We provide here a description of a basic, entry-level method and user interface for automating ultrafast electron microscopy (UEM) experiments. We provide access to the source code and scripts via a GitHub site for ease of implementation or as a starting reference point for those entering or seeking to enter the field. Core instrumentation and physical connections in the UEM lab at Minnesota are described. An application designed and programmed with C++/CLI as Windows Forms in Microsoft Visual Studio - dubbed UEMtomaton - is also presented. It is our hope that this note provides useful insight for current and future UEM researchers.

Journal Article Quantifying Transient Strain and Energy of Coherent Acoustic Phonons with UEM Imaging Get access Daniel Du, Daniel Du University of Minnesota, Minneapolis, Minnesota, United States Search for other works by this author on: Oxford Academic Google Scholar Daniel Cremons, Daniel Cremons University of Minnesota, Minneapolis, Minnesota, United States Search for other works by this author on: Oxford Academic Google Scholar David Flannigan David Flannigan University of Minnesota, Minneapolis, Minnesota, United States Search for other works by this author on: Oxford Academic Google Scholar Microscopy and Microanalysis, Volume 26, Issue S2, 1 August 2020, Pages 212–214, https://doi.org/10.1017/S1431927620013823 Published: 01 August 2020

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This study explored the utility of topically applied polymeric nanoparticle suspensions to target delivery of poorly water-soluble drugs to hair follicles. Several formulations of amorphous drug/polymer nanoparticles were prepared from ethyl cellulose and UK-157,147 (systematic name (3S,4R)-[6-(3-hydroxyphenyl)sulfonyl]-2,2,3-trimethyl-4-(2-methyl-3-oxo-2,3-dihydropyridazin-6-yloxy)-3-chromanol), a potassium channel opener, using sodium glycocholate (NaGC) as a surface stabilizer. Nanoparticle suspensions were evaluated to determine if targeted drug delivery to sebaceous glands and hair follicles could be achieved. In in vitro testing with rabbit ear tissue, delivery of UK-157,147 to the follicles was demonstrated with limited distribution to the surrounding dermis. Delivery to hair follicles was also demonstrated in vivo, based on stimulation of hair growth in tests of 100-nm nanoparticles with a C3H mouse model. The nanoparticles were well-tolerated, with no visible skin irritation. In vivo tests of smaller nanoparticles with a hamster ear model also indicated targeted delivery to sebaceous glands. The nanoparticles released drug rapidly in in vitro nonsink dissolution tests and were stable in suspension for 3 months. The present results show selective drug delivery to the follicle by follicular transport of nanoparticles and rapid release of a poorly water-soluble drug. Thus, nanoparticles represent a promising approach for targeted topical delivery of low-solubility compounds to hair follicles.

A novel nonsteroidal androgen receptor antagonist, (R)-4-(1-benzyl-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)-2-(trifluoromethyl)benzonitrile (1), for the topical control of sebum production is reported. This compound, which is potent, selective, and efficacious in the clinically validated golden Syrian hamster ear animal model, was designed to be delivered to the pilosebaceous unit, the site of action, preferentially by the follicular route.

A series of diphenyl ethers was prepared and evaluated for androgen receptor antagonist activity in human androgen receptor binding and cellular functional assays. Analogs with potent in vitro activities were evaluated for topical in vivo efficacy in the Golden Syrian Hamster ear model. Several compounds showed reduction in wax esters in this validated animal model.

The first examples of thioether-substituted benzonitriles as potential soft-drug androgen receptor antagonists are reported. A number of 4-(alkylthio)- and of 4-(arylthio)-benzonitrile analogs were evaluated in human androgen receptor binding and cellular functional assays. Analogs with potent in vitro binding and cellular activities were evaluated for topical in vivo efficacy in the Golden Syrian hamster ear model. Analogs from both the 4-(alkylthio)- and of 4-(arylthio)-benzonitrile series showed moderate reduction of wax esters in vivo.

4-((1 R,2 R)-2-Hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile [PF-0998425, (-)- 6a] is a novel, nonsteroidal androgen receptor antagonist for sebum control and treatment of androgenetic alopecia. It is potent, selective, and active in vivo. The compound is rapidly metabolized systemically, thereby reducing the risk of unwanted systemic side effects due to its primary pharmacology. (-)- 6a was tested negative in the 3T3 NRU assay, validating our rationale that reduction of conjugation might reduce potential phototoxicity.

A series of substituted 4-aryl-2-trifluoromethylbenzonitrile analogs were evaluated in the human androgen receptor binding and cellular functional assays. Analogs with sufficient in vitro binding and cellular potency (IC50 < 200 nM) were tested in the progesterone receptor binding assay for selectivity and in the Golden Syrian hamster ear model for in vivo efficacy. Within the series, compound 4e was identified to be the most active analog in vivo (wax ester inhibition = 86%).

A series of amino-pyridines were synthesized and evaluated for androgen antagonist activities. Among these compounds, (R)-(+)-6-[methyl-(1-phenyl-ethyl)-amino]-4-trifluoromethyl-nicotinonitrile was the most active example of this class. This compound displayed potent androgen receptor antagonist activity as well as favorable pharmacokinetic characteristics for a potential topical agent. It also demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.

Synthesis, pharmacology, and pharmacokinetic profiles of (1R, 2S)-4-(2-cyano-cyclohexyl-oxy)-2-trifluoromethyl-benzonitrile are reported. This compound demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.