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Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmia.This was a 3-year follow-up study of a multicenter trial that evaluated the efficacy and safety of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed.Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow-up study. Of these, 45 cases were available for analysis after two infants were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 (range, 2.1-9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs 2.6%; P = 0.019) and the duration of fetal effusion was longer (median, 10.5 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI.This multicenter 3-year follow-up study is the first to demonstrate the long-term mortality and morbidity of infants born following protocol-defined transplacental treatment for fetal SVT and AFL. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long-term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Inflammatory processes are essential for the repair processes after myocardial infarction. Among inflammatory cells involved in this process, macrophages play a critical role through polarization in pro-inflammatory M1 or reparative M2 subtype. Pioglitazone, known as a treatment drug for diabetes mellitus, is reported to regulate macrophage polarization toward reparative M2 subtype. Poly L-lactic-co-glycolic acid (PLGA) has been widely accepted as the delivery carrier in drug delivery system (DDS). Here, we aimed to validate the therapeutic effects and investigate the mechanisms of DDS-based treatment using pioglitazone to left ventricular remodeling after myocardial infarction. Pioglitazone-incorporated PLGA microspheres (PGZ-MS) were prepared and the drug release profile was evaluated. The concentration of interleukin-10 secreted from murine bone marrow derived macrophages incubated with PGZ-MS was quantified in the culture supernatant. To validate the therapeutic potential of PGZ-MS in vivo, Sprague-Dawley rats were subjected to permanent left coronary artery ligation to induce myocardial infarction. Mock-MS (100 μg) or PGZ-MS (100 μg) was injected to the infarct region just after induction (n=9–11/group). Cardiac function and left ventricular size were assessed by echocardiography. At 28-day after surgery, rats were sacrificed, and excised hearts were evaluated histologically. PGZ-MS released 1.8±0.3% of incorporated PGZ within 24 hours and 29.5±1.2% within 14 days indicating sustained release of PGZ in vitro. PGZ-MS augmented Interleukin-10 release from bone marrow derived macrophages, indicating polarization toward reparative M2 subtype. PGZ-MS significantly ameliorated cardiac function after myocardial infarction (fractional shortening: MI vs MI+Mock-MS vs MI+PGZ-MS, 24.4±1.1 vs 24.3±1.6 vs 32.2±1.4%; P=0.0035) with reverse remodeling (wall thickness: MI vs MI+Mock-MS vs MI+PGZ-MS, 0.69±0.12 vs 0.71±0.13 vs 1.06±0.09; P=0.03). Immunohistochemical analyses revealed that PGZ-MS enhanced macrophage polarization toward reparative M2 subtype (ratio of reparative M2 macrophages: 0.39±0.03 vs 0.42±0.02 vs 0.54±0.02; P=0.0004) and attenuated apoptosis of cardiomyocytes in the ischemic border zone (MI vs MI+Mock-MS vs MI+PGZ-MS, 2.6±0.2 vs 1.9±0.2 vs 1.2±0.2 cells/field; P=0.002). In the present study, we confirmed that PGZ-MS could realize sustained release of pioglitazone which resulted in sustained effect of macrophage polarization and attenuated left ventricular remodeling accompanied with the amelioration of cardiac dysfunction and cardiomyocytes apoptosis. The strategy of DDS-based macrophage polarization might serve as a promising strategy in cardiac regenerative therapy for ischemic heart disease in the future. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan

Backgrounds Healed plaques in native coronary artery indicate the repair phenomenon of ruptured fibrous caps and erosions [1, 2, 3]. Healed plaques associated with plaque vulnerability [4]. A similar phenomenon is considered to occur in neointima after stent implantation [5]. However, there are few reports in the literature regarding neointimal vulnerability and procedure outcomes of healed tissue in neointima. Objective The aims of this study are to investigate clinical characteristics, slow flow during percutaneous coronary intervention (PCI), and neointimal vulnerability of healed neointima by optical coherence tomography (OCT). Methods We treated 67 lesions by PCI for in-stent restenosis (ISR) and conducted OCT examinations. Healed neointima was defined as neointima having one or more layers with different optical densities and a clear demarcation from underlying components. ISR with healed neointima was found in 49% (33/67) of the lesions. The angiographic slow flow was defined as a decrease of at least 1 grade in TIMI flow during PCI or final TIMI flow grade 0 and 1 or 2, with no evidence of thrombus, spasm, or dissection. Stents with a strut thickness ≥100 μm were classified as thick [6]. Results Compared to ISR without healed neointima, ISR with healed neointima showed significantly longer stent age (102±72 months vs. 31±39 months, p Conclusions ISR with healed neointima was associated with neointimal vulnerability, stent age, stent type, stent strut thickness, stent expansion, antiplatelet therapy, HDL-C and triglycerides levels, and use of ACE-I or ARB. There were no relations between with healed neointima and slow flow during PCI. Funding Acknowledgement Type of funding sources: None.

The rapid transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-driven infection signifies an ultimate challenge to global health, and the development of effective strategies for preventing and/or mitigating its effects are of the utmost importance. In the current study, an in-depth investigation for the understanding of the SARS-CoV-2 inactivation route using graphene oxide (GO) is presented. We focus on the antiviral effect of GO nanosheets on three SARS-CoV-2 strains: Wuhan, B.1.1.7 (U.K. variant), and P.1 (Brazilian variant). Plaque assay and real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that 50 and 98% of the virus in a supernatant could be cleared following incubation with GO (100 μg/mL) for 1 and 60 min, respectively. Transmission electron microscopy (TEM) analysis and protein (spike (S) and nucleocapsid (N) proteins) decomposition evaluation confirm a two-step virus inactivation mechanism that includes (i) adsorption of the positively charged spike of SARS-CoV-2 on the negatively charged GO surface and (ii) neutralization/inactivation of the SARS-CoV-2 on the surface of GO through decomposition of the viral protein. As the interaction of S protein with human angiotensin-converting enzyme 2 (ACE2) is required for SARS-CoV-2 to enter into human cells, the damage to the S protein using GO makes it a potential candidate for use in contributing to the inhibition of the worldwide spread of SARS-CoV-2. Specifically, our findings provide the potential for the construction of an effective anti-SARS-CoV-2 face mask using a GO nanosheet, which could contribute greatly to preventing the spread of the virus. In addition, as the effect of surface contamination can be severe in the spreading of SARS-CoV-2, the development of efficient anti-SARS-CoV-2 protective surfaces/coatings based on GO nanosheets could play a significant role in controlling the spread of the virus through the utilization of GO-based nonwoven cloths, filters, and so on. © 2021 American Chemical Society.

We are performing three-staged development of compact linear accelerators (hereafter linac) with S-band (2.856 GHz, wavelength 105 mm), X-band (9.3 GHz, 32.3 mm) RF (Radio frequency) and Yb fiber laser (283 THz, wavelength 1.06 mm). Recently, we have proposed S-band 40 MeV 40 kW linac for Medical RI (Radioisotope) production of 99Mo/99mTc (g-emitter), 67Cu (b+) and 225Ac (a). X-band 6 MeV linac have been made for pinpoint X-ray dynamic tracking cancer therapy. The electron beam size at the X-ray target is less than 1 mm and X-ray spot size at the cancer is less than 3 mm. Several hardware and software are under construction for dynamic tracking Radiation Therapy (RT) for moving lung cancer. Moreover, as an ultimate compact linac, we are designing and manufacturing a laser dielectric linac of ~1 MeV with Yb fiber laser. Since the wavelength is 1.06 mm, the length of one accelerating structure is tens mm and the electron beam size is ~ 1mm. We plan to use this “On-chip” linac for radiation-induced DNA damage/repair analysis since the sizes of cell and nucleus are about 10 and 1 mm, respectively. We are thinking a system where DNA in a cell nucleus is hit by ~1 mm electron- and ion-beams and observe its repair by proteins and enzymes in live cells in-situ. Finally, we try to contribute to advanced radiation biological research for theranostics (= therapeutics and diagnostics).

