Design and synthesis of amidine-type peptide bond isosteres: application of nitrile oxide derivatives as active ester equivalents in peptide and peptidomimetics synthesis.

Amidine-type peptide bond isosteres were designed based on the substitution of the peptide bond carbonyl (C=O) group with an imino (C=NH) group. The positively-charged property of the isosteric part resembles a reduced amide-type peptidomimetic. The peptidyl amidine units were synthesized by the reduction of a key amidoxime (N-hydroxyamidine) precursor, which was prepared from nitrile oxide components as an aminoacyl or peptidyl equivalent. This nitrile oxide-mediated C-N bond formation was also used for peptide macrocyclization, in which the amidoxime group was converted to peptide bonds under mild acidic conditions. Syntheses of the cyclic RGD peptide and a peptidomimetic using both approaches, and their inhibitory activity against integrin-mediated cell attachment, are presented

Phase Diagram of Pressure-Induced Superconductivity in EuFe2As2 Probed by High-Pressure Resistivity up to 3.2 GPa

We have constructed a pressure$-$temperature ($P-T$) phase diagram of $P$-induced superconductivity in EuFe$_2$As$_2$ single crystals, via resistivity ($\rho$) measurements up to 3.2 GPa. As hydrostatic pressure is applied, an antiferromagnetic (AF) transition attributed to the FeAs layers at $T_\mathrm{0}$ shifts to lower temperatures, and the corresponding resistive anomaly becomes undetectable for $P$ $\ge$ 2.5 GPa. This suggests that the critical pressure $P_\mathrm{c}$ where $T_\mathrm{0}$ becomes zero is about 2.5 GPa. We have found that the AF order of the Eu$^{2+}$ moments survives up to 3.2 GPa without significant changes in the AF ordering temperature $T_\mathrm{N}$. The superconducting (SC) ground state with a sharp transition to zero resistivity at $T_\mathrm{c}$ $\sim$ 30 K, indicative of bulk superconductivity, emerges in a pressure range from $P_\mathrm{c}$ $\sim$ 2.5 GPa to $\sim$ 3.0 GPa. At pressures close to but outside the SC phase, the $\rho(T)$ curve shows a partial SC transition (i.e., zero resistivity is not attained) followed by a reentrant-like hump at approximately $T_\mathrm{N}$ with decreasing temperature. When nonhydrostatic pressure with a uniaxial-like strain component is applied using a solid pressure medium, the partial superconductivity is continuously observed in a wide pressure range from 1.1 GPa to 3.2 GPa.Comment: 7 pages, 6 figures, accepted for publication in Physical Review B, selected as "Editors' Suggestion

Bioinertization of NanoLC/MS/MS Systems by Depleting Metal Ions From the Mobile Phases for Phosphoproteomics

We have successfully developed a bioinertized nanoflow liquid chromatography/tandem mass spectrometry (nanoLC/MS/MS) system for the highly sensitive analysis of phosphopeptides by depleting metal ions from the mobile phase. We found that not only direct contact of phosphopeptides with metal components, but also indirect contact with nanoLC pumps through the mobile phase causes significant losses during the recovery of phosphopeptides. Moreover, electrospray ionization was adversely affected by the mobile phase containing multiple metal ions as well as by the sample solvents contaminated with metal ions used in immobilized metal ion affinity chromatography for phosphopeptide enrichment. To solve these problems, metal ions were depleted by inserting an on-line metal ion removal device containing metal-chelating membranes between the gradient mixer and the autosampler. As a result, the peak areas of the identified phosphopeptides increased an average of 9.9-fold overall and 77-fold for multiply phosphorylated peptides with the insertion of the on-line metal ion removal system. This strategy would be applicable to highly sensitive analysis of other phosphorylated biomolecules by microscale-LC/MS/MS

Pressure-Induced Antiferromagnetic Bulk Superconductor EuFe2_2As2_2

We present the magnetic and superconducting phase diagram of EuFe$_2$As$_2$ for $B \parallel c$ and $B \parallel ab$. The antiferromagnetic phase of the Eu$^{2+}$ moments is completely enclosed in the superconducting phase. The upper critical field vs. temperature curves exhibit strong concave curvatures, which can be explained by the Jaccarino-Peter compensation effect due to the antiferromagnetic exchange interaction between the Eu$^{2+}$ moments and conduction electrons.Comment: submitted to the proceedings of the M2S-IX Toky

Contributions of phase resetting and interlimb coordination to the adaptive control of hindlimb obstacle avoidance during locomotion in rats: a simulation study.

Obstacle avoidance during locomotion is essential for safe, smooth locomotion. Physiological studies regarding muscle synergy have shown that the combination of a small number of basic patterns produces the large part of muscle activities during locomotion and the addition of another pattern explains muscle activities for obstacle avoidance. Furthermore, central pattern generators in the spinal cord are thought to manage the timing to produce such basic patterns. In the present study, we investigated sensory-motor coordination for obstacle avoidance by the hindlimbs of the rat using a neuromusculoskeletal model. We constructed the musculoskeletal part of the model based on empirical anatomical data of the rat and the nervous system model based on the aforementioned physiological findings of central pattern generators and muscle synergy. To verify the dynamic simulation by the constructed model, we compared the simulation results with kinematic and electromyographic data measured during actual locomotion in rats. In addition, we incorporated sensory regulation models based on physiological evidence of phase resetting and interlimb coordination and examined their functional roles in stepping over an obstacle during locomotion. Our results show that the phase regulation based on interlimb coordination contributes to stepping over a higher obstacle and that based on phase resetting contributes to quick recovery after stepping over the obstacle. These results suggest the importance of sensory regulation in generating successful obstacle avoidance during locomotion

冠動脈バイパス術患者における術前アスピリン投与中止時期の検討

研究科: 千葉大学大学院医学薬学府学位:千大院医薬博甲第医1081号博士(医学)千葉大