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Endothelin receptor A (ET

Hindered gas bubble release and limited electron conducting process represent the major bottlenecks for large scale electrochemical water splitting. Both the desorption of bubbles and continuous electron transport are achievable on the surfaces of biomimetic catalytic materials by designing multiscale structural hierarchy. Inspired by the tubular structures of the deep-sea sponges, we fabricated an exceptionally active and binder-free porous nickel tube arrays (PNTA) decorated with NiFe-Zn

The formation of ordered magnetic domains in thin films is important for the magnetic microdevices in spin-electronics, magneto-optics, and magnetic microelectromechanical systems. Although inducing anisotropic stress in magnetostrictive materials can achieve the domain assembly, controlling magnetic anisotropy over microscale areas is challenging. In this work, we realized the microscopic patterning of magnetic domains by engineering stress distribution. Deposition of ferromagnetic thin films on nanotrenched polymeric layers induced tensile stress at the interfaces, giving rise to the directional magnetoelastic coupling to form ordered domains spontaneously. By changing the periodicity and shape of nanotrenches, we spatially tuned the geometric configuration of domains by design. Theoretical analysis and micromagnetic characterization confirmed that the local stress distribution by the topographic confinement dominates the forming mechanism of the directed magnetization.

Frequencies have been the most accurately measured physical quantity since the second was defined in 1967 based on the microwave atomic transition of a Cs atom. Recently, atomic clocks using optical frequency transitions have shown an order of magnitude better accuracy than microwave clocks. Thanks to their high accuracy and resolution, atomic clocks have become a new tool for investigations involving fundamental science and technology, such as the search for dark matter, gravitational wave detection, the temporal variation of fundamental constants, relativistic geodesy, quantum metrology, and the advanced Global Navigation Satellite System (GNSS). In addition, a redefinition of the second based on the optical frequency is expected. In this paper, we review the principles and applications of optical clocks.

Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 μg/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

Integration of plasma and pulsed light or ultraviolet has been investigated for microbial decontamination of foods. However, no studies have reported the microbial disinfection of particulate food using a large-scale system integrating the treatments. In the present study, a large-scale plasma jet-pulsed light-ultraviolet (UV)-C (PPU) system has been developed for the microbial decontamination of particulate foods. The effects of PPU treatment on the inactivation of natural mesophilic aerobic bacteria and yeast and molds of rice germ and the quality properties of rice germ were evaluated at various operation times (3, 5, 7, and 10 min) and sample amount (200, 500, 1,000, and 3,000 g). The efficacy of microbial inactivation of PPU treatment was enhanced with increasing treatment time and decreasing sample amount, and the maximum reduction was observed at 7 min with 200 g samples. The number of the natural bacteria and yeast and mold was reduced to 1.0 and 2.0 log CFU/g from an initial number of 5.7 and 3.7 log CFU/g, respectively. Compared to the individual treatments by atmospheric pressure plasma jet (APPJ) and intense pulsed light (IPL), PPU treatment synergistically inactivated microorganisms while not altering the color, antioxidant activity, or sensory properties of rice germ. The results of this study suggest the potential use of the large-scale PPU treatment system for the microbial decontamination of rice germ while minimizing alterations in quality.

This paper reports an approach to repurpose low-cost, bulk multilayer MoS

Flat metasurfaces with subwavelength meta-atoms can be designed to manipulate the electromagnetic parameters of incident light and enable unusual light-matter interactions beyond the capabilities of the constituent materials themselves. Although hydrogel-based metasurfaces have the potential to control optical properties dynamically in response to environmental conditions, the pattern resolution of these surfaces has typically been limited to microscale features or larger, limiting capabilities at the nanoscale and precluding effective use in metamaterials. This paper reports a general approach to developing reversibly tunable plasmonic metasurfaces with hydrogel meta-atoms at the subwavelength scale. Periodic arrays of hydrogel nanodots with continuously tunable diameters between 180 nm and 240 nm were fabricated on silver substrates, resulting in humidity-responsive surface plasmon polaritons (SPPs) at the nanostructure-metal interfaces. The peaks of the SPPs were controlled reversibly by absorbing or releasing water within the hydrogel matrix; the matrix subsequently generated plasmonic color rendering in the visible spectrum. We demonstrated that metasurfaces designed with these spatially patterned nanodots of varying sizes can benefit applications in anti-counterfeiting and generate multicolored displays with single-nanodot resolution. Furthermore, we showed system versatility exhibited by broadband beam-steering on a phase modulator consisting of hydrogel supercell units in which the size variations of constituent hydrogel nanostructures engineer the wavefront of reflected light from the metasurface.

