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Background: Riociguat is a soluble guanylate cyclase stimulator that improves hemodynamics in patients with pulmonary hypertension (PH). Accumulating evidence implicates the additional effect of riociguat on the increase in cardiac output. However, its mechanisms have not been fully understood. This study aimed to investigate whether riociguat could ameliorate right ventricular (RV) contraction as well as hemodynamics. Methods: We studied 45 patients with pulmonary arterial hypertension (14) or chronic thromboembolic pulmonary hypertension (31) and evaluated hemodynamics, using right-sided heart catheterization, before and after the administration of riociguat. RV function was assessed by echocardiography, including speckle-tracking echocardiography. Results: Riociguat significantly improved the WHO functional class and reduced the mean pulmonary arterial pressure and vascular resistance. In addition, the cardiac index increased. RV remodeling was ameliorated after riociguat administration as assessed by the echocardiographic parameters, such as RV diameter and RV area index. RV function, including RV fractional area change and RV global longitudinal strain, also significantly improved, and their improvement was even observed in patients with mild PH after pulmonary endarterectomy or balloon pulmonary angioplasty. Furthermore, covariance analysis revealed that RV global longitudinal strain and RV fractional area change improved after riociguat administration, even with the same mean pulmonary arterial pressure, implicating the improvement of RV contractile function by riociguat, regardless of RV loading. Conclusions: Riociguat not only improved the hemodynamics of patients with PH but also ameliorated the echocardiographic parameters with RV function. RV strain could detect the subtle improvement in mild PH, and riociguat may have a benefit even after intervention, as assessed by speckle-tracking echocardiography. [ABSTRACT FROM AUTHOR]

Aims: Balloon pulmonary angioplasty (BPA) improves hemodynamics and exercise tolerance in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, its diagnostic and predictive values remain unclear. We investigated the diagnostic and predictive values of BPA by assessing the mechanism of right ventricular (RV) dysfunction. Methods and Results: Hemodynamic improvement was maintained over 6 months in 99 patients with CTEPH who underwent BPA. Notably, 57 of 99 patients showed normalization of pulmonary vascular resistance (PVR) after BPA. The RV mid free wall longitudinal strain (RVMFS) was inversely correlated with the 6‐min walk distance (r = −.35, P =.01) and serum levels of high‐sensitivity cardiac troponin T (hs‐cTNT) (r = −.39, P =.004) 6 months post‐BPA in the PVR‐normalized group. Among all variables analyzed, only the pre‐BPA RVMFS was correlated with the post‐BPA RVMFS (r =.40, P =.001), and the pre‐BPA RVMFS (<−15.8%) was the strongest predictor of post‐BPA normalization of RVMFS (area under the curve 0.80, P =.01, sensitivity 89%, and specificity 63%). The immediate post‐BPA RVMFS showed worsening over 6 months after the procedure (−25.8% to −21.1%) in patients with high serum hs‐cTNT levels (>0.0014 ng/mL). In contrast, we observed an improvement in these values in those with low serum hs‐cTNT levels (−23.6% to −24.4%). Conclusion: RVMFS of −15.8% may be a useful cutoff value to categorize the refractory and non‐refractory stages of disease. Sustained serum hs‐cTNT elevation post‐BPA indicates subclinical RV myocardial injury, with resultant RVMFS deterioration and poor exercise tolerance. [ABSTRACT FROM AUTHOR]

Balloon pulmonary angioplasty (BPA) has emerged as a new treatment strategy for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Improvements in hemodynamic parameters after BPA have been reported, but some patients continue to suffer from reduced exercise tolerance even after the normalization of hemodynamic parameters following BPA. As the amelioration of hemodynamic parameters is reportedly achieved via BPA, we hypothesized that the limiting factors for exercise tolerance in these patients are related to respiratory function. Therefore, we investigated the associations between respiratory function and exercise tolerance, and the mechanisms underlying respiratory dysfunction in patients after BPA. We analyzed 62 patients with CTEPH who underwent 1-year follow-up after BPA. Predictors for reduced exercise tolerance after BPA determined with six-minute walk test were sought from pulmonary hemodynamic and respiratory parameters using logistic regression analysis. After multivariate adjustments, high mean right atrium pressure (mRAP) and high alveolar-arterial oxygen gradient (A-aDO2) were significant predictors for reduced exercise tolerance. Next, we analyzed factors associated with high A-aDO2. Among the pathophysiological causes of high A-aDO2, including ventilation, diffusing capacity, and low ventilation-perfusion ratio, only low ventilation-perfusion ratio caused by high intrapulmonary shunt fraction was associated with high A-aDO2. Impaired oxygenation due to residual high intrapulmonary shunt fraction was associated with reduced exercise tolerance in patients with CTEPH, after receiving BPA. [ABSTRACT FROM AUTHOR]

Both direct exchange and super‐exchange interactions cooperate to realize inter‐spin magnetic interaction in binuclear manganese complex Mn(IV)2O2(NHCHCO2)4 with a di‐μ‐oxo path. We revisited this spin system using DMRG CAS methods and CAS selection procedures. Our results indicate that our previous "dynamically extended spin polarization" (DE‐SP) procedure for organic polyradicals and so forth does not work well. Thus, we have examined another selection procedure, the "dynamically extended super‐exchange" (DE‐SE) procedure. DMRG CASCI [18,18] by UB3LYP(HS)‐UNO(DE‐SE) can realize antiferromagnetic J values similar to experimental ones (−87 cm−1). In addition, all J values between all spin states (HS[septet],IS[quintet],IS[triplet],LS[singlet])were also shown to be correct under sufficiently large M values. © 2018 Wiley Periodicals, Inc. Both direct exchange and super‐exchange interactions cooperate to realize inter‐spin magnetic interaction in binuclear manganese complex Mn(IV)2O2(NHCHCO2)4 with di‐μ‐oxo path. The authors revisit this spin system using DMRG CAS methods and CAS selection procedures. [ABSTRACT FROM AUTHOR]

