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Dairy cattle must allocate energy to milk production and reproduction. Therefore, understanding the envi-ronmental factors that affect conception rates in nul-liparous and primiparous cows is helpful in appropriate feeding management strategies before and after calving. Accordingly, the aim of this study was to investigate the influence of environmental factors before and after the first calving on the conception rate, representing the starting point of milk production. The records of the first artificial insemination (AI) from Holstein nul-liparous cows (n = 533,672) and primiparous cows (n = 516,710) in Hokkaido, Japan, were analyzed using sepa-rate multivariable logistic regression models. The mean conception rates for nulliparous and primiparous cows from 2012 to 2018 were 55.2 and 39.2%, respectively. In both nulliparous and primiparous cows, the conception rate of crossbreeding using Japanese Black (JB) semen was significantly higher than that for purebred Holstein breeding. The conception rate using sexed semen de-creased in the warmer months only in nulliparous cows. Moreover, we grouped primiparous cows according to milk yield during peak lactation (PY; < 25, 25-30, 30-35, >= 35 kg) and the interval from calving to first insemination (CFI; < 60, 60-79, 80-99, >= 100 d), and evaluated their combined effect on the conception rate. Both PY and CFI strongly affected the conception rate in primiparous cows, which decreased with an increase in PY, even for the group with CFI >= 100 d; however, the conception rate increased for a CFI >= 60 d regard-less of PY. Taken together, this study demonstrates the long-term effect of PY and an independent effect of CFI on the conception rate of cows. These results provide guidance for management to execute appropriate AI implementation strategies before and after lactation.

A heavy rainfall event caused by mesoscale convective systems (MCSs) resulted in flooding over areas of Davao City in Mindanao Island, Philippines, on 03 May 2017. The event occurred during the summer season (April–May) under weak large-scale conditions. This study investigated the initiation and development of MCSs by performing high-resolution numerical simulations with the finest grid spacing of 200 m, using the Weather Research and Forecasting (WRF) model. It was found that the merging of two meso-$$\beta$$ β scale convective systems over the west and east of Mount Apo caused the flood-producing rainfall in the Davao area. Results show that the west meso-$$\beta$$ β scale convective system formed over the basin area in Mindanao Island due to moisture advection from sea breeze circulation. In addition, the concave geometry of the Mindanao basin assisted in accumulating moisture which made the basin favorable for convection development. Meanwhile, the precipitating downdrafts generated cold pools wherein the continuous convergence of multiple outflow boundaries resulted in the further development and maintenance of the MCS over the basin. While the east meso-$$\beta$$ β scale convective system developed over the Davao area due to the interaction between southeasterlies (ambient trade winds) and Mount Apo terrain. Merging of the MCSs resulted in the development of a larger meso-$$\beta$$ β scale system. Eventually, the larger meso-$$\beta$$ β scale convective system split and splitted MCSs weakened over time.

Mesoscale convective systems (MCSs) are organized clusters of convection that often bring in heavy to extreme rainfall, which can cause devastating effects such as flooding, landslides, and significant crop and infrastructural damages. Studies on severe weather in the Philippines, a part of the Maritime Continent where frequent and intense convective activities occur, focus predominantly on synoptic-scale systems (e.g., tropical cyclones). The characteristics of MCSs in the Philippines remain understudied. Motivated by this research gap, a long-term MCS climatology over the Philippines was constructed using the global MCS tracking database of Feng et al. (2021), and its large-scale environments are investigated to understand the formation of MCSs. Preliminary results show that large-scale flows largely affect MCS formation. MCSs occur more frequently during the peak of the Asian summer monsoon (JJA), producing large rainfall amounts over the west of the Philippines. Meanwhile, the Asian winter monsoon during DJF has a different effect on MCS formation in the Philippines as it does not directly correspond to high occurrences of MCSs. However, the convective systems during DJF still produce high rainfall amounts over the east of the Philippines. Based on these results, additional analyses for the MCSs during the boreal winter are conducted. Reference:Feng, Z., Leung, L. R., Liu, N., Wang, J., Houze Jr, R. A., Li, J., ... & Guo, J. (2021). A global high-resolution mesoscale convective system database using satellite-derived cloud tops, surface precipitation, and tracking. Journal of Geophysical Research: Atmospheres, 126(8), e2020JD034202.

The program reverse mathematics seeks to identify the minimal axioms needed to prove theorems of ordinary mathematics. In this paper, we develop the reverse mathematics of measure theory and apply these results to the reverse mathematics study of game theory. We address the technical issue of how to develop product measures in reverse mathematics, including formalizing Fubini’s thoerem. We show that weak compactness of probability measures on a compact space is equivalent to arithmetical comprehension over RCA0. The forward direction is again slightly technical. As an application of these results, we prove in ACA0 that any continuous game has a mixed Nash equilibrium.

Quantum computers have the potential to advance material design and drug discovery by performing costly electronic structure calculations. A critical aspect of this application requires optimizing the limited resources of the quantum hardware. Here, we experimentally demonstrate an end-to-end pipeline that focuses on minimizing quantum resources while maintaining accuracy. Using density matrix embedding theory as a problem decomposition technique, and an ion-trap quantum computer, we simulate a ring of 10 hydrogen atoms without freezing any electrons. The originally 20-qubit system is decomposed into 10 two-qubit problems, making it amenable to currently available hardware. Combining this decomposition with a qubit coupled cluster circuit ansatz, circuit optimization, and density matrix purification, we accurately reproduce the potential energy curve in agreement with the full configuration interaction energy in the minimal basis set. Our experimental results are an early demonstration of the potential for problem decomposition to accurately simulate large molecules on quantum hardware. Problem decomposition methods may help to overcome the size limitations of quantum hardware and allow largescale electronic structure simulations. Here, a method to simulate a ten-atom Hydrogen ring by decomposing it into smaller fragments that are amenable to a currently available trapped ion quantum computer is demonstrated experimentally.

