Predicting the wicking rate of nitrocellulose membranes from recipe data: a case study using ANN at a membrane manufacturing in South Korea.

Lateral flow assays have been widely used for detecting coronavirus disease 2019 (COVID-19). A lateral flow assay consists of a Nitrocellulose (NC) membrane, which must have a specific lateral flow rate for the proteins to react. The wicking rate is conventionally used as a method to assess the lateral flow in membranes. We used multiple regression and artificial neural networks (ANN) to predict the wicking rate of NC membranes based on membrane recipe data. The developed ANN predicted the wicking rate with a mean square error of 0.059, whereas the multiple regression had a square error of 0.503. This research also highlighted the significant impact of the water content on the wicking rate through images obtained from scanning electron microscopy. The findings of this research can cut down the research and development costs of novel NC membranes with a specific wicking rate significantly, as the algorithm can predict the wicking rate based on the membrane recipe.

Hypoxia stabilizes SETDB1 to maintain genome stability.

Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element-derived double-stranded RNAs, thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.

Square microchannel enables to focus and orient ellipsoidal Euglena gracilis cells by two-dimensional acoustic standing wave.

Flow cytometry has become an indispensable tool for counting, analyzing, and sorting large cell populations in biological research and medical practice. Unfortunately, it has limitations in the analysis of non-spherically shaped cells due to the variation of their alignment with respect to the flow direction and, hence, the optical interrogation axis, resulting in unreliable cell analysis. Here, we present a simple on-chip acoustofluidic method to fix the orientation of ellipsoidal cells and focus them into a single, aligned stream. Specifically, by generating acoustic standing waves inside a 100 ⋅ 100 µm square-shaped microchannel, we successfully aligned and focused up to 97.7% of a population of Euglena gracilis (an ellipsoidal shaped microalgal species) cells in the center of the microchannel with high precision at a volume rate of 25 to 200 µL min-1. Uniform positioning of ellipsoidal cells is essential for making flow cytometry applicable to the investigation of a greater variety of cell populations and is expected to be beneficial for ecological studies and aquaculture.

Curved Versus Flat Monitors: Interactive Effects of Display Curvature Radius and Display Size on Visual Search Performance and Visual Fatigue.

OBJECTIVE: The aim of this study is to examine the interactive effects of display curvature radius and display size on visual search accuracy, visual search speed, and visual fatigue. BACKGROUND: Although the advantages of curved displays have been reported, little is known about the interactive effects of display curvature radius and size. METHOD: Twenty-seven individuals performed visual search tasks at a viewing distance of 50 cm using eight configurations involving four display curvature radii (400R, 600R, 1200R, and flat) and two display sizes (33″ and 50″). To simulate curved screens, five flat display panels were horizontally arranged with their centers concentrically repositioned following each display curvature radius. RESULTS: For accuracy, speed, and fatigue, 33″-600R and 50″-600R provided the best or comparable-to-best results, whereas 50″-flat provided the worst results. For accuracy and fatigue, 33″-flat was the second worst. The changes in the horizontal field of view and viewing angle due to display curvature as well as the association between effective display curvature radii and empirical horopter (loci of perceived equidistance) can explain these results. CONCLUSION: The interactive effects of display curvature radius and size were evident for visual search performance and fatigue. Beneficial effects of curved displays were maintained across 33″ and 50″, whereas increasing flat display size from 33″ to 50″ was detrimental. APPLICATION: For visual search tasks at a viewing distance of 50 cm, 33″-600R and 50″ 600R displays are recommended, as opposed to 33″ and 50″ flat displays. Wide flat displays must be carefully considered for visual display terminal tasks.

Deubiquitinase OTUD5 is a positive regulator of mTORC1 and mTORC2 signaling pathways.

The mammalian Target of Rapamycin (mTOR) pathway regulates a variety of physiological processes, including cell growth and cancer progression. The regulatory mechanisms of these signals are extremely complex and comprise many feedback loops. Here, we identified the deubiquitinating enzyme ovarian tumor domain-containing protein 5 (OTUD5) as a novel positive regulator of the mTOR complex (mTORC) 1 and 2 signaling pathways. We demonstrated that OTUD5 stabilized ß-transducin repeat-containing protein 1 (ßTrCP1) proteins via its deubiquitinase (DUB) activity, leading to the degradation of Disheveled, Egl-10, and pleckstrin domain-containing mTOR-interacting protein (DEPTOR), which is an inhibitory protein of mTORC1 and 2. We also showed that mTOR directly phosphorylated OTUD5 and activated its DUB activity. RNA sequencing analysis revealed that OTUD5 regulates the downstream gene expression of mTOR. Additionally, OTUD5 depletion elicited several mTOR-related phenotypes such as decreased cell size and increased autophagy in mammalian cells as well as the suppression of a dRheb-induced curled wing phenotype by RNA interference of Duba, a fly ortholog of OTUD5, in Drosophila melanogaster. Furthermore, OTUD5 knockdown inhibited the proliferation of the cancer cell lines with mutations activating mTOR pathway. Our results suggested a positive feedback loop between OTUD5 and mTOR signaling pathway.