In this study, the zero-field splitting parameters ( D , E ) and effective exchange integrals ( J ) for a Mn 12 /Mn 11 Cr mixed crystal were evaluated using ab initio molecular orbital (MO) computations based on the hybrid density functional theory (DFT) methods for Mn 11 Cr ∗ -acetate cluster (Mn 12 and Mn 11 Cr mixing). In this study, Mn 12 -acetate, Mn 11 Cr-acetate, and Mn 12− n Cr n -acetate clusters were focused on. The zero-field splitting (ZFS) parameters are obtained by UB3LYP methods, i.e. −0.339 cm −1 (Mn 12 -acetate) and −0.351 cm −1 (Mn 11 Cr-acetate). The energy barriers were estimated to be 53.7 K and 50.4 K, which showed good agreement with previously reported experimental values of 68.8 K and 56.8 K, respectively. The origin of such anisotropy is assumed to be the eight Mn III ions with d 4 -electrons in their outer ring subunits, where elongated conformation along the axial direction becomes very important and leads to negative D values. The spin networks in these clusters were discussed by using the effective exchange integral sets. The J s value, as estimated by the UB3LYP method revealed that the J 2 , J 3 , and J 3 ′ interactions played important roles in describing the parallel spin ordering in cubane and ring subunits as well as the antiferromagnetic coupling between two subunits. The other interactions, i.e. J 1 , J 1 ′, J 4 , and J 4 ′ somewhat disturbed the spin ordering in the Mn 12 -acetate cluster. The substitution of Mn IV by Cr III did not change the spin network. However, the total S value changed after the substitution. [ABSTRACT FROM AUTHOR]

In this work, we show that the natural orbitals of unrestricted hybrid density functional theory (UHDFT) can be used as the active space orbitals to perform multireference (MR) calculations, for example, the density matrix renormalisation group (DMRG) and Mukherjee-type (Mk) MR coupled-cluster (CC) method. By including a sufficiently large number of these natural orbitals, full-valence (FV) active space can be identified without recourse of the expensive self-consistent procedures for DMRG-SCF. Several useful chemical indices are derived based on the occupation numbers of the natural orbitals for seamless continuation from broken-symmetry (BS) to symmetry-adapted (SA) methods. These procedures are used on 1,3-didehydrobenzene (meta-benzyne) to calculate its singlet (S)-triplet (T) gap. We compare our results to available experiments and computational results obtained by several other groups. We see our procedures as a seamless bridge between single-reference BS methods, such as UHDFT, and the SA MR methods, such as FV DMRG and MkMRCC. [ABSTRACT FROM AUTHOR]

Theoretical examinations of the ferromagnetic coupling in them-phenylene-bis-methylene molecule and its oligomer were carried out. These systems are good candidates for exchange-coupled systems to investigate strong electronic correlations. We studied effective exchange integrals (J), which indicated magnetic coupling between interacting spins in these species. First, theoretical calculations based on a broken-symmetry single-reference procedure, i.e. the UHF, UMP2, UMP4, UCCSD(T) and UB3LYP methods, were carried out with a GAUSSIAN program code under an SR wave function. From these results, theJvalue by the UHF method was largely positive because of the strong ferromagnetic spin polarisation effect. TheJvalue by the UCCSD(T) and UB3LYP methods improved an overestimation problem by correcting the dynamical electronic correlation. Next, magnetic coupling among these spins was studied using the CAS-based method of the symmetry-adapted multireference methods procedure. Thus, the UNO DMRG CASCI (UNO, unrestricted natural orbital; DMRG, density matrix renormalised group; CASCI, complete active space configuration interaction) method was mainly employed with a combination of ORCA and BLOCK program codes. DMRG CASCI calculations in valence electron counting, which included all orbitals to full valence CI, provided the most reliable result, and support the UB3LYP method for extended systems. [ABSTRACT FROM AUTHOR]

In this paper, we have investigated the catalytic mechanism of rat liver arginase using a quantum mechanics/molecular mechanics (QM/MM) approach. The enzyme catalyses the hydrolysis of L-arginine (L-Arg) to generate L-ornithine and urea. The reaction mechanism proposed by the previous experimental studies is well reproduced by the QM/MM computations. The explicit treatment of the protein environment suggests that Glu277 fulfil its role in stabilising and orienting L-Arg before nucleophilic attack by the bridging hydroxide in the first step. We have also found that the proton transfer step involving a hydrogen bond switch is the rate-limiting step. The activation energy is computed to be 9.0 and 5.9 kcal/mol at the UB3LYP-D3/CHARMM22 and UBHandHLYP-D3/CHARMM22 levels, which are comparable to the observed activation barrier of 7.2 kcal/mol. [ABSTRACT FROM AUTHOR]

Summary Polypeptide-tag/small-molecule pairs for specific cellular protein labeling are useful for visualizing cellular proteins and controlling their activity. Here, we report the development of an in vitro evolution-based (poly)peptide tag identification system named the DIVERSE (Directed In Vitro Evolution of Reactive peptide tags via Sequential Enrichment) system. In this system, an extremely diverse (10 14 ) library of peptide tags, displayed by covalent attachment to their encoding cDNAs, is continuously prepared from the DNA library in a one-pot approach. Using this system, we demonstrated de novo creation of non-enzymatically covalent-labeling peptide tags for a synthetic small-molecule target from a random peptide library. Protein labeling with these tags was applicable to N- and C-terminal fusions, multiple different proteins and fluorophores, and intracellular labeling. The DIVERSE system can be used not only for the de novo creation of polypeptide tags but also sequence optimization of existing polypeptide tags from extremely diverse libraries. [ABSTRACT FROM AUTHOR]

Environmental conditions critically affect the expansion behaviour of concrete due to alkali–silica reaction (ASR) and, therefore, must be modelled to predict ASR-induced expansion behaviour. In addition, laboratory tests are important for the provision of useful data for numerical models, since these models often require the calibration of some unknown parameters according to the materials tested. To address this, the authors have developed a testing method for concrete expansion, called the alkali-wrapped concrete prism test (AW-CPT). Predictions using the results of the AW-CPT would be beneficial for the assessment of potential expansion of concrete when exposed to the outdoor environment. In this study, the effects of environmental conditions on ASR-induced expansion behaviours are determined through exposure and laboratory tests. The environmental conditions are modelled and implemented in numerical simulations. The results indicate that solar insolation and rainfall are critical parameters for modelling the environmental conditions as well as ambient temperature and relative humidity. [ABSTRACT FROM AUTHOR]

