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Electric relay manufacture and assembly is an example of high-precision machining followed by an assembly process. During machining, parts exhibit dimensional variance and manufacturers have several techniques and strategies for how to maximise production and improve efficiency when variance is present. One approach is to measure the variance, select parts appropriately for the best match, perform the minimum amount of adjustment and rework, and then perform the assembly. This approach is difficult in practice because measurement errors also occur and confound the knowledge about each part's dimensions. In this paper, we consider a new matching approach to increase the production rate. We propose a part-combination selection method in which a pair of assembly parts in buffers is optimally selected using a target of an estimated assembly error, and an adjustment machine is then optimally selected using a range of estimated assembly errors. Furthermore, we consider an analytical approach to estimate the optimal control parameters for the proposed method that yield the maximum production rate. The analysis results show that the analytical approach can estimate the nearly optimal control parameters, including the nearly maximum production rate in any buffer capacity. The results also show that by installing a small buffer capacity, the production rate can be increased. [ABSTRACT FROM AUTHOR]

In this paper, we study the basic behaviour of jig flow in a closed-loop automatic transfer production system which is installed to mass-produce high quality adhesive products. In this system, machine troubles occur and they cause a stagnation of jig flow. As a result, a drop of jig temperature occurs and decreases the system production rate. First, we develop a model of jig flow considering the temperature of jigs circulating in the system, and using a simulation method, we investigate the effect of the number of input jigs and a method to install buffer storages. Next, we investigate the effect of adding a supplementary heating line to the system in order to minimise a decrease of production rate caused by jigs suffering a remarkable drop of temperature. [ABSTRACT FROM AUTHOR]

Shape identification analysis is carried out to obtain hitherto unknown defect shapes in a structure, based on the finite element and the adjoint variable methods. In this study, a test piece incorporating a known defect shape was employed to solve the shape identification problem. Also reported in this study is the shape identification problem of a cavity in a heated resin test piece made using a 3D printer by employing the temperature pattern observed on the surface of the test piece. The surface temperature of a test piece will not be uniformly distributed if it contains cavities. Practical experiments have confirmed that the characteristic of the temperature distribution depends on the size of the cavity. The thermal physical constants,i.e.the thermal conductivity and the convection coefficient, were identified for a model of the test piece incorporating a cavity based on the experimental data. Shape identification analysis was then carried out. Using numerical analysis, the finite element method was applied to simulate the temperature distribution in the test piece, and the adjoint variable method was employed to identify the cavity's shape. [ABSTRACT FROM AUTHOR]

Adjusting the dosage of renal excretory drugs according to the patient's renal function is essential. Vancomycin necessitates such adjustments due to its potential to cause nephrotoxicity when administered in excess. Creatinine-based equations for assessing the glomerular filtration rate, such as the Cockcroft-Gault and Modification of Diet in Renal Disease equations, are often used for dosage adjustments. However, vancomycin-induced nephrotoxicity sometimes occurs in critically ill patients, even in those with a normal estimated glomerular filtration rate. This case involved a 64-year-old male with cholangitis who developed vancomycin-induced nephrotoxicity. The patient was sarcopenic and had multiple risk factors that predisposed him to drug-induced nephrotoxicity. Moreover, creatinine-based equations may lead to the overestimation of glomerular filtration rate and subsequent vancomycin overdose. This case underscores the need for careful interpretation of creatinine-based assessments. We propose strategies to optimize medication dosing, particularly in patients with sarcopenia, to mitigate such risks., Competing Interests: The authors declare no conflict of interest., (©2024 Tottori University Medical Press.)

Background: Hypertension is one of the major etiologies that cause chronic kidney disease (CKD) and can exacerbate kidney dysfunction. Zinc is an essential trace element playing a role in blood pressure regulation, and zinc deficiency, a common comorbidity in patients with CKD, can cause hypertension. However, the precise mechanism underlying zinc deficiency-induced hypertension is unknown. Sodium (Na + ) retention due to inappropriate Na + reabsorption in the renal tubule is the principal pathophysiology of hypertension. Therefore, this study aimed to investigate the association between zinc deficiency and salt sensitivity., Methods: Adult mice were fed a zinc-adequate (ZnA) or zinc-deficient (ZnD) diet combined with/without high salt in drinking water (HS) for 4 weeks (n = 6 each). Changes in blood pressure, urinary sodium excretion, and the expressions of the proximal tubular Na + transporter, Na + /H + exchanger 3 (NHE3), which mostly contributes to filtered Na + reabsorption and the downstream Na + -Cl - transporter (NCC) were analyzed., Results: Urinary Na + excretion significantly increased in ZnD mice, indicating that zinc deficiency causes natriuresis. NHE3 expressions were significantly suppressed, whereas NCC was upregulated in ZnD mice. Interestingly, the combination of high salt and ZnD diet (HS-ZnD) reversed the urinary Na + loss. The NCC remained activated and NHE3 expressions paradoxically increased in HS-ZnD mice compared with those fed the combination of high salt and ZnA diet. In addition, blood pressure significantly increased only in HS-ZnD mice., Conclusion: The combination of zinc deficiency and high salt causes hypertension. Zinc is associated with salt-sensitivity, potentially through NHE3 and NCC regulation., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

