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Coccolithophore is one type of phytoplankton that forms calcium carbonate plates called coccoliths, and is relatively diverse with about 200 species in the worldʼs oceans. Coccoliths accumulate in massive calcareous deposits on the sea floor that serve as a sedimentary buffer of ocean chemistry and are also a major long-term carbon storage that has a significant impact on the global carbon cycle and climate. Coccolithophores are also a major producer of dimethyl sulfide (DMS) that is the dominant precursor for cloud condensation nuclei in the marine atmosphere; DMS emissions decrease solar radiation due to increasing cloud cover. Coccolithophores play an important role in biogeochemical cycles in the ocean by influencing the oceanic uptake of atmospheric carbon dioxide, and producing calcium carbonate sediments and DMS. Coccolithophores often bloom on massive scales. Around the Japan archipelago, coccolithophore blooms have also been reported; a Gephyrocapsa oceanica bloom in Tokyo Bay and Sagami Bay (1995) and Hakata Bay (2004, 2007, 2008), and a Emiliania huxleyi bloom in Suruga Bay (2007). In mid-May 2020, a massive bloom of coccolithophores were observed in Sagami Bay, Japan, possibly for the first time in 25 years. The bloom was initially observed by the JAXA, GCOM-C ocean color remote sensing satellite “Shikisai” capturing a vast emerald green reflectance image in the bay. Researchers who received the report immediately conducted in situ observations, and found that coccolithophores caused the massive bloom. Coccolithophore is a common yet elusive group in the waters around Japan, and there has only been one report of a bloom observation in Sagami Bay. This study shows the characteristics of the coccolithophore bloom observed in Sagami Bay in 2020 and also reports on the marine environment during the bloom. Water temperature, salinity, nutrients, chlorophyll a, and cell density were collected from field samples. Satellite ocean color data was provided by “Shikisai”. Satellite images on May 13 and 17 in 2020 show that the bloom spread counterclockwise due to counterclockwise coastal currents in Sagami Bay. The species, Gephyrocapsa oceanica, was confirmed using light microscopy and a scanning electron microscope, and was the same species that occurred in 1995. Chlorophyll a concentration and cell density at the surface were 1.2 μg L-1 and 9.0×103 cells mL-1, respectively. NO2- and NO3-concentrations at the surface during the bloom were 0.10 μmol L-1 and 1.83 μmol L-1, respectively, which were relatively higher than previous years. The results suggest that one of the causes of coccolithophore bloom is the relatively high concentration of inorganic nitrogen. Previous studies of prokaryotic and eukaryotic community structure in the coastal areas of Sagami Bay using genetic analysis have reported occurrence of haptophytes and the occurrence of coccolithophores throughout the year. These results suggest that coccolithophores are frequently present in Sagami Bay and form massive blooms in a short time period if environmental conditions are favorable. Further investigation including culture experiments are needed to resolve the details and specific causes.

A station of AErosol RObotic NETwork Ocean Color (AERONET-OC) has been set on the Ariake Observation Tower of Saga University on April, 2018, for verification of the Second generation Global Imager (SGLI)/Global Change Observation Mission-Climate (GCOM-C). Remote sensing reflectance (Rrs) observed by the AERONET-OC was used for verification of SGLI. SGLI Version 1 data underestimated the shortwave Rrs and Rrs (380) and Rrs(412) were mostly negative, while the estimation was improved by Version 2 with the correction of Rrs(412) to be positive. It was indicated that absorptive aerosol was influenced to SGLI atmospheric correction and caused the underestimation of Rrs. Simple linear correction method to improve shortwave Rrs also worked well for specifically Version 1 data. Water constituents, chlorophyll-a (Chl-a), total suspended matter (TSM) and colored dissolved organic matter (CDOM) of the SGLI were also verified by the ship observation data. All constituents were improved from Version 1 to 2 with the correction of Rrs, although Version 2 underestimated Chl-a and CDOM. Simple regression algorithms were also examined with in situ as well as SGLI Rrs data, and it indicated that more sophisticated algorithms may be required. Time series of water constituents derived from AERONET-OC and SGLI data were compared to river discharge and spring–neap tidal cycle. The results indicated that the behavior, such as the increase of Chl-a after river discharge and interaction of Chl-a and TSM with the spring–neap tidal cycles were observed, although estimations of water constituents were not completely separated by the algorithms.

