Analysis of the optical performance of intraocular lenses using profilometric measurements.

Purpose: The aim of this study was to develop a methodology, based on profilometer measurements to assess the optical behaviour of Intraocular Lenses (IOls). The "Modulation Transfer Function through-object" (MTF through-object) based on vergence object displacement was calculated for different pupil sizes and pseudophakic eyes. Tilt and decentration were also analysed in a realistic cornea eye model.

MET-Induced CD73 Restrains STING-Mediated Immunogenicity of EGFR-Mutant Lung Cancer.

Unlabelled: Immunotherapy has shown limited efficacy in patients with EGFR-mutated lung cancer. Efforts to enhance the immunogenicity of EGFR-mutated lung cancer have been unsuccessful to date. Here, we discover that MET amplification, the most common mechanism of resistance to third-generation EGFR tyrosine kinase inhibitors (TKI), activates tumor cell STING, an emerging determinant of cancer immunogenicity (1).

Activation of Tumor-Cell STING Primes NK-Cell Therapy.

Activation of the stimulator of interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding of the mechanism of action of STING agonists in human tumors is key to developing therapeutic combinations that activate effective innate antitumor immunity. Here, we report that malignant pleural mesothelioma cells robustly express STING and are responsive to STING agonist treatment ex vivo.

Analysis and comparison of monofocal, extended depth of focus and trifocal intraocular lens profiles.

To test the feasibility of using profilometers to extract information about IOL surfaces design. A standard monofocal IOL (Tecnis 1), a monofocal IOL that provided some depth of focus (Eyhance), an extended depth of focus IOL based on refractive optics (Mini Well) and a trifocal IOL based on diffractive optics were used in this study (Tecnis Synergy). The surface topography of the IOLs was measured by using a multimode optical profilometer.

New method to improve the quality of vision in cataractous keratoconus eyes.

To analyze using optical simulations if the proper use of a segmented intraocular lens (IOL) can improve the visual outcomes compared to the implantation of a spherical monofocal IOL. The wavefront profile of the Mplus (Oculentis) and a monofocal IOLs with the phase transformation introduced by each IOL were calculated using a Hartmann-Shack wavefront sensor. In addition, the wavefront profile of schematic eye models of various keratoconus conditions was obtained and was propagated to the IOLs.

Dynamic single-cell RNA sequencing identifies immunotherapy persister cells following PD-1 blockade.

Resistance to oncogene-targeted therapies involves discrete drug-tolerant persister cells, originally discovered through in vitro assays. Whether a similar phenomenon limits efficacy of programmed cell death 1 (PD-1) blockade is poorly understood. Here, we performed dynamic single-cell RNA-Seq of murine organotypic tumor spheroids undergoing PD-1 blockade, identifying a discrete subpopulation of immunotherapy persister cells (IPCs) that resisted CD8+ T cell-mediated killing.

Suppression of Myeloid Cell Arginase Activity leads to Therapeutic Response in a NSCLC Mouse Model by Activating Anti-Tumor Immunity.

Background: Tumor orchestrated metabolic changes in the microenvironment limit generation of anti-tumor immune responses. Availability of arginine, a semi-essential amino acid, is critical for lymphocyte proliferation and function. Levels of arginine are regulated by the enzymes arginase 1,2 and nitric oxide synthase (NOS).

Simulation of the Effect of Different Presbyopia-Correcting Intraocular Lenses With Eyes With Previous Laser Refractive Surgery.

Purpose: To simulate the optical performance of three presbyopia-correcting intraocular lenses (IOLs) implanted in eyes with previous laser refractive surgery.

Methods: A simulation of the through-focus modulation transfer function (MTF) was performed for three presbyopia-correcting IOLs (Mplus, Oculentis GmbH, Berlin, Germany; Symfony, Johnson & Johnson Vision, Santa Ana, CA; and Mini Well, SIFI S.p.

In Vitro Aberrometric Assessment of a Multifocal Intraocular Lens and Two Extended Depth of Focus IOLs.

Purpose: To analyze the "in vitro" aberrometric pattern of a refractive IOL and two extended depth of focus IOLs.

Methods: A special optical bench with a Shack-Hartmann wavefront sensor (SH) was designed for the measurement. Three presbyopia correction IOLs were analyzed: Mini WELL (MW), TECNIS Symfony ZXR00 (SYM), and Lentis Mplus X LS-313 MF30 (MP).

Novel Small Molecule Inhibitors of Choline Kinase Identified by Fragment-Based Drug Discovery.

Choline kinase α (ChoKα) is an enzyme involved in the synthesis of phospholipids and thereby plays key roles in regulation of cell proliferation, oncogenic transformation, and human carcinogenesis. Since several inhibitors of ChoKα display antiproliferative activity in both cellular and animal models, this novel oncogene has recently gained interest as a promising small molecule target for cancer therapy. Here we summarize our efforts to further validate ChoKα as an oncogenic target and explore the activity of novel small molecule inhibitors of ChoKα.

Ultrathin high-index metasurfaces for shaping focused beams.

The volume size of a converging wave, which plays a relevant role in image resolution, is governed by the wavelength of the radiation and the numerical aperture (NA) of the wavefront. We designed an ultrathin (λ/8 width) curved metasurface that is able to transform a focused field into a high-NA optical architecture, thus boosting the transverse and (mainly) on-axis resolution. The elements of the metasurface are metal-insulator subwavelength gratings exhibiting extreme anisotropy with ultrahigh index of refraction for TM polarization.

