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Embedded systems have been applied widely, not only to consumer products and industrial machines, but also to new applications such as ubiquitous or sensor networking. The increasing role of software (SW) in embedded system development has caused a great demand for embedded SW engineers, and university education for embedded SW engineering has become important. The embedded software engineers should learn system architecture design and hardware (HW) technologies as well as SW technologies. However, only a few universities offer education courses for embedded software engineering that include system architecture design and HW technologies. This paper proposes a student experiment method that is designed to nurture embedded SW engineers by teaching these technologies. The proposed method includes an experiment for embedded SW development, an experiment for embedded HW development and a HW/SW co-design experiment, which help students learn system architecture design skills such as system modeling, HW/SW tradeoff design, and SW and HW module design. A model of each experiment was developed and evaluated. (Contains 5 tables and 11 figures.)

OBJECTIVE: It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed. RESEARCH DESIGN AND METHODS: The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was >or=126 mg/dl or if participants were taking oral hypoglycemic medications or insulin. RESULTS: During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (>or=42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT. CONCLUSIONS: GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes.Research Design and Methods: Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG >or=126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves.Results: During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001).Conclusions: The combined measurement of FPG and A1C was effective for predicting type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes.Research Design and Methods: The study participants were nondiabetic Japanese men (n = 8,570) aged 40-55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was >or=126 mg/dl or if participants were taking oral hypoglycemic medication or insulin.Results: During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44-2.54) compared with those who had levels between 0.71 and 0.80 mg/dl.Conclusions: Lower serum creatinine increased the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

The technique most widely used to quantitatively measure leg edema is only a pitting edema method. It has recently become possible to digitize B-mode ultrasound images and accurately quantify their brightness using an image-analysis software program. The purpose of this study was to find new indices of the grade of leg skin, to study whether or not analyses of the subcutaneous layer of leg skin on ultrasound images using image-editing software program can be used to evaluate it and to digitize it. Images of 282 subcutaneous layers of leg skin in 141 pregnant women were obtained using a B-scan portable ultrasound device. Rectangular photographs (vertical: skin thickness; horizontal: width of probe) were obtained using an image-editing program, and the luminous intensity (pixel grayscale: 0-255) and thickness of the skin were calculated using a histogram. We investigated the correlation between these parameters and the grade of pitting edema (0-3). There was a significant positive correlation between the grade of pitting edema and the average luminous intensity value, its standard deviation, and the skin thickness (ρ = 0.36, ρ = 0.22, ρ = 0.51, p < 0.0001, respectively). In particular, there was strong positive correlation between the grade of pitting edema and both the total number of pixels in a rectangle × (multiplied by) the average luminous intensity value and the total number of pixels in a rectangle × the standard deviation of the average luminous intensity value (ρ = 0.58 and ρ = 0.59, p < 0.0001, respectively). We could quantitatively evaluate the grade of leg edema by analyzing ultrasound photographs of the subcutaneous layer of the leg skin using an image-editing software program and found new indices to digitize it.

Extracellular matrix (ECM) provides fundamental support for epithelial tissues and controls cell function. The chemistry and mechanical properties of ECM components, including stiffness, elasticity, and fibrillar organization, influence epithelial tissue responses. Here we present a protocol describing the culture and transfer of epithelial acini from Matrigel to collagen gel and an approach to axially align the collagen fibrils by the external gel stretching. This protocol uses the acini of MCF10A cells and needs to be modified for different cell lines. For complete details on the use and execution of this protocol, please refer to Katsuno-Kambe et al. (2021). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Epithelial networks are commonly generated by processes where multicellular aggregates elongate and branch. Here, we focus on understanding cellular mechanisms for elongation using an organotypic culture system as a model of mammary epithelial anlage. Isotropic cell aggregates broke symmetry and slowly elongated when transplanted into collagen 1 gels. The elongating regions of aggregates displayed enhanced cell proliferation that was necessary for elongation to occur. Strikingly, this locoregional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles that were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the extracellular matrix, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry breaking and elongation. This required β1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating locoregional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry., Competing Interests: HK, JT, RJ, JH, SS, AY No competing interests declared, (© 2021, Katsuno-Kambe et al.)

