Abstract
Enhancers are DNA sequences at a long genomic distance from target genes. Recent experiments suggest that enhancers are anchored to the surfaces of condensates of transcription machinery and ...that the loop extrusion process enhances the transcription level of their target genes. Here, we theoretically study the polymer dynamics driven by the loop extrusion of the linker DNA between an enhancer and the promoter of its target gene to calculate the contact probability of the promoter to the transcription machinery in the condensate. Our theory predicts that when the loop extrusion process is active, the contact probability increases with increasing linker DNA length. This finding reflects the fact that the relaxation time, with which the promoter stays in proximity to the surface of the transcriptional condensate, increases as the length of the linker DNA increases. This contrasts the equilibrium case for which the contact probability between the promoter and the transcription machineries is smaller for longer linker DNA lengths.
Purpose To identify the optimal dose of a novel Rho kinase inhibitor, K-115, by assessing dose dependency of the intraocular pressure (IOP)-lowering effects and the safety in patients with primary ...open-angle glaucoma or ocular hypertension. Designs Multicenter, prospective, randomized, placebo-controlled, double-masked, parallel group comparison clinical study. Methods After appropriate washout periods, 210 patients with primary open-angle glaucoma or ocular hypertension were subdivided into 4 groups and were treated with K-115 in concentrations of 0.1%, 0.2%, and 0.4% or placebo twice daily for 8 weeks. The dose response of IOP reduction and the incidence of adverse events by K-115 or placebo were investigated. Results The mean baseline IOP was between 23.0 and 23.4 mm Hg. The mean IOP reductions of the last visit from baseline were −2.2 mm Hg, −3.4 mm Hg, −3.2 mm Hg, and −3.5 mm Hg, respectively, in the placebo, 0.1%, 0.2%, and 0.4% groups at before instillation (9:00); −2.5 mm Hg, −3.7 mm Hg, −4.2 mm Hg, and −4.5 mm Hg at 2 hours after instillation (11:00); and −1.9 mm Hg, −3.2 mm Hg, −2.7 mm Hg, and −3.1 mm Hg at 8 hours after instillation (17:00). The dose-dependent IOP-lowering effect of K-115 was statistically significant at all time points. Also, conjunctival hyperemia was found in 7 (13.0%) of 54 patients for placebo, 23 (43.4%) of 53 patients for the 0.1% group, 31 (57.4%) of 54 patients for the 0.2% group, and 32 (65.3%) of 49 patients for the 0.4% group. Conclusions On the basis of this dose-response study, K-115 0.4% has been selected to be the optimal dose and has the potential to be a promising new agent for glaucoma to control 24-hour IOP by twice-daily dosing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
With the aim of developing an iron ore sinter with a better reducibility, the authors researched the co-firing of green pellets and a sinter mix in a packed bed. First, a physical simulation with a ...simulator for the charging equipment of a sintering machine demonstrated that the green pellets were distributed more strongly to the lowest part of the packed bed because their size is larger than that of the sinter mix. Pot tests based on the simulated pellet distribution proved that it is possible to produce a highly reducible sinter at higher productivity, particularly when a concentrate with a large Blaine surface area is used to produce rigid green pellets. Factors that could reduce product yield were also pointed out, i.e., diffusion of the melt from the sinter mix into the pellets and a larger local heat supply to the sinter mix than is suitable. These factors are thought to hinder the formation of thick and strong bonds in the co-fired sinter bed. A 450 kV class X-ray CT was used to visualize the internal structure of the sinter plugs, and revealed the plug made with the green pellets has higher porosity, which is important for better permeability, but also results in less bond formation, which reduces the yield in a co-fired plug. These findings revealed insights for fully enjoying the advantages of co-firing green pellets and sinter mix, as well as issues to be overcome in order to realize a successful co-firing process.
The pellet making method was studied for production of iron ore pellets with a carbon core. The pellets are to be fired in a sintering machine to produce sintered ores containing carbonaceous ...material. This new raw material for the blast furnace will have advantages such as high reducibility and low slag generation. In this study, pellet making tests were performed using laboratory and pilot scale disc pelletizers with 3 to 5 mm coke breeze, concentrated iron ores and additives in order to construct a method for producing pellets with a carbon core. Scaling-up of the method was considered with four discs with diameters of 0.6, 1.2, 2.0 and 3.5 m. As a result, it was found that there were two strategies for producing pellets with a carbon core at high yield: supplying a suitable level of water with a small droplet size, and spraying water in a specific area where the coke breeze flows on the surface of the contents in the disc. This study demonstrated that iron ore pellets with a carbon core can be obtained at a yield of more than 90% by using the disc pelletizer with the 3.5 m diameter. It was also estimated that a production capacity of 70 t/h can be expected with a 7.5 m diameter disc for commercial scale operation. This achievement of constructing a method for producing pellets with a carbon core was a breakthrough which overcame one of the technical hurdles for the development of sintered ores containing carbonaceous material.