The ubiquitin-proteasome system (UPS) is a major proteolytic system that plays an important role in the regulation of various cell processes, such as cell cycle, stress response, and transcriptional regulation, especially in neurons, and dysfunction of UPS is considered to be a cause of neuronal cell death in neurodegenerative diseases. However, the mechanism of neuronal cell death caused by UPS dysfunction has not yet been fully elucidated. In this study, we investigated the mechanism of neuronal cell death induced by proteasome inhibitors using human neuroblastoma SH-SY5Y cells. Z-Leu-D-Leu-Leu-al (MG132), a proteasome inhibitor, induced apoptosis in SH-SY5Y cells in a concentration- and time-dependent manner. Antioxidants N-acetylcysteine and EUK-8 attenuated MG132-induced apoptosis. Apocynin and diphenyleneiodonium, inhibitors of NADPH oxidase (NOX), an enzyme that produces superoxide anions, also attenuated MG132-induced apoptosis. It was also found that MG132 treatment increased the expression of NOX5, a NOX family member, and that siRNA-mediated silencing of NOX5 and BAPTA-AM, which inhibits NOX5 by chelating calcium, suppressed MG132-induced apoptosis and production of reactive oxygen species in SH-SY5Y cells. These results suggest that MG132 induces apoptosis in SH-SY5Y cells through the production of superoxide anion by NOX5., Competing Interests: Declaration of Competing interest We have no conflicts of interest to declare., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Renal tubular acidosis is the principal clinical feature associated with tubulointerstitial nephritis in patients with primary Sjögren's syndrome. Renal tubular dysfunction due to interstitial nephritis has been considered the underlying pathophysiology connecting renal tubular acidosis and primary Sjögren's syndrome. However, the detailed mechanisms underlying the pathophysiology of renal tubular acidosis in primary Sjögren's syndrome is not fully understood., Case Presentation: A 30-year-old woman was admitted with complaints of weakness in the extremities. The patient was hospitalized thirteen years earlier for similar issues and was diagnosed with hypokalemic paralysis due to distal renal tubular acidosis with primary Sjögren's syndrome. This diagnosis was based on a positive Schirmer's test. Besides, anti-Sjögren's syndrome-related antigen A was also detected. Laboratory tests indicated distal RTA; however, a renal biopsy showed no obvious interstitial nephritis. Laboratory tests conducted during the second admission indicated distal renal tubular acidosis. Therefore, a renal biopsy was performed again, which revealed interstitial nephritis. Histological analysis of acid-base transporters revealed the absence of vacuolar type H + -ATPases in the collecting duct. The vacuolar type H + -ATPase was also absent in the past renal biopsy, suggesting that the alteration in acid-base transporters is independent of interstitial nephritis., Conclusions: This case study demonstrates that vacuolar-type H + -ATPases are associated with distal renal tubular acidosis, and distal renal tubular acidosis precedes interstitial nephritis in patients with primary Sjögren's syndrome., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Graphene nanoflakes are widely utilized as high-performance molecular devices due to their chemical stability and light weight. In the present study, the interaction of aluminum species with graphene nanoflake (denoted as GR-Al) has been investigated using the density functional theory (DFT) method to elucidate the doping effects of Al metal on the electronic states of GR. The mechanisms of the diffusion of Al on GR surface and the hydrogen storage of GR-Al were also investigated in detail. The neutral, mono-, di-, and trivalent Al ions (expressed as Al, Al + , Al 2+ , and Al 3+ , respectively) were examined as the Al species. The DFT calculations showed that the charge transfer interaction between Al and GR plays an important role in the binding of Al species to GR. The diffusion path of Al on GR surface was determined: the barrier heights of Al diffusion were calculated to be 2.1-2.8 kcal mol -1 , which are lower than Li + on GR (7.2 kcal/mol). The possibility of using GR-Al for hydrogen storage was also discussed on the basis of the theoretical results.

Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 ( BACH1 ), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway.

In patients with chronic kidney disease, it is necessary to identify the etiology of glomerular disease. Renal biopsy is the gold standard for assessing the underlying pathology; however, it has the risk of potential complications. We have established a urinary fluorescence imaging technique to assess enzymatic activity using an activatable fluorescent probe targeting two enzymes: gamma-glutamyl transpeptidase and dipeptidyl-peptidase. The urinary fluorescence images can be easily obtained by adding an optical filter to the microscope with short incubation of the fluorescent probes. Urinary fluorescence imaging could help to assess underlying etiologies of kidney diseases and is a potential non-invasive qualitative assessment technique for kidney diseases in patients with diabetes. Key features Non-invasive assessment of kidney disease. Urinary fluorescent imaging with enzyme-activatable fluorescent probes. Enables differentiation of diabetic kidney disease and glomerulonephritis., Competing Interests: Competing interestsThis research was founded by JSPS KAKENHI, grant number JP22K16242 (T.I.)., (Copyright © 2023 The Authors; exclusive licensee Bio-protocol LLC.)

When performing renal biopsy, it is necessary to identify the cortex, where glomeruli are exclusively distributed, to ensure the quality of the specimen for histological diagnosis. However, conventional methods using a stereomicroscope or magnifying lens often fail to clarify the quality of the specimen. We have established a fluorescent-based imaging technique for the on-site assessment of renal biopsy specimens. The fluorescent images can be easily obtained by adding an optical filter to the microscope and with a short incubation of an activatable fluorescent probe. This novel imaging technique can be applied to renal biopsy specimens for distinguishing the renal cortex., Competing Interests: Competing interests The authors declare that they have no financial or non-financial conflicts of interest., (Copyright © 2022 The Authors; exclusive licensee Bio-protocol LLC.)

Uromodulin, a urinary protein synthesized and secreted from the thick ascending limb (TAL) of the loop of Henle, is associated with hypertension through the activation of sodium reabsorption in the TAL. Uromodulin is a potential target for hypertension treatment via natriuresis. However, its biological function in epithelial cells of the distal nephron segment, particularly the collecting duct, remains unknown. Herein, we examined the regulation of uromodulin production during water deprivation in vivo as well as the effect of uromodulin on the activity of the water channel aquaporin-2 (AQP2) in vitro and in vivo using transgenic mice. Water deprivation upregulated uromodulin production; immunofluorescence experiments revealed uromodulin adhesion on the apical surface of the collecting duct. Furthermore, the activation of AQP2 was attenuated in mice lacking uromodulin. Uromodulin enhanced the phosphorylation and apical trafficking of AQP2 in mouse collecting duct cells treated with the vasopressin analog dDAVP. The uromodulin-induced apical trafficking of AQP2 was attenuated via endocytosis inhibitor treatment, suggesting that uromodulin activates AQP2 through the suppression of endocytosis. This study provides novel insights into the cross-talk between TAL and the collecting duct, and indicates that the modulation of uromodulin is a promising approach for diuresis and hypertension treatment.

A clear identification of the etiology of glomerular disease is essential in patients with diabetes. Renal biopsy is the gold standard for assessing the underlying nephrotic pathology; however, it has the risk for potential complications. Here, we aimed to investigate the feasibility of urinary fluorescence imaging using an enzyme-activatable probe for differentiating diabetic kidney disease and the other glomerular diseases. Hydroxymethyl rhodamine green (HMRG)-based fluorescent probes targeting gamma-glutamyl transpeptidase (GGT) and dipeptidyl-peptidase (DPP) were used. Urinary fluorescence was compared between groups which were classified by their histopathological diagnoses (diabetic kidney disease, glomerulonephritis, and nephrosclerosis) as obtained by ultrasound-guided renal biopsy. Urinary fluorescence was significantly stronger in patients with diabetic kidney disease compared to those with glomerulonephritis/nephrosclerosis after DPP-HMRG, whereas it was stronger in patients with nephrosclerosis than in patients with glomerulonephritis after GGT-HMRG. Subgroup analyses of the fluorescence performed for patients with diabetes showed consistent results. Urinary fluorescence imaging using enzyme-activatable fluorescence probes thus represents a potential noninvasive assessment technique for kidney diseases in patients with diabetes.

