Room-temperature ammonia gas sensing via Au nanoparticle-decorated TiO2 nanosheets.

A high-performance gas sensor operating at room temperature is always favourable since it simplifies the device fabrication and lowers the operating power by eliminating a heater. Herein, we fabricated the ammonia (NH3) gas sensor by using Au nanoparticle-decorated TiO2 nanosheets, which were synthesized via two distinct processes: (1) preparation of monolayer TiO2 nanosheets through flux growth and a subsequent chemical exfoliation and (2) decoration of Au nanoparticles on the TiO2 nanosheets via hydrothermal method. Based on the morphological, compositional, crystallographic, and surface characteristics of this low-dimensional nano-heterostructured material, its temperature- and concentration-dependent NH3 gas-sensing properties were investigated. A high response of ~ 2.8 was obtained at room temperature under 20 ppm NH3 gas concentration by decorating Au nanoparticles onto the surface of TiO2 nanosheets, which generated oxygen defects and induced spillover effect as well.

Acceleration of NO2 gas sensitivity in two-dimensional SnSe2 by Br doping.

The authors report a Br doping effect on the NO2 gas sensing properties of a two-dimensional (2D) SnSe2 semiconductor. Single crystalline 2D SnSe2 samples with different Br contents are grown by a simple melt-solidification method. By analyzing the structural, vibrational as well as electrical properties, it can be confirmed that the Br impurity substitutes on the Se-site in SnSe2 serving as an efficient electron donor. When we measure the change of resistance under a 20 ppm NO2 gas flow condition at room temperature, both responsivity and response time are drastically improved by Br doping from 1.02% and 23 s to 3.38% and 15 s, respectively. From these results, it can be concluded that Br doping plays a key role for encouraging the charge transfer efficiency from the SnSe2 surface to the NO2 molecule by elaborating Fermi level in 2D SnSe2.

Experimental study of superheating of tin powders.

An unstable energy-unbalanced state such as superheating or supercooling is often unexpectedly observed because a factor of energy depends not only on the temperature but is a product of temperature (T) and entropy (S). Thus, at the same temperature, if the entropy is different, the total energy of the system can be different. In such cases, the temperature-change-rate cannot match the entropy-change-rate, which results in a hysteresis curve for the temperature/entropy relationship. Due to the difference between the temperature- and entropy-change-rates, properties of a material, such as the boiling and freezing points, can be extended from point to area. This study confirmed that depending on the heating rate, tin powders exhibit different melting points. Given the contemporary reinterpretation of many energy-non-equilibrium phenomena that have only been discussed on the basis of temperature, this study is expected to contribute to the actual expansion of scientific/engineering applications.

Interface treatment using amorphous-carbon and its applications.

Breakthrough process technologies have been introduced that can increase the chemical sensitivity of an interface at which reactions occur without significantly altering the physico-chemical properties of the material. Such an interfacial treatment method is based on amorphous-carbon as a base so that fluids can be deposited, and the desired thickness and quality of the deposition can be ensured irrespective of the interface state of the material. In addition, side effects such as diffusion and decreasing strength at the interface can be avoided. This is simpler than existing vacuum-based deposition technology and it has an unmatched industrial advantage in terms of economics, speed, accuracy, reliability, accessibility, and convenience. In particular, this amorphous-carbon interface treatment technology has been demonstrated to improve gas-sensing characteristics of NO2 at room temperature.

Synthesis of Au/SnO2 nanostructures allowing process variable control.

Theoretical advances in science are inherently time-consuming to realise in engineering, since their practical application is hindered by the inability to follow the theoretical essence. Herein, we propose a new method to freely control the time, cost, and process variables in the fabrication of a hybrid featuring Au nanoparticles on a pre-formed SnO2 nanostructure. The above advantages, which were divided into six categories, are proven to be superior to those achieved elsewhere, and the obtained results are found to be applicable to the synthesis and functionalisation of other nanostructures. Furthermore, the reduction of the time-gap between science and engineering is expected to promote the practical applications of numerous scientific theories.

Severe Fever with Thrombocytopenia Syndrome Virus Infection or Mixed Infection with Scrub Typhus in South Korea in 2000-2003.