For the management of rotating machines, machine learning (ML) has been researched with the use of feature parameters that have physical and statistical meanings of vibration signals. Genetic algorithm (GA) and principal component analysis (PCA) are the algorithms used for the selection or extraction process of the features; equipment condition. This study proposes a new method to maximize the advantages of the extraction and selection algorithms, thereby improving the fault classification performance. The proposed method is estimated in a variety of equipment conditions by selecting and extracting the effective features for status classification. To evaluate the performance of the fault classification through feature selection and extraction of the ML, a comparative analysis with the proposed method and the original method is also performed. With Lab-scale gearbox, several types of fault tests are conducted, and seven different fault types of equipment conditions, including the normal status, are simulated. The results of the experiments show that, the performance of classification of GA for feature selection is 85%, while PCA for feature extraction is 53%. The performance result of the proposed method for fault classification is 95%, meaning that the performance of fault diagnosis is more efficient in terms of discriminative learning than the original method. Therefore, the proposed method with feature extraction and selection algorithm can improve the fault classification performance by 10% and more for fault diagnosis through ML.

The angle-variable tunable optical filter was strictly fabricated by two strategies of nanoimprint-coupled metal nanopatterning with improved cost-effectiveness and accessibility. The tunable optical properties and the performances of two strategies were experimentally examined and turned out to be well matched to numerical results. Tunable properties are obtained by three factors: size of fabricated Ag nanodisks, incident illumination angle, and fabrication strategies. The resonant extinction peak shifts were identified to show a large increase along with the increase in fabricated Ag disk size and increase in the incidence angle of illumination. When comparing a fabrication strategy, it was confirmed that the sample fabricated by the strip-off method has better stability on color changes with a consistent dependency on the incident angle. The presented strategies of fabrication are technically viable for obtaining well-defined plasmonic nanostructures so that it has the feasibility to apply for fascinating optical applications including display or tunable optical filters.

Fibroblast Growth Factor 7 (FGF7), a growth factor specific to epithelial cells, has attracted attention as a therapeutic protein. However, FGF7 has a limitation in its use due to low protein stability. Here, the mutations were designed to increase the stability of FGF7 by analyzing its 3D structure and sequence of other FGFs. Palifermin, N-terminal truncated FGF7 is known to have improved stability and was used as control protein in our study. The K126 and K178 were substituted into glutamate to form salt bridge with the neighboring residue R175 respectively and A120C mutation was introduced in close vicinity to disulfide bond between C133 and C137. The data of Circular Dichroism (CD) showed that all mutant proteins tested had higher Tm value than Palifermin and Tm of A120C/K126E/K178E FGF7 mutant protein was 15.24 °C higher than that of Palifermin. The results of cell proliferation activity and soluble protein analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) after 37 °C or 45 °C incubation exhibited that the stability of A120C mutant protein and A120C-including mutant proteins was improved. These results suggest that the mutation of amino acid in close vicinity to disulfide bond and the salt bridge at the surface of FGF7 enhanced thermal stability and make FGF7 more useful for pharmaceutical and cosmetical application.

Background Alzheimer's disease (AD) is characterized by to neuronal cell death and neuroinflammation. Neurofibrillary tangle (NFTs) is one of the neuropathological hallmarker of AD. Also our previous study indicated that bee venom leads to neuroprotective effects in a lipopolysaccharide (LPS)-induced AD mouse model. Thus, in this study we investigated whether that phospholipase A2 (PLA2) reduces tau phosphorylation and neuroinflammation, and thus ameliorates AD development. Results To validate pathological activities in in vivo, we examined of the inhibitory effect of bvPLA2 on memory loss and tau phosphorylation as well as neuroinflammation by subcutaneous injection of bvPLA2 (0.5 mg/kg) to Tg2576 mice. For in vitro study, we examined the effect of bvPLA2 on cell death, tau pathology and neuroinflammation by treatment of bvPLA2 in LPS-activated PC12 cells. Our study showed that bvPLA2 mitigated memory impairment and spatial memory in Tg2576 mice, Agreed with the memory improvement, tau level and phosphorylation of tau were decreased by bvPLA2 treatment. Expression level of pro-inflammatory cytokines and inflammation-related proteins were also decreased in the brain of bvPLA2-treated Tg2576 mice. Conclusions Consideration of reduced tau level and phosphorylation of tau, GSK3β phosphorylation was studied. Phosphorylated GSK3β on Ser9 was significantly increased by treatment of bvPLA2, but a phosphorylated GSK3β on Tyr216 was significantly decreased in the Tg2576 mice brains. These data thus indicate that bvPLA2 prevents memory impairment through reduction of tau phosphorylation.

