Dissolution characteristics of granulated coal ash in different saline water conditions

Granulate coal ash (GCA) has been widely used for improving both sediment and water environments in littoral regions. Dissolved ions from GCA have been pointed out to play an important role in the improvements of sediment and water environments. As the dissolution characteristics of a material in solvent depend on the solvent characteristics, this study attempts to clarify the dissolution characteristics of GCA under different saline water conditions. This may provide useful information for practical uses of GCA in different water environments. The experimental results showed that GCA dissolved more with increasing salinity of solvent. This suggests that GCA is more active in saline water environment rather than freshwater environment. Interestingly, larger releases of calcium ions were confirmed when the solvent salinity was higher than 1000?mg/L. This was because the calcium ions of calcium silicate hydrate (C–S–H) present in GCA were replaced by the sodium ions present in solvent. The solubility of C–S–H present in GCA was low comparing with that of C–S–H gels. Only 40% of the total C–S–H were influenced by the high salinity concentration (higher than 1000?mg/L). Furthermore, a higher solubility of GCA was observed after combusting GCA. Our results suggest that GCA should be combusted at 200?°C prior to use for obtaining a higher performance in improving water and sediment environments.     

Effects of induced anisotropy on multiple liquefaction properties of sand with initial static shear

The multiple liquefaction phenomenon has been attracting the attention of more and more researchers and engineers since the 2010–2011 Christchurch Earthquakes and the 2011 Great East Japan Earthquake. However, little has been known about the multiple liquefaction properties of sloped grounds. In this study, therefore, multiple liquefaction tests that consider the initial static shear stress, which have never been conducted before, were carried out with a special designed apparatus, the stacked-ring shear apparatus. A series of multiple liquefaction tests revealed that induced anisotropy, which is weak against the loading opposite to the direction of the initial static shear stress, was produced by the liquefaction of a sloped ground. As a result, a significant decrease in the liquefaction resistance during the next cyclic of shearing occurred. The indicators which influenced the magnitude of anisotropy were also discussed from the perspective of the reconsolidation procedures, the magnitude of initial static shear stress, and the type of ending of the previous liquefaction stage. In addition, it turned out that in the multiple liquefaction test with a larger initial static shear stress, the re-liquefaction resistance was higher because the shear stress opposite to the direction of the initial static shear stress, causing large negative dilatancy due to anisotropy, was smaller in that test.     

Trifluoromethyl Dihydrothiazine-Based β-Secretase (BACE1) Inhibitors with Robust Central β-Amyloid Reduction and Minimal Covalent Binding Burden

The β-site amyloid precursor protein cleaving enzyme 1 (BACE1, also known as β-secretase) is a promising target for the treatment of Alzheimer's disease. A pK_a lowering approach over the initial leads was adopted to mitigate hERG inhibition and P-gp efflux, leading to the design of 6-CF₃ dihydrothiazine 8 (N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-cyanopicolinamide). Optimization of 8 led to the discovery of 15 (N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide) with an excellent balance of potency, hERG inhibition, P-gp efflux, and metabolic stability. Oral administration of 8 elicited robust Aβ reduction in dog even at 0.16 mg/kg. Reflecting the reduced hERG inhibitory activity, no QTc prolongation was observed at high doses. The potential for reactive metabolite formation of 15 was realized in a nucleophile trapping assay using [¹⁴C]-KCN in human liver microsomes. Utilizing covalent binding (CVB) in human hepatocytes and the maximum projected human dosage, the daily CVB burden of 15 was calculated to be at an acceptable value of below 1 mg/day. However, hepatotoxicity was observed when 15 was subjected to a two-week tolerance study in dog, which prevented further evaluation of this compound.     

Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders

A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data.     

Vaporized Hydrogen Peroxide and Ozone Gas Synergistically Reduce Prion Infectivity on Stainless Steel Wire

Prions are infectious agents causing prion diseases, which include Creutzfeldt–Jakob disease (CJD) in humans. Several cases have been reported to be transmitted through medical instruments that were used for preclinical CJD patients, raising public health concerns on iatrogenic transmissions of the disease. Since preclinical CJD patients are currently difficult to identify, medical instruments need to be adequately sterilized so as not to transmit the disease. In this study, we investigated the sterilizing activity of two oxidizing agents, ozone gas and vaporized hydrogen peroxide, against prions fixed on stainless steel wires using a mouse bioassay. Mice intracerebrally implanted with prion-contaminated stainless steel wires treated with ozone gas or vaporized hydrogen peroxide developed prion disease later than those implanted with control prion-contaminated stainless steel wires, indicating that ozone gas and vaporized hydrogen peroxide could reduce prion infectivity on wires. Incubation times were further elongated in mice implanted with prion-contaminated stainless steel wires treated with ozone gas-mixed vaporized hydrogen peroxide, indicating that ozone gas mixed with vaporized hydrogen peroxide reduces prions on these wires more potently than ozone gas or vaporized hydrogen peroxide. These results suggest that ozone gas mixed with vaporized hydrogen peroxide might be more useful for prion sterilization than ozone gas or vaporized hydrogen peroxide alone.     