Wide-awake local anesthesia has many advantages. We describe a new method to use wide-awake local anesthesia with more flexibility. A 32-year-old man with a severe right-hand contracture after an iatrogenic tourniquet accident during an anterolateral thigh flap for a partial hand amputation underwent contracture release using external fixation after proximal row carpectomy and subsequent tenolysis. We performed most of the tenolysis procedure under general anesthesia and the final stage with an intraoperative assessment of active finger movement and dissection under local anesthesia. He regained his grip strength 2.5 years post-injury. General anesthesia is useful to treat a surgical site with extensive hard scars, whereas local anesthesia is useful for adjusting tension in an awake patient. The indication for wide-awake surgery is yet to be established; our method of combining general and local anesthesia in the tenolysis procedure illustrates the possibilities in expanding this method.

Tank-binding kinase 1 (TBK1) is a Ser/Thr kinase involved in many intracellular processes including innate immunity, cell cycle, and apoptosis. TBK1 is also important for phosphorylating autophagy adaptors critical in selective autophagic removal of damaged mitochondria (mitophagy). However, the mechanism by which TBK1 is activated by PINK1/Parkin-mediated mitophagy remains largely unknown. Here, we show that the autophagy adaptor OPTN provides a unique platform for TBK1 activation. The OPTN-ubiquitin and OPTN-autophagy machinery interaction axes facilitate assembly of the OPTN-TBK1 complex at a contact site between damaged mitochondria and the autophagosome formation site. This assembly point serves as a positive feedback loop for TBK1 activation by accelerating hetero-autophosphorylation of the protein. Furthermore, expression of monobodies engineered in this study against OPTN impaired assembly of OPTN at the contact sites as well as the subsequent activation of TBK1 and mitochondrial degradation. Taken together the findings reveal that a positive reciprocal relationship between OPTN and TBK1 initiates autophagosome biogenesis on damaged mitochondria.

Background/aim To evaluate the effectiveness and safety of nivolumab plus ipilimumab for untreated metastatic renal cell carcinoma in real-world clinical practice in Japan based on 1-year follow-up results. Patients and methods This multicentre, retrospective study analysed 45 metastatic renal cell carcinoma patients who received nivolumab plus ipilimumab between August 2018 and January 2019 in Japan. Data were extracted from patients' medical records. Subgroup analyses were performed based on baseline demographic data and treatment history. Results The objective response rate was 42.5% (complete response rate: 10.0%). The 12-month overall survival rate was 81.4% and the progression-free survival rate was 56.1%. Thirty-five patients (77.8%) showed any grade treatment-related adverse events and 17 (37.8%) showed grade ≥3 treatment-related adverse events, with no significant difference in safety between subgroups. Conclusion The effectiveness and safety of nivolumab plus ipilimumab in real-world clinical practice with 1-year follow-up were comparable with those of the CheckMate 214 trial.

We propose load noise analysis components for small core-form transformers (1 MVA–20 MVA) using computational fluid-structure coupled calculations that consider the electromagnetic force, transformer structure and fluid (oil). The proposed technique has two beneficial aspects: coil modeling using shell elements of the finite element method (FEM), and acoustic noise analysis using a combination of boundary element method transmission path simulation and FEM structural simulation. The shell element model, which includes structural bending information, is less computationally intensive for simulations than solid models because it uses larger element sizes. Lighter simulations enable easier redesign for noise reduction. Additionally, division of the simulation process into individual structural vibrations, transmission paths, and radiation processes makes it easier to find a remodeling point without performing a complete simulation. We illustrate the importance of avoiding coincidence of the natural frequencies of the coils and the electromagnetic force and present a practical noise reduction study. This technique can be implemented using a light simulation that was proposed to confirm the remodeling effects. Using the proposed analysis method along with a ray tracing method, we can construct a frontloading design simulation tool to determine the transformer specifications and the substation's geographical features.

