A bis‐copper(II)–[d‐βVal3,7]ascidiacyclamide complex enveloping two square pyramids and sharing an apex atom from a carbonate anion

The four azole rings place structural restrictions on ascidiacyclamide (ASC). As a result, the structure of ASC exists in an equilibrium between two major forms (i.e. folded and square). [d ‐βVal^3,7]Ascidiacyclamide (βASC) was synthesized by replacing two d ‐Val‐Thz (Val is valine and Thz is thiazole) blocks with d ‐β‐Valine (D‐βVal‐Thz). This modification expands the peptide ring; the original 24‐membered macrocycle of ASC becomes a 26‐membered ring. Circular dichroism (CD) spectra showed that, in solution, the structural equilibrium is maintained with βASC, but the folded form is dominant. A copper complex was prepared, namely [[d ‐βVal^3,7]ascidiacyclamide(2?)]aqua‐μ‐carbonato‐dicopper(II) monohydrate, [Cu₂(C₃₈H₅₄N₈O₆S₂)(CO₃)(H₂O)]·H₂O, to determine the effect of the change in ring size on the coordinated structure. The obtained bis‐Cu^II–βASC complex contains two water molecules and a carbonate anion. Two Cu^II ions are chelated by three N‐donor atoms of two Thz–Ile–Oxz (Ile is isoleucine and Oxz is oxazoline) units. An O atom of the carbonate anion bridges two Cu^II ions, forming two square pyramids. These features are similar to the previously reported structure of the Cu^II–ASC complex, but the two pyramids are enveloped inside the peptide and share one apex. In the Cu^II–ASC complex, the apex of each square pyramid is an O atom of a water molecule, and the two pyramids are oriented toward the outside of the peptide. The incorporated β‐amino acids of βASC make the space inside the peptide large enough to envelop the two square pyramids. The observed structural changes in the bis‐Cu^II–βASC complex arising from ring expansion are particularly interesting in the context of the previously reported structure of the Cu^II–ASC complex.     

[Leu2]Gramicidin S preserves the structural properties of its parent peptide and forms helically aligned β‐sheets

For crystallographic analysis, Leu was substituted for Orn in Gramicidin S (LGS) to suppress interactions with hydrophilic solvent molecules, which increased the flexibility of the Orn side chains, leading to disorder within the crystals. The asymmetric unit (C₆₂H₉₄N₁₀O₁₀·1.296C₃H₈O·1.403H₂O) contains three LGS molecules (A, B and C) forming β‐turn and intramolecular β‐sheet structures. With the exception of one motif in molecule C, d ‐Phe‐Pro turn motifs (Phe is phenylalanine and Pro is proline) were classed as type II′ β‐turns. The peptide backbones twist slightly to the right along the long axis of the molecule. The puckering of Pro is in a Cγ‐endo or twisted Cγ‐endo–Cβ‐exo form. Flanking molecules are arranged such that the angles (A…B = 104°, B…C = 139° and C…A = 117°) form helical β‐sheets. Solvent molecules interact with the peptide backbones supporting the β‐sheets. The forms of the replacement Leu side chains are consistent with the e‐form of the Orn side chain in GS analogues. No hydrophilic region composed of solvent molecules, such as that observed in Gramicidin S hydrochloride (GS·HCl) crystals, was found. The perturbation of αH chemical shifts and coupling constants of CONH showed that the structural properties of GS·HCl and LGS are similar to each other in solution. CD spectra also supported the structural similarity. With the sequence cyclo(–Val–Leu–Leu–d ‐Phe–Pro–)₂ (Val is valine and Leu is leucine), LGS lacks the amphiphilicity and antimicrobial activity of parental Gramicidin S (GS). However, the structure of LGS reflects the structural characteristics of GS and no disordering inconvenient for structural analysis was found. Thus, LGS could be a novel scaffold useful for studying β‐turn and sheet structures.     

