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This study presents a preliminary investigation of a new strategy for detecting and classifying road hazards, such as potholes and bumps, based on rack force estimation of electric power steering (EPS) systems. The numerous studies on road hazard detection have primarily focused on computer-vision systems, including cameras or light detection, and ranging and vertical vibration signals measured by accelerometers mounted on suspension systems. However, conventional methods are prone to reduced accuracy owing to their susceptibility to vibrations transmitted from road surfaces to vehicles. Accordingly, considerable room for detection accuracy improvement remains. Herein, we explore a novel approach that leverages the steering rack force generated in the EPS system, considering that potholes and bumps induce vertical and lateral forces on the tire’s contact patch, resulting in a net force generated by such tire moments on the vehicle steering rack. We propose an algorithm that uses an improved Kalman filter (KF) with an unknown input, combining the capabilities of a conventional KF with a disturbance observer. This algorithm aims to estimate the rack force by utilizing measurements of the steering torque and angle inputs. The estimated rack force provides features that serve as the basis for classifying road hazards. The classification performance was evaluated using metrics calculated from confusion matrix, such as accuracy, precision, recall, and F1. The proposed road hazard detection and classification algorithm was not only rigorously simulated using SIMULINK® with CarSim® software, but also is experimentally validated through in-vehicle tests.

Abstract Global longitudinal strain (GLS) is a valuable indicator of subclinical myocardial dysfunction. Whether the effect of aging on subclinical left ventricular dysfunction is sex-specific is not well documented. This study aimed to identify age-related changes in GLS according to sex in patients with a normal left ventricular ejection fraction (LVEF). In this cross-sectional, single-center cohort study in Korea, participants who underwent GLS measurement using 2D speckle-tracking echocardiography were retrospectively reviewed, and participants with normal LVEF (≥ 55%) without documented cardiovascular disease were included. Reduced GLS was defined as absolute values below 18%. Of 682 study participants (mean age, 58; female, 51.5%), 209 (30.6%) had reduced GLS. Females with reduced GLS were older than those with normal GLS (68 vs. 58 years, P 66 years old had significantly higher risk of reduced GLS (Odds ratio 2.66; 95% CI 1.22–5.76; P = 0.014). In participants with normal LVEF, GLS decreased with age in females but not in males. Particularly, females aged 66 years and older had a significantly higher risk of reduced GLS. These findings suggest that GLS could be a valuable parameter for assessing subclinical cardiac dysfunction, especially in older females.

Abstract Excessive polyethylene terephthalate (PET) waste causes a variety of problems. Extensive research focused on the development of superior PET hydrolases for PET biorecycling has been conducted. However, template enzymes employed in enzyme engineering mainly focused on IsPETase and leaf-branch compost cutinase, which exhibit mesophilic and thermophilic hydrolytic properties, respectively. Herein, we report a PET hydrolase from Cryptosporangium aurantiacum (CaPETase) that exhibits high thermostability and remarkable PET degradation activity at ambient temperatures. We uncover the crystal structure of CaPETase, which displays a distinct backbone conformation at the active site and residues forming the substrate binding cleft, compared with other PET hydrolases. We further develop a CaPETaseM9 variant that exhibits robust thermostability with a T m of 83.2 °C and 41.7-fold enhanced PET hydrolytic activity at 60 °C compared with CaPETaseWT. CaPETaseM9 almost completely decompose both transparent and colored post-consumer PET powder at 55 °C within half a day in a pH-stat bioreactor.

Abstract Background Statin treatment increases the risk of new-onset diabetes mellitus (NODM); however, data directly comparing the risk of NODM among individual statins is limited. We compared the risk of NODM between patients using pitavastatin and atorvastatin or rosuvastatin using reliable, large-scale data. Methods Data of electronic health records from ten hospitals converted to the Observational Medical Outcomes Partnership Common Data Model (n = 14,605,368 patients) were used to identify new users of pitavastatin, atorvastatin, or rosuvastatin (atorvastatin + rosuvastatin) for ≥ 180 days without a previous history of diabetes or HbA1c level ≥ 5.7%. We conducted a cohort study using Cox regression analysis to examine the hazard ratio (HR) of NODM after propensity score matching (PSM) and then performed an aggregate meta-analysis of the HR. Results After 1:2 PSM, 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin + rosuvastatin users (33,477 person-years of follow-up) were pooled from 10 databases. The meta-analysis of the HRs demonstrated that pitavastatin resulted in a significantly reduced risk of NODM than atorvastatin + rosuvastatin (HR 0.72; 95% CI 0.59–0.87). In sub-analysis, pitavastatin was associated with a lower risk of NODM than atorvastatin or rosuvastatin after 1:1 PSM (HR 0.69; CI 0.54–0.88 and HR 0.74; CI 0.55–0.99, respectively). A consistently low risk of NODM in pitavastatin users was observed when compared with low-to-moderate-intensity atorvastatin + rosuvastatin users (HR 0.78; CI 0.62–0.98). Conclusions In this retrospective, multicenter active-comparator, new-user, cohort study, pitavastatin reduced the risk of NODM compared with atorvastatin or rosuvastatin.