The 13th Symposium on Polar Science/Interdisciplinary sessions [IA] Arctic research, Thu. 17 Nov.

The 13th Symposium on Polar Science/Interdisciplinary sessions [IA] Arctic research, Thu. 17 Nov.

Recently, the demand for realizing micromachining through small-diameter tools has increased. When performing microfabrication using a numerically controlled machine tool, a machining error may be introduced if the relative position of the tool tip and workpiece surface deviates during tool change. Therefore, it is critical to determine this relative position in an actual machining condition at a specific spindle speed. We are currently developing an air bearing turbine spindle with a built-in acoustic emission sensor that can detect the contact of the tool tip with the workpiece surface in real time. The acoustic emission (AE) signal generated at the tool tip can be accurately detected by placing the AE sensor in direct contact with the tool end surface inside the main shaft floated by air. In this study, we investigated the possibility of contact detection between the tool tip and the workpiece surface at the submicrometer level through the proposed spindle. The results of the performed evaluation experiments indicated that by using the spindle with a built-in acoustic emission sensor, the contact of the small-diameter tool tip with the workpiece surface could be detected with damage to the workpiece at the submicrometer level on average.

OBJECTIVE Maintaining cervical lordosis (CL) after laminoplasty is important for indirect decompression of the spinal cord. This study aimed to identify preoperative dynamic radiographic predictors for the loss of CL after laminoplasty. METHODS We retrospectively analyzed 141 consecutive patients who underwent cervical laminoplasty for cervical myelopathy. The following radiographic parameters were measured before surgery and at 1 year of follow-up: CL, C7 slope, C2-7 sagittal vertical axis (SVA), C2-7 range of motion (ROM), CL in flexion, CL in extension, ROM of flexion (Flex ROM), and ROM of extension. The CL ratio (CLR) was defined as 100 × Flex ROM/ C2-7 ROM. ΔCL was defined as postoperative CL minus preoperative CL. Patients were classified into 2 groups: group K (kyphotic change group, ΔCL ≤ -10) and group C (control group, ΔCL > -10). RESULTS The patient population comprised 94 men and 47 women (mean age, 70.9 ± 9.4 years), with 24 patients (17.0%) classified into group K. CL, C7 slope, and CLR were significantly higher in group K than in group C. The groups did not significantly differ in age, sex, C2-7 SVA, and C2-7 ROM. On multivariable analysis, the CLR was significantly associated with postoperative kyphotic changes. On receiver-operating characteristic curve analysis (area under the curve = 0.717, p < 0.001), the cutoff value for CLR was 68.9%, with sensitivity and specificity of 87.5% and 57.3%, respectively. CONCLUSION The CLR, reflecting the balance between flexion and extension mobility, was identified as a novel predictor for CL loss after laminoplasty, with a cutoff value of 68.9%.

Alien species are exposed to novel species interactions in invaded ecosystems, and predators are important components of biotic resistance against aliens. The apple snail Pomacea canaliculata (Lamarck) (Architaenioglossa: Ampullariidae) was introduced to many countries, and causes severe problems including damage to young rice plants. Biotic resistance against the apple snail is generally weak in modernized rice fields, but carrion crows Corvus corone Linnaeus (Passeriformes: Corvidae) are observed to prey on apple snails. Thus, we investigated predation on the apple snails by the crows in three locations in Japan, and compared predation pressure, prey size, and predation methods among locations and different months/years in Ehime Prefecture. Carrion crows preyed on relatively small snails among subadults and adults in paddy fields. Predation rate within 1.2 m from the levee was as high as 87.1% in Ehime, 14.1% in Fukuoka (both in 2 days), and 1.1% in Nara (in 4 days). Thus, predation by crows is considered to be effective in reducing the density of snails in paddy fields in Ehime and possibly in Fukuoka. However, the period of predation and the intensity of predation varied from year to year in Ehime over a 3-year study period.