CaMK phosphatase (CaMKP/POPX2/PPM1F) is a Ser/Thr protein phosphatase that belongs to the PPM family. Accumulating evidence suggests that CaMKP is involved in the pathogenesis of various diseases, including cancer. To clarify the relationship between CaMKP activity and human breast cancer cell motility, we examined the phosphatase activity of CaMKP in cell extracts. CaMKP activity assays of the immunoprecipitates prepared from the cell extract revealed that cells exhibiting higher motility had higher CaMKP activity, with no significant differences in the specific activity being observed. Two CaMKP-specific inhibitors, 1-amino-8-naphthol-4-sulfonic acid (ANS) and 1-amino-8-naphthol-2,4-disulfonic acid (ANDS), inhibited the migration of highly invasive MDA-MB-231 breast cancer cells without significant cytotoxicity, while an inactive analog, naphthionic acid, did not. Furthermore, the cells lost their elongated morphology and assumed a rounded shape following treatment with ANS, whereas they retained their elongated morphology following treatment with naphthionic acid. Consistent with these findings, ANS and ANDS significantly enhanced the phosphorylation level of CaMKI, a cellular substrate of CaMKP, while naphthionic acid did not. The present data suggest that CaMKP could be a novel therapeutic target for cancer metastasis.

Reducing the age at first calving (AFC) in dairy heifers may decrease replacement costs, while the acceleration of body growth could affect milk productivity. A lower bodyweight (BW) at first calving may increase calving problems and compromise the subsequent reproductive performance.This retrospective study aimed to investigate the effect of AFC and BW prior to calving on milk productivity, the incidence of calving problems (difficult calving and stillbirth) and reproductive performance during the first lactation. Multivariate analysis was conducted using a total of 203 calving records from 1999 to 2012 for one herd of Holstein heifers. The AFC was categorised as young, moderate, old and very old (22.5, 22.5 to24.0, 24.0 to25.5, ≥25.5 months) and the heifer BW before first calving was grouped into low, moderate, high and very high (≤625, 626-654, 655-683, ≥684 kg), respectively.The incidence of difficult calving and the prevalence of stillbirth were significantly higher in the animals with low BW compared with the heifers with moderate and high BW. Even so, there was no adverse impact on reproductive performance. There was a significant association between the lifetime daily milk yield and AFC; the highest mean value for yield was recorded for the heifers in the young AFC group, which was significantly different from heifers in the moderate and old age groups.In this experimental herd, a reduction in AFC could increase the profitability during the first lactation.

Background Valproic acid (VPA) is a clinically used antiepileptic drug, but it is associated with a significant risk of a low verbal intelligence quotient (IQ) score, attention-deficit hyperactivity disorder and autism spectrum disorder in children when it is administered during pregnancy. Prenatal VPA exposure has been reported to affect neurogenesis and neuronal migration and differentiation. In addition, growing evidence has shown that microglia and brain immune cells are activated by VPA treatment. However, the role of VPA-activated microglia remains unclear. Methods Pregnant female mice received sodium valproate on E11.5. A microglial activation inhibitor, minocycline or a CCR5 antagonist, maraviroc was dissolved in drinking water and administered to dams from P1 to P21. Measurement of microglial activity, evaluation of neural circuit function and expression analysis were performed on P10. Behavioral tests were performed in the order of open field test, Y-maze test, social affiliation test and marble burying test from the age of 6 weeks. Results Prenatal exposure of mice to VPA induced microglial activation and neural circuit dysfunction in the CA1 region of the hippocampus during the early postnatal periods and post-developmental defects in working memory and social interaction and repetitive behaviors. Minocycline, a microglial activation inhibitor, clearly suppressed the above effects, suggesting that microglia elicit neural dysfunction and behavioral disorders. Next-generation sequencing analysis revealed that the expression of a chemokine, C–C motif chemokine ligand 3 (CCL3), was upregulated in the hippocampi of VPA-treated mice. CCL3 expression increased in microglia during the early postnatal periods via an epigenetic mechanism. The CCR5 antagonist maraviroc significantly suppressed neural circuit dysfunction and post-developmental behavioral disorders induced by prenatal VPA exposure. Conclusion These findings suggest that microglial CCL3 might act during development to contribute to VPA-induced post-developmental behavioral abnormalities. CCR5-targeting compounds such as maraviroc might alleviate behavioral disorders when administered early.

