Shape optimized acoustic metagratings for anomalous refraction under strong thermoviscous effects.

The recent development of microacoustic metagratings opens up promising possibilities for manipulating acoustic wavefronts passively, particularly in applications such as flat acoustic lenses and ultra-high frequency ultrasound imaging. The emergence of two-photon polymerization has made it feasible to precisely manufacture microscopic structures, as required when metagratings are scaled to MHz frequencies in airborne ultrasound. Nevertheless, the downsizing process presents another hurdle as the increased thermoviscous effects result in substantial losses that must be considered during the design phase.

Realistic prediction and engineering of high-Q modes to implement stable Fano resonances in acoustic devices.

Quasi-bound states in the continuum (QBICs) coupling into the propagating spectrum manifest themselves as high-quality factor (Q) modes susceptible to perturbations. This poses a challenge in predicting stable Fano resonances for realistic applications. Besides, where and when the maximum field enhancement occurs in real acoustic devices remains elusive.

Sound attenuation enhancement of acoustic meta-atoms via coupling.

Arrangements of acoustic meta-atoms, better known as acoustic metamaterials, are commonly applied in acoustic cloaking, for the attenuation of acoustic fields or for acoustic focusing. A precise design of single meta-atoms is required for these purposes. Understanding the details of their interaction allows improvement of the collective performance of the meta-atoms as a system, for example, in sound attenuation.

Willis Coupling-Induced Acoustic Radiation Force and Torque Reversal.

Acoustic meta-atoms serve as the building blocks of metamaterials, with linear properties designed to achieve functions such as beam steering, cloaking, and focusing. They have also been used to shape the characteristics of incident acoustic fields, which led to the manipulation of acoustic radiation force and torque for development of acoustic tweezers with improved spatial resolution. However, acoustic radiation force and torque also depend on the shape of the object, which strongly affects its scattering properties.

Acoustofluidics 24: theory and experimental measurements of acoustic interaction force.

The motion of small objects in acoustophoresis depends on the acoustic radiation force and torque. These are nonlinear phenomena originating from wave scattering, and consist of primary and secondary components. The primary radiation force is the force acting on an object due to the incident field, in the absence of other objects.

Topological Supercavity Resonances in the Finite System.

Acoustic resonant cavities play a vital role in modern acoustical systems. The ultrahigh quality-factor resonances are highly desired for some applications such as high-resolution acoustic sensors and acoustic lasers. Here, a class of supercavity resonances is theoretically proposed and experimentally demonstrated in a coupled acoustic resonator system, arising from the merged bound states in the continuum (BICs) in geometry space.

Microacoustic Metagratings at Ultra-High Frequencies Fabricated by Two-Photon Lithography.

The recently proposed bianisotropic acoustic metagratings offer promising opportunities for passive acoustic wavefront manipulation, which is of particular interest in flat acoustic lenses and ultrasound imaging at ultra-high frequency ultrasound. Despite this fact, acoustic metagratings have never been scaled to MHz frequencies that are common in ultrasound imaging. One of the greatest challenges is the production of complex microscopic structures.

Reducing the Toxicity of Designer Aminoglycosides as Nonsense Mutation Readthrough Agents for Therapeutic Targets.

A significant proportion of genetic disease cases arise from truncation of proteins caused by premature termination codons. In eukaryotic cells some aminoglycosides cause readthrough of premature termination codons during protein translation. Inducing readthrough of these codons can potentially be of therapeutic value in the treatment of numerous genetic diseases.

Sound trapping in an open resonator.

The ability of sound energy confinement with high-quality factor resonance is of vital importance for acoustic devices requiring high intensity and hypersensitivity in biological ultrasonics, enhanced collimated sound emission (i.e. sound laser) and high-resolution sensing.

Dual Glycolate Oxidase/Lactate Dehydrogenase A Inhibitors for Primary Hyperoxaluria.

Both glycolate oxidase (GO) and lactate dehydrogenase A (LDHA) influence the endogenous synthesis of oxalate and are clinically validated targets for treatment of primary hyperoxaluria (PH). We investigated whether dual inhibition of GO and LDHA may provide advantage over single agents in treating PH. Utilizing a structure-based drug design (SBDD) approach, we developed a series of novel, potent, dual GO/LDHA inhibitors.

Redefining the Histone Deacetylase Inhibitor Pharmacophore: High Potency with No Zinc Cofactor Interaction.

A novel series of histone deacetylase (HDAC) inhibitors lacking a zinc-binding moiety has been developed and described herein. HDAC isozyme profiling and kinetic studies indicate that these inhibitors display a selectivity preference for HDACs 1, 2, 3, 10, and 11 via a rapid equilibrium mechanism, and crystal structures with HDAC2 confirm that these inhibitors do not interact with the catalytic zinc. The compounds are nonmutagenic and devoid of electrophilic and mutagenic structural elements and exhibit off-target profiles that are promising for further optimization.

Discovery of an Anion-Dependent Farnesyltransferase Inhibitor from a Phenotypic Screen.

By employing a phenotypic screen, a set of compounds, exemplified by , were identified which potentiate the ability of histone deacetylase inhibitor vorinostat to reverse HIV latency. Proteome enrichment followed by quantitative mass spectrometric analysis employing a modified analogue of as affinity bait identified farnesyl transferase (FTase) as the primary interacting protein in cell lysates. This ligand-FTase binding interaction was confirmed via X-ray crystallography and temperature dependent fluorescence studies, despite lacking structural and binding similarity to known FTase inhibitors.

Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Action.

The programmed cell death protein 1 (PD-1) signaling axis is among the most important therapeutic targets in modern oncology. Aurigene Discovery Technologies Ltd. (Aurigene) has patented a series of peptidomimetic small molecules derived from the PD-1 protein sequence for use in targeting the interaction between PD-1 and its ligand, PD-L1.

Bandwidth and size limits of achromatic printed-circuit metasurfaces.

Metasurfaces can implement a wide variety of wave-manipulation functions with sub-wavelength layers. They are typically created from resonant elements, thus their refraction properties depend strongly on frequency. The resulting chromatic aberration is undesirable for most applications, motivating recent efforts in the development of achromatic metasurfaces.

Ultrathin tunable terahertz absorber based on MEMS-driven metamaterial.

The realization of high-performance tunable absorbers for terahertz frequencies is crucial for advancing applications such as single-pixel imaging and spectroscopy. Based on the strong position sensitivity of metamaterials' electromagnetic response, we combine meta-atoms that support strongly localized modes with suspended flat membranes that can be driven electrostatically. This design maximizes the tunability range for small mechanical displacements of the membranes.

Discovery and optimization of 2-pyridinone aminal integrase strand transfer inhibitors for the treatment of HIV.

HIV integrase strand transfer inhibitors (InSTIs) represent an important class of antiviral therapeutics with proven efficacy and excellent tolerability for the treatment of HIV infections. In 2007, Raltegravir became the first marketed strand transfer inhibitor pioneering the way to a first-line therapy for treatment-naïve patients. Challenges with this class of therapeutics remain, including frequency of the dosing regimen and the genetic barrier to resistance.

Strong terahertz absorption in all-dielectric Huygens' metasurfaces.

We propose an all dielectric metamaterial that acts as a perfect terahertz absorber without a ground plane. The unit cell consists of a dielectric cylinder embedded in a low index material. In order to achieve near-perfect terahertz absorption (99.

Elastic metamaterials for tuning circular polarization of electromagnetic waves.

Electromagnetic resonators are integrated with advanced elastic material to develop a new type of tunable metamaterial. An electromagnetic-elastic metamaterial able to switch on and off its electromagnetic chiral response is experimentally demonstrated. Such tunability is attained by harnessing the unique buckling properties of auxetic elastic materials (buckliballs) with embedded electromagnetic resonators.

Electrically tunable terahertz metamaterials with embedded large-area transparent thin-film transistor arrays.

Engineering metamaterials with tunable resonances are of great importance for improving the functionality and flexibility of terahertz (THz) systems. An ongoing challenge in THz science and technology is to create large-area active metamaterials as building blocks to enable efficient and precise control of THz signals. Here, an active metamaterial device based on enhancement-mode transparent amorphous oxide thin-film transistor arrays for THz modulation is demonstrated.

Tunable Meta-Liquid Crystals.

Meta-liquid crystals, a novel form of tunable 3D metamaterials, are proposed and experimentally demonstrated in the terahertz frequency regime. A morphology change under a bias electric field and a strong modulation of the transmission are observed. In comparison to conventional liquid crystals, there is considerable freedom to prescribe the electromagnetic properties through the judicious design of the meta-atom geometry.

Discovery of 2-Pyridinone Aminals: A Prodrug Strategy to Advance a Second Generation of HIV-1 Integrase Strand Transfer Inhibitors.

The search for new molecular constructs that resemble the critical two-metal binding pharmacophore required for HIV integrase strand transfer inhibition represents a vibrant area of research within drug discovery. Here we present the discovery of a new class of HIV integrase strand transfer inhibitors based on the 2-pyridinone core of MK-0536. These efforts led to the identification of two lead compounds with excellent antiviral activity and preclinical pharmacokinetic profiles to support a once-daily human dose prediction.

Spontaneous chiral symmetry breaking in metamaterials.

Spontaneous chiral symmetry breaking underpins a variety of areas such as subatomic physics and biochemistry, and leads to an impressive range of fundamental phenomena. Here we show that this prominent effect is now available in artificial electromagnetic systems, enabled by the advent of magnetoelastic metamaterials where a mechanical degree of freedom leads to a rich variety of strong nonlinear effects such as bistability and self-oscillations. We report spontaneous symmetry breaking in torsional chiral magnetoelastic structures where two or more meta-molecules with opposite handedness are electromagnetically coupled, modifying the system stability.

An overview of patented small molecule stearoyl coenzyme-A desaturase inhibitors (2009 - 2013).

Introduction: Stearoyl coenzyme-A desaturase (SCD) is a critical lipogenic enzyme that converts a range of unsaturated lipids to their corresponding monounsaturated fatty acids. Genetic and enzyme-knockdown experiments have suggested an important role of SCD1 in the regulation of various metabolic disorders. With the prognostication that SCD-inhibition may serve to remediate various metabolic diseases, several pharmaceutical companies have embarked on the development of small-molecule SCD-inhibitors, with over 100 patent applications by 17 companies being reported to date.

Flexible helices for nonlinear metamaterials.

The successful fabrication and experimental verification of a novel metamaterial based on flexible metallic helices is reported. The helices undergo compression under the influence of incident radiation, demonstrating a nonlinear chiral electromagnetic response, associated with the power-dependent change in the helix pitch. This design is promising for application to power-dependent polarization rotation of propagating waves.