Built-in RNA-mediated chaperone (chaperna) for antigen folding tailored to immunized hosts.

High-quality antibody (Ab) production depends on the availability of immunologically relevant antigens. We present a potentially universal platform for generating soluble antigens from bacterial hosts, tailored to immunized animals for Ab production. A novel RNA-dependent chaperone, in which the target antigen is genetically fused with an RNA-interacting domain (RID) docking tag derived from the immunized host, promotes the solubility and robust folding of the target antigen. We selected the N-terminal tRNA-binding domain of lysyl-tRNA synthetase (LysRS) as the RID for fusion with viral proteins and demonstrated the expression of the RID fusion proteins in their soluble and native conformations; immunization predominantly elicited Ab responses to the target antigen, whereas the "self" RID tag remained nonimmunogenic. Differential immunogenicity of the fusion proteins greatly enriched and simplified the screening of hybridoma clones of monoclonal antibodies (mAbs), enabling specific and sensitive serodiagnosis of MERS-CoV infection. Moreover, mAbs against the consensus influenza hemagglutinin stalk domain enabled a novel assay for trivalent seasonal influenza vaccines. The Fc-mediated effector function was demonstrated, which could be harnessed for the design of next-generation "universal" influenza vaccines. The nonimmunogenic built-in antigen folding module tailored to a repertoire of immunized animal hosts will drive immunochemical diagnostics, therapeutics, and designer vaccines.

Physicochemical code for quinary protein interactions in Escherichia coli.

How proteins sense and navigate the cellular interior to find their functional partners remains poorly understood. An intriguing aspect of this search is that it relies on diffusive encounters with the crowded cellular background, made up of protein surfaces that are largely nonconserved. The question is then if/how this protein search is amenable to selection and biological control. To shed light on this issue, we examined the motions of three evolutionary divergent proteins in the Escherichia coli cytoplasm by in-cell NMR. The results show that the diffusive in-cell motions, after all, follow simplistic physical-chemical rules: The proteins reveal a common dependence on (i) net charge density, (ii) surface hydrophobicity, and (iii) the electric dipole moment. The bacterial protein is here biased to move relatively freely in the bacterial interior, whereas the human counterparts more easily stick. Even so, the in-cell motions respond predictably to surface mutation, allowing us to tune and intermix the protein's behavior at will. The findings show how evolution can swiftly optimize the diffuse background of protein encounter complexes by just single-point mutations, and provide a rational framework for adjusting the cytoplasmic motions of individual proteins, e.g., for rescuing poor in-cell NMR signals and for optimizing protein therapeutics.

A prediction model for renal artery stenosis using carotid ultrasonography measurements in patients undergoing coronary angiography.

BACKGROUND: Carotid intima-media thickness (CIMT) and carotid atherosclerotic plaque (CAP) are well-known indicators of atherosclerosis. However, few studies have reported the value of CIMT and CAP for predicting renal artery stenosis (RAS). We investigated the predictive value of CIMT and CAP for RAS and propose a model for predicting significant RAS in patients undergoing coronary angiography (CAG). METHODS: Consecutive patients who underwent renal angiography at the time of CAG in a single center in 2011 were included. RAS ≥50% was considered significant. Multiple logistic regression analysis with step-down variable selection method was used to select the best model for predicting significant RAS and bootstrap resampling was used to validate the best model. A scoring system for predicting significant RAS was developed by adding the closest integers proportional to the coefficients of the regression formula. RESULTS: Significant RAS was observed in 60 of 641 patients (9.6%) who underwent CAG. Hypertension, diabetes, significant coronary artery disease (CAD) and chronic kidney disease (CKD) stage ≥3 were more prevalent in patients with significant RAS. Mean age, CIMT and number of anti-hypertensive medications (AHM) were higher and body mass index (BMI) and total cholesterol level were lower in patients with significant RAS. Multiple logistic regression analysis identified significant CAD (odds ratio (OR) 5.6), unilateral CAP (OR 2.6), bilateral CAP (OR 4.9), CKD stage ≥3 (OR 4.8), four or more AHM (OR 4.8), CIMT (OR 2.3), age ≥67 years (OR 2.3) and BMI <22 kg/m2 (OR 2.4) as independent predictors of significant RAS. The scoring system for predicting significant RAS, which included these predictors, had a sensitivity of 83.3% and specificity of 81.6%. The predicted frequency of the scoring system agreed well with the observed frequency of significant RAS (coefficient of determination r2 = 0.957). CONCLUSIONS: CIMT and CAP are independent predictors of significant RAS. The proposed scoring system, which includes CIMT and CAP, may be useful for predicting significant RAS in patients undergoing CAG.

