Reheating processes after Starobinsky inflation in old-minimal supergravity

We study reheating processes and its cosmological consequences in the Starobinsky model embedded in the old-minimal supergravity. First, we consider minimal coupling between the gravity and matter sectors in the higher curvature theory, and transform it to the equivalent standard supergravity coupled to additional matter superfields. We then discuss characteristic decay modes of the inflaton and the reheating temperature $T_{\rm R}$. Considering a simple model of supersymmetry breaking sector, we estimate gravitino abundance from inflaton decay, and obtain limits on the masses of gravitino and supersymmetry breaking field. We find $T_{\rm R}\simeq 1.0\times10^9$ GeV and the allowed range of gravitino mass as $10^4$ GeV $\lesssim m_{3/2} \lesssim 10^5$ GeV, assuming anomaly-induced decay into the gauge sector as the dominant decay channel.Comment: 24 pages, 1 figure, appendix added for clarification, typos fixed, results unchanged, version accepted in JHE

Clinically Significant Nonperfusion Areas on Widefield OCT Angiography in Diabetic Retinopathy

[Purpose] To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. [Design] Prospective, cross-sectional, observational study. [Participants] One hundred and forty-four eyes of 114 patients with diabetes. [Methods] Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. [Main Outcome Measures] The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. [Results] The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102–1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001–1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. [Conclusions] The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. [Financial Disclosure(s)] Proprietary or commercial disclosure may be found after the references

Spared nerve injury後のマウス後根神経節におけるNGFとBDNFの発現

Neuropathic pain is initiated by a primary lesion in the peripheral nervous system and spoils quality of life. Neurotrophins play important roles in the development and transmission of neuropathic pain. There are conflicting reports that the dorsal root ganglion (DRG) in an injured nerve contribute to neuropathic pain, whereas several studies have highlighted the important contribution of the DRG in a non-injured nerve. Clarifying the role of neurotrophins in neuropathic pain is problematic because we cannot distinguish injured and intact neurons in most peripheral nerve injury models. In the present study, to elicit neuropathic pain, we used the spared nerve injury (SNI) model, in which injured DRG neurons are distinguishable from intact ones, and mechanical allodynia develops in the intact sural nerve skin territory. We examined nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in the DRGs of SNI model mice. NGF and BDNF levels increased in the injured L3 DRG, while NGF decreased in the intact L5 DRG. These data offer a new point of view on the role of these neurotrophins in neuropathic pain induced by peripheral nerve injury.博士（医学）・甲第698号・平成31年3月15日© 2018 Elsevier B.V. All rights reserved

A new prognostic index for overall survival in malignant pleural mesothelioma: the rPHS (regimen, PS, histology or stage) index.

First published online: April 2, 2015[Objective] Existing prognostic indices for malignant pleural mesothelioma do not incorporate the recent advances in oncology care. The purpose of this study was to provide a prognostic index for overall survival in malignant pleural mesothelioma patients treated with chemotherapy with pemetrexed or best supportive care in the recent clinical setting. [Methods] A retrospective cohort study was performed in two hospitals in Japan (2007–13). The primary outcome was overall survival. The Cox proportional hazards model was used for multivariable analyses to identify prognostic factors. A final model was chosen based on both clinical and statistical significance. [Results] A total of 283 patients (chemotherapy: n = 228, best supportive care: n = 55) were enrolled in the study. On multivariate analysis, regimen including platinum plus pemetrexed, a performance status >0, non-epithelial histological type and Stage IV disease predicted poor overall survival in chemotherapy patients. As hazard ratios of individual risk factors were approximately similar, a prognostic index for overall survival was constructed by counting the risk factors. Median overall survival in chemotherapy patients decreased by each one-point increase in this count: 1030 days for zero; 658 days for one; 373 days for two; 327 days for three; 125 days for four. Internal validation using the bootstrapping technique showed robustness of the model (c-index, 0.677; 95% confidence interval, 0.624–0.729). Further, the discrimination was consistent in best supportive care patients (c-index, 0.799; 95% confidence interval, 0.725–0.874). [Conclusions] This novel index can provide clinicians and malignant pleural mesothelioma patients with a better framework for discussing prognosis at the time of diagnosis

Small serum protein-1 changes the susceptibility of an apoptosis-inducing metalloproteinase HV1 to a metalloproteinase inhibitor in habu snake (Trimeresurus flavoviridis)

Viperidae snakes containing various venomous proteins also have several anti-toxic proteins in their sera. However, the physiological function of serum protein has been elucidated incompletely. Small serum protein (SSP)-1 is a major component of the SSPs isolated from the serum of a Japanese viper, the habu snake (Trimeresurus flavoviridis). It exists in the blood as a binary complex with habu serum factor (HSF), a snake venom metalloproteinase inhibitor. Affinity chromatography of the venom on an SSP-1-immobilized column identified HV1, an apoptosis-inducing metalloproteinase, as the target protein of SSP-1. Biacore measurements revealed that SSP-1 was bound to HV1 with a dissociation constant of 8.2 Â 10 À8 M. However, SSP-1 did not inhibit the peptidase activity of HV1. Although HSF alone showed no inhibitory activity or binding affinity to HV1, the SSP-1HSF binary complex bound to HV1 formed a ternary complex that non-competitively inhibited the peptidase activity of HV1 with a inhibition constant of 5.1 AE 1.3 Â 10 À9 M. The SSP-1HSF complex also effectively suppressed the apoptosis of vascular endothelial cells and caspase 3 activation induced by HV1. Thus, SSP-1 is a unique protein that non-covalently attaches to HV1 and changes its susceptibility to HSF. Keywords: apoptosis/proteinase inhibitor/small serum protein/snake serum/snake venom metalloproteinase. Abbreviations: ADAM, a disintegrin and metalloproteinase; ADAMTS, ADAM with thrombospondin type-1 motif; CRISP-3, cysteine-rich secretory protein-3; Dnp, dinitrophenyl; HSF, habu serum factor; HVR, hypervariable region; K i , inhibition constant; Mca, (7-methoxycoumarin-4-yl)-acetyl; MDC, metalloproteinase/disintegrin/ cysteine-rich; MMP, matrix metalloproteinase; PSP94, prostatic secretory protein of 94 amino acids; SSP, small serum protein; SVMP, snake venom metalloproteinase; VEC, vascular endothelial cell

