•To assess the damage of concrete structure subjected to freeze-thawed effects.•A method to monitor AE activity of core samples under uniaxial compressive loading was investigated.•The degree of ...damage was visualized using X-ray CT images.•Quantification of concrete damage was analyzed relation between AE parameter and spatial statistics of cracks.
The durability of concrete structures decreases easily due to such environmental effects. For effective maintenance of concrete structures, it is necessary to evaluate not only the values of mechanical properties but also the degree of damage. In this study, damage estimation of concrete is proposed to be performed, applying AE and X-ray CT. Testing concrete core samples were taken from reinforced concrete columns of an existing canal, which is strongly affected by freeze and thawed process. Thus, a relation between AE and X-ray CT parameters is correlated, and the damage of concrete is quantitatively estimated using AE and X-ray CT.
Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with higher transmission potential have been emerging globally, including SARS-CoV-2 variants from the United Kingdom ...and South Africa. We report 4 travelers from Brazil to Japan in January 2021 infected with a novel SARS-CoV-2 variant with an additional set of mutations.
The generation of DNA damage causes mutations and consequently cancer. Reactive oxygen species are important sources of DNA damage and some mutation signatures found in human cancers. ...8-Oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) is one of the most abundant oxidized bases and induces a G→T transversion mutation at the modified site. The damaged G base also causes untargeted base substitution mutations at the G bases of 5′-GpA-3′ dinucleotides (action-at-a-distance mutations) in human cells, and the cytosine deaminase apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) is involved in the mutation process. The deaminated cytosine, i.e., uracil, bases are expected to be removed by uracil DNA glycosylase. Most of the substitution mutations at the G bases of 5′-GpA-3′ might be caused by abasic sites formed by the glycosylase. In this study, we expressed the uracil DNA glycosylase inhibitor from Bacillus subtilis bacteriophage PBS2 in human U2OS cells and examined the effects on the GO-induced action-at-a-distance mutations. The inhibition of uracil DNA glycosylase increased the mutation frequency, and in particular, the frequency of G→A transitions. These results indicated that uracil DNA glycosylase, in addition to APOBEC3, is involved in the untargeted mutation process induced by GO.
•To assess the damage of concrete structure subjected to freeze-thawed effects.•A method to monitor AE energy activity of core samples under uniaxial compressive loading was investigated.•The degree ...of damage was visualized using X-ray CT images.•Quantification of concrete damage was analyzed relation between AE energy parameter and accumulation of cracks.
As a detailed inspection of a concrete structure in service, core samples are usually drilled out and then mechanical properties are measured. In this study, damage estimation of freeze-thawed concrete from concrete-core samples is developed, applying acoustic emission (AE) method. By the authors, the quantitative damage evaluation of concrete has been proposed in RILEM TC −212ACD, by applying AE and damage mechanics in the compression test. In this study, characteristics evaluation of cracking damage effects in concrete mechanical properties by detected AE energy in core test. Prior to the compression test, distribution of micro-cracks in a concrete-core sample is inspected by helical X-ray computer tomography (CT). Then, freeze-thawed damaged samples are tested by the compression test with AE monitoring. Concrete-core samples were taken out of a channel structures in Hokkaido, Japan which is extremely developed cracking damage. Thus, it is demonstrated that the concentration of material damage could be evaluated by comparing geometrical characteristics of cracks with the “energy rate” of AE generation, which is analyzed by AE parameter analysis. A relation between AE energy rate, physical properties and geometrical properties of void is correlated, and thus the damage of concrete is qualitatively estimated by AE parameters.
OX40 is crucial for T-cell differentiation and memory induction. The anti-OX40 antibody, rocatinlimab inhibits the OX40 pathway. We evaluated the efficacy and safety of rocatinlimab in adults with ...moderate-to-severe atopic dermatitis.
This multicentre, double-blind, placebo-controlled phase 2b study was done at 65 secondary and tertiary sites in the USA, Canada, Japan, and Germany. Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria or local diagnostic criteria) with moderate-to-severe disease activity, as defined by an Eczema Area and Severity Index (EASI) score of 16 or more, validated Investigator's Global Assessment for Atopic Dermatitis score of 3 (moderate) or 4 (severe), and affected body surface area 10% or higher at both screening and baseline, with documented history (within 1 year) of inadequate response to topical medications or if topical treatments were medically inadvisable. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous rocatinlimab every 4 weeks (150 mg or 600 mg) or every 2 weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. Percentage change from baseline in EASI score was assessed as the primary endpoint at week 16 and during the active extension and follow-up in all randomly assigned patients exposed to study drug with a post-baseline EASI score at week 16 or earlier according to the group they were randomly assigned to. Safety was assessed in all randomly assigned patients exposed to study drug; patients were analysed according to the group they were randomly assigned to. The study is registered with ClinicalTrials.gov, NCT03703102.
Between Oct 22, 2018, and Oct 21, 2019, 274 patients (114 42% women, 160 58% men; mean age 38·0 years SD 14·5) were randomly assigned to one of the rocatinlimab groups (217 79% patients) or to the placebo group (57 21% patients). Compared with placebo (−15·0 95% CI −28·6 to −1·4), significant least-squares mean percent reductions in EASI score at week 16 were observed in all rocatinlimab groups (rocatinlimab 150 mg every 4 weeks −48·3 −62·2 to −34·0, p=0·0003; rocatinlimab 600 mg every 4 weeks −49·7 −64·3 to −35·2, p=0·0002; rocatinlimab 300 mg every 2 weeks −61·1 −75·2 to −47·0, p<0·0001; and rocatinlimab 600 mg every 2 weeks −57·4 −71·3 to −43·4, p<0·0001). The most common adverse events during the double-blind period in patients receiving rocatinlimab (adverse events ≥5% of patients in the total rocatinlimab group and more common than the placebo group) were pyrexia (36 17% patients), nasopharyngitis (30 14% patients), chills (24 11% patients), headache (19 9% patients), aphthous ulcer (15 7% patients), and nausea (13 6% patients). There were no deaths.
