Increased expression and phosphorylation of liver glutamine synthetase in well-differentiated hepatocellular carcinoma tissues from patients infected with hepatitis C virus

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers, and chronic infection with hepatitis C virus (HCV) is thought to be one of the main causes in Japan. To identify diagnostic or therapeutic biomarkers for HCC associated with HCV (HCV-HCC), we tried to elucidate the factors related to the products from cancerous tissues of HCV-infected patients. From proteomic differential display analysis of liver tissue samples from HCV-HCC cancerous tissues and corresponding non-cancerous tissues from patients, three protein spots of the same molecular mass (42 kDa), whose expression increased in well-differentiated cancerous tissues, were detected. Although their pI were different, they were identified as glutamine synthetase (GS) by PMF with MALDI-TOF MS and by Western blotting using anti-GS specific mAb. Immunohistochemical analysis showed that tumor tissue consists of two parts, GS-positive cell and GS-negative cell regions, suggesting that GS-producing cells grew in the tumor tissue as a nodule in nodules. The tryptic peptides of the most acidic GS isoform lost the signal of 899.5 Da, corresponding a peptide of SASIRIPR, and gained a signal of 1059.5 Da, which was submitted to PSD analysis. PSD analysis showed the neutral loss by elimination of two phosphate groups, supposed to be on serine residues of the 899.5-Da peptide, from serine 320 to arginine 327 in GS. PMF followed by PSD analysis is thought to be useful for the determination of phosphorylation sites of proteins showing molecular heterogeneity.     

Photomagnetism of a sym‐cis‐Dithiocyanato Iron(II) Complex with a Tetradentate N,N′‐Bis(2‐pyridylmethyl)1,2‐ethanediamine Ligand

A comprehensive study of the magnetic and photomagnetic behaviors of cis‐[Fe(picen)(NCS)₂] (picen=N,N′‐bis(2‐pyridylmethyl)1,2‐ethanediamine) was carried out. The spin‐equilibration was extremely slow in the vicinity of the thermal spin‐transition. When the cooling speed was slower than 0.1 K min^?1, this complex was characterized by an abrupt thermal spin‐transition at about 70 K. Measurement of the kinetics in the range 60–70 K was performed to approach the quasi‐static hysteresis loop. At low temperatures, the metastable HS state was quenched by a rapid freezing process and the critical T(TIESST) temperature, which was associated with the thermally induced excited spin‐state‐trapping (TIESST) effect, was measured. At 10 K, this complex also exhibited the well‐known light‐induced excited spin‐state‐trapping (LIESST) effect and the T(LIESST) temperature was determined. The kinetics of the metastable HS states, which were generated from the freezing effect and from the light‐induced excitation, was studied. Single‐crystal X‐ray diffraction as a function of speed‐cooling and light conditions at 30 K revealed the mechanism of the spin‐crossover in this complex as well as some direct relationships between its structural properties and its spin state. This spin‐crossover (SCO) material represents a fascinating example in which the metastability of the HS state is in close vicinity to the thermal spin‐transition region. Moreover, it is a beautiful example of a complex in which the metastable HS states can be generated, and then compared, either by the freezing effect or by the LIESST effect.     

Cyano‐Bridged MnIII?MIII Single‐Chain Magnets with MIII=CoIII,FeIII, MnIII,and CrIII

A series of isostructural cyano‐bridged Mn^III(h.s.)–M^III(l.s.) alternating chains, [Mn^III(5‐TMAMsalen)M^III(CN)₆] ? 4H₂O (5‐TMAMsalen^2?=N,N′‐ethylenebis(5‐trimethylammoniomethylsalicylideneiminate), Mn^III(h.s.)=high‐spin Mn^III, M^III(l.s.)=low‐spin Co^III, Mn? Co ; Fe^III, Mn? Fe ; Mn^III, Mn? Mn ; Cr^III, Mn? Cr ) was synthesized by assembling [Mn^III(5‐TMAMsalen)]³⁺ and [M^III(CN)₆]^3?. The chains present in the four compounds, which crystallize in the monoclinic space group C2/c, are composed of an [‐Mn^III‐NC‐M^III‐CN‐] repeating motif, for which the ‐NC‐M^III‐CN‐ motif is provided by the [M^III(CN)₆]^3? moiety adopting a trans bridging mode between [Mn^III(5‐TMAMsalen)]³⁺ cations. The Mn^III and M^III ions occupy special crystallographic positions: a C₂ axis and an inversion center, respectively, forming a highly symmetrical chain with only one kind of cyano bridge. The Jahn–Teller axis of the Mn^III(h.s.) ion is perpendicular to the N₂O₂ plane formed by the 5‐TMAMsalen tetradentate ligand. These Jahn–Teller axes are all perfectly aligned along the unique chain direction without a bending angle, although the chains are corrugated with an Mn‐N_axis‐C angle of about 144°. In the crystal structures, the chains are well separated with the nearest inter‐chain M???M distance being relatively large at 9 Å due to steric hindrance of the bulky trimethylammoniomethyl groups of the 5‐TMAMsalen ligand. The magnetic properties of these compounds have been thoroughly studied. Mn? Fe and Mn? Mn display intra‐chain ferromagnetic interactions, whereas Mn? Cr is characterized by an antiferromagnetic exchange that induces a ferrimagnetic spin arrangement along the chain. Detailed analyses of both static and dynamic magnetic properties have demonstrated without ambiguity the single‐chain magnet (SCM) behavior of these three systems, whereas Mn? Co is merely paramagnetic with S_Mn=2 and D/k_B=?5.3 K (D being a zero‐field splitting parameter). At low temperatures, the Mn? M compounds with M=Fe, Mn, and Cr display remarkably large M versus H hysteresis loops for applied magnetic fields along the easy magnetic direction that corresponds to the chain direction. The temperature dependence of the associated relaxation time for this series of compounds systematically exhibits a crossover between two Arrhenius laws corresponding to infinite‐chain and finite‐chain regimes for the SCM behavior. These isostructural hetero‐spin SCMs offer a unique series of alternating [‐Mn‐NC‐M‐CN‐] chains, enabling physicists to test theoretical SCM models between the Ising and Heisenberg limits.     