In this multi-messenger astronomy era, all the observational probes are improving their sensitivities and overall performance. The Focusing on Relativistic universe and Cosmic Evolution (FORCE) mission, the product of a JAXA/NASA collaboration, will reach a 10 times higher sensitivity in the hard X-ray band ($E >$ 10~keV) in comparison with any previous hard X-ray missions, and provide simultaneous soft X-ray coverage. FORCE aims to be launched in the early 2030s, providing a perfect hard X-ray complement to the ESA flagship mission Athena. FORCE will be the most powerful X-ray probe for discovering obscured/hidden black holes and studying high energy particle acceleration in our Universe and will address how relativistic processes in the universe are realized and how these affect cosmic evolution. FORCE, which will operate over 1--79 keV, is equipped with two identical pairs of supermirrors and wideband X-ray imagers. The mirror and imager are connected by a high mechanical stiffness extensible optical bench with alignment monitor systems with a focal length of 12~m. A light-weight silicon mirror with multi-layer coating realizes a high angular resolution of $, 12 pages, 8 figures. Proceedings of SPIE Astronomical Telescopes and Instrumentation 2022

Strategies for one-pot peptide ligation enable chemists to access synthetic proteins at a high yield in a short time. Herein, we report a novel one-pot multi-segments ligation strategy using N-terminal thiazolidine (Thz) peptide and a newly designed formaldehyde scavenger. Among the designed 2-aminobenzamide-based aldehyde scavengers, 2-amino-5-methoxy-N',N'-dimethylbenzohydrazide (AMDBH) can remarkably convert Thz into unprotected cysteine at pH 4.0. Furthermore, AMDBH degrades Thz at a considerably low rate at pH 7.5, and thioester degradation caused by this scavenger is negligible. As a result, we have developed an efficient one-pot peptide ligation strategy by simply repetitively changing the pH with AMDBH. Finally, we synthesize mono-ubiquitinated histone H2A.Z (209 amino acids) via AMDBH-mediated one-pot four-segment peptide ligation in good yield.

Background Nivolumab plus ipilimumab combination therapy is one of the standard therapies for untreated renal cell carcinoma patients with an International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor risk. We have previously reported the 1-year analysis results of the effectiveness and safety of nivolumab plus ipilimumab combination therapy in the real-world setting in Japan. Here, we report the effectiveness of nivolumab plus ipilimumab combination therapy and of second-line therapy, using 2-year analysis. Methods This retrospective observational study enrolled Japanese patients with previously untreated metastatic renal cell carcinoma who initiated nivolumab plus ipilimumab combination therapy between August 2018 and January 2019. Data were collected from patients’ medical records at baseline and at 3 months, 1 year and 2 years after the last enrollment. Results Of the 45 patients enrolled, 10 patients (22.2%) each had non-clear cell renal cell carcinoma and Eastern Cooperative Oncology Group performance status ≥2 at baseline. Median follow-up period was 24.0 months; objective response rate was 41.5%, with 6 patients achieving complete response; median progression-free survival was 17.8 months and 24-month progression-free survival and overall survival rates were 41.6 and 59.1%, respectively. Second-line therapy achieved an objective response rate of 20%; median progression-free survival was 9.8 months. Median progression-free survival 2 was 26.4 months. Conclusions The effectiveness of nivolumab plus ipilimumab combination therapy at 2-year analysis in the real-world setting in Japan was comparable to that reported in CheckMate 214. The current analysis also demonstrated the effectiveness of second-line therapy after nivolumab plus ipilimumab combination therapy.

