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A long-term high-fat diet (HFD) causes obesity and changes in renal lipid metabolism and lysosomal dysfunction in mice, causing renal damage. Sodium-glucose co-transporter inhibitors, including phlorizin, exert nephroprotective effects in patients with chronic kidney disease, but the underlying mechanism remains unclear. A HFD or standard diet was fed to adult C57BL/6J male mice, and phlorizin was administered. Lamellar body components of the proximal tubular epithelial cells (PTECs) were investigated. After phlorizin administration in HFD-fed mice, sphingomyelin and ceramide in urine and tissues were assessed and label-free quantitative proteomics was performed using kidney tissue samples. Mitochondrial elongation by fusion was effective in the PTECs of HFD-fed obese mice under phlorizin administration, and many lamellar bodies were found in the apical portion of the S2 segment of the proximal tubule. Phlorizin functioned as a diuretic, releasing lamellar bodies from the apical membrane of PTECs and clearing the obstruction in nephrons. The main component of the lamellar bodies was sphingomyelin. On the first day of phlorizin administration in HFD-fed obese mice, the diuretic effect was increased, and more sphingomyelin was excreted through urine than in vehicle-treated mice. The expressions of three peroxisomal β-oxidation proteins involved in fatty acid metabolism were downregulated after phlorizin administration in the kidneys of HFD-fed mice. Fatty acid elongation protein levels increased with phlorizin administration, indicating an increase in long-chain fatty acids. Lamellar bodies accumulated in the proximal renal tubule of the S2 segment of the HFD-fed mice, indicating that the urinary excretion of lamellar bodies has nephroprotective effects. [ABSTRACT FROM AUTHOR]

Transonic and supersonic flutter characteristics of a delta wing configuration with external stores were computationally simulated, and the aerodynamic influence of the stores on the flutter characteristics was investigated. Delta wings with one and two external stores were considered. Unsteady aerodynamics of the wing with external stores were evaluated using Navier-Stokes equations, and equations of motion based on a modal approach were applied to the structural dynamics. These equations were coupled using a subiteration approach. The computational results showed that the flutter dynamic pressures were reduced for a wide range of Maeb numbers when the external stores were attached. The flutter dynamic pressures also decreased as the number of external stores increased. In the case of one external store, the aerodynamic influence of the store could be divided into two regions according to the Mach number. It was found that neglecting the aerodynamic influence of the store led to an overestimation of the flutter dynamic pressures in the supersonic flow region. In the ease of two external stores, the aerodynamic influence of the stores on the flutter boundary appeared only at one supersonic Mach number, unlike the ease of one external store. Additional flutter analysis using a different store size and unsteady aerodynamic analysis with forced oscillations indicated that the interference position of the shock wave generated ahead of the external store on the lower surface was a key factor in determining the flutter boundary, and the shock wave oscillation may have acted as a negative damping on the wing motion.

This study numerically investigates the effects of stratified temperature distributions on the end-gas combustion mode in a constant volume reactor. The initial temperature in the reactor was globally stratified with linear gradients. The effects of negative temperature coefficient (NTC) characteristics are addressed through a comparison between the results of a non-NTC fuel and an NTC fuel. The compressible Navier–Stokes equations are solved with detailed chemistry. The results show that the addition of large temperature gradients such as −10 or −5 K/cm can prevent the pressure wave development associated with end-gas autoignition, and the knocking intensity is significantly reduced. In contrast, small temperature gradients such as −1 K/cm lead to the generation of the developing detonation mode and thus to large knocking intensities. In the NTC fuel case, the knocking intensity becomes relatively large because the spatial gradient of the ignition delay time decreases even with the addition of large temperature gradients, especially in the NTC regime. Based on all the results, a correlation is presented between the initial temperature and the reaction front speed (the spatial gradient of the ignition delay time) for the prediction of end-gas combustion mode. The correlation suggests that the possibility of preventing large knocking intensities by temperature gradients is reduced under high-pressure conditions because of the increase in the reaction front speed. Consequently, this study suggests that very large temperature gradients would be required under high-pressure conditions to prevent large knocking intensities under the concept of thermal stratification. [ABSTRACT FROM AUTHOR]