Studies on Nepalese crude drugs. XXIX. Chemical constituents of Dronapuspi, the whole herb of Leucas cephalotes SPRENG

From the whole herb of Leucas cephalotes SPRENG., new labdane-, norlabdane- and abietane-type diterpenes named leucasdins A (1), B (2) and C (3), respectively, and two protostane-type triterpenes named leucastrins A (4) and B (5) were isolated, together with a known triterpene, oleanolic acid, five sterols, 7-oxositosterol, 7-oxostigmasterol, 7alpha-hydroxysitosterol, 7alpha-hydroxystigmasterol and stigmasterol, and eight flavones, 5-hydroxy-7,4'-dimethoxyflavone, pillion, gonzalitosin I, tricin, cosmosin, apigenin 7-O-beta-D-(6-O-p-coumaroyl)glucopyranoside, anisofolin A and luteolin 4'-O-beta-D-glucuronopyranoside. The structures of 1--5 were determined as (3S,6R,8R,9R,13S,16S)-9,13,15,16-bisepoxy-3,16-diacetoxy-6-formyloxylabdane, (3S,6R)-3-acetoxy-6-formyloxy-iso-ambreinolide, (4R,9S,12R,13R)-12,13-dihydroxyabiet-7-en-18-oic acid, (3S,17S,20S,24S)-3,20-dihydroxy-24-methylprotost-25-en, and (3S,17S,20S,24S)-3,20,24-trihydroxyprotost-25-en respectively, based on spectral and chemical data.     

Sulfur-containing polymers. X. Aromatic poly(sulfenyl thiocarbonates)

Aromatic poly(sulfenyl thiocarbonates) have been synthesized by the interfacial polycondensation of bis(dithiocarbonyl chlorides) with bisphenols. Bisphenols having the hydroxyl groups on separate rings gave polymers in high yields. The inherent viscosities of the polymers ranged from 0.22 to 0.51. In general, they were soluble in chloroform, sym-tetrachloroethane, hexamethylphosphoramide, m-cresol, and dimethylformamide and formed transparent tough films on evaporation of chloroform solutions. Almost all of the polymers were amorphous and gave melt-spun fibers. The polymer films decomposed upon ultraviolet irradiation with liberation of carbonyl sulfide.     

Determination of estrogens and their conjugates in water using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry

An analytical procedure for the determination of steroid estrogens and their conjugates was developed and applied to aqueous environmental samples. The analytes of 15 compounds were solid-phase extracted and fractionated into two fractions: one containing unconjugated (free) steroids and the other containing conjugates (sulfates and glucuronides). Identification and quantification were carried out using liquid chromatography coupled with tandem mass spectrometry. The recoveries for each compound ranged from 57 to 116% and reproducibilities represented as RSD ranged from 2.9 to 17%. Some of the sulfates and free compounds were detected in environmental samples, whereas most of the conjugates were below the detection limits.     

Simultaneous determination of hydrophilic amino acid enantiomers in mammalian tissues and physiological fluids applying a fully automated micro-two-dimensional high-performance liquid chromatographic concept

A validated two-dimensional HPLC system combining a microbore-monolithic ODS column and a narrowbore-enantioselective column has been established for a sensitive and simultaneous analysis of hydrophilic amino acid enantiomers (His, Asn, Ser, Gln, Arg, Asp, allo-Thr, Glu and Thr) and the non-chiral amino acid, Gly, in biological samples. To accomplish this goal, the amino acids were first tagged with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) to the respective fluorescent NBD derivatives which were separated in the first dimension by a micro-reversed-phase column. The automatically collected fractions of the target peaks were then transferred to the second dimension consisting of a Pirkle type enantioselective column generating separation factors higher than 1.13 for all the enantiomeric target analytes. The system was validated using standard amino acids and a rat plasma sample, and analytically satisfactory calibration and precision results were obtained. The present 2D-HPLC system enables the fully automated determination of hydrophilic amino acid enantiomers in mammalian samples. The d-isomers of all the investigated 9 amino acids were found in rat urine but at various enantiomeric ratios.     

Two-dimensional residual charge density distribution measurement of surface leader

The charge density distribution of the surface leader has never been measured before. Because the surface leader usually covers a long distance, and the surface potential caused by leader discharge is usually very high, this creates difficulties in measuring the potential distribution of the surface leader. In this paper, with a feedback type electrostatic probe based on a field-nullify technique, a charge density distribution scanning system is developed. A two-layer structure pipe is designed to lower the surface potential after discharge. In this way, the surface potential distribution caused by the residual charge of the leader discharge under the application voltage as high as to 40 kV can be measured. The surface charge density distribution including the leader and streamer is perfectly measured, which is in good agreement with the photograph.     

