Absorption of Horseradish Peroxidase (HRP) In Vitro Across Bovine Jejunal and Ileal Epithelia Around the Time of Weaning

Using the everted sac methodology as well as an Ussing chamber, we investigated changes in the absorption of horseradish peroxidase (EC 1.11.1.7, HRP (40 kDa)) in jejunum and ileum segments isolated from male Holstein cattle around the time of weaning (6 to 15 wks old). By the everted sac method, HRP transport (HRP concentration on the serosal side sampled after a 60-min-incubation) at 15 wks of age was significantly greater than that at 6 wks of age, in both segments of the intestine. Absorption was not significantly different between the jejunum and ileum. Addition of Na^+/K^+ ATPase inhibitor (ouabain, 1 mM) did not cause any significant change in HRP absorption, whereas Na^+/H^+ anti-transporter inhibitor (amiloride, 1μM) significantly increased the absorption in both sacs at 8 wks of age. By the Ussing chamber method, there were no significant differences between the values for Jsm and Jms, while the Jnet value was nearly zero for both epithelia. In addition, the flux (Jms) of Lucifer yellow, a cell-membrane-impermeable fluorescence dye, was significantly greater at 6 than at 13 wks of age in the ileal epithelia, although the flux was significantly greater in the jejunal than the ileal epithelia at both ages. From these findings, we conclude that: 1) bovine jejunal and ileal epithelia are able to absorb a large molecule such as the HRP protein; 2) HRP transport occurs in a concentration-dependent manner and may in part be via a paracellular pathway; 3) the increased HRP transport shown at 15 wks of age may not be caused by an increased use of the paracellular pathway.horseradish peroxidaseabsorptiontransportcal

Modeling and emergence of flapping flight of butterfly based on experimental measurements

The objective of this paper is to clarify the principle of stabilization in flapping-of-wing flight of a butterfly, which is a rhythmic and cyclic motion. For this purpose, a dynamics model of a butterfly is derived by Lagrange’s method, where the butterfly is considered as a rigid multi-body system. For the aerodynamic forces, a panel method is applied. Validity of the mathematical models is shown by an agreement of the numerical result with the measured data. Then, periodic orbits of flapping-of-wing flights are searched in order to fly the butterfly models. Almost periodic orbits are obtained, but the model in the searched flapping-of-wing flight is unstable. This research, then, studies how the wake-induced flow and the flexibly torsional wing’s effect on the flight stability. Numerical simulations demonstrate that both the wake-induced flow and the flexible torsion reduces the flight instability. Because the obtained periodic flapping-of-wing flight is unstable, a feedback control system is designed, and a stable flight is realized

Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC

Purpose: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. Patients and methods: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). Results: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with Conclusions: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870)

Reexamination of Refrigeration Power of the LHD Cryogenic System After Fire and Restart of Operation

The Large Helical Device (LHD), built in the 1990s, is a heliotron-type fusion plasma experimental device with the world\u27s first fully superconducting magnetic confinement system. The LHD cryogenic system operated stably for 18 years from 1998 to 2015 with high availability exceeding 99%. Unfortunately, in August 2015, a fire occurred in the cold box of the He refrigerator during maintenance, and nonmetallic components such as multilayer insulation films, temperature sensors, and measuring instruments were burnt down. Repair work started in November 2015 and completed at the end of July 2016. In August 2016, a test operation of the He refrigerator was conducted, and the refrigeration power was compared with that measured in the initial performance test conducted in 1995. The measured equivalent refrigeration power at 4.4 K was 9.19 kW, representing a decrease ~2% from the value of 9.38 kW measured in 1995. We attributed this slight decrease in refrigeration power to performance deterioration owing to aging over 18 years and not to the fire. The LHD restarted operation in January 2017, and its 19th operational cycle for a deuterium plasma experiment was conducted successfully up to August 2017. This paper reports the operational history and restart of the LHD superconducting magnet and cryogenic system

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

CCES Discussion Paper Series Center for Research on Contemporary Economic Systems Differential Income Taxation and Tiebout Sorting *

Abstract This study examines optimal nonlinear income taxes when individuals differ in their preference for a public good and labor productivity. We consider two regions, of which one provides a higher quality public service than the other, thus inducing individuals to "vote with their feet." In addition, the government implements a region-specific income tax schedule to reflect the difference in benefits from the public service between the regions in the tax system. We show that if two characteristics are independently distributed and the first derivative of the social welfare function is strictly convex, the marginal tax rate in the region providing the higher quality public service is lower since the participation effect is greater than the mechanical effect. Further, we numerically find that the correlation can be substantial in differentiating income tax schedules, although labor mobility weakens the differentiation of marginal tax rates on the basis of a positive correlation between the two characteristics. JEL Classification: H20, H4

Optimal human capital policies under the endogenous choice of educational types

This study examines optimal human capital policies under non-linear labor and capital income taxes in the presence of consumption value of education in a two-period setting. We show that when individuals can choose educational types differing by the relative importance of consumption value and production value, education subsidies for low-type individuals should not equal an efficient level that offsets distortions induced by non-linear taxes on labor and capital income. Our findings imply that education policy does not restore efficiency, or the Diamond-Mirrlees production efficiency theorem fails. Moreover, capital income taxation is optimal, which means that the Atkinson-Stiglitz theorem breaks down.20 p

Optimal human capital policies under the endogenous choice of educational types

Revised versionThis study examines optimal human capital policies under non-linear labor and capital income taxes in the presence of consumption value of education in a two-period setting. We show that when individuals can choose educational types differing by the relative importance of consumption value and production value, education subsidies for low-type individuals should not equal an efficient level that offsets distortions induced by non-linear taxes on labor and capital income. Our findings imply that education policy does not restore efficiency, or the Diamond-Mirrlees production efficiency theorem fails. Moreover, capital income taxation is optimal, which means that the Atkinson-Stiglitz theorem breaks down.33 p