Engineered surface waves in hyperbolic metamaterials.

We analyzed surface-wave propagation that takes place at the boundary between a semi-infinite dielectric and a multilayered metamaterial, the latter with indefinite permittivity and cut normally to the layers. Known hyperbolization of the dispersion curve is discussed within distinct spectral regimes, including the role of the surrounding material. Hybridization of surface waves enable tighter confinement near the interface in comparison with pure-TM surface-plasmon polaritons.

Fragment growing and linking lead to novel nanomolar lactate dehydrogenase inhibitors.

Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway. Cancer cells rely heavily on glycolysis instead of oxidative phosphorylation to generate ATP, a phenomenon known as the Warburg effect. The inhibition of LDH-A by small molecules is therefore of interest for potential cancer treatments.

Left-handed metamaterial coatings for subwavelength-resolution imaging.

We report on a procedure to improve the resolution of far-field imaging by using a neighboring high-index medium that is coated with a left-handed metamaterial. The resulting plot can also exhibit an enhanced transmission by considering proper conditions to retract backscattering. Based on negative refraction, geometrical aberrations are considered in detail since they may cause a great impact in this sort of diffraction-unlimited imaging by reducing its resolution power.

Considerations on the electromagnetic flow in Airy beams based on the Gouy phase.

We reexamine the Gouy phase in ballistic Airy beams (AiBs). A physical interpretation of our analysis is derived in terms of the local phase velocity and the Poynting vector streamlines. Recent experiments employing AiBs are consistent with our results.

Algorithm for correcting the keratometric estimation error in normal eyes.

Purpose: To obtain an accurate algorithm for calculating the keratometric index that minimizes the errors in the calculation of corneal power assuming only a single corneal surface in the range of corneal curvatures of the normal population.

Methods: Corneal power was calculated by using the classical keratometric index and also by using the Gaussian equation. Differences between types of calculation of corneal power were determined and modeled by regression analysis.

Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen.

Activating gene rearrangements of anaplastic lymphoma kinase (ALK) have been identified as driver mutations in non-small-cell lung cancer, inflammatory myofibroblastic tumors, and other cancers. Crizotinib, a dual MET/ALK inhibitor, has demonstrated promising clinical activity in patients with non-small-cell lung cancer and inflammatory myofibroblastic tumors harboring ALK translocations. Inhibitors of driver kinases often elicit kinase domain mutations that confer resistance, and such mutations have been successfully predicted using in vitro mutagenesis screens.

Nondiffracting Bessel plasmons.

We report on the existence of nondiffracting Bessel surface plasmon polaritons (SPPs), advancing at either superluminal or subluminal phase velocities. These wave fields feature deep subwavelength FWHM, but are supported by high-order homogeneous SPPs of a metal/dielectric (MD) superlattice. The beam axis can be relocated to any MD interface, by interfering multiple converging SPPs with controlled phase matching.

Three-dimensional point spread function and generalized amplitude transfer function of near-field flat lenses.

We derive a nonsingular, polarization-dependent, 3D impulse response that provides unambiguously the wave field scattered by a negative-refractive-index layered lens and distributed in its image volume. By means of a 3D Fourier transform, we introduce the generalized amplitude transfer function in order to gain a deep insight into the resolution power of the optical element. In the near-field regime, fine details containing some depth information may be transmitted through the lens.

Diffraction-free beams in thin films.

The propagation and transmission of Bessel beams through nano-layered structures has been discussed recently. Within this framework we recognize the formation of unguided diffraction-free waves with the spot size approaching and occasionally surpassing the limit of a wavelength when a Bessel beam of any order n is launched onto a thin material slab with grazing incidence. On the basis of the plane-wave representation of cylindrical waves, a simple model is introduced providing an exact description of the transverse pattern of this type of diffraction-suppressed localized wave.

Free-space delay lines and resonances with ultraslow pulsed Bessel beams.

We investigate the ultraslow motion of polychromatic Bessel beams in unbounded, nondispersive media. Control over the group velocity is exercised by means of the angular dispersion of pulsed Bessel beams of invariant transverse spatial frequency, which spontaneously emerge from near-field generators. Temporal dynamics in transients and resonances over homogeneous delay lines (dielectric slabs) are also examined.

Angular spectrum of diffracted wave fields with apochromatic correction.

We report on compensation of diffraction-induced angular dispersion of ultrashort pulses up to a second order. A strategy for chromatic correction profits from high dispersion of kinoform-type zone plates. Ultraflat dispersion curves rely on a saddle point that may be tuned at a prescribed wavelength.

Differential toolbox to shape dispersion behavior in photonic crystal fibers.

We present an analytical procedure to compute the first derivatives of the propagation constants with respect to several structural parameters in photonic crystal fibers (PCFs). From them we can easily evaluate the same derivatives of other directly related magnitudes. The above derivatives provide the trend of the magnitude at issue, which allows us to take advantage of a gradient-based algorithm to shape the properties of the guiding structure.

Multiplexed G-protein-coupled receptor Ca2+ flux assays for high-throughput screening.

An early drug discovery approach focusing on gene families can benefit from strategies that exploit common signaling mechanisms to more effectively identify and characterize novel chemical lead structures. Multiplexing, defined as the screening of multiple targets within the same experiment, is an example of this strategy. Here, the authors describe a technique that allows multiplexing of a common assay type used to study G-protein-coupled receptors: changes in intracellular Ca2+ levels as measured by Molecular Device's fluorometric imaging plate reader (FLIPR).