Simultaneous pursuit of out-of-sample performance and sparsity in index tracking portfolios

Index tracking is a passive investment strategy in which a fund (e.g., an ETF: exchange traded fund) manager purchases a set of assets to mimic a market index. The tracking error, i.e., the difference between the performances of the index and the portfolio, may be minimized by buying all the assets contained in the index. However, this strategy results in a considerable transaction cost and, accordingly, decreases the return of the constructed portfolio. On the other hand, a portfolio with a small cardinality may result in poor out-of-sample performance. Of interest is, thus, constructing a portfolio with good out-of-sample performance, while keeping the number of assets invested in small (i.e., sparse). In this paper, we develop a tracking portfolio model that addresses the above conflicting requirements by using a combination of L0- and L2-norms. The L2-norm regularizes the overdetermined system to impose smoothness (and hence has better out-of-sample performance), and it shrinks the solution to an equally-weighted dense portfolio. On the other hand, the L0-norm imposes a cardinality constraint that achieves sparsity (and hence a lower transaction cost). We propose a heuristic method for estimating portfolio weights, which combines a greedy search with an analytical formula embedded in it. We demonstrate that the resulting sparse portfolio has good tracking and generalization performance on historic data of weekly and monthly returns on the Nikkei 225 index and its constituent companies.     

Parametric harmonic-to-fundamental ratio contrast echocardiography: a novel approach to identification and accurate measurement of left ventricular area under variable levels of ultrasound signal attenuation

Objectives

We introduced a harmonic-to-fundamental ratio (HFR) of the radiofrequency (RF) signals that reduces confounding effects of attenuation. We studied whether HFR analysis of RF signals received from contrast microbubbles allows accurate measurement of the left ventricular (LV) cavity area under varying levels of attenuation.

Background

Attenuation is a fundamental problem in ultrasound imaging and limits the use of clinical echocardiography.

Methods

RF data from short axis systolic and diastolic scans were obtained from 14 open-chest dogs following left-atrial bolus of Optison. Attenuation was induced by interposed silicone pads calibrated to induce 7 dB or 14 dB reductions of the backscattered RF signal. RF images were reconstructed from the RF signals, HFR values calculated for each image pixel for 0 dB, 7 dB and 14 dB attenuation conditions, and LV area obtained by summation of “LV cavity pixels”. A reference LV cavity area was obtained from endocardial border tracings in enhanced scans by experts.

Results

Correlation of the HFR-defined and reference areas at systole was R = 0.95, R = 0.94, and R = 0.91 for 0 dB, 7 dB and 14 dB levels of attenuation, respectively, and at diastole was R = 0.95 for 0 dB, 7 dB and 14 dB levels of attenuation. The mean difference from both systolic and diastolic values was <1.45 cm² (i.e. negligible) in all attenuation settings.

Conclusion

Our novel HFR method supports precise measurement of the LV cavity area in contrast images with simulated high attenuation of ultrasound signals.     

Synthesis and In Vitro Biological Evaluation of Psoralen‐Linked Fullerenes

Photodynamic therapy (PDT) is a widely used medicinal treatment for the cancer therapy that utilizes the combination of a photosensitizer (PS) and light irradiation. In this study, we synthesized two novel C₆₀ fullerene derivatives, compounds 1 and 2 , with a psoralen moiety that can covalently bind to DNA molecules via cross‐linking to pyrimidine under photoirradiation. Along with several fullerene derivatives, the biological properties of several novel compounds have been evaluated. Compounds 1 and 2 , which have been shown to induce the production of hydroxyl radicals using several ROS detecting reagents, induced DNA strand breaks with relatively weak activities in the in vitro detection system using a supercoiled plasmid. However, the psoralen‐bound fullerene with carboxyl groups ( 2 ) only showed genotoxicity in the genotoxicity assay system of the umu test. Compound 2 was also seen to have cytotoxic activities in several cancer cell lines at higher doses compared to water‐soluble fullerenes.