Mapping of a New Deformation Region around

We performed the first direct mass measurements of neutron-rich scandium, titanium, and vanadium isotopes around the neutron number 40 at the RIKEN RI Beam Factory using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{58-60}Sc, ^{60-62}Ti, and ^{62-64}V were measured for the first time. The experimental results show that the two-neutron separation energies in the vicinity of ^{62}Ti increase compared to neighboring nuclei. This shows that the masses of Ti isotopes near N=40 are affected by the Jahn-Teller effect. Therefore, a development of Jahn-Teller stabilization appears below the Cr isotopes, and the systematics in Sc, Ti, and V isotopes suggest that ^{62}Ti is located close to the peak of the Jahn-Teller effect.

How Different is the Core of

The structure of a neutron-rich ^{25}F nucleus is investigated by a quasifree (p,2p) knockout reaction at 270A MeV in inverse kinematics. The sum of spectroscopic factors of π0d_{5/2} orbital is found to be 1.0±0.3. However, the spectroscopic factor with residual ^{24}O nucleus being in the ground state is found to be only 0.36±0.13, while those in the excited state is 0.65±0.25. The result shows that the ^{24}O core of ^{25}F nucleus significantly differs from a free ^{24}O nucleus, and the core consists of ∼35% ^{24}O_{g.s.}. and ∼65% excited ^{24}O. The result may infer that the addition of the 0d_{5/2} proton considerably changes neutron structure in ^{25}F from that in ^{24}O, which could be a possible mechanism responsible for the oxygen dripline anomaly.

Excitation of the Isovector Spin Monopole Resonance via the Exothermic

The (^{12}N, ^{12}C) charge-exchange reaction at 175 MeV/u was developed as a novel probe for studying the isovector spin giant monopole resonance (IVSMR), whose properties are important for better understanding the bulk properties of nuclei and asymmetric nuclear matter. This probe, now available through the production of ^{12}N as a secondary rare-isotope beam, is exothermic, is strongly absorbed at the surface of the target nucleus, and provides selectivity for spin-transfer excitations. All three properties enhance the excitation of the IVSMR compared to other, primarily light-ion, probes, which have been used to study the IVSMR thus far. The ^{90}Zr(^{12}N,^{12}C) reaction was measured and the excitation energy spectra up to about 70 MeV for both the spin-transfer and non-spin-transfer channels were deduced separately by tagging the decay by γ emission from the ^{12}C ejectile. Besides the well-known Gamow-Teller and isobaric analog transitions, a clear signature of the IVSMR was identified. By comparing with the results from light-ion reactions on the same target nucleus and theoretical predictions, the suitability of this new probe for studying the IVSMR was confirmed.

Magic Nature of Neutrons in

We perform the first direct mass measurements of neutron-rich calcium isotopes beyond neutron number 34 at the RIKEN Radioactive Isotope Beam Factory by using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{55-57}Ca are determined for the first time to be -18650(160), -13510(250), and -7370(990) keV, respectively. We examine the emergence of neutron magicity at N=34 based on the new atomic masses. The new masses provide experimental evidence for the appearance of a sizable energy gap between the neutron 2p_{1/2} and 1f_{5/2} orbitals in ^{54}Ca, comparable to the gap between the neutron 2p_{3/2} and 2p_{1/2} orbitals in ^{52}Ca. For the ^{56}Ca nucleus, an open-shell property in neutrons is suggested.

Spectroscopy of Pionic Atoms in

We observed the atomic 1s and 2p states of π^{-} bound to ^{121}Sn nuclei as distinct peak structures in the missing mass spectra of the ^{122}Sn(d,^{3}He) nuclear reaction. A very intense deuteron beam and a spectrometer with a large angular acceptance let us achieve a potential of discovery, which includes the capability of determining the angle-dependent cross sections with high statistics. The 2p state in a Sn nucleus was observed for the first time. The binding energies and widths of the pionic states are determined and found to be consistent with previous experimental results of other Sn isotopes. The spectrum is measured at finite reaction angles for the first time. The formation cross sections at the reaction angles between 0° and 2° are determined. The observed reaction-angle dependence of each state is reproduced by theoretical calculations. However, the quantitative comparison with our high-precision data reveals a significant discrepancy between the measured and calculated formation cross sections of the pionic 1s state.