Patients with pulmonary arterial hypertension (PAH) can harbor mutations in several genes, most commonly in BMPR2. However, disease penetrance in patients with BMPR2 mutations is low. In addition, most patients do not carry known PAH gene mutations, suggesting that other factors determine susceptibility to PAH. To begin to identify additional genomic factors contributing to PAH pathogenesis, we exposed 32 mouse strains to chronic hypoxia. We found that the PL/J strain has extremely high right ventricular systolic pressure (RVSP; 86.58 mm Hg) but minimal lung remodeling. To identify potential genomic factors contributing to the high RVSP, RNAseq analysis of PL/J lung mRNAs and microRNAs (miRNAs) after hypoxia was performed, and it demonstrated that 4 of 43 upregulated miRNAs in the Dlk1-Dio3 imprinting region are predicted to target T cell marker mRNAs. These target mRNAs, as well as the numbers of T cells were downregulated. In addition, C5a and its receptor, C5AR1, were increased. Analysis of Rho-associated protein kinase (Rock) 2 mRNA expression, in the RhoA/Rock pathway, demonstrated a significant increase in PL/J. Inhibition of Rock2 ameliorated a portion of the elevated RVSP. In addition, we identified miR-150-5p as a potential regulator of Rock2 expression. In conclusion, we identified two possible pathways contributing to the hypoxia pulmonary hypertension phenotype of extreme RVSP elevation: aberrant T cell expression driven by hypoxia-induced miRNAs and increased expression of C5a and C5AR1. We suggest that the PL/J mouse will be a good model for seeking mechanism(s) of RVSP elevation in hypoxia-induced PAH.

Treatment of unresectable canine squamous cell carcinoma (SCC) remains challenging and new therapeutic strategies are needed. Survivin is a member of the inhibitor of apoptosis protein family and its inhibitor, YM155, is a potential anti-tumour agent. In the present study, 10 canine tumour cell lines (representing eight different tumour types) were screened for sensitivity to YM155; the drug potently inhibited the growth of the HAPPY SCC cell line. The growth inhibitory properties of YM155 were then examined in more detail using a panel of seven SCC cell lines. YM155 inhibited the growth of the cell lines HAPPY and SQ4; in contrast to the other lines in the panel, these two cell lines had high levels of expression of survivin. In HAPPY cells, YM155 inhibited expression of the survivin gene at the transcriptional level. In contrast, YM155 down-regulated survivin at the post-transcriptional level in SQ4 cells. YM155 suppressed cell growth in HAPPY cells, mostly via induction of apoptosis, but this was not the case in SQ4 cells. Two canine SCC cell lines with high cellular expression of survivin were sensitive to YM155. The possible underlying mechanisms of the cytotoxic effect of YM155 in these cell lines were different. One cell line had down-regulation of survivin mRNA and protein expression, associated with induction of apoptotic cell death. The other cell line had post-transcriptional down-regulation of survivin expression and subsequent induction of non-apoptotic cell death. Targeting survivin with YM155 is a potential approach for the treatment of canine SCCs with high expression of survivin.

Background Two false-positive tuberculosis (TB) cases in Yamagata Prefecture, Japan, 2016. Objective To report the effectiveness of comparative genomics of Mycobacterium tuberculosis for identification of cross-contamination cases. Design Case report of laboratory cross-contamination. Results Beginning with detection of an identical genotype in two M. tuberculosis strains using variable number of tandem repeat typing, we suspected M. tuberculosis cross-contamination of specimens collected in a mycobacteriology laboratory based on epidemiological investigations. This suspicion was confirmed using comparative genomics of the two M. tuberculosis strains and a strain from an epidemiologically unrelated specimen from the same batch as the two strains in the mycobacteriology laboratory. All strains had an identical genomic sequence with no single nucleotide variants. Conclusion Comparative genomics, which offers the highest discrimination power, is a potent tool for identifying laboratory cross-contamination using epidemiological investigations.

