Nanowatt-Level Photoactivated Gas Sensor Based on Fully-Integrated Visible MicroLED and Plasmonic Nanomaterials.

Photoactivated gas sensors that are fully integrated with micro light-emitting diodes (µLED) have shown great potential to substitute conventional micro/nano-electromechanical (M/NEMS) gas sensors owing to their low power consumption, high mechanical stability, and mass-producibility. Previous photoactivated gas sensors mostly have utilized ultra-violet (UV) light (250-400 nm) for activating high-bandgap metal oxides, although energy conversion efficiencies of gallium nitride (GaN) LEDs are maximized in the blue range (430-470 nm). This study presents a more advanced monolithic photoactivated gas sensor based on a nanowatt-level, ultra-low-power blue (λpeak  = 435 nm) µLED platform (µLP). To promote the blue light absorbance of the sensing material, plasmonic silver (Ag) nanoparticles (NPs) are uniformly coated on porous indium oxide (In2 O3 ) thin films. By the plasmonic effect, Ag NPs absorb the blue light and spontaneously transfer excited hot electrons to the surface of In2 O3 . Consequently, high external quantum efficiency (EQE, ≈17.3%) and sensor response (ΔR/R0 (%) = 1319%) to 1 ppm NO2 gas can be achieved with a small power consumption of 63 nW. Therefore, it is highly expected to realize various practical applications of mobile gas sensors such as personal environmental monitoring devices, smart factories, farms, and home appliances.

Nanogap Formation Using a Chromium Oxide Film and Its Application as a Palladium Hydrogen Switch.

Developing high response hydrogen sensors manufacturable in a large scale is desirable in hydrogen industry. In this study, a chromium oxidation-based nanogap formation process was developed to fabricate a hydrogen switch with suspended palladium and gold films having a tens of nanometer-sized gap. The nanogap was formed by using oxidized chromium as a self-alignment shadow mask. The hydrogen switch operates by the principle of volume expansion of palladium upon exposure to the hydrogen gas and the current reading by closing of a nanogap formed between suspended palladium and gold films. Further improvement of the sensor performance was achieved by optimizing the design parameters such as suspended film lengths and thicknesses. The fabricated palladium nanogap hydrogen sensor showed an ultrahigh sensitivity of ΔI/I0 > 108 with a fast response time (22 s) to 4% hydrogen. The complementary metal-oxide-semiconductor-compatible fabrication of the hydrogen switch is easily scalable with low manufacturing cost.

Two Distinct Mechanisms of Inhibition of LpxA Acyltransferase Essential for Lipopolysaccharide Biosynthesis.

The lipopolysaccharide biosynthesis pathway is considered an attractive drug target against the rising threat of multi-drug-resistant Gram-negative bacteria. Here, we report two novel small-molecule inhibitors (compounds 1 and 2) of the acyltransferase LpxA, the first enzyme in the lipopolysaccharide biosynthesis pathway. We show genetically that the antibacterial activities of the compounds against efflux-deficient Escherichia coli are mediated by LpxA inhibition. Consistently, the compounds inhibited the LpxA enzymatic reaction in vitro. Intriguingly, using biochemical, biophysical, and structural characterization, we reveal two distinct mechanisms of LpxA inhibition; compound 1 is a substrate-competitive inhibitor targeting apo LpxA, and compound 2 is an uncompetitive inhibitor targeting the LpxA/product complex. Compound 2 exhibited more favorable biological and physicochemical properties than compound 1 and was optimized using structural information to achieve improved antibacterial activity against wild-type E. coli. These results show that LpxA is a promising antibacterial target and imply the advantages of targeting enzyme/product complexes in drug discovery.

Adsorption properties of advanced functional materials against gaseous formaldehyde.