Cyclic structures can increase the proteolytic stability and conformational rigidity of peptides, and N-alkylation of the peptide backbone can make peptides more cell-permeable and resistant to proteolysis. Therefore, cyclic N-alkyl amino acids are expected to be useful building blocks to increase simultaneously these pharmacological properties of peptides. In this study, we screened various cyclic N-alkyl amino acids for their ribosomal incorporation into peptides and identified cyclic N-alkyl amino acids that can be efficiently and successively incorporated. We also demonstrated genetic code reprogramming for reassigning 16 NNU codons to 16 different cyclic N-alkyl amino acids with high fidelity to synthesize highly N-alkylated polycyclic peptidomimetics and an mRNA-displayed library of completely N-alkylated polycyclic peptidomimetics by using our recently developed TRAP (transcription/translation coupled with association of puromycin linker) display. In vitro selection from a highly diverse library of such completely N-alkylated polycyclic peptidomimetics could become a powerful means to discover small-molecule ligands such as drug candidates that can be targeted to biomolecules inside living cells. [ABSTRACT FROM AUTHOR]

Histogram equalization (HE) is a simple and effective method for contrast enhancement as it can automatically define the gray-level transformation function based on the distribution of gray levels included in an image. HE fails to produce satisfactory results for a broad variety of low-contrast images because HE does not use the spatial features included in the input image. This paper proposes a novel contrast enhancement method using not only the conventional histogram but also the differential gray-level histogram of the input image. The differential gray-level histogram contains edge information from the input image. Edge information is one of the important spatial features of the image. We can extract the regions that are to be emphasized by using both the conventional histogram and the differential gray-level histogram. The input histogram is modified by the histogram of the extracted regions. The gray-level transformation function is derived using the modified histogram. [ABSTRACT FROM AUTHOR]

Here, we describe a novel method that enables high-speed in vitro selection of functional peptides, peptidomimetics, and proteins via a simple procedure. We first developed a new cell-free translation system, the TRAP system (transcription–translation coupled with association of puromycin linker), which automatically produces a polypeptide library through a series of sequential reactions: transcription, association of puromycin-DNA linker, translation, and conjugation between the nascent polypeptide and puromycin-DNA linker. We then applied the TRAP system for the selection of macrocyclic peptides against human serum albumin. Six rounds of selection using TRAP display were performed in approximately 14 h, yielding macrocyclic peptides with nanomolar affinity to their target protein. Because TRAP display enables high-speed selection of functional polypeptides, it will facilitate the generation of various polypeptides that are useful for biological and therapeutic applications. [ABSTRACT FROM AUTHOR]

The presence of a nonproteinogenic moiety in a nonstandard peptide often improves the biological properties of the peptide. Nonstandard peptide libraries are therefore used to obtain valuable molecules for biological, therapeutic, and diagnostic applications. Highly diverse non-standard peptide libraries can be generated by chemically or enzymatically modifying standard peptide libraries synthesized by the ribosomal machinery, using posttranslational modifications. Alternatively, strategies for encoding non-proteinogenic amino acids into the genetic code have been developed for the direct ribosomal synthesis of non-standard peptide libraries. In the strategies for genetic code expansion, non-proteinogenic amino acids are assigned to the nonsense codons or 4-base codons in order to add these amino acids to the universal genetic code. In contrast, in the strategies for genetic code reprogramming, some proteinogenic amino acids are erased from the genetic code and non-proteinogenic amino acids are reassigned to the blank codons. Here, we discuss the generation of genetically encoded non-standard peptide libraries using these strategies and also review recent applications of these libraries to the selection of functional non-standard peptides. [ABSTRACT FROM AUTHOR]

Abstract: The effective exchange integrals (J(HB)) of the Heisenberg spin model have been evaluated by using the ab initio MO and based on Hartree–Fock (HF) and density functional theory (DFT) for organic magnetic metals, the (EDT-TTFVO)2FeBr4 crystal based on the X-ray crystallographic structures at 113K. In order to study the magnetic properties, we proposed some of the pairs, where the direct (d–d) and indirect (d–π–d) magnetic couplings between Fe(III) d-spins (S =5/2) without/with π-dimer spins (S =1/2) were calculated, respectively. The effective exchange integrals were evaluated by using UB3LYP method, and principal J values were 0.5, −0.1 and 0.4K. From these results, it is found that there were three dimensional spin arrangements of Fe(III) d-spins. The Quantum Monte Carlo (QMC) simulations had been carried out with our calculated J values to evaluate the magnetic susceptibility for this molecular crystal, reproducing the experimental tendency. [Copyright &y& Elsevier]

Abstract: Intermolecular interactions in nano-porous crystals were studied theoretically as related to adsorption properties. The crystal [Rh2bza4pyz] n , which had been reported by Mori, Takamizawa and their co-workers in detailed, was employed in this study. As adsorbed magnetic radicals, a oxygen molecule (O2; S =1) was treated. Adsorption energies ΔE ads are defined for quantitative discussion for host–guest interaction. From the calculated results by our MO calculations, weak attractive interactions between adsorbed O2 and surrounding four ph-groups (delegated to benzene) existed. In addition, stable structure of O2 molecules over one benzene molecule was studied. From the results, parallel structure is more stable than perpendicular structure. Physisorption phenomena in intermediate distance region (R =3.4Å) contributes to energy stabilization. [Copyright &y& Elsevier]

Abstract: Computational methods were developed for ground-state searches of Heisenberg model spin clusters in which spin sites were represented by classical spin vectors. Simulated annealing, continuous genetic algorithm, and particle swarm optimization methods were applied for solving the problems. Because the results of these calculations were influenced by the settings of optimization parameters, effective parameter settings were also investigated. The results indicated that a continuous genetic algorithm is the most effective method for ground-state searches of Heisenberg model spin clusters, and that a mutation operator plays an important role in this genetic algorithm. These results provide useful information for solving physically or chemically important continuous optimization problems. [Copyright &y& Elsevier]