Upon food digestion, the gut microbiota plays a pivotal role in energy metabolism, thus affecting the development of type 2 diabetes (DM). We aimed to examine the influence of the composition of selected nutrients consumed on the association between the gut microbiota and DM. This cross-sectional study of a general population was conducted on 1019 Japanese volunteers. Compared with non-diabetic subjects, diabetic subjects had larger proportions of the genera Bifidobacterium and Streptococcus but smaller proportions of the genera Roseburia and Blautia in their gut microbiotas. The genera Streptococcus and Roseburia were positively correlated with the amounts of energy (p = 0.027) and carbohydrate and fiber (p = 0.007 and p = 0.010, respectively) consumed, respectively. In contrast, the genera Bifidobacterium and Blautia were not correlated with any of the selected nutrients consumed. Cluster analyses of these four genera revealed that the Blautia-dominant cluster was most negatively associated with DM, whereas the Bifidobacterium-dominant cluster was positively associated with DM (vs. the Blautia-dominant cluster; odds ratio 3.97, 95% confidence interval 1.68–9.35). These results indicate the possible involvement of nutrient factors in the association between the gut microbiota and DM. Furthermore, independent of nutrient factors, having a Bifidobacterium-dominant gut microbiota may be a risk factor for DM compared to having a Blautia-dominant gut microbiota in a general Japanese population.

Background: Diabetic dyslipidemia is characterized by elevated levels of triglyceride-rich lipoproteins and reduced levels of HDL-cholesterol (HDL-C) . Low levels of HDL-C are associated with an increased risk of atherosclerotic cardiovascular disease, because HDL protects against atherosclerosis through multiple mechanisms include removal of excess cholesterol from macrophages. HDL can also influence cholesterol homeostasis in pancreatic β-cell. It is noteworthy that absence of ATP-binding cassette transporter A1 (ABCA1) , which is a cellular cholesterol transporter and regulates islet cholesterol efflux, results in islet cholesterol overload and impaired insulin release in mice. We examined the associations of cholesterol efflux and insulin secretion in MIN6 cells with polyphenols that is reported to increase cholesterol efflux. Methods: Murine MIN6 cells were labeled with 3H-cholesterol and incubated with ApoA1 (μg/ml) or HDL (25 μg/ml) for 24 hours. The percentage cholesterol efflux was calculated by dividing the media-derived radioactivity by the sum of the radioactivity in the media and the cells. The effect of polyphenols on the cholesterol efflux was studied, adding that into the medium before the analysis of the cholesterol efflux. Insulin secretion was assessed by ELISA as the concentration of insulin in the culture medium. The mRNA expression of ABCA1 and ABCG1 were determined by real-time Quantitative RT-PCR. Results: Under the existence of polyphenols (isorhamnetin) , the ApoA1 or HDL-mediated cholesterol efflux had significantly increased by 1.4% or 1.8%, respectively (n=4, p Conclusion: These data suggest that isorhamnetin increases cholesterol efflux and insulin secretion in MIN6 cells. Isorhamnetin could be the interesting candidate to investigate the new treatment for patients with diabetes mellitus. Disclosure K.Matsuki: None. Y.Kimura: None. K.Matsumura: None. J.Tanabe: None. H.Murakami: None. M.Daimon: None. Funding JSPS KAKENHI Grant Number 20K11549