Locomotion of soft robots typically relies on control of multiple inflatable actuators by electronic computers and hard valves. Soft pneumatic oscillators can reduce the demand on controllers by generating complex movements required for locomotion from a single, constant input pressure, but either have been constrained to low rates of flow of air or have required complex fabrication processes. Here, we describe a pneumatic oscillator fabricated from flexible, but inextensible, sheets that provides high rates of airflow for practical locomotion by combining three instabilities: out-of-plane buckling of the sheets, kinking of tubing attached to the sheets, and a system-level instability resulting from connection of an odd number of pneumatic inverters made from these sheets in a loop. This device, which we call a "buckling-sheet ring oscillator" (BRO), directly generates movement from its own interaction with its surroundings and consists only of readily available materials assembled in a simple process-specifically, stacking acetate sheets, nylon film, and double-sided tape, and attaching an elastomeric tube. A device incorporating a BRO is capable of both translational and rotational motion over varied terrain (even without a tether) and can climb upward against gravity and downward against the buoyant force encountered under water. ispartof: SCIENCE ROBOTICS vol:7 issue:63 ispartof: location:United States status: published

As optical clocks are improved to reach the frequency uncertainty below the 10−17 level, the frequency shift due to the blackbody radiation (BBR) has been one of the major systematic effects hindering further improvement. To evaluate the BBR shift of an Yb optical lattice clock at KRISS, we installed an in-vacuum BBR shield and made radiation thermometry using a black-coated-sphere thermal probe. After we quantitatively measured the conduction loss of the thermal probe and the effects of all the external radiation sources, we determined the temperature at the atom trap site with an uncertainty of 13 mK, which corresponds to an uncertainty of 0.22 mHz in the clock frequency (a fractional frequency of 4.2 × 10−19). The total uncertainty of the BBR shift including the atomic response is 9.5 × 10−19.

We developed a shutter driven by a solenoid to switch on/off the atomic beam of optical lattice clocks developed at KRISS [C. Y. Park et al., Metrologia 50, 119 (2013), S. Lee et al., New J. Phys. 18, 033030 (2016), H. Kim et al., Jpn. J. Appl. Phys. 56, 050302 (2017), and H. Kim et al., Metrologia 58, 055007 (2021)]. The shutter design was focused on long lifetime and compatibility with an ultra-high vacuum (UHV) environment. Thus, the solenoid was designed to be easily installed and removed from the air-side of a CF flange of the shutter. The flag in the vacuum-side moves only with the simple spring action of a sheet of a metal plate without any frictional movement of mechanical parts. All parts in the vacuum-side were made of metals (stainless steel and pure iron) to be baked over the temperature of 200 °C for UHV. The flag head of the shutter displaces up to 10 mm (5 mm) with a response time of 50 (30 ms) and 80 ms (10 ms) for the opening-action and the closing-action, respectively. The lifetime was tested up to 6 × 106 cycles with no performance degradation. We expect the actual lifetime to be much longer than this by virtue of its friction-free design.

Our previous big data analyses reported a strong association between CHI3L1 expression and lung tumor development. In this present study, we investigated whether a CHI3L1-inhibiting natural compound, ebractenoid F, inhibits lung cancer cell growth and migration and induces apoptosis. Ebractenoid F concentration-dependently (0, 17, 35, 70 µM) and significantly inhibited the proliferation and migration of A549 and H460 lung cancer cells and induced apoptosis. In the mechanism study, we found that ebractenoid F bound to CHI3L1 and suppressed CHI3L1-associated AKT signaling. Combined treatment with an AKT inhibitor, LY294002, and ebractenoid F synergistically decreased the expression of CHI3L1. Moreover, the combination treatment further inhibited the growth and migration of lung cancer cells and further induced apoptosis, as well as the expression levels of apoptosis-related proteins. Thus, our data demonstrate that ebractenoid F may serve as a potential anti-lung cancer compound targeting CHI3L1-associated AKT signaling.