Abstract: The selective oxidation of ethene to acetic acid in the vapor phase over solid acid-supported Pd catalyst was investigated to elucidate the reaction mechanism and the roles of Pd and acidic sites in promoting the reaction. Two catalysts, Pd–H4SiW12O40/SiO2 and Pd/WO3–ZrO2, exhibited high catalytic activity. Variations in product distribution with contact time, the requirement for the presence of water vapor for the reaction to occur, and the reactivities of possible reaction intermediates indicated that acetic acid is formed via an acetaldehyde intermediate which is produced in a Wacker-type reaction, while the role of the acid sites is to re-oxidize Pd0 into Pd2+ in the presence of O2. It was concluded that catalytic efficiency is dependent on maximization of the interface between metallic Pd and acidic surface by establishing an appropriate ratio of Pd and acidic sites. [Copyright &y& Elsevier]

Summary: Natural peptide products often contain N-methylated backbones, and such a modification plays a crucial role in making natural peptides peptidase resistant and membrane permeable. Here, we demonstrate the ribosomal synthesis of N-methyl-peptides by means of genetic code reprogramming. Two key technologies, a ribozyme-based de novo tRNA acylation (flexizyme) system and an E. coli reconstituted cell-free translation (PURE) system, were used in order to reassign arbitrarily chosen codons to N α-methylated amino acids (Meaa). Using this combination, we determined the general structural requirement of “accessible”Meaa and demonstrated their multiple incorporations into the nascent peptide chain according to the assignments made on mRNA, giving linear and cyclic N-methyl-peptides in high purities. This platform technology offers a convenient tool for the construction of N-methyl-peptide libraries, potentially leading to the discovery of therapeutic peptides. [Copyright &y& Elsevier]

Abstract: Although prostaglandin I2 is used to treat pulmonary hypertension (PH), continuous intravenous administration is necessary. We investigated whether human PGIS (hPGIS) gene transfer using adeno-associated virus (AAV) vector was effective in treating an animal model of PH. PH was induced by subjecting mice to 10% O2. Type 1-AAV-hPGIS was injected into the left thigh muscle after 24h. Significant PH was induced at 8 weeks, but AAV-hPGIS administration significantly inhibited the increase in RV systolic pressure. PH-induced BNP up-regulation in the RV was reduced to the control level. The severe medial thickening of pulmonary arteries in PH was significantly suppressed by AAV-hPGIS. The hPGIS gene was detected only on the injected side. No pathological changes were observed at the injected site. At 24 weeks, all PH mice were deceased, but 47% of AAV-hPGIS-treated mice survived. This study demonstrated that AAV-hPGIS administration was effective in treating PH and prolonging survival. [Copyright &y& Elsevier]

Abstract: Adsorption properties of magnetic species in nano-porous crystals were studied theoretically. The crystal [Rh2bza4pyz] n , which had been reported by Mori, Takamizawa and their co-workers in detailed, was employed in this study. As adsorbed magnetic radicals, a oxygen molecule (O2; S =1) was treated. From the results by our MO calculations, weak magnetic interactions between O2 molecules in cavities existed. Two types of magnetic interactions (ferro- and antiferro-magnetic) made alignment of trimer spin structure. Our theoretical calculations analyzed not only position but also orientation of the adsorbed O2 molecules. For the position, cloud of mass densities of O2 molecules by MD simulation showed stacking styles in nano-pores statistically. Number of adsorbed gas was estimated to be 3.00 molecules/unit. For the orientation, a certain adsorbed O2 molecule was stabilized by contribution of the two next O2 molecules as well as four phenyl groups. [Copyright &y& Elsevier]

Inter-dimer magnetic interactions (J ab(D) ) between (BEDT-TTF) 2 + • dimers in the κ-(BEDT-TTF) 2 Cu 2 (CN) 3 crystal has been studied theoretically. In these crystals, triangular lattice structure with spin frustration has been discovered and experimental studies have been performed by several research groups. We have calculated the inter-dimer J ab(D) values by using several methods. In addition, we have analyzed the spin lattice with optimization of θ angle in classical Heisenberg spin model and with numerical diagonalization in quantum Heisenberg spin model. [ABSTRACT FROM AUTHOR]

Abstract: The one-dimensional intermolecular ferromagnetic interaction of a charge-transfer (CT) complex, (BDTA)[Ni(mnt)2] (BDTA: 1,3,2-benzodithiazolyl, mnt: maleonitriledithiolate), is studied by the Kohn–Sham hybrid density functional method, in order to understand the mechanism of the magnetism. All possible effective exchange integrals, J, between the spin pairs of the system indicate that a ferromagnetic interaction (J =172cm−1) exists along the b-axis. Magnetic susceptibility, simulated with the ab initio determined J values by the quantum Monte Carlo (QMC) method, is qualitatively consistent with that measured experimentally. [Copyright &y& Elsevier]

Our theoretical efforts toward molecule-based magnetic conductors and superconductors on the basis of ab initio Hamiltonians and effective model Hamiltonians are summarized in relation to recently developed DNA-based molecular materials. Guanine and adenine derivatives coupling with organic radicals (R) are investigated as possible π–R components. To elucidate electronic and magnetic properties of these species, effective exchange integrals (Jab) for magnetic clusters are calculated by ab initio hybrid density functional (HDFT) methods. The ab initio Jab values are numerically reproduced by using model Hamiltonians such as the t-J, Kondo, Anderson, and RKKY models. The theoretical possibilities of organic magnetic conductors are elucidated on the basis of these models for self-assembled DNA wires, sheets, and related materials. The use of these materials for nanoscale molecular electronic devices is also elucidated theoretically in relation to an important role of electron–electron repulsion effect for quantum electron transport, together with the electron-exchange interaction in the Kondo effect. The implications of the calculated results are finally discussed to obtain a unified picture of many p–d, π–d, and π–R molecule-based systems with strong electron correlations. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [ABSTRACT FROM AUTHOR]