Candidate Resonant Tetraneutron State Populated by the

A candidate resonant tetraneutron state is found in the missing-mass spectrum obtained in the double-charge-exchange reaction ^{4}He(^{8}He,^{8}Be) at 186 MeV/u. The energy of the state is 0.83±0.65(stat)±1.25(syst) MeV above the threshold of four-neutron decay with a significance level of 4.9σ. Utilizing the large positive Q value of the (^{8}He,^{8}Be) reaction, an almost recoilless condition of the four-neutron system was achieved so as to obtain a weakly interacting four-neutron system efficiently.

Identification of the ß+ isovector spin monopole resonance via the 208Pb and 90Zr(t,3He) reactions at 300 MeV/u.

The double-differential cross sections for the (208)Pb and (90)Zr(t,(3)He) reactions at 300 MeV/u have been measured at the RI Beam Factory at RIKEN. This was the first physics experiment with the SHARAQ magnetic spectrometer. The combined analysis of the present (t,(3)He) data and previous (n,p) data provides the clearest identification for the ß(+) isovector spin monopole resonance both in the (208)Tl and (90)Y nuclei, and puts the observations of this giant resonance on a firm foundation. The measured distributions of the (t,(3)He) monopole cross sections were well reproduced by the distorted-wave Born approximation calculation, where the target transition density was calculated with the self-consistent Hartree-Fock plus random-phase approximation using the T43 Skyrme interaction. A major part of the expected ß(+) isovector spin monopole strength was found in the measured cross section spectra.

[Hepatic metabolism and transport of bilirubin and other organic anions].

Most of bilirubin, bile acids and other organic anions are preferentially taken up by the liver and excreted into bile. Recently many transporters on the sinusoidal and canalicular membranes of the hepatocytes have been reported for each ligand. complementary DNA was cloned for human Na+/taurocholate cotransporting polypeptide (NTCP) which mediates sodium dependent secondary active hepatic uptake of bile acids. For the hepatic uptake of non-bile acid-organic anions such as bilirubin, at least 4 transporters are postulated, i.e., bilirubin/BSP binding protein (BBBP), organic anion binding protein (OABP), bilitranslocase, and organic anion transporting polypeptide (OATP). In the hepatocytes, bilirubin is glucuronidated in the endoplasmic reticulum. The gene for UDP-glucuronosyltransferase (UGT) 1 family has been elucidated and differential splicing from several exons 1 (A to J) results in forming isozymes of UGT 1 including bilirubin UGT. At the canalicular membranes, two main ATP-dependent organic anion transporters have been reported, i.e., canalicular bile salt transporter (cBST) for bile acids and canalicular multispecific organic anion transporter (cMOAT) for non-bile acid organic anions. Recently multidrug resistance protein (MRP) is reported closely related to or identical to cMOAT. These canalicular ATP-dependent transporters are called ABC (ATP-binding cassette) transporters.

Congenital pseudarthrosis of the clavicle. Histologic examination for the etiology of the disease.

The etiology of congenital pseudarthrosis of the clavicle remains obscure. The authors treated a 5-year-old boy with this rare disease. Clinical history and radiographs confirmed the diagnosis. Surgical treatment of resection of the pseudarthrosis, autologous bone graft, and internal fixation with a small AO plate led to successful bone union. Histologic analysis of the pseudarthrosis showed that there were cartilaginous caps on the proximal and distal bony ends. The appearance of the cartilaginous caps were equivalent to that of developing physes. They were adding new bone to the bony ends, which also was confirmed by preoperative tetracycline labeling. These observations support the hypothesis that the pseudarthrosis is caused by failure of 2 ossification centers to fuse, as was previously proposed by others.

Purification and Characterization of Ethyl 2-Methyl-3-oxobutanoate Reductase from Klebsiella pneumoniae IF03319.

An enzyme that catalyzes a reduction of ethyl 2-methyl-3-oxobutanoate (1) to ethyl (2R,3S) 3-hydroxy- 2-methylbutanoate was found in Klebsiella pneumoniae IFO 3319 cells. The enzyme was isolated from the cells and purified 250-fold by ammonium sulfate fractionation, ion exchange chromatography, affinity chromatography, and gel filtration. The purified enzyme was found to be a monomer protein with a molecular weight of approximately 31,000 and an isoelectric point of 6.2. It was NADPH-dependent and had maximum activity at pH 7.0 and 45°C for the reduction and at pH 10.0 and 45°C for oxidation. The Km's at pH 7.0 were 5.6 mM for 1 and 12.5 mM for benzyl 2-methyl-3-oxobutanoate, respectively. Esters of 2-oxocycloalkane carboxylic acids as well as esters of 2-methyl-3-oxobutanoic acid served as substrates, and the corresponding reduced products were obtained with high stereoselectivity.

