Aging and Clonal Behavior of Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) are the only cell population that possesses both a self-renewing capacity and multipotency, and can give rise to all lineages of blood cells throughout an organism’s life. However, the self-renewal capacity of HSCs is not infinite, and cumulative evidence suggests that HSCs alter their function and become less active during organismal aging, leading ultimately to the disruption of hematopoietic homeostasis, such as anemia, perturbed immunity and increased propensity to hematological malignancies. Thus, understanding how HSCs alter their function during aging is a matter of critical importance to prevent or overcome these age-related changes in the blood system. Recent advances in clonal analysis have revealed the functional heterogeneity of murine HSC pools that is established upon development and skewed toward the clonal expansion of functionally poised HSCs during aging. In humans, next-generation sequencing has revealed age-related clonal hematopoiesis that originates from HSC subsets with acquired somatic mutations, and has highlighted it as a significant risk factor for hematological malignancies and cardiovascular diseases. In this review, we summarize the current fate-mapping strategies that are used to track and visualize HSC clonal behavior during development or after stress. We then review the age-related changes in HSCs that can be inherited by daughter cells and act as a cellular memory to form functionally distinct clones. Altogether, we link aging of the hematopoietic system to HSC clonal evolution and discuss how HSC clones with myeloid skewing and low regenerative potential can be expanded during aging.     

Mutation Analysis of Radioresistant Early-Stage Cervical Cancer

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRAS^mt/SMAD4^mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRAS^mt/SMAD4^mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRAS^mt/SMAD4^mt cancer cells. These data indicate that the KRAS^mt/SMAD4^mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRAS^mt/SMAD4^mt signature.     

Effect of morphology on shear viscosity for binary blends of polycarbonate and polystyrene

The structure and rheological properties of binary blends of polycarbonate (PC) and polystyrene (PS) were investigated using various PS samples with different molecular weights, namely PS1k (M_w = 1,000), PS53k (M_w = 53,000), and PS240k (M_w = 240,000). The blends with PS53k and PS240k show phase-separated structures, whereas the blend with PS1k is miscible. The shear viscosity decreases greatly on addition of PS53k and PS240k, especially at high shear rates, which would be a great advantage at processing operations. Because the nonlinear response occurs in the small strain region for multilayered films of PC and PS240k, the origin of the significant viscosity drop for the phase-separated system is interfacial slippage at the phase boundary.     

Surface improvement on water and oil affinities and absorption rate of PVA/Tung oil-coated paperboard and fiberboard

A novel coating material on paperboard and fiberboard from poly(vinyl alcohol) (PVA) modified with Tung oil was developed. The PVA/Tung oil coating was cured at several conditions: 25, 40, 50, and 60°C, in the presence of two types of catalysts, i.e., thermal catalyst using potassium persulfate (KPS) and redox catalyst using KPS and sodium thiosulfate. The chemical crosslinked structure of PVA/Tung oil-coating films was confirmed by FTIR. The result indicated the decrease in the double bonds of Tung oil by crosslinking reaction, especially at 60°C. In comparison with the same curing temperature, the films with redox catalyst showed more reduction in the number of double bonds of Tung oil. DMA results of the PVA/Tung oil-coating materials with redox catalyst showed the lowering of the heights of both β transition peak of Tung oil and α transition peak of PVA. FTIR and DMA results confirmed the more efficient crosslinking reaction of redox catalytic system than that of the thermal catalytic system. The water resistance and mechanical properties of these coating materials exhibited better values as projected to higher curing temperature and redox catalyst. SEM images showed the smooth surface of PVA/Tung oil covered on the paperboards with ~72 µm in thickness. The contact angle of water or oil drop and dynamic change in contact angle on the surfaces of PVA/Tung oil-coated paperboards and fiberboards were investigated. The results show the contact angles for both water and oil were lower than those of the uncoated ones, indicating the improvement of water and oil affinities of the PVA/Tung oil-coating materials. The dynamic changes in contact angle of the coated ones also decreased, suggesting the reduction in water and oil absorption rates of these coated substrates.     

Optical Properties of Dysprosium-Doped Low-Phonon-Energy Glasses for a Potential 1.3 μm Optical Amplifier

Dysprosium-doped glasses were prepared in the system of gallium-based sulfide, tellurite, zirconium-baed and indium-based fluorides and their optical properties were studied. From the absorption cross sections of five f-f bands, three Judd-Ofelt parameters, ω _t ( t = 2, 4, 6), of Dy³⁺ ion were determined. The compositional variaton of the ω₂value showed the order sulfide > tellurite > fluorozirconate > fluoroindate, whereas the ω₆ value showed the opposite tendency. Compositional variaton of the fluorescence intensity ratio of the (⁴F_9/2⁶H_13/2)/(⁴F_9/2)→⁶H_15/2) is explained by the ratio of ω₂/ω₆ of doped Dy³⁺. The emission probabilities A and the branching ratio β from ⁶H_9/2 and ⁶F_11/2 levels, which are the doublet initial level of the 1.3 μm luminescence, were calculated for the glasses, and it was found that both values showed a tendency similar to that of ω₂ against the glass composition. In the sulfide glass, A was 2.6 × 10³S^-1 and β was 93%, both the highest in all of the glasses investigated. By 1.06 μm pumping of a Nd: YAG laser, the sulfide glass showed strong 1.3 μm emission and the lifetime was 25 μs, resulting in a quantum efficiency of 7%. This value is higher than that of the Pr³⁺:¹G₄ level in ZBLAN glass with β= 60%.     

