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Estimating the temperature and mass of dust in high-$z$ galaxies is essential for discussions of the origin of dust in the early Universe. However, this suffers from limited sampling of the infrared spectral-energy distribution. Here we present an algorithm for deriving the temperature and mass of dust in a galaxy, assuming dust to be in radiative equilibrium. We formulate the algorithm for three geometries: a thin spherical shell, a homogeneous sphere, and a clumpy sphere. We also discuss effects of the mass absorption coefficients of dust at ultraviolet and infrared wavelengths, $\kappa_{\rm UV}$ and $\kappa_{\rm IR}$, respectively. As an example, we apply the algorithm to a normal, dusty star-forming galaxy at $z=7.5$, A1689zD1, for which three data points in the dust continuum are available. Using $\kappa_{\rm UV}=5.0\times10^4$ cm$^2$ g$^{-1}$ and $\kappa_{\rm IR}=30(\lambda/100\mu m)^{-\beta}$ cm$^2$ g$^{-1}$ with $\beta=2.0$, we obtain dust temperatures of 38--70~K and masses of $10^{6.5-7.3}$ M$_\odot$ for the three geometries considered. We obtain similar temperatures and masses from just a single data point in the dust continuum, suggesting the usefulness of the algorithm for high-$z$ galaxies with limited infrared observations. In the clumpy-sphere case, the temperature becomes equal to that of the usual modified black-body fit, because an additional parameter describing the clumpiness works as an adjuster. The best-fit clumpiness parameter is $\xi_{\rm cl}=0.1$, corresponding to $\sim10$\% of the volume filling factor of the clumps in this high-$z$ galaxy if the clump size is $\sim10$ pc, similar to that of giant molecular clouds in the local Universe., Comment: MNRAS accepted

We investigated the absorption spectra of crystalline plagioclase feldspar, using natural and synthetic samples with a wide compositional range, in the infrared region. And we also carried out cryogenic measurements for synthetic anorthite. In the absorption spectra, systematic spectroscopic variations that depend on the chemical composition were observed, in terms of characteristic features such as the number of absorption peaks, shift of peak location and variety of peak width and intensity. Since, plagioclase feldspar is considered as a reasonable mineral species formed in oxygen rich circumstellar environments from the viewpoint of the equilibrium condensation sequence, our spectral data obtained in this work is expected to be used widely in the field of astronomical mineralogy.

Interplanetary dust particles contain grains of glass with embedded metals and sulfides (GEMS; i.e., amorphous silicate grains with diameters of a few hundred nanometers containing Fe nanoinclusions and Fe sulfide particles), which are considered to be among the building blocks of the solar system. To explore that GEMS grains formed during the condensation process, condensation experiments were carried out in Si–Mg–Fe–Al–Ca–Ni–O and Mg–Si–Fe–Ca–Al–Na–O systems using an induction thermal plasma furnace. In all experimental runs, spherical grains (mostly composed of amorphous silicate) with diameter

Mid-infrared spectroscopic observations of oxygen-rich asymptotic giant branch (AGB) stars show the common presence of dust species that have a broad feature at ∼11–12 μm. Chemically synthesized amorphous alumina (Al2O3) is widely accepted as the source of this emission, although it is not obvious that amorphous alumina can condense in circumstellar conditions. We performed condensation experiments of Al–Si–Mg–O and Mg–Al–O gases using induction thermal plasma systems, in which small particles condense from vapors with a steep temperature gradient. The condensates were analyzed using X-ray diffraction and Fourier transform infrared spectroscopy, and observed with a transmission electron microscope. The condensed nanoparticles from the Al and O gases were transition aluminas based on face-centered cubic (fcc) packed oxygen (δ- and λ-alumina, and an unknown phase). The fcc oxygen frameworks were maintained in the condensed alumina containing small amounts of Mg and Si. Condensates from the gases of Al:Mg = 99:1 and 95:5 had δ- and γ-alumina structures. Particles with λ- and γ-alumina structures formed from starting materials of Al:Si = 9:1 and Al:Si:Mg = 8:1:1, respectively. Amorphous silica-rich particles condensed from gases of Al/(Si+Al) μm broad emission of alumina-rich stars is not amorphous alumina, but is transition alumina containing ∼10% Si.

The chronic donor organ shortage has led to the production of transgenic animals. We assume that cells or organs derived from possible animal donors carrying a large amount of α-galactosyl epitopes should not be transplanted into humans, because a corresponding amount of immunosuppressants would be needed to prolong the survival of such xenografts in the recipients. This may not only make the recipients compromised hosts but also introduce some unknown or uncontrollable pathogens into society at large. We also assume that gene manipulation itself should not be a detriment to possible transgenic animals. To explore possibilities that not only can minimize the possible detrimental factors to humans, such as α-galactosyl epitopes, but also can minimize the possible detriment to transgenic animals, such as random integration of the extraneous genes with or without uncontrollable regulatory sequences, we have produced a DNA construct that replaces the mouse oc(1,3)-galactosyltransferase gene (GT) with the human a(1,2)-fucosyltransferase (FT) minigene (promoterless for the expression of FT) at the GT locus. The mouse fibrosarcoma cell line, L929, was transfected with the construct. Colonies were obtained after incubation with non-heat-inactivated human serum. Southern blot analysis demonstrated that one allele of the mouse GT gene was replaced with the FT minigene at the GT locus without integration of any selectable marker genes. The immunostaining analysis with lectins showed that the transfectants expressed H antigens, which suggested that H antigens were expressed by the intrinsic GT promoter. Thus gene replacement, knock-in, of the mouse GT with the human FT without integration of any selectable marker genes in the GT locus was shown to be possible. This is especially important in producing transgenic animals for the clinical application of xenografts into humans.

