Gate-tunable quantum dot formation between localized-resonant states in a few-layer MoS2.

We demonstrate a gate-tunable quantum dot (QD) located between two potential barriers defined in a few-layer MoS2. Although both local gates used to tune the potential barriers have disorder-induced QDs, we observe diagonal current stripes in current resonant islands formed by the alignment of the Fermi levels of the electrodes and the energy levels of the disorder-induced QDs, as evidence of the gate-tunable QD. We demonstrate that the charging energy of the designed QD can be tuned in the range of 2-6 meV by changing the local-gate voltages in ∼1 V.

Maternal Outcomes and Clinical Characteristics of COVID-19 in Korean Pregnant Women during the Early Period of the Pandemic.

The present study aimed to compare the clinical characteristics and outcomes between pregnant women and non-pregnant women of childbearing age (20-49 years old) diagnosed with coronavirus disease 2019 (COVID-19) during the initial stage of the COVID-19 pandemic in the Republic of Korea. This nationwide observational study included the information of COVID-19 patients collected by the Korea Disease Control and Prevention Agency from January 2020 to April 2021. Among 5,647 COVID-19 patients, 2,444 (43.3%) were women of childbearing age and 19 were pregnant. None of the pregnant women died. However, 4 deaths occurred among non-pregnant women aged 20-49 years. None of the 19 pregnant women with COVID-19 were admitted to the intensive care unit: they were admitted to the general ward, and none of them required supplemental oxygen. In conclusion, none of the pregnant women with COVID-19 experienced severe infection or death, unlike non-pregnant women of childbearing age.

Tunneling Spectroscopy for Electronic Bands in Multi-Walled Carbon Nanotubes with Van Der Waals Gap.

Various intriguing quantum transport measurements for carbon nanotubes (CNTs) based on their unique electronic band structures have been performed adopting a field-effect transistor (FET), where the contact resistance represents the interaction between the one-dimensional and three-dimensional systems. Recently, van der Waals (vdW) gap tunneling spectroscopy for single-walled CNTs with indium-metal contacts was performed adopting an FET device, providing the direct assignment of the subband location in terms of the current-voltage characteristic. Here, we extend the vdW gap tunneling spectroscopy to multi-walled CNTs, which provides transport spectroscopy in a tunneling regime of ~1 eV, directly reflecting the electronic density of states. This new quantum transport regime may allow the development of novel quantum devices by selective electron (or hole) injection to specific subbands.

Gate-voltage-induced reversible electrical phase transitions in Mo0.67W0.33Se2 devices.

Tunable electrical phase transitions based on the structural and quantum-state phase transitions in two-dimensional transition-metal dichalcogenides have attracted attention in both semiconducting electronics and quantum electronics applications. Here, we report gate-voltage-induced reversible electrical phase transitions in Mo0.67W0.33Se2 (MoWSe) field-effect transistors prepared on SiO2/Si substrates. In gate-induced depletion regions of the 2H phase, an electrical current resumes flow at 150 K < T < 200 K with decreasing T irrespective of the layer number (n) for MoWSe when n < 20. The newly appearing electron-doped-type conducting channel again enters the 2H-phase region when the back-gate voltage increases, accompanied by the negative differential transconductance for four-layer and monolayer devices or by a deflection point in the transfer curves for a multilayer device. The thermal activation energies of the new conducting and 2H-phase branches differ by one order of magnitude at the same gate voltage for both the four-layer and monolayer cases, indicating that the electrical band at the Fermi level was modified. The hysteresis measurements for the gate voltage were performed with a five-layer device, which confirms the reversible electrical transition behavior. The possible origins of the nucleated conducting phase in the depletion region of the 2H phase of MoWSe are discussed.

Indium-contacted van der Waals gap tunneling spectroscopy for van der Waals layered materials.

