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1.
Pharm Res ; 40(1): 3-25, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36735106

ABSTRACT

Endothelial cells play critical roles in circulatory homeostasis and are also the gateway to the major organs of the body. Dysfunction, injury, and gene expression profiles of these cells can cause, or are caused by, prevalent chronic diseases such as diabetes, cardiovascular disease, and cancer. Modulation of gene expression within endothelial cells could therefore be therapeutically strategic in treating longstanding disease challenges. Lipid nanoparticles (LNP) have emerged as potent, scalable, and tunable carrier systems for delivering nucleic acids, making them attractive vehicles for gene delivery to endothelial cells. Here, we discuss the functions of endothelial cells and highlight some receptors that are upregulated during health and disease. Examples and applications of DNA, mRNA, circRNA, saRNA, siRNA, shRNA, miRNA, and ASO delivery to endothelial cells and their targets are reviewed, as well as LNP composition and morphology, formulation strategies, target proteins, and biomechanical factors that modulate endothelial cell targeting. Finally, we discuss FDA-approved LNPs as well as LNPs that have been tested in clinical trials and their challenges, and provide some perspectives as to how to surmount those challenges.


Subject(s)
Nanoparticles , Nucleic Acids , Endothelial Cells/metabolism , Liposomes/metabolism , Gene Transfer Techniques , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism
2.
J Vasc Interv Radiol ; 32(10): 1488-1491, 2021 10.
Article in English | MEDLINE | ID: mdl-34602161

ABSTRACT

Several workflow changes were implemented in a large academic interventional radiology practice, including separation of inpatient and outpatient services, early start times, and using an adaptive learning system to predict case length tailored to individual physicians. Metrics including procedural volume, on-time start, accuracy at predicting case length, and room shutdown time were assessed before and after the intervention. Considerable improvements were seen in accuracy of first case start times, predicting block times, and last case encounter ending times. It is proposed that with improved role clarity, interventional radiologists can regain control over their schedules, utilize work hours more efficiently, and improve work-life balance.


Subject(s)
Radiology, Interventional , Work-Life Balance , Humans , Inpatients , Radiologists , Workflow
4.
Phys Rev Lett ; 122(10): 107801, 2019 Mar 15.
Article in English | MEDLINE | ID: mdl-30932628

ABSTRACT

An achiral, bent-core mesogen forms several tilted smectic liquid crystal phases, including a nonpolar, achiral de Vries smectic A which transitions to a chiral, ferroelectric state in applied electric fields above a threshold. At lower temperature, a chiral, ferrielectric phase with a periodic, supermolecular modulation of the tilt azimuth, indicated by a Bragg peak in carbon-edge resonant soft x-ray scattering, is observed. The absence of a corresponding resonant umklapp peak identifies the superlayer structure as a twist-bend-like helix that is only weakly modulated by the smectic layering.

5.
Materials (Basel) ; 10(11)2017 Nov 09.
Article in English | MEDLINE | ID: mdl-29120371

ABSTRACT

We have previously reported the first realization of an orthogonal ferroelectric bent-core SmAPF phase by directed design in mesogens with a single tricarbosilane-terminated alkoxy tail. Given the potentially useful electrooptic properties of this phase, including analog phase-only electrooptic index modulation with optical latching, we have been exploring its "structure space", searching for novel SmAPF mesogens. Here, we report two classes of these-the first designed to optimize the dynamic range of the index modulation in parallel-aligned cells by lowering the bend angle of the rigid core, and the second expanding the structure space of the phase by replacing the tricarbosilane-terminated alkyl tail with a polyfluorinated polyethylene glycol oligomer.

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