Ultrafast Time Dynamics of Plasmonic Fractional Orbital Angular Momentum.

The creation and manipulation of optical vortices, both in free space and in two-dimensional systems such as surface plasmon polaritons (SPPs), has attracted widespread attention in nano-optics due to their robust topological structure. Coupled with strong spatial confinement in the case of SPPs, these plasmonic vortices and their underlying orbital angular momentum (OAM) have promise in novel light-matter interactions on the nanoscale with applications ranging from on-chip particle manipulation to tailored control of plasmonic quasiparticles. Until now, predominantly integer OAM values have been investigated. Here, we measure and analyze the time evolution of fractional OAM SPPs using time-resolved two-photon photoemission electron microscopy and near-field optical microscopy. We experimentally show the field's complex rotational dynamics and observe the beating of integer OAM eigenmodes at fractional OAM excitations. With our ability to access the ultrafast time dynamics of the electric field, we can follow the buildup of the plasmonic fractional OAM during the interference of the converging surface plasmons. By adiabatically increasing the phase discontinuity at the excitation boundary, we track the total OAM, leading to plateaus around integer OAM values that arise from the interplay between intrinsic and extrinsic OAM.

Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas.

BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas. METHODS: We generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR molecules containing various hinge, transmembrane, and co-stimulatory domains. These were lentivirally transduced into primary T cells and tested for antitumor activity in in vitro and in vivo B-cell lymphoma models. RESULTS: We found that the novel anti-CD79b monoclonal antibody was highly specific and bound only to human CD79b and no other cell surface protein. In testing the various CD79b-targeting CAR molecules, superior antitumor efficacy in vitro and in vivo was found for a CAR consisting CD8α hinge and transmembrane domains, an OX40 co-stimulatory domain, and a CD3ζ signaling domain. This CD79b CAR specifically recognized human CD79b-expressing lymphoma cell lines but not CD79b knock-out cell lines. CD79b CAR T cells, generated from T cells from either healthy donors or patients with lymphoma, proliferated, produced cytokines, degranulated, and exhibited robust cytotoxic activity in vitro against CD19+ and CD19- lymphoma cell lines and patient-derived lymphoma tumors relapsing after prior CD19 CAR T-cell therapy. Furthermore, CD79b CAR T cells were highly efficient at eradicating pre-established lymphoma tumors in vivo in three aggressive lymphoma xenograft models, including two cell line-derived xenografts and one patient-derived xenograft. Notably, these CAR T cells did not demonstrate any significant tonic signaling activity or markers of exhaustion. CONCLUSION: Our results indicated that this novel CD79b CAR T-cell therapy product has robust antitumor activity against B-cell lymphomas. These results supported initiation of a phase 1 clinical trial to evaluate this product in patients with relapsed or refractory B-cell lymphomas.

Heterogeneous cardiac sympathetic innervation gradients promote arrhythmogenesis in murine dilated cardiomyopathy.

Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve fibers versus controls. Further, the severity of transmural innervation gradients was correlated with VAs. Transmural innervation gradients were also identified in human left ventricular free wall samples from DCM versus controls. We investigated mechanisms underlying this relationship by in silico studies in 1D, 2D, and 3D models of failing and normal human hearts, finding that arrhythmogenesis increased as heterogeneity in sympathetic innervation worsened. Specifically, both DCM-induced myocyte electrical remodeling and spatially inhomogeneous innervation gradients synergistically worsened arrhythmogenesis. Thus, heterogeneous innervation gradients in DCM promoted arrhythmogenesis. Restoration of homogeneous sympathetic innervation in the failing heart may reduce VAs.

Mosquito surveillance on U.S military installations as part of a Japanese encephalitis virus detection program: 2016 to 2021.

