First-principles accurate total-energy surfaces for polar structural distortions of BaTiO3, PbTiO3, and SrTiO3: consequences to structural transition temperatures

Specific forms of the exchange correlation energy functionals in first-principles density functional theory-based calculations, such as the local density approximation (LDA) and generalized-gradient approximations (GGA), give rise to structural lattice parameters with typical errors of -2% and 2%. Due to a strong coupling between structure and polarization, the order parameter of ferroelectric transitions, they result in large errors in estimation of temperature dependent ferroelectric structural transition properties. Here, we employ a recently developed GGA functional of Wu and Cohen [Phys. Rev. B 73, 235116 (2006)] and determine total-energy surfaces for zone-center distortions of BaTiO3, PbTiO3, and SrTiO3, and compare them with the ones obtained with calculations based on standard LDA and GGA. Confirming that the Wu and Cohen functional allows better estimation of structural properties at 0 K, we determine a new set of parameters defining the effective Hamiltonian for ferroelectric transition in BaTiO3. Using the new set of parameters, we perform molecular-dynamics (MD) simulations under effective pressures p=0.0 GPa, p=-2.0 GPa, and p=-0.005T GPa. The simulations under p=-0.005T GPa, which is for simulating thermal expansion, show a clear improvement in the cubic to tetragonal transition temperature and c/a parameter of its ferroelectric tetragonal phase, while the description of transitions at lower temperatures to orthorhombic and rhombohedral phases is marginally improved. Our findings augur well for use of Wu-Cohen functional in studies of ferroelectrics at nano-scale, particularly in the form of epitaxial films where the properties depend crucially on the lattice mismatch.Comment: 10 pages, 7 figures, 3 tables, resubmitted to PR

A Novel Therapeutic and Prophylactic Vaccine (HVJ-Envelope / Hsp65 DNA + IL-12 DNA) against Tuberculosis Using the Cynomolgus Monkey Model

AbstractWe have developed a novel tuberculosis (TB) vaccine; a combination of the DNA vaccines expressing mycobacterial heat shock protein 65 (HSP65) and interleukin 12 (IL-12) delivered by the hemagglutinating virus of Japan (HVJ)-envelope and –liposome (HSP65 + IL-12/HVJ). An IL-12 expression vector (IL-12DNA) encoding single-chain IL-12 proteins comprised of p40 and p35 subunits were constructed. This vaccine provided remarkable protective efficacy in mouse and guinea pig models compared to the BCG vaccine on the basis of C.F.U of number of TB, survival, an induction of the CD8 positive CTL activity and improvement of the histopathological tuberculosis lesions. This vaccine also provided therapeutic efficacy against multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB) (prolongation of survival time and the decrease in the number of TB in the lung) in murine models. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This novel vaccine provided a higher level of the protective efficacy than BCG based upon the assessment of mortality, the ESR, body weight, chest X-ray findings and immune responses. All monkeys in the control group (saline) died within 8 months, while 50% of monkeys in the HSP65+hIL-12/HVJ group survived more than 14 months post-infection (the termination period of the experiment). Furthermore, the BCG priming and HSP65 + IL-12/HVJ vaccine (booster) by the priming-booster method showed a synergistic effect in the TB-infected cynomolgus monkey (100% survival). In contrast, 33% of monkeys from BCG Tokyo alone group were alive (33% survival). Furthermore, this vaccine exerted therapeutic efficacy (100% survival) and augmentation of immune responses in the TB-infected monkeys. These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical trials

BMP-2/6 Heterodimer Is More Effective than BMP-2 or BMP-6 Homodimers as Inductor of Differentiation of Human Embryonic Stem Cells

Bone Morphogenetic Protein (BMP) signaling pathways are involved in differentiation of stem cells into diverse cell types, and thus BMPs can be used as main guidance molecules for in vitro differentiation of human stem cells.We have analyzed the ability for inducing differentiation of the heterodimer BMP-2/BMP-6 (BMP-2/6) compared to the homodimers BMP-2 or BMP-6, using human embryonic stem (hES) cells H9 as model system. When incubated in a medium with high concentration of basic fibroblastic growth factor (FGF2), 100 ng/ml of human recombinant BMPs induced morphological changes and differentiation of hES cells in 24 to 48 hours. After 5 days, expression of differentiation markers was induced and quantified by quantitative PCR (qPCR) and flow cytometry. BMP-2/6 exhibited stronger activity for the induction of the expression of trophectodermal (CDX2) and endodermal (SOX17, GATA4, AFP) markers than BMP-2 or BMP-6 homodimers. BMP-2/6 also induced the expression of BMPR2 gene more effectively than BMP-2 or BMP-6 when used at the same concentration and time. Moreover, the percentage of cells expressing the surface endodermal marker CXCR4 was also increased for the heterodimer when compared to both homodimers. BMP-2/6 was a more potent activator of Smad-dependent (SMAD1/5) and Smad-independent signaling (mitogen-activated protein kinases ERK and p38) than BMP-2 and BMP-6, and the activation of these pathways might play a role in its increased potency for inducing hES cell differentiation.Therefore, we conclude that BMP-2/6 is more potent than BMP-2 or BMP-6 for inducing differentiation of hES cells, and it can be used as a more powerful substitute of these BMPs in in vitro differentiation guidance

Adrenomedullin and tumour microenvironment

Adrenomedullin (AM) is a regulatory peptide whose involvement in tumour progression is becoming more relevant with recent studies. AM is produced and secreted by the tumour cells but also by numerous stromal cells including macrophages, mast cells, endothelial cells, and vascular smooth muscle cells. Most cancer patients present high levels of circulating AM and in some cases these higher levels correlate with a worst prognosis. In some cases it has been shown that the high AM levels return to normal following surgical removal of the tumour, thus indicating the tumour as the source of this excessive production of AM. Expression of this peptide is a good investment for the tumour cell since AM acts as an autocrine/paracrine growth factor, prevents apoptosis-mediated cell death, increases tumour cell motility and metastasis, induces angiogenesis, and blocks immunosurveillance by inhibiting the immune system. In addition, AM expression gets rapidly activated by hypoxia through a HIF-1α mediated mechanism, thus characterizing AM as a major survival factor for tumour cells. Accordingly, a number of studies have shown that inhibition of this peptide or its receptors results in a significant reduction in tumour progression. In conclusion, AM is a great target for drug development and new drugs interfering with this system are being developed

Evaluation of kinetic performance for men's suit jacket in exercise of shoulder joint

This paper describes the kinetic performance evaluation of suit jacket by measurement of clothing pressure. Subjects wearing three suit jacket of different size performed three different exercises involving the rotation of the upper limbs. The clothing pressure was measured by the air-pack sensor and the partial compression feeling and the constrained feeling were evaluated by subjects. From the result, it was found that (1) the values of clothing pressure at the arm, the front of armhole and the scapula were correlated with the scores of compression feeling at same points, (2) the Weber-Fechner's law was applicable to the relation between the clothing pressure and the compressive feeling, and the clothing pressure values which gave subjects the low and the moderate compression feelings were 1.2kpa and 3.6 kPa, (3) the values of clothing pressure at the arm, the front and back of armhole and the scapula were correlated with the constrained feeling, and the clothing pressure measurement at these points was available to evaluate the kinetic performance of suit jacket.ArticleSen'i Gakakishi. 63(6): 159-164 (2007)journal articl