The housing types (HST) in which dairy cows are kept and the feeding systems (FDS) used differ among farmers in Japan. Here, we investigated the genetic relationships among conception rate at first insemination (CR) and milk production traits (PROD) during the first 3 lactations of Holstein cows by using a multiple-trait model that considered the trait values of herds with different HST [tiestall (TSL) barn, freestall (FS) barn, or grazing (GZ)] and FDS as separate traits. Milk production and conception records of Holstein cows in the Hokkaido region of Japan (283,611 records for first lactation, 253,902 for second, and 181,197 for third) were analyzed. We categorized herds with TSL or FS into 2 types of FDS for cows: separate feeding (SF) of roughage plus concentrate or feeding of total mixed ration, in which roughage and concentrates were mixed before feeding. The PROD analyzed were cumulative milk, fat, and protein yields within 305 d and lactation persistency, which we defined as the difference between milk yields at 240 and 60 d in milk. We estimated the heritabilities for CR or PROD within each HST or HST × FDS group and the genetic correlations between these traits within each group or across different groups within each lactation by using a 3-HST (TSL, FS, and GZ) × 2-trait (CR and each PROD) or 2-HST (TSL and FS) × 2-FDS × 2-trait animal model. Heritability estimates for CR in GZ were higher than those in TSL or FS, and genetic correlations for CR between GZ and TSL or FS barns were weaker than those between TSL and FS barns. In addition, genetic correlations between CR and PROD in GZ were weaker than those in TSL and FS barns. In the comparison among the 4 HST × FDS except GZ, heritability estimates for CR in FS × SF were higher than those in the others, and genetic correlations for CR between FS × SF and the other systems were relatively weak. These results indicated that differences in the production system for Holstein cows influence genotypic effects in terms of the cows' ability to conceive and the genetic relationships between fertility traits and milk production traits.

Although acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever (ARF) are well-known complications of group A streptococcus infection, concomitant occurrence of both diseases is rare. We report an 11-year-old Japanese girl with primary Sjögren's syndrome complicated by acute renal failure about 2 weeks after the onset of pharyngitis. Although histopathological findings of the kidney were not confirmative, APSGN was suggested by the spontaneous recovery of her renal function, typical latent period with high levels of antistreptolysin O and low serum levels of C3 but not of C4. In addition, cardiac hypomotility and regurgitation of the 4 valves progressed in the convalescent phase of APSGN, which was accompanied by elevation of serum C-reactive protein and plasma brain natriuretic peptide (BNP) levels. Myocarditis was suggested by delayed gadolinium-enhancement of cardiac walls on cardiac magnetic resonance imaging. She was diagnosed with APSGN and ARF and was treated with a combination of short course prednisolone and prophylactic penicillin G. There is no relapse of renal or cardiac symptoms during 6 years follow-up. Unexpected elevation of plasma BNP in a convalescent stage of APSGN suggests the development of ARF. Underlying Sjögren's syndrome (SS) may modify the histopathological findings and make it difficult to differentiate APSGN from CTD-associated nephritis such as lupus nephritis (LN) even by renal biopsy.

To determine the optimal voluntary waiting period to first service after calving for maximizing the lifetime productivity of cows in a dairy herd, we simulated the changes in lifetime productivity due to increasing the number of days from calving to first service. We also assessed the effects of changes in the maximum number of services within a lactation, maximum number of calvings, and calf sale prices on lifetime productivity. We evaluated lifetime productivity as lifetime average productivity, that is, the sum of daily revenues from milk and calf sales from first calving to culling. The lifetime productivity at ≤65 days to first service was low because of the low conception rate during early lactation. In addition, lifetime productivity at ≥185 days to first service decreased as the number of days to first service increased. The number of days to first service for maximum lifetime productivity decreased as the maximum number of calvings increased. Furthermore, the decrease in lifetime productivity associated with decreasing the maximum number of services within a lactation from five to four was greater than that when the maximum number of calvings was decreased from six to five.

Prenatal and postnatal biphasic increases in plasma testosterone levels derived from perinatal testes are considered critical for defeminizing/masculinizing the brain mechanism that regulates sexual behavior in male rats. Hypothalamic kisspeptin neurons are indispensable for stimulating GnRH and downstream gonadotropin, as well as the consequent testicular testosterone production/release in adult male rats. However, it is unclear whether kisspeptin is responsible for the increase in plasma testosterone levels in perinatal male rats. The present study aimed to investigate the role of Kiss1/kisspeptin in generating perinatal plasma LH and the consequent testosterone increase in male rats by comparing the plasma testosterone and LH profiles of wild-type (Kiss1

We present our results for the kaon semileptonic form factors calculated by using two sets of the PACS10 configuration, whose physical volumes are more than (10 fm)4 at the physical light and strange quark masses in the Nf = 2+1 lattice QCD. The configurations were generated using the Iwasaki gauge action and Nf = 2 + 1 stout-smeared clover quark action. The form factors near zero momentum transfer q 2 can be calculated thanks to the large volume. Using our data, a q 2 interpolation and continuum extrapolation are carried out simultaneously. The value of |Vus | is determined using the result of the form factors at q 2 = 0 in the continuum limit. Our result of |Vus| is compared with the one determined from the CKM matrix unitarity and with those determined using recent lattice results.

We present preliminary results for the axial, scalar and tensor charges of the nucleon measured in 2+1 flavor QCD with the physical light quarks ($m_\pi=135$ MeV). Our simulations are carried out with gauge configurations generated by the PACS Collaboration with the stout-smeared $O(a)$ improved Wilson fermions and Iwasaki gauge action at a single lattice spacing of $0.085\ (\mathrm{fm})$. There are two lattice ensembles of the PACS gauge configurations, which have physical lattice sizes over $(10\ \mathrm{fm})^4$ and $(5\ \mathrm{fm})^4$, respectively. We compute the nucleon three-point correlation functions in the axial, scalar, and tensor channels. For the renormalization, we use the Rome-Southampton method as the intermediate scheme in order to evaluate the renormalization constants for the scalar and tensor currents in fully nonperturbative manner. We then evaluate the renormalized values of the scalar and tensor charges ($g_S$ and $g_T$) in the $\overline{\rm MS}$ scheme at the renormalization scale of 2 GeV with a help of the continuum perturbation theory for the matching between two schemes. We compare our preliminary results of $g_S$ and $g_T$ with those of other collaboration results., Comment: 5 pages, 5 figures, Proceedings of the 24th International Spin Symposium, October 18-22, 2021, Matsue, Japan

