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Abstract: The failure pressure of pipe with wall thinning was investigated by using three-dimensional elastic–plastic finite element analyses (FEA). With careful modeling of the pipe and flaw geometry in addition to a proper stress–strain relation of the material, FEA could estimate the precise burst pressure obtained by the tests. FEA was conducted by assuming three kinds of materials: line pipe steel, carbon steel, and stainless steel. The failure pressure obtained using line pipe steel was the lowest under the same flaw size condition, when the failure pressure was normalized by the value of unflawed pipe defined using the flow stress. On the other hand, when the failure pressure was normalized by the results of FEA obtained for unflawed pipe under various flaw and pipe configurations, the failure pressures of carbon steel and line pipe steel were almost the same and lower than that of stainless steel. This suggests that the existing assessment criteria developed for line pipe steel can be applied to make a conservative assessment of carbon steel and stainless steel. [Copyright &y& Elsevier]

Abstract: Burst tests using wall-thinned pipe of carbon steel for high-temperature use were conducted in order to examine the influence of length of wall-thinning on burst pressure. Then, three-dimensional elastic-plastic large deformation finite element analyses (EP-FEA) were performed to accurately predict the burst pressure obtained by the tests. The failure pressure corresponding to the burst pressure in tests was defined as the maximum pressure during the analysis including the instability condition after the peak of pressure. The results showed that the failure pressure obtained by EP-FEA agreed well with the experimental results. Finally, failure pressures of wall-thinned pipes with various sizes, thicknesses, flaw lengths and depths were examined by EP-FEA with the same procedure of analysis as validated in this paper. The results showed that, from the standpoint of influence of flaw length on failure pressure, it is preferable to normalize flaw length by pipe mean radius of the unflawed section R rather than by shell parameter (Rt)0.5, where t is the thickness of the unflawed section. [Copyright &y& Elsevier]

After a brain insult, ATP is released from injured cells and activates microglia. The microglia that are activated in this way then release a range of bioactive substances, one of which is tumor necrosis factor (TNF). The release of TNF appears to be dependent on the P2X[sub7] receptor. The inhibitors 1,4-diamino-2, 3-dicyano-1, 4-bis[2-amino-phenylthio] butadiene (U0126), anthra[1,9-cd] pyrazol-6(2H)-one (SP600125), and 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl) IH-imidazole (SB203580), which target MEK (mitogen- activated protein kinase kinase), INK (c-Jun N-terminal kinase), and p38, respectively, all potently suppress the production of TNF in ATP-stimulated microglia, whereas the production of TNF mRNA is strongly inhibited by U0126 and SP600125. SB203580 did not affect the increased levels of TNF mRNA but did prevent TNF mRNA from accumulating in the cytoplasm. The ATP-provoked activation of JNK and p38 [but not extracellular signal-regulated kinase (ERK)] could be inhibited by brilliant blue G, a P2X[sub7] receptor blocker, and by genistein and 4-amino-5-br(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-D]pyrimidine, which are general and src-family-specific tyrosine ki- nase inhibitors, respectively. Most important, we found that treatment of the microglia in neuron-microglia cocultures with the P2X[sub7] agonist 2'-3'-O(benzoyl-benzoyl) ATP led to significant reductions in glutamate-induced neuronal cell death, and that either TNF-α converting enzyme inhibitor or anti-TNF readily suppressed the protective effect implied by this result. Together, these findings indicate that both FRK and JNK are involved in the regulation of TNF mRNA expression, that p38 is involved in the nucleocytoplasmic transport of TNF mRNA, and that a PTK (protein tyrosine kinase), possibly a member of the src family, acts downstream of the P2X[sub7] receptor to activate INK and p38. Finally, our data suggest that P2X[sub7] receptor-activated microglia protect neurons... [ABSTRACT FROM AUTHOR]