A novel energy efficient path for nitrogen fixation using a non-thermal arc.

Plasma-assisted nitrogen fixation is a promising sustainable and clean alternative to the classical Haber-Bosch process. However, the high energy consumption and low production rate of plasma-assisted nitrogen fixation limit its application. This study shows that the non-thermal (non-equilibrium) enhancement of the arc plasma significantly reduces the energy consumption of nitrogen fixation. The highest energy efficiency with high NO selectivity is observed with a low specific energy input (SEI). However, the highest production rate is reached at a high SEI. The studied process offers high NO selectivity (up to 95%) with low energy consumption (∼48 GJ per tN) at 0.1 kJ L-1 SEI, which is much lower than the previously reported value of plasma-assisted atmospheric nitrogen fixation and is close to that of the Haber-Bosch process.

Fatal vascular complications during transradial percutaneous coronary intervention: A case report.

RATIONALE: Vascular complications of transradial percutaneous coronary intervention (PCI) are rare and usually occur at the access site below the elbow. However, vessels along the tract of the wire or catheter can be injured at any point, causing various types of bleeding complications. PATIENT CONCERNS: A 57-year-old man visited due to chest discomfort. Coronary angiography showed significant stenosis at the distal right coronary artery (RCA). Immediately after the coronary guidewire was passed through the distal RCA, he started a vigorous cough. The voice changed, dyspnea occurred within minutes, and lip cyanosis and stridor were observed. After endotracheal intubation, successful stenting of the distal RCA was achieved. He was extubated at 30 minutes after coronary stenting, but 1-hour post-extubation, his blood pressure suddenly decreased to 70/50 mmHg. DIAGNOSIS: Mediastinal widening was newly noted on chest X-ray, and blood hemoglobin was decreased. Contrast-enhanced chest computed tomography showed mediastinal hematoma, tracheal compression, and hemothorax. Contrast extravasation was noted in the terminal branches of the inferior thyroid artery on brachiocephalic angiography. INTERVENTIONS: Successful hemostasis was achieved with endovascular embolization therapy using a Tornado embolization microcoil, Gelfoam gelatin sponge, and Histoacryl glue. The next day, the mediastinal hemorrhage was drained by mediastinoscopy. The endotracheal intubation and ventilator care were maintained for 2 days, and 6 units of packed red blood cells were transfused. Antithrombotics were used to prevent stent thrombosis, and antibiotics to control infection, respectively. OUTCOMES: After successful hemostasis, thrombocytosis and high on-treatment platelet reactivity that disappeared at 2 weeks post-discharge were noted. Follow-up chest imaging showed the normalized mediastinal widening. At 14 months post-discharge, the patient remains healthy. LESSONS: As life-threating vascular complications, such as brachiocephalic, subclavian vessel dissection, and vessel perforation in the internal mammary, costocervical, and thyrocervical arteries, can occur anytime during transradial PCI, the intervention cardiologist should be well aware of it and have the appropriate countermeasures implemented in the routine procedure.

Plasma jet assisted carbonization and activation of coffee ground waste.

