Towards Co-Operative Beaming Displays: Dual Steering Projectors for Extended Projection Volume and Head Orientation Range.

Existing near-eye displays (NEDs) have trade-offs related to size, weight, computational resources, battery life, and body temperature. A recent paradigm, beaming display, addresses these trade-offs by separating the NED into a steering projector (SP) for image presentation and a passive headset worn by the user. However, the beaming display has issues with the projection area of a single SP and has severe limitations on the head orientation and pose that the user can move. In this study, we distribute dual steering projectors in the scene to extend the head orientation and pose of the beaming display by coordinating the dual projections on a passive headset. For cooperative control of each SP, we define a geometric model of the SPs and propose a calibration and projection control method designed for multiple projectors. We present implementations of the system along with evaluations showing that the precision and delay are 1.8 ∼ 5.7 mm and 14.46 ms, respectively, at a distance of about 1 m from the SPs. From this result, our prototype with multiple SPs can project images in the projection area ($20\ \text{mm} \times 30\ \text{mm}$) of the passive headset while extending the projectable head orientation. Furthermore, as applications of cooperative control by multiple SPs, we show the possibility of multiple users, improving dynamic range and binocular presentation.

StainedSweeper: Compact, Variable-Intensity Light-Attenuation Display with Sweeping Tunable Retarders.

Light Attenuation Displays (LADs) are a type of Optical See-Through Head-Mounted Display (OST-HMD) that present images by attenuating incoming light with a pixel-wise polarizing color filter. Although LADs can display images in bright environments, there is a trade-off between the number of Spatial Light Modulators (SLMs) and the color gamut and contrast that can be expressed, making it difficult to achieve both high-fidelity image display and a small form factor. To address this problem, we propose StainedSweeper, a LAD that achieves both the wide color gamut and the variable intensity with a single SLM. Our system synchronously controls a pixel-wise Digital Micromirror Device (DMD) and a nonpixel polarizing color filter to pass light when each pixel is the desired color. By sweeping this control at high speed, the human eye perceives images in a time-multiplexed, integrated manner. To achieve this, we develop the OST-HMD design using a reflective Solc filter as a polarized color filter and a color reproduction algorithm based on the optimization of the time-multiplexing matrix for the selected primary color filters. Our proof-of-concept prototype showed that our single SLM design can produce subtractive images with variable contrast and a wider color gamut than conventional LADs.

Histological and biochemical changes in lymphatic vessels after skeletal muscle injury induced by lengthening contraction in male mice.

Lymphatic vessels are actively involved in the recovery process of inflamed tissues. However, the changes in intramuscular lymphatic vessels during inflammation caused by skeletal muscle injury remain unclear. Therefore, the purpose of this study was to clarify the changes in lymphatic vessels after skeletal muscle injury. The left tibialis anterior muscles of male mice were subjected to lengthening contractions (LC) for inducing skeletal muscle injury, and samples were collected on Days 2, 4, and 7 for examining changes in both the skeletal muscles and intramuscular lymphatic vessels. With hematoxylin-eosin staining, the inflammatory response was observed in myofibers on Days 2 and 4 after LC, whereas regeneration of myofibers was found on Day 7 after LC. The number and area of intramuscular lymphatic vessels analyzed by immunohistochemical staining with an antibody against lymphatic vessel endothelial hyaluronan receptor 1 were significantly increased only on Day 4 after LC. Based on the abovementioned results, intramuscular lymphatic vessels undergo morphological changes such as increase under the state of muscle inflammation. This study demonstrated that the morphology of intramuscular lymphatic vessels undergoes significant changes during the initial recovery phase following skeletal muscle injury.

Low-Latency Beaming Display: Implementation of Wearable, 133 µs Motion-to-Photon Latency Near-Eye Display.

This paper presents a low-latency Beaming Display system with a 133 µs motion-to-photon (M2P) latency, the delay from head motion to the corresponding image motion. The Beaming Display represents a recent near-eye display paradigm that involves a steerable remote projector and a passive wearable headset. This system aims to overcome typical trade-offs of Optical See-Through Head-Mounted Displays (OST-HMDs), such as weight and computational resources. However, since the Beaming Display projects a small image onto a moving, distant viewpoint, M2P latency significantly affects displacement. To reduce M2P latency, we propose a low-latency Beaming Display system that can be modularized without relying on expensive high-speed devices. In our system, a 2D position sensor, which is placed coaxially on the projector, detects the light from the IR-LED on the headset and generates a differential signal for tracking. An analog closed-loop control of the steering mirror based on this signal continuously projects images onto the headset. We have implemented a proof-of-concept prototype, evaluated the latency and the augmented reality experience through a user-perspective camera, and discussed the limitations and potential improvements of the prototype.