Flat metasurfaces with subwavelength meta-atoms can be designed to manipulate the electromagnetic parameters of incident light and enable unusual light-matter interactions. Although hydrogel-based metasurfaces have the potential to control optical properties dynamically in response to environmental conditions, the pattern resolution of these surfaces has been limited to microscale features or larger, limiting capabilities at the nanoscale, and precluding effective use in metamaterials. This paper reports a general approach to developing tunable plasmonic metasurfaces with hydrogel meta-atoms at the subwavelength scale. Periodic arrays of hydrogel nanodots with continuously tunable diameters are fabricated on silver substrates, resulting in humidity-responsive surface plasmon polaritons (SPPs) at the nanostructure-metal interfaces. The peaks of the SPPs are controlled reversibly by absorbing or releasing water within the hydrogel matrix, the matrix-generated plasmonic color rendering in the visible spectrum. This work demonstrates that metasurfaces designed with these spatially patterned nanodots of varying sizes benefit applications in anti-counterfeiting and generate multicolored displays with single-nanodot resolution. Furthermore, this work shows system versatility exhibited by broadband beam-steering on a phase modulator consisting of hydrogel supercell units in which the size variations of constituent hydrogel nanostructures engineer the wavefront of reflected light from the metasurface.

Radio frequency (RF) magnetron-sputtered TiO2 (RS-TiO2) is investigated as a hole-blocking layer for perovskite solar cells. RS-TiO2 shows conformal, dense, and efficiently electron transferable pr...

This Perspective focuses on the design of hierarchical structures in deformable thin materials by patterning mechanical instabilities. Fabrication of three-dimensional (3D) structures with multiple length scales-starting at the nanoscale-can result in on-demand surface functionalities from the modification of the mechanical, chemical, and optical properties of materials. Conventional top-down lithography, however, cannot achieve 3D patterns over large areas (cm

This paper investigates the correlation between the random lasing properties of organic waveguides made by poly-(9-9dioctylfluorene) (PFO) thin films and the morphology of wrinkled corrugated substrates. The capability to individually control the wrinkle wavelength, shape, and height allows us to separately investigate their role on the sample emission properties. We demonstrate that the main parameter determining the presence of coherent random lasing is the substrate roughness and that, contrary to what could be qualitatively expected, as the roughness increases, coherent random lasing is progressively reduced. Coherent random lasing is observed only for a substrate roughness below 33 nm, while higher roughness leads to amplified spontaneous emission (up to 70 nm) or to the absence of light amplification in the film (above 70 nm). We demonstrate that this result is due to a progressive reduction of the light amplification efficiency in the PFO film, evidencing that coherent random lasing can be obtained only with a right interplay between light amplification and scattering. Besides clarifying the basic aspects of random lasing in organic waveguides, our work opens the way to the realization of organic random lasers with predictable emission properties, thanks to the high control level of the scattering properties of the wrinkled corrugated surfaces.

Indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan catabolising enzyme, is known as a tumour cell survival factor that causes immune escape in several types of cancer. Flavonoids of Sophora flavescens have a variety of biological benefits for humans; however, cancer immunotherapy effect has not been fully investigated. The flavonoids (1–6) isolated from S. flavescens showed IDO1 inhibitory activities (IC50 4.3–31.4 µM). The representative flavonoids (4–6) of S. flavescens were determined to be non-competitive inhibitors of IDO1 by kinetic analyses. Their binding affinity to IDO1 was confirmed using thermal stability and surface plasmon resonance (SPR) assays. The molecular docking analysis and mutagenesis assay revealed the structural details of the interactions between the flavonoids (1–6) and IDO1. These results suggest that the flavonoids (1–6) of S. flavescens, especially kushenol E (6), as IDO1 inhibitors might be useful in the development of immunotherapeutic agents against cancers.

