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To identify Hf species and quantitatively evaluate their acid properties, combined measurement of infrared (IR) and temperature-programmed desorption (TPD) with deuterated acetonitrile (CD 3 CN) as probe molecule was performed on Hf-Beta and HfO 2 /Si-Beta. IR spectra of CD 3 CN adsorbed on Hf-Beta showed five types of Hf species including framework open and closed Hf sites, extra-framework HfO 2 , and two types of Hf species bearing hydroxy groups. IR measurement showed structural change in Hf-Beta upon exposing to water vapor with generation of the two types of Hf species bearing hydroxy groups. Integrated molar extinction coefficients for C N stretching vibration of CD 3 CN adsorbed on these Hf species were estimated and the number of each Hf acid site was calculated. Acid strength of these Hf species was estimated from CD 3 CN-TPD measurement in combination with IR; the acid strength of the open and closed Hf sites, extra-framework HfO 2 species, and the other Hf species was found to be strong, moderate, and weak, respectively. [Display omitted] • CD 3 CN IR-TPD can distinguish and quantify Hf species on Hf-Beta zeolite. • IR measurement distinguished five types of Hf species present on Hf-Beta. • Integrated molar extinction coefficients for adsorbed CD 3 CN were estimated. • The number of each Hf acid site was calculated. • Acid strength of these Hf species was estimated by TPD measurement of CD 3 CN. [ABSTRACT FROM AUTHOR]

Bombesin-receptor-subtype-3 (BB 3 receptor) is a G-protein-coupled-orphan-receptor classified in the mammalian Bombesin-family because of high homology to gastrin-releasing peptide (BB 2 receptor)/neuromedin-B receptors (BB 1 receptor). There is increased interest in BB 3 receptor because studies primarily from knockout-mice suggest it plays roles in energy/glucose metabolism, insulin-secretion, as well as motility and tumor-growth. Investigations into its roles in physiological/pathophysiological processes are limited because of lack of selective ligands. Recently, a selective, peptide-antagonist, Bantag-1, was described. However, because BB 3 receptor has low-affinity for all natural, Bn-related peptides, little is known of the molecular basis of its high-affinity/selectivity. This was systematically investigated in this study for Bantag-1 using a chimeric-approach making both Bantag-1 loss-/gain-of-affinity-chimeras, by exchanging extracellular (EC) domains of BB 3 /BB 2 receptor, and using site-directed-mutagenesis. Receptors were transiently expressed and affinities determined by binding studies. Bantag-1 had >5000-fold selectivity for BB 3 receptor over BB 2 /BB 1 receptors and substitution of the first EC-domain (EC1) in loss-/gain-of affinity-chimeras greatly affected affinity. Mutagenesis of each amino acid difference in EC1 between BB 3 receptor/BB 2 receptor showed replacement of His 107 in BB 3 receptor by Lys 107 (H107K-BB 3 receptor-mutant) from BB 2 receptor, decreased affinity 60-fold, and three replacements [H107K, E11D, G112R] decreased affinity 500-fold. Mutagenesis in EC1’s surrounding transmembrane-regions (TMs) demonstrated TM2 differences were not important, but R127Q in TM3 alone decreased affinity 400-fold. Additional mutants in EC1/TM3 explored the molecular basis for these changes demonstrated in EC1, particularly important is the presence of aromatic-interactions by His 107 , rather than hydrogen-bonding or charge–charge interactions, for determining Bantag-1 high affinity/selectivity. In regard to Arg 127 in TM3, both hydrogen-bonding and charge–charge interactions contribute to the high-affinity/selectivity for Bantag-1. [ABSTRACT FROM AUTHOR]

An increase in the resistance of electrode materials due to the formation of electrode/electrolyte interphases (EEI) induces capacity loss and power fading in lithium-ion batteries, and hence, is a significant problem that hinders the extension of battery lifetime. Previous studies have reported that the increase in the resistance of one electrode is affected by the other electrode, suggesting that the crosstalk reaction plays a crucial role in the increase in the resistance of the electrodes. In this study, to understand the resistance increase mechanism in relation to the crosstalk reaction, lithium-ion cells with a LiNi 1/2 Mn 3/2 O 4 (LNMO) electrode with various materials (Li metal, graphite, Li[Li 1/3 Ti 5/3 ]O 4 , and LiFePO 4) as a negative electrode were examined via potentiostatic charge tests. The rate of increase in resistance of the LNMO electrodes against capacity due to side reactions depends on the electrode potential of the negative electrode: a lower electrode potential of the negative electrode slows down the rate of increase in resistance of the LNMO electrodes. Based on these results, an explanation for the resistance increase was provided by taking into consideration the crosstalk reaction. The crosstalk reaction reduces the amount of oxidative decomposition products generated at the LNMO electrode by consuming these products at the negative electrode; i.e., the resistance increase by EEI formation is minimized. A cell design based on the proposed mechanism, wherein the lower electrode potential of the negative electrode suppresses the increase in resistance of the positive electrodes, will open up the possibility of batteries with a long life. [ABSTRACT FROM AUTHOR]