Neural distortion fields for spatial calibration of wide field-of-view near-eye displays.

We propose a spatial calibration method for wide field-of-view (FoV) near-eye displays (NEDs) with complex image distortions. Image distortions in NEDs can destroy the reality of the virtual object and cause sickness. To achieve distortion-free images in NEDs, it is necessary to establish a pixel-by-pixel correspondence between the viewpoint and the displayed image. Designing compact and wide-FoV NEDs requires complex optical designs. In such designs, the displayed images are subject to gaze-contingent, non-linear geometric distortions, which explicit geometric models can be difficult to represent or computationally intensive to optimize. To solve these problems, we propose neural distortion field (NDF), a fully-connected deep neural network that implicitly represents display surfaces complexly distorted in spaces. NDF takes spatial position and gaze direction as input and outputs the display pixel coordinate and its intensity as perceived in the input gaze direction. We synthesize the distortion map from a novel viewpoint by querying points on the ray from the viewpoint and computing a weighted sum to project output display coordinates into an image. Experiments showed that NDF calibrates an augmented reality NED with 90° FoV with about 3.23 pixel (5.8 arcmin) median error using only 8 training viewpoints. Additionally, we confirmed that NDF calibrates more accurately than the non-linear polynomial fitting, especially around the center of the FoV.

Inhibition of Melanoma Cell-Intrinsic Tim-3 Stimulates MAPK-Dependent Tumorigenesis.

T-cell immunoglobulin mucin family member 3 (Tim-3) is an immune checkpoint receptor that dampens effector functions and causes terminal exhaustion of cytotoxic T cells. Tim-3 inhibitors are under investigation in immuno-oncology (IO) trials, because blockade of T-cell-Tim-3 enhances antitumor immunity. Here, we identify an additional role for Tim-3 as a growth-suppressive receptor intrinsic to melanoma cells. Inhibition of melanoma cell-Tim-3 promoted tumor growth in both immunocompetent and immunocompromised mice, while melanoma-specific Tim-3 overexpression attenuated tumorigenesis. Ab-mediated Tim-3 blockade inhibited growth of immunogenic murine melanomas in T-cell-competent hosts, consistent with established antitumor effects of T-cell-Tim-3 inhibition. In contrast, Tim-3 Ab administration stimulated tumorigenesis of both highly and lesser immunogenic murine and human melanomas in T-cell-deficient mice, confirming growth-promoting effects of melanoma-Tim-3 antagonism. Melanoma-Tim-3 activation suppressed, while its blockade enhanced, phosphorylation of pro-proliferative downstream MAPK signaling mediators. Finally, pharmacologic MAPK inhibition reversed unwanted Tim-3 Ab-mediated tumorigenesis in T-cell-deficient mice and enhanced desired antitumor activity of Tim-3 interference in T-cell-competent hosts. These results identify melanoma-Tim-3 blockade as a mechanism that antagonizes T-cell-Tim-3-directed IO therapeutic efficacy. They further reveal MAPK targeting as a combination strategy for circumventing adverse consequences of unintended melanoma-Tim-3 inhibition. SIGNIFICANCE: Tim-3 is a growth-suppressive receptor intrinsic to melanoma cells, the blockade of which promotes MAPK-dependent tumorigenesis and thus counteracts antitumor activity of T-cell-directed Tim-3 inhibition.

Distinct antibody clones detect PD-1 checkpoint expression and block PD-L1 interactions on live murine melanoma cells.

Monoclonal antibodies (abs) targeting the programmed cell death 1 (PD-1) immune checkpoint pathway have revolutionized tumor therapy. Because T-cell-directed PD-1 blockade boosts tumor immunity, anti-PD-1 abs have been developed for examining T-cell-PD-1 functions. More recently, PD-1 expression has also been reported directly on cancer cells of various etiology, including in melanoma. Nevertheless, there is a paucity of studies validating anti-PD-1 ab clone utility in specific assay types for characterizing tumor cell-intrinsic PD-1. Here, we demonstrate reactivity of several anti-murine PD-1 ab clones and recombinant PD-L1 with live B16-F10 melanoma cells and YUMM lines using multiple independent methodologies, positive and negative PD-1-specific controls, including PD-1-overexpressing and PD-1 knockout cells. Flow cytometric analyses with two separate anti-PD-1 ab clones, 29F.1A12 and RMP1-30, revealed PD-1 surface protein expression on live murine melanoma cells, which was corroborated by marked enrichment in PD-1 gene (Pdcd1) expression. Immunoblotting, immunoprecipitation, and mass spectrometric sequencing confirmed PD-1 protein expression by B16-F10 cells. Recombinant PD-L1 also recognized melanoma cell-expressed PD-1, the blockade of which by 29F.1A12 fully abrogated PD-1:PD-L1 binding. Together, our data provides multiple lines of evidence establishing PD-1 expression by live murine melanoma cells and validates ab clones and assay systems for tumor cell-directed PD-1 pathway investigations.