Abstract: Inter-dimer magnetic interactions (J ab(D)) between BETS donors in the κ-BETS2FeCl4 crystal were studied theoretically by using of ab initio MO and DFT methods. These interaction parameters can describe spin properties. In cluster of four BETS molecules with two holes, more accurate J ab(D) values were evaluated directly, though such J ab(D) values were already evaluated from inter-molecular magnetic interaction (J ab(M)) with the approximate equation J ab(D) = J ab(M)/2. In cluster of six molecules with three holes, competition of three antiferromagnetic interaction was discussed. Necessity of calculation under periodic condition and for surrounding cluster was introduced. [Copyright &y& Elsevier]

Abstract: In order to inquire into the mechanism of the change in the magnetism of spiro-biphenalnyls, intermolecular magnetic interaction has been investigated in terms of the effective exchange integral of the Heisenberg model for dimeric pairs of diethyl-substituted spiro-biphenalenyl. Variation of the magnetic interaction with respect to temperature has been evaluated for X-ray crystallographic structures at several temperature points by Kohn–Sham hybrid-DFT. The intermolecular magnetic interactions have been calculated for the π-dimers to be antiferromagnetic at each temperature, which has decreased by approximately 30% in the magnitude from 100 to 173K. In addition, the interactions have been almost none at 100 and 173K except for one pair and the remaining pair had ferromagnetic interaction. Therefore, it has been found that the change in their magnetism is understood by the formation of a ferromagnetic dimer-pair at 173K. Moreover, the natural orbital analysis for the electronic structure of diethyl-substituted spiro-biphenelenyl has shown our solutions are essentially identified to Haddon’s proposal in terms of the valence bond picture. [Copyright &y& Elsevier]

Theoretical calculations of ab initio molecular orbital and density functional theory calculations were carried out in order to investigate magnetic interaction in one‐dimensional spin chains. Effective exchange integral (Jab) values are useful parameters in studying magnetic interaction in spin systems. Chemical indices also were evaluated to represent stability of broken symmetry spin. For one set of spin chains, alignment of hydrogen atoms as the most simple organic cluster was employed. Number of H atoms in employed models is two and 50 with interatomic distance 2.1 Å. In addition, copper bromide chains (CunBrm) were also studied. Simple molecules Br2‐Cu‐Br2‐Cu‐Br2 (without apical‐Br) and Br2‐CuBr‐Br2‐CuBr‐Br2 (with apical‐Br) were employed for simple model structure. Four parameters (r, a, b, and c) can fix the structure and study parameter dependency of Jab values. For experimental studies, Sugimoto and his coworkers have reported synthesis and experimental studies for complex of both CunBrm chains and TTF‐derivative donor. Magnetic behavior in only CunBrm chains was investigated in detail by several ab initio methods. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004 [ABSTRACT FROM AUTHOR]

Our theoretical efforts towards molecule-based magnetic conductors and superconductors on the basis of ab initio Hamiltonians and effective model Hamiltonians are summarized in relation to recently developed π–d systems, for which transition metal complexes have been used as spin sources. Organic π-electron donors or acceptors coupling with organic radicals (R) are also investigated as possible π–R interaction systems. In order to elucidate electronic and magnetic properties of these species, effective exchange integrals (Jab) for magnetic clusters are calculated by ab initio hybrid density functional (HDFT) methods. The ab initio Jab values are numerically reproduced by using model Hamitonians such as t–J, Kondo, Anderson and RKKY models. Theoretical possibilities of magnetic conductors and spin-mediated superconductors are elucidated on the basis of these models in the intermediate region for metal–insulator transitions. Interrelationships among magnetism, superconductivity and fluctuations in strongly correlated electron systems are discussed on the basis of the SO(5) and three-dimensional quantum electrodynamics (QED3) theories. External magnetic field effects such as Jaccarino–Peter effect are also examined for elucidation of magnetic field induced superconductivity. Implications of the calculated results are finally discussed in order to obtain a unified picture of many p–d, π–d and π–R molecule-based systems with strong electron correlations. [Copyright &y& Elsevier]

Intermolecular magnetic interaction of some donors, i.e. BEDT-TTF, BETS, TMTTF and TMTSF, in some organic superconductive crystals were studied theoretically by using ab initio MO and DFT methods. In addition, donor arrangements in both κ- and λ-phases crystals are also focused. For this purpose we employed κ-BETS2FeCl4 and λ-BETS2FeCl4 crystals for BETS salts; κ-(BEDT-TTF)2Cu[N(CN)2]X (X=Cl, Br and I) and κ-(BEDT-TTF)2Cu(NCS)2 crystals for BEDT-TTF salts; TMTTF2PF6 and TMTSF2PF6 crystals for TMTTF and TMTSF salts. For these systems all the effective exchange integral (Jab) values between two donors and between donor and counter anions were successfully evaluated. In addition the other effective parameters (tab, Ueff) were also obtained. Finally relationship between integral pair (J, J′) and transition temperature (TSC) was discussed. The two- and one-dimensional magnetic networks are essential for these crystals. [Copyright &y& Elsevier]

The effective exchange integrals (J[sub ab(M)]) between two cation radicals of title compounds in the Heisenberg model were calculated by ab initio molecular orbital (MO) and density functional theory (DFT) methods, together with hybrid DFT methods. The J[sub ab(D)] values between two dimer mono-cation radicals were also estimated assuming J[sub ab(D)] ≈ J[sub ab(M)]/2. It is found that the spin lattice obtained by the ab initio method is square planar and linear in BEDT-TTF and BETS planes, respectively, although other previous calculations show that spin lattice in the BEDT-TTF plane is a triangular one. The J[sub ab] and overlap integrals (s[sub ab]) values by the ab initio methods were used to determine transfer integral (t[sub ab]) and Coulomb repulsion (U[sub eff]) parameters of the Hubbard model, which were compared with those of the previous results. Implications of the calculated results are discussed in relation to the spin-mediated mechanism for superconductivity. [ABSTRACT FROM AUTHOR]