Background: The prognostic value of whole vessel plaque quantification has not been fully understood. Objectives: We aimed to investigate the clinical relevance of whole vessel plaque quantification on coronary computed tomography angiography. Methods: In a total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography, high-risk plaque characteristics (HRPC) included minimum lumen area 0.80, the number of HRVC was significantly associated with the risk of VOCO (HR: 2.54; 95% CI: 1.77-3.64) and enhanced the predictability for VOCO of % diameter stenosis and the number of HRPC (P < 0.001). In a landmark analysis at 2 years, the number of HRVC showed sustained prognostic implications beyond 2 years, but the number of HRPC did not. Conclusions: Whole vessel plaque quantification can provide incremental predictability for low FFR and additive prognostic value in deferred vessels with high FFR over anatomical severity and lesion plaque characteristics. (CCTA-FFR Registry for Risk Prediction; NCT04037163)

Malate dehydrogenase (MDH) is one of the key enzymes for succinic acid (SA) bioproduction. Here, the authors report biochemical and structural analyses of various MDHs to reveal amino acids influencing the specific activity and susceptibility to substrate inhibition, and achieve industrial-level SA production.

Abstract Background The lignin peroxidase isozyme H8 from the white-rot fungus Phanerochaete chrysosporium (LiPH8) demonstrates a high redox potential and can efficiently catalyze the oxidation of veratryl alcohol, as well as the degradation of recalcitrant lignin. However, native LiPH8 is unstable under acidic pH conditions. This characteristic is a barrier to lignin depolymerization, as repolymerization of phenolic products occurs simultaneously at neutral pH. Because repolymerization of phenolics is repressed at acidic pH, a highly acid-stable LiPH8 could accelerate the selective depolymerization of recalcitrant lignin. Results The engineered LiPH8 was in silico designed through the structural superimposition of surface-active site-harboring LiPH8 from Phanerochaete chrysosporium and acid-stable manganese peroxidase isozyme 6 (MnP6) from Ceriporiopsis subvermispora. Effective salt bridges were probed by molecular dynamics simulation and changes to Gibbs free energy following mutagenesis were predicted, suggesting promising variants with higher stability under extremely acidic conditions. The rationally designed variant, A55R/N156E-H239E, demonstrated a 12.5-fold increased half-life under extremely acidic conditions, 9.9-fold increased catalytic efficiency toward veratryl alcohol, and a 7.8-fold enhanced lignin model dimer conversion efficiency compared to those of native LiPH8. Furthermore, the two constructed salt bridges in the variant A55R/N156E-H239E were experimentally confirmed to be identical to the intentionally designed LiPH8 variant using X-ray crystallography (PDB ID: 6A6Q). Conclusion Introduction of strong ionic salt bridges based on computational design resulted in a LiPH8 variant with markedly improved stability, as well as higher activity under acidic pH conditions. Thus, LiPH8, showing high acid stability, will be a crucial player in biomass valorization using selective depolymerization of lignin.

Abstract Metallosphaera sedula is a thermoacidophilic autotrophic archaeon known to utilize the 3-hydroxypropionate/4-hydroxybutyrate cycle (3-HP/4-HB cycle) as carbon fixation pathway. 3-Hydroxypropionyl-CoA dehydratase (3HPCD) is an enzyme involved in the 3-HP/4-HB cycle by converting 3-hydroxypropionyl-CoA to acryloyl-CoA. To elucidate the molecular mechanism of 3HPCD from M. sedula (Ms3HPCD), we determined its crystal structure in complex with Coenzyme A (CoA). Ms3HPCD showed an overall structure and the CoA-binding mode similar to other enoyl-CoA hydratase (ECH) family enzymes. However, compared with the other ECHs, Ms3HPCD has a tightly formed α3 helix near the active site, and bulky aromatic residues are located at the enoyl-group binding site, resulting in the enzyme having an optimal substrate binding site for accepting short-chain 3-hydroxyacyl-CoA as a substrate. Moreover, based on the phylogenetic tree analysis, we propose that the 3HPCD homologues from the phylum Crenarchaeota have an enoyl-group binding pocket similar to that of bacterial short-chain ECHs.