Objective: Equol (Eq) , a metabolite produced from soy isoflavone daidzein by intestinal bacteria, exhibits estrogen activity and may exert effects on glucose metabolism. Eq levels vary extensively depending on the capability for Eq production and amounts of daidzein consumed. We examined the relationship between Eq levels and type 2 diabetes mellitus. Research Design and Methods: Among 1,395 outpatients with diabetes at our hospital, 147 subjects (age: 70-89 years) were recruited (DM group) . Also, 147 age-/sex-matched non-DM subjects were recruited from 1,113 individuals who underwent routine health examinations (non-DM group) . As the estrogenic effect of Eq becomes apparent after menopause, the subjects were age restricted. Eq producers (EqPr) were determined based on the logarithm of the ratio of urinary Eq to the concentration of daidzein with a cut-off value of −1.75. Results: Urinary daidzein (p=0.03) and Eq concentrations (p=0.01) were significantly lower in the DM group versus the non-DM group. The proportion of EqPr differed significantly between the groups (38.8% and 53.1%, respectively; p=0.01) . However, analyses with sex-based stratification showed such difference only in women; the proportion of EqPr was 31.4% and 52.8%, respectively (p Conclusion: In postmenopausal women, EqPr were less diabetic; this status appears to be protective against DM. Eq levels increased in parallel with the amount of daidzein consumed in EqPr, but not in non-EqPr. Therefore, Eq supplements and/or enteric bacteria transplantation, rather than dietary intervention, may be effective in preventing DM in non-EqPr. Disclosure K.Hamaura: None. H.Murakami: None. A.Tamura: None. Y.Nishiya: None. S.Mizushiri: None. M.Daimon: None.

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2021-02-08, 資料番号: PA2110016000

Purpose: We report the efficacy of pre- and post-operative showering for preventing surgical site infections (SSIs) and urethrocutaneous fistula after hypospadias surgery. Materials and Methods: In 2006, standardised pre- and postoperative showering was introduced for hypospadias patients. Showering involves washing the genitals and groin 2 h preoperatively as well as immediately after the removal of a stent postoperatively. Data from 520 procedures performed on 376 hypospadias patients by a single surgeon from 1996 to 2015 were collected prospectively. The shower (S) group comprised 258 patients (372 procedures) and the nonshower group comprised 118 patients (148 procedures). Management protocols were identical for two groups. Results: Patient demographics were similar. SSIs were significantly less in the S group (0% vs. 2.0%; P < 0.05). The incidence of fistulas was lower in the S group (2.0% vs. 6.3%). The mean duration of follow-up was significantly shorter in the S group (3.6 vs. 12.8 years; P < 0.05) but longer than the mean time taken for complications to develop (0.4 years). Conclusions: Our results suggest that pre- and post-operative showering may contribute to preventing SSIs and fistulas in hypospadias patients.

The application of organometallic compounds for protein science has received attention. Recently, total chemical protein synthesis using transition metal complexes has been developed to produce various proteins bearing site-specific posttranslational modifications (PTMs). However, in general, significant amounts of metal complexes were required to achieve chemical reactions of proteins bearing a large number of nucleophilic functional groups. Moreover, syntheses of medium-size proteins (>20 kDa) were plagued by time-consuming procedures due to cumbersome purification and isolation steps, which prevented access to variously decorated proteins. Here, we report a one-pot multiple peptide ligation strategy assisted by an air-tolerant organoruthenium catalyst that showed more than 50-fold activity over previous palladium complexes, leading to rapid and quantitative deprotection on a protein with a catalytic amount (20 mol%) of the metal complex even in the presence of excess thiol moieties. Utilizing the organoruthenium catalyst, heterochromatin factors above 20 kDa, such as linker histone H1.2 and heterochromatin protein 1α (HP1α), bearing site-specific PTMs including phosphorylation, ubiquitination, citrullination, and acetylation have been synthesized. The biochemical assays using synthetic proteins revealed that the citrullination at R53 in H1.2 resulted in the reduced electrostatic interaction with DNA and the reduced binding affinity to nucleosomes. Furthermore, we identified a key phosphorylation region in HP1α to control its DNA-binding ability. The ruthenium chemistry developed here will facilitate the preparation of a variety of biologically and medically significant proteins containing PTMs and non-natural amino acids.