The computational cost of the boundary-condition-enforced immersed boundary method (IBM) increases in the order of \(\mathcal{O}(N^2)\) as the number of Lagrangian points, \(N\), increases. This is ...due to the time-consuming calculation of the correction operator in the diffuse-interface IBM to enforce the no-slip boundary condition. In this study, a computationally efficient IBM algorithm for an extruded wall geometry is developed, and the correction operator calculation is significantly simplified while maintaining the accuracy of the solution. This method takes advantage of the geometrical symmetricity to apply several matrix simplifications, which result in a huge increase in the computational efficiency and an improved scalability of \(\mathcal{O}(max(N, N^2/r^2))\) (\(r\): the number of grid points towards the extruded direction). The boundary-condition-enforced IBM for an extruded wall geometry is applicable to the numerical simulations of the flow around a wall surface that satisfies both (a) an extruded wall geometry that retains the same cross-section geometry and (b) an Eulerian grid that is either uniform or whose stretch rate towards the extruded direction is constant. As this type of geometry is commonly studied to investigate the fundamental behavior of the fluid, the presented algorithm has wide applications. Several calculations are conducted to demonstrate the higher computational efficiency of the presented algorithm compared with that of the original algorithm. The results show improvements in computational efficiency of up to 2,800 times for the correction operator calculation and 160 times for the overall IBM calculations compared with the original algorithm while retaining the computational accuracy.
Chemotherapy-induced nausea and vomiting (CINV) can affect a patient's quality of life, leading to poor compliance with further treatments. Previous studies have provided minimal data about ...carboplatin-based regimens. Female sex is a known risk factor for CINV. The purpose of this study was to evaluate palonosetron plus single-dose dexamethasone (DEX) for preventing CINV caused by carboplatin plus paclitaxel combination therapy (TC regimen) in patients with gynecologic cancers.
Patients were recruited for this phase-II, multicenter, randomized trial from 12 hospitals in Hokkaido, Japan. Eligible patients were women with uterine cervical, endometrial or ovarian cancer scheduled to receive conventional TC regimen or dose-dense TC regimen; 116 patients were randomly assigned to receive palonosetron in combination with 1-day DEX or 3-day DEX.
During the overall period, complete response (CR) was observed in 67.9% (95% confidence interval, 53.7-80.1) of patients in the 3-day DEX arm, and 60.7% (95% confidence interval, 46.8-73.5) of patients in the 1-day DEX arm; CR was significantly lower in the 1-day DEX arm if motion sickness was already present (P = 0.0370). In the severe hyperemesis gravidarum cohort, CR in the 1-day DEX arm tended to be lower than in the 3-day DEX arm.
Combination therapy of palonosetron and 1-day DEX was effective for subjects undergoing a TC regimen for gynecologic cancers. However, the possibility of reduced efficacy of 1-day only DEX therapy in women undergoing a TC regimen could not be refuted and requires further investigation.
Generally, baking powder contains aluminum compounds (alum) as the acidic agent. However, because ingredients such as potassium aluminum sulfate (PAS) may affect the nervous system, the Codex ...Alimentarius Commission has recommended restricting its use in infants. Instead of alum, therefore, glucono-δ-lactone (GDL) has been developed for use as a substitute. The addition of PAS or GDL to batter increased the pancake volume as well as the ratio of insoluble proteins, as fractionated by Osborne’s method. The addition of hydrogen peroxide (HP) also resulted in similar effects in pancakes.
Introduction: We recently reported the results of a prospective multicenter randomised controlled trial comparing pancolonic observation using a newly developed NBI (CF-HQ290I) and panchromoendoscopy ...(PCE) for surveillance colonoscopy in UC patients. The results revealed that the NBI observation was not inferior to PCE for the detection of both neoplastic lesions (13.4% vs 9.0%; P=0.33) and colitisassociated dysplasia or cancer (CC/D) (6.3% vs 4.9%; P=0.86). Moreover, the total examination time of NBI (15.0 min) was significantly shorter than that of PCE (19.8 min) (P<0.01). This sub-analysis aimed to evaluate the relevant factors or NBI findings of the background mucosa of CC/D in the preceding Navigator Study (UMIN000013527). Methods: In total, 263 patients were randomised to the PCE group (n=130) and the NBI group (n=133). Surveillance colonoscopy in both groups was performed mainly with targeted biopsy. The pathological diagnoses were made by two expert pathologists who performed including immunohistochemical staining (p53, Ki-67) while being blinded to clinical information. Results: The median number of biopsy samples was not different between the two groups (1.80/case in NBI, 1.85/case in PCE; P=0.88). Multivariate analysis demonstrated that age (OR 1.05, 95% CI 1.02-1.08, P<0.01) and past history of CC/D (OR 4.26, 95% CI 1.29-14.05, P=0.02) were the relevant factors for the detection of neoplastic lesions, and past history of CC/D (OR 5.70, 95% CI 1.33-24.50, P=0.02) was the relevant factor for the detection of CC/D. CC/D was significantly more frequently detected than sporadic adenoma in cases in which the background mucosa had an obscure vascular pattern or scar rather than a fair view of the vascular pattern or out of range for inflammation (OR 25.0, 95% CI 3.80-164.4, P<0.01). Conclusion: In the Navigator Study, a past history of endoscopic resection or detection of dysplasia on random biopsy was the relevant factor for the detection of CC/D. The NBI findings of the background mucosa were useful in differentiating CC/D and sporadic adenoma.