Poly(ethylene terephthalate) (PET) is a widely used plastic and its accumulation in the environment has become global problem. Here the authors report the crystal structure of a Ideonella sakaiensis PET-degrading enzyme and propose a molecular mechanism for PET degradation.

Background The objective of the study was to evaluate the predictive value of plasma D-dimer at admission after acute ischemic stroke, and to assess its effect on short-term functional outcome. Methods Fasting plasma D-dimer was measured in 290 consecutive patients (61.7% men, mean age 67.0±12.3 years) within 3 days after the onset of acute ischemic stroke. The outcomes were measured at 3-months after stroke onset, by the modified Rankin Scale (mRS). Results Atrial fibrillation, hypertension, diabetes and involvement of the insular cortex, the levels of serum high sensitive C-reactive protein and D-dimer, as well as incidence of women and age, were all significantly higher in the poor outcome group (P

In spite of the popularity of ensemble streamflow predictions (ESP), data necessary to produce these predictions are still limited in many countries. This study developed an ensemble flood forecasting methodology for an urban catchment in Korea where only deterministic forecasts of three-hour rainfall accumulations are provided twice a day. The forecasted ensembles of rainfall were created using a time-lagged ensemble approach and used in a rainfall-runoff model to generate ensemble flood forecasts. An auto-regressive (AR) processor was then applied to the input and output ensembles to improve the accuracy of the flood forecasts. The Jungrang catchment was selected to evaluate the performance of the proposed methodology. This is one of the urban areas vulnerable to flooding. From 1991 to 2010, there were 154 fatalities and 5,278 injured victims resulting from flooding. An accuracy evaluation using observations from 2002 to 2009 found that the time-lagged ensemble approach alone produced significant bias but the AR processor reduced the relative error percentage of the peak discharge from 60% to 10% and also decreased the peak timing error from more than 10 h to less than 3 h, on average. The proposed methodology is easy and inexpensive to implement with the existing products and models and thus can be immediately activated until a new product for forecasted meteorological ensembles is officially issued in Korea.

Metallosphaera sedula is a thermoacidophilic archaeon and has an incomplete TCA/glyoxylate cycle that is used for production of biosynthetic precursors of essential metabolites. Citrate synthase from M. sedula (MsCS) is an enzyme involved in the first step of the incomplete TCA/glyoxylate cycle by converting oxaloacetate and acetyl-CoA into citrate and coenzyme A. To elucidate the inhibition properties of MsCS, we determined its crystal structure at 1.7 Å resolution. Like other Type-I CS, MsCS functions as a dimer and each monomer consists of two distinct domains, a large domain and a small domain. The oxaloacetate binding site locates at the cleft between the two domains, and the active site was more closed upon binding of the oxaloacetate substrate than binding of the citrate product. Interestingly, the inhibition kinetic analysis showed that, unlike other Type-I CSs, MsCS is non-competitively inhibited by NADH. Finally, amino acids and structural comparison of MsCS with other Type-II CSs, which were reported to be non-competitively inhibited by NADH, revealed that MsCS has quite unique NADH binding mode for non-competitive inhibition.

In Ebstein's anomaly, maximal expansion in the atrialized right ventricle (RV) occurs during early diastole, whereas that of the functional RV occurs in late diastole, resulting in diastolic dyssynchronous expansion (DSE). We quantitatively assessed DSE and identified preoperative factors correlated with persistent DSE after surgery. Seventeen patients diagnosed with Ebstein's anomaly in whom transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) images available were retrospectively analyzed for quantitative DSE assessment and 10 patients who underwent surgery and postoperative TTE available were additionally analyzed for postoperative DSE. Severity of DSE was assessed by the time difference of maximal expansion between the atrialized and functional RV divided by the cardiac cycle length × 100 ("DSE index"). Relations between DSE and, clinical, electrophysiologic parameters and the severity of tricuspid valve (TV) tethering (the RV length / tethering height during diastole: "Tethering index") were assessed. In total patients, median DSE index and tethering index were 30.3 and 2.1 respectively, and the DSE index was correlated with tethering index (rs = 0.664, P = 0.004). In 10 patients who underwent surgery, this association remained after surgery and at 2-year follow up. Tethering index ≥2.5 separated patients with and without persistent DSE. In conclusion, DSE exists in Ebstein's anomaly. DSE index is related to the tethering index and DSE persists postoperatively if tethering index ≥ 2.5. As the persistent DSE might possibly impede the optimal recovery of RV function after surgery, severity of TV tethering should take into account in considering surgery.

