548 research outputs found
Transport and Magnetic Properties of R1-xAxCoO3 (R=La, Pr and Nd; A=Ba, Sr and Ca)
Transport and magnetic measurements have been carried out on perovskite
Co-oxides R1-xAxCoO3 (R=La, Pr, and Nd; A=Ba, Sr and Ca; 0<x<0.5: All sets of
the R and A species except Nd1-xBaxCoO3 have been studied.). With increasing
the Sr- or Ba-concentration x, the system becomes metallic ferromagnet with
rather large magnetic moments. For R=Pr and Nd and A=Ca, the system approaches
the metal- insulator phase boundary but does not become metallic. The magnetic
moments of the Ca-doped systems measured with the magnetic field H=0.1 T are
much smaller than those of the Ba- and Sr-doped systems. The thermoelectric
powers of the Ba- and Sr-doped systems decrease from large positive values of
lightly doped samples to negative ones with increasing doping level, while
those of Ca-doped systems remain positive. These results can be understood by
considering the relationship between the average ionic radius of R1-xAx and the
energy difference between the low spin and intermediate spin states. We have
found the resistivity-anomaly in the measurements of Pr1-xCaxCoO3 under
pressure in the wide region of x, which indicates the existence of a phase
transition different from the one reported in the very restricted region of
x~0.5 at ambient pressure [Tsubouchi et al. Phys. Rev. B 66 (2002) 052418.]. No
indication of this kind of transition has been observed in other species of R.Comment: 9 pages, 8 figures. J. Phys. Soc. Jpn. 72 (2003) No.
Evidence that MEK1 positively promotes interhomologue double-strand break repair
During meiosis there is an imperative to create sufficient crossovers for homologue segregation. This can be achieved during repair of programmed DNA double-strand breaks (DSBs), which are biased towards using a homologue rather than sister chromatid as a repair template. Various proteins contribute to this bias, one of which is a meiosis specific kinase Mek1. It has been proposed that Mek1 establishes the bias by creating a barrier to sister chromatid repair, as distinct from enforcing strand invasion with the homologue. We looked for evidence that Mek1 positively stimulates strand invasion of the homologue. This was done by analysing repair of DSBs induced by the VMA1-derived endonuclease (VDE) and flanked by directly repeated sequences that can be used for intrachromatid single-strand annealing (SSA). SSA competes with interhomologue strand invasion significantly more successfully when Mek1 function is lost. We suggest the increase in intrachromosomal SSA reflects an opportunistic default repair pathway due to loss of a MEK1 stimulated bias for strand invasion of the homologous chromosome. Making use of an inhibitor sensitive mek1-as1 allele, we found that Mek1 function influences the repair pathway throughout the first4–5 h of meiosis. Perhaps reflecting a particular need to create bias for successful interhomologue events before chromosome pairing is complete
Transport and Magnetic Studies on the Spin State Transition of Pr1-xCaxCoO3 up to High Pressure
Transport and magnetic measurements and structural and NMR studies have been
carried out on (Pr1-yR'y)1-xAxCoO3 {R'=(rare earth elements and Y); A=(Ca, Ba
and Sr)} at ambient pressure or under high pressure. The system exhibits a
phase transition from a nearly metallic to an insulating state with decreasing
temperature T, where the low spin (LS) state of Co3+ is suddenly stabilized.
For y=0, we have constructed a T-x phase diagram at various values of the
external pressure p. It shows that the (T, x) region of the low temperature
phase, which is confined to a very narrow region around x=0.5 at ambient
pressure, expands as p increases, suggesting that the transition is not due to
an order-disorder type one. For the occurrence of the transition, both the Pr
and Ca atoms seem to be necessary. The intimate relationship between the local
structure around the Co ions and the electronic (or spin) state of Co3+ ions is
discussed: For the smaller unit cell volume or the smaller volume of the CoO6
octahedra and for the larger tilting angle of the octahedra, the temperature of
the transition becomes higher. The role of the carriers introduced by the
doping of the A atoms, is also discussed. By analyzing the data of 59Co-NMR
spectra and magnetic susceptibilities of Pr1-xCaxCoO3 the energy separations
among the different spin states of Co3+ and Co4+ are roughly estimated.Comment: 15 pages, 15 figures, 2 tables, submitted to J. Phys. Soc. Jp
Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety
<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) stimulates hepatocyte proliferation, and also acts as an anti-apoptotic factor. Therefore, HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF (rh-HGF), including a phase I/II study of patients with fulminant hepatitis (FH) or late-onset hepatic failure (LOHF), in order to examine the safety, pharmacokinetics, and clinical efficacy of this molecule.</p> <p>Methods</p> <p>Potential adverse effects identified through preclinical safety tests with rh-HGF include a decrease in blood pressure (BP) and an increase in urinary excretion of albumin. Therefore, we further investigated the effect of rh-HGF on circulatory status and renal toxicity in preclinical animal studies. In a clinical trial, 20 patients with FH or LOHF were evaluated for participation in this clinical trial, and four patients were enrolled. Subjects received rh-HGF (0.6 mg/m<sup>2</sup>/day) intravenously for 12 to 14 days.</p> <p>Results</p> <p>We established an infusion method to avoid rapid BP reduction in miniature swine, and confirmed reversibility of renal toxicity in rats. Although administration of rh-HGF moderately decreased BP in the participating subjects, this BP reduction did not require cessation of rh-HGF or any vasopressor therapy; BP returned to resting levels after the completion of rh-HGF infusion. Repeated doses of rh-HGF did not induce renal toxicity, and severe adverse events were not observed. Two patients survived, however, there was no evidence that rh-HGF was effective for the treatment of FH or LOHF.</p> <p>Conclusions</p> <p>Intravenous rh-HGF at a dose of 0.6 mg/m<sup>2 </sup>was well tolerated in patients with FH or LOHF; therefore, it is desirable to conduct further investigations to determine the efficacy of rh-HGF at an increased dose.</p
Pif1- and Exo1-dependent nucleases coordinate checkpoint activation following telomere uncapping
In the absence of the telomere capping protein Cdc13, budding yeast telomeres erode, resulting in checkpoint arrest. This study shows that the helicase Pif1, known as a telomerase inhibitor, also has a direct role in the resection of uncapped telomeres, acting in parallel to the nuclease Exo1
Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1
A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis
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