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Hydroxyapatite is mineralized along the long axis of collagen fiber during osteogenesis. Mimicking such biomineralization has great potential to control inorganic structures and is fast becoming an important next-generation inorganic synthesis method. Inorganic matter synthesized by biomineralization can have beautiful and functional structures that cannot be created artificially. In this study, we applied biomineralization to the synthesis of the only photocatalyst in practical use today, titanium dioxide (TiO(2)). The photocatalytic activity of TiO(2) mainly relates to three properties: morphology, crystal phase, and light-use efficiency. To optimize TiO(2) morphology, we used a simple sequential peptide as an organic template. TiO(2) mineralized by a β-sheet peptide nanofiber template forms fiber-like shapes that are not observed for mineralization by peptides in the shape of random coils. To optimize TiO(2) crystal phase, we mineralized TiO(2) with the template at 400 °C to transform it into the rutile phase and at 700 °C to transform it into a mixed phase of anatase and rutile. To optimize light-use efficiency, we introduced nitrogen atoms of the peptide into the TiO(2) structure as doped elemental material during sintering. Thus, this biomineralization method enables control of inorganic morphology, crystal phase, and light-use efficiency in a single process.

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X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons.

NY-ESO-1 specific humoral responses are frequently observed in patients with various types of NY-ESO-1 antigen expressing tumors. In a large proportion of NY-ESO-1 antibody-positive patients of NY-ESO-1-specific CD8 T-cells can also be detected suggesting that monitoring of the NY-ESO-1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY-ESO-1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY-ESO-1 protein formulated with cholesterol-bearing hydrophobized pullulan (CHP-NY-ESO-1) and investigated the humoral immune responses against NY-ESO-1. Seven patients were NY-ESO-1 antibody-negative and 2 patients were positive prior to vaccination. Vaccination with CHP-NY-ESO-1 resulted in the induction or increase of NY-ESO-1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY-ESO-1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY-ESO-1 antibody-positive cancer patients. A peptide spanning amino acids 91-108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero-positive patients, being the most dominant antigenic epitope in NY-ESO-1 for antibody recognition in cancer patients. In conclusion, we showed that CHP-NY-ESO-1 protein vaccination had a potent activity for inducing humoral immune responses against NY-ESO-1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY-ESO-1.

Purpose: XAGE-1 was originally identified by the search for PAGE/GAGE-related genes using expressed sequence tag database and was shown to exhibit characteristics of cancer/testis-like antigens. Four transcript variants XAGE-1a, XAGE-1b, XAGE-1c, and XAGE-1d have been identified thus far.We recently identified XAGE-1b as a dominant antigen recognized by sera from lung adenocarcinoma patients.We here investigated the mRNA expression of four XAGE-1variants and XAGE-1protein expression in non^small cell lung cancer (NSCLC). Humoral immune response to XAGE-1b was also evaluated in patients. Experimental Design: Forty-nine NSCLC specimens were analyzed for the expression of four XAGE-1 transcript variants by conventional 30-cycle and real-time reverse transcription-PCR and XAGE-1 protein expression by immunohistochemistry. Sera from 74 patients were analyzed for XAGE-1b antibody production by ELISA and Western blot. Results: XAGE-1b and XAGE-1d mRNA were detected in 15 and 6 of 49 lung cancer specimens, respectively. No XAGE-1a or XAGE-1c mRNA expression was observed. XAGE-1b mRNA expression was observed in 14 of 31 (45%) adenocarcinoma and 1 of 18 (6%) lung cancer with other histologic types. Immunohistochemical analysis using a XAGE-1 monoclonal antibody showed that 14 of 15 XAGE-1b mRNA-positive and 3 of 34 XAGE-1b mRNA-negative specimens expressed XAGE-1protein. Seropositivity was observed in 5 of 56 patients with adenocarcinoma, whereas none of 18 patients with other histologic types produced XAGE-1b antibody. Conclusion: XAGE-1b is highly and strongly expressed in lung adenocarcinoma and immunogenic in patients, suggesting that XAGE-1b is a promising antigen for immunotherapy against lung adenocarcinoma.

Organic monolayer films with the same functional groups as collagen were prepared by a Langmuir-Blodgett (LB) method and the LB monolayers were soaked in a simulated body fluid. Nucleation of hydroxyapatite (HA) took place on the monolayers of the carboxyl group, while no nucleation occurred on the monolayers of amino groups. From IR spectra analyses it was found that an interfacial interaction between carboxyl groups and Ca ions was important for the HA nucleation, causing the formation of HA crystals from the simulated body environment.

Geophysical models of the electrical conductivity of the Earth's mantle based on the observed variations of electric and magnetic fields at the surface of the Earth yield estimates of about 1 S m −1 for the conductivity of the uppermost lower mantle 1,2 . But laboratory conductivity measurements on silicate perovskite (thought to be the dominant constituent of the lower mantle) at high pressures have given conflicting estimates of mantle conductivity, ranging from less than 10 −5 up to 1 S m −1 (refs 3-6). Here we present measurements of the electrical conductivity of perovskite in a multi-anvil press at conditions appropriate for the uppermost lower mantle (pressures up to 23 GPa and temperatures up to 2,000 K). We find that the geophysical estimate of lower-mantle electrical conductivity can be well explained by the conductivity of the perovskite component of a low-oxygen-fugacity mantle composed of pyrolite 7 (the assemblage of mineral phases thought to broadly represent that of the Earth's mantle), assuming a standard geotherm. Our results also indicate that the temperature dependence of perovskite conductivity at lower-mantle temperatures and pressures is significantly larger than shown previously; extrapolations of low-temperature conductivity measurements to the higher temperatures of the lower mantle should therefore be treated with caution.The starting material, Mg 0.93 Fe 0.07 SiO 3 enstatite, was synthesized from Mg and Fe metals and tetraethylorthosilicate at 1,450 K for 3 h at an oxygen partial pressure near the iron-wüstite buffer. The broad X-ray diffraction peaks suggest that this enstatite was poorly crystallized and highly reactive. For a pyrolitic mantle 7 , perovskite of this composition is expected at the top of the lower mantle, on the basis of Fe-Mg partitioning experiments between perovskite and magnesiowüstite 8 .Details of the experimental method have been given elsewhere 9 . The powdered sample was embedded in an Al 2 O 3 ring and sandwiched between Fe disks. The oxidation state of the sample was kept at or below the iron-wüstite buffer. The sample is connected in series with a reference resistance of 101 kQ. A sinusoidal a.c. voltage (0.01 Hz and 1 V peak-to-peak ) was applied to this circuit, and the voltages on the sample and the reference were monitored by two digital voltmeters. The impedance of the sample was obtained from the product of the reference resistance and the ratio of the sample to reference voltage.Only one experiment succeeded at a pressure of 23 GPa. In the first heating cycle of this experiment, the conductivity measure-* Present address: National Institute for Research in Inorganic Materials, Tsukuba, Japan. ments were made in 100 K steps from 300 to 2,000 K. After the measurement at 2,000 K, the sample was quenched, and measurements were repeated from 300 K to higher temperatures. The measurement in the second cycle was stopped at 900 K; we have to avoid back-transformation of perovskite to ilmenite in the second cycle, and confirm formation of perovskite in the f...