The NLRP3 inflammasome has been implicated in the pathogenesis of various inflammatory diseases and is activated by particulate stimulants. Oral epithelial keratinocytes are frequently exposed to ...metal nanoparticles. In this study, we examined the effects of gold, silver, and palladium nanoparticles, which are frequently used for dental metal alloys on cell proliferation, cytotoxicity, autophagy, lysosomal functions, and NLRP3 inflammasome activation using the immortalized human oral keratinocyte cell line RT-7. The metal nanoparticles were agglomerated in the membrane vesicles in RT-7 cells and suppressed cell proliferation and increased lactate dehydrogenase activity as well as the proportion of apoptotic cells. Silver and palladium nanoparticles induced autophagy and lysosomal dysfunctions and all metal nanoparticles tested triggered the secretion of IL-1β through caspase-1 activation. Furthermore, the epithelium obtained from patients with oral lichenoid lesions (OLLs) had robust NLRP3, ASC, caspase-1, and IL-1β-positive keratinocytes and cDNA microarray showed significant elevation in the mRNA levels of NLRP3. These results suggest that internalized metal nanoparticles in oral mucosal epithelial cells activate the NLRP3 inflammasome through the induction of lysosomal damage and autophagy dysfunction. This process may be involved in the pathogenesis of OLL and suggest its potential as an alternative target for OLL therapy.
•Sliver, gold, and palladium nanoparticles were agglomerated in membrane vesicles of oral keratinocytes.•Sliver, gold, and palladium nanoparticles suppressed proliferation and induced apoptotsis in oral kereatinocytes.•Silver nanoparticles induced autophagy and lysosomal dysfunctions.•Sliver, gold, and palladium nanoparticles triggered the secretion of IL-1β through caspase-1 activation.•Clinical specimens from patients with OLL had robust NLRP3, ASC, caspase-1, and IL-1β-positive keratinocytes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Polymeric nanoparticles with diameters of ≤100 nm are employed in various fields owing to their unique properties. However, their environmental effects are concerning because of the large amounts of ...surfactants used during polymerization. Here, we fabricated nanoparticles without the use of surfactants via soap-free emulsion polymerization using melamine foam (MF), which is a thermosetting foam resin with a 3D micro-network structure, as a reactor. The particle size, which could be finely tuned by changing the porosity of the MF, correlated with the flow resistance of the MF. In addition, new particles were generated during seed polymerization within the MF, indicating that heterocoagulation was suppressed, which inhibited particle growth and yielded nanosized particles. This study provides a novel, green method of synthesizing polymeric nanoparticles, which are widely used in medical fields, without surfactants.
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•Polymeric particles with size of ≤100 nm were synthesized using melamine foam (MF).•The particle size could be controlled by adjusting the porosity of MF.•The particle growth via heterocoagulation was controlled in the MF by suppressing the fluidity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In order to control the interfacial adhesion between carbon fibers and thermoplastic resins, poly(methyl methacrylate) (PMMA) particles have been adsorbed on the carbon fiber surfaces using an ...electrophoresis process. The amount of PMMA particles adsorbed on the modified carbon fibers was varied using the electrophoresis technique performed in polymer colloids for a short time. Additionally, the interfacial shear strength between the modified carbon fiber and the resin was controlled by a modification of the present process. An improved interaction and a strengthened surface adhesion between the carbon fiber coated with particles and the PMMA resin were observed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The spectral features of energy donors and acceptors and the relationship between them in photosynthetic light-harvesting proteins are crucial for photofunctions of these proteins. Engineering energy ...donors and acceptors in light-harvesting proteins affords the means to increase our understanding of their photofunctional mechanisms. Herein, we demonstrate the conversion of energy-donating B800 bacteriochlorophyll (BChl) a to 3-acetyl chlorophyll (AcChl) a in light-harvesting complex 3 (LH3) from Rhodoblastus acidophilus by in situ oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. AcChl a in the B800 site exhibited a Qy band that was 111 nm blue-shifted with respect to BChl a in oxidized LH3. The structure of LH3 was barely influenced by the oxidation process, based on circular dichroism spectroscopy and size-exclusion chromatography evidence. In oxidized LH3, AcChl a transferred excitation energy to B820 BChl a, but the rate of excitation energy transfer (EET) was lower than in native LH3. The intracomplex EET in oxidized LH3 was slightly faster than in oxidized light-harvesting complex 2 (LH2). This difference is rationalized by an increase in overlap of the luminescence band of AcChl a with the long tail of the B820 absorption band in oxidized LH3 compared with that of the B850 band in oxidized LH2.
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IJS, KILJ, NUK, PNG, UL, UM
The influence of repeated lockdowns on mental health and social isolation is unknown. We conducted a longitudinal study of the influence of repeated mild lockdowns during two emergency declarations ...in Japan, in May 2020 and February 2021. The analyses included 7893 people who participated in all online surveys. During repeated mild lockdowns, mental and physical symptoms decreased overall, while loneliness increased and social networks decreased. Subgroup analyses revealed that depression and suicidal ideation did not decrease only in the younger age group (aged 18-29 years) and that younger and middle-aged people (aged 18-49 years), women, people with a history of treatment for mental illness, and people who were socially disadvantaged in terms of income had higher levels of mental and physical symptoms at all survey times. Additionally, comprehensive extraction of the interaction structure between depression, demographic attributes, and psychosocial variables indicated that loneliness and social networks were most closely associated with depression. These results indicate that repeated lockdowns have cumulative negative effects on social isolation and loneliness and that susceptible populations, such as young people and those with high levels of loneliness, require special consideration during repeated lockdown situations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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