Severe fever with thrombocytopenia syndrome is a tick-borne viral disease, with a high mortality rate that was first reported in China in 2009. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, a bacterium transmitted to humans through chigger mite bites. Severe fever with thrombocytopenia syndrome and scrub typhus are endemic to South Korea. To investigate evidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection or mixed infection with scrub typhus in South Korea, we examined 2,329 sera samples collected from patients presenting from November 1, 2000, to November 1, 2003, for the diagnosis of rickettisal diseases at Seoul National University, Seoul, South Korea. We found retrospective evidence of SFTSV infection or mixed infection with scrub typhus in South Korea in 2000-2003. Severe fever with thrombocytopenia syndrome virus infections in South Korea occurred before previously reported cases and were more concurrent with those in China. It is important to consider SFTSV infection in patients with scrub typhus.

Fast Semiconductor-Metal Bidirectional Transition by Flame Chemical Vapor Deposition.

A simple yet powerful flame chemical vapor deposition technique is proposed that allows free control of the surface morphology, microstructure, and composition of existing materials with regard to various functionalities within a short process time (in seconds) at room temperature and atmospheric pressure as per the requirement. Since the heat energy is directly transferred to the material surface, the redox periodically converges to the energy dynamic equilibrium depending on the energy injection time; therefore, bidirectional transition between the semiconductor/metal is optionally available. To demonstrate this, a variety of Sn-based particles were created on preformed SnO2 nanowires, and this has been interpreted as a new mechanism for the response and response times of gas-sensing, which are representative indicators of the most surface-sensitive applications and show one-to-one correspondence between theoretical and experimental results. The detailed technologies derived herein are clearly influential in both research and industry.

Immunization with a recombinant antigen composed of conserved blocks from TSA56 provides broad genotype protection against scrub typhus.

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Despite the wide range of approaches explored during the last seventy years, an effective prophylactic vaccine is not yet available. Here, we developed a novel recombinant antigen derived from conserved regions of 56 kDa type-specific antigen (TSA56), a major outer membrane protein responsible for genetic heterogeneity and antigenicity, and evaluated it as a protective vaccine antigen. Our findings demonstrate that immunization with conserved blocks of TSA56 (cTSA56) not only provides protective immunity against lethal challenges with the homologous genotype, but also confers significantly better protection against heterologous genotypes than TSA56. Adoptive transfer of CD4+ or CD8+ T cells from immunized mice provided significantly enhanced protection against lethal challenge, whereas immune B cells failed to do so, indicating that cellular immunity against the conserved epitopes plays a protective role. Moreover, immunization with a 10-mer peptide mixture, screened from CD8+ T cell epitopes within the conserved region of TSA56, provided enhanced protection against lethal challenge with O. tsutsugamushi. Therefore, this novel recombinant antigen is a promising candidate for scrub typhus vaccine against a wide range of O. tsutsugamushi genotypes.

New type of doping effect via metallization of surface reduction in SnO2.

The use of conventional doping methods requires consideration of not only the energy connection with the base material but also the limits of the type and doping range of the dopant. The scope of the physico-chemical change must be determined from the properties of the base material, and when this limit is exceeded, a large energy barrier must be formed between the base material and the dopant as in a heterojunction. Thus, starting from a different viewpoint, we introduce a so-called metallization of surface reduction method, which easily overcomes the disadvantages of existing methods while having the effect of doping the base material. Such new synthetic techniques enable sequential energy arrangements-gradients from the surface to the centre of the material-so that free energy transfer effects can be obtained as per the energies in the semiconducting band, eliminating the energy discontinuity of the heterojunction.

Incorporation of Pt Nanoparticles on the Surface of TeO2-Branched Porous Si Nanowire Structures for Enhanced Room-Temperature Gas Sensing.