CaMK phosphatase (CaMKP/PPM1F/POPX2) is a Mn

application/pdf, Only a few, principal, weather stations in Japanese prefectures have the daily humidity records required to calculate the temperature–humidity index (THI) as a dairy cow heat-stress indicator. We compared three heat-stress indices: (1) THI calculated from daily average temperature and daily relative humidity at a principal weather station (PTHI); (2) daily average temperature at each herd's closest local weather station (TEMP); and (3) THI calculated from daily average temperature at each herd's closest local weather station and daily relative humidity at the principal weather station (HTHI). We used daily records from 532 provincial weather stations and test-day records of milk production from Days 6 to 305 post-first-calving in Holsteins to compare the indices as indicators of heat-stress effects on milk yield and somatic cell score (SCS). The models used the BLUPF90 package to analyze the effects of herd–year, calving age, days in milk, and PTHI, TEMP, or HTHI. We estimated each model's mean square error (MSE) and compared suitabilities among indices for each trait. TEMP heat-stress thresholds were ~18°C (milk yield) and 15–20°C (SCS). The MSE of the HTHI model was the smallest, but no significant differences were found among the indices for milk yield. © 2022 Japanese Society of Animal Science.

We present a direct calculation for the first derivative of the isovector nucleon form factors with respect to the momentum transfer ${q}^{2}$ using the lower moments of the nucleon 3-point function in the coordinate space. Our numerical simulations are performed using the ${N}_{f}=2+1$ nonperturbatively $O(a)$-improved Wilson quark action and Iwasaki gauge action near the physical point, corresponding to the pion mass ${M}_{\ensuremath{\pi}}=138\text{ }\text{ }\mathrm{MeV}$, on a $(5.5\text{ }\text{ }\mathrm{fm}{)}^{4}$ lattice at a single lattice spacing of $a=0.085\text{ }\text{ }\mathrm{fm}$. In the momentum derivative approach, we can directly evaluate the mean square radii for the electric, magnetic, and axial-vector form factors, and also the magnetic moment without the ${q}^{2}$ extrapolation to the zero momentum point. These results are compared with the ones determined by the standard method, where the ${q}^{2}$ extrapolations of the corresponding form factors are carried out by fitting models. We find that the new results from the momentum derivative method are obtained with a larger statistical error than the standard method, but with a smaller systematic error associated with the data analysis. Within the total error range of the statistical and systematic errors combined, the two results are in good agreement. On the other hand, two variations of the momentum derivative of the induced pseudoscalar form factor at the zero momentum point show some discrepancy. It seems to be caused by a finite volume effect, since a similar trend is not observed on a large volume, but seen on a small volume in our pilot calculations at a heavier pion mass of ${M}_{\ensuremath{\pi}}=510\text{ }\text{ }\mathrm{MeV}$. Furthermore, we discuss an equivalence between the momentum derivative method and the similar approach with the point splitting vector current.

Miyazaki Urological Cancer Database (MUCD) is a web-based database containing background, treatment, and prognosis of patients with prostate, renal, and urothelial cancers diagnosed in Miyazaki. We entered information on patients diagnosed with urothelial carcinoma from 2014 to 2018 at 4 of the 17 facilities that diagnose urothelial carcinoma in Miyazaki Prefecture. We analyzed the overall survival for bladder cancer and upper urinary tract cancer, and examined its correlation with the presence of symptoms, urine cytology, and clinical TNM classification. There were 487 patients with urothelial carcinoma, comprising 372 (76%) with bladder cancer and 115 (24%) with upper tract urinary cancer. In the bladder cancer group, 301 (81%) patients had symptomatic disease and 119 (32%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 248 (67%), 94 (26%), 19 (5%) and 11 (3%) patients, respectively. In the upper urinary tract cancers group, 89 (76%) had symptomatic disease and 41 (36%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 45 (39%), 37 (32%), 11 (10%) and 22 (19%) patients, respectively. The 3-year survival rates for bladder and upper urinary tract cancer were 83.4% and 67.8%, respectively. TNM classification (≤T1 vs ≥T2≥) was significantly associated with overall survival (bladder cancer : HR＝7.07, 95% CI＝3.13-16.0, p＜0.0001 ; upper tract urinary cancer : HR＝6.33, 95% CI＝2.13-18.8, p＝0.0009). The prognosis of patients with urothelial carcinoma diagnosed in multiple institutions could be evaluated using MUCD. The clinical T stage was significantly associated with overall survival in patients with bladder cancer and patients with upper urinary tract cancer.

We previously showed that the antiepileptic drug levetiracetam (LEV) inhibits microglial activation, but the mechanism remains unclear. The purpose of this study was to identify the target of LEV in microglial activity suppression. The mouse microglial BV-2 cell line, cultured in a ramified form, was pretreated with LEV and then treated with lipopolysaccharide (LPS). A comprehensive analysis of LEV targets was performed by cap analysis gene expression sequencing using BV-2 cells, indicating the transcription factors BATF, Nrf-2, FosL1 (Fra1), MAFF, and Spic as candidates. LPS increased AP-1 and Spic transcriptional activity, and LEV only suppressed AP-1 activity. FosL1, MAFF, and Spic mRNA levels were increased by LPS, and LEV only attenuated FosL1 mRNA expression, suggesting FosL1 as an LEV target. FosL1 protein levels were increased by LPS treatment and decreased by LEV pretreatment, similar to FosL1 mRNA levels. The FosL1 siRNA clearly suppressed the expression of TNFα and IL-1β. Pilocarpine-induced status epilepticus increased hippocampus FosL1 expression, along with inflammation. LEV treatment significantly suppressed FosL1 expression. Together, LEV reduces FosL1 expression and AP-1 activity in activated microglia, thereby suppressing neuroinflammation. LEV might be a candidate for the treatment of several neurological diseases involving microglial activation.