The electrical phase transition in van der Waals (vdW) layered materials such as transition-metal dichalcogenides and Bi2Sr2CaCu2O8+x (Bi-2212) high-temperature superconductor has been explored using various techniques, including scanning tunneling and photoemission spectroscopies, and measurements of electrical resistance as a function of temperature. In this study, we develop one useful method to elucidate the electrical phases in vdW layered materials: indium (In)-contacted vdW tunneling spectroscopy for 1T-TaS2, Bi-2212 and 2H-MoS2. We utilized the vdW gap formed at an In/vdW material interface as a tunnel barrier for tunneling spectroscopy. For strongly correlated electron systems such as 1T-TaS2 and Bi-2212, pronounced gap features corresponding to the Mott and superconducting gaps were respectively observed at T = 4 K. We observed a gate dependence of the amplitude of the superconducting gap, which has potential applications in a gate-tunable superconducting device with a SiO2/Si substrate. For In/10 nm-thick 2H-MoS2 devices, differential conductance shoulders at bias voltages of approximately ± 0.45 V were observed, which were attributed to the semiconducting gap. These results show that In-contacted vdW gap tunneling spectroscopy in a fashion of field-effect transistor provides feasible and reliable ways to investigate electronic structures of vdW materials.

Evaluation of a lateral flow assay-based IFN-γ release assay as a point-of-care test for the diagnosis of latent tuberculosis infection.

INTRODUCTION: We compared the performance of a fluorescence lateral flow assay (ichroma™ IGRA-TB) with the QuantiFERON-TB Gold PLUS (QFT-PLUS) for the diagnosis of latent tuberculosis infection (LTBI) in patients with immune-mediated inflammatory diseases (IMID) prior to receiving biologics therapy. METHOD: The comparability of the ichroma™ IGRA-TB assay with the QFT-PLUS assay for the diagnosis of LTBI was determined in prospectively enrolled patients with IMID prior to receiving biologics between August 2018 and October 2019. To determine the best cut-off value of the ichroma™ IGRA-TB, an ROC curve analysis was performed. RESULTS: Patients with IMID (n = 145) had inflammatory bowel disease (n = 83; 57.2%), rheumatoid arthritis (n = 44; 30.3%), or spondyloarthropathy (n = 18; 12.4%). The median age was 40.5 (interquartile range: 27.0-56.0), 72 (49.7%) were men, and 140 (96.6%) received BCG vaccination. With the manufacturer-recommended cut-off values, 11 (7.6%) and 20 (13.8%) patients showed positive results with the ichroma™ IGRA-TB and QFT-PLUS tests, respectively. The overall agreement between the two tests was 91.0% with a Cohen's kappa value of 0.535 (95% confidence interval: 0.317-0.754). ROC curve analysis of the QFT-PLUS results showed that a cut-off value of > 0.21 IU/mL would improve the performance of the ichroma™ IGRA-TB. Using the new cut-off value, the concordance rate was improved to 93.1% with a Cohen's kappa value of 0.668 (95% confidence interval: 0.478-0.858). CONCLUSIONS: The ichroma™ IGRA-TB could be used as a point-of-care test for LTBI screening in IMID patients before starting biologics, especially in resource-limited settings. Key Points • The ichroma™ IGRA-TB is an automated fluorescence lateral flow assay-based IGRA. • The test has advantages like short turn-around time, low-cost, and ease of use. • The ichroma™ IGRA-TB showed high agreement with the QuantiFERON-TB Gold In-Tube in patients with chronic immune-mediated inflammatory diseases before starting biologics.

Fermentation of Chestnut (Catanea crenata Sieb) Inner Shell Enhances Anti-Obesity Effects in 3T3-L1 and C3H10T1/2 Adipocytes.

Chestnut inner shell (CIS) is rich in phenols and flavonoids such as gallic acid and ellagic acid, which are known to exhibit effective antioxidant and anti-obesity properties. Fermentation using lactic acid bacteria can enhance the physiological activity by increasing the contents of such functional ingredients. In this study, we evaluated the anti-obesity effects of a CIS extract subjected to a fermentation process (fermented CIS [FCIS]). Treatment with CIS and FCIS extracts (125, 250, and 500 µg/mL) increased cell viability and did not induce apoptosis, indicating no toxicity. The extract suppressed the gene expression of adipogenic factors, peroxisome proliferation-activated receptor gamma, CCAAT/enhancer binding protein (C/EBP) alpha, and C/EBP beta (by 7.75% and 67.59%, 21.41% and 66.27% in 500 µg/mL, respectively), and consequently suppressed the expression of downstream lipogenic factors such as fatty acid synthase, stearoyl CoA desaturase-1, citrate synthase, and ATP citrate lyase. The expression of factors involved in fat catabolism and ß-oxidation increased in a dose-dependent manner, thereby preventing fat accumulation. This observation was consistent with the significant decrease in the staining intensity for lipid droplets, which indicated that lipid accumulation was decreased by 15.46% and 29.44% in 3T3L-1 and 27.01% and 46.68% in C3H10T1/2. Together, these results demonstrate the higher anti-obesity effects of FCIS extract than that of CIS extract, indicating the potential applicability of FCIS as an effective natural raw material to curb obesity.

