To develop a mechanistic bacterial dose–response model, based on the concept of Key Events Dose–Response Framework (KEDRF), this study aimed to investigate the invasion of intestinal model cells ...(Caco‐2) by Salmonella Typhimurium and Listeria monocytogenes and described the behaviour of both pathogens as a mathematical model using Bayesian inference. Monolayer‐cultured Caco‐2 cells (approximately 105 cells) were co‐cultured with various concentrations (103–107 colony forming unit CFU ml−1) of Salm. Typhimurium and L. monocytogenes for up to 9 h to investigate the invasion of the pathogens into the Caco‐2 cells. While an exposure of ≥103 CFU ml−1 of Salm. Typhimurium initiated the invasion of Caco‐2 cells within 3 h, much less exposure (102 CFU ml−1) of L. monocytogenes was sufficient for invasion within the same period. Furthermore, while the maximum number of invading Salm. Typhimurium cells reached by approximately 103 CFU cm−2 for 6‐h exposure, the invading maximum numbers of L. monocytogenes cells increased by approximately 106 CFU cm−2 for the same exposure period. The invasion kinetics of both the pathogens was successfully described as an asymptotic exponential mathematical model using Bayesian inference. The developed pathogen invasion model allowed the estimation of probability of Salm. Typhimurium and L. monocytogenes infection, based on the physiological natures of digestion process, which was comparable to the published dose–response relationship. The invasion models developed in the present study will play a key role in the development of an alternative pathogen dose–response model based on KEDRF concept.
Significance and Impact of the Study: This study described the invasion of small intestinal epithelial‐like cells by Salmonella Typhimurium and Listeria monocytogenes using a mathematical model and statistical variation using Bayesian inference. The invasion model enabled the estimation of infection probability based on the assumptions of human digestion process. The infection probability of Salm. Typhimurium, estimated from the invasion model, was comparable to the results reported in literature. Both invasion model and the calculation procedure for infection probability would contribute to the development of an alternative mechanistic dose–response model based on the concept of Key Events Dose–Response Framework for the two pathogens.
Atomic diffusion bonding of quartz glass wafers using thin Ti films, with SiO2 underlayers on wafer surfaces, provides 100% light transmittance at the bonded interface along with strong bonding ...energy, after post-bonded low-temperature annealing. Cross-section images obtained using transmission electron microscopy show that the bonded interface after annealing at 350 °C consists of amorphous structure including nanocrystalline grains. Structural analysis using electron energy loss spectroscopy shows that post-bonded annealing enhances oxidation of Ti with oxygen dissociated from SiO2 underlayers, and that Ti oxides form close to TiO2 or Ti4O7. This oxidation provides 100% light transmittance with high bonding strength attributable to the annealing. Moreover, we applied this technique for bonding glass and sapphire wafers using SiO2-Nb2O5 underlayers, demonstrating that 100% light transmittance and control of refractive index matching are achieved simultaneously at the bonded interface.
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN ...in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10(-8); odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.
Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. ...In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography–tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.
Global Lightning and Sprite Measurements on Japanese Experiment Module (JEM‐GLIMS) is a space mission to conduct the nadir observations of lightning discharges and transient luminous events (TLEs). ...The main objectives of this mission are to identify the horizontal distribution of TLEs and to solve the occurrence conditions determining the spatial distribution. JEM‐GLIMS was successfully launched and started continuous nadir observations in 2012. The global distribution of the detected lightning events shows that most of the events occurred over continental regions in the local summer hemisphere. In some events, strong far‐ultraviolet emissions have been simultaneously detected with N2 1P and 2P emissions by the spectrophotometers, which strongly suggest the occurrence of TLEs. Especially, in some of these events, no significant optical emission was measured by the narrowband filter camera, which suggests the occurrence of elves, not sprites. The VLF receiver also succeeded in detecting lightning whistlers, which show clear falling‐tone frequency dispersion. Based on the optical data, the time delay from the detected lightning emission to the whistlers was identified as ∼10 ms, which can be reasonably explained by the wave propagation with the group velocity of whistlers. The VHF interferometer conducted the spaceborne interferometric observations and succeeded in detecting VHF pulses. We observed that the VHF pulses are likely to be excited by the lightning discharge possibly related with in‐cloud discharges and measured with the JEM‐GLIMS optical instruments. Thus, JEM‐GLIMS provides the first full set of optical and electromagnetic data of lightning and TLEs obtained by nadir observations from space.
Key Points
JEM‐GLIMS started continuous nadir observations of lightning and TLEs from ISS
Optical instruments succeeded in characterizing lightning and TLE emissions
Properties of lightning discharges exciting VHF pulses were first identified
High aspect ratio SiO2/SiN (ON) stacked layer etching using hydrofluorocarbon gases was conducted with various ratios of H, F, and C to achieve higher etching rates and precise profile control. The ...experimental gases were C3HF5, C4HF5, C4H2F4, C4H2F6, C4H4F6 and C5H2F10. The oxygen gas flow rate and mixing ratio were optimized to maximize mask selectivity while avoiding clogging at the top of the mask. For comparison, C4F6/CH2F2/Ar/O2, and C4F6/C4F8/CH2F2/Ar/O2 were used as reference gas mixtures. The initial screening narrowed the candidate pool to 3 gases: C3HF5, C4H2F6, and C4H4F6. At equivalent power, the C3HF5 condition achieved a 15% faster ON etch rate, and C4H2F6 achieved a 9% faster ON etch rate compared to the reference condition. Only C4H4F6 showed a worse ON etch rate than the reference (∼33%) due to severe mask clogging. Furthermore, C3HF5 achieved a 29% faster ON etch rate under high power conditions. It also achieved a 57% faster ON etch rate without excessively compromising selectivity or bow CD expansion after optimization. We report detailed comparisons of etch rate and clogging while controlling the CD profile in the ON stack process.