In this study the microstructure and the mechanical properties of Pb-2.5Ag-2Sn solder, the most used die attach material for power devices, were investigated. Simple lap joints with different microstructure in the solder joint layer were fabricated by changing the temperature profile of soldering process. The microstructure was significantly changed by the release of tin from inside the solder joint layer during the melting process of the solder. As the tin release continued, the microstructure tended to become finer and when the tin was depleted, the microstructure changed to coarser. Among mechanical properties of the solder joint, the fatigue life was much sensitive to changes in its microstructure; long fatigue life was obtained for the solder joint layer with Ag-Sn finely dispersed structure. These results indicate that to obtain a reliable Pb-2.5Ag-2Sn solder joint layer, it is necessary to understand growth mechanisms and design an appropriate microstructure.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

The wheat and cotton growth condition in Uzbekistan was observed using medium spatial and high temporal resolution satellite - Sentinel-2 and demonstrated potentiality of growth monitoring technique in the future. The satellite data are preprocessed and corrected by band spectral adjustment for integration of different sensor data. Through the correction improvements and operational processing technique, the satellite data have been harmonically processed and allow to capture crop growth conditions of different regions as Samarkand and Tashkent with different crop types as grain, cotton, rice and others.

Recently, a repair method by bonding patch plates is being applied to corroded steel structures. However, one of the issues of patch plate bonding repair is the brittle debonding of the patch plates. Generally, when the delamination of the patch plates occurs, the composite effect acting between the steel members and patch plates abruptly decreases. Therefore, to prevent the brittle debonding of the patch plates, a repair method combining an adhesive and stud bolts is proposed. Till date, tensile and compressive tests have been performed for the proposed method. In this study, plate bending tests were conducted to verify the effectiveness of this method under bending conditions. Furthermore, two types of epoxy resin-based adhesives were prepared to evaluate the effectiveness of the proposed method with different adhesive properties. The test results show that the proposed method is able to prevent the brittle debonding of the patch plates in the case of both epoxy resins.

Background Perceived social isolation (SI), the subjective sense of feelings of loneliness or isolation, has a negative impact on health outcomes, particularly in older adults. Although SI may also contribute to poor prognosis in patients with HF, evidence on the relationship between SI and outcomes in patients with HF is limited. Purpose The aim of this study was to investigate the relationship between SI and hospital readmission in patients with HF. Methods This study was a single center prospective cohort study. We consecutively enrolled 203 patients (mean age 72.9±11.7) who admitted for acute HF or exacerbation of chronic HF. At hospital discharge, we assessed perceived SI by using Lubben Social Network Scale - 6 (LSNS-6). Lower scores in LSNS-6 represents greater SI. Study outcome was rehospitalization for worsening HF within 180 days after discharge. We selected the optimal cutoff point of LSNS-6 that predict a worse outcome by the receiver operating characteristic (ROC) curve analysis. We investigate the association between SI and 180-days HF rehospitalization by using Cox proportional-hazard models, controlling for potential confounding factors. Results During follow up, A total of 40events (19.7%) were observed. The optimal cut-off point of LSNS-6 score was 17 points (the area under the ROC curve: 0.62, p Conclusion The present study shows that SI is a independent predictor of HF rehospitalization in patients with HF. Assessing SI in the clinical practice with a brief screening tool may help identify patients with heart failure at greater risk of rehospitalization.