Genomic and pathogenic characterization of RTX toxin producing Rodentibacter sp. that is closely related to Rodentibacter haemolyticus.

Rodentibacter spp. are opportunistic pathogens that are often isolated from the upper respiratory tracts of laboratory rodents. In particular, R. pneumotropicus and R. heylii require considerable caution in rodent colonies, as they cause lethal pneumonia in rodents. A new species, R. haemolyticus, has recently been classified in the genus, and a very closely related strain, Rodentibacter sp. strain JRC, has been isolated in Japan. This study focused on strain JRC by performing genomic and pathogenic analyses. Draft genome sequencing of strain JRC identified several genes coding for putative virulent proteins, including hemolysin and adhesin. Furthermore, we found a new RTX (repeats-in-structural toxin) toxin gene in the genome, which was predicted to produce a critical virulence factor (RTXIA) similar to Enterobacteriaceae. The concentrated culture supernatant containing RTX toxin (RTXIA) showed cytotoxicity toward RAW264.7 cells. Pre-incubation with anti-CD11a attenuated the cytolysis, suggesting that the concentrated culture supernatant containing RTXIA is cell surface LFA-1 mediated cytolysin. Experimental infection of strain JRC intranasally with 5 female BALB/c-Rag2-/- mice showed 60% lethality and was not significantly different from those of R. pneumotropicus ATCC 35149T using the log-rank test. Combined with our finding that RTXIA has an almost identical amino acid sequence (98% identity) to that of R. haemolyticus 1625/19T, these results strongly suggest that RTXIA-producing strain JRC (and related R. haemolyticus) is pathogenic to immunodeficient rodents, and both agents should be excluded in laboratory rodent colonies.

Focal surface occlusion.

This paper proposes focal surface occlusion to provide focal cues of occlusion masks for multiple virtual objects at continuous depths in an occlusion-capable optical see-through head-mounted display. A phase-only spatial light modulator (PSLM) that acts as a dynamic free-form lens is used to conform the focal surface of an occlusion mask to the geometry of the virtual scene. To reproduce multiple and continuous focal blurs while reducing the distortion of the see-through view, an optical design based on afocal optics and edge-based optimization to exploit a property of the occlusion mask is established. The prototype with the PSLM and transmissive liquid crystal display can reproduce the focus blur of occluded objects at multiple and continuous depths with a field of view of 14.6°.

Morphological and biochemical changes of lymphatic vessels in the soleus muscle of mice after hindlimb unloading.

INTRODUCTION/AIMS: Lymphatic vessels are responsible for the removal of metabolic waste from body tissues. They also play a crucial role in skeletal muscle functioning thorough their high-energy metabolism. In this study we investigated whether disuse muscle atrophy induced by hindlimb unloading is associated with an alteration in the number of lymphatic vessels and differential expression of lymphangiogenic factors in the soleus muscle. METHODS: Male C57BL/6 mice were subjected to tail suspension (TS) for 2 or 4 weeks to induce soleus muscle atrophy. After TS, lymphatic and blood capillaries in the soleus muscle were visualized and counted by double staining with LYVE-1 and CD31. The protein and mRNA levels of vascular endothelial growth factor (VEGF)-C, VEGF-D, and vascular endothelial growth factor receptor-3 were measured by Western blotting and real-time reverse transcript polymerase chain reaction, respectively. RESULTS: TS for 2 weeks resulted in a significant decrease in the number of blood capillaries compared with controls. However, there was no significant change in the number of lymphatic capillaries. By contrast, TS for 4 weeks resulted in a significant decrease in the number of lymphatic and blood capillaries. We observed a significant decrease in the mRNA levels of VEGF-C and VEGF-D in mice subjected to TS for 4 weeks. DISCUSSION: The decrease of intramuscular lymphatic vessels may a crucial role in the process of muscle atrophy.

