In order to elucidate roles of the 2'-O-methylation of pyrimidine nucleotide residues of tRNAs, conformations of 2'-O-methyluridylyl(3'----5')uridine (UmpU), 2'-O-methyluridine 3'-monophosphate (Ump), and 2'-O-methyluridine (Um) in 2H2O solution were analyzed by one- and two-dimensional proton NMR spectroscopy and compared with those of related nucleotides and nucleoside. As for UpU and UmpU, the 2'-O-methylation was found to stabilize the C3'-endo form of the 3'-nucleotidyl unit (Up-/Ump-moiety). This stabilization of the C3'-endo form is primarily due to an intraresidue effect, since the conformation of the 5'-nucleotidyl unit (-pU moiety) was only slightly affected by the 2'-O-methylation of the 3'-nucleotide unit. In fact even for Up and Ump, the 2'-O-methylation significantly stabilizes the C3'-endo form by 0.8 kcal/.mol-1. By contrast, for nucleosides (U and Um), the C3'-endo form is slightly stabilized by 0.1 kcal/.mol-1. Accordingly, the stabilization of the C3'-endo form by the 2'-O-methylation is primarily due to the steric repulsion among the 2-carbonyl group, the 2'-O-methyl group and the 3'-phosphate group in the C2'-endo form. For some tRNA species, 2-thiolation of pyrimidine residues is found in positions where the 2'-O-methylation is found for other tRNA species.(ABSTRACT TRUNCATED AT 250 WORDS)

Interacting quantum many-body systems constitute a fascinating research field because they form quantum liquids with remarkable properties and universal behaviour The idea is that they behave as an ensemble of non-interacting 'quasi-particles'. However, non-equilibrium properties have still to be established and remain a key issue of many-body physics. Here, we show a precise experimental demonstration of Landau Fermi liquid theory extended to the non-equilibrium regime in a zero-dimensional system. Combining transport and ultra-sensitive current noise measurements, we have unambiguously identified the SU(2) (ref. The Kondo effect19 is a typical example of a quantum manybody effect, where a localized spin is screened by the surrounding conduction electrons at low temperature to form a unique correlated ground state. The Kondo state is described well by the Fermi liquid theory at equilibrium 1,9 , which makes it an ideal testbed to go beyond equilibrium. To unveil the universal behaviour of nonequilibrium Fermi liquid 11 , we have used the current fluctuations or shot noise in a Kondo-correlated nanotube quantum dot 18 . When electrons are transmitted through this system, the scattering induces the shot noise, which sensitively reflects the nature of the quasi-particles 20 , as shown in the upper panel of Fig. 1a. A remarkable prediction of the non-equilibrium Fermi liquid theory is that the residual interaction between quasi-particles creates an additional scattering of two quasi-particles which enhances the noise (see the lower panel of Fig. 1a) 10,12-15 . This two-particle scattering is characterized by an effective charge e * larger than e (electron charge). This value, closely related to the Wilson ratio, is universal for the Fermi liquid in the Kondo regime as it depends only on the symmetry group of the system [13][14][15] . Although some aspects of Kondo-associated noise have been reported 8,16,17 , a rigorous, selfconsistent treatment in a regime where universal results apply is at the core of the present work. Actually, by investigating the same nanotube quantum dot in the spin degenerate SU(2) Kondo regime and in the spin-orbit degenerate SU(4) regime, the noise is proved to contain distinct signatures of these two symmetries, confirming theoretical developments of Fermi liquid theory out of equilibrium.In our experiment, we measured the conductance and current noise through a carbon nanotube quantum dot grown by chemical vapour deposition 21 . Iron catalyst was deposited on an oxidized undoped silicon wafer and exposed to 10 mbar of acetylene for 9 s at 900• C. The nanotube was connected with a Pd(6 nm)/Al(70 nm) bilayer deposited by e-gun evaporation. The distance between the contacts is 400 nm and a side gate electrode is deposited to tune the potential of the quantum dot (see Fig. 1b). A magnetic field of 0.08 T is applied to suppress superconductivity of the contacts. To measure accurately the shot noise, our sample is connected to a resonant (2.58 MHz) LC circuit thermalized at the mixing chambe...