Bombesin receptor subtype-3 (BRS-3) is an orphan G-protein coupled receptor which is classified in the bombesin receptor (BnR) family with which it shares high homology. It is present widely in the central nervous system and peripheral tissues and primarily receptor-knockout studies suggest it is involved in metabolic-glucose-insulin homeostasis, feeding and other CNS behaviors, gastrointestinal motility and cancer growth. However, the role of BRS-3 physiologically or in pathologic disorders has been not well defined because the natural ligand is unknown. Until recently, no selective agonists/antagonists were available; however, recently synthetic high-affinity agonists, chiral-diazepines nonpeptide-analogs (3F, 9D, 9F, 9G) with low CNS penetrance, were described, but are not well-categorized pharmacologically or in different labarotory species. The present study characterizes the affinities, potencies, selectivities of the chiral-diazepine BRS-3 agonists in human and rodents (mice,rat). In human BRS-3 receptors, the relative affinities of the chiral-diazepines was 9G > 9D > 9F > 3F; each was selective for BRS-3. For stimulating PLC activity, in h-BRS-3 each of the four chiral diazepine analogs was fully efficacious and their relative potencies were: 9G (EC 50 : 9 nM) > 9D (EC 50 : 9.4 nM) > 9F (EC 50 : 39 nM) > 3F (EC 50 : 48 nM). None of the four chiral diazepine analogs activated r,m,h-GRPR/NMBR. The nonpeptide agonists showed marked differences from each other and a peptide agonist in receptor-coupling-stiochiometry and in affinities/potencies in different species. These results demonstrate that chiral diazepine analogs (9G, 9D, 9F, 3F) have high/affinity/potency for the BRS-3 receptor in human and rodent cells, but different coupling-relationships and species differences from a peptide agonist. [ABSTRACT FROM AUTHOR]

A series of water-insoluble cyclodextrin polymers (CDP) was prepared by crosslinking β-cyclodextrin (CD) with polyethylene glycol diglycidyl ether (PEGDE). Similarly, a reference CDP was prepared using ethylene glycol diglycidyl ether (EGDE). Increasing the feed ratio of PEGDE to CD in the reaction mixture led to high degrees of crosslinking. Relaxation measurements revealed structural homogeneity among the CDPs, which exhibited mobilities that strongly depended on the chain lengths of the crosslinking agents. In addition, all the CDPs displayed high encapsulation abilities toward bisphenol A (BPA) in aqueous media. In particular, the CDP sample with a low degree of crosslinking by PEGDE showed the highest encapsulation ability toward BPA. In contrast, the CDP crosslinked by EGDE exhibited low encapsulation ability because its highly dense structure, which results from the short chain lengths of the crosslinking agents, hinders the penetration of BPA molecules. [ABSTRACT FROM AUTHOR]

• Capability of neural networks to fluid flow estimation problems is investigated. • We especially focus on a practical viewpoint regarding robust training. • We consider estimation of flow field from wall information in different problems. • The wall shear stress is found to significantly contribute to the estimation. • We also demonstrate some approaches to raise robustness against lacked information. State estimation from limited sensor measurements is ubiquitously found as a common challenge in a broad range of fields including mechanics, astronomy, and geophysics. Fluid mechanics is no exception — state estimation of fluid flows is particularly important for flow control and processing of experimental data. However, strong nonlinearities and spatio-temporal high degrees of freedom of fluid flows cause difficulties in reasonable estimations. To handle these issues, neural networks (NNs) have recently been applied to the fluid flow estimation instead of conventional linear methods. The present study focuses on the capability of NNs to various fluid flow estimation problems from a practical viewpoint regarding robust training. Three types of unsteady laminar and turbulent flows are considered for the present demonstration: 1. square cylinder wake, 2. turbulent channel flow, and 3. laminar to turbulent transitional boundary layer. We utilize a convolutional neural network (CNN) to estimate velocity fields from sectional sensor measurements. To assess the practicability of the CNN models, physical quantities required for the input and robustness against lack of sensors are investigated. We also examine the effectiveness of several considerable approaches for model training to gain more robustness against the lack of sensors. The knowledge acquired through the present study in terms of effective training approaches can be transferred towards practical machine learning in fluid flow modeling. [ABSTRACT FROM AUTHOR]