Dendritic spines constitute the major compartments of excitatory post-synapses. They undergo activity-dependent enlargement, which is thought to increase the synaptic efficacy underlying learning and memory. The activity-dependent spine enlargement requires activation of signaling pathways leading to promotion of actin polymerization within the spines. However, the molecular machinery that suffices for that structural plasticity remains unclear. Here, we demonstrate that shootin1a links polymerizing actin filaments in spines with the cell-adhesion molecules N-cadherin and L1-CAM, thereby mechanically coupling the filaments to the extracellular environment. Synaptic activation enhances shootin1a-mediated actin-adhesion coupling in spines. Promotion of actin polymerization is insufficient for the plasticity; the enhanced actin-adhesion coupling is required for polymerizing actin filaments to push against the membrane for spine enlargement. By integrating cell signaling, cell adhesion, and force generation into the current model of actin-based machinery, we propose molecular machinery that is sufficient to trigger the activity-dependent spine structural plasticity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Epithelia are active materials where mechanical tension governs morphogenesis and homeostasis. But how that tension is regulated remains incompletely understood. We now report that caveolae control epithelial tension and show that this is necessary for oncogene-transfected cells to be eliminated by apical extrusion. Depletion of caveolin-1 (CAV1) increased steady-state tensile stresses in epithelial monolayers. As a result, loss of CAV1 in the epithelial cells surrounding oncogene-expressing cells prevented their apical extrusion. Epithelial tension in CAV1-depleted monolayers was increased by cortical contractility at adherens junctions. This reflected a signaling pathway, where elevated levels of phosphoinositide-4,5-bisphosphate (PtdIns(4,5)P 2 ) recruited the formin, FMNL2, to promote F-actin bundling. Steady-state monolayer tension and oncogenic extrusion were restored to CAV1-depleted monolayers when tension was corrected by depleting FMNL2, blocking PtdIns(4,5)P 2 , or disabling the interaction between FMNL2 and PtdIns(4,5)P 2 . Thus, caveolae can regulate active mechanical tension for epithelial homeostasis by controlling lipid signaling to the actin cytoskeleton., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Serum gamma-glutamyltransferase has been recognized as the risk factor of cardiovascular and metabolic diseases. However, the association between serum gamma-glutamyltransferase and the risk of chronic kidney disease is not well known, and no prospective studies have examined separately the relationship of serum gamma-glutamyltransferase with the risk of proteinuria versus that of low estimated glomerular filtration rate (eGFR)., Methods: We prospectively followed 9,341 Japanese men who did not have low eGFR, proteinuria, or diabetes, and did not take antihypertensive medications at entry for the analysis of proteinuria, and we followed 9,299 men for the analysis of low eGFR. We defined "persistent proteinuria" as proteinuria detected two or more times consecutively and persistently as ≥1+ on urine dipstick at the annual check-up until the end of follow-up. Low eGFR was defined as eGFR <60 mL/min/1.73 m 2 ., Results: During the 11-year observation period, 151 men developed persistent proteinuria and 1,276 men developed low eGFR. In multivariate models, the highest quartile (≥71 IU/L) of serum gamma-glutamyltransferase was independently related to the development of persistent proteinuria (hazard ratio 3.39; 95% confidence interval, 1.92-5.97) compared with the lowest quartile (≤25 IU/L). In joint analysis of alcohol consumption and serum gamma-glutamyltransferase, non-drinkers in the highest tertile (≥58 IU/L) of serum gamma-glutamyltransferase had the highest risk of persistent proteinuria. However, there was no association between serum gamma-glutamyltransferase and low eGFR., Conclusion: In middle-aged Japanese men, elevated serum gamma-glutamyltransferase was independently associated with future persistent proteinuria, but not with low eGFR.

