic agents used to treat these conditions are limited by a short therapeutic window, irreversibility, and major risk of hemorrhage.
View Article and Find Full Text PDFCell Chem Biol
May 2019
Department of Molecular Genetics and Microbiology Graduate Program, Duke University, Durham, NC, USA; Department of Surgery, Duke University, Durham, NC, USA. Electronic address:
Biopharmaceuticals have become increasingly attractive therapeutic agents and are often PEGylated to enhance their pharmacokinetics and reduce their immunogenicity. However, recent human clinical trials have demonstrated that administration of PEGylated compounds can evoke anti-PEG antibodies. Considering the ubiquity of PEG in commercial products and the presence of pre-existing anti-PEG antibodies in patients in large clinical trials evaluating a PEG-modified aptamer, we investigated how anti-PEG antibodies effect the therapeutic activities of PEGylated RNA aptamers.
View Article and Find Full Text PDFJ Vis Exp
September 2018
Department of Neurological Surgery, Ohio State University;
Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, we have translated a vascular injury model from a small animal into a large animal (canine), with slight modifications that can be used for pre-clinical screening of prophylactic and thrombolytic agents. In addition to the surgical methods, the modified protocol describes the step-by-step methods to assess carotid artery canalization by angiography, detailed instructions to process both the brain and carotid artery for histological analysis to verify carotid canalization and cerebral hemorrhage, and specific parameters to complete an assessment of downstream thromboembolic events by utilizing magnetic resonance imaging (MRI).
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