There is increasing demand for essential fatty acids (EFAs) from non-fish sources such as microalgae, which are considered a renewable and sustainable biomass. The open raceway system (ORS) is an affordable system for microalgae biomass cultivation for industrial applications. However, seasonal variations in weather can affect biomass productivity and the quality of microalgal biomass. The aim of this study was to determine the feasibility of year-round Tetraselmis sp. cultivation in a semi-ORS in Korea for biomass and bioactive lipid production. To maximize biomass productivity of Tetraselmis sp., f medium was selected because it resulted in a significantly higher biomass productivity (1.64 ± 0.03 g/L) and lower omega-6/omega-3 ratio (0.52/1) under laboratory conditions than f/2 medium (0.70/1). Then, we used climatic data-based building information modeling technology to construct a pilot plant of six semi-ORSs for controlling culture conditions, each with a culture volume of 40,000 L. Over 1 year, there were no significant variations in monthly biomass productivity, fatty acid composition, or the omega-6/omega-3 ratio; however, the lipid content correlated significantly with photosynthetic photon flux density. During year-round cultivation from November 2014 to October 2017, areal productivity was gradually increased by increasing medium salinity and injecting CO2 gas into the culture medium. Productivity peaked at 44.01 g/m2/d in October 2017. Throughout the trials, there were no significant differences in average lipid content, which was 14.88 ± 1.26%, 14.73 ± 2.44%, 12.81 ± 2.82%, and 13.63 ± 3.42% in 2014, 2015, 2016, and 2017, respectively. Our results demonstrated that high biomass productivity and constant lipid content can be sustainably maintained under Korean climate conditions.

Endothelin receptor A (ETA), a class A G-protein-coupled receptor (GPCR), is involved in the progression and metastasis of colorectal, breast, lung, ovarian, and prostate cancer. We overexpressed and purified human endothelin receptor type A in Escherichia coli and reconstituted it with lipid and membrane scaffold proteins to prepare an ETA nanodisc as a functional antigen with a structure similar to that of native GPCR. By screening a human naive immune single-chain variable fragment phage library constructed in-house, we successfully isolated a human anti-ETA antibody (AG8) exhibiting high specificity for ETA in the β-arrestin Tango assay and effective inhibitory activity against the ET-1-induced signaling cascade via ETA using either a CHO-K1 cell line stably expressing human ETA or HT-29 colorectal cancer cells, in which AG8 exhibited IC50 values of 56 and 51 nM, respectively. In addition, AG8 treatment repressed the transcription of inhibin βA and reduced the ETA-induced phosphorylation of protein kinase B and extracellular regulated kinase. Furthermore, tumor growth was effectively inhibited by AG8 in a colorectal cancer mouse xenograft model. The human anti-ETA antibody isolated in this study could be used as a potential therapeutic for cancers, including colorectal cancer.

Locomotion of an organism interacting with an environment is the consequence of a symmetry-breaking action in space-time. Here we show a minimal instantiation of this principle using a thin circular sheet, actuated symmetrically by a pneumatic source, using pressure to change shape nonlinearly via a spontaneous buckling instability. This leads to a polarized, bilaterally symmetric cone that can walk on land and swim in water. In either mode of locomotion, the emergence of shape asymmetry in the sheet leads to an asymmetric interaction with the environment that generates movement--via anisotropic friction on land, and via directed inertial forces in water. Scaling laws for the speed of the sheet of the actuator as a function of its size, shape, and the frequency of actuation are consistent with our observations. The presence of easily controllable reversible modes of buckling deformation further allows for a change in the direction of locomotion in open arenas and the ability to squeeze through confined environments--both of which we demonstrate using simple experiments. Our simple approach of harnessing elastic instabilities in soft structures to drive locomotion enables the design of novel shape-changing robots and other bioinspired machines at multiple scales.

