Development and Evaluation of a Robust Sandwich Immunoassay System Detecting Serum WFA-Reactive IgA1 for Diagnosis of IgA Nephropathy

Aberrant glycosylation of IgA1 is involved in the development of IgA nephropathy (IgAN). There are many reports of IgAN markers focusing on the glycoform of IgA1. None have been clinically applied as a routine test. In this study, we established an automated sandwich immunoassay system for detecting aberrant glycosylated IgA1, using Wisteria floribunda agglutinin (WFA) and anti-IgA1 monoclonal antibody. The diagnostic performance as an IgAN marker was evaluated. The usefulness of WFA for immunoassays was investigated by lectin microarray. A reliable standard for quantitative immunoassay measurements was designed by modifying a purified IgA1 substrate. A validation study using multiple serum specimens was performed using the established WFA-antibody sandwich automated immunoassay. Lectin microarray results showed that WFA specifically recognized N-glycans of agglutinated IgA1 in IgAN patients. The constructed IgA1 standard exhibited a wide dynamic range and high reactivity. In the validation study, serum WFA-reactive IgA1 (WFA+-IgA1) differed significantly between healthy control subjects and IgAN patients. The findings indicate that WFA is a suitable lectin that specifically targets abnormal agglutinated IgA1 in serum. We also describe an automated immunoassay system for detecting WFA+-IgA1, focusing on N-glycans.     

Iterative Path Integral Approach to Nonlinear Stochastic Optimal Control Under Compound Poisson Noise

Nonlinear stochastic optimal control theory has played an important role in many fields. In this theory, uncertainties of dynamics have usually been represented by Brownian motion, which is Gaussian white noise. However, there are many stochastic phenomena whose probability density has a long tail, which suggests the necessity to study the effect of non‐Gaussianity. This paper employs Lévy processes, which cause outliers with a significantly higher probability than Brownian motion, to describe such uncertainties. In general, the optimal control law is obtained by solving the Hamilton–Jacobi–Bellman equation. This paper shows that the path‐integral approach combined with the policy iteration method is efficiently applicable to solve the Hamilton–Jacobi–Bellman equation in the Lévy problem setting. Finally, numerical simulations illustrate the usefulness of this method.     

Cumulative Damage Mechanism of Short Fiber type C/SiC under Compression

This study investigated cumulative damage mechanisms of short fiber type C/SiC under compression. To measure mechanical properties (unloading modulus and permanent strain) before fracture, repeated loading–unloading tests were conducted using a strain gage. Damage was observed to assess characteristics of crack density, length, number, and propagation angle. Furthermore, relations between mechanical properties and damage characteristics were elucidated by application of Basista’s equations and by substituting crack densities inferred from damage observations. Stress–strain relations revealed nonlinear behavior. The unloading modulus did not change, but the permanent strain increased. Cracks propagated mainly between fibers, without fiber fracture, connecting other cracks in the direction of orientation 0 deg to 30 deg to the compressive axis. We estimated permanent strain using Basista’s equations and damage characteristics. Estimates roughly agreed with experiment results, suggesting that the permanent strain increase is attributable to closed crack sliding and friction caused by increased crack density.     

Self‐Degradable Lipid‐Like Materials Based on “Hydrolysis accelerated by the intra‐Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery

RNA‐based therapeutics is a promising approach for curing intractable diseases by manipulating various cellular functions. For eliciting RNA (i.e., mRNA and siRNA) functions successfully, the RNA in the extracellular space must be protected and it must be delivered to the cytoplasm. In this study, the development of a self‐degradable lipid‐like material that functions to accelerate the collapse of lipid nanoparticles (LNPs) and the release of RNA into cytoplasm is reported. The self‐degradability is based on a unique reaction “Hydrolysis accelerated by intra‐Particle Enrichment of Reactant (HyPER).” In this reaction, a disulfide bond and a phenyl ester are essential structural components: concentrated hydrophobic thiols that are produced by the cleavage of the disulfide bonds in the LNPs drive an intraparticle nucleophilic attack to the phenyl ester linker, which results in further degradation. An oleic acid‐scaffold lipid‐like material that mounts all of these units (ssPalmO‐Phe) shows superior transfection efficiency to nondegradable or conventional materials. The insertion of the aromatic ring is unexpectedly revealed to contribute to the enhancement of endosomal escape. Since the intracellular trafficking is a sequential process that includes cellular uptake, endosomal escape, the release of mRNA, and translation, the improvement in each process synergistically enhances the gene expression.     