Japanese encephalitis virus (JEV) continues to circulate throughout Southeast Asia and the Western Pacific where approximately 3 billion people in 24 countries are at risk of infection. Surveillance targeting the mosquito vectors of JEV was conducted at four military installations on Okinawa, Japan, between 2016 and 2021. Out of a total of 10,426 mosquitoes from 20 different species, zero were positive for JEV. The most abundant mosquito species collected were Aedes albopictus (36.4%) followed by Culex sitiens (24.3%) and Armigeres subalbatus (19%). Statistically significant differences in mosquito species populations according to location were observed. Changes in land use over time appear to be correlated with the species and number of mosquitoes trapped in each location. JEV appears to be absent from mosquito populations on Okinawa, but further research on domestic pigs and ardeid birds is warranted.

Modulation of Cathodoluminescence by Surface Plasmons in Silver Nanowires.

The waveguide modes in chemically-grown silver nanowires on silicon nitride substrates are observed using spectrally- and spatially-resolved cathodoluminescence (CL) excited by high-energy electrons in a scanning electron microscope. The presence of a long-range, travelling surface plasmon mode modulates the coupling efficiency of the incident electron energy into the nanowires, which is observed as oscillations in the measured CL with the point of excitation by the focused electron beam. The experimental data are modeled using the theory of surface plasmon polariton modes in cylindrical metal waveguides, enabling the complex mode wavenumbers and excitation strength of the long-range surface plasmon mode to be extracted. The experiments yield insight into the energy transfer mechanisms between fast electrons and coherent oscillations in surface charge density in metal nanowires and the relative amplitudes of the radiative processes excited in the wire by the electron.

Thin film notch filters as platforms for biological image processing.

Many image processing operations involve the modification of the spatial frequency content of images. Here we demonstrate object-plane spatial frequency filtering utilizing the angular sensitivity of a commercial spectral bandstop filter. This approach to all-optical image processing is shown to generate real-time pseudo-3D images of transparent biological and other samples, such as human cervical cancer cells. This work demonstrates the potential of non-local, non-interferometric approaches to image processing for uses in label-free biological cell imaging and dynamical monitoring.

Nanophotonics enhanced coverslip for phase imaging in biology.

The ability to visualise transparent objects such as live cells is central to understanding biological processes. Here we experimentally demonstrate a novel nanostructured coverslip that converts phase information to high-contrast intensity images. This compact device enables real-time, all-optical generation of pseudo three-dimensional images of phase objects on transmission. We show that by placing unstained human cancer cells on the device, the internal structure within the cells can be clearly seen. Our research demonstrates the significant potential of nanophotonic devices for integration into compact imaging and medical diagnostic devices. The nanophotonics enhanced coverslip (NEC) enables ultra-compact phase imaging of samples placed directly on top of the device. Visualisation of artificial phase objects and unstained biological cells is demonstrated.

Ultrafast vector imaging of plasmonic skyrmion dynamics with deep subwavelength resolution.

Plasmonic skyrmions are an optical manifestation of topological defects in a continuous vector field. Identifying them requires characterization of the vector structure of the electromagnetic near field on thin metal films. Here we introduce time-resolved vector microscopy that creates movies of the electric field vectors of surface plasmons with subfemtosecond time steps and a 10-nanometer spatial scale. We image complete time sequences of propagating surface plasmons as well as plasmonic skyrmions, resolving all vector components of the electric field and their time dynamics, thus demonstrating dynamic spin-momentum coupling as well as the time-varying skyrmion number. The ability to image linear optical effects in the spin and phase structures of light in the single-nanometer range will allow for entirely novel microscopy and metrology applications.

Discovery and Development of S6821 and S7958 as Potent TAS2R8 Antagonists.

In humans, bitter taste is mediated by 25 TAS2Rs. Many compounds, including certain active pharmaceutical ingredients, excipients, and nutraceuticals, impart their bitter taste (or in part) through TAS2R8 activation. However, effective TAS2R8 blockers that can either suppress or reduce the bitterness of these compounds have not been described. We are hereby reporting a series of novel 3-(pyrazol-4-yl) imidazolidine-2,4-diones as potent and selective TAS2R8 antagonists. In human sensory tests, S6821 and S7958, two of the most potent analogues from the series, demonstrated efficacy in blocking TAS2R8-mediated bitterness and were selected for development. Following data evaluation by expert panels of a number of national and multinational regulatory bodies, including the US, the EU, and Japan, S6821 and S7958 were approved as safe under conditions of intended use as bitter taste blockers.