Intense efforts have been made to eliminate toxic volatile organic compounds (VOCs) in indoor environments, especially formaldehyde (FA). In this study, the removal performances of gaseous FA using two metal-organic frameworks, MOF-5 and UiO-66-NH2, and two covalent-organic polymers, CBAP-1 (EDA) and CBAP-1 (DETA), along with activated carbon as a conventional reference material, were evaluated. To assess the removal capacity of FA under near-ambient conditions, a series of adsorption experiments were conducted at its concentrations/partial pressures of both low (0.1-0.5 ppm/0.01-0.05 Pa) and high ranges (5-25 ppm/0.5-2.5 Pa). Among all tested materials at the high-pressure region ㅐ (e.g., at 2.5 ppm FA), a maximum adsorption capacity of 69.7 mg g-1 was recorded by UiO-66-NH2. Moreover, UiO-66-NH2 also displayed the best 10% breakthrough volume (BTV10) of 534 L g-1 (0.5 ppm FA) to 2963 L g-1 (0.1 ppm FA). In contrast, at the high concentration test (at 5, 10, and 25 ppm FA), the maximum BTV10 values were observed as: 137 (UiO-66-NH2), 144 (CBAP-1 (DETA)), and 36.8 L g-1 (CBAP-1 (EDA)), respectively. The Langmuir isotherm model was observed to be a better fit of the adsorption data than the Freundlich model under most of the tested conditions. The superiority of UiO-66-NH2 was attributed to the van der Waals interactions between the linkers (framework) and the hydrocarbon "tail" (FA) coupled with interactions between its open metal sites and the FA carbonyl groups. This study demonstrated the good potential of these advanced functional materials toward the practical removal of gaseous FA in indoor environments.

Palladium-Decorated Silicon Nanomesh Fabricated by Nanosphere Lithography for High Performance, Room Temperature Hydrogen Sensing.

A hydrogen (H2 ) gas sensor based on a silicon (Si) nanomesh structure decorated with palladium (Pd) nanoparticles is fabricated via polystyrene nanosphere lithography and top-down fabrication processes. The gas sensor shows dramatically improved H2 gas sensitivity compared with an Si thin film sensor without nanopatterns. Furthermore, a buffered oxide etchant treatment of the Si nanomesh structure results in an additional performance improvement. The final sensor device shows fast H2 response and high selectivity to H2 gas among other gases. The sensing performance is stable and shows repeatable responses in both dry and high humidity ambient environments. The sensor also shows high stability without noticeable performance degradation after one month. This approach allows the facile fabrication of high performance H2 sensors via a cost-effective, complementary metal-oxide-semiconductor (CMOS) compatible, and scalable nanopatterning method.

A structured loop modulates coupling between the substrate-binding and dimerization domains in the multidrug resistance transporter EmrE.

Secondary active transporters undergo large conformational changes to facilitate the efflux of substrates across the lipid bilayer. Among the smallest known transport proteins are members of the small multidrug resistance (SMR) family that are composed of four transmembrane (TM) domains and assemble into dimers. An unanswered question in the SMR field is how the dimerization domain (TM4) is coupled with the substrate-binding chamber (TM1-3). To provide insight for this essential aspect of ion-coupled transport, we carried out a structure-function study on the SMR protein EmrE using solid-state NMR spectroscopy in lipid bilayers and resistance assays in Escherichia coli. The chemical shifts for EmrE were consistent with ß-strand secondary structure for the loop connecting TM3 and TM4. Based on these structural results, EmrE mutants were created to ascertain whether a specific loop length and composition were necessary for function. A linker encompassing six extra Gly residues relative to wild-type EmrE failed to give resistance; however, the number of residues in the loop was not the only criterion for a functional efflux pump. Replacement of the central hydrophobic residue with Gly (L83G) also conferred no ethidium resistance phenotype, which supported the conclusion that the structure and length of the loop were both essential for ion-coupled transport. Taken together with a bioinformatics analysis, a structured linker is likely conserved across the SMR family to play an active role in mediating the conformational switch between inward-open and outward-open states necessary for drug efflux. These findings underscore the important role loops can play in mediating efflux.

A Miniature Protein Stabilized by a Cation-π Interaction Network.

The design of folded miniature proteins is predicated on establishing noncovalent interactions that direct the self-assembly of discrete thermostable tertiary structures. In this work, we describe how a network of cation-π interactions present in proteins containing "WSXWS motifs" can be emulated to stabilize the core of a miniature protein. This 19-residue protein sequence recapitulates a set of interdigitated arginine and tryptophan residues that stabilize a distinctive ß-strand:loop:PPII-helix topology. Validation of the compact fold determined by NMR was carried out by mutagenesis of the cation-π network and by comparison to the corresponding disulfide-bridged structure. These results support the involvement of a coordinated set of cation-π interactions that stabilize the tertiary structure.

Involvement of distinct arrestin-1 elements in binding to different functional forms of rhodopsin.