Background Polypharmacy creates an increased patient's burden by drug-drug interactions and poor adherence. However, there are very few studies available evaluating the association of polypharmacy with hospital readmission in patients with heart failure (HF). Purpose The aim of this study was to investigate the impact of polypharmacy on hospital readmission for HF. Methods We enrolled 1253 patients who were hospitalized with acute heart failure (AHF) or acute exacerbation of chronic heart failure in the Kitakawachi Clinical Background and Outcome of Heart Failure Registry (KICKOFF Registry) from April 2015 to July 2018 (age 78.1±11.5 years, male 51.4%). Our Registry is a prospective multicenter community-based cohort study of HF patients in Japan. The inclusion criteria for the registry was a diagnosis of HF during hospitalization according to the Framingham criteria, and there were no exclusion criteria. From data at discharge, we collected data on clinical characteristics, medication schedule, and social backgrounds. We defined polypharmacy as the use of seven or more medications. The primary end point was HF rehospitalization within 1 year after discharge. Cox proportional hazards regression analysis was used to describe the association between polypharmacy and 1-year HF rehospitalization, controlling for potential confounding factors. Results In this study, the prevalence of polypharmacy was 59.7% of all patients. Patients with polypharmacy were more likely to have comorbidities such as hypertension, dyslipidemia, diabetes, chronic kidney disease, coronary artery disease and dementia. They also had lower EF (50.9±0.64 vs 53.6±0.80, p Conclusion Polypharmacy is an independent predictor of hospital readmission for HF. Our study suggests the need for developing an effective strategy to choose the appropriate drugs in patients with HF. Acknowledgement/Funding Nakajima Steel Pipe

Background Recent guidelines have stated that reduced left ventricular ejection fraction (LVEF) is the gold standard marker for identifying patients at risk for cardiac mortality. Although reduced LVEF identifies patients at an increased risk of cardiac arrest, sudden cardiac deaths (SCDs) occur considerably more often in patients with relatively preserved LVEF. Current guidelines on SCD risk stratification do not adequately cover this general population pool. Several noninvasive electrocardiographic (ECG) risk stratifiers that reflect depolarization abnormality, repolarization abnormality, and autonomic imbalance have been evaluated so far. With current therapeutic advances using new medicines or devices, an LVEF is often preserved in patients with structural heart disease (SHD). However, the usefulness of noninvasive ECG markers for risk stratification in such a patient population has not yet been elucidated. Purpose This study aimed to assess clinical indices and ECG markers based on 24-hour Holter ECG recordings for predicting cardiac mortality in patients with SHD who have left ventricular dysfunction (LVD) but relatively preserved LVEF. Methods In total, 1,829 patients were enrolled into the Japanese Multicenter Observational Prospective Study (JANIES study). In this study, we analyzed data of 719 patients (569 men, age 64±13 years) with SHD including mainly ischemic heart disease (65.8%). As ECG markers based on 24-hour Holter recordings, nonsustained ventricular tachycardia (NSVT), ventricular late potentials, and heart rate turbulence (HRT) were assessed. The primary endpoint was all-cause mortality, and the secondary endpoint was fatal arrhythmic events. Results During a mean follow-up of 21±11 months, all-cause mortality was eventually observed in 39 patients (5.4%). Among those patients, 32 patients (82%) suffered from cardiac causes such as heart failure and arrhythmia. Multivariate Cox regression analysis showed that after adjustment for age and LVEF, documented NSVT (hazard ratio=2.82, 95% confidence interval [CI]: 1.38–5.76, P=0.005) and abnormal HRT (hazard ratio=2.31, 95% CI: 1.15–4.65, P=0.02) were significantly associated with the primary endpoint. These two ECG markers also had significant predictive values with the secondary endpoint. The combined assessment documented NSVT and abnormal HRT improved predictive accuracy. Conclusion This study demonstrated that combined assessment of documented NSVT and abnormal HRT based on 24-hour Holter ECG recordings are recommended for predicting future serious events in SHD patients who have relatively preserved LVEF. Acknowledgement/Funding Grants-in-Aid (21590909, 24591074, and 15K09103 to T.I.) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technol