Background Inhibiting enteropeptidase, a gut serine protease regulating protein digestion, suppresses food intake and ameliorates obesity and diabetes in mice. However, the effects of enteropeptidase inhibition on kidney parameters are largely unknown. Here, we evaluated the chronic effects of an enteropeptidase inhibitor, SCO-792, on kidney function, albuminuria and kidney pathology in spontaneously hypercholesterolaemic (SHC) rats, a rat chronic kidney disease (CKD) model. Methods SCO-792, an orally available enteropeptidase inhibitor, was administered [0.03% and 0.06% (w/w) in the diet] to 20-week-old SHC rats showing albuminuria and progressive decline in glomerular filtration rate (GFR) for five weeks. The effects of SCO-792 and the contribution of amino acids to these effects were evaluated. Results SCO-792 increased the faecal protein content, indicating that SCO-792 inhibited enteropeptidase in SHC rats. Chronic treatment with SCO-792 prevented GFR decline and suppressed albuminuria. Moreover, SCO-792 improved glomerulosclerosis and kidney fibrosis. Pair feeding with SCO-792 (0.06%) was less effective in preventing GFR decline, albuminuria and renal histological damage than SCO-792 treatment, indicating the enteropeptidase-inhibition-dependent therapeutic effects of SCO-792. SCO-792 did not affect the renal plasma flow, suggesting that its effect on GFR was mediated by an improvement in filtration fraction. Moreover, SCO-792 increased hydrogen sulphide production capacity, which has a role in tissue protection. Finally, methionine and cysteine supplementation to the diet abrogated SCO-792-induced therapeutic effects on albuminuria. Conclusions SCO-792-mediated inhibition of enteropeptidase potently prevented GFR decline, albuminuria and kidney fibrosis; hence, it may have therapeutic potential against CKD. [ABSTRACT FROM AUTHOR]

Coarse-grained molecular dynamics simulations were performed to elucidate the capillary flow process of liquid state capillary underfill (CUF), a sealing resin material. First, we ran a wettability simulation with the CUF consisting of a monomer with small and large fillers. We observed that a certain amount of the monomer spreads ahead on the substrate, while many fillers are left inside the droplet. This was confirmed by subsequent mean square deviation (MSD), which showed that the monomer had a higher MSD, 25–45 σ2, than the small and large fillers, which were 0.4–1.4 σ2 and 0.02–0.2 σ2, respectively. When one part of large fillers was replaced with small fillers, small fillers helped accelerate the wetting dynamics because they could move fast. However, when the small filler ratio was high (20%), the MSD of small fillers decreased. Next, we performed a capillary flow simulation in which the CUF flowed between parallel walls and observed that it formed a ridgeline at the upper wall edge. Small fillers contributed to a decreased flow time. However, when the small filler ratio was even higher, the flow time increased. Then, the small fillers slowed themselves down, as shown in the MSD. This is due to an increase in monomer interactions and less space to move. We also found that the bleed length decreased with an increase in the small filler ratio. This study clarified the effects of filler usage on the flow time and bleed length and contributed to new insight into the capillary actions and material design relevant to CUF. [ABSTRACT FROM AUTHOR]

Smoking during pregnancy has been shown to restrict fetal growth, depending on the duration of smoking. OBJECTIVE: To examine the relationship between timing of smoking cessation during pregnancy and anthropometric indices of newborns. METHODS: Mothers and neonates enrolled in the JECS (Japan Environment and Children's Study), a nationwide birth cohort study, were examined. Patients with full-term neonates were included in the analysis, and 73,025 mother–neonate pairs with complete data were identified. The mothers were classified into six groups according to smoking status during pregnancy (nonsmokers [Q1, n=44,198]; ex-smokers who quit before pregnancy [Q2, n=16,461]; ex-smokers who quit in the first trimester [Q3, n=8,948]; ex-smokers who quit in the second trimester [Q4, n=498]; ex-smokers who quit in the third trimester [Q5, n=651]; and smokers who smoked throughout pregnancy [Q6, n=2,269)]). Data on smoking were based on questionnaires administered in the first, second, or third trimester and 1 month after delivery. The primary outcomes were birth weight, height, and head circumference. RESULTS: Compared with nonsmokers (Q1), no adverse outcomes were observed for ex-smokers who quit before pregnancy (Q2). The mean adjusted weights of male and female neonates were 135 g and 125 g lower, respectively, in Q6 participants than in Q1 participants. Comparing Q1 and Q6 participants, height was 0.6 cm and 0.7 cm smaller for male and female neonates, respectively. Head circumference in neonates of Q6 participants was 0.3 cm and 0.3 cm smaller for male and female neonates, respectively, than that in Q1 participants. Across all three measures, smoking cessation in the first and second trimester reduced the differential in outcomes between nonsmokers and individuals who smoked throughout pregnancy. CONCLUSION: Smoking during pregnancy is associated with reduced newborn birth weight, height, and head circumference. Earlier smoking cessation during pregnancy reduces the adverse effects of smoking on fetal growth. [ABSTRACT FROM AUTHOR]