Beaming Displays.

Existing near-eye display designs struggle to balance between multiple trade-offs such as form factor, weight, computational requirements, and battery life. These design trade-offs are major obstacles on the path towards an all-day usable near-eye display. In this work, we address these trade-offs by, paradoxically, removing the display from near-eye displays. We present the beaming displays, a new type of near-eye display system that uses a projector and an all passive wearable headset. We modify an off-the-shelf projector with additional lenses. We install such a projector to the environment to beam images from a distance to a passive wearable headset. The beaming projection system tracks the current position of a wearable headset to project distortion-free images with correct perspectives. In our system, a wearable headset guides the beamed images to a user's retina, which are then perceived as an augmented scene within a user's field of view. In addition to providing the system design of the beaming display, we provide a physical prototype and show that the beaming display can provide resolutions as high as consumer-level near-eye displays. We also discuss the different aspects of the design space for our proposal.

Computational Phase-Modulated Eyeglasses.

We present computational phase-modulated eyeglasses, a see-through optical system that modulates the view of the user using phase-only spatial light modulators (PSLM). A PSLM is a programmable reflective device that can selectively retardate, or delay, the incoming light rays. As a result, a PSLM works as a computational dynamic lens device. We demonstrate our computational phase-modulated eyeglasses with either a single PSLM or dual PSLMs and show that the concept can realize various optical operations including focus correction, bi-focus, image shift, and field of view manipulation, namely optical zoom. Compared to other programmable optics, computational phase-modulated eyeglasses have the advantage in terms of its versatility. In addition, we also presents some prototypical focus-loop applications where the lens is dynamically optimized based on distances of objects observed by a scene camera. We further discuss the implementation, applications but also discuss limitations of the current prototypes and remaining issues that need to be addressed in future research.

Cessation of electrically-induced muscle contraction activates autophagy in cultured myotubes.

Exercise is known to improve skeletal muscle function. The mechanism involves muscle contraction-induced activation of the mTOR pathway, which plays a central role in protein synthesis. However, mTOR activation blocks autophagy, a recycling mechanism with a critical role in cellular maintenance/homeostasis. These two responses to muscle contraction look contradictory to the functional improvement of exercise. Herein, we investigate these paradoxical muscle responses in a series of active-inactive phases in a cultured myotube model receiving electrical stimulation to induce intermittent muscle contraction. Our model shows that (1) contractile activity induces mTOR activation and muscle hypertrophy but blocks autophagy, resulting in the accumulation of damaged proteins, while (2) cessation of muscle contraction rapidly activates autophagy, removing damaged protein, yet a prolonged inactive state results in muscle atrophy. Our findings provide new insights into muscle biology and suggest that not only muscle contraction, but also the subsequent cessation of contraction plays a substantial role for the improvement of skeletal muscle function.

StainedView: Variable-Intensity Light-Attenuation Display with Cascaded Spatial Color Filtering for Improved Color Fidelity.

We present StainedView, an optical see-through display that spatially filters the spectral distribution of light to form an image with improved color fidelity. Existing light-attenuation displays have limited color fidelity and contrast, resulting in a degraded appearance of virtual images. To use these displays to present virtual images that are more consistent with the real world, we require three things: intensity modulation of incoming light, spatial color filtering with narrower bandwidth, and appropriate light modulation for incoming light with an arbitrary spectral distribution. In StainedView, we address the three requirements by cascading two phase-only spatial light modulators (PSLMs), a digital micromirror device, and polarization optics to control both light intensity and spectrum distribution. We show that our design has a 1.8 times wider color gamut fidelity (75.8% fulfillment of sRGB color space) compared to the existing single-PSLM approach (41.4%) under a reference white light. We demonstrated the design with a proof-of-concept display system. We further introduce our optics design and pixel-selection algorithm for the given light input, evaluate the spatial color filter, and discuss the limitation of the current prototype.

Light Attenuation Display: Subtractive See-Through Near-Eye Display via Spatial Color Filtering.

We present a display for optical see-through near-eye displays based on light attenuation, a new paradigm that forms images by spatially subtracting colors of light. Existing optical see-through head-mounted displays (OST-HMDs) form virtual images in an additive manner-they optically combine the light from an embedded light source such as a microdisplay into the users' field of view (FoV). Instead, our light attenuation display filters the color of the real background light pixel-wise in the users' see-through view, resulting in an image as a spatial color filter. Our image formation is complementary to existing light-additive OST-HMDs. The core optical component in our system is a phase-only spatial light modulator (PSLM), a liquid crystal module that can control the phase of the light in each pixel. By combining PSLMs with polarization optics, our system realizes a spatially programmable color filter. In this paper, we introduce our optics design, evaluate the spatial color filter, consider applications including image rendering and FoV color control, and discuss the limitations of the current prototype.