By happy chance, the founding of Traffic in 1999 coincided with a clutch of reports that documented the endocytosis and recycling of classical cadherin adhesion receptors. This stimulated a concerted effort to elucidate the molecular regulation of cadherin endocytosis and to identify its functional implications. In particular, endocytosis provided new perspectives to understand how cadherins are modulated during tissue morphogenesis. In this short article, we consider some of what we have learnt about this problem and identify open questions for future research., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Metabolically healthy obesity seems to be a unique phenotype for the risk of cardiometabolic diseases. However, it is not known whether this phenotype is associated with the risk of proteinuria., Methods: Study subjects were 9,185 non-diabetic Japanese male workers aged 40-55 years who had no proteinuria, an estimated glomerular filtration rate ≥60 mL/min/1.73 m 2 , no history of cancer, and no use of antihypertensive or lipid-lowering medications at baseline. Obesity was defined as body mass index ≥25.0 kg/m 2 . Metabolic health was defined as the presence of no Adult Treatment Panel III components of the metabolic syndrome criteria, excluding waist circumference, and metabolic unhealth was defined as the presence of one or more metabolic syndrome components, excluding waist circumference. "Consecutive proteinuria" was considered positive if proteinuria was detected twice consecutively as 1+ or higher on urine dipstick at annual examinations to exclude chance proteinuria as much as possible., Results: During the 81,660 person-years follow-up period, we confirmed 390 cases of consecutive proteinuria. Compared with metabolically healthy non-obesity, metabolically healthy obesity was not associated with the risk of consecutive proteinuria (multiple-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.37-1.99), but metabolically unhealthy non-obesity with ≥2 metabolic syndrome components (HR 1.77; 95% CI, 1.30-2.42), metabolically unhealthy obesity with one component (HR 1.71; 95% CI, 1.12-2.61), and metabolically unhealthy obesity with ≥2 metabolic syndrome components (HR 2.77; 95% CI, 2.01-3.82) were associated with an increased risk of consecutive proteinuria., Conclusions: Metabolically healthy obesity did not increase the risk of consecutive proteinuria in Japanese middle-aged men.

Microorganisms with medium-chain alkane-producing activity are promising for the bio-production of drop-in fuel. In this study, we screened for microorganisms producing tridecane from tetradecanal. The activity of aldehyde decarbonylation was found in a wide range of microbes. In particular, the genus Klebsiella in the Enterobacteriaceae family was found to have a high ability to produce alkanes from aldehydes via enzyme catalyzed reaction., (Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: We examined prospectively which of the four blood pressure (BP) components (systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP], and mean arterial pressure [MAP]) was best in predicting the risk of proteinuria., Methods: This prospective study included 9341 non-diabetic Japanese middle-aged men who had no proteinuria and an estimated glomerular filtration rate ≥60 mL/min/1.73 m 2 and were not taking antihypertensive medications at entry. Persistent proteinuria was defined if proteinuria was detected two or more times consecutively and persistently at the annual examination until the end of follow-up. We calculated the difference in values of Akaike's information criterion (ΔAIC) in comparison of the BP components-added model to the model without them in a Cox proportional hazards model., Results: During the 84,587 person-years follow-up period, we confirmed 151 cases of persistent proteinuria. In multiple-adjusted models that included a single BP component, the hazard ratios for persistent proteinuria for the highest quartile of SBP, PP, and MAP were 3.11 (95% confidence interval [CI], 1.79-5.39), 1.87 (95% CI, 1.18-2.94), and 2.21 (95% CI, 1.33-3.69) compared with the lowest quartile of SBP, PP, and MAP, respectively. The hazard ratio for the highest quartile of DBP was 2.69 (95% CI, 1.65-4.38) compared with the second quartile of DBP. Of all models that included a single BP component, those that included SBP alone or DBP alone had the highest values of ΔAIC (14.0 and 13.1, respectively) in predicting the risk of persistent proteinuria., Conclusions: Of all BP components, SBP and DBP were best in predicting the risk of persistent proteinuria in middle-aged Japanese men., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Moderate alcohol consumption has been reported to be associated with a decreased risk of cardiometabolic diseases. Whether drinking pattern is associated with the risk of proteinuria is unknown., Methods: Study subjects were 9154 non-diabetic Japanese men aged 40-55 years, with an estimated glomerular filtration rate ≥60 mL/min/1.73 m(2), no proteinuria, and no use of antihypertensive medications at entry. Data on alcohol consumption were obtained by questionnaire. We defined "consecutive proteinuria" as proteinuria detected twice consecutively as 1+ or higher on urine dipstick at annual examinations., Results: During the 81 147 person-years follow-up period, 385 subjects developed consecutive proteinuria. For subjects who reported drinking 4-7 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was significantly associated with a decreased risk of consecutive proteinuria (hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.36-0.80) compared with non-drinkers. However, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with an increased risk of consecutive proteinuria (HR 1.78; 95% CI, 1.01-3.14). For subjects who reported drinking 1-3 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was associated with a decreased risk of consecutive proteinuria (HR 0.76; 95% CI, 0.51-1.12), and alcohol consumption of ≥69.1 g ethanol/drinking day was associated with an increased risk of consecutive proteinuria (HR 1.58; 95% CI, 0.72-3.46), but these associations did not reach statistical significance., Conclusions: Men with frequent alcohol consumption of 0.1-23.0 g ethanol/drinking day had the lowest risk of consecutive proteinuria, while those with frequent alcohol consumption of ≥69.1 g ethanol/drinking day had an increased risk of consecutive proteinuria.

