LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity.

Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that catalyzes the formation of symmetric dimethylarginine in a number of nuclear and cytoplasmic proteins. Although the cellular functions of PRMT5 have not been fully unraveled, it has been implicated in a number of cellular processes like RNA processing, signal transduction, and transcriptional regulation. PRMT5 is ubiquitously expressed in most tissues and its expression has been shown to be elevated in several cancers including breast cancer, gastric cancer, glioblastoma, and lymphoma.

Solution and displacement in monolayer and multilayer binary films of SF6 and CF4 on graphite.

Infrared reflection absorption spectroscopy is used to study the evolution of binary physisorbed films on graphite. A predeposited monolayer of SF6 is exposed to slowly increasing pressure of CF4 at constant temperature between 80 and 113 K. Shifts in the frequencies of the dominant vibrational mode of each species due to resonant dipole-dipole coupling serve as proxies for the areal density of each species in the monolayer.

Effect of vector asymmetry of radially polarized beams in solid immersion microscopy.

We theoretically and experimentally investigate the effect of imperfect vector symmetry on radially polarized beams focused by an aplanatic solid immersion lens at a numerical aperture of 3.3. We experimentally achieve circularly symmetric focused spot with a full-width-half-maximum of ~λ0/5.

Radially polarized Bessel-Gauss beams: decentered Gaussian beam analysis and experimental verification.

We derive solutions for radially polarized Bessel-Gauss beams in free-space by superimposing decentered Gaussian beams with differing polarization states. We numerically show that the analytical result is applicable even for large semi-aperture angles, and we experimentally confirm the analytical expression by employing a fiber-based mode-converter.

Acetylene frequency references in gas-filled hollow optical fiber and photonic microcells.

Gas-filled hollow optical fiber references based on the P(13) transition of the ν1+ν3 band of 12C2H2 promise portability with moderate accuracy and stability. Previous realizations are corrected (<1σ) by using proper modeling of a shift due to line-shape. To improve portability, a sealed photonic microcell is characterized on the 12C2H2 ν1+ν3 P(23) transition with somewhat reduced accuracy and stability.

Emission and nonradiative decay of nanodiamond NV centers in a low refractive index environment.

The nitrogen vacancy (NV) center is the most widely studied single optical defect in diamond with great potential for applications in quantum technologies. Development of practical single-photon devices requires an understanding of the emission under a range of conditions and environments. In this work, we study the properties of a single NV center in nanodiamonds embedded in an air-like silica aerogel environment which provides a new domain for probing the emission behavior of NV centers in nanoscale environments.

The pre-clinical absorption, distribution, metabolism and excretion properties of IPI-926, an orally bioavailable antagonist of the hedgehog signal transduction pathway.

1. IPI-926 is a novel semisynthetic cyclopamine derivative that is a potent and selective Smoothened inhibitor that blocks the hedgehog signal transduction pathway. 2.

Porous silicon nanocrystals in a silica aerogel matrix.

Silicon nanoparticles of three types (oxide-terminated silicon nanospheres, micron-sized hydrogen-terminated porous silicon grains and micron-size oxide-terminated porous silicon grains) were incorporated into silica aerogels at the gel preparation stage. Samples with a wide range of concentrations were prepared, resulting in aerogels that were translucent (but weakly coloured) through to completely opaque for visible light over sample thicknesses of several millimetres. The photoluminescence of these composite materials and of silica aerogel without silicon inclusions was studied in vacuum and in the presence of molecular oxygen in order to determine whether there is any evidence for non-radiative energy transfer from the silicon triplet exciton state to molecular oxygen adsorbed at the silicon surface.

Structure of plasmonic aerogel and the breakdown of the effective medium approximation.

A method for making aerogel doped with gold nanoparticles (GNPs) produces a composite material with a well-defined localized surface plasmon resonance peak at 520 nm. The width of the extinction feature indicates the GNPs are well dispersed in the aerogel, making it suited to optical study. A simple effective medium approximation cannot explain the peak extinction wavelengths.

Update on multidetector computed tomography angiography of the abdominal aorta.

Multidetector computed tomography angiography (MDCTA) allows high spatial resolution, including nearly isotropic submillimeter resolution in the X, Y, and Z planes, and rapid image acquisition in a single breath hold, with greatly enhanced diagnostic capabilities over conventional CT. MDCTA has largely replaced digital subtraction angiography because it is faster, less invasive, and provides more information. When technical parameters are optimized, it provides the radiologist with the information needed to diagnose life threatening diseases of the aortoiliac system, gives critical information for the vascular surgeon or interventional radiologist to treat that disease, and identifies subsequent complications related to therapy.

Large-core acetylene-filled photonic microcells made by tapering a hollow-core photonic crystal fiber.

We report on kagomé-lattice photonic microcells with low losses, large outer diameters, and large cores. The large (40-70microm) cores are accommodated by tapering the fibers and splicing the reduced ends to a single-mode fiber. We demonstrate the repeatability of this process and obtain splice losses of 0.

Tapered fibers embedded in silica aerogel.

We have embedded thin tapered fibers (with diameters down to 1 microm) in silica aerogel with low loss. The aerogel is rigid but behaves refractively like air, protecting the taper without disturbing light propagation along it. This enables a new class of fiber devices exploiting volume evanescent interactions with the aerogel itself or with dopants or gases in the pores.

Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926).

Recent evidence suggests that blocking aberrant hedgehog pathway signaling may be a promising therapeutic strategy for the treatment of several types of cancer. Cyclopamine, a plant Veratrum alkaloid, is a natural product antagonist of the hedgehog pathway. In a previous report, a seven-membered D-ring semisynthetic analogue of cyclopamine, IPI-269609 (2), was shown to have greater acid stability and better aqueous solubility compared to cyclopamine.

Synthesis of lipidated green fluorescent protein and its incorporation in supported lipid bilayers.

Herein we report a semisynthetic method of producing membrane-anchored proteins. Ligation of synthetic lipids with designed anchor structures to proteins was performed using native chemical ligation (NCL) of a C-terminal peptide thioester and an N-terminal cysteine lipid. This strategy mimics the natural glycosylphosphatidylinositol (GPI) linkage found in many natural membrane-associated proteins; however, the synthetic method utilizes simple lipid anchors without glycans.

Homogeneous glycopeptides and glycoproteins for biological investigation.

Protein glycosylation is widely recognized as a modulator of protein structure, localization, and cell-cell recognition in multicellular systems. Glycoproteins are typically expressed as mixtures of glycoforms, their oligosaccharides being generated by a template-independent biosynthetic process. Investigation of their function has been greatly assisted by sources of homogeneous material.

Stereoselective synthesis of myo-inositol via ring-closing metathesis: a building block for glycosylphosphatidylinositol (GPI) anchor synthesis.

Here we report a concise stereoselective synthesis of myo-inositol via ring-closing metathesis. A readily available bis-Weinreb amide of D-tartrate served as a key intermediate. [reaction: see text]