A Framework for a Large-Scale Machine Tool With Long Coarse Linear Axes Under Closed-Loop Volumetric Error Compensation

A large-scale machine tool is typically very inefficient in size, cost, and energy consumption. Some large parts only have a set of machining features, each of which is within a small local region, and their location should meet position and orientation tolerances. In such a machining application, as a more cost- and energy-effective alternative, this paper presents the concept of a “portable” machine tool, where a small machining platform, with the capability to machine each local machining feature in the required accuracy, is moved by long coarse linear axes. The coarse axes only perform the point-to-point positioning to each machining feature and fixed by servo control during the machining. They do not have sufficient positioning repeatability. To ensure the position/orientation accuracy of each machining feature without having highly repeatable coarse axes, this paper proposes the application of a tracking interferometer to measure all the error motions of coarse axes, and then to perform their compensation. This can be seen as a closed-loop feedback control for coarse axes using the tracking interferometer in the loop. The proposed concept is demonstrated by the experiments with its prototype using a six-degrees of freedom robot moved by two coarse linear axes

Inhibitory Effects of Ecklonia cava Extract on High Glucose-Induced Hepatic Stellate Cell Activation

Nonalcoholic steatohepatitis (NASH) is a disease closely associated with obesity and diabetes. A prevalence of type 2 diabetes and a high body mass index in cryptogenic cirrhosis may imply that obesity leads to cirrhosis. Here, we examined the effects of an extract of Ecklonia cava, a brown algae, on the activation of high glucose-induced hepatic stellate cells (HSCs), key players in hepatic fibrosis. Isolated HSCs were incubated with or without a high glucose concentration. Ecklonia cava extract (ECE) was added to the culture simultaneously with the high glucose. Treatment with high glucose stimulated expression of type I collagen and α-smooth muscle actin, which are markers of activation in HSCs, in a dose-dependent manner. The activation of high glucose-treated HSCs was suppressed by the ECE. An increase in the formation of intracellular reactive oxygen species (ROS) and a decrease in intracellular glutathione levels were observed soon after treatment with high glucose, and these changes were suppressed by the simultaneous addition of ECE. High glucose levels stimulated the secretion of bioactive transforming growth factor-β (TGF-β) from the cells, and the stimulation was also suppressed by treating the HSCs with ECE. These results suggest that the suppression of high glucose-induced HSC activation by ECE is mediated through the inhibition of ROS and/or GSH and the downregulation of TGF-β secretion. ECE is useful for preventing the development of diabetic liver fibrosis

The BH3-Only SNARE BNip1 Mediates Photoreceptor Apoptosis in Response to Vesicular Fusion Defects

SummaryIntracellular vesicular transport is important for photoreceptor function and maintenance. However, the mechanism underlying photoreceptor degeneration in response to vesicular transport defects is unknown. Here, we report that photoreceptors undergo apoptosis in a zebrafish β-soluble N-ethylmaleimide-sensitive factor attachment protein (β-SNAP) mutant. β-SNAP cooperates with N-ethylmaleimide-sensitive factor to recycle the SNAP receptor (SNARE), a key component of the membrane fusion machinery, by disassembling the cis-SNARE complex generated in the vesicular fusion process. We found that photoreceptor apoptosis in the β-SNAP mutant was dependent on the BH3-only protein BNip1. BNip1 functions as a component of the syntaxin-18 SNARE complex and regulates retrograde transport from the Golgi to the endoplasmic reticulum. Failure to disassemble the syntaxin-18 cis-SNARE complex caused BNip1-dependent apoptosis. These data suggest that the syntaxin-18 cis-SNARE complex functions as an alarm factor that monitors vesicular fusion competence and that BNip1 transforms vesicular fusion defects into photoreceptor apoptosis

超高強度間欠性運動パフォーマンスに及ぼす異なる種類の糖質摂取の影響

Purpose The purpose of this study was to elucidate the effects of different types of carbohydrate （glucose, fructose, trehalose） fluids on high-intensity intermittent exercise performance after intake. Methods The participants were seven healthy male students. Using a bicycle ergometer, they first exercised at a constant load for 60 min （intensity 80% VT）. Thereafter, they performed the first set（ Wingate test×3 bouts） and ingested one type of fluid after completion. Next, they exercised at the same constant load for 30 min, and soon after completion performed the second set. Finally, they performed a constant-load exercise for 30 min, followed by the third set. Blood glucose and lactic acid concentrations were measured over time in blood samples obtained from a finger. Results Blood glucose concentration rose significantly at 15 min after intake of a carbohydrate fluid. After 30 min, blood glucose concentration with glucose intake was significantly higher than with other fluids intake（ P<0.01）. No significant difference in performance was seen with carbohydrate fluid intake as compared with water intake. The decrease in amount of work in the third set was significantly smaller with trehalose intake than with water（ P<0.05）. Discussion Blood glucose concentration before the second set of high-intensity intermittent exercise rose to 120 mg/dl with glucose intake, though there was no effect on performance. This is thought to be because catecholamine was secreted as a result of the first set of high-intensity intermittent exercise and free fatty acid concentrations in the blood increased as a result. Furthermore, fat oxidation was accelerated from the subsequent aerobic exercise, and the glycolyt ic system was not readily used. Free fatty acids may thus have inhibitory effects on glucose metabolism that limit performance. The characteristic of moderate absorption of trehalose may have preserved energy until the latter part and mitigated a decrease in performance in the third set

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Synergistic Anticancer Activities of Natural Substances in Human Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is highly resistant to currently available chemotherapeutic agents. The clinical outcome of HCC treatment remains unsatisfactory. Therefore, new effective and well-tolerated therapy strategies are needed. Natural products are excellent sources for the development of new medications for disease treatment. Recently, we and other researchers have suggested that the combined effect of natural products may improve the effect of chemotherapy treatments against the proliferation of cancer cells. In addition, many combination treatments with natural products augmented intracellular reactive oxygen species (ROS). In this review we will demonstrate the synergistic anticancer effects of a combination of natural products with chemotherapeutic agents or natural products against human HCC and provide new insight into the development of novel combination therapies against HCC