Universal properties of entangled many-body states are controlled by their symmetry and quantum fluctuations. By the magnetic-field tuning of the spin-orbital degeneracy in a Kondo-correlated quantum dot, we have modified quantum fluctuations to directly measure their influence on the many-body properties along the crossover from SU(4) to SU(2) symmetry of the ground state. High-sensitive current noise measurements combined with the nonequilibrium Fermi liquid theory clarify that the Kondo resonance and electron correlations are enhanced as the fluctuations, measured by the Wilson ratio, increase along the symmetry crossover. Our achievement demonstrates that nonlinear noise constitutes a measure of quantum fluctuations that can be used to tackle quantum phase transitions.

No abstract

No abstract

Japan 5'-Alkyl(aryl)thio-5'-deoxynucleosides [alkyl(aryl)nucleoside sulphides] were prepared in high yields by the reaction of nucleosides with dialkyl or diaryl disulphides in the presence of tri-n-butylphosphine. The method is widely applicable to the synthesis of unsymmetrical sulphides.

Claudin‐4 (CLDN‐4), a tight‐junction protein, is overexpressed in various malignant tumors, including gastric, colorectal, pancreatic, and breast cancers. However, CLDN‐4 is also expressed in normal tissues, including the liver, pancreas, kidney, and small intestine. Whether CLDN‐4 is an effective and safe target for cancer therapy has been unclear owing to the lack of a binder with both CLDN‐4 specificity and cross‐reactivity to human and murine cells. In this study, we successfully generated a rat anti‐CLDN‐4 monoclonal antibody (5D12) that was specific to, and cross‐reactive with, human and mouse CLDN‐4. 5D12 recognized the second extracellular domain of human CLDN‐4 in a conformation‐dependent manner. A human–rat chimeric IgG1 of 5D12 (xi‐5D12) activated the Fcγ IIIa receptor, indicating the activation of antibody‐dependent cellular cytotoxicity in CLDN‐4‐expressing cells. Moreover, xi‐5D12 significantly suppressed tumor growth in mice bearing human colorectal and gastric tumors without apparent adverse effects, such as weight loss or liver and kidney damage. These results suggest that CLDN‐4 is a potent target for cancer therapy and that an anti‐CLDN‐4 antibody is a promising candidate anticancer agent.

The reactions of silyl phosphites, i.e., tris (trimethylsilyl) phosphite (1), diethyl trimethylsilyl phosphite (11), and bis(trimethylsilyl) ethyl phosphite (12), with a variety of -halo carbonyl compounds gave the 1:1 carbonyl addition products (6,13, and 14), enol phosphates (5 and 26), and/or 2-oxophosphonates (4 and 25). Substituents on the phosphites and the -halo carbonyl compounds have influenced the product ratios. The results of these reactions strongly suggest that the Perkow reaction proceeds via an initial attack of phosphite on the carbonyl carbon of the -halo carbonyl compound. Treatment of bis(trimethylsilyl) 1-[ (trimethylsilyl)oxy] -2-halo phosphonates (6) with sodium methoxide in methanol followed by retrimethylsilylation gave bis(trimethylsilyl) 1,2-epoxy phosphonates (17), bis(trimethylsilyl) 2-oxo phosphonates (4), and bis(trimethylsilyl) methyl phosphate (21). On the other hand, diethyl l-hydroxy-2-halo phosphonates (22) were converted by treatment with different bases to 1,2-epoxy phosphonates (23) predominantly in good yields. When some of tri-n-butyltin alkoxides were used as bases, enol phosphates (26) were obtained selectively. Several bis(trimethylsilyl) esters obtained in the above reactions were successfully converted to the corresponding monoanilinium salts in high yields by treatment with aniline-containing alcohols.