Potential curves and high and low spin energy gaps for radical clusters were calculated by spin polarized molecular orbital methods. Through-space effective exchange integrals (J[sub ab]) and relative energies of spin projected low spin states by post-Hartree-Fock (HF) calculation were reproduced by the hybrid density functional theory (DFT) method. The hybrid parameters that could reproduce post-HF values such as UCCSD(T)'s for each model had close relations with the instabilities of those systems. Information entropy and related chemical indices were used to estimate the magnitude of the instabilities. A magnetic effective density functional (MEDF) scheme for spin clusters was proposed for practical computation of J[sub ab] values in molecular magnetic materials. [ABSTRACT FROM AUTHOR]

Cooperation of antiferromagnetism and superconductivity is achieved and reported by Kobayashi and his co-workers. For the BETS related crystals, κ-(BETS) 2 FeCl 4 (BETS=bis(ethylenedithio)tetraselenafulvalene), effective exchange integrals ( J ab ) between two BETS + molecules (Step I) and between BETS + and FeCl 4 - molecules (Step II) are very important to reveal superconductivity and successfully evaluated in our treatments. organic superconductor effective exchange integral BETS ab initio MO DFT [ABSTRACT FROM AUTHOR]

The detailed theoretical studies for TCNQ/TCNQ -· salts, which possess ferromagnetic hysteresis at relative high temperature, were carried out. The calculations based on ab initio molecular orbital (MO) and density functional (DFT) theories were carried out to evaluate the intermolecular effective exchange integrals and transfer integrals. In addition, we employed the "hybrid DFT method" based on instability of chemical bonds and successfully studied their spin densities. From the results it was found the remarkable singlet dimer structure is dominant. In addition, quasi-one-dimensional structure was found because of nonzero charge transfer. [ABSTRACT FROM AUTHOR]

We report a methodology for the ribosomal synthesis of backbone-cyclized peptides involving genetic code reprogramming to introduce one or more nonproteinogenic amino acids. Expression of linear peptides bearing a cysteine-proline dipeptide sequence followed by glycolic acid results in self-rearrangement to a C-terminal diketopiperadine-thioester, which non-enzymatically generates a cyclized peptide. We demonstrate the ribosomal synthesis of several naturally occurring backbone-cyclized peptides and a library based on a bicyclic scaffold, and we identify bioactive sequences by screening and deconvolution. [ABSTRACT FROM AUTHOR]

The article presents a study regarding ribosomal synthesis of polypeptoids and peptoids-peptide hybrids. It demonstrates messenger ribonucleic acid (mRNA) directed synthesis of linear polypeptoids and cyclic peptoid. It also discusses the translation machinery which allows programmable genetic code and peptide chains.

This research is based on a Systematic Evolution of Ligands by EXponential enrichment, also referred to as in vitro selection against the extracellular domain of human interleukin-17 receptor A (IL-17RA). Pull-down assay via quantitative polymerase chain reaction and chemiluminescence detection showed that the cloned RNA with the enriched sequence bound to human IL-17RA and inhibited the interaction between IL-17RA and human interleukin-17A (IL-17A). We also revealed that the newly discovered IL-17RA-binding RNA aptamer bound to cellular IL-17RA, inhibited the cellular IL-17RA/IL-17A interaction, and antagonized cellular IL-17A signaling. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether the change in computed tomography pulmonary angiography (CTPA) metrics after balloon pulmonary angioplasty (BPA) can predict treatment effect in chronic thromboembolic pulmonary hypertension (CTEPH) patients. Methods: This study included 82 CTEPH patients who underwent both CTPA and right heart catheterization (RHC) before and at the scheduled time of 6 months after BPA. The diameters of the main pulmonary artery (dPA), ascending aorta (dAA), right atrium (dRA), right ventricular free wall thickness (dRVW), and right and left ventricles (dRV, dLV) were measured on CTPA. The correlation of the New York Heart Association functional class (NYHA FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) level, and calculated CT metrics with a decrease in mean pulmonary artery pressure (ΔmPAP) using RHC (used as the reference for BPA effect) was investigated. Using multiple regression analysis, independent variables were also identified. Results: In univariate analysis, clinical indicators (NYHA FC, 6MWD, and BNP level) improved significantly after BPA and were significantly correlated with ΔmPAP (p < 0.01). In the univariate analysis of CTPA parameters, dPA, dRA, dPA/dAA ratio, dRVW, and dRV/dLV ratio decreased significantly and were significantly correlated with ΔmPAP (p < 0.01). Multivariate analysis demonstrated that decreased dPA (p = 0.001) and decreased dRA (p = 0.039) on CTPA were independent predictive factors of ΔmPAP. Conclusions: Decreased dPA and dRA on CTPA could predict a decrease in mPAP after BPA, thus potentially eliminating unnecessary invasive catheterization. Key Points: • The reduction in mean pulmonary artery pressure after balloon pulmonary angioplasty in CTEPH patients was significantly correlated with the clinical indices improvement and CTPA parameter decrease. • The decreased diameter of the main pulmonary artery and the decreased diameter of the right atrium on CTPA were independent predictors of mean pulmonary artery pressure reduction. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Effect of balloon pulmonary angioplasty on respiratory function in patients with chronic thromboembolic pulmonary hypertension," by M. Akizuki and colleagues in the 2017 issue.