Studies on community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP) related to the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in Asia are scarce. This study aimed to ...investigate the epidemiological and microbiological determinants of hospitalised CAP and PP after PCV13 was introduced in Japan. This observational hospital-based surveillance study included children aged ⩽15 years, admitted to hospitals in and around Chiba City, Japan. Participants had bacterial pneumonia based on a positive blood or sputum culture for bacterial pathogens. Serotype and antibiotic-susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae isolates from patients with bacterial pneumonia were assessed. The CAP hospitalisation rate per 1000 child-years was 17.7, 14.3 and 9.7 in children aged <5 years and 1.18, 2.64 and 0.69 in children aged 5-15 years in 2008, 2012 and 2018, respectively. There was a 45% and 41% reduction in CAP hospitalisation rates, between the pre-PCV7 and PCV13 periods, respectively. Significant reductions occurred in the proportion of CAP due to PP and PCV13 serotypes. Conversely, no change occurred in the proportion of CAP caused by H. influenzae. The incidence of hospitalised CAP in children aged ⩽15 years was significantly reduced after the introduction of PCV13 in Japan. Continuous surveillance is necessary to detect emerging PP serotypes.
We present high-resolution H-band polarized intensity (FWHM = 0".1:14 AU) and L'-band imaging data (FWHM = 0".11: 15 AU) of the circumstellar disk around the weak-lined T Tauri star PDS 70 in ...Centaurus at a radial distance of 28 AU (0".2) up to 210 AU (1".5). In both images, a giant inner gap is clearly resolved for the first time, and the radius of the gap is ~70 AU. Our data show that the geometric center of the disk shifts by ~6 AU toward the minor axis. We confirm that the brown dwarf companion candidate to the north of PDS 70 is a background star based on its proper motion. As a result of spectral energy distribution fitting by Monte Carlo radiative transfer modeling, we infer the existence of an optically thick inner disk at a few AU. Combining our observations and modeling, we classify the disk of PDS 70 as a pre-transitional disk. Furthermore, based on the analysis of L'-band imaging data, we put an upper limit of ~30 to ~50 M sub(J) on the mass of companions within the gap. Taking into account the presence of the large and sharp gap, we suggest that the gap could be formed by dynamical interactions of sub-stellar companions or multiple unseen giant planets in the gap.
The formation scenario of a gapped disk, i.e., transitional disk, and its asymmetry is still under debate. Proposed scenarios such as disk-planet interaction, photoevaporation, grain growth, ...anticyclonic vortex, eccentricity, and their combinations would result in different radial distributions of the gas and the small (sub-μm size) and large (millimeter size) dust grains as well as asymmetric structures in a disk. Optical/near-infrared (NIR) imaging observations and (sub-)millimeter interferometry can trace small and large dust grains, respectively; therefore multi-wavelength observations could help elucidate the origin of complicated structures of a disk. Here we report Submillimeter Array observations of the dust continuum at 1.3 mm and {sup 12}CO J = 2 → 1 line emission of the pre-transitional protoplanetary disk around the solar-mass star PDS 70. PDS 70, a weak-lined T Tauri star, exhibits a gap in the scattered light from its disk with a radius of ∼65 AU at NIR wavelengths. However, we found a larger gap in the disk with a radius of ∼80 AU at 1.3 mm. Emission from all three disk components (the gas and the small and large dust grains) in images exhibits a deficit in brightness in the central region of the disk, in particular, the dust disk in small and large dust grains has asymmetric brightness. The contrast ratio of the flux density in the dust continuum between the peak position to the opposite side of the disk reaches 1.4. We suggest the asymmetries and different gap radii of the disk around PDS 70 are potentially formed by several (unseen) accreting planets inducing dust filtration.
We report high-resolution (0.07 arcsec) near-infrared polarized intensity images of the circumstellar disk around the star 2MASS J16042165-2130284 obtained with HiCIAO mounted on the Subaru 8.2 m ...telescope. We present our H-band data, which clearly exhibit a resolved, face-on disk with a large inner hole for the first time at infrared wavelengths. We detect the centrosymmetric polarization pattern in the circumstellar material as has been observed in other disks. Elliptical fitting gives the semimajor axis, semiminor axis, and position angle (P.A.) of the disk as 63 AU, 62 AU, and -14degrees, respectively. The disk is asymmetric, with one dip located at P.A.s of ~85degrees. Our observed disk size agrees well with a previous study of dust and CO emission at submillimeter wavelength with Submillimeter Array. Hence, the near-infrared light is interpreted as scattered light reflected from the inner edge of the disk. Our observations also detect an elongated arc (50 AU) extending over the disk inner hole. It emanates at the inner edge of the western side of the disk, extending inward first, then curving to the northeast. We discuss the possibility that the inner hole, the dip, and the arc that we have observed may be related to the existence of unseen bodies within the disk.
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