Active oxygen species generated from photoexcited fullerene (C60) as potential medicines: O2-* versus 1O2

To characterize fullerenes (C(60) and C(70)) as photosensitizers in biological systems, the generation of active oxygen species, through energy transfer (singlet oxygen (1)O(2)) and electron transfer (reduced active oxygen radicals such as superoxide anion radical O(2)(-)* and hydroxyl radical *OH), was studied by a combination of methods, including biochemical (DNA-cleavage assay in the presence of various scavengers of active oxygen species), physicochemical (EPR radical trapping and near-infrared spectrometry), and chemical methods (nitro blue tetrazolium (NBT) method). Whereas (1)O(2) was generated effectively by photoexcited C(60) in nonpolar solvents such as benzene and benzonitrile, we found that O(2)(-)* and *OH were produced instead of (1)O(2) in polar solvents such as water, especially in the presence of a physiological concentration of reductants including NADH. The above results, together with those of a DNA cleavage assay in the presence of various scavengers of specific active oxygen species, indicate that the active oxygen species primarily responsible for photoinduced DNA cleavage by C(60) under physiological conditions are reduced species such as O(2)(-)* and *OH.     

Gastric pH profile and its control in fasting beagle dogs

The gastric pH of fasting beagle dogs was measured by using an ion-selective field effect transistor pH sensor. In addition, a novel procedure to control the gastric pH in fasting beagle dogs was investigated. Inter- and intra-day variations in the gastric pH of the dogs were observed. The gastric pH of the dogs could be controlled by a single intravenous administration of omeprazole, an H+, K+-adenosine triphosphatase (ATPase) inhibitor (1 mg/0.25 ml/kg). The pH in the stomach was 6.6 +/- 0.2 (mean +/- S.D., n = 6) at 1 h after the omeprazole treatment, and this level of pH was maintained for a period of at least 3 h. Beagle dogs in which the gastric pH has been controlled by omeprazole are considered to be useful as an animal model to be used for the pharmaceutical evaluation of drugs in subjects with a low acidity level.     

Malycorins A--C, New lycopodium alkaloids from Lycopodium phlegmaria

A novel C(19)N-type Lycopodium alkaloid, malycorin A (1) consisting of a serratinane skeleton with 2-propanol unit has been isolated from the club moss Lycopodium phlegmaria, together with two new C(16)N-type alkaloids, malycorins B (2) and C (3), and the structures and relative stereochemistry were elucidated on the basis of spectroscopic data.     

High-throughput sorting of nanoliter droplets enabled by a sequentially addressable dielectrophoretic array

Droplet microfluidics has emerged as a powerful tool for a diverse range of biomedical and industrial applications such as single-cell analysis, directed evolution, and metabolic engineering. In these applications, droplet sorting has been effective for isolating small droplets encapsulating molecules, cells, or crystals of interest. Recently, there is an increased interest in extending the applicability of droplet sorting to larger droplets to utilize their size advantage. However, sorting throughputs of large droplets have been limited, hampering their wide adoption. Here, we report our demonstration of high-throughput fluorescence-activated droplet sorting of 1 nL droplets using an upgraded version of the sequentially addressable dielectrophoretic array (SADA), which we reported previously. The SADA is an array of electrodes that are individually and sequentially activated/deactivated according to the speed and position of a droplet passing nearby the array. We upgraded the SADA by increasing the number of driving electrodes constituting the SADA and incorporating a slanted microchannel. By using a ten-electrode SADA with the slanted microchannel, we achieved fluorescence-activated droplet sorting of 1 nL droplets at a record high throughput of 1752 droplets/s, twice as high as the previously reported maximum sorting throughput of 1 nL droplets.     

Identification of a constitutive law for trabecular bone samples under remodeling in the framework of irreversible thermodynamics

We construct in the present paper constitutive models for bone remodeling based on micromechanical analyses at the scale of a representative unit cell (RUC) including a porous trabecular microstructure. The time evolution of the microstructure is simulated as a surface remodeling process by relating the surface growth remodeling velocity to a surface driving force incorporating a (surface) Eshelby tensor. Adopting the framework of irreversible thermodynamics, a 2D constitutive model based on the setting up of the free energy density and a dissipation potential is identified from FE simulations performed over a unit cell representative of the trabecular architecture obtained from real bone microstructures. The static and evolutive effective properties of bone at the scale of the RUC are obtained by combining a methodology for the evaluation of the average kinematic and static variables over a prototype unit cell and numerical simulations with controlled imposed first gradient rates. The formulated effective growth constitutive law at the scale of the homogenized set of trabeculae within the RUC is of viscoplastic type and relates the average growth strain rate to the homogenized stress tensor. The postulated model includes a power law function of an effective stress chosen to depend on the first and second stress invariants. The model coefficients are calibrated from a set of virtual testing performed over the RUC subjected to a sequence of loadings. Numerical simulations show that overall bone growth does not show any growth kinematic hardening. The obtained results quantify the strength and importance of different types of external loads (uniaxial tension, simple shear, and biaxial loading) on the overall remodeling process and the development of elastic deformations within the RUC.     