The efficacy of extensive balloon pulmonary angioplasty (BPA) beyond hemodynamic improvement in chronic thromboembolic pulmonary hypertension (CTEPH) patients has been verified. However, the relationship between extensive BPA in CTEPH patients after partial hemodynamic improvement and exercise tolerance or quality of life (QOL) remains unclear. We prospectively enrolled 22 CTEPH patients (66±10 years, females: 59%) when their mean pulmonary artery pressure initially decreased to <30 mmHg during BPA sessions. Hemodynamic and echocardiographic data, cardiopulmonary exercise testing, and QOL scores using the 36-item short form questionnaire (SF-36) were evaluated at enrollment (entry), just after the final BPA session (finish), and at the 6-month follow-up (follow-up). We analyzed whether extensive BPA improves exercise capacity and QOL scores over time. Moreover, the clinical characteristics leading to improvement were elucidated. The peak oxygen uptake (VO2) showed significant improvement at entry, finish, and follow-up (17.3±5.5, 18.4±5.9, and 18.9±5.3 mL/kg/min, respectively; P<0.001). Regarding the QOL, the physical component summary (PCS) scores significantly improved (32±11, 38±13, and 43±13, respectively; P<0.001), but the mental component summary scores remained unchanged. Linear regression analysis revealed that age and a low peak VO2 at entry were predictors of improvement in peak VO2, while low PCS scores and low TAPSE at entry were predictors of improvement in PCS scores. In conclusion, extensive BPA led to improved exercise tolerance and physical QOL scores, even in CTEPH patients with partially improved hemodynamics. [ABSTRACT FROM AUTHOR]

This review article describes a historical perspective of elucidation of the nature of the chemical bonds of the high-valent transition metal oxo (M=O) and peroxo (M-O-O) compounds in chemistry and biology. The basic concepts and theoretical backgrounds of the broken-symmetry (BS) method are revisited to explain orbital symmetry conservation and orbital symmetry breaking for the theoretical characterization of four different mechanisms of chemical reactions. Beyond BS methods using the natural orbitals (UNO) of the BS solutions, such as UNO CI (CC), are also revisited for the elucidation of the scope and applicability of the BS methods. Several chemical indices have been derived as the conceptual bridges between the BS and beyond BS methods. The BS molecular orbital models have been employed to explain the metal oxyl-radical character of the M=O and M-O-O bonds, which respond to their radical reactivity. The isolobal and isospin analogy between carbonyl oxide R2C-O-O and metal peroxide LFe-O-O has been applied to understand and explain the chameleonic chemical reactivity of these compounds. The isolobal and isospin analogy among Fe=O, O=O, and O have also provided the triplet atomic oxygen (3O) model for non-heme Fe(IV)=O species with strong radical reactivity. The chameleonic reactivity of the compounds I (Cpd I) and II (Cpd II) is also explained by this analogy. The early proposals obtained by these theoretical models have been examined based on recent computational results by hybrid DFT (UHDFT), DLPNO CCSD(T0), CASPT2, and UNO CI (CC) methods and quantum computing (QC). [ABSTRACT FROM AUTHOR]

Balloon pulmonary angioplasty (BPA) has emerged as an effective treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Renal function has been identified as a prognostic marker in patients with pulmonary hypertension in previous studies. We, therefore, aimed to investigate the clinical parameters associated with improvements in renal function in patients with CTEPH. A total of 45 consecutive patients with inoperable CTEPH undergoing BPA (mean age 62.2 ± 15.1 years) were included in the study. We evaluated the patients' clinical characteristics at baseline and at 1-year post-BPA, and investigated the association between renal function and hemodynamic parameters, including right heart function. Hemodynamics and renal function showed sustained improvements at 1 year after BPA in 64.4% of patients. Improved estimated glomerular filtration rate (eGFR) was significantly correlated with increased cardiac index (r = 0.433, p = 0.003) and mixed venous oxygen saturation (SvO2; r = 0.459, p = 0.002), and with decreased mean pulmonary arterial pressure (r = − 0.420, p = 0.004) and pulmonary vascular resistance (r = -− 0.465, p = 0.001). Multivariate analysis revealed that an increase in SvO2 immediately after the final BPA was associated with improved eGFR after the 1st year (odds ratio 1.041; 95% confidence interval 1.004–1.078; P = 0.027). The cut-off value for predicting improved eGFR was an increase in SvO2 after the final BPA of >125.4% over the baseline value (specificity 100%, sensitivity 24.1%). In conclusion, BPA improved symptoms, right heart function, hemodynamics, and renal function up to the chronic phase. Increasing SvO2 by >125.4% above baseline in the acute phase is important for improving renal function at 1 year after BPA in CTEPH patients. [ABSTRACT FROM AUTHOR]

The free‐energy landscape is an important factor for understanding the conformational equilibria of chemical reactions, and many techniques have been developed to calculate the potential of the mean force. Unfortunately, these methods require a previous knowledge of the system for calculations because the results depend on the reaction coordinates. In this study, we combine the scaled hypersphere search method with the umbrella integration method to obtain the transition states on free‐energy landscapes and minimum‐free‐energy paths (MFEPs). With this approach, the MFEP connections between known and unknown equilibrium points are constructed without the prior knowledge of the free‐energy landscape. The problem of reaction coordinates can be solved by using a multidimensional, fully automated interrogation of MFEPs for acquiring the potential of mean force. The efficiency of the proposed method is demonstrated by applying it to alanine dipeptide and alanine tripeptide. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We report a computational study on the dioxygenation reaction of the substrate flavonolate (fla) by a synthetic model complex [Cu 2+ (idpa)(fla − )] + (idpa = 3,3′-iminobis( N , N -dimethylpropylamine) and related species mimicking quercetin 2,4-dioxygenases. It is found that the reaction mechanism obtained for the present biomimetic complexes is substantially different from the plausible enzymatic reaction. All model complexes favor a single electron transfer from flavonolate to dioxygen over a valence tautomerism [Cu 2+ (idpa)(fla − ) ↔ Cu + (idpa)(fla )], and a subsequent intersystem crossing and a ring-closure lead to a formation of a 1,2-dioxetane intermediate instead of undergoing a direct formation of a precursor endoperoxide. The generation of the 1,2-dioxetane intermediate is shown to be the rate-determining step and inclusion of a carboxylate co-ligand can enhance the reactivity, rendering this process barrier-free. We have also proposed for the first time a pathway, which can circumvent a non-enzymatic reaction by involving conversion from the 1,2-dioxetane to the endoperoxide with lower barriers. [ABSTRACT FROM AUTHOR]