Real-time digital simulator with digital/analog conversioninterface for testing power instruments

The need for real-time simulation stems from the fact that in many practical situations it is desirable to analyze the dynamic behavior of a large power system with advanced equipment that has complex and high-speed performance. Analog simulators are effective, however they impose serious limitations on the size of the system that is being modeled. The authors have studied and developed a real-time digital simulator using a hypercube computer, and realized real-time performance available for the analysis of large power systems. As the second step of the study, they developed a digital/analog conversion interface for testing actual power instruments. The interface exchanges the variables of fundamental frequency domain in the real-time digital simulator, and the variables of exact time domain in the analog equipment connected to the simulator. In this paper, the authors describe the detail of the digital/analog conversion interface of the real-time digital simulator for testing advanced power instruments. Its conversion algorithm, system configuration of the simulator with the interface, and experimental results are also presented     

Japanese cedar pollinosis in children in our allergy clinic

Recently, it is pointed out that the incidence of Japanese cedar pollinosis has increased in children. We studied on the rate of sensitization and the onset of the disease in children under sixteen who visited allergy clinic in the Department of Otorhinolaryngology in Mie University Hospital. The percentage of positive rate of skin test and IgE antibodies of house dust mite was about 80 to 90% in 1981, 1991, and 1996. However, the percentage of positive rate of skin test and IgE antibodies of Japanese cedar pollen was 43% and 26%, respectively in 1981, but both increased to 58% in 1996. Most of Japanese cedar pollinosis patients also had house dust mite allergy. Among 115 pediatric patients who visited our allergy clinics in the past seven years, 32.2% were allergic to house dust mite alone, 8.6% were allergic to Japanese cedar pollen alone, 40.9% were allergic to both, and 6.1% were allergic to house dust mite, Japanese cedar pollen, and orchard grass pollen. 68% of the total 115 patients were boys, but significantly more girls had the pollinosis. 17.4% of those who are sensitized to the pollen were asymptomatic during the pollen season. Thus, it was confirmed that the rate of children sensitized to the pollen has apparently increased for the past twenty years. We should take care of those children who are sensitized to the pollen but asymptomatic during the pollen season.     

Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects

Vascular surgery can be safely performed in approximately 60% of patients with advanced peripheral vascular disease, because of the high frequency of concomitant coronary artery disease and consequent increased risk of perioperative cardiac complications. The aim of this study was to validate the hypothesis that endovascular revascularization could be safely applied to high-cardiac-risk patients with a lower incidence of perioperative cardiac complications. One hundred and fourteen patients with peripheral vascular disease referred for revascularization underwent preoperatively a clinical and echocardiographic evaluation, at rest and under dipyridamole stress test, to assess the cardiac risk. Patients with high clinical score (according to Goldman and Detsky), or low left ventricular ejection fraction at rest, or positive dipyridamole stress test, were considered at high cardiac risk. To record adverse cardiac events, all patients were monitored during surgery, postoperatively, and followed up for 18 months after hospital discharge. Forty-eight patients (42%) were found to be at high cardiac risk. In this high-cardiac-risk group, endovascular surgery was performed in 37/48 patients (77%) (group A), while the remaining 11/48 patients (23%) were bypassed with open surgery (group B). Postoperative cardiac complications occurred in 16% of patients in group A and in 45% of patients in group B with two deaths (p < 0.05). At follow-up, 51% of patients in group A and 44% of patients in group B had suffered late cardiac events (p=ns), with 10 deaths in group A and three deaths in group B (p=ns). Limb salvage rate was similar in the two groups (95% group A, 100% group B; p=ns). These data show that high-cardiac-risk patients with limb-threatening ischemia have significantly less perioperative cardiac complications when treated by endovascular procedures instead of bypass surgery. Follow-up data on cardiac events confirm the severity of concomitant coronary artery disease in patients with peripheral vascular disease.