Novel core-shell structure hard carbon/Si-carbon composites are prepared, and their electrochemical performances as an anode material for lithium-ion batteries are reported. Three different types of shell coating are applied using Si-carbon, Si-carbon black-carbon and Si-carbon black-carbon/graphite nanosheets. It appears that the use of n-Si/carbon black/carbon composite particles in place of n-Si for the shell coating is of great importance to achieve enhanced electrochemical performances from the core-shell composite samples, and additional wrapping with graphite nanosheets leads to a more stable cycle performance of the core-shell composites.

BackgroundData are limited regarding outcomes of deferred lesions in patients with angiographically insignificant stenosis but low fractional flow reserve (FFR). We investigated the natural history of angiographically insignificant stenosis with low FFR among patients who underwent routine 3‐vessel FFR measurement. Methods and ResultsFrom December 2011 to March 2014, 1136 patients with 3298 vessels underwent routine 3‐vessel FFR measurement (3V FFR‐FRIENDS study, ClinicalTrials.gov identifier NCT01621438), and this study analyzed the 2‐year clinical outcomes of 1024 patients with 2124 lesions with angiographically insignificant stenosis (percentage of diameter stenosis 0.80 versus low FFR ≤0.80). The primary end point was outcome of major adverse cardiovascular events (a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization) at 2 years. Mean angiographic percentage of diameter stenosis and FFR of total lesions were 32.5±10.3% and 0.91±0.08%, respectively. Among the total lesions with angiographically insignificant stenosis, 8.7% showed low FFR (185 lesions). The incidence of lesions with low FFR was 2.5%, 3.8%, 9.0%, and 15.1% in categories of percentage of diameter stenosis

The voltage-gated potassium channel, Kv1.3, and the Ca2+-activated potassium channel, KCa3.1, regulate membrane potentials in T cells, thereby controlling T cell activation and cytokine production. However, little is known about the expression and function of potassium channels in human effector memory (EM) CD8+ T cells that can be further divided into functionally distinct subsets based on the expression of the interleukin (IL)-7 receptor alpha (IL-7Rα) chain. Herein, we investigated the functional expression and roles of Kv1.3 and KCa3.1 in EM CD8+ T cells that express high or low levels of the IL-7 receptor alpha chain (IL-7Rαhigh and IL-7Rαlow, respectively). In contrast to the significant activity of Kv1.3 and KCa3.1 in IL-7Rαhigh EM CD8+ T cells, IL-7Rαlow EM CD8+ T cells showed lower expression of Kv1.3 and insignificant expression of KCa3.1. Kv1.3 was involved in the modulation of cell proliferation and IL-2 production, whereas KCa3.1 affected the motility of EM CD8+ T cells. The lower motility of IL-7Rαlow EM CD8+ T cells was demonstrated using transendothelial migration and motility assays with intercellular adhesion molecule 1- and/or chemokine stromal cell-derived factor-1α-coated surfaces. Consistent with the lower migration property, IL-7Rαlow EM CD8+ T cells were found less frequently in human skin. Stimulating IL-7Rαlow EM CD8+ T cells with IL-2 or IL-15 increased their motility and recovery of KCa3.1 activity. Our findings demonstrate that Kv1.3 and KCa3.1 are differentially involved in the functions of EM CD8+ T cells. The weak expression of potassium channels in IL-7Rαlow EM CD8+ T cells can be revived by stimulation with IL-2 or IL-15, which restores the associated functions. This study suggests that IL-7Rαhigh EM CD8+ T cells with functional potassium channels may serve as a reservoir for effector CD8+ T cells during peripheral inflammation.

Lysine decarboxylase (LDC) catalyzes the decarboxylation of l-lysine to produce cadaverine, an important industrial platform chemical for bio-based polyamides. However, due to high flexibility at the pyridoxal 5-phosphate (PLP) binding site, use of the enzyme for cadaverine production requires continuous supplement of large amounts of PLP. In order to develop an LDC enzyme from Selenomonas ruminantium (SrLDC) with an enhanced affinity for PLP, we introduced an internal disulfide bond between Ala225 and Thr302 residues with a desire to retain the PLP binding site in a closed conformation. The SrLDCA225C/T302C mutant showed a yellow color and the characteristic UV/Vis absorption peaks for enzymes with bound PLP, and exhibited three-fold enhanced PLP affinity compared with the wild-type SrLDC. The mutant also exhibited a dramatically enhanced LDC activity and cadaverine conversion particularly under no or low PLP concentrations. Moreover, introduction of the disulfide bond rendered SrLDC more resistant to high pH and temperature. The formation of the introduced disulfide bond and the maintenance of the PLP binding site in the closed conformation were confirmed by determination of the crystal structure of the mutant. This study shows that disulfide bond-mediated spatial reconstitution can be a platform technology for development of enzymes with enhanced PLP affinity.