A new gas sensor working in room temperature, which is compatible with silicon fabrication technology is presented. Porous silicon nanowires (NWs) were synthesized by metal-assisted chemical etching method and then TeO2 NWs branches were attached to their stem by thermal evaporation of Te powders in the presence of air. Afterwards TeO2 branched porous Si NWs were functionalized by Pt via sputtering followed by low temperature thermal annealing. Scanning electron microscopy, transmission electron microscopy and energy-dispersive X-ray spectroscopy collectively confirmed successful formation of TeO2 branched porous Si NWs functionalized by Pt nanoparticles. Their gas sensing properties in the presence of CO, C6H6 and C7H8 were tested at room temperature, for Si wafer, pristine porous Si NWs, pristine TeO2 branched porous Si NWs, and Pt functionalized TeO2 branched porous Si NWs sensors. Pt functionalized TeO2 branched porous Si NWs have higher responses to all tested gases than the other sensors. The origin of high response is discussed in detail. This new room temperature gas sensor can open a new aperture for development of gas sensors with minimum energy consumption which are compatible with silicon fabrication technology.

Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015.

The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several "superspreading" events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.

A Type I Interferon and IL-10 Induced by Orientia tsutsugamushi Infection Suppresses Antigen-Specific T Cells and Their Memory Responses.

Despite the various roles of type I interferon (type I IFN) responses during bacterial infection, its specific effects in vivo have been poorly characterized in scrub typhus caused by Orientia tsutsugamushi infection. Here, we show that type I IFNs are primarily induced via intracellular nucleic acids sensors, including RIG-I/MAVS and cGAS/STING pathways, during O. tsutsugamushi invasion. However, type I IFN signaling did not significantly affect pathogenesis, mortality, or bacterial burden during primary infection in vivo, when assessed in a mice model lacking a receptor for type I IFNs (IFNAR KO). Rather, it significantly impaired the induction of antigen-specific T cells and reduced memory T cell responses. IFNAR KO mice that recovered from primary infection showed stronger antigen-specific T cell responses, especially Th1, and more efficiently controlled bacteremia during secondary infection than wild type mice. Enhanced IL-10 expression by macrophages in the presence of type I IFN signaling might play a significant role in the suppression of antigen-specific T cell responses as neutralization or knock-out (KO) of IL-10 increased T cell responses in vitro. Therefore, induction of the type I IFN/IL-10 axis by O. tsutsugamushi infection might play a significant role in the suppression of T cell responses and contribute to the short longevity of cell-mediated immunity, often observed in scrub typhus patients.

Porous Si nanowires for highly selective room-temperature NO2 gas sensing.

We report the room-temperature sensing characteristics of Si nanowires (NWs) fabricated from p-Si wafers by a metal-assisted chemical etching method, which is a facile and low-cost method. X-ray diffraction was used to the the study crystallinity and phase formation of Si NWs, and product morphology was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). After confirmation of Si NW formation via the SEM and TEM micrographs, sensing tests were carried out at room temperature, and it was found that the Si NW sensor prepared from Si wafers with a resistivity of 0.001-0.003 Ω.cm had the highest response to NO2 gas (Rg/Ra = 1.86 for 50 ppm NO2), with a fast response (15 s) and recovery (30 s) time. Furthermore, the sensor responses to SO2, toluene, benzene, H2, and ethanol were nearly negligible, demonstrating the excellent selectivity to NO2 gas. The gas-sensing mechanism is discussed in detail. The present sensor can operate at room temperature, and is compatible with the microelectronic fabrication process, demonstrating its promise for next-generation Si-based electronics fused with functional chemical sensors.

Comparative Study of Two Droplet-Based Dissolving Microneedle Fabrication Methods for Skin Vaccination.

Dissolving microneedles (DMNs) have been widely studied in medical applications due to their pain-free administration, superior efficiency, and safe drug delivery. In skin vaccination, preserving the activity of the encapsulated antigen is an important consideration, as antigen activity is lost during DMN fabrication because of various stress factors. These stress factors vary between fabrication methods and each method affects the antigen's activity to different degrees. In this study, the activity of encapsulated antigens delivered by DMNs is compared between two recently developed DMN fabrication methods; droplet-born air blowing (DAB) and centrifugal lithography (CL) for a model scrub typhus vaccine antigen, ScaA. Although the in vitro analysis of ScaA-loaded DMNs (ScaA-DMNs) does not show any differences in physical properties depending on the fabrication methods, the immunogenicity of the CL-produced ScaA-DMN is significantly higher based on cytokine measurement and humoral immunity. DAB and CL differ in their solidification conditions, suggesting that solidification factors critically affect the encapsulated antigen's activity. ScaA-DMNs may also be stably stored for 4 weeks at room temperature. In conclusion, CL is a superior DMN fabrication method compared with DAB, and this study proves that DMN is feasible and practical for skin vaccination.

Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus.

Dipeptidyl peptidase 4 (DPP4) is a receptor for MERS-CoV. The soluble form of DPP4 (sDPP4) circulates systematically and can competitively inhibit MERS-CoV entry into host cells. Here, we measured the concentration of sDPP4 in the plasma and sputa of 14 MERS-CoV-infected patients of various degrees of disease severity. The concentration of sDPP4 in the plasma of MERS patients (474.76 ±â€¯108.06 ng/ml) was significantly lower than those of healthy controls (703.42 ±â€¯169.96 ng/ml), but there were no significant differences among the patient groups. Interestingly, plasma levels of IL-10 and EGF were negatively and positively correlated with sDPP4 concentrations, respectively. The sDPP4 levels in sputa were less than 300 ng/ml. Viral infection was inhibited by 50% in the presence of more than 8000 ng/ml of sDPP4. Therefore, sDPP4 levels in the plasma of MERS patients are significantly reduced below the threshold needed to exert an antiviral effect against MERS-CoV infection.

Longevity of antibody and T-cell responses against outer membrane antigens of Orientia tsutsugamushi in scrub typhus patients.

Scrub typhus, caused by Orientia tsutsugamushi infection, has been a serious public health issue in the Asia-Pacific region, with rising incidence and sporadic outbreaks. However, human protective immunity against specific antigens has been poorly characterized for this bacterium. In addition, immunity produced in early vaccine trials or even after natural infections, did not last long and had poor cross-reactivity among various genotypes. Here, we systematically investigated the kinetics and magnitude of specific adaptive immunity against two membrane antigens, 56 kDa type-specific antigen (TSA56) and surface cell antigen A (ScaA), that are involved in bacterial adhesion and invasion of the host in 64 recovered scrub typhus patients. Antibody responses to the bacterial antigens in patients were generally short-lived and waned to baseline levels 2 years after recovery. The anti-TSA56 IgG responses were predominantly composed of the IgG1 and IgG3 subclasses and persisted for up to 1 year after recovery, whereas IgG specific to ScaA primarily consisted of more transient IgG1, with limited responses by other subclasses. Cellular immunity, including CD4 and CD8 T-cells specific to membrane antigens, also rapidly declined from 1 year after infection, as measured by enzyme-linked immunospot (ELISPOT) assays and flow cytometry. The short longevity of antigen-specific adaptive immunity might be attributable to limited memory responses, as observed in earlier vaccine studies using whole bacterial antigens. Finally, we identified HLA-A*0201-restricted and highly conserved CD8 T-cell epitopes in the TSA56 antigen, which may be valuable tools for assessing cellular immunity against O. tsutsugamushi and developing an effective scrub typhus vaccine.

Microwave-Assisted Synthesis of Graphene-SnO2 Nanocomposites and Their Applications in Gas Sensors.

We obtained extremely high and selective sensitivity to NO2 gas by fabricating graphene-SnO2 nanocomposites using a commercial microwave oven. Structural characterization revealed that the products corresponded to agglomerated structures of graphene and SnO2 particles, with small secondary SnOx (x ≤ 2) nanoparticles deposited on the surfaces. The overall oxygen atomic ratio was decreased with the appearance of an SnOx (x < 2) phase. By the microwave treatment of graphene-SnO2 nanocomposites, with the graphene promoting efficient transport of the microwave energy, evaporation and redeposition of SnOx nanoparticles were facilitated. The graphene-SnO2 nanocomposites exhibited a high sensor response of 24.7 for 1 ppm of NO2 gas, at an optimized temperature of 150 °C. The graphene-SnO2 nanocomposites were selectively sensitive to NO2 gas, in comparison with SO2, NH3, and ethanol gases. We suggest that the generation of SnOx nanoparticles and the SnOx phase in the matrix results in the formation of SnO2/SnO2 homojunctions, SnO2/SnOx (x < 2) heterojunctions, and SnO2/graphene heterojunctions, which are responsible for the excellent sensitivity of the graphene-SnO2 nanocomposites to NO2 gas. In addition, the generation of surface Sn interstitial defects is also partly responsible for the excellent NO2 sensing performance observed in this study.