Varifocal Occlusion for Optical See-Through Head-Mounted Displays using a Slide Occlusion Mask.

We propose a varifocal occlusion technique for optical see-through head-mounted displays (OST-HMDs). Occlusion in OST-HMDs is a powerful visual cue that enables depth perception in augmented reality (AR). Without occlusion, virtual objects rendered by an OST-HMD appear semi-transparent and less realistic. A common occlusion technique is to use spatial light modulators (SLMs) to block incoming light rays at each pixel on the SLM selectively. However, most of the existing methods create an occlusion mask only at a single, fixed depth-typically at infinity. With recent advances in varifocal OST-HMDs, such traditional fixed-focus occlusion causes a mismatch in depth between the occlusion mask plane and the virtual object to be occluded, leading to an uncomfortable user experience with blurred occlusion masks. In this paper, we thus propose an OST-HMD system with varifocal occlusion capability: we physically slide a transmissive liquid crystal display (LCD) to optically shift the occlusion plane along the optical path so that the mask appears sharp and aligns to a virtual image at a given depth. Our solution has several benefits over existing varifocal occlusion methods: it is computationally less demanding and, more importantly, it is optically consistent, i.e., when a user loses focus on the corresponding virtual image, the mask again gets blurred consistently as the virtual image does. In the experiment, we build a proof-of-concept varifocal occlusion system implemented with a custom retinal projection display and demonstrate that the system can shift the occlusion plane to depths ranging from 25 cm to infinity.

HySAR: Hybrid Material Rendering by an Optical See-Through Head-Mounted Display with Spatial Augmented Reality Projection.

Spatial augmented reality (SAR) pursues realism in rendering materials and objects. To advance this goal, we propose a hybrid SAR (HySAR) that combines a projector with optical see-through head-mounted displays (OST-HMD). In an ordinary SAR scenario with co-located viewers, the viewers perceive the same virtual material on physical surfaces. In general, the material consists of two components: a view-independent (VI) component such as diffuse reflection, and a view-dependent (VD) component such as specular reflection. The VI component is static over viewpoints, whereas the VD should change for each viewpoint even if a projector can simulate only one viewpoint at one time. In HySAR, a projector only renders the static VI components. In addition, the OST-HMD renders the dynamic VD components according to the viewer's current viewpoint. Unlike conventional SAR, the HySAR concept theoretically allows an unlimited number of co-located viewers to see the correct material over different viewpoints. Furthermore, the combination enhances the total dynamic range, the maximum intensity, and the resolution of perceived materials. With proof-of-concept systems, we demonstrate HySAR both qualitatively and quantitatively with real objects. First, we demonstrate HySAR by rendering synthetic material properties on a real object from different viewpoints. Our quantitative evaluation shows that our system increases the dynamic range by 2.24 times and the maximum intensity by 2.12 times compared to an ordinary SAR system. Second, we replicate the material properties of a real object by SAR and HySAR, and show that HySAR outperforms SAR in rendering VD specular components.

A Survey of Calibration Methods for Optical See-Through Head-Mounted Displays.

Optical see-through head-mounted displays (OST HMDs) are a major output medium for Augmented Reality, which have seen significant growth in popularity and usage among the general public due to the growing release of consumer-oriented models, such as the Microsoft Hololens. Unlike Virtual Reality headsets, OST HMDs inherently support the addition of computer-generated graphics directly into the light path between a user's eyes and their view of the physical world. As with most Augmented and Virtual Reality systems, the physical position of an OST HMD is typically determined by an external or embedded 6-Degree-of-Freedom tracking system. However, in order to properly render virtual objects, which are perceived as spatially aligned with the physical environment, it is also necessary to accurately measure the position of the user's eyes within the tracking system's coordinate frame. For over 20 years, researchers have proposed various calibration methods to determine this needed eye position. However, to date, there has not been a comprehensive overview of these procedures and their requirements. Hence, this paper surveys the field of calibration methods for OST HMDs. Specifically, it provides insights into the fundamentals of calibration techniques, and presents an overview of both manual and automatic approaches, as well as evaluation methods and metrics. Finally, it also identifies opportunities for future research.