Optical image processing with metasurface dark modes.

Here we consider image processing using the optical modes of metasurfaces with an angle-dependent excitation. These spatially dispersive modes can be used to directly manipulate the spatial frequency content of an incident field, suggesting their use as ultra-compact alternatives for analog optical information processing. A general framework for describing the filtering process in terms of the optical transfer functions is provided. In the case where the relevant mode cannot be excited with a normally incident plane wave (a dark mode), high-pass filtering is obtained. We provide examples demonstrating filtering of both amplitude and pure phase objects.

Mesoscale surface plasmons: modelling and imaging using near-field scanning optical microscopy.

Meso-scale plasmons are supported by structures with dimensions on the order of tens of plasmon wavelengths. Metal structures at this length-scale are promising for the design and engineering of structures to direct the flow of optical energy and generate high intensity, localized electric fields. The near-field optical properties of mesoscale crystalline gold plates were examined using near-field scanning optical microscopy with a focus on the effects of modifying morphology and excitation conditions. Excitation of surface plasmon polaritons (SPPs) at plate edges and their subsequent propagation and interference as radial waves across the surface results in nodes of enhancement of the near-field on the plate surface at specific positions within the plate. The spatial position of the near-field enhancement may be directed by controlling either, or both, the boundary conditions (plate shape) and polarization of the excitation light.

Cathodoluminescence as a probe of the optical properties of resonant apertures in a metallic film.

Here we present the results of an investigation of resonances of azimuthal trimer arrangements of rectangular slots in a gold film on a glass substrate using cathodoluminescence (CL) as a probe. The variation in the CL signal collected from specific locations on the sample as a function of wavelength and the spatial dependence of emission into different wavelength bands provides considerable insight into the resonant modes, particularly sub-radiant modes, of these apertures. By comparing our experimental results with electromagnetic simulations we are able to identify a Fabry-Pérot mode of these cavities as well as resonances associated with the excitation of surface plasmon polaritons on the air-gold boundary. We obtain evidence for the excitation of dark (also known as sub-radiant) modes of apertures and aperture ensembles.

Plasmonic circuit for second-order spatial differentiation at the subwavelength scale.

We suggest a plasmonic nanodevice for performing the second-order spatial derivative of light fields. The device consists of five gold nanorods arranged to evanescently couple to each other so that emit cross-polarized output proportional to the second-order differentiation of the incident wave. A theoretical model based on the electrostatic eigenmode analysis is derived and numerical simulations using the finite-difference time-domain methods are provided as supporting evidence. It is shown in both the analytic and numerical methods that the proposed plasmonic circuit performs second-order differentiation of the phase of the incident light field in transmission mode with a subwavelength planar resolution. The resolution of 0.29 λ-1 is numerically demonstrated for a 20 nm thick circuit at the wavelength of 700 nm. The suggested plasmonic device has potential application in miniaturized systems for all-optical computation.

Spatial Release From Masking in Adults With Bilateral Cochlear Implants: Effects of Distracter Azimuth and Microphone Location.

Purpose: The primary purpose of this study was to derive spatial release from masking (SRM) performance-azimuth functions for bilateral cochlear implant (CI) users to provide a thorough description of SRM as a function of target/distracter spatial configuration. The secondary purpose of this study was to investigate the effect of the microphone location for SRM in a within-subject study design. Method: Speech recognition was measured in 12 adults with bilateral CIs for 11 spatial separations ranging from -90° to +90° in 20° steps using an adaptive block design. Five of the 12 participants were tested with both the behind-the-ear microphones and a T-mic configuration to further investigate the effect of mic location on SRM. Results: SRM can be significantly affected by the hemifield origin of the distracter stimulus-particularly for listeners with interaural asymmetry in speech understanding. The greatest SRM was observed with a distracter positioned 50° away from the target. There was no effect of mic location on SRM for the current experimental design. Conclusion: Our results demonstrate that the traditional assessment of SRM with a distracter positioned at 90° azimuth may underestimate maximum performance for individuals with bilateral CIs.