Patients treated with rocatinlimab had progressive improvements in atopic dermatitis, which was maintained in most patients after treatment discontinuation. Treatment was well tolerated.
Kyowa Kirin.
This study evaluated the influence of illuminance and color temperature of ambient light on the trueness, precision, and scanning time of a digital impression.
Master data were acquired with a ...high-accuracy coordinate-measuring machine. The illuminance of ambient light was set at 0lux, 500lux, and 2500lux with a light-emitting diode (LED). Using a conversion filter, the color temperature was set at 3900 Kelvin (K) (yellow), 4100K (orange), 7500K (white), and 19,000K (blue). There were thus a total of 12 possible lighting conditions. The reference model was scanned five times under each condition by an intraoral scanner. Trueness was calculated as the mean difference between the master data and experimental data. Precision was calculated as the mean difference between the repeated scans in each test group. Statistical analysis was performed with two-way analysis of variance (ANOVA) and post hoc Tukey’s multiple comparison test. The significance level was 0.05.
For trueness, the mean deviation was significantly lower at 500lux than at 0lux and 2500lux. At 500lux, the mean deviation was significantly lower at 3900K than at other temperatures. Regardless of the color temperature, the scanning time was significantly longer at 2500lux than at other illuminance levels.
The 3900K and 500lux condition is the most appropriate lighting condition for taking a digital impression. This condition is typical of clinical settings. High illuminance ambient light increased the scanning time.
Guanine oxidation occurs in both DNA and the cellular nucleotide pool, and one of the major products is 8-hydroxyguanine (8-oxo-7,8-dihydroguanine). The mutagenic potentials of this oxidized base ...have been examined in various experimental systems. In this review, we summarize the mutagenicity of the base in mammalian cells. We also describe the effects of specialized DNA polymerases, DNA repair proteins, and nucleotide pool sanitization enzymes.
Single-stranded (ss) DNAs are utilized in various molecular biological and biotechnological applications including the construction of double-stranded DNAs with a DNA lesion, and are commonly ...prepared by using chimeric phage-plasmids (phagemids) plus M13-derived helper phages. However, the yields of ss DNA with these methods are poorly reproducible, and multiple factors must be optimized. In this report, we describe a new arabinose-inducible ss phagemid production method without helper phage infection. The newly exploited DNA derived from VCSM13 expresses the pII protein, which initiates ss DNA synthesis, under the control of the araBAD promoter. In addition, the packaging signal is deleted in the DNA to reduce the contamination of the phage-derived ss DNA. The phagemid DNA of interest, carrying the M13 origin of replication and the packaging signal, was introduced into bacterial cells maintaining the modified VCSM13 DNA as a plasmid, and the ss phagemid DNA production was induced by arabinose. The DNA recovered from the phage particles had less contamination from VCSM13 DNA, as compared to the conventional method. Moreover, we extended the method to purify the ss DNAs by using an anion-exchange column, to avoid the use of hazardous chemicals. Using this combination of methods, large quantities of phagemid ss DNAs of interest can be consistently obtained.
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is generally used for booster vaccination of infants in Europe and the United States to avoid increased ...reactogenicity after diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccination. However, Japan has extended the use of additional DTaP vaccination without reducing the antigen dose for diphtheria and pertussis in adolescents and adults, despite limited reports on its safety in adults. This prospective, observational, questionnaire-based study investigated the occurrence of adverse events (AEs) following DTaP vaccination between June 2018 and June 2019 in participants aged 10 years or older. Of the 250 eligible participants, 235 (94%) responded regarding AEs. Among them, 133 (56.6%) reported AEs, of which 39 reported systemic AEs (16.6%) and 120 reported local AEs (51.1%) attributed to DTaP vaccination. The incidence of local AEs was markedly higher with DTaP vaccination than with non-DTaP vaccination (51.1% vs. 10.5%), and AEs appeared later (P < 0.01) and lasted longer (P < 0.01) with DTaP vaccination. However, more than 75% of these AEs resolved within 7 days. DTaP vaccination was not associated with any serious AEs. These results indicate that the DTaP vaccine can be widely used as a booster in adults as an alternative to the Tdap vaccine.
Oxidatively damaged bases induce mutations and are involved in cancer initiation. 8-Oxo-7,8-dihydroguanine (G°, 8-hydroxyguanine) is an abundant oxidized base that induces targeted G:C→T:A ...transversions in human cells, as well as untargeted base substitution (action-at-a-distance) mutations of the G bases of 5′-GpA-3′ dinucleotides. The action-at-a-distance mutations become more frequent than the targeted transversions when the amount of Werner syndrome (WRN) protein is decreased. In this study, OGG1, the major DNA glycosylase for the damaged base, and WRN were knocked down in isolation and in combination in human U2OS cells, and a shuttle plasmid carrying G° was introduced into the knockdown cells. Interestingly, fewer action-at-a-distance mutations were observed in the WRN plus OGG1 double knockdown cells, as compared to the WRN single knockdown cells. These results indicated the paradoxical role of OGG1, as an accelerator of the action-at-a-distance mutations by the oxidized guanine base.
•8-Oxo-7,8-dihydroguanine induces untargeted base substitution mutations.•OGG1 is the major DNA glycosylase for the oxidized base.•Knockdown of Werner syndrome (WRN) protein enhances the untargeted mutations.•OGG1 knockdown suppresses the increase in the mutations by the WRN reduction.•The paradoxical role of OGG1 in the untargeted mutations is indicated.
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