CRISPR-Cas9–Mediated TIM3 Knockout in Human Natural Killer Cells Enhances Growth Inhibitory Effects on Human Glioma Cells

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Natural Killer (NK) cells are potent cytotoxic effector cells against tumor cells inducing GBM cells; therefore, NK cell based- immunotherapy might be a promising target in GBM. T cell immunoglobulin mucin family member 3 (TIM3), a receptor expressed on NK cells, has been suggested as a marker of dysfunctional NK cells. We established TIM3 knockout in NK cells, using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9). Electroporating of TIM3 exon 2- or exon 5-targeting guide RNA- Cas9 protein complexes (RNPs) inhibited TIM3 expression on NK cells with varying efficacy. T7 endonuclease I mutation detection assays showed that both RNPs disrupted the intended genome sites. The expression of other checkpoint receptors, i.e., programmed cell death 1 (PD1), Lymphocyte-activation gene 3 (LAG3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and TACTILE (CD96) were unchanged on the TIM3 knockout NK cells. Real time cell growth assays revealed that TIM3 knockout enhanced NK cell–mediated growth inhibition of GBM cells. These results demonstrated that TIM3 knockout enhanced human NK cell mediated cytotoxicity on GBM cells. Future, CRISPR-Cas9 mediated TIM3 knockout in NK cells may prove to be a promising immunotherapeutic alternative in patient with GBM.     

Development of entertainment balloon robot system for an indoor event venue

This project revolves around the combination of different state-of-the-art concepts to create balloon robots which can be used for entertainment purposes. The goal is having multiple robots perform a choreographed flight on preset paths to make use of the “dead space” over the crowd of an event, either as part of the show or displaying information and advertisements. As the balloon is flying on a defined trajectory, a tracking system for its position is needed. For this purpose, several infrared cameras monitor the position of a marker attached to the balloon. The main challenge is overcoming the instabilities of the system to ensure a smooth and precise flight, resulting from the balloons structure: the balloon is filled with helium to counteract the forces of gravity and, therefore, minimize the work needed to keep its momentum. Finding a way to achieve this optimization and the precision mentioned beforehand is the task that we will present and solve in this paper.     

Precise Control of Temperature Rising Speed of Wafer during Rapid Thermal Processing

In rapid thermal processing of a semiconductor wafer, it is important to keep a given temperature rising speed of the wafer during the temperature rising process. We made an experimental apparatus to measure the temperature rising speed of a ceramic ball of 2 mm in diameter heated with four halogen lamp heaters. The heating rate of the halogen lamp heaters was controlled by computer to keep a given temperature rising speed of 50 ℃/s with a controlling time interval of 0.1 s. We examined the effect of various heating control methods on the error of the temperature rising speed of the ceramic ball. We found that a combined method of control with prepared correlation and PID （proportional integral derivative） control is a good method to decrease the error of the temperature rising speed. The average error of the temperature rising speed is 0.5 ℃/s, and the repetition error is almost zero for the temperature rising speed of 50 ℃/s from 330 ℃ to 370 ℃. We also measured the effects of artificial control delay time and measuring error of the monitoring temperature on the error of the temperature rising speed.     

Application of water mimics on preparation of eicosapentaenoic and docosahexaenoic acids containing glycerolipids

To obtain enhanced incorporation of highly unsaturated fatty acids and recovery of glycerolipid products, organic solvents with high dielectric constants (water mimics) were substituted for part of the essential water for lipase activation to study their effect on acidolysis and transesterification. In acidolysis/transesterification of fish oil triglycerides and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), Lipozyme IM-60 with ethylene glycol as a water mimic enhanced the incorporation of EPA and suppressed the hydrolysis of synthesized glycerolipid. On the other hand, transesterification between soy phosphatidylcholine and EPA was enhanced by a water and propylene glycol combination. In a nonaqueous medium that contained appropriate amounts of water and organic solvents (water mimics), Lipozyme IM-60 increased transesterification of EPA into soy phosphatidylcholine. Simultaneously, the recovered glycerolipid products showed decreased hydrolysis of newly synthesized EPA- and DHA-containing glycerolipids.