Activation of plasma kinin system correlates with severe coagulation disorders in patients with ovarian hyperstimulation syndrome.

The aim of this study was to evaluate status of plasma kinin system in patients with ovarian hyperstimulation syndrome (OHSS), in order to investigate whether activation of the plasma kinin system correlates with increased blood coagulability. In the first part of the study, concentrations of plasma prekallikrein (PK) in OHSS cycles (n = 13) were monitored from the day of human chorionic gonadotrophin (HCG) administration to the mid-luteal phase, and were compared with those of control cycles (n = 17). The average value of PK in OHSS cycles began to decrease on day 8, and by day 10 was significantly lower than that of control cycles (86 +/- 6 versus 106 +/- 4%, P <0.01). The time course of changes in PK concentration correlated well with the clinical condition of OHSS patients. In the second part of the study, we obtained data from 26 patients who were hospitalized because of severe OHSS, to investigate the correlation between PK and other haemostatic markers. OHSS patients with severe PK reduction (<80% normal, n = 9) demonstrated significantly higher values of plasma thrombin-antithrombin III and plasmin-alpha2 antiplasmin, and more severe haemoconcentration, compared to those OHSS patients who had no reduction in PK (n = 17). In conclusion, our data suggest that activation of the plasma kinin system occurs specifically and occasionally in OHSS patients, and is associated with increased blood coagulability. Thus, when an OHSS patient demonstrates a low value of plasma PK, more careful management is required to prevent thromboembolic complications.

Pravastatin transport across the hepatocyte canalicular membrane requires both ATP and a transmembrane pH gradient.

Hepatic excretion of non-bile acid organic anions is reported to be ATP-dependent and a defect of this transport has been reported in congenitally jaundiced rats, animal models of human Dubin-Johnson syndrome. To investigate the effect of the transmembrane pH gradient on hepatocyte canalicular membrane transport of ATP-dependent organic anions, uptake of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase-inhibiting organic anion, by hepatocyte canalicular membrane vesicles was observed in the presence or absence of transmembrane pH gradients. Uptake was assessed by a rapid filtration technique. ATP-dependent pravastatin uptake was stimulated in the presence of a transmembrane pH gradient (in > out) in Sprague-Dawley (SD) rats. Uptake was dependent on both pravastatin and ATP concentrations and showed saturation kinetics. After intravenous injection of [14C]-pravastatin (0.3 mumol), 81% of the dose was excreted in the bile within 35 min in SD rats, whereas only 20% was excreted in the bile in Eisai hyperbilirubinuria rats. ATP and the pH gradient also co-stimulated the uptake of pravastatin in Eisai hyperbilirubinuria rats, although the K(m) was much higher and Vmax was much lower than corresponding values in SD rats. This coincided well with the marked reduction in vivo biliary excretion of pravastatin in jaundiced rats.

Interference with transforming growth factor-beta/ Smad3 signaling results in accelerated healing of wounds in previously irradiated skin.

Transforming growth factor (TGF)-beta regulates many aspects of wound repair including inflammation, chemotaxis, and deposition of extracellular matrix. We previously showed that epithelialization of incisional wounds is accelerated in mice null for Smad3, a key cytoplasmic mediator of TGF-beta signaling. Here, we investigated the effects of loss of Smad3 on healing of wounds in skin previously exposed to ionizing radiation, in which scarring fibrosis complicates healing. Cutaneous wounds made in Smad3-null mice 6 weeks after irradiation showed decreased wound widths, enhanced epithelialization, and reduced numbers of neutrophils and myofibroblasts compared to wounds in irradiated wild-type littermates. Differences in breaking strength of wild-type and Smad3-null wounds were not significant. As shown previously for neutrophils, chemotaxis of primary dermal fibroblasts to TGF-beta required Smad3, but differentiation of fibroblasts to myofibroblasts by TGF-beta was independent of Smad3. Previous irradiation-enhanced induction of connective tissue growth factor mRNA in wild-type, but not Smad3-null fibroblasts, suggested that this may contribute to the heightened scarring in irradiated wild-type skin as demonstrated by Picrosirius red staining. Overall, the data suggest that attenuation of Smad3 signaling might improve the healing of wounds in previously irradiated skin commensurate with an inhibition of fibrosis.