Prader-Willi syndrome (PWS) is often related to severe obesity and diabetes mellitus (DM). Clinical findings suggesting the benefits of glucagon-like peptide-1 (GLP-1) receptor agonists for glycemic control of DM in PWS have been recently increasing. However, there are only a few reports describing the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors for PWS. We present a diabetic female with PWS, whose glycemic control was deteriorated at the age of 19 but improved to a certain extent by introducing the GLP-1 analog liraglutide. At the age of 20, the SGLT2 inhibitor empagliflozin was administered. Subsequently, her HbA1c level and body weight markedly decreased. Improvement in both insulin resistance and secretion was observed during the subsequent six months. In addition to GLP-1 receptor agonists, SGLT2 inhibitors may be a potential approach for the management of DM in PWS, especially in young patients whose pancreatic insulin secretion capabilities are still preserved.

Background and Objectives: Identification of microbial community composition is very important for understanding the degradation kinetics of pollutants in water. This study was conducted to isolate and to identify the microbial communities of Kurose River water and to investigated the biodegradation kinetics of fenitrothion by identified microbial strains. Materials and Methods: Microbial community composition was investigated using differential display-denaturing gradient gel electrophoresis (DGGE). Identification of microbial isolates was carried out using 16S rRNA gene sequence analysis. Biodegradation of fenitrothion was carried out using High-performance liquid chromatography and gas chromatography-mass spectrometry analysis. Results: The results showed that the degradation of fenitrothion in Kurose River water occurred because of various bacterial isolates. Moreover, the degradation rate of fenitrothion in Kurose River water at different sampling sites depended on the microbial content and the chemical composition of the water. The bacteria isolated from the Kurose River identified as Pseudomonas putida and Flavobacterium sp. The degradation rate of fenitrothion by the isolated bacteria was lower in river water than in artificial growth media. The identified degradation products of fenitrothion were amino-fenitrothion and 3-methyl-4-nitrophenol. Conclusion: The microbial community and chemical composition of the Kurose River water significantly affect the fate and biodegradation kinetics of fenitrothion. Molecular identifications of microbial community structures of aquatic systems are very useful for interpretation of the fate and degradation kinetics of fenitrothion.

The Palaeolithic–Neolithic transition in East Asia is characterised by the transformation of mobile hunter-gatherer groups into sedentary communities. The existence of ‘ice-age’ pottery in the Japanese archipelago, however, is inconsistent with claims that directly link climatic warming with sedentism and the development of ceramics. Here, the authors reconsider the chronology and palaeoenvironment of the Maedakochi site in Tokyo. New AMS dating and environmental data suggest that intensified inland fishing in cold environments, immediately prior to the Late Glacial warm period, created conditions conducive to sedentism and the development of subsistence-related pottery.

Conception rate with the use of sexed semen is lower than that with the use of conventional semen, posing a major problem in the dairy industry. The aim of this study was to understand the risk factors that affect the conception rate after artificial insemination (AI) with conventional and sexed semen using field data. The records of the first insemination in Holstein heifers with conventional (n = 41,857) and sexed semen (n = 45,465) in Hokkaido, Japan were analyzed. The mean conception rate after Al from 2012 to 2016 was 56.9% with conventional semen and 47.3% with sexed semen. A multivariable logistic regression model including the effects of year, heifer age, time of the year, semen type, service sire, and their interactions was used to evaluate the interaction effect of heifer age and time of the year by semen type on the conception rate. In the analysis using heifer age, we found that heifers inseminated with sexed semen were approximately 21 days younger than those inseminated with conventional semen. Interestingly, in early, warmer months (Jun, Jul, and Aug), the conception rate after AI with sexed semen significantly decreased compared with that after Al with conventional semen (P < 0.01). Our results showed that more careful implementation of Al is required for a stable conception using sexed semen, particularly during warmer months.

application/pdf, We used daily records from provincial Japanese weather stations and monthly test-day records of milk production to investigate the length of the lags in the responses of cows’ milk yield and somatic cell score (SCS) to heat stress (HS). We also investigated the HS thresholds in milk yield and SCS. Data were a total of 17,245,709 test-day records for milk and SCS in Holstein cows that had calved for the first time between 2000 and 2015, along with weather records from 60 weather stations. Temperature–humidity index (THI) values were estimated by using average daily temperature and average daily relative humidity. Adjusted THI values were calculated by using temperature, relative humidity, wind speed, and solar radiation. The model contained herd, calving year, month of test day, age group, days in milk, and THI as a fixed effect. THIs for each day from 14days before the test day until the test day were used to represent the HS effects. The HS occurring 3days, and between 8 and 10days, before the test day had the greatest effect on the milk yield and SCS, respectively. The threshold THI values for the HS effect were about 60–65 for both traits. © 2019 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science