Direct immobilization of functional single-chain variable fragment antibodies (scFvs) onto a polystyrene plate by genetic fusion of a polystyrene-binding peptide (PS-tag).

Single-chain Fv antibodies (scFv) genetically fused with polystyrene-binding peptides (PS-tags, (PS19-1; RAFIASRRIRRP, PS19-6; RIIIRRIRR)) were generated by recombinant Escherichia coli for direct and site-specific immobilization of scFv on polystyrene supports with high antigen-binding activity. PS-tag-fused scFvs (scFv-PS-tags) specific for human C-reactive protein (CRP) were successfully over-expressed as an inclusion body and were refolded using the batch-dilution method. When scFv-PS-tags were immobilized on a hydrophilic PS (phi-PS) plate in the presence of Tween 20, they showed high antigen-binding activity comparable to, or greater than, that of a whole monoclonal antibody (mAb) on a hydrophobic PS (pho-PS) plate, which has been the exclusive method for enzyme-linked immunosorbent assay (ELISA). Furthermore, when a scFv-PS-tag was used as a ligand antibody in one- and two-step ELISA, the assay time was reduced without loss of sensitivity. These results indicate that strong and specific attachment of PS-tags onto the phi-PS surface prevented scFv conformational changes and consequently, the high antigen-binding activities of scFvs were preserved. Nearly identical results were obtained by use of PS-tag-fused scFvs with different VH/VL pairs. Therefore, a variety of scFvs could be functionalized onto phi-PS plates by genetic fusion of PS-tags. ScFv-PS-tags, which possess high antigen-binding activity on the phi-PS plate, are more useful ligand antibodies than whole mAbs. Thus, scFv-PS-tags are applicable in both clinical diagnosis and proteomic research.

A Feasibility Study for Diagnosis of Latent Tuberculosis Infection Using an IGRA Point-of-Care Platform in South Korea.

PURPOSE: This study aimed to evaluate ichroma™ IGRA-TB, a novel point-of-care platform for assaying IFN-γ release, and to compare it with QuantiFERON-TB Gold In-Tube (QFT-GIT) for identifying Mycobacterium tuberculosis (M. tb) infection. MATERIALS AND METHODS: We recruited 60 healthy subjects, and blood samples were obtained in QFT-GIT blood collection tubes. The blood collection tubes were incubated at 37°C, and culture supernatant was harvested after 18-24 hours. IFN-γ responses were assessed by the ichroma™ IGRA-TB cartridge and the QFT-GIT IFN-γ enzyme-linked immunosorbent assay. Three active TB patients were recruited as a positive control for M. tb infection. RESULTS: The area under the receiver operating characteristic curve of the ichroma™ IGRA-TB test for differentiating between infected and non-infected individuals was 0.9706 (p<0.001). Inconsistent positivity between the two tests was found in three participants who showed weak positive IFN-γ responses (<1.0 IU/mL) with QFT-GIT. However, the two tests had excellent agreement (95.2%, κ=0.91, p<0.001), and a very strong positive correlation was observed between the IFN-γ values of both tests (r=0.91, p<0.001). CONCLUSION: The diagnostic accuracy demonstrated in this study indicates that the ichroma™ IGRA-TB test could be used as a rapid diagnostic method for detecting latent TB infection. It may be particularly beneficial in resource-limited places that require cost-effective laboratory diagnostics.

Rational screening of antibodies and design of sandwich enzyme linked immunosorbant assay on the basis of a kinetic model.