Imaging the Nonlinear Plasmoemission Dynamics of Electrons from Strong Plasmonic Fields.

We use subcycle time-resolved photoemission microscopy to unambiguously distinguish optically triggered electron emission (photoemission) from effects caused purely by the plasmonic field (termed "plasmoemission"). We find from time-resolved imaging that nonlinear plasmoemission is dominated by the transverse plasmon field component by utilizing a transient standing wave from two counter-propagating plasmon pulses of opposite transverse spin. From plasmonic foci on flat metal surfaces, we observe highly nonlinear plasmoemission up to the fifth power of intensity and quantized energy transfer, which reflects the quantum-mechanical nature of surface plasmons. Our work constitutes the basis for novel plasmonic devices such as nanometer-confined ultrafast electron sources as well as applications in time-resolved electron microscopy.

Short-range surface plasmonics: Localized electron emission dynamics from a 60-nm spot on an atomically flat single-crystalline gold surface.

We experimentally and theoretically visualize the propagation of short-range surface plasmon polaritons using atomically flat single-crystalline gold platelets on silicon substrates. We study their excitation and subfemtosecond dynamics via normal-incidence two-photon photoemission electron microscopy. By milling a plasmonic disk and grating structure into a single-crystalline gold platelet, we observe nanofocusing of the short-range surface plasmon polariton. Localized two-photon ultrafast electron emission from a spot with a smallest dimension of 60 nm is observed. Our novel approach opens the door toward reproducible plasmonic nanofocusing devices, which do not degrade upon high light intensity or heating due to the atomically flat surface without any tips, protrusions, or holes. Our nanofoci could also be used as local emitters for ultrafast electron bunches in time-resolved electron microscopes.

Luminescence of a Transition Metal Complex Inside a Metamaterial Nanocavity.

Modification of the local density of optical states using metallic nanostructures leads to enhancement in the number of emitted quanta and photocatalytic turnover of luminescent materials. In this work, the fabrication of a metamaterial is presented that consists of a nanowire separated from a metallic mirror by a polymer thin film doped with a luminescent organometallic iridium(III) complex. The large spin-orbit coupling of the heavy metal atom results in an excited state with significant magnetic-dipole character. The nanostructured architecture supports two distinct optical modes and their assignment achieved with the assistance of numerical simulations. The simulations show that one mode is characterized by strong confinement of the electric field and the other by strong confinement of the magnetic field. These modes elicit drastic changes in the emitter's photophysical properties, including dominant nanocavity-derived modes observable in the emission spectra along with significant increases in emission intensity and the total decay rate. A combination of simulations and momentum-resolved spectroscopy helps explain the mechanism of the different interactions of each optical mode supported by the metamaterial with the excited state of the emitter.

Combined Electric and Acoustic Stimulation With Hearing Preservation: Effect of Cochlear Implant Low-Frequency Cutoff on Speech Understanding and Perceived Listening Difficulty.