Major immunotherapy challenges include a limited number of predictive biomarkers and the unusual imaging features post-therapy, such as pseudo-progression, which denote immune infiltrate-mediated tumor enlargement. Such phenomena confound clinical decision-making, since the cancer may eventually regress, and the patient should stay on treatment. We prospectively evaluated serial, blood-derived cell-free DNA (cfDNA) (baseline and 2-3 weeks post-immune checkpoint inhibitors [ICIs]) for variant allele frequency (VAF) and blood tumor mutation burden (bTMB) changes (next-generation sequencing) (N = 84 evaluable patients, diverse cancers). Low vs. high cfDNA-derived average adjusted ΔVAF (calculated by a machine-learning model) was an independent predictor of higher clinical benefit rate (stable disease ≥6 months/complete/partial response) (69.2% vs. 22.5%), and longer median progression-free (10.1 vs. 2.25 months) and overall survival (not reached vs. 6.1 months) (all P < .001, multivariate). bTMB changes did not correlate with outcomes. Therefore, early dynamic changes in cfDNA-derived VAF were a powerful predictor of pan-cancer immunotherapy outcomes., Competing Interests: SK serves as a consultant for Foundation Medicine, receives speaker fees from Roche and research grants from ACT Genomics, Sysmex, Konica Minolta, and OmniSeq. JJA and LK have no disclosures. BL, SWC, DBF, DQ, RH, JH, PG, and HML are employed by Ambry Genetics, and NK, TI, and MK are employed by Konica Minolta, Inc., when they are working on this project. RK receives research funding from Genentech, Incyte, Merck, Serono, Pfizer, Sequenom, Foundation Medicine, Grifols, and Guardant, as well as consultant fees from Loxo, X Biotech, NeoMed, and Actuate Therapeutics; speaker fees from Roche; and an ownership interest in IDbyDNA and Curematch, Inc., and is a Board member of CureMatch and CureMetrix, Inc., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health issues associated with the metabolic syndrome. Although NASH is a known risk factor of CKD, the mechanisms linking these two diseases remain poorly understood. We aimed to investigate alterations in the kidney complicated with dyslipidemia in an established NASH mouse model. Male C57BL6/J mice were fed with control diet or high-fat diet (HFD), containing 40% fat, 22% fructose, and 2% cholesterol for 16 weeks. Metabolic characteristics, histological changes in the kidney, endoplasmic reticulum (ER) stress, apoptosis, and fibrosis were evaluated by histological analysis, immunoblotting, and quantitative reverse transcription-polymerase chain reaction. Levels of serum aspartate aminotransferase, alanine aminotransferase, alkali-phosphatase, total cholesterol, and urinary albumin were significantly higher in mice fed with HFD. Remarkable steatosis, glomerular hypertrophy, and interstitial fibrosis were also shown in in the kidney by leveraging HFD. Furthermore, HFD increased the mRNA expression levels of Casp3, Tgfb1, and Nfe2l2 and the protein level of BiP. We observed the early changes of CKD and speculate that the underlying mechanisms that link CKD and NASH are the induction of ER stress and apoptosis. Further, we observed the activation of Nfe2l2 in the steatosis-induced CKD mouse model. This NASH model holds implications in investigating the mechanisms linking dyslipidemia and CKD., Competing Interests: The authors have declared that no competing interests exist.

Background: Sarcopenia is strongly associated with long-term mortality in patients undergoing hemodialysis. The diagnostic modalities used to assess muscle mass, such as bioimpedance analysis and dual-energy X-ray absorption measurement, have limitations for application in patients on hemodialysis. Therefore, there is a need to establish a simple index for assessing muscle mass that can be universally performed in patients on hemodialysis., Methods: Patients on maintenance hemodialysis were included in this study. Laboratory tests, skeletal muscle mass measured by bioimpedance analysis, and clinical records were obtained retrospectively. The creatinine generation rate (CGR) was calculated from the pre- and postdialysis blood tests using a kinetic model as the index for whole-body muscle mass. Correlations between the CGR and skeletal muscle mass were investigated, and the cut-off value for muscle wasting was determined. Kaplan-Meier survival analysis was performed to investigate the feasibility of the CGR for predicting long-term survival., Results: Among the 130 patients included, eight were diagnosed with sarcopenia by bioimpedance analysis. The CGR was positively correlated with skeletal muscle mass (r = 0.454, p < 0.001). Multiple linear regression analysis revealed that age and sex independently influenced the CGR. The patients were classified into two groups according to age- and sex-adjusted CGRs. During a median follow-up period of 32 months, the Kaplan-Meier survival analysis showed that patients with low CGR showed significantly poor long-term prognosis (p = 0.002)., Conclusion: The CGR is a simple index for muscle mass and can predict long-term mortality in patients on hemodialysis., (© 2021. Japanese Society of Nephrology.)