The consumption of fish now involves a risk of methylmercury (MeHg) exposure but also provides the benefit of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) such as docosahexaenoic acid (DHA). Some epidemiological studies have suggested that the intake of DHA can alleviate the neurotoxicity of MeHg, but the underlying mechanism is not known. Herein, we observed that pretreatment with 0.1–1 µM DHA suppressed MeHg-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells and mouse primary neuronal cells. These effects of DHA were canceled in the presence of the retinoid X receptor (RXR) antagonist UVI3003. An RXR agonist, bexarotene, suppressed the cytotoxicity of MeHg. DHA also suppressed the MeHg-induced production of reactive oxygen species (ROS) via an induction of antioxidant genes (catalase and SOD1). Pretreatment with DHA did not change the incorporation of MeHg. We showed previously that in the brain, the intake of DHA increased the level of 19,20-DHDP, which is the metabolite produced by cytochrome P450 and soluble epoxide hydrolase from DHA. In the present study, we observed that 19,20-DHDP also suppressed neurotoxicity from MeHg. These results indicate that DHA and its metabolites have a protective role in MeHg-induced neurotoxicity.

A new method for calculating nuclear magnetic shielding in solutions is developed based on the reference interaction site model self-consistent field (RISM-SCF) with spatial electron density distribution (SEDD). In RISM-SCF-SEDD, the electrostatic interaction between the solute and the solvent is described by considering the spread of electron to obtain more realistic electronic structure in solutions. It is thus expected to allow us to predict more quantitative chemical shifts of a wide variety of chemical species in solutions. In this study, the method is applied to a water molecule in water and is validated by examining the dependence of the solvent temperature and density on chemical shifts. The dependence of solvent species is also investigated, and more accurate results are obtained for polar solvents compared to the previous RISM-SCF study. Another application example of this method is the 15N chemical shifts of two azines in water, which is difficult to predict with the polarizable continuum model (PCM). Our results are in good agreement with the previous quantum mechanical/molecular mechanics study and experimental results. It is also shown that our method gives more realistic results for methanol and acetone than the PCM.

Quantum computers have the potential to perform accurate and efficient electronic structure calculations, enabling the simulation of properties of materials. However, today’s noisy, intermediate-scale quantum (NISQ) devices have a limited number of qubits and gate operations due to the presence of errors. Here, we propose a systematically improvable end-to-end pipeline to alleviate these limitations. Our proposed resource-efficient pipeline combines problem decomposition techniques for compact molecular representations, circuit optimization methods for compilation, solving the eigenvalue problem on advanced quantum hardware, and error-mitigation techniques in post-processing the results. Using the density matrix embedding theory for compact representation, and an ion-trap quantum computer, we simulate a ring of 10 hydrogen atoms taking into account all electrons equally and explicitly in the electronic structure calculation. In our experiment, we simulated the largest molecular system on a quantum computer within chemical accuracy with respect to total molecular energy calculated by the full CI method. Our methods reduce the number of qubits required for high-accuracy quantum simulations by an order of magnitude in the present work, enabling the simulation of larger, more industrially relevant molecules using NISQ devices. They are further systematically improvable as devices’ computational capacity continues to grow.

The 11th Symposium on Polar Science/Special session: [S] Accelerating Arctic research: Recent progress and future prospect of Arctic research, Poster presentations, Mon. 16 Nov. - Fri. 18 Dec.

Docosahexaenoic acid (DHA) has been shown to have neuroprotective effects in Parkinson's disease, but the underlying mechanism has not been fully elucidated. DHA is metabolized to DHA epoxides (EDPs) and hydroxides by cytochrome P450s (P450s), and EDPs are further hydroxylated to the corresponding diols, dihydroxydocosapentaenoic acids (DHDPs) by soluble epoxide hydrolase (sEH). In the present study, we investigated the roles of these DHA metabolites in the beneficial effects of DHA supplementation on a rotenone-induced rat model of Parkinson's disease. Metabolite analysis by LC-MS revealed that CYP2A1, 2C11, 2C13, 2C23, and 2E1 contributed to the formation of EDPs, and these P450s and sEH were expressed in the rat brain. We found that DHA supplementation in rats improved the motor dysfunction induced by rotenone. In addition, DHA reversed the decrease in tyrosine hydroxylase and the increase in lipid peroxidation generated by rotenone in the striatum. DHA supplementation also induced mRNA expression of antioxidant genes, such as sod1 and catalase, and Nrf2 protein expression in the striatum. However, these effects of DHA supplementation were eliminated by cosupplementation with the sEH inhibitor TPPU. Supplementation with DHA increased the amount of 19,20-DHDP in the rat brain, while the amount of EDPs was not significantly increased. In addition, TPPU suppressed the increase in DHDPs and increased EDPs in the brain. In PC12 cells, 19,20-DHDP increased the mRNA levels of sod1 and catalase along with Nrf2 induction. This study suggests that DHA metabolites-DHDPs generated by P450s and sEH-have an important role in improving rotenone-induced Parkinson's disease.

We used test‐day records and daily records from provincial weather stations in Japan to evaluate heat tolerance (HT) in Holstein cows according to a random regression test‐day model. Data were a total of 1,641,952 test‐day records for heritability estimates and 17,245,694 test‐day records for genetic evaluation of HT by using milk yield and somatic cell score (SCS) in Holstein cows that had calved for the first time in 2000 through 2015. Temperature–humidity index (THI) values were estimated by using average daily temperature and average daily relative humidity records from 60 provincial Japanese weather stations. The model contained herd–test‐day, with lactation curves on days in milk within month–age group as a fixed effect. General additive genetic effect and HT of additive genetic effect were included as random effects. The threshold value of THI was set to 60. For milk yield, estimated mean heritabilities were lower during heat stress (THI = 78; 0.20 and 0.28) than when below the heat stress threshold (THI ≤ 60; 0.26 and 0.31). For SCS, heritability estimates (range 0.08–0.10) were similar under all heat stress conditions. Genetic trends of HT indicated that EBVs of HT are changing in an undesirable direction.