Solution NMR spectroscopy of labeled arrestin-1 was used to explore its interactions with dark-state phosphorylated rhodopsin (P-Rh), phosphorylated opsin (P-opsin), unphosphorylated light-activated rhodopsin (Rh*), and phosphorylated light-activated rhodopsin (P-Rh*). Distinct sets of arrestin-1 elements were seen to be engaged by Rh* and inactive P-Rh, which induced conformational changes that differed from those triggered by binding of P-Rh*. Although arrestin-1 affinity for Rh* was seen to be low (K(D) > 150 µM), its affinity for P-Rh (K(D) ~80 µM) was comparable to the concentration of active monomeric arrestin-1 in the outer segment, suggesting that P-Rh generated by high-gain phosphorylation is occupied by arrestin-1 under physiological conditions and will not signal upon photo-activation. Arrestin-1 was seen to bind P-Rh* and P-opsin with fairly high affinity (K(D) of~50 and 800 nM, respectively), implying that arrestin-1 dissociation is triggered only upon P-opsin regeneration with 11-cis-retinal, precluding noise generated by opsin activity. Based on their observed affinity for arrestin-1, P-opsin and inactive P-Rh very likely affect the physiological monomer-dimer-tetramer equilibrium of arrestin-1, and should therefore be taken into account when modeling photoreceptor function. The data also suggested that complex formation with either P-Rh* or P-opsin results in a global transition in the conformation of arrestin-1, possibly to a dynamic molten globule-like structure. We hypothesize that this transition contributes to the mechanism that triggers preferential interactions of several signaling proteins with receptor-activated arrestins.

Cold denaturation of a protein dimer monitored at atomic resolution.

Protein folding and unfolding are crucial for a range of biological phenomena and human diseases. Defining the structural properties of the involved transient species is therefore of prime interest. Using a combination of cold denaturation with NMR spectroscopy, we reveal detailed insight into the unfolding of the homodimeric repressor protein CylR2. Seven three-dimensional structures of CylR2 at temperatures from 25 °C to -16 °C reveal a progressive dissociation of the dimeric protein into a native-like monomeric intermediate followed by transition into a highly dynamic, partially folded state. The core of the partially folded state seems critical for biological function and misfolding.

Intrinsic conformational plasticity of native EmrE provides a pathway for multidrug resistance.

EmrE is a multidrug resistance efflux pump with specificity to a wide range of antibiotics and antiseptics. To obtain atomic-scale insight into the attributes of the native state that encodes the broad specificity, we used a hybrid of solution and solid-state NMR methods in lipid bilayers and bicelles. Our results indicate that the native EmrE dimer oscillates between inward and outward facing structural conformations at an exchange rate (k(ex)) of ~300 s(-1) at 37 °C (millisecond motions), which is ~50-fold faster relative to the tetraphenylphosphonium (TPP(+)) substrate-bound form of the protein. These observables provide quantitative evidence that the rate-limiting step in the TPP(+) transport cycle is not the outward-inward conformational change in the absence of drug. In addition, using differential scanning calorimetry, we found that the width of the gel-to-liquid crystalline phase transition was 2 °C broader in the absence of the TPP(+) substrate versus its presence, which suggested that changes in transporter dynamics can impact the phase properties of the membrane. Interestingly, experiments with cross-linked EmrE showed that the millisecond inward-open to outward-open dynamics was not the culprit of the broadening. Instead, the calorimetry and NMR data supported the conclusion that faster time scale structural dynamics (nanosecond-microsecond) were the source and therefore impart the conformationally plastic character of native EmrE capable of binding structurally diverse substrates. These findings provide a clear example how differences in membrane protein transporter structural dynamics between drug-free and bound states can have a direct impact on the physical properties of the lipid bilayer in an allosteric fashion.

The quiet renaissance of protein nuclear magnetic resonance.

From roughly 1985 through the start of the new millennium, the cutting edge of solution protein nuclear magnetic resonance (NMR) spectroscopy was to a significant extent driven by the aspiration to determine structures. Here we survey recent advances in protein NMR that herald a renaissance in which a number of its most important applications reflect the broad problem-solving capability displayed by this method during its classical era during the 1970s and early 1980s.

Full genomic analysis of a human rotavirus G1P[8] strain isolated in South Korea.