Toxoplasma gondii, a ubiquitous, intracellular parasite of the phylum Apicomplexa, infects an estimated one-third of the human population as well as a broad range of warm-blooded animals. We have observed that some tyrosine kinase inhibitors suppressed the growth of T. gondii within host ARPE-10 cells. Among them, afatinib, human epithermal growth factor receptor 2 and 4 (HER2/4) inhibitor, may be used as a therapeutic agent for inhibiting parasite growth with minimal adverse effects on host. In this report, we conducted a proteomic analysis to observe changes in host proteins that were altered via infection with T. gondii and the treatment of HER2/4 inhibitors. Secreting proteins were subjected to a procedure of micor basic reverse phase liquid chromatography, nano-liquid chromatography-mass spectrometry, and ingenuity pathway analysis serially. As a result, the expression level of heterogeneous nuclear ribonucleoprotein K, semaphorin 7A, a GPI membrane anchor, serine/threonine-protein phosphatase 2A, and calpain small subunit 1 proteins were significantly changed, and which were confirmed further by western blot analysis. Changes in various proteins, including these 4 proteins, can be used as a basis for explaining the effects of T. gondii infections and HER2/4 inhibitors.

We demonstrate a fiber delay line-based direct comb-line stabilization with 6X10-15 frequency instability within 1 s. Two combs could be simultaneously stabilized to a single fiber delay-line with ~1-Hz relative linewidth and ~20-Hz absolute linewidth.

We investigated strontium oxide (SrO) as an interlayer material to enhance the UV stability of a CH3NH3PbI3 perovskite solar cell. Moisture and over 400 nm wavelength of light were excluded to investigate the effect of UV light only. Two different interlayer fabrication processes were examined to optimize the performance of this solar cell. Devices fabricated by dipping for 30 min in SrO solution exhibited photoconversion efficiencies of 15.5%, whereas those fabricated with 60-min dipping showed photoconversion efficiencies of 15% and exhibited local Sr agglomeration. Devices with SrO displayed lower initial efficiencies than those without any SrO layer (17.6%), However, a device without SrO retained only 34.4% of its initial efficiency after 100 h of UV exposure. In contrast, SrO-incorporated devices retained almost 60.0% of their initial efficiency. Severe μ-PL mapping intensity degradation was observed in devices that did not include the interlayer, but no degradation was observed in those with the SrO interlayer. This can be attributed to the passivation of the degradation sites by SrO.

Advanced satellite-based frequency transfers by two-way carrier-phase (TWCP) and integer precise point positioning have been performed between the National Institute of Information and Communications Technology and Korea Research Institute of Standards and Science. We confirm that the disagreement between them is less than $1\times 10^{-16}$ at an averaging time of several days. In addition, an overseas frequency ratio measurement of Sr and Yb optical lattice clocks was directly performed by TWCP. We achieved an uncertainty at the mid-10−16 level after a total measurement time of 12 h. The frequency ratio was consistent with the recently reported values within the uncertainty.

One of the most interesting topics in physical science and materials science is the creation of complex wrinkled structures on thin-film surfaces because of their several advantages of high surface area, localized strain, and stress tolerance. In this study, a significant step was taken toward solving limitations imposed by the fabrication of previous artificial wrinkles. A universal method for preparing hierarchical three-dimensional wrinkle structures of thin films on a multiple scale (e.g., nanometers to micrometers) by sequential wrinkling with different skin layers was developed. Notably, this method was not limited to specific materials, and it was applicable to fabricating hierarchical wrinkles on all of the thin-film surfaces tested thus far, including those of metals, two-dimensional and one-dimensional materials, and polymers. The hierarchical wrinkles with multiscale structures were prepared by sequential wrinkling, in which a sacrificial layer was used as the additional skin layer between sequences. For example, a hierarchical MoS2 wrinkle exhibited highly enhanced catalytic behavior because of the superaerophobicity and effective surface area, which are related to topological effects. As the developed method can be adopted to a majority of thin films, it is thought to be a universal method for enhancing the physical properties of various materials.

Recently, the need for rapid, reliable, and low-cost drug susceptibility testing (DST) methods has increased due to the emergence of multidrug-resistant Mycobacterium tuberculosis. Colorimetric methods of DST provide results more quickly than standard culture methods and are inexpensive than molecular methods. Thus, colorimetric methods, such as the nitrate reductase assay (NRA), are being recommended. We searched Medline PubMed for reports on the NRA for DST of M. tuberculosis written in English and published within the last five years. We selected 20 reports on six major anti-TB drugs and conducted a meta-analysis using Meta-Disc software. The pooled sensitivities for isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, and kanamycin were 95.4%, 96.4%, 91.5%, 93.1%, 99.3%, and 88.4%, and the pooled specificities were 98.5%, 99.2%, 92.9%, 97.8%, 97.4%, and 99.4%, respectively. The area under the summary receiver operator curve for all drugs was 0.9723-0.9952. The time to results (TTR) for the direct and indirect NRAs was 7-28days and 6-15days, respectively. Quality assessments were conducted using the quality of diagnostic accuracy studies tool (QUADAS-2) items, and most reports showed good performance. However, ethambutol, streptomycin, and kanamycin showed relatively low sensitivity. We performed a quantitative NRA in liquid media at various inoculum concentrations. The TTR at 4.94×106, 1.67×104, and 2.27×102CFU/mL was 4, 14, and 14days, respectively. The minimum absorbance and nitrite concentration for positive samples were 0.8 and 168μM, respectively. We propose a quantitative standard to determine sample positivity to address the problems with the current standard NRA which is much less expensive than the conventional assay conducted on solid medium.