Crack-Healing Behavior of Si3N4/SiC Ceramics under Cyclic Stress and Resultant Fatigue Strength at the Healing Temperature

Si₃N₄/SiC composite ceramics were sintered and subjected to three-point bending. A semi-elliptical surface crack of 100 μm surface length was made on each specimen. The crack-healing behavior under cyclic stress of 5 Hz, and resultant cyclic fatigue strengths at healing temperatures of 1100° and 1200°C, were systematically investigated. The main conclusions are as follows: (1) Si₃N₄/SiC composite ceramics have an excellent ability to heal a crack at 1100° and 1200°C. (2) This sample could heal a crack even under cyclic stress at a frequency of 5 Hz. (3) The crack-healed sample exhibited quite high cyclic fatigue strength at each crack-healing temperature, 1100° and 1200°C.     

Diffusion process of amino acids in polymer supports for solid‐phase peptide synthesis as studied by pulsed‐field‐gradient spin‐echo proton nuclear magnetic resonance

The diffusion coefficient (D) values of tert‐butyloxycarbonyl‐glycine, tert‐butyloxycarbonyl‐L ‐tryptophan, tert‐butyloxycarbonyl‐L ‐phenylalanine (Boc‐Phe), and 9‐fluorenylmethoxycarbonyl‐L ‐phenylalanine in Merrifield polystyrene (MPS) gels, poly(ethylene glycol)‐grafted polystyrene (PEG–PS) gels, and crosslinked ethoxylate acrylate (CLEAR) gels, as used in solid‐phase peptide synthesis, were determined by the pulsed‐field‐gradient spin‐echo ¹H‐NMR method. From these experimental results, it was found that the amino acids in MPS gels, PEG–PS gels, and CLEAR gels with N,N‐dimethylformamide‐d₇ (DMF‐d₇) as a solvent had multidiffusion components within a measurement timescale of 10 ms. The D value of Boc‐Phe in polystyrene gels (1% divinylbenzene crosslinked) with tetrahydrofuran‐d₈ was much larger than that in the same gels with DMF‐d₇. Furthermore, the required time in which an amino acid transferred from a reactive site to a reactive site was estimated, within which the solvents and amino acids in the polymer supports diffused in the swollen beads.© 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 413–421, 2003     

Solubility of NiO in Al2O3

Solubility of NiO in Al₂O₃ was determined by electron probe microanalysisy A diffusion couple method was used by coupling an NiO-doped Al₂O₃ polycrystal to a pure single crystal of Al₂O₃. The solubility of NiO in Al₂O₃ in air was 230 wt ppm (157 at. ppm of cations) and 170 wt ppm (116 at. ppm) at 2073 and 1973 K, respectively. The solubility of NiO in Al₂O₃ obtained in this work was compared with our previous work of the solubility of MgO in Al₂o₃.     

Numerical analysis of coupled transport and reaction phenomena in an anode-supported flat-tube solid oxide fuel cell

Heat and mass transfer with electrochemical reaction in an anode-supported flat-tube solid oxide fuel cell (FT-SOFC) is studied by means of three-dimensional numerical simulation. The distributions of the reaction fields in the anode-supported FT-SOFC are found to be similar to those in the planar SOFC with co-flow arrangement. However, in comparison with the latter, the concentration and activation overpotentials of the former can be reduced by additional reactant diffusion through the porous rib of the fuel channel. Parametric survey reveals that, for a fixed activation overpotential model, the output voltage can be improved by increasing the pore size of anode, while the cross-sectional geometry has smaller effect on the cell performance. Based on the results of three-dimensional simulation, we also develop a simplified numerical model of anode-supported FT-SOFC, which takes into account the concentration gradients in the thick anode of complex cross-sectional geometry. The simplified model can sufficiently predict the output voltage as well as the distributions of temperature and current density with very low computational cost. Thus, it can be used as a powerful tool for surveying wide range of anode-supported FT-SOFC design parameters.     

Carbon Dioxide Sensor Mechanism of Porous Hydroxyapatite Ceramics

Hydroxyapatite and Cl⁻ -containing hydroxyapatite powders are prepared and characterized. Reversible substitution of CO^2-₃ for OH⁻ at the surface is presumed to be responsible for the sensor function. The role of Cl⁻, which is necessary to realize the sensor function and is incorporated during soaking treatment, is considered as follows. It may reduce the strain caused by the incorporation of CO^2-₃ (which is larger than OH⁻), and, hence, promote the reversible substitution reaction. This behavior is presumed because Cl⁻ -containing hydroxyapatite samples exhibit sensor characteristics typical of CO₂ without any treatment.