E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.     

Quantification of the Phase Transformation Kinetics in High Chromium Cast Irons Using Dilatometry and Metallographic Techniques

Metallurgical and Materials Transactions A - Further development of high chromium cast irons (HCCI) is based on tailoring the microstructure, necessitating an accurate control over the phase...     

Simulation of producer gas flameless combustion with fresh reactant diluted by hot flue gas

Flameless combustion is considered as a flexible and efficient combustion process for low heating value gas fuel. This paper presents numerical simulations of premixed flameless combustion using producer gas as a fuel. Different initial conditions of the premixed fresh reactant (air/fuel mixture) and dilution levels are taken into account for the investigation. The numerical simulations were investigated using a network of chemical reactor models with the detailed reaction mechanism of GRI‐Mech 3.0. A threshold dilution level for flameless combustion fuelled by producer gas was determined. The numerical results show that dilution of the fresh reactant with hot combustion products and initial fresh reactant temperature play important roles in flameless combustion formation and its auto‐ignition behaviour, rather than equivalence ratio of the fresh reactant. In the flameless combustion regime, temperature and chemical concentrations were reduced while chemical kinetics process was decelerated, resulting in delay of the auto‐ignition process.     

Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates

Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.     

Well‐defined,environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications

In this study, both naturally occurring and artificial amino acids were successfully transformed into the corresponding urethane derivatives using diphenyl carbonate. The urethanes thus prepared could be efficiently cyclized into amino acid N‐carboxyanhydrides (NCAs) without the requirement of phosgene. In addition, the presence of primary amines converted the urethane derivatives into NCAs and initiated the ring‐opening polymerization of the in situ formed NCAs, allowing for the well‐defined synthesis of polypeptides. These polypeptides contained initiating ends functionalized by an amine‐derived residue and propagating ends bearing the reactive amino group. By precise control of the structures of the polypeptides, various polypeptide conjugates such as block copolymers and graft copolymers were successfully synthesized as designed, and their applications in antifouling coatings against proteins, drug delivery systems and biosensors were demonstrated. © 2019 Society of Chemical Industry     

Measurements of thermal-neutron capture cross-section of Cesium-135 by applying mass spectrometry

ABSTRACT

The thermal-neutron capture cross-section (σ₀) and resonance integral (I₀) were measured for the ¹³⁵Cs(n,γ)¹³⁶Cs reaction by an activation method and mass spectrometry. Because of difficulty in the preparation of pure ¹³⁵Cs samples, we used ¹³⁵Cs contained as an impurity in a normally available ¹³⁷Cs standard solution. An isotope ratio of ¹³⁵Cs and ¹³⁷Cs in a standard ¹³⁷Cs solution was measured by mass spectrometry to quantify ¹³⁵Cs. Cesium-135 impurity along with the ¹³⁷Cs standard solution was irradiated at the hydraulic conveyer of the research reactor in the Institute for Integral Radiation and Nuclear Science, Kyoto University. Wires of Co/Al and Au/Al alloys were used as neutron monitors to measure thermal-neutron fluxes and epi-thermal Westcott’s indices at an irradiation position. A gadolinium filter was used to measure the σ₀, and a value of 0.133 eV was taken as the cut-off energy. Gamma-ray spectroscopy was used to measure induced activities of ¹³⁷Cs, ¹³⁶Cs and monitor wires. On the basis of Westcott’s convention, the σ₀ and I₀ values were derived as 8.57 ± 0.25 barn, and 45.3 ± 3.2 barn, respectively. The value of σ₀ obtained in the present study agreed within the limits of uncertainties with the past-reported value of 8.3 ± 0.3 barn.     

Study on estimating electric potential in space between parallel electrodes

We have been studying on estimating distribution of permittivity between measurement electrodes using capacitance and electric potential. Two arc electrodes were separated by long distance and there electrodes were surrounded by additional electrodes respectively. In past research work, we carried out numerical electric analysis for calculating the capacitance and electric potential using Finite Element Method (FEM) and compared with experimental and numerical results. The capacitance values were almost agreed with experimental and numerical results. However, the electric potential values were different between experimental and numerical results in conventional studies. In this paper, we proposed an equivalent circuit including the stray capacity and measurement method for capacitance, the electric potential in space between long distance electrodes was estimated.     

High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman’s correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.     

Experimental study of neutron counting in a zero-power reactor driven by a neutron source inherent in highly enriched uranium fuels

Even a zero-power reactor core containing highly enriched uranium has a weak neutron source inherent in uranium 235, and consequently, a neutron counter placed closely to the core without external neutron source registers a certain counting rate. The study of the counting is very important for zero-power reactor physics experiments with a high precision. In this experimental study, first, at a shutdown state of the UTR-Kinki reactor without start-up neutron source, a pulse height distribution of output signals from a neutron proportional counter was measured to confirm that these signals resulted from neutron detections. At several subcritical states of the UTR, then, the Feynman-α analysis was carried out to confirm that the neutrons detected by the counter must be fission neutrons multiplied by fission chain reactions. The correlation amplitude measured in the Feynman-α analysis was much higher than that measured in a previous drive by start-up source. Further, it was also confirmed that the subcriticality dependence of neutron counting rate followed the source multiplication formula. This feature indicated that the one-point model was very successful in the subcritical range including the shutdown state.