Investigation of cathodic reaction in SOFCs and PCFCs by using patterned thin film model electrodes

In recent years, fuel cells operating at relatively high temperatures, such as solid oxide fuel cells (SOFCs) using an oxide ion conducting electrolyte and proton ceramics fuel cells (PCFCs) using an proton conducting electrolyte, attract attentions as high-efficient energy-conversion devices. For further enhancements of the performance and the durability of SCFCs and PCFCs, it is essential to understand the electrode reactions. In particular, the knowledge on the dominant reaction path in the electrodes would help us to optimize the material and the microstructure of the electrode. Please click Additional Files below to see the full abstract

Population pharmacokinetic modeling of GS‐441524, the active metabolite of remdesivir, in Japanese COVID‐19 patients with renal dysfunction

腎障害患者におけるレムデシビルの薬物動態モデルを構築 --新型コロナウイルス感染症治療薬の適正使用に向けて--. 京都大学プレスリリース. 2021-11-25.Remdesivir, a prodrug of the nucleoside analog GS-441524, plays a key role in the treatment of coronavirus disease 2019 (COVID-19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID-19 with special characteristics. In this study, we aimed to measure serum GS-441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS-441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (Vd) of GS-441524. A one-compartment model described serum GS-441524 concentration data. The CL and Vd of GS-441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS-441524 using retrospectively obtained serum GS-441524 concentrations in Japanese patients with COVID-19, which would be helpful for optimal individualized therapy of remdesivir

Comparative Study of Subseafloor Microbial Community Structures in Deeply Buried Coral Fossils and Sediment Matrices from the Challenger Mound in the Porcupine Seabight

Subseafloor sedimentary environments harbor remarkably diverse microbial communities. However, it remains unknown if the deeply buried fossils in these sediments play ecological roles in deep microbial habitats, or whether the microbial communities inhabiting such fossils differ from those in the surrounding sediment matrix. Here we compare the community structures of subseafloor microbes in cold-water coral carbonates (Madrepora oculata and Lophelia pertusa) and the clay matrix. Samples were obtained from the Challenger Mound in the Porcupine Seabight at Site U1317 Hole A during the Integrated Ocean Drilling Program Expedition 307. DNA was extracted from coral fossils and the surrounding sedimentary matrix at 4, 20, and 105 m below the seafloor. 16S rRNA genes of Bacteria and Archaea were amplified by PCR, and a total of 213,792 16S rRNA gene-tagged sequences were analyzed. At the phylum level, dominant microbial components in both habitats consisted of Proteobacteria, Firmicutes, Nitrospirae, Chloroflexi, and Miscellaneous Crenarchaeota Group (MCG) at all three of the depths examined. However, at the genus and/or species level (similarity threshold 97.0%), the community compositions were found to be very different, with 69–75 and 46–57% of bacterial and archaeal phylotypes not overlapping in coral fossils and the clay matrix, respectively. Species richness analysis revealed that bacterial communities were generally more diverse than archaea, and that the diversity scores of coral fossils were lower than those in sediment matrix. However, the evenness of microbial communities was not significantly different in all the samples examined. No eukaryotic DNA sequences, such as 18S rRNA genes, were obtained from the corals. The findings suggested that, even at the same or similar depths, the sedimentological characteristics of a habitat are important factors affecting microbial diversity and community structure in deep subseafloor sedimentary habitats

Exploring indicators of genetic selection using the sniffer method to reduce methane emissions from Holstein cows

Objective This study aimed to evaluate whether the methane (CH4) to carbon dioxide (CO2) ratio (CH4/CO2) and methane-related traits obtained by the sniffer method can be used as indicators for genetic selection of Holstein cows with lower CH4 emissions. Methods The sniffer method was used to simultaneously measure the concentrations of CH4 and CO2 during milking in each milking box of the automatic milking system to obtain CH4/CO2. Methane-related traits, which included CH4 emissions, CH4 per energy-corrected milk, methane conversion factor (MCF), and residual CH4, were calculated. First, we investigated the impact of the model with and without body weight (BW) on the lactation stage and parity for predicting methane-related traits using a first on-farm dataset (Farm 1; 400 records for 74 Holstein cows). Second, we estimated the genetic parameters for CH4/CO2 and methane-related traits using a second on-farm dataset (Farm 2; 520 records for 182 Holstein cows). Third, we compared the repeatability and environmental effects on these traits in both farm datasets. Results The data from Farm 1 revealed that MCF can be reliably evaluated during the lactation stage and parity, even when BW is excluded from the model. Farm 2 data revealed low heritability and moderate repeatability for CH4/CO2 (0.12 and 0.46, respectively) and MCF (0.13 and 0.38, respectively). In addition, the estimated genetic correlation of milk yield with CH4/CO2 was low (0.07) and that with MCF was moderate (−0.53). The on-farm data indicated that CH4/CO2 and MCF could be evaluated consistently during the lactation stage and parity with moderate repeatability on both farms. Conclusion This study demonstrated the on-farm applicability of the sniffer method for selecting cows with low CH4 emissions