To create strains that have high productivity of lactic acid without neutralization, a genome-wide screening for strains showing hyper-resistance to 6% l-lactic acid (pH 2.6) was performed using the gene deletion collection of Saccharomyces cerevisiae. We identified 94 genes whose disruption led to resistance to 6% lactic acid in rich medium. We also found that multiple combinations of Δdse2, Δscw11, Δeaf3, and/or Δsed1 disruption led to enhanced resistance to lactic acid depending upon their combinations. In particular, the quadruple disruptant Δdse2Δscw11Δeaf3Δsed1 grew well in 6% lactic acid with the shortest lag phase. We then introduced an exogenous lactate dehydrogenase gene (LDH) into those single and multiple disruptants to evaluate their productivity of lactic acid. It was found that the quadruple disruptant displaying highest lactic-acid resistance showed a 27% increase of lactic-acid productivity as compared with the LDH-harboring wild-type strain. These observations suggest that disruption of multiple genes whose deletion leads to lactic-acid resistance is an effective way to enhance resistance to lactic acid, leading to high lactic-acid productivity without neutralization., (Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes. However, the relationship between drinking patterns, such as the weekly frequency of alcohol consumption and the quantity per drinking day, and the incidence of type 2 diabetes has not been sufficiently addressed., Methods: Study participants included 10 631 Japanese men aged 40-55 years without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was ≥7.0 mmol/l or if participants were taking diabetes medications. Data on alcohol consumption were obtained from questionnaires., Results: During the 37 172 person-years of follow-up, we confirmed 878 cases of type 2 diabetes. Frequent alcohol consumption was associated with a low risk of type 2 diabetes. Compared to non-drinkers, the multiple-adjusted HR for those who drank 4-7 days weekly was 0.76 (95% CI, 0.63 to 0.92). To assess the association between drinking pattern and type 2 diabetes, we examined the joint association of the weekly frequency and the quantity per drinking day with type 2 diabetes. Men who consumed 0.1-2.0 or 2.1-4.0 US standard drinks per drinking day on 4-7 days weekly had a lower risk of type 2 diabetes (HR 0.74, 95% CI 0.58 to 0.95; HR 0.74, 95% CI 0.60 to 0.91, respectively) compared to non-drinkers., Conclusions: More frequent alcohol consumption lowered the risk of type 2 diabetes. Light to moderate alcohol consumption per drinking day on 4-7 days weekly lowered the risk of type 2 diabetes compared to non-drinkers.