Summary The novel WBN/Kob-Leprfa (fa/fa) congenic rat strain is considered a useful rat model of type 2 diabetes mellitus (T2DM). Accumulating findings suggest that low-grade inflammation is a causative factor in T2DM and that circulating levels of inflammatory cytokines are associated with insulin resistance. However, inflammatory cytokine profiles and their correlations with T2DM development/progression in fa/fa rats have not been studied. In this study, we found that the fa/fa rats had considerably high plasma levels of interleukin (IL)-1α. Abundant cecal IL-1α mRNA expression and cecal inflammation with infiltrating IL-1α-producing macrophages was observed in fa/fa rats. Bone marrow derived macrophages from fa/fa rats expressed high levels of IL-1α upon lipopolysaccharide stimulation. Furthermore, Syphacia muris infection, which delays the onset of T2DM, reduced both plasma and cecal IL-1α levels in fa/fa rats. These results suggest that macrophage infiltration and IL-1α secretion comprise an important part of T2DM development and that S. muris infection inhibits pro-inflammatory cytokine expression in fa/fa rats.

Mild winters influenced by global warming have increased the incidence of erratic flowering (‘flowering disorder’) in Japanese pear (Pyrus pyrifolia Nakai) trees in Japan. To discover how, when and what kind of disorder/damage occur in pear flower buds, we observed axillary flower buds of two cultivars, ‘Kosui’ (a mid-chill cultivar) and ‘Niitaka’ (a high-chill cultivar), grown at five locations. We focused on the phenology from autumn 2015 to spring 2016, when temperatures were higher than for average years, especially from September to January, and large fluctuations occurred due to El Niño. During the blooming season in the spring of 2016, both the percentage of blooming flower buds and the number of florets per flower bud decreased in trees located at lower latitudes (with lower chilling accumulation) with a more severe problem in ‘Niitaka’ than in ‘Kosui’. As shown by forcing excised shoots, the onset and release of endodormancy occurred earlier in ‘Kosui’ than ‘Niitaka’ and occurred earlier in trees growing at higher latitudes than at lower latitudes (warmer regions). The freezing tolerance of flower buds, measured as the lethal temperature for 50% survival (LT50), was similar for the cultivars beginning in autumn and reached maximum levels, LT50 values of less than −12 °C, between late-December and mid-January in both cultivars, except for those in Kagoshima (the lowest latitude), where the maximum LT50 was only −5 °C throughout the season. We propose that warmer autumn–winter temperatures may prevent the acquisition of freezing tolerance, disturb endodormancy progression and disrupt floral organ development, thereby causing flowering disorder in pear trees. The risk of occurrence of flowering disorder in pear may be higher in high-chill cultivars than in low- or mid-chill cultivars and at lower latitudes compared with higher latitudes.

This study aimed to evaluate the ability of chewing gum containing sodium metaphosphate (SMP) to remove coffee stains from enamel

High precision distant frequency transfer techniques are desired to compare the advanced atomic frequency standards (AFS), which are newly developed by metrological research institutes in the world. Fiber-link frequency transfer is the technique of current highest highest accuracy, although distance of comparison is limited by fiberlink. Two-way satellite time and frequency transfer (TWSTFT) is the technique used for high precision time and frequency transfer. Its drawbacks are dependency on geographical availability of satellite and running cost including transponder of satellite, radio signal transmission license. Space geodetic techniques such as Global Navigation Satellite Systems (GNSS) and Very Long Baseline Interferometry (VLBI) observations are passive method as the next choices for time and frequency transfer. VLBI observation determines the spatial coordinates of the station and clock difference simultaneously. The analysis is theoretically based on inertial reference frame using natural radio source fixed in celestial sphere. These features have advantages of VLBI in the aspect of long term stability of comparison than the other space techniques which uses artificial signal sources. We have developed a broadband VLBI system named GALA-V [1], which is designed for advanced delay precision with observing broad observation frequency range (3-14GHz).