Publications by authors named "J D Bath"

119 Publications

Strategies for Constructing and Operating DNA Origami Linear Actuators.

Small 2021 May 4:e2007704. Epub 2021 May 4.

Department of Physics, University of Oxford, Parks Road, Oxford, OX1 3PU, UK.

Linear actuators are ubiquitous components at all scales of engineering. DNA nanotechnology offers a unique opportunity for bottom-up assembly at the molecular scale, providing nanoscale precision with multiple methods for constructing and operating devices. In this paper, DNA origami linear actuators with up to 200 nm travel, based on a rail threading a topologically locked slider, are demonstrated. Two strategies, one- and two-pot assembly, are demonstrated whereby the two components are folded from one or two DNA scaffold strands, respectively. In order to control the position of the slider on the rail, the rail and the inside of the slider are decorated with single-stranded oligonucleotides with distinct sequences. Two positioning strategies, based on diffusion and capture of signaling strands, are used to link the slider reversibly to determined positions on the rail with high yield and precision. These machine components provide a basis for applications in molecular machinery and nanoscale manufacture including programmed chemical synthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/smll.202007704DOI Listing
May 2021

Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series.

J Med Chem 2021 May 20;64(9):6085-6136. Epub 2021 Apr 20.

Infectious Diseases Research Collaboration, Kampala, Uganda.

Dihydroorotate dehydrogenase (DHODH) has been clinically validated as a target for the development of new antimalarials. Experience with clinical candidate triazolopyrimidine DSM265 () suggested that DHODH inhibitors have great potential for use in prophylaxis, which represents an unmet need in the malaria drug discovery portfolio for endemic countries, particularly in areas of high transmission in Africa. We describe a structure-based computationally driven lead optimization program of a pyrrole-based series of DHODH inhibitors, leading to the discovery of two candidates for potential advancement to preclinical development. These compounds have improved physicochemical properties over prior series frontrunners and they show no time-dependent CYP inhibition, characteristic of earlier compounds. Frontrunners have potent antimalarial activity against blood and liver schizont stages and show good efficacy in SCID mouse models. They are equally active against and field isolates and are selective for DHODHs versus mammalian enzymes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.1c00173DOI Listing
May 2021

Progression of Changes in Vascular Surgery Practices during the Novel Corona Virus SARS-CoV-2 Pandemic.

Ann Vasc Surg 2021 Apr 6. Epub 2021 Apr 6.

Division of Vascular and Endovscular Surgery, Department of Surgery, Saint Louis University, St. Louis, MO. Electronic address:

Introduction: The novel coronavirus SARS-CoV-2 (COVID-19) has spread rapidly since it was identified. We sought to understand its effects on vascular surgery practices stratified by VASCON surgical readiness level and determine how these effects have changed during the course of the pandemic.

Methods: All members of the Vascular and Endovascular Surgery Society were sent electronic surveys questioning the effects of COVID-19 on their practices in the early pandemic in April (EP) and four months later in the pandemic in August (LP) 2020.

Results: Response rates were 206/731 (28%) in the EP group and 108/731 (15%) in the LP group (P < 0.0001). Most EP respondents reported VASCON levels less than 3 (168/206,82%), indicating increased hospital limitations while 6/108 (6%) in the LP group reported this level (P < 0.0001). The EP group was more likely to report a lower VASCON level (increased resource limitations), and decreased clinic, hospital and emergency room consults. Despite an increase of average cases/week to pre-COVID-19 levels, 46/108 (43%) of LP report continued decreased compensation, with 57% reporting more than 10% decrease. Respondents in the decreased compensation group were more likely to have reported a VASCON level 3 or lower earlier in the pandemic (P = 0.018). 91/108(84%) of LP group have treated COVID-19 patients for thromboembolic events, most commonly acute limb ischemia (76/108) and acute DVT (76/108). While the majority of respondents are no longer delaying the vascular surgery cases, 76/108 (70%) feel that vascular patient care has suffered due to earlier delays, and 36/108 (33%) report a backlog of cases caused by the pandemic.

Conclusions: COVID-19 had a profound effect on vascular surgery practices earlier in the pandemic, resulting in continued detrimental effects on the provision of vascular care as well as compensation received by vascular surgeons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.avsg.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023786PMC
April 2021

Multiple Chimney Endografts (ChEVAR) for Ruptured Pararenal Aortic Aneurysm.

Ann Vasc Surg 2021 Apr 6. Epub 2021 Apr 6.

Division of Vascular Surgery, University of Missouri, Columbia, MO, USA. Electronic address:

We present a ruptured pararenal abdominal aortic aneurysm (AAA) repaired with a complex three-vessel chimney EVAR (ChEVAR). This technique allows for rapid sealing of the aneurysm with branch preservation and avoids complex open aortic surgery. This case report highlights techniques and pitfalls from ChEVAR repair in the emergency setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.avsg.2021.01.119DOI Listing
April 2021