Combination Treatment with GSK126 and Pomalidomide Induces B-Cell Differentiation in EZH2 Gain-of-Function Mutant Diffuse Large B-Cell Lymphoma.

Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), regulates genes involved in cell lineage and differentiation through methylating lysine 27 on histone H3 (H3K27me3). Recurrent gain-of-function mutations of EZH2 have been identified in various cancer types, in particular, diffuse large B-cell lymphoma (DLBCL), through large-scale genome-wide association studies and EZH2 depletion or pharmacological inhibition has been shown to exert an antiproliferative effect on cancer cells, both in vitro and in vivo. In the current study, a combination of pomalidomide and GSK126 synergistically inhibited the growth of EZH2 gain-of-function mutant Diffuse large B-cell lymphoma (DLBCL) cells. Furthermore, this synergistic effect appeared to be dependent on cereblon (CRBN), a cellular receptor of pomalidomide, but not degradation of IKAROS family zinc finger 1 (IKZF1) or IKAROS family zinc finger 3 (IKZF3). RNA sequencing analyses revealed that co-treatment with GSK126 and pomalidomide induced specific gene sets involved in B-cell differentiation and apoptosis. Synergistic growth inhibition and B-cell differentiation were further validated in xenograft mouse models. Our collective results provide a molecular basis for the mechanisms underlying the combined therapeutic effects of PRC2 inhibitors and pomalidomide on EZH2-mutated DLBCL.

Curved TVs improved watching experience when display curvature radii approached viewing distances: Effects of display curvature radius, viewing distance, and lateral viewing position on TV watching experience.

Although watching TV often involves multiple viewing distances and viewers, less attention has been paid to the effects of display curvature radius, viewing distance, and lateral viewing position on TV watching experience. This study examined the effects of four display curvature radii (2300R, 4000R, 6000R, and flat), two viewing distances (2.3 m and 4 m), and five lateral viewing positions (P1-P5; 0, 35, 70, 105, and 140 cm off-center) on seven TV watching experience elements (spatial presence, engagement, ecological validity, negative effects, visual comfort, image quality, and user satisfaction). Fifty-six individuals (14 per display curvature radius) were seated in pairs to watch videos, each time at a different viewing position (2 viewing distances × 5 paired lateral viewing positions). The spatial presence and engagement increased when display curvature radius approached a viewing distance and lateral viewing position approached P1, with 4000R-4m-P1 (display curvature radius-viewing distance-lateral viewing position) providing the best results. Lateral viewing position alone significantly affected five TV watching experience elements; the spatial presence and engagement decreased at P3-P5, and ecological validity, image quality, and user satisfaction decreased at P4-P5. However, display curvature radius alone did not appreciably affect TV watching experience, and viewing distance alone significantly affected visual comfort only, with a 4-m viewing distance increasing visual comfort. This study demonstrated that effective display curvature radii for watching TV are viewing distance-dependent, and less off-center lateral viewing positions (P1-P2) are recommended for TV watching experience. Finally, among the TV watching experience elements, engagement explained user satisfaction to the greatest degree.

Disordered region of cereblon is required for efficient degradation by proteolysis-targeting chimera.

Proteolysis targeting chimeras (PROTACs) are an emerging strategy for promoting targeted protein degradation by inducing the proximity between targeted proteins and E3 ubiquitin ligases. Although successful degradation of numerous proteins by PROTACs has been demonstrated, the elements that determine the degradability of PROTAC-targeted proteins have not yet been explored. In this study, we developed von Hippel-Lindau-Cereblon (VHL-CRBN) heterodimerizing PROTACs that induce the degradation of CRBN, but not VHL. A quantitative proteomic analysis further revealed that VHL-CRBN heterodimerizing PROTACs induced the degradation of CRBN, but not the well-known immunomodulatory drug (IMiD) neo-substrates, IKAROS family zinc finger 1 (IKZF1) and -3 (IZKF3). Moreover, truncation of disordered regions of CRBN and the androgen receptor (AR) attenuated their PROTAC-induced degradation, and attachment of the disordered region to stable CRBN or AR facilitated PROTAC-induced degradation. Thus, these results suggest that the intrinsically disordered region of targeted proteins is essential for efficient proteolysis, providing a novel criterion for choosing degradable protein targets.

Ambivalent effects of display curvature on smartphone usability.

The current study examined the effects of display curvature and hand length on various smartphone usability measures. In total, 20 young participants completed reading, image viewing, video watching, calling, and texting using four smartphone devices with distinct display curvatures. Diverse usability measures related to these tasks were obtained. The four curvatures (flat, horizontally convex, vertically concave, and horizontally concave) each demonstrated both beneficial and detrimental effects; however, hand size effects were non-significant across all usability measures. No single fixed display curvature was found to be beneficial across all considered smartphone usability measures, indicating multiple curvatures (e.g. combinations of flat and vertically concave curvatures) are required from a single smartphone model rather than a single fixed curvature to improve an overall smartphone usability. Such varying curvatures are feasible with bendable displays. Comprehensive usability evaluations, especially focusing on grip comfort and image distortion, are needed when applying display curvatures on small devices.