For the evaluation of novel therapeutic agents for diabetic kidney disease (DKD), it is desirable to examine their efficacy in animal models by using the glomerular filtration rate (GFR) as an index. For this purpose, animal models that demonstrate a short‐term GFR decline because of disease progression are required. Therefore, we aimed to develop such an animal model of DKD by using obese type 2 diabetic spontaneously diabetic Torii (SDT) fatty rats treated with salt loading by drinking water containing sodium chloride with or without unilateral nephrectomy. As a result, we have found that 0.3% salt loading with unilateral nephrectomy or 0.8% salt loading alone caused a rapid GFR decline, hypertension and rapid development of tubulointerstitial fibrosis. Moreover, the addition of losartan to a mixed diet suppressed the GFR decline in SDT fatty rats treated with 0.3% salt loading with unilateral nephrectomy. These results suggest that the model of SDT fatty rats treated with 0.3% salt loading and unilateral nephrectomy could be used as a hypertensive DKD model for evaluating therapeutic agents based on suppression of GFR decline. [ABSTRACT FROM AUTHOR]

Maladaptive proximal tubule (PT) repair has been implicated in kidney fibrosis through induction of cell-cycle arrest at G2/M. We explored the relative importance of the PT DNA damage response (DDR) in kidney fibrosis by genetically inactivating ataxia telangiectasia and Rad3-related (ATR), which is a sensor and upstream initiator of the DDR. In human chronic kidney disease, ATR expression inversely correlates with DNA damage. ATR was upregulated in approximately 70% of Lotus tetragonolobus lectin-positive (LTL+) PT cells in cisplatin-exposed human kidney organoids. Inhibition of ATR resulted in greater PT cell injury in organoids and cultured PT cells. PT-specific Atr-knockout (ATRRPTC-/-) mice exhibited greater kidney function impairment, DNA damage, and fibrosis than did WT mice in response to kidney injury induced by either cisplatin, bilateral ischemia-reperfusion, or unilateral ureteral obstruction. ATRRPTC-/- mice had more cells in the G2/M phase after injury than did WT mice after similar treatments. In conclusion, PT ATR activation is a key component of the DDR, which confers a protective effect mitigating the maladaptive repair and consequent fibrosis that follow kidney injury. [ABSTRACT FROM AUTHOR]

Recent studies show that some human malaria parasite species Plasmodium falciparum and P.vivax parasitize erythroblasts; however, the biological and clinical significance of this is unclear. To investigate further, we generated a rodent malaria parasite (P. yoelii 17XNL) expressing GFP-ovalbumin (OVA). Its infectivity to erythroblasts was confirmed and parasitized erythroblasts were capable of initiating malaria infections. Experiments showed that MHC class I molecules were highly expressed on parasitized erythroblasts. As CD8+ T cells recognize MHC class I and peptide complexes on target cells and are involved in protection or pathology against malaria, we examined whether erythroblasts are targeted by CD8+ T cells. Purified non-parasitized erythroblasts pulsed with OVA peptides were recognized by OVA-specific CD8+ T cells. Crucially, parasitized erythroblasts isolated from GFP-OVA-, but not GFP- infected-mice, activated OT-I CD8+ T cells, indicating that CD8+ T cells recognize parasitized erythroblasts in an antigen-specific manner. [ABSTRACT FROM AUTHOR]

Abstract: The oxygen-depolarized cathode has become attractive by reducing energy consumption and also CO2 emissions. The initial gas-diffusion electrode was for a three-compartment cell in which the alkaline electrolyte was separated from the oxygen feeder. During the electrolysis, the electrolyte penetrated into the hydrophobic gas-diffusion layer. Thus the pores in the diffusion layer were flooded with the electrolyte and the performance decreased. We proposed a new gas-diffusion electrode (GDE) having a large pore radius for a two-compartment cell in which the GDE was pressed on the membrane, and the electrolyte was transported through the GDE. The previous electrode was used for a three-compartment cell, which contained the anolyte, catholyte and oxygen-feeder compartments. First, a model analysis was made to simulate the cathodic overpotential curves of the GDE''s for the two-compartment and three-compartment cells. Experiments were made using a half cell for the cathodic polarization curve and a zero-gap cell for testing the increased durability. The two-compartment cell with Ag–CC (carbon cloth) had the highest performance among the GDE''s. However, the decrease in performance during a longer period, such as 600 days, was considered to be due to catalyst aggregation and not flooding the pores based on the cathodic potential curve and the SEM images. [Copyright &y& Elsevier]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]