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Numerical simulations on ammonia/hydrogen/air detonation are performed using a detailed reaction model to investigate the cellular instability and detonation dynamics as a function of hydrogen content. The UT-LCS model that includes 32 species and 213 elementary reactions is used in the present simulations. The fifth-order target compact nonlinear scheme captured the unstable detonation dynamics and the complicated flow structure including the propagation of a sub-transverse wave. The simulation performed with different hydrogen dilutions shows that the detonation propagates at the Chapman–Jouguet velocity for all cases, and the cell size for the ammonia/hydrogen mixing ratio α = 0.3 becomes approximately 10 times larger than that for α = 1.0 (hydrogen/air mixture). A transverse detonation produces a finescale cellular structure on the computed maximum pressure history. This complex shock formation is similar to those of a spinning detonation and two-dimensional propane/oxygen detonation. The cellular irregularity increases with decreasing hydrogen content because ammonia destabilizes the detonation cellular structure with a reduced activation energy of more than approximately 8.

Although the pathophysiology of chronic obstructive pulmonary disease (COPD) is multifactorial, central airway collapse is reported to have a great impact on symptom severity. In COPD patients, positive pressure formed by hyperinflated lungs compressing the tracheal wall and negative changes in intratracheal static pressure due to rapid expiratory flow velocity at the beginning of expiration collapse the trachea. This phenomenon can be explained by fluid dynamics theory. Our hypothesis is that ventilatory strategy focusing on minimization of expiratory flow rate may be advantageous for patients receiving mechanical ventilation for COPD. If appropriate counter pressure could be applied on exhalation, patients may be able to exhale slowly with reduced expiratory flow rates which may prevent negative changes of the intratracheal static pressure. We devised a new conceptual ventilation mode \"minimized expiratory flow rate ventilation (MExV)\" which applies regulated counter pressure on exhalation. The conceptual waveforms of \"minimized expiratory flow rate ventilation\" including flow rate, volume, and airway pressure are shown, compared with typical waveforms of the conventional ventilation modes.

Interestingly, the Chapman–Jouguet detonation velocity ( $\\def \\xmlpi #1{}\\def \\mathsfbi #1{\\boldsymbol {\\mathsf {#1}}}\\let \\le =\\leqslant \\let \\leq =\\leqslant \\let \\ge =\\geqslant \\let \\geq =\\geqslant \\def \\Pr {\\mathit {Pr}}\\def \\Fr {\\mathit {Fr}}\\def \\Rey {\\mathit {Re}}D_{CJ}$ ) based on a one-dimensional and steady model compares well with the measured data. For the spinning detonation, in particular, this agreement is particularly notable, since the flow is highly three-dimensional and unsteady; perpendicular to the leading shock front, a transverse detonation wave (TDW) spins periodically. In the wake of this TDW, a secondary flow, called here the cross-current, appears which is orthogonal to the leading shock. Despite the presence of these cross-currents, the $D_{CJ}$ agreement remains remarkably satisfactory, and we investigate the reason for this, for spinning detonation in a tube. First, we focus on the origin of the cross-current. The cross-current, driven by the shock pressure, arises initially across a warped shock frontal surface, and both its sign and magnitude depend on the local slopes of the shock surface. The cross-current undergoes further pressure-driven transitions, with its magnitude eventually diminishing downstream and reducing the flow to a quasi-one-dimensional one. Second, regarding the unsteadiness, under the assumptions that the TDW spins at constant angular wave speed and the flow is steady in the frame rotating with it, the unsteady energy equation becomes integrable, resulting in the invariance of the so-called rothalpy. Also, in the integral forms of the mass and momentum balance, the unsteady terms drop out. Taken together, in the far field the governing equations are reduced to being one-dimensional and steady. From these the $D_{CJ}$ follows immediately, which appears to be the reason for the enduring usefulness of the $D_{CJ}$ . The results of the analysis are confirmed with computational fluid dynamics (CFD). Additionally, the area-averaged flow profiles are found to display more than a passing resemblance to the Zeldovitch–Von Neumann–Doering (ZND) model.

In the present work, operation characteristics of a disk-type rotating detonation engine (DRDE) with a constant chamber area were experimentally studied for various total mass flow rates and a wide variety of equivalence ratios of hydrogen–air mixtures. From the direct visualizations, the rotating detonation wave was found to propagate near the outer wall of the combustion chamber, regardless of the wave mode. For the present test conditions, single- and double-wave modes are observed, depending on the equivalence ratio of the mixture. The pressure gain was evaluated based on a one-dimensional flow model together with the chamber static pressure measured with the capillary tube average pressure technique. Although the present DRDE configuration provided a negative pressure gain for all the test conditions, it was found that the single-wave mode was superior to the double-wave mode in terms of the pressure gain.