l-Pipecolic acid is a key component of biologically active molecules and a pharmaceutically important chiral building block. It can be stereoselectively produced from l-lysine by a two-step ...bioconversion involving l-lysine alpha-oxidase and â.sup.1-piperideine-2-carboxylae (Pip2C) reductase. In this study, we focused on an l-lysine alpha-oxidase from Scomber japonicus that was originally identified as an apoptosis-inducing protein (AIP) and applied the enzyme to one-pot fermentation of l-pipecolic acid in Escherichia coli. A synthetic gene coding for an AIP was expressed in E. coli, and the recombinant enzyme was purified and characterized. The purified enzyme was determined to be a homodimer with a molecular mass of 133.9 kDa. The enzyme essentially exhibited the same substrate specificity as the native enzyme. Optimal temperature and pH for the enzymatic reaction were 70 °C and 7.4, respectively. The enzyme was stable below 60 °C and at a pH range of 5.5-7.5 but was markedly inhibited by Co.sup.2+. To establish a one-pot fermentation system for the synthesis of optically pure l-pipecolic acid from dl-lysine, an E. coli strain carrying a plasmid encoding AIP, Pip2C reductase from Pseudomonas putida, lysine racemase from P. putida, and glucose dehydrogenase from Bacillus subtilis was constructed. The one-pot process produced 45.1 g/L of l-pipecolic acid (87.4 % yield from dl-lysine) after a 46-h reaction with high optical purity (>99.9 % enantiomeric excess).
The discovery of a series of 6-(4-pyridyl)pyrimidin-4(3H)-ones derived from a hit compound with low molecular weight and sufficient chemical space is reported. Transformation of substituents led to ...subnanomolar potent inhibitors with in vivo tau phoshorylation lowering activity.
We established a steroidogenic human ovarian granulosa-like tumor cell
line, designated KGN, from a patient with invasive ovarian granulosa
cell carcinoma. KGN had a relatively long population ...doubling time of
about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A
steroid analysis of the cultured medium by RIA performed 5 yr after the
initiation of culture showed that KGN was able to secrete pregnenolone
and progesterone, and both dramatically increased after stimulation
with (Bu)2cAMP. However, little or no secretion of
17α-hydroxylated steroids, dehydroepiandrosterone, androstenedione,
or estradiol was observed. The aromatase activity of KGN was relatively
high and was further stimulated by (Bu)2cAMP or FSH. These
findings showed a pattern similar to that of steroidogenesis in human
granulosa cells, thus allowing analysis of naturally occurring
steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN
was also observed, which mimicked the physiological regulation of
apoptosis in normal human granulosa cells. Based on these findings,
this cell line is considered to be a very useful model for
understanding the regulation of steroidogenesis, cell growth, and
apoptosis in human granulosa cells.
Within the nuclear receptor superfamily, Nur77, Nurr1, and NOR1 constitute the nuclear receptor subfamily 4 group A. Modulation of NOR1 function would be therapeutic potential for diseases related to ...dysfunction of NOR1, including extraskeletal myxoid chondrosarcoma and autoimmune diseases. By screening arachidonate metabolites for their capacity of transcriptional activation, we have identified prostaglandin (PG) A2 as a transactivator for NOR1. PGA2 acted as a potent activator of NOR1-dependent transcription through the GAL4-based reporter system. The putative ligand-binding domain (LBD) of the receptor directly bound PGA2, and LBD-deleted receptor showed little transcriptional activation by PGA2. Primary cultured spleen cells derived from transgenic mice overexpressing NOR1, showed higher sensitivity to PGA2 compared to those from wild-type mice. These observations suggest that PGA2 can serve as a transactivator of NOR1, and thus suggest a possibility of pharmacological modulation of the NOR1 pathways by PGA2-related compounds.
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