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

Diversification of Orientia tsutsugamushi genotypes by intragenic recombination and their potential expansion in endemic areas.

BACKGROUND: Scrub typhus is a mite-borne febrile disease caused by O. tsutsugamushi infection. Recently, emergence of scrub typhus has attracted considerable attention in several endemic countries in Asia and the western Pacific. In addition, the antigenic diversity of the intracellular pathogen has been a serious obstacle for developing effective diagnostics and vaccine. METHODOLOGY/PRINCIPAL FINDINGS: To understand the evolutionary pathway of genotypic diversification of O. tsutsugamushi and the environmental factors associated with the epidemiological features of scrub typhus, we analyzed sequence data, including spatiotemporal information, of the tsa56 gene encoding a major outer membrane protein responsible for antigenic variation. A total of 324 tsa56 sequences covering more than 85% of its open reading frame were analyzed and classified into 17 genotypes based on phylogenetic relationship. Extensive sequence analysis of tsa56 genes using diverse informatics tools revealed multiple intragenic recombination events, as well as a substantially higher mutation rate than other house-keeping genes. This suggests that genetic diversification occurred via frequent point mutations and subsequent genetic recombination. Interestingly, more diverse bacterial genotypes and dominant vector species prevail in Taiwan compared to other endemic regions. Furthermore, the co-presence of identical and sub-identical clones of tsa56 gene in geographically distant areas implies potential spread of O. tsutsugamushi genotypes. CONCLUSIONS/SIGNIFICANCE: Fluctuation and diversification of vector species harboring O. tsutsugamushi in local endemic areas may facilitate genetic recombination among diverse genotypes. Therefore, careful monitoring of dominant vector species, as well as the prevalence of O. tsutsugamushi genotypes may be advisable to enable proper anticipation of epidemiological changes of scrub typhus.

Constitutive activation of T cells by γ2-herpesviral GPCR through the interaction with cellular CXCR4.

Members of the herpesviral family use multiple strategies to hijack infected host cells and exploit cellular signaling for their pathogenesis and latent infection. Among the most intriguing weapons in the arsenal of pathogenic herpesviruses are the constitutively active virally-encoded G protein-coupled receptors (vGPCRs). Even though vGPCRs contribute to viral pathogenesis such as immune evasion and proliferative disorders, the molecular details of how vGPCRs continuously activate cellular signaling are largely unknown. Here, we report that the vGPCR of Herpesvirus saimiri (HVS), an oncogenic γ2-herpesvirus, constitutively activates T cells via a heteromeric interaction with cellular CXCR4. Constitutive T cell activation also occurs with expression of the vGPCR of Kaposi's sarcoma-associated herpesvirus (KSHV), but not the vGPCR of Epstein-Barr virus. Expression of HVS vGPCR down-regulated the surface expression of CXCR4 but did not induce the degradation of the chemokine receptor, suggesting that vGPCR/CXCR4 signaling continues in cytosolic compartments. The physical association of vGPCR with CXCR4 was demonstrated by proximity ligation assay as well as immunoprecipitation. Interestingly, the constitutive activation of T cells by HVS vGPCR is independent of proximal T cell receptor (TCR) signaling molecules, such as TCRß, Lck, and ZAP70, whereas CXCR4 silencing by shRNA abolished T cell activation by vGPCRs of HVS and KSHV. Furthermore, previously identified inactive vGPCR mutants failed to interact with CXCR4. These findings on the positive cooperativity of vGPCR with cellular CXCR4 in T cell activation extend our current understanding of the molecular mechanisms of vGPCR function and highlight the importance of heteromerization for GPCR activity.