Effects of display curvature and task duration on proofreading performance, visual discomfort, visual fatigue, mental workload, and user satisfaction.

This study examined the effects of display curvature and task duration on proofreading performance, visual discomfort, visual fatigue, mental workload, and user satisfaction. Five 27″ rear-screen mock-ups with distinct curvature radii (600R, 1140R, 2000R, 4000R, and flat) were used. Ten individuals per display curvature completed a series of four 15 min comparison-proofreading trials at a 600 mm viewing distance. Only proofreading speed benefited from display curvature, with 600R providing the highest mean proofreading speed. Proofreading speed increased and accuracy decreased for all display curvatures over the 1 h proofreading period. Visual discomfort, visual fatigue, and mental workload increased during the first 15 min of proofreading. A decrease in critical fusion frequency during that period indicated increases in visual fatigue and mental workload. A short break between 15 min proofreading tasks could be considered to prevent further degradation of task performance and ocular health.

Determining Ergonomic Smartphone Forms With High Grip Comfort and Attractive Design.

OBJECTIVE: The authors aimed to identify ergonomic smartphone forms by investigating the effects of hand length, four major smartphone dimensions (height, width, thickness, and edge roundness), and smartphone mass on grip comfort and design attractiveness. BACKGROUND: Despite their potential effect on grip comfort and design attractiveness, the dimensions specified above have never been simultaneously considered in a study investigating smartphone gripping. METHOD: Seventy-two young individuals participated in a three-stage study. Stage 1 determined the ranges of the four smartphone dimensions suitable for grip comfort and identified the strengths of their influences. Stage 2 investigated the effects of width and thickness (determined to have the greatest influence) on grip comfort and design attractiveness. Mock-ups of varying masses were fabricated using the dimensions determined during the first two stages to investigate the effect of mass on grip comfort and design attractiveness in Stage 3. RESULTS: Phone width was found to significantly influence grip comfort and design attractiveness, and the dimensions of 140 × 65 (or 70) × 8 × 2.5 mm (height × width × thickness × edge roundness) provided high grip comfort and design attractiveness. The selected dimensions were fit with a mass of 122 g, with masses in the range of 106-137 g being comparable. CONCLUSION: The findings of this study contribute to ergonomic smartphone design developments by specifying dimensions and mass that provide high grip comfort and design attractiveness. APPLICATION: The dimensions and mass determined in this study should be considered for improving smartphone design grip comfort and attractiveness.

Effects of Display Curvature, Presbyopia, and Task Duration on Visual Fatigue, Task Performance, and User Satisfaction.

OBJECTIVE: This study examined the effects of display curvature, presbyopia, and task duration on visual fatigue, task performance, and user satisfaction. BACKGROUND: Although curved displays have been applied to diverse display products, and some studies reported their benefits, it is still unknown whether the effects of display curvature are presbyopia-specific. METHOD: Each of 64 individuals (eight nonpresbyopes and eight presbyopes per display curvature) performed four 15-min proofreading tasks at one display curvature radius setting (600R, 1140R, 4000R, and flat; mm). Diverse measurements were obtained to assess visual fatigue, task performance, and user satisfaction. RESULTS: The mean pupil diameter was the largest with 1140R, indicating this curvature radius was associated with the least development of visual fatigue; 600R was comparable with 1140R in terms of pupil diameter. The presbyopic group showed a 28.5% slower proofreading speed compared with the nonpresbyopic group, whereas their proofreading accuracy was comparable. For both groups, the mean visual fatigue increased significantly during the first 15 min of proofreading, as indicated by a decrease of 0.11 mm in the mean pupil diameter, an increase of 3.8 in the mean bulbar conjunctival redness, and an increase of 9.13 in the mean eye complaint questionnaire score. CONCLUSION: The effect of display curvature was not presbyopia-specific. Low visual fatigue was observed with 1140R and 600R. APPLICATION: Display curvature radii near or in the range of 600R and 1140R and frequent breaks are recommended for both presbyopic and nonpresbyopic groups to reduce their visual fatigue due to visual display terminal tasks.

Effects of display curvature, display zone, and task duration on legibility and visual fatigue during visual search task.

This study examined the effects of display curvature (400, 600, 1200 mm, and flat), display zone (5 zones), and task duration (15 and 30 min) on legibility and visual fatigue. Each participant completed two 15-min visual search task sets at each curvature setting. The 600-mm and 1200-mm settings yielded better results than the flat setting in terms of legibility and perceived visual fatigue. Relative to the corresponding centre zone, the outermost zones of the 1200-mm and flat settings showed a decrease of 8%-37% in legibility, whereas those of the flat setting showed an increase of 26%-45% in perceived visual fatigue. Across curvatures, legibility decreased by 2%-8%, whereas perceived visual fatigue increased by 22% during the second task set. The two task sets induced an increase of 102% in the eye complaint score and a decrease of 0.3 Hz in the critical fusion frequency, both of which indicated an increase in visual fatigue. In summary, a curvature of around 600 mm, central display zones, and frequent breaks are recommended to improve legibility and reduce visual fatigue.