Lewis acid-mediated radical cyclization: stereocontrol in cascade radical addition-cyclization-trapping reactions

An efficient approach for achieving radical cyclizations by using hydroxamate ester as a coordination tether with Lewis acid was studied. The chiral Lewis acid-mediated cascade radical addition-cyclization-trapping reaction proceeded smoothly with good enantio- and diastereoselectivities, providing various chiral γ-lactams.     

Capacity switching options under rivalry and uncertainty

Deregulated infrastructure industries exhibit stiff competition for market share. Firms may be able to limit the effects of competition by launching new projects in stages. Using a two-stage real options model, we explore the value of such flexibility. We first demonstrate that the value of investing in a sequential manner for a monopolist is positive but decreases with uncertainty. Next, we find that a typical duopoly firm’s value relative to a monopolist’s decreases with uncertainty as long as the loss in market share is high. Intriguingly, this result is reversed for a low loss in market share. We finally show that this loss in value is reduced if a firm invests in a sequential manner and specify the conditions under which sequential capacity expansion is more valuable for a duopolist firm than for a monopolist.     

Magnetic interactions in A-site-ordered perovskites LnCu3(Ge(3/4)Ga(1/4))4O12 (Ln = La, Dy)

A-site-ordered perovskites LaCu(3)(Ge(3/4)Ga(1/4))(4)O(12) and DyCu(3)(Ge(3/4)Ga(1/4))(4)O(12) were synthesized, and their magnetism was investigated. Ferromagnetic ordering of the square-planar-coordinated Cu(2+) spins was observed at 12-13 K in both compounds, and the Dy(3+) moment in DyCu(3)(Ge(3/4)Ga(1/4))(4)O(12) stayed paramagnetic below T(C). The decoupling of the magnetic behavior of Cu(2+) and Dy(3+) sublattices revealed the weak magnetic interaction between Cu(2+) and Dy(3+).     

Molecular Transformation to Pyrroles,Pentafulvenes, and Pyrrolopyridines by [2+2] Cycloaddition of Propargylamines with Tetracyanoethylene

In this paper, we describe an efficient and atom-economical synthesis of highly functionalized pyrroles, pentafulvenes, and pyrrolopyridines by [2+2] cycloaddition–retroelectrocyclization of N-substituted propargylamines with tetracyanoethylene, followed by the treatment of the resulting tetracyanobutadiene derivatives with silica gel. In this reaction, silica gel plays an important role to promote the intramolecular cyclization to afford the heterocyclic products from the tetracyanobutadiene intermediates. The products were obtained selectively depending on the substituent on the nitrogen atom of the starting propargylamines.     

Variation of Microenvironment around Auramine O Molecules Doped in Silica Prepared from Tetramethoxysilane

Silica gel doped with Auramine O (AuO), which is known as a microscopic viscosity probe through fluorescence spectra, was prepared by the sol-gel method using tetramethoxysilane (TMOS) as a starting alkoxide. Fluorescence spectra from the starting solution to the dry gel were measured to pursue the variation of microscopic viscosity around the AuO molecules during the sol-gel process. The fluorescence intensity of AuO did not change at the gelation point, indicating that the microscopic viscosity around AuO did not change during the sol-to-gel transformation. The intensity was, however, increased largely in the drying process; the internal motion of AuO molecules became largely restricted by the surrounded silica matrix during the drying process.     

Gamma-ray irradiation effect of spin crossover iron/III/ complexes

Gamma-ray irradiations for various spin crossover iron/III/ complexes were performed in order to examine the spin transition mechanism. The difference of the spin transition mechanisms was reflected in the differences of the fractions that the electronic state of iron atoms changed to low-spin at low temperature and the results were explained by using a phenomenological model.