We report a thorough comparison between the spin-unrestricted semi-empirical molecular orbital (SE-UMO) and density functional theory (UDFT) calculations for a variety of π-conjugated diradical molecules which exhibit through-bond magnetic exchange interactions. The spin-unrestricted neglect of diatomic differential overlap (NDDO)-based methods (UPM6 and UrPM6) and self-consistent charge density functional tight-biding (UDFTB) are examined. The UCAM-B3LYP method is used as a representative of UDFT. We have found that NDDO-based and UDFTB methods give different performances with respect to the results of UCAM-B3LYP. The degree of diradical character in the target systems decreases in the order of UPM6 > UrPM6 ≈ UCAM-B3LYP > UDFTB. The conventional UPM6 and UDFTB calculations tend to overestimate and underestimate the diradical character, respectively, whereas UrPM6 is able to provide much the same results as UCAM-B3LYP. This is convincing evidence that UrPM6 will be useful for in silico screening of materials science at much lower computational cost. [ABSTRACT FROM AUTHOR]

Background For treatment of chronic thromboembolic pulmonary hypertension (CTEPH), the evaluation of segmental pulmonary perfusion is important. There are no previous reports about lung subtraction iodine mapping (LSIM) computed tomography (CT) for evaluation of segmental pulmonary perfusion in patients with CTEPH, using lung perfusion SPECT/CT (LPS) as the reference. Methods 50 patients (age, 60.7 ± 16.7 years) with known or suspected CTEPH were enrolled in this study. Non-contrast chest CT and CT pulmonary angiography (CTPA) were performed on a 320-detector row CT system. Then, based on a non-rigid registration followed by subtraction of non-contrast images from contrast-enhanced images, color-coded LSIM images were generated. LPS was performed using a SPECT/CT system within a period of 2 months, and served as the reference standard. LSIM and CTPA images were evaluated in a blinded manner for the detection of pulmonary perfusion defects on a segment-by-segment basis. Results The sensitivity, specificity, accuracy, and positive and negative predictive values of LSIM for the detection of segmental perfusion defects were 95% (734/773), 84% (107/127), 93% (841/900), 97% (734/754) and 73% (107/146), respectively, while the corresponding values for CTPA were 65% (505/773), 61% (78/127), 65% (583/900), 91% (505/554) and 23% (78/346). Generalized estimating equations analyses revealed a significantly better performance of LSIM than that of CTPA regarding the sensitivity, accuracy, and positive and negative predictive values (all P < 0.0001). Conclusions LSIM is a feasible technique for segment-based evaluation of pulmonary perfusion in patients with CTEPH, and it provides a significantly higher diagnostic accuracy compared with CTPA. [ABSTRACT FROM AUTHOR]

Definitive diagnosis of familial hypercholesterolemia (FH) is paramount for the risk management of patients and their relatives. The present study aimed to investigate the frequency of gene variants contributing to low-density lipoprotein cholesterol (LDL-C) metabolism and their clinical relevance in patients with early-onset coronary artery disease (EOCAD). Among 63 consecutive patients with EOCAD (men <55 years or women <65 years) who underwent percutaneous coronary intervention (PCI) from 2013 to 2019 at Keio University Hospital, 52 consented to participate in this retrospective study. Targeted sequencing of LDLR, PCSK9, APOB, and LDLRAP1 was performed. Of the 52 patients enrolled (42 men; mean age: 50 ± 6 years), one (LDLR, c.1221_1222delCGinsT) harbored a pathogenic mutation, and one (APOB, c.10591A>G) harbored variants of uncertain significance. Both the patients harboring the variants were male, showing no history of diabetes mellitus or chronic kidney disease, no family history of EOCAD, and no physical findings of FH (i.e., tendon xanthomas or Achilles tendon thickening). Patients harboring the LDLR variant had three-vessel disease, were on a statin prescription at baseline, and had stable LDL-C levels; however, the case showed a poor response to the intensification of medication after PCI. Approximately 3.8% of patients with EOCAD harbored variants of gene related to LDL-C metabolism; there were no notable indicators in the patients' background or clinical course to diagnose FH. Given the difficulty in diagnosing FH based on clinical manifestations and family history, genetic testing could enable the identification of hidden risk factors and provide early warnings to their relatives. [ABSTRACT FROM AUTHOR]

Background: The clinical significance of obstructive sleep apnea (OSA) in pulmonary hypertension (PH) patients remains unclear. We investigated the hemodynamics and serum troponin T concentrations associated with OSA in PH patients.Methods: Cross-sectional study was performed on data from 97 clinically stable PH patients. Using overnight sleep study, we evaluated apnea-hypopnea index (AHI) and divided patients into two groups: none-to-mild OSA (AHI < 15/h, N = 81) and moderate-to-severe OSA (AHI ≥ 15/h, N = 16). Clinical, hemodynamic, and laboratory data were compared with OSA severity.Results: Moderate-to-severe OSA patients had higher pulmonary vascular resistance (PVR; 6.5 [5.7-12.9] vs 4.4 [2.9-6.4] Wood units, p = 0.001) and mean pulmonary artery pressure (mPAP; 37 [30-49] vs 30 [22-37] mmHg, p = 0.045), and a lower cardiac index (2.2 [1.6-2.6] vs 2.8 [2.3-3.5] L/min/m2, p = 0.001) than those without. There was no association between plasma B-type natriuretic peptide (BNP) or serum C-reactive protein levels and OSA. However, high-sensitivity troponin T (hs-TnT) level was significantly higher in moderate-to-severe OSA patients (13 [8-18] vs 6 [4-10] ng/L, p <0.001). The hs-TnT level positively correlated with the plasma BNP level, mPAP, PVR, AHI, obstructive apnea index, and 6-min walking distance. After adjustment for age, estimated glomerular filtration rate, hypertension, smoking, and plasma BNP level, moderate-to-severe OSA was an independent factor for determining the plasma level of log hs-TnT level (β = 0.419, 95% confidence interval 0.119-0.718, p = 0.007).Conclusions: Moderate-to-severe OSA is associated with impaired hemodynamics and subclinical myocardial damage in PH patients. Thus, OSA-related myocardial injury may play a role in hemodynamic destabilization with its associated poor prognosis. [ABSTRACT FROM AUTHOR]