Aspartate aminotransferase from Corynebacterium glutamicum (CgAspAT) is a PLP-dependent enzyme that catalyzes the production of L-aspartate and α-ketoglutarate from L-glutamate and oxaloacetate in L-lysine biosynthesis. In order to understand the molecular mechanism of CgAspAT and compare it with those of other aspartate aminotransferases (AspATs) from the aminotransferase class I, we determined the crystal structure of CgAspAT. CgAspAT functions as a dimer, and the CgAspAT monomer consists of two domains, the core domain and the auxiliary domain. The PLP cofactor is found to be bound to CgAspAT and stabilized through unique residues. In our current structure, a citrate molecule is bound at the active site of one molecule and mimics binding of the glutamate substrate. The residues involved in binding of the PLP cofactor and the glutamate substrate were confirmed by site-directed mutagenesis. Interestingly, compared with other AspATs from aminotransferase subgroup Ia and Ib, CgAspAT exhibited unique binding sites for both cofactor and substrate; moreover, it was found to have unusual structural features in the auxiliary domain. Based on these structural differences, we propose that CgAspAT does not belong to either subgroup Ia or Ib, and can be categorized into a subgroup Ic. The phylogenetic tree and RMSD analysis also indicates that CgAspAT is located in an independent AspAT subgroup.

Atrial fibrillation is the most common arrhythmia and is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM). Although left atrial (LA) remodeling and dysfunction are known to associate with the development of atrial fibrillation in HCM, the changes of the LA in HCM patients remain unclear. This study aimed to evaluate the changes in LA size and mechanical function in HCM patients compared to control subjects and to determine the characteristics of HCM associated with LA remodeling and dysfunction.Seventy-nine HCM patients (mean age, 54 ± 11 years; 76% were men) were compared to 79 age- and sex-matched controls (mean age, 54 ± 11 years; 76% were men) and 20 young healthy controls (mean age, 33 ± 5 years; 45% were men). The LA diameter, volume, and mechanical function, including global strain (ε), were evaluated by 2D-speckle tracking echocardiography. The phenotype of HCM, maximal left ventricular (LV) wall thickness, LV mass, and presence and extent of late gadolinium enhancement (LGE) were evaluated with cardiac magnetic resonance imaging.HCM patients showed increased LA volume index, impaired reservoir function, and decreased LA ε compared to the control subjects. When we divided the HCM group according to a maximal LA volume index (LAVImax) of 38.7 ml/m2 or LA ε of 21%, no significant differences in the HCM phenotype and maximal LV wall thickness were observed for patients with LAVImax >38.7 ml/m2 or LA ε ≤21%. Conversely, the LV mass index was significantly higher both in patients with maximal LA volume index >38.7 ml/m2 and with LA ε ≤21% and was independently associated with LAVImax and LA ε. Although the LGE extent was increased in patients with LA ε ≤21%, it was not independently associated with either LAVImax or LA ε.HCM patients showed progressed LA remodeling and dysfunction; the determinant of LA remodeling and dysfunction was LV mass index rather than LV myocardial fibrosis by LGE-magnetic resonance imaging.

Lysine decarboxylase (LDC) is a crucial enzyme for acid stress resistance and is also utilized for the biosynthesis of cadaverine, a promising building block for bio-based polyamides. We determined the crystal structure of LDC from Selenomonas ruminantium (SrLDC). SrLDC functions as a dimer and each monomer consists of two distinct domains; a PLP-binding barrel domain and a sheet domain. We also determined the structure of SrLDC in complex with PLP and cadaverine and elucidated the binding mode of cofactor and substrate. Interestingly, compared with the apo-form of SrLDC, the SrLDC in complex with PLP and cadaverine showed a remarkable structural change at the PLP binding site. The PLP binding site of SrLDC contains the highly flexible loops with high b-factors and showed an open-closed conformational change upon the binding of PLP. In fact, SrLDC showed no LDC activity without PLP supplement, and we suggest that highly flexible PLP binding site results in low PLP affinity of SrLDC. In addition, other structurally homologous enzymes also contain the flexible PLP binding site, which indicates that high flexibility at the PLP binding site and low PLP affinity seems to be a common feature of these enzyme family.

BACKGROUND: The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES. METHODS: The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months. RESULTS: The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P=0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P=0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P=0.34) were comparable between the 2 groups. CONCLUSIONS: In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES. [ABSTRACT FROM AUTHOR]