Activated carbon has been extensively utilized to adsorb pollutants generated by industrial activities. There have been many attempts to efficiently produce activated carbon from spent coffee grounds in the field of environmental technology. In this study, the feasibility of the novel production of activated carbon from coffee ground waste using a plasma jet was evaluated. A rotating gliding arc generator was designed that used an N2 plasma jet for the carbonization process and a CO2 plasma jet for the activation process. It was confirmed that the coffee ground waste could be carbonized and activated by the two plasma jets in the same reactor. The characteristics of the surface morphologies of the activated carbon samples varied depending on the plasma treatment conditions, such as the electric power of the plasma jet and the treatment time. The results implied that the adsorption capacity of the activated carbon could be optimized by regulating the pore size and distribution based on the plasma treatment conditions with regard to the molecular size of the target adsorbate.

Comparison of the accuracy and errors of blood pressure measured by 2 types of non-mercury sphygmomanometers in an epidemiological survey.

A few studies have compared auscultation and oscillometric devices with the mercury sphygmomanometer (MS) reference values for blood pressure (BP) measurement in an epidemiologic survey.Four trained observers recorded BP measurements from 766 subjects from general Korean population in 2014 and 2015. Measurements were repeated 3 times for each device, alternately using an MS and 2 electronic devices (EDs; Greenlight 300 vs Omron HEM-907), together with a randomized device sequence. The BP measurement difference was defined as BP measured by MS minus BP obtained by ED, and the absolute error as the absolute value of the difference.Mean differences in systolic BP (SBP) were -0.52 and -0.62 mmHg and those of diastolic BP (DBP) were -0.78 and 6.23 mmHg (P < .01) in the Greenlight and Omron device group, respectively. The concordance correlation coefficients were 0.97 and 0.94 for SBP and 0.95 and 0.76 for DBP in the Greenlight and Omron group, respectively (P < .05). Kappa values for the Joint National Committee 7 BP classification were 0.84 and 0.74 for Greenlight and Omron group, respectively. The prevalence of normotension, prehypertension and hypertension were 53.5%, 33.9%, and 12.5% with the MS and 59.8%, 29.0%, and 11.2% with the ED in the Omron group (P = .03, McNemar test), whereas they were insignificant in the Greenlight group.The Greenlight 300 may be a good alternative to the MS, and the Omron HEM-907 has good accuracy in SBP measurement. Due to the measurement error in DBP, Omron HEM-907 was inferior to the Greenlight device.

Successful coronary stenting in a patient with factor V deficiency in the absence of fresh frozen plasma transfusion: Case report.

RATIONALE: Drug-eluting stent (DES) implantation in a patient with factor V deficiency (F5D) is very complex. No antithrombotic therapy study has been reported for F5D patients who undergo a coronary stenting procedure. PATIENT CONCERNS: A 73-year-old woman presented with chest discomfort and exertional dyspnea. Coronary stenting was performed successfully using DES stents. DIAGNOSES: The D-dimer, prothrombin time, and partial thromboplastin time prolongation persisted from admission until 24 hours after coronary stenting. Epistaxis and blood-tinged sputum occurred on day 3. The antiplatelet therapy measured using a Multiplate Analyzer was adequate, and other laboratory findings except factor V activity (14%) were within normal ranges; she was diagnosed with F5D based on low factor V activity. INTERVENTIONS: While taking 90 mg of ticagrelor and 100 mg of aspirin daily, the patient revisited due to recurrent epistaxis, hemoptysis, and coughing on day 26. Epistaxis and hemoptysis stopped after the aspirin was discontinued. Finally, the daily maintenance dose was reduced to 90 mg of ticagrelor once. OUTCOMES: She led healthy life for 9 months without any recurrent symptoms and the test results also were stabilized. LESSONS: We report a case of an F5D patient who underwent coronary stenting in the absence of frozen fresh plasma transfusion who received successful maintenance therapy using a single antiplatelet agent (90 mg of ticagrelor/day) with recurrent multiple mucosal bleeding events after coronary stenting.

Doping effects on trimerization and magnetoelectric coupling of single crystal multiferroic (Y,Lu)MnO3.