OBJECTIVE: The primary objective of this study was to assess the effect of electric and acoustic overlap for speech understanding in typical listening conditions using semidiffuse noise. DESIGN: This study used a within-subjects, repeated measures design including 11 experienced adult implant recipients (13 ears) with functional residual hearing in the implanted and nonimplanted ear. The aided acoustic bandwidth was fixed and the low-frequency cutoff for the cochlear implant (CI) was varied systematically. Assessments were completed in the R-SPACE sound-simulation system which includes a semidiffuse restaurant noise originating from eight loudspeakers placed circumferentially about the subject's head. AzBio sentences were presented at 67 dBA with signal to noise ratio varying between +10 and 0 dB determined individually to yield approximately 50 to 60% correct for the CI-alone condition with full CI bandwidth. Listening conditions for all subjects included CI alone, bimodal (CI + contralateral hearing aid), and bilateral-aided electric and acoustic stimulation (EAS; CI + bilateral hearing aid). Low-frequency cutoffs both below and above the original "clinical software recommendation" frequency were tested for all patients, in all conditions. Subjects estimated listening difficulty for all conditions using listener ratings based on a visual analog scale. RESULTS: Three primary findings were that (1) there was statistically significant benefit of preserved acoustic hearing in the implanted ear for most overlap conditions, (2) the default clinical software recommendation rarely yielded the highest level of speech recognition (1 of 13 ears), and (3) greater EAS overlap than that provided by the clinical recommendation yielded significant improvements in speech understanding. CONCLUSIONS: For standard-electrode CI recipients with preserved hearing, spectral overlap of acoustic and electric stimuli yielded significantly better speech understanding and less listening effort in a laboratory-based, restaurant-noise simulation. In conclusion, EAS patients may derive more benefit from greater acoustic and electric overlap than given in current software fitting recommendations, which are based solely on audiometric threshold. These data have larger scientific implications, as previous studies may not have assessed outcomes with optimized EAS parameters, thereby underestimating the benefit afforded by hearing preservation.

Effect of motion on speech recognition.

The benefit of spatial separation for talkers in a multi-talker environment is well documented. However, few studies have examined the effect of talker motion on speech recognition. In the current study, we evaluated the effects of (1) motion of the target or distracters, (2) a priori information about the target and distracter spatial configurations, and (3) target and distracter location. In total, seventeen young adults with normal hearing were tested in a large anechoic chamber in two experiments. In Experiment 1, seven stimulus conditions were tested using the Coordinate Response Measure (Bolia et al., 2000) speech corpus, in which subjects were required to report the key words in a target sentence presented simultaneously with two distracter sentences. As in previous studies, there was a significant improvement in key word identification for conditions in which the target and distracters were spatially separated as compared to the co-located conditions. In addition, 1) motion of either talker or distracter resulted in improved performance compared to stationary presentation (talker motion yielded significantly better performance than distracter motion) 2) a priori information regarding stimulus configuration was not beneficial, and 3) performance was significantly better with key words at 0° azimuth as compared to -60° (on the listener's left). Experiment 2 included two additional conditions designed to assess whether the benefit of motion observed in Experiment 1 was due to the motion itself or to the fact that the motion conditions introduced small spatial separations in the target and distracter key words. Results showed that small spatial separations (on the order of 5-8°) resulted in improved performance (relative to co-located key words) whether the sentences were moving or stationary. These results suggest that in the presence of distracting messages, motion of either target or distracters and/or small spatial separation of the key words may be beneficial for sound source segregation and thus for improved speech recognition.

Assessment of Aedes albopictus (Skuse) (Diptera: Culicidae) clutch size in wild and laboratory populations.

Aedes albopictus (Skuse) is an invasive mosquito species found across the southern U.S. with range expansion into many northern states. Intra- and interspecific larval competition have been evaluated for Ae. albopictus with respect to subsequent adult size, immature and adult survivability, and its capacity to vector pathogens as an adult. However, limited data are available on egg production as related to larval rearing conditions. Because Ae. albopictus is a container-inhabiting mosquito that oviposits in resource-limited habitats, it is found under variable density-dependent conditions. Therefore, we examined the impact of specific rearing conditions on Ae. albopictus clutch size and adult body size; comparing the egg production values and wing lengths from known developmental densities to those from field-collected populations. Field populations varied significantly among collection sites in mean clutch size (23 to 46). These clutch sizes were comparable to the mean clutch sizes of females reared at the larval densities of nine (20 eggs) and three (53 eggs) larvae per 3 ml of water in the laboratory. Field populations experienced density-dependent effects impacting adult mosquito size. Mosquitoes from the four sample sites had mean wing lengths of 1.99, 2.47, 2.51, and 2.54 mm, which were less than the mean wing length of mosquitoes reared at larval densities of three larvae per 3 ml of water (2.57 mm).