We present the calculation of the $K_{l3}$ form factors with $N_f = 2 + 1$ nonperturbatively $O(a)$-improved Wilson quark action and Iwasaki gauge action at the physical point on a large volume of (10.9 fm)$^3$ at one lattice spacing of $a = 0.085$ fm. We extract the form factors from 3-point functions with three different time separations between the source and sink operators to confirm suppression of excited state contributions. The form factors are calculated in very close to the zero momentum transfer, $q^2 = 0$, thanks to the large volume, so that stable interpolations to $q^2 = 0$ are carried out. Using our form factors, we obtain the form factor at $q^2 = 0$, $f_+(0) = 0.9603(16)(^{+14}_{\ -4})(44)(19)(1)$, where the first, second, and fifth errors are statistical, systematic errors from fit functions and the isospin breaking effect, respectively. The third and fourth errors denote the finite lattice spacing effects estimated from the renormalization factor and contribution beyond the leading order SU(3) chiral perturbation theory (ChPT). The result of $f_+(0)$ yields the Cabibbo-Kobayashi-Maskawa (CKM) matrix element, $|V_{us}| = 0.2255(13)(4)$, where the first error comes from our calculation and the second from the experiment. This value is consistent with the ones determined from the unitarity of the CKM matrix and the $K_{l2}$ decay within one standard deviation, while it is slightly larger than recent lattice calculations by at most 1.5 $\sigma$. Furthermore, we evaluate the shape of the form factors and the phase space integral from our results. We confirm that those results are consistent with the experiment, and also $|V_{us}|$ determined with our phase space integral agrees with the one in the above.

Background/Aims: Calcineurin inhibitors (CNIs) such as cyclosporine A (CsA) and tacrolimus are immunosuppressants that are frequently used as “key drugs” in the fields of transplantation, steroid resistance, refractory nephrotic syndrome, and autoimmune disease. However, long-term CNI use causes nephrotoxicity, the features of which are arteriolar hyalinosis, tubular atrophy, striped interstitial fibrosis, and focal segmental glomerulosclerosis (FSGS). We investigated whether FSGS in CNI-induced nephrotoxicity is associated with CD44-positive glomerular parietal epithelial cells (PECs), which play a significant role in experimental and human FSGS pathogenesis. Methods: We utilized the mouse model of CsA-induced nephrotoxicity, as well as controls. Histopathological and functional data were sequentially collected from 1 to 25 weeks after CsA injection. Glomerular expression of CD44 was immunohistochemically evaluated, as were markers for glomerular podocytes and PECs. Results: Glomerular CD44 expression occurred from 2 weeks after CsA injection and gradually increased in the CsA group. CD44-positive glomerular cells showed coexpression of claudin-1 (PEC marker) but not of synaptopodin (podocyte marker). From 20 weeks after CsA injection, the cells formed a bridge between Bowman’s capsule and the capillary tuft. These features are compatible with those of activated PECs, in which increased foot process effacement leads to bridge formation, and subsequently to an increase in glomerulosclerosis and a decrease in the expression of podocyte markers from 20 weeks. Conclusion: CD44-positive (activated) PECs reflect extremely early podocyte injury in the progression of FSGS formation and may be a good marker for early detection of CNI-induced nephrotoxicity.

application/pdf, Genotype by environment interaction (G × E) effects for lactating cows’ fertility traits may differ with lactation number when accounting for herd production level. Our objective here was to investigate the genetic correlations among three fertility traits in cows and lactation persistency within and across herds with different milk-production levels by using lactation records of Japanese Holstein cows (475,446 records for first lactation, 378,540 for second, and 265,560 for third). Herds with data were categorized into three groups (LOW, MID, and HIGH) based on the average herd-year effects in each herd for 305-day milk yield at the first lactation. The fertility traits evaluated were conception rate at first insemination (CR); number of inseminations (NI); and days open (DO). Lactation persistency (PER) was defined as the difference between milk yields at 240 and 60 days in milk. Genetic parameters were estimated within each lactation by using a multiple-trait model that considered the traits of different herd milk-production groups (HPGs) as separate traits. The genetic correlations among fertility traits were estimated by using a three HPG × three-trait animal model; for those between fertility traits and PER we used a three HPG × two-trait (each fertility trait and PER) animal model. The genetic correlations among fertility traits were strong, whereas those between fertility traits and PER were weak and undesirable; most of the values did not differ significantly among HPGs or lactations. Some of the genetic correlations of CR or NI among different HPGs for the second and third lactations were lower than those for the first lactation. These findings suggest that G × E effects on a cow's ability to conceive with respect to herd production level are larger in later lactations than in the first lactation. © 2018

The majority of computational methods for predicting toxicity of chemicals are typically based on "nonmechanistic" cheminformatics solutions, relying on an arsenal of QSAR descriptors, often vaguely associated with chemical structures, and typically employing "black-box" mathematical algorithms. Nonetheless, such machine learning models, while having lower generalization capacity and interpretability, typically achieve a very high accuracy in predicting various toxicity endpoints, as unambiguously reflected by the results of the recent Tox21 competition. In the current study, we capitalize on the power of modern AI to predict Tox21 benchmark data using merely simple 2D drawings of chemicals, without employing any chemical descriptors. In particular, we have processed rather trivial 2D sketches of molecules with a supervised 2D convolutional neural network (2DConvNet) and demonstrated that the modern image recognition technology results in prediction accuracies comparable to the state-of-the-art cheminformatics tools. Furthermore, the performance of the image-based 2DConvNet model was comparatively evaluated on an external set of compounds from the Prestwick chemical library and resulted in experimental identification of significant and previously unreported antiandrogen potentials for several well-established generic drugs.