Hexagonal RMnO3 is a multiferroic compound with a giant spin-lattice coupling at an antiferromagnetic transition temperature, Lee et al (2008 Nature 451 805). Despite extensive studies over the past two decades, the origin and underlying microscopic mechanism of strong spin-lattice coupling remain very much elusive. In this study, we have tried to address this problem by measuring the thermal expansion and dielectric constant of doped single crystals Y1-x Lu x MnO3 where x = 0, 0.25, 0.5, 0.75, and 1.0. From these measurements, we confirm that there is a progressive change in the physical properties with doping. At the same time, all our samples exhibit clear anomalies at T N, even in the samples where x = 0.5 and 0.75. This is opposed to some earlier ideas, which suggests an unusual doping dependence of the anomaly. Our work reveals yet another interesting facet of the spin-lattice coupling issue in hexagonal RMnO3.

Impact of Visit-to-Visit Variability in Systolic Blood Pressure on Cardiovascular Outcomes in Korean National Health Insurance Service-National Sample Cohort.

BACKGROUND: Despite an association between visit-to-visit blood pressure (BP) variability (VV-BPV) and cardiovascular (CV) outcomes, many studies performed during the past 4 years have shown conflicting results. This study investigated the impact of VV-BPV on CV outcomes in the Korean National Health Insurance Service (NHIS) database-National Sample Cohort. METHODS: From the 2002 Korean NHIS database (n = 47,851,928), sample subjects with 3 or more BP measurements (n = 51,811) were divided into 2 groups according to a 10 mm Hg cutoff in the SD of systolic BP (SD-SBP). The CV outcomes of these groups were compared by sensitivity analyses using various sampling methods. RESULTS: Irrespective of sampling method, subjects with SD-SBPs ≥10 mm Hg had higher rates of CV events or death, nonfatal myocardial infarction (MI) or stroke, and total mortality, but were not associated with CV mortality. The hazard ratios for CV events or death, nonfatal MI or stroke, CV mortality, and total mortality were 1.43 (95% confidence interval [CI], 1.25-1.63, P < 0.01), 1.45 (95% CI, 1.27-1.65, P < 0.01), 1.32 (95% CI, 0.89-1.94, P = 0.17), and 1.18 (95% CI, 1.01-1.38, P = 0.04), respectively. CONCLUSIONS: Increased VV-BPV was an independent risk factor for future CV outcomes, independent of mean BP status, even in normotensive subjects and in all subgroups, except females. Similar VV-BPV values in the sensitivity analyses suggest VV-BPV is a reproducible phenomenon, reflecting the various types of intrinsic physiologic properties.

Two Distinct Responses of Left Ventricular End-Diastolic Pressure to Leg-Raise Exercise in Euvolemic Patients with Exertional Dyspnea.

BACKGROUND AND OBJECTIVES: Few studies have invasively assessed diastolic functional reserve and serial changes in left ventricular hemodynamics in euvolemic patients with exertional dyspnea. In this study, sequential changes in left ventricular end-diastolic pressure (LVEDP) to leg-raise exercise were measured invasively in patients with early heart failure with preserved ejection fraction (HFpEF) to determine the association between these serial changes and echocardiographic results or clinical features. SUBJECTS AND METHODS: During their hospital stay, 181 patients with early HFpEF underwent left cardiac catheterization, coronary angiography, and transthoracic echocardiography (TTE). Leg-raise exercise was performed in two stages: during cardiac catheterization and again during TTE. RESULTS: Compared with the initial values, all the invasively measured LVEDP values increased significantly during the leg-raise exercise, whereas the septal e/e' ratio remained unchanged. Active leg-raise led to increased LVEDP, which caused dyspnea. The severity of symptoms correlated with the level and extent of changes in LVEDP. At the end of active leg-raise, LVEDP decreased in 40 patients (22.1%), who were younger and had significantly lower e/e' ratios. On multivariate analysis to predict the response of LVEDP to active leg-raise, age and the septal e/e' ratio remained significant predictors. CONCLUSION: Despite having similar LVEDP values at rest, patients may respond to exercise with different LVEDP levels and clinical manifestations, depending on their diastolic capacity. The leg-raise exercise in early HFpEF can elucidate individual diastolic profiles, and the LVEDP response to the leg-raise test may serve as a useful criterion in stratifying patients with early HFpEF with respect to functional reserve.