Recent studies have demonstrated much larger variability in the total number of nephrons in normal populations than previously suspected. In addition, it has been suggested that individuals with a low nephron number may have an increased lifetime risk of hypertension or renal insufficiency, emphasizing the importance of evaluating the nephron number in each individual. In view of the fact that all previous reports of the nephron number were based on analyses of autopsy kidneys, the identification of surrogate markers detectable in living subjects is needed in order to enhance understanding of the clinical significance of this parameter. In this review, we summarize the clinicopathological factors and findings indicating a reduction in the nephron number, focusing particularly on those found at the time of a preserved renal function.

Objective A glycosylated transmembrane protein, CD147, has been implicated in regulating lymphocyte responsiveness and leukocyte recruitment. As lupus nephritis (LN) often follows a relapsing-remitting disease course, accurate understanding of the disease activity would be extremely helpful in improving prognosis. Unfortunately, neither clinical nor serological data can accurately reflect the histological features of LN. The present study investigated whether CD147 can accurately predict pathological features of LN. Methods Plasma and spot urine samples were collected from 64 patients who underwent renal biopsy between 2008 and 2011. Disease activity for LN tissues was evaluated using the biopsy activity index, and compared to levels of biomarkers including CD147. Results In LN tissues, CD147 induction was striking in injured glomeruli and infiltrating inflammatory cells, but not in damaged tubules representing atrophy. Plasma CD147 levels accurately reflected the histological disease activity. However, prediction using a single molecule would be quite difficult because of the complex pathogenesis of LN. The diagnostic accuracy of multiplex parameters indicated that the combination including plasma CD147 might yield excellent diagnostic abilities for guiding ideal LN therapy. Conclusion Plasma CD147 levels might offer useful insights into disease activity as a crucial biomarker in patients with LN.

IntroductionCoronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population.Methods and analysisThis multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse.Ethics and disseminationThe study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals.Trial registration numberjRCTs041220126.

Methods for estimating nephron number in a clinical setting may be useful for predicting renal outcomes. This study aimed to establish such a method using unenhanced computed tomography (CT) and biopsy-based stereology. Patients or living kidney donors simultaneously subjected to enhanced and unenhanced CT examinations were randomly assigned to development and validation groups. The enhanced CT-measured arterial phase and the venous phase images of kidneys were regarded as the true values for cortical volume and parenchymal volume, respectively. Linear multiple regression analysis was used to create models for estimating cortical volume using explanatory variables including unenhanced CT-measured parenchymal volume. Nephron number was determined as the product of cortical volume and the glomerular density in biopsies of donors. Five equations for estimating cortical volume were created and verified. In donors, estimated nephron number by unenhanced CT was consistent with that by enhanced CT, with minimal errors in all models (636–655 ± 210–219 vs. 648 ± 224 × 10 3 /kidney). Clinical characteristics combined with parenchymal volume did not improve the equation over parenchymal volume alone. These results support the feasibility of estimating nephron number by a combination of unenhanced CT and biopsy-based stereology, with a possible application for renal disease patients who are often not suitable for contrast media.

Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence. Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2). The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases. Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial.

Ganglioside as an endogenous growth suppressor for glomerular mesangial cells. Glomerular mesangial cells potentially secrete many growth-modulating substances that could regulate mesangial cell proliferation. To date, however, the properties of such factors have not been fully evaluated. For that purpose, conditioned medium (CM) from mesangial cells was used for cross-feeding experiments. Cell proliferation was evaluated by 3H-thymidine incorporation assay and direct cell counting. The growth-regulatory molecule was further characterized using biochemical techniques. Cross-feeding this CM to mesangial cells in vitro, despite stimulation with platelet-derived growth factor (PDGF), effectively suppressed the cells' synthesis of DNA in a dose-dependent manner. The inhibitory substance derived from mesangial cells was less than 3 kD in molecular mass, was heat stable, and was insensitive to proteinase K. After neuraminidase digestion, this inhibitory activity was lost. These data indicated that the inhibiting substance bore the typical features of gangliosides, which are multifunctional glycolipids that reside in cell membrane. Gangliosides were abundant in the CM from mesangial cells, as detected by metabolic radiolabeling and thin-layer chromatography (TLC). This result suggested that mesangial cells constitutively shed gangliosides. The growth suppressive activity in the CM was blunted when mesangial cells were pretreated with the ganglioside synthesis inhibitor d-threo-1-phenyl-2-decanoylamino-3–morpholino-1-propanol-HCl (d-threo-PDMP; 20 μmol/L) in accordance with the decreased ganglioside content in cells. Finally, gangliosides isolated from CM of mesangial cells suppressed PDGF-induced DNA synthesis of mesangial cells. These results suggest that mesangial cells constitutively shed gangliosides that then suppress the division of these cells in an autocrine-like manner.