Homogeneous Oligomeric Ligands Prepared via Radical Polymerization that Recognize and Neutralize a Target Peptide

Abiotic ligands that bind to specific biomolecules have attracted attention as substitutes for biomolecular ligands, such as antibodies and aptamers. Radical polymerization enables the production of robust polymeric ligands from inexpensive functional monomers. However, little has been reported about the production of monodispersed polymeric ligands. Herein, we present homogeneous ligands prepared via radical polymerization that recognize epitope sequences on a target peptide and neutralize the toxicity of the peptide. Taking advantage of controlled radical polymerization and separation, a library of multifunctional oligomers with discrete numbers of functional groups was prepared. Affinity screening revealed that the sequence specificity of the oligomer ligands strongly depended on the number of functional groups. The process reported here will become a general step for the development of abiotic ligands that recognize specific peptide sequences.     

Approximating a class of combinatorial problems with rational objective function

In the late seventies, Megiddo proposed a way to use an algorithm for the problem of minimizing a linear function a ₀ + a ₁ x ₁ + . . . + a _n x _n subject to certain constraints to solve the problem of minimizing a rational function of the form (a ₀ + a ₁ x ₁ + . . . + a _n x _n )/(b ₀ + b ₁ x ₁ + . . . + b _n x _n ) subject to the same set of constraints, assuming that the denominator is always positive. Using a rather strong assumption, Hashizume et al. extended Megiddo’s result to include approximation algorithms. Their assumption essentially asks for the existence of good approximation algorithms for optimization problems with possibly negative coefficients in the (linear) objective function, which is rather unusual for most combinatorial problems. In this paper, we present an alternative extension of Megiddo’s result for approximations that avoids this issue and applies to a large class of optimization problems. Specifically, we show that, if there is an α-approximation for the problem of minimizing a nonnegative linear function subject to constraints satisfying a certain increasing property then there is an α-approximation (1/α-approximation) for the problem of minimizing (maximizing) a nonnegative rational function subject to the same constraints. Our framework applies to covering problems and network design problems, among others.     

A note on the angular distribution of the characteristic surface loss intensity of electrons with non-normal incidence to the foils

By using a quantized theory of non-radiative surface plasmon in a semi-infinite electron gas, where retardation is taken into account, the differential surface loss intensity of electrons in a metal foil is calculated for the case of non-normal incidence of electron to the metal surface. The result shows that the differential surface loss intensity neither has a zero at θ = 0 for the case of normal incidence nor has a zero at a forward direction (θ ≠ 0, φ = 0) for the case of non-normal incidence, whose existences were predicted by electrostatic theories, but diverges as 1/θ at θ = 0 for both cases. It is also shown that, when the angle of incidence is greater than a certain critical value, there is a region of direction to which incident electrons can be scattered by exciting any one of surface plasmons with three different wave vectors.     

The Effects of Comprehensive Exercise Program on the Adjustments of Standing Balance in Community-Dwelling Elderly Persons

The objective of this study was to assess the effect of comprehensive exercise program widely accepted as a community-based physical intervention for the prevention of falling in the elderly persons on their controlling standing balance. Twenty-six community-dwelling elderly persons (13 males and females; 69.8 ± 2.8 years old) participated in this study. Daily exercise was comprised of walking for more than 30 min, stretching, muscle strengthening and balance exercise without exercise equipments. The intervention was continued for three months. Indicators of standing balance related to static balance, dynamic balance and postural response were measured before and after the intervention. As an effect of the intervention on static balance, the sway of center of pressure (COP) in the static stance significantly increased. In the dynamic balance, significant improvements were observed in one leg standing time, the 10-m gait time, functional reach. Additionally, the maximal movable length of COP which subjects can move voluntarily to right and left significantly increased. In the postural response, the integrated electromyography (IEMG) induced by postural response for sudden postural perturbation significantly decreased in the lower leg muscles. Since less muscular activities were sufficient to maintain posture, it was suggested that postural response was elicited more efficiently following the intervention. This study suggested that the comprehensive exercise program, which has been widely introduced as community-based interventions for the prevention of falling, have extensive effects on the control of standing balance covering static balance, dynamic balance and postural response in the elderly persons.     

Development of a liquid chromatography/time-of-flight mass spectrometric method for the simultaneous determination of trichothecenes, zearalenone and aflatoxins in foodstuffs

A liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) method based on time-of-flight MS (TOFMS) with a real-time reference mass correction technique was developed for the simultaneous determination of Fusarium mycotoxins (nivalenol, deoxynivalenol, fusarenon X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, HT-2 toxin, T-2 toxin, diacetoxyscirpenol, zearalenone) and Aspergillus mycotoxins (aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2) in corn, wheat, cornflakes and biscuits. Samples were cleaned up with a MultiSep #226 column. Detection of the mycotoxins was carried out in exact mass chromatograms with a mass window of 0.03 Th. Calibration curves were linear from 2 to 200 ng x mL(-1) for trichothecenes and zearalenone, and 0.2 to 20 ng x mL(-1) for aflatoxins, by 20 microL injection. The limits of detection ranged from 0.1 to 6.1 ng x g(-1) in foodstuffs analyzed in this study. The LC/TOFMS method was found to be suitable for the screening of multiple mycotoxins in foodstuffs rapidly and with high sensitivity, and its performance was demonstrated for the confirmation for target mycotoxins.     