A rotavirus G1P[8] strain C1-81 was isolated from a 5-month-old female infant admitted to hospital with fever and severe diarrhea in Incheon, South Korea. To investigate its full genomic relatedness and its group, the full genome of strain C1-81 was determined. Based on a full genome classification system, C1-81 was shown to possess the typical Wa-like genotype constellation: G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. On the basis of sequence similarities, the strain was shown to be the closest related strain to contemporary human rotavirus strains with recent strains isolated in Asia. This C1-81 strain showed the highest degree of nucleic acid similarity (98.8% and 97%) to G1 B4633-03 and P[8] (Thai-1604 and Dhaka8-02), respectively. This is the first report that group A rotavirus was analyzed with G1P[8] in South Korea. The study of the complete genome of the virus will help understanding of the evolution of rotavirus.

Deep-learning-based gas identification by time-variant illumination of a single micro-LED-embedded gas sensor.

Electronic nose (e-nose) technology for selectively identifying a target gas through chemoresistive sensors has gained much attention for various applications, such as smart factory and personal health monitoring. To overcome the cross-reactivity problem of chemoresistive sensors to various gas species, herein, we propose a novel sensing strategy based on a single micro-LED (µLED)-embedded photoactivated (µLP) gas sensor, utilizing the time-variant illumination for identifying the species and concentrations of various target gases. A fast-changing pseudorandom voltage input is applied to the µLED to generate forced transient sensor responses. A deep neural network is employed to analyze the obtained complex transient signals for gas detection and concentration estimation. The proposed sensor system achieves high classification (~96.99%) and quantification (mean absolute percentage error ~ 31.99%) accuracies for various toxic gases (methanol, ethanol, acetone, and nitrogen dioxide) with a single gas sensor consuming 0.53 mW. The proposed method may significantly improve the efficiency of e-nose technology in terms of cost, space, and power consumption.

New insights into surface behavior of dimethylated arsenicals on montmorillonite using X-ray absorption spectroscopy.

Although recent studies have revealed the occurrence of dimethylated arsenicals, little is known about their behavior in environment. This study investigates the adsorption behavior of dimethylarsinic acid (DMAV), dimethyldithioarsinic acid (DMDTAV), and dimethylmonothioarsinic acid (DMMTAV) on montmorillonite. Complicated transformations among arsenicals under normal environmental conditions were also considered. Our results clearly demonstrate that DMDTAV was oxidized to DMMTAV, which was relatively stable but partially transformed to DMAV when exposed to air during adsorption. The transformed DMAV exhibited high adsorption affinities for montmorillonite, while DMMTAV and DMDTAV were not appreciably retained by montmorillonite for 48 h. This is the first study to provide insights into DMDTAV oxidation under environmental conditions. X-ray absorption near edge structure and extended X-ray absorption fine structure studies confirmed that most of the adsorbed arsenicals on montmorillonite were DMAV. The significantly different bonding characteristics of each adsorbed DMAV provide direct evidence for the transformation of DMAV from DMDTAV and DMMTAV. Our study suggests the importance of incorporating the DMMTAV in the realistic risk management for soil environments because it is highly toxic, easily transformed from DMDTAV, and stable in the environment.

Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action.

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is considered an attractive therapeutic target in multiple inflammatory and autoimmune disorders. In addition to its known biologic activities, MIF can also function as a tautomerase. Several small molecules have been reported to be effective inhibitors of MIF tautomerase activity in vitro. Herein we employed a robust activity-based assay to identify different classes of novel inhibitors of the catalytic and biological activities of MIF. Several novel chemical classes of inhibitors of the catalytic activity of MIF with IC(50) values in the range of 0.2-15.5 microm were identified and validated. The interaction site and mechanism of action of these inhibitors were defined using structure-activity studies and a battery of biochemical and biophysical methods. MIF inhibitors emerging from these studies could be divided into three categories based on their mechanism of action: 1) molecules that covalently modify the catalytic site at the N-terminal proline residue, Pro(1); 2) a novel class of catalytic site inhibitors; and finally 3) molecules that disrupt the trimeric structure of MIF. Importantly, all inhibitors demonstrated total inhibition of MIF-mediated glucocorticoid overriding and AKT phosphorylation, whereas ebselen, a trimer-disrupting inhibitor, additionally acted as a potent hyperagonist in MIF-mediated chemotactic migration. The identification of biologically active compounds with known toxicity, pharmacokinetic properties, and biological activities in vivo should accelerate the development of clinically relevant MIF inhibitors. Furthermore, the diversity of chemical structures and mechanisms of action of our inhibitors makes them ideal mechanistic probes for elucidating the structure-function relationships of MIF and to further determine the role of the oligomerization state and catalytic activity of MIF in regulating the function(s) of MIF in health and disease.