Background and Objectives: Glomerular hyperfiltration and albuminuria accompanied by early-stage diabetic kidney disease predict future renal failure. Cigarette smoking has reported to be associated with elevated GFR in cross-sectional studies and with renal deterioration in longitudinal studies. The degree of glomerular hyperfiltration and proteinuria associated with smoking, which presumably is a phenomenon of early renal damage, has not been investigated in a satisfying manner so far., Design, Setting, Participants, & Measurements: This study included 10,118 Japanese men aged 40 to 55 years without proteinuria or renal dysfunction at entry. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation for Japanese. Glomerular hyperfiltration was defined as estimated GFR ≥117.0 ml/min per 1.73 m(2), which was the upper 2.5th percentile value of estimated GFR in the total population. Proteinuria was detected using standard dipstick., Results: During the 6-year observation period, there were 449 incident cases of glomerular hyperfiltration and 1653 cases of proteinuria. Current smokers had a 1.32-time higher risk for the development of glomerular hyperfiltration and a 1.51-time higher risk for proteinuria than nonsmokers after adjustment for baseline age, body mass index, systolic and diastolic BP, antihypertensive medication, diabetes, alcohol consumption, regular leisure-time physical activity, and estimated GFR. Both daily and cumulative cigarette consumption were associated with an increased risk for glomerular hyperfiltration and proteinuria in a dose-response manner., Conclusions: In middle-aged Japanese men, smoking was associated with an increased risk of glomerular hyperfiltration and dipstick proteinuria. Of importance, past smokers did not exhibit any increased risk for these conditions.

Polylactate (PLA) is synthesized as a representative bio-based polyester by the chemo-bio process on the basis of metal catalyst-mediated chemical polymerization of lactate (LA) supplied by microbial fermentation. To establish the one-step microbial process for synthesis of LA-based polyesters, we explored whether polyhydroxyalkanoate (PHA) synthase would exhibit polymerizing activity toward a LA-coenzyme A (CoA), based on the fact that PHA monomeric constituents, especially 3-hydroxybutyrate (3HB), are structurally analogous to LA. An engineered PHA synthase was discovered as a candidate by a two-phase in vitro polymerization system previously developed. An LA-CoA producing Escherichia coli strain with a CoA transferase gene was constructed, and the generation of LA-CoA was demonstrated by capillary electrophoresis/MS analysis. Next, when the engineered PHA synthase gene was introduced into the resultant recombinant strain, we confirmed the one-step biosynthesis of the LA-incorporated copolyester, P(6 mol% LA-co-94 mol% 3HB), with a number-average molecular weight of 1.9 x 10(5), as revealed by gel permeation chromatography, gas chromatography/MS, and NMR.

Human plasma contains two actin-binding proteins, plasma gelsolin and vitamin D-binding protein. These proteins are considered to play an important role in the disposition of actin derived from injured tissue. To evaluate this actin-scavenger system, gelsolin concentrations were measured in serial plasma samples obtained from patients with acute liver injury using an enzyme-linked immunosorbent assay. Plasma gelsolin levels in 43 healthy persons were 226 +/- 52 micrograms/mL. They were markedly reduced to 80 +/- 40 micrograms/mL in 14 patients with an early stage of acute hepatitis and returned to normal levels of 232 +/- 38 micrograms/mL as the disease resolved. Moreover, they showed a significant negative correlation with serum aminotransferase and bilirubin levels. In 7 patients with hepatocellular carcinoma, plasma gelsolin levels rapidly decreased from 182 +/- 42 to 87 +/- 41 micrograms/mL after transcatheter arterial embolization therapy. Because plasma gelsolin is not a hepatic protein, the decreased levels are considered to depend exclusively on the extent of actin leakage from the injured liver.