Purpose As there have been few reports on quantitative analysis of inter-institutional results for independent monitor unit (MU) verification, we performed a multi-institutional study of verification to show the feasibility of applying the 3–5% action levels used in the U.S. and Europe, and also to show the results of inter-institutional comparisons. Methods A total of 5936 fields were collected from 12 institutions. We used commercial software employing the Clarkson algorithm for verification after a validation study of measurement and software comparisons was performed. The doses generated by the treatment planning systems (TPSs) were retrospectively analyzed using the verification software. Results Mean ± two standard deviations of all locations were 1.0 ± 3.6%. There were larger differences for breast (4.0 ± 4.0%) and for lung (2.5 ± 5.8%). A total of 80% of the fields with differences over 5% of the action level involved breast and lung targets, with 7.2 ± 5.4%. Inter-institutional comparisons showed various systematic differences for field shape for breast and differences in the fields were attributable to differences in reference point placement for lung. The large differences for breast and lung are partially attributable to differences in the methods used to correct for heterogeneity. Conclusions The 5% action level may be feasible for verification; however, an understanding of larger differences in breast and lung plans is important in clinical practice. Based on the inter-institutional comparisons, care must be taken when determining an institution-specific action level from plans with different field shape settings and incorrectly placed reference points.

We have explored the effects of 20(S)-protopanaxadiol (aPPD), a naturally derived ginsenoside, against androgen receptor (AR) positive castration resistant prostate cancer (CRPC) xenograft tumors and have examined its interactions with AR. In silico docking studies for aPPD binding to AR, alongside transactivation bioassays and in vivo efficacy studies were carried out in the castration-resistant C4-2 xenograft model. Immunohistochemical (IHC) and Western blot analyses followed by evaluation of AR, apoptotic, cell cycle and proliferative markers in excised tumors was performed. The growth of established CRPC tumors was inhibited by 53% with aPPD and a corresponding decrease in serum PSA was seen compared to controls. The IHC data revealed that Ki-67 was significantly lower for aPPD treated tumors and was associated with elevated p21 and cleaved caspase-3 expression, compared to vehicle treatment. Furthermore, aPPD decreased AR protein expression in xenograft tumors, while significantly upregulating p27 and Bax protein levels. In vitro data supporting this suggests that aPPD binds to and significantly inhibits the N-terminal or the DNA binding domains of AR. The AR androgen binding site docking score for androgen (dihydrotestosterone) was −11.1, while that of aPPD was −7.1. The novel findings described herein indicate aPPD potently inhibits PCa in vivo partly via inhibition of a site on the AR N-terminal domain. This manifested as cell cycle arrest and concurrent induction of apoptosis via an increase in Bax, cleaved-caspase-3, p27 and p21 expression.

A $320\times 240$ back-illuminated (BI) time-of-flight CMOS image sensor with 10- $\mu \text{m}$ current-assisted photonic demodulator (CAPD) pixels has been developed. The BI pixel structure maximizes fill factor, allows for flexible transistor positioning, and makes the light path independent of the metal layers. The BI-CAPD pixel, which has relatively thinner substrate than that of front-illuminated CAPD, makes it possible to generate steeper electric-potential gradient in the vertical direction of the substrate, and results in 80% modulation contrast at 100-MHz modulation frequency. A higher modulation contrast contributes to suppress system power consumption as the sensor integration time for reaching specific signal-to-noise ratio is reduced. Alternatively, it contributes to improve depth accuracy when integration time is fixed.

Nanoparticle corona phases, especially those surrounding anisotropic particles, are central to determining their catalytic, molecular recognition, and interfacial properties. It remains a longstanding challenge to chemically synthesize and control such phases at the nanoparticle surface. In this work, the supramolecular chemistry of rosette nanotubes (RNTs), well-defined hierarchically self-assembled nanostructures formed from heteroaromatic bicyclic bases, is used to create molecularly precise and continuous corona phases on single-walled carbon nanotubes (SWCNTs). These RNT-SWCNT (RS) complexes exhibit the lowest solvent-exposed surface area (147.8 ± 60 m

We present results for the axial, scalar and tensor isovector-couplings (gA, gS and gT) of the nucleon obtained from 2+1 flavor QCD with the physical light quark masses (Mπ = 135 MeV). Our calculations are performed at a single lattice spacing of 0.085 fm, but with two large volumes of (10.9 fm)4 and (5.5 fm)4. The configurations are generated by the PACS Collaboration with nonperturbatively 𝒪(a) improved Wilson quark action and Iwasaki gauge action. The result of gA is a good indicator for determination of gS and gT with respect to accuracy and precision. Our result of gA well reproduces the experimental value within a statistical error of less than 2%. As for gS and gT, we compute the renormalization constants at the scale of 2 GeV in the ̅M̅S scheme through the RI/SMOM(γμ) intermediate scheme, and then obtain gS = 0.927(83)stat(22)syst and gT = 1.036(6)stat(20)syst.