The present study proposes a localized thickened flame (LTF) model for the accurate prediction of flame propagation and autoignition timing. The unresolved-scale terms appeared in spatially-filtered governing equations due to thin flame structures are constructed under a physical constraint in which laminar flame speed is maintained. A high-order derivative is introduced to dynamically localize the effects of the LTF in the regions of unresolved propagating flame. The model is also designed such that the thickened flame is resolved by the same number of grid points for any grid size used. Therefore, a user-specified constant in the model does not need to be adjusted depending on the employed grid size. Laminar flame propagation problems are used to validate the performance of the proposed LTF model and determine the appropriate value of the user-specified constant. The results using a one-dimensional constant-volume reactor demonstrate that the LTF successfully captures the accurate flame propagation behaviors under elevated pressure conditions, while not affecting the end-gas autoignition timing, even on relatively coarse grid resolutions. The high-order derivative in the LTF serves as a dynamic parameter for detecting the thinning flame under elevated pressure conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Niemann-Pick type C (NPC) is a lysosomal lipid storage disease with mutation of NPC1/NPC2 genes, which transport lipids in the endosome and lysosome, and various neurological symptoms. NPC patients also develop hepatosplenomegaly or liver disorder in the neonatal period, and 10% suffer severe liver failure. Neonatal hemochromatosis (NH) is a liver disorder characterized by hepatic and extrahepatic siderosis. Although the etiology of NH is unclear, recent reports suggest that the gestational alloimmune mechanism is the cause of NH. Herein, we report a Japanese NPC patient initially diagnosed as NH. Case report A 5-day-old boy was transferred to our hospital with severe cholestatic liver failure. Congenital infections and metabolic screening were negative, and NH was suspected. However intra and extrahepatic siderosis were not found. As his liver deteriorated rapidly, liver transplantation was performed at 19 days old. The explanted liver showed cirrhosis, and strong C5b-9 complex staining of hepatocytes, so NH was diagnosed. From the age of one and a half years, he developed regression, vertical supranuclear gaze palsy and cataplexy. Fibroblast filipin staining was strong, blood oxysterol was high, and there were compound heterozygous mutations in NPC1 ,p.[(F288L)];[(K1206N)]. The patient was then diagnosed as NPC and started on miglustat. Conclusion Neonatal liver failure was initially diagnosed as NH. Later, the patient developed various neurological symptoms characteristic of NPC. Neurological follow-up of children who develop NH is required. [ABSTRACT FROM AUTHOR]

Background: Acute encephalopathy (AE) is defined by the Japanese guidelines as the acute disturbance of consciousness (Glasgow coma scale [GCS] score ≤11) that persists for >24 h. We have often encountered, however, cases of prolonged mild disturbance of consciousness (PMDC) with GCS score >11, meaning that they do not fit the guideline definition of AE. The reports of these cases have been relatively sparse, and the nosological position, prognosis, and other characteristics remain unknown. To clarify the characteristics of PMDC we compared cases of PMDC with cases of AE. Methods: This study was a retrospective observational study at a tertiary children's hospital in Japan. We studied children with a diagnosis of AE or PMDC between January 2011 and August 2016. Results: Thirteen cases of PMDC and 19 cases of AE were identified during the study period. PMDC patients more frequently had hyponatremia (P < 0.01), paradoxical arousal response on electroencephalogram (P = 0.010), normal computed tomography (CT; P = 0.025), and normal magnetic resonance imaging (MRI; P < 0.01) than the AE patients. Sequelae were more frequently observed in AE than in PMDC patients (P = 0.011). Conclusions: PMDC has different characteristics to AE with regard to hyponatremia, paradoxical arousal response, CT or MRI findings, and prognosis. Despite the differences, PMDC might also be regarded as being a milder member of the wide variety of AE and related diseases. [ABSTRACT FROM AUTHOR]