Nanostructured surfaces with quasi-random geometries can manipulate light over broadband wavelengths and wide ranges of angles. Optimization and realization of stochastic patterns have typically relied on serial, direct-write fabrication methods combined with real-space design. However, this approach is not suitable for customizable features or scalable nanomanufacturing. Moreover, trial-and-error processing cannot guarantee fabrication feasibility because processing-structure relations are not included in conventional designs. Here, we report wrinkle lithography integrated with concurrent design to produce quasi-random nanostructures in amorphous silicon at wafer scales that achieved over 160% light absorption enhancement from 800 to 1,200 nm. The quasi-periodicity of patterns, materials filling ratio, and feature depths could be independently controlled. We statistically represented the quasi-random patterns by Fourier spectral density functions (SDFs) that could bridge the processing-structure and structure-performance relations. Iterative search of the optimal structure via the SDF representation enabled concurrent design of nanostructures and processing.

We characterize wrinkling on the surfaces of prestrained polystyrene sheets coated with thin polytetrafluoroethylene skins using a combination of mechanical strain measurements and 3D finite element simulations. The simulations show that wrinkle wavelength increases with skin thickness, in agreement with a well-known continuum model and recent experiments. The wrinkle amplitudes also increase with strain. Nanoinclusions, such as holes and patterned lines, influence wrinkle patterns over limited distances, and these distances are shown to scale with the wrinkle wavelengths. Good agreement between experimental and simulated influence distances is observed. The inclusions provide strain relief, and they behave as if they are attracting adjacent material when the sheets are under strain. The wrinkles have stiffnesses in much the same way as do polymers (but at different length scales), a property that is quantified for polymers using persistence lengths. We show that the concept of persistence length can be useful in characterizing the wrinkle properties that we have observed. However, the calculated persistence lengths do not vary systematically with thickness and strain, as interactions between neighboring wrinkles produce confinement that is analogous to the kinetic confinement of polymers.

We show that submicron-sized patterns can be imprinted into soft, recombinant-engineered protein hydrogels (here elastin-like proteins, ELP) by transferring wavy patterns from polydimethylsiloxane (PDMS) molds. The high-precision topographical tunability of the relatively stiff PDMS is translated to a bio-responsive, soft material, enabling topographical cell response studies at elastic moduli matching those of tissues. Aligned and unaligned wavy patterns with mold periodicities of 0.24-4.54 μm were imprinted and characterized by coherent anti-Stokes Raman scattering and atomic force microscopy. The pattern was successfully transferred down to 0.37 μm periodicity (width in ELP: 250 ± 50 nm, height: 70 ± 40 nm). The limit was set by inherent protein assemblies (diameter: 124-180 nm) that formed due to lower critical solution temperature behavior of the ELP during molding. The width/height of the ELP ridges depended on the degree of hydration; from complete dehydration to full hydration, ELP ridge width ranged from 79 ± 9% to 150 ± 40% of the mold width. The surface of the ridged ELP featured densely packed protein aggregates that were larger in size than those observed in bulk/flat ELP. Adipose-derived stem cells (ADSCs) oriented along hydrated aligned patterns with periodicities ≥0.60 μm (height ≥170 ± 100 nm), while random orientation was observed for smaller distances/amplitudes, as well as flat and unaligned wavy ELP surfaces. Hence, micro-molding of ELP is a promising approach to create tissue-mimicking, hierarchical architectures composed of tunable micron-sized structures with nano-sized protein aggregates, which opens the way for orthogonal screening of cell responses to topography and cell-adhesion ligands at relevant elastic moduli.