Integrated analysis of the conformation of a protein-linked spin label by crystallography, EPR and NMR spectroscopy.

Long-range structural information derived from paramagnetic relaxation enhancement observed in the presence of a paramagnetic nitroxide radical is highly useful for structural characterization of globular, modular and intrinsically disordered proteins, as well as protein-protein and protein-DNA complexes. Here we characterized the conformation of a spin-label attached to the homodimeric protein CylR2 using a combination of X-ray crystallography, electron paramagnetic resonance (EPR) and NMR spectroscopy. Close agreement was found between the conformation of the spin label observed in the crystal structure with interspin distances measured by EPR and signal broadening in NMR spectra, suggesting that the conformation seen in the crystal structure is also preferred in solution. In contrast, conformations of the spin label observed in crystal structures of T4 lysozyme are not in agreement with the paramagnetic relaxation enhancement observed for spin-labeled CylR2 in solution. Our data demonstrate that accurate positioning of the paramagnetic center is essential for high-resolution structure determination.

Monolithic Micro Light-Emitting Diode/Metal Oxide Nanowire Gas Sensor with Microwatt-Level Power Consumption.

High-performance, monolithic photoactivated gas sensors based on the integration of gas-sensitive semiconductor metal oxide nanowires on micro light-emitting diodes (µLEDs) are introduced. The µLEDs showed improved irradiance and energy conversion efficiency (i.e., external quantum efficiency, EQE), as the size of LEDs was reduced from 200 × 200 µm2 (irradiance of 46.5 W/cm2 and EQE of 4%) to 30 × 30 µm2 (irradiance of 822.4 W/cm2 and EQE of 9%). Gas-sensitive zinc oxide (ZnO) nanowires were directly synthesized on top of the µLED through a hydrothermal reaction. The direct contact between the sensing component and µLED sensor platform leads to high light coupling efficiency, minimizing power consumption of the sensor. Furthermore, the sensing performance (i.e., sensitivity) at optimal operating power was improved as the LED size was reduced. The smallest fabricated gas sensor (active area = 30 × 30 µm2) showed excellent NO2 sensitivity (ΔR/R0 = 605% to 1 ppm NO2) at the optimal operating power (∼184 µW). In addition, the sensor showed a low limit of detection (∼14.9 ppb) and robustness to high humidity conditions, which demonstrate its potential for practical applications in mobile internet of things (IoT) devices.

Nanoporous Silicon Thin Film-Based Hydrogen Sensor Using Metal-Assisted Chemical Etching with Annealed Palladium Nanoparticles.

This article reports a nanoporous silicon (Si) thin-film-based high-performance and low-power hydrogen (H2) sensor fabricated by metal-assisted chemical etching (MaCE). The nanoporous Si thin film treated with Pd-based MaCE showed improvement over a flat Si thin film sensor in H2 response (ΔI/I0 = 4.36% → 12.4% for 0.1% H2). Furthermore, it was verified that the combination of thermal annealing of Pd and subsequent MaCE on the Si thin film synergistically enhances the H2 sensitivity of the sensor by 65 times as compared to the flat Si thin film sensor (ΔI/I0 = 4.36% → 285% for 0.1% H2). This sensor also showed a very low operating power of 1.62 µW. After the thermal treatment, densely packed Pd nanoparticles agglomerate due to dewetting, which results in a higher surface-to-volume ratio by well-defined etched holes, leading to an increase in sensor response.

Structural properties of pore-forming oligomers of alpha-synuclein.

Soluble oligomers are potent toxins in many neurodegenerative diseases, but little is known about the structure of soluble oligomers and their structure-toxicity relationship. Here we prepared on-pathway oligomers of the 140-residue protein alpha-synuclein, a key player in Parkinson's disease, at concentrations an order of magnitude higher than previously possible. The oligomers form ion channels with well-defined conductance states in a variety of membranes, and their beta-structure differs from that of amyloid fibrils of alpha-synuclein.