In vitro selection and chemical modification of proteins to add binding affinity

早大学位記番号:新7180早稲田大

Connected vehicle data for crash hotspots

Identifying crash hotspots help traffic engineers implementing countermeasures to improve transportation system safety. However, given it typically takes 12 to 18 months to obtain crash reports, the crash hotspots based on actual crash reports might not be applicable (as the hotspot locations often change). In order to identify hotspots more timely than current practice, we have investigated the basic safety message (BSM) including equipped vehicle deceleration data at every 0.1 seconds from connected vehicles. Based on the safety pilot study data from April 2013, we proposed “extreme braking event” as a crash surrogate. The extreme braking event was defined as a longitudinal deceleration rate greater than 0.6 g (or 19.32 ft/s2). When comparison was made between the actual crash (i.e., crash rate) and the extreme braking event (i.e., event rate based on the number of equipped vehicles) at the same freeway segments in the city of Ann Arbor, the proposed extreme braking event showed high correlation (over 0.7). In addition, top 5 actual crash hotspots (about 50% of crashes out of 38 segments) were identified by using top 8 extreme braking event measures. Thus, our research indicates that the proposed extreme braking event measure has of great potential to identify crash hotspots in timely manner than the current practice based on delayed crash reports

Association between statin treatment and new-onset diabetes mellitus: a population based case–control study

Abstract Background Several studies suggest that statin may increase the risk of new-onset diabetes mellitus (NODM). This study aimed to evaluate the association between the duration and recent use of statin, and the risk of NODM, based on population-based data sets. Methods We used the South Korean National Health Insurance Service National Sample Cohort database for this nationwide case–control study. Of the 1 million participants, 6417 participants with NODM in 2012–2013 and 32,085 controls without diabetes (1:5 propensity score matched with age, sex, index year, and year of diabetes diagnosis) were included. In these patients, we examined the statin prescription record for 3 years preceding the outcome. We used conditional logistic regression to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Results After adjustment of covariates, there were no significant differences in the risk of NODM when analyzed according to cumulative use days. The risk of NODM was increased only in the short-term and recent user group (OR 1.48, 95% CI 1.21 to 1.82) whose cumulative prescription days are less than 6 months and whose last prescription is within 6 months of diagnosis. Conclusions The risk of NODM was not associated with an increase in the cumulative duration of statin use or with non-recent use. Only recent short-term use of statin was associated with an increased risk of NODM. Diabetes screening are warranted during initial statin therapy

Association between body mass index and mortality in the Korean elderly: A nationwide cohort study.

The objective of this study was to investigate the relationship between body mass index (BMI) and mortality in the elderly. This study was a nation-wide population-based retrospective cohort study of the National Health Insurance System-Senior Database (NHIS-SD). In this study, a total of 75,856 subjects were identified and selected from among 251,593 individuals aged ≥ 65 years who underwent health screening at least once between 2009 and 2012 and who had no history of diabetes, cardiovascular disease, stroke, cancer, or chronic obstructive pulmonary disease (COPD). The subjects of this study were followed-up until 2013 to identify the total mortality and the cause-specific mortality of 6 groups divided according to BMI. The hazard ratio (HR) by reference group (23 ≤ BMI < 25 kg/m2) of each group was calculated. A significant increase in the HR with a decreased BMI was observed in the group with a BMI < 23 kg/m2, whereas the HR in the group with a BMI ≥ 25 kg/m2 was not significantly different than that of the reference group (23 ≤ BMI < 25 kg/m2). This pattern was also seen in the subgroup analyses in relation to age, smoking history, alcohol use, exercise level, and socioeconomic status. In this study, we found that a low BMI was a risk factor for death in the elderly and that no significant difference in mortality was seen in the elderly with a BMI of 25 or over. In terms of an optimal BMI in the elderly, it is important to maintain an appropriately healthy range of BMI with the aim of preventing weight loss

Paintable Decellularized‐ECM Hydrogel for Preventing Cardiac Tissue Damage

Abstract The tissue‐specific heart decellularized extracellular matrix (hdECM) demonstrates a variety of therapeutic advantages, including fibrosis reduction and angiogenesis. Consequently, recent research for myocardial infarction (MI) therapy has utilized hdECM with various delivery techniques, such as injection or patch implantation. In this study, a novel approach for hdECM delivery using a wet adhesive paintable hydrogel is proposed. The hdECM‐containing paintable hydrogel (pdHA_t) is simply applied, with no theoretical limit to the size or shape, making it highly beneficial for scale‐up. Additionally, pdHA_t exhibits robust adhesion to the epicardium, with a minimal swelling ratio and sufficient adhesion strength for MI treatment when applied to the rat MI model. Moreover, the adhesiveness of pdHA_t can be easily washed off to prevent undesired adhesion with nearby organs, such as the rib cages and lungs, which can result in stenosis. During the 28 days of in vivo analysis, the pdHA_t not only facilitates functional regeneration by reducing ventricular wall thinning but also promotes neo‐vascularization in the MI region. In conclusion, the pdHA_t presents a promising strategy for MI treatment and cardiac tissue regeneration, offering the potential for improved patient outcomes and enhanced cardiac function post‐MI

Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes

The importance of evaluating the cardiotoxicity potential of common chemicals as well as new drugs is increasing as a result of the development of animal alternative test methods using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Bisphenol A (BPA), which is used as a main material in plastics, is known as an endocrine-disrupting chemical, and recently reported to cause cardiotoxicity through inhibition of ion channels in CMs even with acute exposure. Accordingly, the need for the development of alternatives to BPA has been highlighted, and structural analogues including bisphenol AF, C, E, F, and S have been developed. However, cardiotoxicity data for analogues of bisphenol are not well known. In this study, in order to evaluate the cardiotoxicity potential of analogues, including BPA, a survival test of hiPSC-CMs and a dual-cardiotoxicity evaluation based on a multi-electrode array were performed. Acute exposure to all bisphenol analogues did not affect survival rate, but spike amplitude, beat period, and field potential duration were decreased in a dose-dependent manner in most of the bisphenols except bisphenol S. In addition, bisphenols, except for bisphenol S, reduced the contractile force of hiPSC-CMs and resulted in beating arrest at high doses. Taken together, it can be suggested that the developed bisphenol analogues could cause cardiotoxicity even with acute exposure, and it is considered that the application of the MEA-based dual-cardiotoxicity evaluation method can be an effective help in the development of safe alternatives

Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling

The AKT signaling pathway plays critical roles in the resolution of inflammation. However, the underlying mechanisms of anti-inflammatory regulation and signal coordination remain unclear. Here, we report that anti-inflammatory AKT signaling is coordinated by glutamyl-prolyl-tRNA synthetase 1 (EPRS1). Upon inflammatory activation, AKT specifically phosphorylates Ser999 of EPRS1 in the cytoplasmic multi-tRNA synthetase complex, inducing release of EPRS1. EPRS1 compartmentalizes AKT to early endosomes via selective binding to the endosomal membrane lipid phosphatidylinositol 3-phosphate and assembles an AKT signaling complex specific for anti-inflammatory activity. These events promote AKT activation-mediated GSK3β phosphorylation, which increase anti-inflammatory cytokine production. EPRS1-deficient macrophages do not assemble the early endosomal complex and consequently exacerbate inflammation, decreasing the survival of EPRS1-deficient mice undergoing septic shock and ulcerative colitis. Collectively, our findings show that the housekeeping protein EPRS1 acts as a mediator of inflammatory homeostasis by coordinating compartment-specific AKT signaling