Density Functional Perturbation Theory to Predict Piezoelectric Properties

Among the various computational methods in materials science, only first-principles calculation based on the density functional theory has predictability for unknown material. Especially, density functional perturbation theory (DFPT) can effectively calculate the second derivative of the total energy with respect to the atomic displacement. By using DFPT method, we can predict piezoelectric constants, dielectric constants, elastic constants, and phonon dispersion relationship of any given crystal structure. Recently, we established the computational technique to decompose piezoelectric constants into each atomic contribution, which enable us to gain deeper insights to understand the piezoelectricity of material. Therefore, in this chapter, we will introduce the computational framework to predict piezoelectric properties of polar material by means of DFPT and details of decomposition technique of piezoelectric constants. Then, we will show some case studies to predict and discover new piezoelectric material

Effectiveness of Fluconazole for Pulmonary Aspergilloma and Its Concentration in Lung Tissue

Fluconazole was administered to two male patients aged 41 and 70 years with pulmonary aspergilloma, the diagnosis of which was based on "fungus balls" on chest X-ray films, isolation of Aspergillus from the sputum and positive serum precipitation antibody against Aspergillus. The patients received a 100 to 200 mg oral daily dose of fluconazole for six months. The fungus balls shrank and disappeared and Aspergillus culture and the serum antibody became negative. No recurrence has been observed during the two years since the end of treatment. To determine the mechanism by which fluconazole was effective in the treatment of pulmonary aspergilloma, drug levels in the blood and normal and affected lung tissues were determined in 14 patients who received surgery for lung resection. The patients generally received a 200 mg oral daily dose of fluconazole for four days prior to the surgery, during which samples of blood and healthy and affected lung tissues were collected for the determination of fluconazole levels by HPLC. The average fluconazole concentration was 8.2 μ/ml in the blood (14 patients), 9.4 μg/g in healthy lung tissue (10 patients) and 7.7 μg/g in lung lesions (12 patients). Although the results suggested that the drug was well distributed into the blood and lung tissue when administered at an oral dose of 200 mg, the drug levels obtained were found to be far below the growth inhibitory level of fluconazole against Aspergillus. Therefore, it may be essential for the future development of antifungal agents and for a better understanding of the pharmacological action of fluconazole to evaluate the mechanism by which the drug exerts its therapeutic effect on aspergilloma at below its growth inhibitory level

A Shell-less Tokamak “NOVA”

A description is given of the experimental shell-less Tokamak NOVA. This apparatus is designed to investigate the stabilization of plasmas in a shell-less Tokamak device, first by the programand the feedback-control of the vertical magnetic field, and then by controlling the radial distribution of the longitudinal plasma current, The basic concepts of design and the constructional data of the principal components are shown, together with some results of preliminary experiments

Analysis of the normal transition event of the LHD helical coils

Normal transitions and a subsequent quench were experienced with the pool-cooled helical coils of the Large Helical Device (LHD) during its excitation test. Although the initiated normal zone once started to recover, a disruptive transverse propagation followed and triggered an emergency discharging program. The cryogenic stability of the composite-type superconductor has been studied by sample experiments as well as by numerical calculations. Due to the rather long magnetic diffusion time constant in the pure Al stabilizer, transient stability of the conductor seems to play an important role for driving finite propagation of a normal zone. The cause of the final quench is also discussed from the viewpoint of cooling deterioration due to a possible accumulation of He bubble

Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathy

WSTĘP. Zbadanie wpływu inhibitora reduktazy aldozy, epalrestatu, na wczesną fazę neuropatii autonomicznej i somatycznej u chorych na cukrzycę typu 2 przez ocenę odruchu źrenicznego na światło oraz minimalnej latencji fali F. MATERIAŁ I METODY. Badanie objęło 30 chorych na cukrzycę z podkliniczną lub łagodną neuropatią cukrzycową, których losowo przydzielono do grupy kontrolnej (n = 15) lub do grupy leczonej epalrestatem (150 mg/d., n = 15). Po 24 tygodniach przeprowadzono badanie odruchu źrenicznego na światło, testy włókien autonomicznych układu sercowo-naczyniowego oraz badanie przewodzenia nerwowego. WYNIKI. Korzystny wpływ epalrestatu na odruch źreniczny na światło zaobserwowano w odniesieniu do minimalnej średnicy po bodźcu świetlnym (p = 0,044), wskaźnika zwężenia (p = 0,014) oraz maksymalnej szybkości zwężania (p = 0,008). Spośród testów autonomicznych układu sercowo-naczyniowego leczenie epalrestatem spowodowało poprawę wskaźnika najdłuższego odstępu RR podczas wydechu do najkrótszego odstępu RR w czasie wdechu obserwowanego podczas testu głębokiego oddychania (p = 0,037). Minimalna latencja fali F nerwów pośrodkowego oraz piszczelowego uległa istotnemu skróceniu w grupie chorych leczonych epalrestatem (odpowiednio p = 0,002 oraz p = 0,001); nie stwierdzono jednak istotnego wpływu na prędkość przewodzenia nerwowego w nerwach czuciowych oraz ruchowych. WNIOSKI. Powyższe obserwacje sugerują, że epalrestat może korzystnie działać we wczesnej fazie neuropatii cukrzycowej oraz że odruch źreniczny na światło i minimalna latencja fali F mogą stanowić przydatne wskaźniki neuropatii cukrzycowej.INTRODUCTION. The present study was conducted to investigate the effect of an aldose reductase inhibitor, epalrestat, on autonomic and somatic neuropathy at an early stage in type 2 diabetic patients by assessing the pupillary light reflex and minimum latency of the F-wave. MATERIAL AND METHODS. A total of 30 diabetic patients with subclinical or mild diabetic neuropathy were randomly allocated to a control group (n = 15) and epalrestat (150 mg/day) group (n = 15). After 24 weeks, the pupillary light reflex test, cardiovascular autonomic function tests, and nerve conduction study were performed. RESULTS. The beneficial effect of epalrestat on the pupillary light reflex was observed in the minimum diameter after light stimuli (P = 0.044), constriction ratio (P = 0.014), and maximum velocity of constriction (P = 0.008). Among cardiovascular autonomic nerve functions, the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing was significantly improved by epalrestat (P = 0.037). Minimum latencies of F-wave of median and tibial motor nerves were significantly shortened by epalrestat (P = 0.002 and P = 0.001, respectively); however, no significant effects were observed in motor or sensory nerve conduction velocity. CONCLUSIONS. These observations suggest that epalrestat may have therapeutic value at the early stage of diabetic neuropathy and that the pupillary light reflex and minimum latency of F-wave may be useful indicators of diabetic neuropathy