Synthesis of nitrogen-containing heterocycles. 8. Preparation and ring-opening of spiro[cycloalkane-[1′,2′,4′]triazolo[1′,5′-c]pyrimidine] derivatives

Diaminomethylene- and aminomethylthiomethylenehydrazones [2] of cyclic ketones 1–8 readily reacted with ethoxymethylenemalononitrile to give spiro[cycloalkane-1,2′-[1,2′,4′]triazolo[1,5′-c]pyrimidine-8′-carbonitrile] derivatives 12–19 through the electrocyclic reaction of the initially formed condensation products 26 in moderate to high yields. The spiro[cyclopentanetriazolopyrimidine] derivatives underwent ring-opening at the cycloalkane moiety upon heating in solution to give 2-alkyl-5-substituted-[1,2,4]triazolo[1,5-c]pyrimidine-8′-carbonitriles 20–23 . When an alkyl substituent was introduced into the cyclopentane ring, cleavage of the spiro compounds occurred preferentially at the cyclopentane moiety between the spiro carbon and the more branched one. In contrast, the cyclohexane ring, especially of spiro-5-amino-triazolopyrimidines 17 and 18 strongly resisted to ring-opening under similar conditions, but those of 5-methylthiotriazolopyrimidines 14 gave up to 17 percent of cleavage after prolonged heating in hot ethanol. 2-t-Butyl-5-methylthio-2,3-dihydro[1,2,4]triazolo[1,5-c]pyrimidine-8-carbonitrile 25 [R³ = C(CH₃)₃] was highly susceptible to the cleavage even at room temperature and produced the corresponding 2-unsubstituted triazolopyrimidine 24 with loss of the t-butyl group.     

Synthesis of 1-(5,6-dihydro-2H-thiopyran-2-yl)uracil by a Pummerer-type thioglycosylation reaction: the regioselectivity of allylic substitution

1-(5,6-Dihydro-2H-thiopyran-2-yl)uracil derivatives, a new 4′-thio-D4-nucleoside analogue, were synthesized by reacting 5,6-dihydro-2H-thiopyran sulfoxide and persilylated uracil in a Pummerer-type thioglycosylation reaction. The reaction of 5-alkyl substituted dihydrothiopyran sulfoxide 7 only gave 1-(dihydrothiopyran-2-yl)uracil 9. On the other hand, the reaction with a 5-siloxy substituted derivative of 7 resulted in a mixture of products with the uracil moiety at either the α- or the γ-position. The use of a prolonged reaction time resulted in the exclusive formation of the 4-substituted dihydrothiopyran derivative 10. The result suggests that an equilibrium is operative in the formation of the α- and γ-adducts and that the latter should be more thermodynamically stable than the former. This conclusion was also supported by theoretical calculations.     

Syntheses and Properties of Graphyne Fragments: Trigonally Expanded Dehydrobenzo[12]annulenes

We present herein the synthesis and properties of the largest hitherto unknown graphyne fragment, namely trigonally expanded tetrakis(dehydrobenzo[12]annulene)s (tetrakis‐DBAs). Intramolecular three‐fold alkyne metathesis reactions of hexakis(arylethynyl)DBAs 9 a and 9 b using Fürstner’s Mo catalyst furnished tetrakis‐DBAs 8 a and 8 b substituted with tert‐butyl or branched alkyl ester groups in moderate and fair yields, respectively, demonstrating that the metathesis reaction of this protocol is a powerful tool for the construction of graphyne fragment backbones. For comparison, hexakis(arylethynyl)DBAs 9 c – g have also been prepared. The one‐photon absorption spectrum of tetrakis‐DBA 8 a bearing tert‐butyl groups revealed a remarkable bathochromic shift of the absorption cut‐off (λ_cutoff) compared with those of previously reported graphyne fragments due to extended π‐conjugation. Moreover, in the two‐photon absorption spectrum, 8 a showed a large cross‐section for a pure hydrocarbon because of the planar para‐phenylene‐ethynylene conjugation pathways. Hexakis(arylethynyl)‐DBAs 9 c – e and 9 g and tetrakis‐DBA 8 b bearing electron‐withdrawing groups aggregated in chloroform solutions. Comparison between the free energies of 9 e and 8 b bearing the same substituents revealed the more favorable association of the latter due to stronger π–π interactions between the extended π‐cores. Polarized optical microscopy observations, DSC, and XRD measurements showed that 8 b and 9 e with branched alkyl ester groups displayed columnar rectangular mesophases. By the time‐resolved microwave conductivity method, the columnar rectangular phase of 8 b was shown to exhibit a moderate charge‐carrier mobility of 0.12 cm² V^?1 s^?1. These results indicate that large graphyne fragments can serve as good organic semiconductors.     

Bioinert surface to protein adsorption with higher generation of dendrimer SAMs

Interactions between proteins and biomaterial surfaces correlate with many important phenomena in biological systems. Such interactions have been used to develop various artificial biomaterials and applications, in which regulation of non-specific protein adsorption has been achieved with bioinert properties. In this research, we investigated the protein adsorption behavior of polymer brushes of dendrimer self-assembled monolayers (SAMs) with other generations. The surface adsorption properties of proteins with different pI values were examined on gold substrates modified with poly(amidoamine) dendrimer SAMs. The amount of fibrinogen adsorption was greater than that of lysozyme, potentially because of the surface electric charge. However, as the generations increased, protein adsorption decreased regardless of the surface charge, suggesting that protein adsorption was also affected by density of terminal group.