The distribution of cerebral atherosclerosis is influenced by race and sex but not by other vascular risk factors. In our patient population, intracranial disease is as common a cause of cerebral ischemia as extracranial carotid disease.

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Self-assembly of block-copolymers provides a route to the fabrication of small (size, <50 nm) and dense (pitch, <100 nm) features with an accuracy that approaches even the demanding specifications for nanomanufacturing set by the semiconductor industry. A key requirement for practical applications, however, is a rapid, high-resolution method for patterning block-copolymers with different molecular weights and compositions across a wafer surface, with complex geometries and diverse feature sizes. Here we demonstrate that an ultrahigh-resolution jet printing technique that exploits electrohydrodynamic effects can pattern large areas with block-copolymers based on poly(styrene-block-methyl methacrylate) with various molecular weights and compositions. The printed geometries have diameters and linewidths in the sub-500 nm range, line edge roughness as small as ∼45 nm, and thickness uniformity and repeatability that can approach molecular length scales (∼2 nm). Upon thermal annealing on bare, or chemically or topographically structured substrates, such printed patterns yield nanodomains of block-copolymers with well-defined sizes, periodicities and morphologies, in overall layouts that span dimensions from the scale of nanometres (with sizes continuously tunable between 13 nm and 20 nm) to centimetres. As well as its engineering relevance, this methodology enables systematic studies of unusual behaviours of block-copolymers in geometrically confined films.

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Gold nanoparticles protected with thiophene-terminated alkanethiols having different alkane chain lengths have been synthesized, and vapor-sensing properties of their spin-coated films have been investigated. Transmission electron microscopy and measurement of the sulfur and gold peak areas of the films by X-ray photoelectron spectroscopy indicate gold core diameters in the 3−5-nm range. Exposure of the films to chloroform, toluene, hexane, and ethanol vapors results in significant and selective increases in electrical resistance, with the response to the vapors having the following order:  toluene > chloroform > hexane ≫ ethanol. The magnitude of the maximum resistance change correlates well with solubility properties of the protected gold nanoparticles, as determined by optical absorbance spectroscopy and the energy of the gold plasmon. The detection sensitivity of the films increases with increasing alkanethiol chain length. These data are consistent with a sensing mechanism in which organic vapors cause swelling of the nanoparticle film, resulting in increased distance between the gold cores. In the case of ethanol, a decrease in resistance occurs at high vapor concentration, presumably due to an increase in the dielectric constant of the medium between the cores.

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Summary Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway, and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG+/− mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-Seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR.