Direct evidence of electronic ferroelectricity in YbFe2O4 using neutron diffraction and nonlinear spectroscopy.

We report the first observation of room temperature spontaneous electric polarization in an electronic ferroelectric material, a YbFe2O4 single crystal. The observation was based on second harmonic generation (SHG), a nonlinear optical process. Tensor analysis of the SHG signal revealed that this material has a polar charge superstructure with Cm symmetry. This result settles the long-term discussion on the uncertainty about electronic ferroelectric properties, including the charge order structure. We present a complete picture of the polar charge ordering of this material via consistent results from two different characterization methods. The SHG signal shows the same temperature dependence as the superlattice signal observed in neutron diffraction experiments. These results prove ferroelectric coupling to electron ordering in YbFe2O4, which results in electronic ferroelectricity which is enabled by the real space ordering of iron cations with different valences. The existence of electronic ferroelectricity holds promise for future electronics technologies where devices run a thousand times faster than frequency of the present CPU (a few gigahertz) embedded in smartphones, etc.

Ultrafast electronic state conversion at room temperature utilizing hidden state in cuprate ladder system.

Photo-control of material properties on femto- (10(-15)) and pico- (10(-12)) second timescales at room temperature has been a long-sought goal of materials science. Here we demonstrate a unique ultrafast conversion between the metallic and insulating state and the emergence of a hidden insulating state by tuning the carrier coherence in a wide temperature range in the two-leg ladder superconductor Sr(14-x)Ca(x)Cu24O41 through femtosecond time-resolved reflection spectroscopy. We also propose a theoretical scenario that can explain the experimental results. The calculations indicate that the holes injected by the ultrashort light reduce the coherence among the inherent hole pairs and result in suppression of conductivity, which is opposite to the conventional photocarrier-doping mechanism. By using trains of ultrashort laser pulses, we successively tune the carrier coherence to within 1 picosecond. Control of hole-pair coherence is shown to be a realistic strategy for tuning the electronic state on ultrafast timescales at room temperature.

Probing the metal-insulator phase transition in the (DMEDO-EBDT)2PF6 single crystal by optical measurements.

The temperature and polarization dependence of the optical reflectivity  spectra of a quasi-one-dimensional 1/4-filled band system, (DMEDO-EBDT)(2)PF(6), have been investigated. We observed clear anisotropy in the electronic structures corresponding to the anisotropic transport properties. The appearance of a charge gap (E(g) > 0.1 eV) and transfer of the spectral weight accompanied by the metal-insulator phase transition were clearly observed. In addition, a split of the intramolecular vibrational modes was observed, which strongly suggested the existence of charge disproportionation in the low temperature phase. We also observed a photoinduced reflectivity change, which implied the occurrence of a photoinduced phase transition from the low temperature insulating phase to the high temperature metallic phase.

Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma.

Recent advances in neuroblastoma (NB) research addressed that epigenetic alterations such as hypermethylation of promoter sequences, with consequent silencing of tumor-suppressor genes, can have significant roles in the tumorigenesis of NB. However, the exact role of epigenetic alterations, except for DNA hypermethylation, remains to be elucidated in NB research. In this paper, we clarified the direct binding of MYCN to Bmi1 promoter and upregulation of Bmi1 transcription by MYCN. Mutation introduction into an MYCN binding site in the Bmi1 promoter suggests that MYCN has more important roles in the transcription of Bmi1 than E2F-related Bmi1 regulation. A correlation between MYCN and polycomb protein Bmi1 expression was observed in primary NB tumors. Expression of Bmi1 resulted in the acceleration of proliferation and colony formation in NB cells. Bmi1-related inhibition of NB cell differentiation was confirmed by neurite extension assay and analysis of differentiation marker molecules. Intriguingly, the above-mentioned Bmi1-related regulation of the NB cell phenotype seems not to be mediated only by p14ARF/p16INK4a in NB cells. Expression profiling analysis using a tumor-specific cDNA microarray addressed the Bmi1-dependent repression of KIF1Bbeta and TSLC1, which have important roles in predicting the prognosis of NB. Chromatin immunoprecipitation assay showed that KIF1Bbeta and TSLC1 are direct targets of Bmi1 in NB cells. These findings suggest that MYCN induces Bmi1 expression, resulting in the repression of tumor suppressors through Polycomb group gene-mediated epigenetic chromosome modification. NB cell proliferation and differentiation seem to be partially dependent on the MYCN/Bmi1/tumor-suppressor pathways.

Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999.

We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies.

Ultrasonic propagation of a metallic domain in Pr0.5Ca0.5CoO3 undergoing a photoinduced insulator-metal transition.

Femtosecond optical response was investigated on a perovskite-type cobalt oxide, Pr0.5Ca0.5CoO3 during an insulator-metal (I-M) transition accompanied with the change in spin configuration. After photoirradiation at 30 K, the reflectivity showed a sudden and large increase with subsequent variation depending on the observed photon energy. An exact calculation of Maxwell's equations for the Pr0.5Ca0.5CoO3 after the photoirradiation enabled us to observe the ultrafast dynamics of I-M phase transition and the motion of the photonically created metallic domain at the velocity of ultrasonic wave.

Ultrafast photoinduced insulator-ferromagnet transition in the perovskite manganite Gd0.55Sr0.45MnO3.

We have investigated the ultrafast spin and charge dynamics in the course of a photoinduced phase transition from an insulator with short-range charge order and orbital order (OO) to a ferromagnetic metal in perovskite-type Gd0.55Sr0.45MnO3. Transient reflectivity changes suggest that the metallic state is formed just after the photoirradiation and decays within approximately 1 ps. The magnetization, however, increases with the time constant of 0.5 ps and decays in approximately 10 ps. The relatively slow increase of the magnetization is attributable to the magnetic-field-induced alignment of ferromagnetic domains in the initially produced metallic state and its slow decay to the partial recovery of the OO.

Magnetic field switching between the two orbital-ordered states in DyVO3.

The critical phase competition between different spin-orbital-ordered states has been investigated for the DyVO3 single crystal. As temperature is lowered, the compound exhibits a reentrant spin and orbital ordering (SO and OO) transition: C-->G-->C type for SO and G-->C-->G type for OO. It was found that a magnetic field also drives the phase transition from C to G for OO and concomitantly from G to C for SO, the latter of which is coupled with the metamagnetic transition of the Dy 4f moments. The mechanism of this novel magnetic-field-induced orbital switching is discussed.

Coherent control of charge and lattice dynamics in a photoinduced neutral-to-ionic transition of a charge-transfer compound.

Coherent control of a charge-lattice coupled oscillation associated with the neutral (N)-ionic (I) transition was successfully demonstrated for a charge-transfer (CT) compound, tetrathiafulvalene-p-chloranil, with use of double femtosecond laser pulses. By changing the interval of the two laser pulses, amplitude of the oscillation in the reflectivity for the intramolecular transition band sensitive to the degree of CT was periodically changed. With increase of the pump intensity, the oscillation amplitude was dramatically enhanced. Such an enhancement is discussed in terms of the cooperative nature of the N-I transition.

Variation of the electronic structure in systematically synthesized Sr2MO4 (M = Ti, V, Cr, Mn, and Co).

We have systematically synthesized single-crystalline thin films of layered perovskites Sr2MO4 (M = Ti, V, Cr, Mn, and Co) which cannot be obtained in a form of bulk crystal apart from M = Mn. The two-dimensional electronic structure of these M4+ oxides, ranging from a correlated insulator to a ferromagnetic metal, has been investigated by using their optical conductivity spectra with polarizations E is perpendicular to c and E is parallel to c, which reveal systematic variation of the correlated charge gap, Mott-Hubbard gap, or charge-transfer gap. Temperature dependence of the gap-transition spectra is argued in the light of possible spin and/or orbital ordering.

One-dimensional orbital excitations in vanadium oxides.

The d electron orbital is a hidden but important degree of freedom controlling novel properties of transition-metal oxides. A one-dimensional orbital system is especially intriguing due to its enhanced quantum fluctuation. We present a combined experimental and theoretical study on the Raman scattering spectra in perovskite oxides NdVO(3) and LaVO(3) to prove that the quasi-one-dimensional orbital chain described by fermionic pseudospinons bears orbital excitations exchanging occupied orbital states on the neighboring sites, termed a two-orbiton in analogy with two-magnon.

Optical magnetoelectric effect in a submicron patterned magnet.

The optical magnetoelectric effect, which is a nonreciprocal directional dichroic response, has been demonstrated in a submicron patterned magnet by monitoring the diffracted visible or near-infrared light intensity. An artificial magnetic superstructure is composed of chevron shaped ">" islands made of the ferromagnetic permalloy Ni(80)Fe(20) with a pitch of 1 microm on silicon substrate, in which both space inversion and time reversal symmetry are broken simultaneously. On the basis of the light-polarization angle and magnetic field H dependence, and also comparing the results with the those of the submicron square patterns, we show that the optical magnetoelectric effect emerges as the finite change (approximately 10(-3) at room temperature in H of 500 Oe) of the diffracted intensity.

Metallic ferromagnet with square-lattice CoO2 sheets.

A single-crystalline film of Sr2CoO4 with square-lattice CoO2 sheets (K2NiF4-type structure) was synthesized, and its electronic properties were characterized. The compound exhibited both ferromagnetic and metallic behaviors, with a fairly high Curie temperature T(C) of approximately 250 K, in contrast to the superconductivity recently found in a triangular-lattice CoO2-sheet compound. The film's large magnetoresistance with current perpendicular to the CoO2 plane showed field-hysteretic behavior analogous to tunneling magnetoresistance. The electronic structure of Sr2CoO4 was also investigated to characterize the quasi-two-dimensional ferromagnetic metal state in terms of optical spectroscopy and first-principles calculation.

Change of electronic structure in Ca2RuO4 induced by orbital ordering.

Optical conductivity spectra sigma(omega) were used to investigate the effect of orbital ordering on the electronic structure of Ca2RuO4. Our LDA+U calculation predicts Ru 4d(xy) ferro-orbital ordering at the ground state, and well explains the present sigma(omega) as well as the reported O 1s x-ray absorption spectra. Variation of temperature (T) causes a large change of spectral weight over several eV as well as collapse of a charge gap accompanied by elongation of the c-axis Ru-O bond length. These results clearly indicate that the d(xy) orbital ordering plays a crucial role in the metal-insulator transition and the T-dependent electronic structure on a large energy scale.

Management of haemophilia B inhibitor patients with anaphylactic reactions to FIX concentrates.

Allergic reactions to concentrates containing factor IX (FIX) are serious complications in the treatment of haemophilia B patients with inhibitor. We have established a therapeutic protocol for such cases using an initial skin test followed by step-wise infusions of FIX concentrates under hydrocortisone cover. We have successfully treated three patients whose treatment with FIX had been suspended.

Severe factor VII deficiency with recurrent intracranial haemorrhages owing to double heterozygosity for a splice site mutation of an IVS4 and a novel nonsense mutation in exon 8 (Gln211-->Term).

Genetic analysis of a 10-month-old Japanese baby boy with recurrent intrathoracic bleeding, cerebral haemorrhages and gastrointestinal bleeding secondary to severe factor VII (FVII) deficiency revealed evidence of two distinct mutations of FVII: a splice site mutation of G-->A at nucleotide 6071 in the IVS4 splice site and a novel nonsense mutation (Gln211-->Term) in exon 8. His bleeding was difficult to control without prophylactic infusion of FVII. We detected a heterozygous splice site mutation of the IVS4 in his mother and a heterozygous nonsense mutation in exon 8 (Gln211-->Term) in his father. The parents' FVII levels are both 50% of normal controls. The FVII:C in plasma from the proband was < 1.5% of normal controls. FVII:antigen (Ag) was < 1% of normal controls, using a monoclonal antibody (mAb) hVII-B101/1 that specifically reacts with FVII epidermal growth factor 1 (EGF-1), and 5% of normal controls, using a rabbit polyclonal antibody against human FVII. After immunoadsorption with mAb hVII-B101/B1-Sepharose 4B, FVII levels of both the proband and his mother were 5% of normal controls; after immunoadsorption the FVII levels of normal subjects were < 1%. We hypothesize that secretion of a small amount of dysfunctional FVII lacking EGF-1 into the circulation accounts for this observation.

Ferroelectric valence transition and phase diagram of a series of charge-transfer complexes of 4,4'-dimethyltetrathiafulvalene and tetrahalo-p-benzoquinones.

Variation of the ferroelectric phase transition has been investigated for a series of isomorphous donor (D)-acceptor (A) charge-transfer complexes composed of 4,4'-dimethyltetrathiafulvalene (DMTTF) and tetrahalo-p-benzoquinones by measurements of dielectric susceptibility, X-ray diffraction, and infrared molecular vibrational spectra. The neutral-ionic phase transition of DMTTF-p-chloranil at 65 K accompanies a dielectric peak anomaly associated with the DA stack dimerization. Successive halogen replacement by bromine in the component tetrahalo-p-benzoquinone molecule expands the lattice along the DA stack of the DMTTF complex, and reduces the critical temperature steeply toward zero temperature in an analogous way to the critical behavior of quantum ferroelectrics. The 2,6-dibromo-substituted compound showing the behavior of the quantum paraelectricity is located in the immediate vicinity of the quantum critical point of this phase diagram as signified also by enhancement of the ionicity, the dielectric susceptibility, and the dynamical dimeric distortion at the lowest temperature.

How does heme axial ligand deletion affect the structure and the function of cytochrome b(562)?

We have recently generated a new mutant of cytochrome b(562) (cytb(562)) in which Met7, one of the axial heme ligands, is replaced by Ala (M7A cytb(562)). The M7A cytb(562) can bind heme and the UV-visible absorption spectrum is of a typical high-spin ferric heme. To investigate the effect of the lack of Met7 ligation on the structural integrity of cytb(562), thermal transition analyses of M7A cytb(562) were conducted. From the thermodynamic parameters obtained, it is concluded that the folding of M7A cytb(562) is comparable to the apoprotein despite the presence of heme. On the other hand, exogenous ligands such as cyanide and azide ions are readily bound to the heme iron, indicating that the axial coordination site is available for substrate binding. The peroxidase activity of this mutant is thus examined to evaluate new enzymatic function at this site and M7A cytb(562) was found to catalyze an oxidation reaction of aromatic substrates with hydrogen peroxide. These observations demonstrate that the Met7/His102 bis-ligation to the heme iron is crucial for the stable folding of cytb(562), whereas the functional conversion of cytb(562) is successfully achieved by the loose folding together with the open coordination site.

Delay of the diagnostic lumbar puncture and intrathecal chemotherapy in children with acute lymphoblastic leukemia who undergo routine corticosteroid testing: Tokyo Children's Cancer Study Group study L89-12.

PURPOSE: To determine the effects of eliminating initial lumbar punctures in 418 consecutively treated children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Patients were enrolled onto a trial conducted in central Japan between 1989 and 1992. Treatment consisted of standard four-drug induction therapy followed by a risk-based intensification phase, reinduction therapy, late intensification, and remission maintenance therapy (total of 104 weeks). The initial lumbar puncture, with an intrathecal injection of chemotherapy, was performed after 1 week of prednisolone sensitivity testing (day 8). End points included response to prednisolone, CNS status at the time of the day 8 lumbar puncture, subsequent adverse events in CNS and bone marrow, and event-free survival (EFS). RESULTS: The remission induction rate was 93.1% with a 6-year EFS rate (+/- SE) of 68.7% +/- 2.4%, which is similar to historical results for patients who received their diagnostic lumbar puncture and first instillation of intrathecal chemotherapy on day 0. Overall, 84.5% of the patients had good responses to prednisolone, whereas 15.5% had poor responses. Clinical outcome was strikingly better for the good responders (6-year EFS, 74.1% +/- 2.5% compared with 40.1% +/- 6.4% for patients with poor responses), suggesting that omission of intrathecal chemotherapy did not alter the predictive value of drug sensitivity testing. Eighteen patients experienced CNS relapse as their first adverse event (cumulative risk, 5.1%; 95% confidence interval, 2.7% to 7.4%), coincident with reports from groups using conventional strategies of CNS clinical management. Bleeding into the CSF at the time of the day 8 lumbar puncture was apparent in 29 cases (8.1%), but leukemic blasts were identified in only two. CONCLUSION: Delay of the initial lumbar puncture and intrathecal injection of chemotherapy seems to be feasible in children with ALL. Further controlled evaluations are needed to establish the validity of this conclusion.