Human lysophosphatidic acid receptor 1 (LPA1 ) is a G-protein coupled receptor that mediates various biological functions such as proliferation, platelet aggregation, smooth muscle contraction, and tumor cell invasion. For dissection of the molecular function of LPA1 , a recombinant LPA1 was overexpressed in Escherichia coli membrane fractions and purified to homogeneity by single affinity chromatography. The purified LPA1 was stabilized with an amphiphilic polymer that was synthesized by the coupling of octylamine, glucosamine, and diethylaminoproylamine at the carboxylic groups of poly-γ-glutamic acid. The complex of purified LPA1 and amphiphilic polymer showed a monodisperse oligomer and specific binding to LPA with apparent Ki values of 30 μM. Compared with the Gs protein, it also showed selective binding to the alpha subunit of the Gi protein. These results indicate that recombinant LPA1 in an amphiphilic polymer complex has an active conformation for interaction with ligands and G-proteins.

Precise prediction of the antigens that bind to major histocompatibility complex (MHC) molecules is one of the most important steps for many immune response-related studies including identification of neoantigen capable of recognizing cancer cells for the implementation of personalized immunotherapy as well as vaccine/therapeutic protein development. To overcome the limitations of the limited prediction performance of the existing models, we developed a new convolutional neural network (CNN)-based epitope prediction model by incorporating new features including protein sequence vectors (Prot2Vec), chemical and structural characteristics of an epitope and MHC molecule. Our new model is optimized to achieve better prediction performance than the conventional methods when validated with a benchmark dataset from the Immune Epitope Database (IEDB). Along with the new prediction model, we also developed a web-based framework, called Kepre, to provide interfaces to our novel CNN-based epitope prediction functionalities. Kepre provides a user-friendly and automated interface for epitope prediction. Upon the researcher's submission of a sequence of interest, Kepre predicts the binding probability between the sequence and each type of the MHC molecules. Kepre runs the prediction analysis on high-throughput computing infrastructure and provides the prediction results in a user-interactable GUI and also in a pdf formatted report file.

This paper provides a novel best in the domain automatic classifier of sleep stages based on wrist photoplethysmography and 3D-accelerometer data obtained from smartwatches. The sleep is classified into rapid-eye-movement (REM), Light, Deep, or Wake stages. State of the art classifiers based on wearable sensors suffer from motion artifacts and apnea events. Proposed novel techniques of artifacts and apnea events elimination result in the high accuracy of sleep stages classification and robustness to apnea events. The model provides the Cohen's Kappa score of 0.65 and accuracy of 0.80 on 254 night-logs of 173 subjects with a broad distribution of apnea-hypopnea index until 90. The approach is applicable to unobtrusive sleep monitoring by wearables.

Indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan catabolising enzyme, is known as a tumour cell survival factor that causes immune escape in several types of cancer. Flavonoids of Sophora flavescens have a variety of biological benefits for humans; however, cancer immunotherapy effect has not been fully investigated. The flavonoids (1–6) isolated from S. flavescens showed IDO1 inhibitory activities (IC50 4.3–31.4 µM). The representative flavonoids (4–6) of S. flavescens were determined to be non-competitive inhibitors of IDO1 by kinetic analyses. Their binding affinity to IDO1 was confirmed using thermal stability and surface plasmon resonance (SPR) assays. The molecular docking analysis and mutagenesis assay revealed the structural details of the interactions between the flavonoids (1–6) and IDO1. These results suggest that the flavonoids (1–6) of S. flavescens, especially kushenol E (6), as IDO1 inhibitors might be useful in the development of immunotherapeutic agents against cancers., Graphical Abstract

This paper reports a scalable approach to achieve spatially selective graphene functionalization using multiscale wrinkles. Graphene wrinkles were formed by relieving the strain in thermoplastic polystyrene substrates conformally coated with fluoropolymer and graphene skin layers. Chemical reactivity of a fluorination process could be tuned by changing the local curvature of the graphene nanostructures. Patterned areas of graphene nanowrinkles and crumples followed by a single-process plasma reaction resulted in substrates with regions having different fluorination levels. Notably, conductivity of the functionalized graphene nanostructures could be locally tuned as a function of feature size without affecting the mechanical properties.