1/f-type fluctuation of electron transmission in one-dimensional disordered systems

A universal feature of 1/f-type fluctuation is numerically observed in the system-size n dependence of the transmission amplitude t_n in various one-dimensional disordered systems. The power spectrum P(f) of the transmission coefficient T(n)=|t_n|² exhibits the power law of 1/f², irrespective to the type of disorder of the system whether it is of short-range or of long-range correlation. That of the phase θ_t(n) of t_n also does the universal power law of 1/f^1.4.     

Equivalent mechanical properties of textile monolayers from discrete asymptotic homogenization

The determination of the effective mechanical moduli of textiles from mechanical measurements is usually difficult due to their discrete architecture, which makes micromechanical analyses a relevant alternative to access those properties. Micropolar continuum models describing the effective mechanical behavior of woven fabric monolayers are constructed from the homogenization of an identified repetitive pattern of the textile within a representative unit cell. The interwoven yarns within the textile are represented as a network of trusses connected by nodes at their crossover points. These trusses have extensional and bending rigidities to allow for yarn stretching and flexion, and a transverse shear deformation is additionally considered. Interactions between yarns at the crossover points are captured by beam segments connecting the nodes. The woven fabric is modeled after homogenization as an anisotropic planar continuum with two preferred material directions in the mean plane of the textile. Based on the developed methodology, the effective mechanical properties of plain weave and twill are evaluated, including their bending moduli and characteristic flexural lengths. A satisfactory agreement is obtained between the effective moduli obtained by homogenization and numerical values obtained by finite element simulations performed over periodic unit cells.     

Evaluation of commercial immunoassays for the detection of estrogens in water by comparison with high-performance liquid chromatography tandem mass spectrometry HPLC–MS/MS (QqQ)

In this work four different commercially available enzyme-linked immunosorbent assays (ELISA) (from Japan EnviroChemicals, Ltd., Tokyo, Japan) were evaluated in terms of performance for the rapid screening of estrogens in different water matrices, including natural and spiked samples from urban wastewater, river water and ground water. All four test kits are based on monoclonal antibodies. The compounds detected by these immunoassays are (1) 17-β-estradiol, (2) estrone, (3) 17-α-ethynyl estradiol and (4) estrogens in general, with high recognition properties for 17-β-estradiol, estrone and estriol. Standards were prepared in water containing 10% (v/v) methanol. The IC ₅₀ (corresponding to the 50% of the effective concentration) values, the dynamic ranges, and the limits of detection of the ELISA kits were 0.060–0.304 μg/L, 0.05–5 μg/L and 0.05 μg/L, respectively. All samples were extracted by solid-phase extraction (SPE) beforehand, and the evaluation was carried out by comparing the results obtained by ELISA with those obtained by HPLC–MS/MS using a triple quadrupole (QqQ) instrument. In addition, two different solid-phase extraction procedures were carried out and compared. Except for moderate overestimation in the results observed with the ELISA kits in the analysis of complex wastewater samples, the results obtained using all of the tested techniques were generally in very good agreement.      

Computing the variance of a conditional expectation via non-nested Monte Carlo

Computing the variance of a conditional expectation has often been of importance in uncertainty quantification. Sun et al. has introduced an unbiased nested Monte Carlo estimator, which they call $1\frac{1}{2}$-level simulation since the optimal inner-level sample size is bounded as the computational budget increases. In this letter, we construct unbiased non-nested Monte Carlo estimators based on the so-called pick-freeze scheme due to Sobol’. An extension of our approach to compute higher order moments of a conditional expectation is also discussed.     

Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity

A novel class of 6-indolypyridine-3-carbonitrile derivatives were synthesized and evaluated for antiproliferative activities to establish structure–activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, ethyl cyanoacetate, and ammonium acetate in the presence of piperidine as a catalyst, using a microwave irradiation method or a traditional thermal method. This was followed by chlorination for compounds 13a–e and subsequent nucleophilic substitution of the chlorine group by ethylenediamine at C₂ position of the pyridine ring. The antiproliferative activity of these new nicotinonitriles was evaluated against human ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7), and cervix adenocarcinoma (HeLa) cells. Among all compounds, 2-((2-aminoethyl)amino)-4-aryl-6-indolylnicotinonitriles series (15a, 15b, 15d, and 15e) exhibited higher antiproliferative activity on the three cancer cell lines with IC₅₀ values of 4.1–13.4 μM.