Mechanical Stimulation-Induced Calcium Signaling by Piezo1 Channel Activation in Human Odontoblast Reduces Dentin Mineralization

Odontoblasts play critical roles in dentin formation and sensory transduction following stimuli on the dentin surface. Exogenous stimuli to the dentin surface elicit dentinal sensitivity through the movement of fluids in dentinal tubules, resulting in cellular deformation. Recently, Piezo1 channels have been implicated in mechanosensitive processes, as well as Ca(2+) signals in odontoblasts. However, in human odontoblasts, the cellular responses induced by mechanical stimulation, Piezo1 channel expression, and its pharmacological properties remain unclear. In the present study, we examined functional expression of the Piezo1 channel by recording direct mechanical stimulation-induced Ca(2+) signaling in dentin matrix protein 1 (DMP-1)-, nestin-, and dentin sialophosphoprotein (DSPP)-immunopositive human odontoblasts. Mechanical stimulation of human odontoblasts transiently increased intracellular free calcium concentration ([Ca(2+)](i)). Application of repeated mechanical stimulation to human odontoblasts resulted in repeated transient [Ca(2+)](i) increases, but did not show any desensitizing effects on [Ca(2+)](i) increases. We also observed a transient [Ca(2+)](i) increase in the neighboring odontoblasts to the stimulated cells during mechanical stimulation, showing a decrease in [Ca(2+)](i) with an increasing distance from the mechanically stimulated cells. Application of Yoda1 transiently increased [Ca(2+)](i). This increase was inhibited by application of Gd(3+) and Dooku1, respectively. Mechanical stimulation-induced [Ca(2+)](i) increase was also inhibited by application of Gd(3+) or Dooku1. When Piezo1 channels in human odontoblasts were knocked down by gene silencing with short hairpin RNA (shRNA), mechanical stimulation-induced [Ca(2+)](i) responses were almost completely abolished. Piezo1 channel knockdown attenuated the number of Piezo1-immunopositive cells in the immunofluorescence analysis, while no effects were observed in Piezo2-immunopositive cells. Alizarin red staining distinctly showed that pharmacological activation of Piezo1 channels by Yoda1 significantly suppressed mineralization, and shRNA-mediated knockdown of Piezo1 also significantly enhanced mineralization. These results suggest that mechanical stimulation predominantly activates intracellular Ca(2+) signaling via Piezo1 channel opening, rather than Piezo2 channels, and the Ca(2+) signal establishes intercellular odontoblast-odontoblast communication. In addition, Piezo1 channel activation participates in the reduction of dentinogenesis. Thus, the intracellular Ca(2+) signaling pathway mediated by Piezo1 channels could contribute to cellular function in human odontoblasts in two ways: (1) generating dentinal sensitivity and (2) suppressing physiological/reactional dentinogenesis, following cellular deformation induced by hydrodynamic forces inside dentinal tubules

Mendelian Randomization on hs-CRP and eGFR

Background: Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches. Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively. Results: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval [CI], −0.019 to 0.020 and −0.003; 95% CI, −0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 0.005; 95% CI, −0.020 to 0.010 and −0.004; 95% CI, −0.020 to 0.012, respectively). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: −0.008; 95% CI, −0.058 to 0.042; IVAsian: 0.001; 95% CI, −0.036 to 0.036). Conclusion: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR

Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population

Genome-wide association studies (GWAS) have successfully identified about 70 genomic loci associated with breast cancer. Owing to the complexity of linkage disequilibrium and environmental exposures in different populations, it is essential to perform regional GWAS for better risk prediction. This study aimed to investigate the genetic architecture and to assess common genetic risk model of breast cancer with 6,669 breast cancer patients and 21,930 female controls in the Japanese population. This GWAS identified 11 genomic loci that surpass genome-wide significance threshold of P < 5.0 × 10−8 with nine previously reported loci and two novel loci that include rs9862599 on 3q13.11 (ALCAM) and rs75286142 on 21q22.12 (CLIC6-RUNX1). Validation study was carried out with 981 breast cancer cases and 1,394 controls from the Aichi Cancer Center. Pathway analyses of GWAS signals identified association of dopamine receptor medicated signaling and protein amino acid deacetylation with breast cancer. Weighted genetic risk score showed that individuals who were categorized in the highest risk group are approximately 3.7 times more likely to develop breast cancer compared to individuals in the lowest risk group. This well-powered GWAS is a representative study to identify SNPs that are associated with breast cancer in the Japanese population