An association of atrial arrhythmias with takotsubo cardiomyopathy (TTC) has not been described previously. Here we report a 65-year-old male patient with TTC. The sudden appearance of atrioventricular block and subsequent bradycardia are believed to be key contributing factors for the development of TTC. Both ventricular tachyarrhythmia and various atrial arrhythmias, such as atrial flutter and atrial fibrillation, were observed during the initial management of the patient's TTC. We speculate that both the left ventricular contractile dysfunction and the arrhythmogenic activities may share a common underlying etiology in advanced heart failure patients with TTC. < Learning objective: We describe a case of TTC complicated by ventricular tachycardia, atrial tachyarrhythmias, and an atrioventricular conduction disturbance and discuss the etiology of arrhythmogenic activities in TTC.> [ABSTRACT FROM AUTHOR]

Abstract: Alcohol dehydrogenase (ADH) was immobilized on the film of poly[1-(2-carboxyethy] pyrrole], which was prepared by electrochemical polymerization of 1-(2-carboxyethyl)pyrrole. The film exhibited a stable conductivity of 10−4-10−3 S/cm over the temperature range 0-200°C. A significant amount of ADH (50-100g/cm2) was immobilized on the polymer film by use of a condensing reagent. Although activity of ADH was decreased by the immobilization, the ADH-immobilized polymer film showed amperometric response to ethanol at +0.85V vs. SCE in the presence of nicotinamide adenine dinucleotide (a redox mediator). These results demonstrate that the polymer film acts as both an ADH-supporting layer and a conductive medium in the alcohol-driven amperometric device. [Copyright &y& Elsevier]

Pituitary adenylate cyclase-activating polypeptide (PACAP) has widespread physiological/pathophysiological actions and there is increased interest for its use therapeutically, especially in the CNS (neuroprotection). Unfortunately, no selective PACAP-analogs exist for PACAP-preferring PAC1-receptors, primarily because of its high sequence identity to VIP and particularly, because of the inability of structure–function studies to separate the pharmacophore of PAC1-R from VPAC1-R, which has high affinity for PACAP and VIP. The present study attempted to develop PAC1-R-selective agonists primarily by making conformationally restricted PACAP-analogs in positions important for receptor-selectivity/affinity. Forty-six PACAP-related-analogs were synthesized with substitutions in positions 1–4, 14–17, 20–22, 28, 34, 38 and receptor-selectivity determined in PAC1-R,VPAC1-R,VPAC2-R-transfected or native cells from binding or cAMP-generation experiments. Fifteen PACAP-analogs had 6–78-fold higher affinities for PAC1-R than VPAC1-R and 13 were agonists. Although binding-affinities correlated significantly with agonist potency, the degree of receptor-spareness varied markedly for the different PACAP-analogs, resulting in selective potencies for activating the PAC1 receptor over the VPAC1 receptor from 0- to 103-fold. In addition, a number of PACAP-analogs were identified that had high selectivity for PAC1-R over VPAC2-R as well as PACAP-analogs that could prove more useful therapeutically because of substitutions known to extend their half-lives (substitutions at potential sites of proteolysis and attachment of long-chain fatty acids). This study provides for the first time a separation of the pharmacophores for PAC1-R and VPAC1-R, resulting in PACAP-related analogs that are PAC1-R-preferring. Some of these analogs, or their modifications, could prove useful as therapeutic agents for various diseases. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hydrogel was prepared from crosslinking of β-cyclodextrin and carboxymethylcellulose. [•] The hydrogel showed water-swelling capacity of the 200–70mL/g-polymer. [•] Prepared hydrogels retain adsorption ability toward bisphenol A. [•] The hydrogel is expect to be a soft material useful for removal organic pollutants. [ABSTRACT FROM AUTHOR]

The yeast Cyc8p-Tup1p protein complex is a general transcriptional corepressor of genes involved in many different physiological processes. Herein, we present the crystal structure of the Tup1p N-terminal domain (residues 1-92), essential for Tup1p self-assembly and interaction with Cyc8p. This domain tetramerizes to form a novel antiparallel four-helix bundle. Coiled coil interactions near the helical ends hold each dimer together, whereas interdimeric association involves only two sets of two residues located toward the chain centers. A mutagenesis study confirmed that the nonpolar residues responsible for the association of the protomers as dimers are also required for transcriptional repression. An additional structural study demonstrated that the domain containing an Leu62→Arg mutation that had been shown not to bind Cyc8p exhibits an altered structure, distinct from the wild type. This altered structure explains why the mutant cannot bind Cyc8p. The data presented herein highlight the importance of the architecture of the Tup1p N-terminal domain for self-association. [ABSTRACT FROM AUTHOR]