Gene and dietary calcium interaction effects on brachial-ankle pulse wave velocity.

BACKGROUND & AIM: Understanding the lifestyle and genetic factors that affect pulse wave velocity (PWV) may provide clues to preventing atherosclerotic cardiovascular events. The aim of this study is to investigate genome-wide genetic and dietary calcium (Ca) intake interaction effects on brachial-ankle pulse wave velocity (baPWV). METHODS: The baPWV was measured, and Ca intake was quantified by administering a food frequency questionnaire (FFQ) to 3198 participants, which included men and women (≥40 years) from the Korean Multi-Rural communities Cohort study (MRCohort). The interaction effects of dietary Ca intake and 19 single-nucleotide polymorphisms (SNPs) on baPWV were assessed using the general linear models. RESULTS: Dietary Ca intake was not significantly associated with baPWV or any type of SNP among the subjects herein. In men, however, the adducin1 (ADD1) rs4961_C SNP had a significant dietary Ca intake-dependent effect on mean baPWV (pinteraction = 0.002). In women, the interaction of zinc finger proteins 618 (ZNF618) rs10817542_A with dietary Ca intake played a significant and key role in mean baPWV (pinteraction = 0.001). In the results of ADD1 rs4961_C in men and ZNF618 rs10817542_A in women, the minor allele-lowest Ca intake tertile (T1) group had significantly higher mean baPWV value than other subgroups of Ca intake tertile-genotype cross-classification whereas genotype was not a significant effector on mean baPWV values among highest Ca intake subgroups (T3). CONCLUSIONS: The baPWV, a phenotype of arterial stiffness, can be modulated in subjects through regulation of dietary Ca intake, particularly in subjects with more vulnerable genotypes.

Robust singlet dimers with fragile ordering in two-dimensional honeycomb lattice of Li2RuO3.

When an electronic system has strong correlations and a large spin-orbit interaction, it often exhibits a plethora of mutually competing quantum phases. How a particular quantum ground state is selected out of several possibilities is a very interesting question. However, equally fascinating is how such a quantum entangled state breaks up due to perturbation. This important question has relevance in very diverse fields of science from strongly correlated electron physics to quantum information. Here we report that a quantum entangled dimerized state or valence bond crystal (VBC) phase of Li2RuO3 shows nontrivial doping dependence as we perturb the Ru honeycomb lattice by replacing Ru with Li. Through extensive experimental studies, we demonstrate that the VBC phase melts into a valence bond liquid phase of the RVB (resonating valence bond) type. This system offers an interesting playground where one can test and refine our current understanding of the quantum competing phases in a single compound.

Large in-plane deformation of RuO6 octahedron and ferromagnetism of bulk SrRuO3.

SrRuO3 is a ferromagnetic metal with several unusual physical properties such as zero thermal expansion below Tc, so-called Invar behavior. Another anomalous feature is that the a-axis lattice constant is larger than the b-axis lattice constant, a clear deviation from the predictions of the Glazer structural description with rigid RuO6 octahedron motion. Using high resolution neutron diffraction techniques, we show how these two structural anomalies arise from the irregular in-plane deformation, i.e. plastic behavior of the RuO6 octahedron, a weak band Jahn-Teller distortion. We further demonstrate that the ferromagnetic instability of SrRuO3 is related to the temperature-induced localization of Ru 4d bands.

Antiferromagnetic ordering in Li2MnO3 single crystals with a two-dimensional honeycomb lattice.

Li(2)MnO(3) consists of a layered Mn honeycomb lattice separated by a single layer of LiO(6) octahedra along the c-axis. By using single crystal Li(2)MnO(3) samples, we have examined the physical properties and carried out both powder and single crystal neutron diffraction studies to determine that Mn moments order antiferromagnetically at T(N) = 36 K with an ordered magnetic moment of 2.3 µ(B) perpendicular to the ab plane. We have also discovered that about 35% of the full magnetic entropy is released in the supposedly simple paramagnetic phase, indicative of unusual spin dynamics at higher temperature.