Background: Hyporesponsiveness to erythropoietin stimulating agent (ESA) is associated with poor outcomes in patients with chronic kidney disease. Although ESA hyporesponsiveness and sarcopenia have a common pathophysiological background, clinical evidence linking them is scarce. The purpose of the study was to investigate the relationship between ESA responsiveness and skeletal muscle mass in hemodialysis patients., Methods: This cross-sectional study analyzed 70 patients on maintenance hemodialysis who were treated with ESA. ESA responsiveness was evaluated by erythropoietin resistance index (ERI), calculated as a weekly dose of ESA divided by body weight and hemoglobin (IU/kg/week/dL), and a weekly dose of ESA/hemoglobin (IU/week/dL). A dose of ESA is equivalated to epoetin β. Correlations between ESA responsiveness and clinical parameters including skeletal muscle mass were analyzed., Results: Among the 70 patients, ERI was positively correlated to age (p < 0.002) and negatively correlated to height (p < 0.001), body weight (p < 0.001), BMI (p < 0.001), skeletal muscle mass (p < 0.001), transferrin saturation (TSAT) (p = 0.049), and zinc (p = 0.006). In the multiple linear regression analysis, TSAT, zinc, and skeletal muscle mass were associated with ERI and weekly ESA dose/hemoglobin., Conclusions: Skeletal muscle mass was the independent predictor for ESA responsiveness as well as TSAT and zinc. Sarcopenia is another target for the management of anemia in patients with hemodialysis.

Background: Sarcopenia is a major health issue especially in patients on maintenance hemodialysis. Low skeletal muscle mass is included in the diagnostic criteria for sarcopenia. The skeletal muscle mass is usually evaluated by modalities such as bioimpedance analysis (BIA) or dual-energy X-ray absorptiometry, however the assessment of skeletal muscle mass using computed tomography (CT) images has not been established. The purpose of the study was to investigate the feasibility of the assessment of skeletal muscle mass using CT images in hemodialysis patients., Methods: Skeletal muscle mass index (SMI) was measured by BIA and psoas muscle index (PMI) was measured by cross-sectional CT images in 131 patients. The relationship between SMI and PMI and the diagnostic ability of PMI for low muscle mass were evaluated. Furthermore, the patients were followed up and long-term survival in patients with low and high PMI were compared., Results: PMI measured at the L3 vertebral level was strongly correlated with SMI (r = 0.597, p < 0.001). Age, sex, and SMI were the influencing factors for PMI. Patients with low PMI showed higher incidence rates of mortality during the follow up., Conclusions: PMI assessed by CT image can be an alternative to BIA in patients on hemodialysis.

Carbon materials such as graphene nanoflakes (GRs), carbon nanotubes, and fullerene can be widely used for hydrogen storage. In general, metal doping of these materials leads to an increase in their H 2 storage density. In the present study, the binding energies of H 2 to Mg species on GRs, GR-Mg m + ( m = 0-2), were calculated using density functional theory calculations. Mg has a wide range of atomic charges. In the case of GR-Mg ( m = 0, Mg atom), the binding energy of one H 2 molecule is close to 0, whereas those for m = 1 (Mg + ) and 2 (Mg 2+ ) are 0.23 and 13.2 kcal/mol ( n = 1), respectively. These features suggest that GR-Mg 2+ has a strong binding affinity toward H 2 , whereas GR-Mg + has a weak binding energy. In addition, it was found that the first coordination shell is saturated by four H 2 molecules, GR-Mg 2+ -(H 2 ) n ( n = 4). Next, direct ab initio molecular dynamics calculations were carried out for the electron-capture process of GR-Mg 2+ -(H 2 ) n and a hole-capture process of GR-Mg + -(H 2 ) n ( n = 4). After electron capture, the H 2 molecules left and dissociated from GR-Mg + : GR-Mg 2+ -(H 2 ) n + e - → GR-Mg + + (H 2 ) n (H 2 is released into the gas phase). In contrast, the H 2 molecules were bound again to GR-Mg 2+ after the hole capture of GR-Mg + : GR-Mg + + (H 2 ) n (gas phase) + hole → GR-Mg 2+ -(H 2 ) n . On the basis of these calculations, a model device with reversible H 2 adsorption-desorption properties was designed. These results strongly suggest that the GR-Mg system is capable of H 2 adsorption-desorption reversible storage., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)