A rational strategy for the rapid establishment of a sensitive sandwich enzyme linked immunosorbant assay was developed. The kinetic properties required for the solid-phase and enzyme-conjugated antibodies of sandwich ELISA were determined rationally on the basis of a kinetic model describing antibody-antigen interaction. Some antibodies possessing the required kinetic properties against a model antigen, C-reactive protein (CRP), were successfully isolated from a phage antibody library under the screening conditions that were designed on the basis of simulation results. The best combination of solid-phase and enzyme-conjugated antibodies that gives the most sensitive sandwich ELISA was determined by simulation on the basis of the apparent association and dissociation rate constants of the isolated antibodies. It was confirmed by experiment that the sandwich ELISA using the best combination of antibodies was actually the most sensitive one. Our strategy would be useful for the rapid establishment of sensitive sandwich ELISAs compared with the traditional hybridoma method in which the best condition is determined by trial and error.

Simulation model for predicting limit of detection and range of quantitation of competitive enzyme-linked immunosorbent assay.

The limit of detection (LOD) and range of quantitation (ROQ) of competitive enzyme-linked immunosorbent assay (ELISA) were determined from a model describing the calibration curve and precision profile of the assay. The calibration curve is given by solving the differential equations describing the change in the concentrations of an antigen-antibody complex and an enzyme-conjugated antigen-antibody complex by a Runge-Kutta method. The precision profile is described in terms of possible error sources such as the pipetting volumes of the analyte, enzyme-conjugated antigen, antibody and substrate solutions, calibration curve and inherent absorbances between the wells in an ELISA plate. An appropriate concentration of the enzyme-conjugated antigen that balances a low detection limit and sufficient color development was found to be in a narrow range, which is consistent with the empirical rule. The optimum conditions for competitive ELISA using an antibody with a kinetic property can be designed from our model.

Validation of a method for predicting the precision, limit of detection and range of quantitation in competitive ELISA.

The mathematical model for predicting the precision, limit of detection (LOD) and range of quantitation (ROQ) in a competitive enzyme-linked immunosorbent assay (ELISA) proposed by Hayashi et al. (Anal. Chem., 2004, 76, 1295) was validated. The model describes the relative standard deviation (RSD) of concentration estimates by the RSDs of pipetting volumes of analyte, enzyme-conjugated antigen, antibody and substrate solutions, and the standard deviation (SD) of inherent absorbances between the wells in an ELISA plate. For 6 kinds of direct competitive ELISA kits, the LOD and ROQ predicted by the model agreed well with those obtained by experiments with real samples. It was also confirmed that the model is applicable to the prediction of uncertainty that depends on the pipetting error of the viscous antiserum solution. The model was demonstrated to be useful for estimating the LOD and ROQ of competitive ELISA.

The use of an engineered single chain variable fragment in a localized surface plasmon resonance method for analysis of the C-reactive protein.

A gold nanorod (GNR) based LSPR sensor has been developed for label-free detection of C-reactive protein (CRP). The sensor utilizes a single chain variable fragment (scFv) as a receptor to bind CRP. The results of this effort show that CRP in human serum can be quantitatively detected at lower than 1 ng mL(-1).

A dual gold nanoparticle conjugate-based lateral flow assay (LFA) method for the analysis of troponin I.

For signal amplification without an additional operation step in a gold nanoparticle (AuNP)-based lateral flow assay (LFA), a new and simple method utilizing two AuNP-antibody conjugates was developed. The 1st conjugate was the AuNP immobilized with an anti-troponin I antibody and blocked with bovine serum albumin (BSA), and the 2nd conjugate was the AuNP immobilized with an anti-BSA antibody and blocked with human serum albumin. The two conjugates were encapsulated in different pads, respectively. A scheme of the LFA system is described in the part A of first figure. The size of the two conjugates was very critical in the detection sensitivity of troponin I. When 10nm for the 1st and 40 nm for the 2nd were used, the detection sensitivity increased about a 100-fold compared to the conventional LFA. We could detect as low as 0.01 ng/mL troponin I in 10 min using the dual AuNP conjugate-based LFA, which was successfully applied in the analysis of serum samples of patients with myocardial infarction.