This following article is written for Prof. Abba Kastin's Festschrift, to add to the tribute to his important role in the advancement of the role of peptides in physiological, as well as pathophysiological processes. There have been many advances during the 35 years of his prominent role in the Peptide field, not only as editor of the journal Peptides, but also as a scientific investigator and editor of two volumes of the Handbook of Biological Active Peptides [146,147] . Similar to the advances with many different peptides, during this 35 year period, there have been much progress made in the understanding of the pharmacology, cell biology and the role of (bombesin) Bn receptors and their ligands in various disease states, since the original isolation of bombesin from skin of the European frog Bombina bombina in 1970 [76] . This paper will briefly review some of these advances over the time period of Prof. Kastin 35 years in the peptide field concentrating on the advances since 2007 when many of the results from earlier studies were summarized [128,129] . It is appropriate to do this because there have been 280 articles published in Peptides during this time on bombesin-related peptides and it accounts for almost 5% of all publications. Furthermore, 22 Bn publications we have been involved in have been published in either Peptides [14,39,55,58,81,92,93,119,152,216,225,226,231,280,302,309,355,361,362] or in Prof. Kastin's Handbook of Biological Active Peptides [137,138,331] . [ABSTRACT FROM AUTHOR]

Bombesin receptor subtype (BRS)-3 is a G protein coupled receptor (GPCR) for the bombesin (BB)-family of peptides. BRS-3 is an orphan GPCR and little is known of its physiological role due to the lack of specific agonists and antagonists. PD168368 is a nonpeptide antagonist for the neuromedin B (NMB) receptor (R) whereas PD176252 is a nonpeptide antagonist for the gastrin releasing peptide (GRP) R and NMBR but not BRS-3. Here nonpeptide analogs of PD176252 e.g. the S-enantiomer ML-18, and the R-enantiomer, EMY-98, were investigated as BRS-3 antagonists using lung cancer cells. ML-18 and EMY-98 inhibited specific 125 I-BA1 (DTyr-Gln-Trp-Ala-Val-βAla-His-Phe-Nle-NH 2 )BB 6-14 binding to NCI-H1299 lung cancer cells stably transfected with BRS-3 with IC 50 values of 4.8 and >100 μM, respectively. In contrast, ML-18 bound with lower affinity to the GRPR and NMBR with IC 50 values of 16 and >100 μM, respectively. ML-18 (16 μM), but not its enantiomer EMY-98, inhibited the ability of 10 nM BA1 to elevate cytosolic Ca 2+ in a reversible manner using lung cancer cells loaded with FURA2-AM. ML-18 (16 μM), but not EMY-98, inhibited the ability of 100 nM BA1 to cause tyrosine phosphorylation of the EGFR and ERK in lung cancer cells. ML-18 but not EMY-98 inhibited the proliferation of lung cancer cells. The results indicate that ML-18 is a nonpeptide BRS-3 antagonist that should serve as a template to improve potency and selectivity. [ABSTRACT FROM AUTHOR]

Abstract: Vasoactive intestinal peptide (VIP) attenuates experimental acute pancreatitis (AP) by inhibition of cytokine production from inflammatory cells. It has been suggested that reactive oxygen species (ROS) as well as cytokines play pivotal roles in the early pathophysiology of AP. This study aimed to clarify the effect of VIP on the oxidative condition in pancreas, especially pancreatic acinar cells (acini). Hydrogen peroxide (H2O2)-induced intracellular ROS, assessed with CM-H2DCFDA, increased time- and dose-dependently in acini isolated from rats. Cell viability due to ROS-induced cellular damage, evaluated by MTS assay, was decreased with ≥100μmol/L H2O2. VIP significantly inhibited ROS production from acini and increased cell viability in a dose-dependent manner. Expression of antioxidants including catalase, glutathione reductase, superoxide dismutase (SOD) 1 and glutathione peroxidase was not altered by VIP except for SOD2. Furthermore, Nox1 and Nox2, major components of NADPH oxidase, were expressed in pancreatic acini, and significantly increased after H2O2 treatment. Also, NADPH oxidase activity was provoked by H2O2. VIP decreased NADPH oxidase activity, which was abolished by PKA inhibitor H89. These results suggested that VIP affected the mechanism of ROS production including NADPH oxidase through induction of a cAMP/PKA pathway. In conclusion, VIP reduces oxidative stress in acini through the inhibition of NADPH oxidase. These results combined with findings of our previous study suggest that VIP exerts its protective effect in pancreatic damage, not only through an inhibition of cytokine production, but also through a reduction of the injury caused by oxidative stress. [Copyright &y& Elsevier]