Hyperacute rejection (from pig to human) is thought to result from activation of complement initiated by the binding of host natural antibodies to α-galactosyl (α-Gal) epitopes of donor endothelial cells. However, α-Gal epitope shares a common precursor with H antigen in humans. This means that H antigens as well as α-Gal epitopes are synthesized in a competitive manner by different enzymes. We thought that it would be possible to convert α-Gal epitopes into H antigens by introducing cDNA of α(1,2)-fucosyltransferase (α1–2FT) into porcine cells, and so, pig embryos were microinjected with αl-2FT cDNA. Transgenic pigs that carried α1–2FT were thus established. Cytotoxicity of fibrocytes derived from skin of transgenic pig was measured by 51Cr release assay, which showed that H antigen-expressing cells were significantly resistant to a challenge with human sera. These experiments indicate that our method provides a new strategy which contributes to a successful discordant xenotransplantation.

異種臓器移植は脳死ドナー不足を解決する有力な手段であるが, 移植後早期に生ずる超急性拒絶反応が最大の問題である.我々は, in vitroで補体制御因子遺伝子導入の効果を検討するとともに, アデノウイルス法を用いてin vivoでの遺伝子導入の可能性を検討した.その結果, 補体制御因子遺伝子導入により異種免疫反応は効果的に抑制されること, アデノウイルス法での遺伝子導入は特に異種移植ドナーとして最適と考えられているブタ肝臓で有効であることが明らかとなった.以上より, 遺伝子治療の技術のひとつであるアデノウイルス法は遺伝子制御による異種移植に有効であることが示唆された.

Although tumors can activate vascular endothelial growth factor (VEGF) promoter in host stromal cells, the relative contribution to VEGF production of host versus tumor cells and the resulting vascular response have not been quantitated to date. To this end, we implanted VEGF-/- and wild-type (WT) embryonic stem (ES) cells in transparent dorsal skin windows in severe combined immunodeficient mice. VEGF-/- ES cell-derived tumors produced approximately 50% of VEGF compared with the WT tumors, suggesting significant contribution of host stromal cells. To discern the hypoxia-induced hypoxia inducible factor (HIF)-1alpha --hypoxia response element (HRE) --VEGF signaling cascade, we also examined tumors derived from HIF-1alpha-/- and HRE-/- ES cells. As expected, the VEGF protein level in HIF-1alpha-/- ES tumors was intermediate between VEGF-/- and WT ES cell tumors. Surprisingly, HRE-/- ES tumors produced the same level of VEGF as the VEGF-/- ES tumors, suggesting a critical role of HRE in tumor cell VEGF production. Angiogenesis in these tumors was proportional to their VEGF levels (VEGF-/- approximate to HRE-/-HIF-1alpha-/-WT). In contrast, vascular permeability, leukocyte-endothelial adhesion, and tumor growth were reduced in VEGF-/- and HRE-/- tumors but were comparable in HIF-1a-/- and WT tumors. This discrepancy suggests that different intracellular signaling pathways may be involved in each of these functions of VEGF. More importantly, these data suggest that host cells are active players in tumor angiogenesis and growth and need to be taken into account in the design of any therapeutic strategy.

Recent studies in experimental animals have shown that combining antiangiogenic therapy with radiation can enhance tumor response. Whether this enhancement is mainly attributable to angiogenesis inhibition, endothelial cell radiosensitivity, tumor cell apoptosis, or a decrease in the number of hypoxic cells (improved oxygenation) is not known. We designed this study to discern the role of tumor oxygenation. We chose an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody (mAb) which has a known target, human VEGF. We also measured interstitial fluid pressure (IFP) to test the hypothesis that the decreased vascular permeability induced by the anti-VEGF mAb can lower IFP. The effect of anti-VEGF mAb on vascular density, partial oxygen tension (pO2), and apoptosis was also measured. Athymic NCr/Sed nu/nu mice bearing 6-mm xenograft of the human glioblastoma multiforme (U87), or colon adenocarcinoma (LS174T) were treated with anti-VEGF mAb injected i.p. on alternate days for a total of six injections at a dosage of 100 microg/injection/mouse. For combined anti-VEGF and radiation, single radiation doses were given under normal blood flow (20 and 30 Gy) or clamped hypoxic conditions (30 and 40 Gy) 24 h after the sixth injection of mAb. The inhibition of the growth of U87 and LS174T tumors by the anti-VEGF mAb was associated with a significant reduction in tumor vascular density and a relatively small increase in the number of apoptotic cells. Compared with size-matched controls, IFP decreased by 74% in LS174T, and 73% in U87 in mice treated with anti-VEGF mAb. After antibody treatment PO2 increased significantly in U87, but did not change in LS174T tumors. Combined treatment induced in U87 tumors a tumor-growth delay (TGD) which was greater than additive; in LS174T except for the 40-Gy hypoxic group, the effect was only additive. In both U87 and LS174T the TGD induced by the antibody was independent of oxygen levels in the tumor at the time of radiation. The fact that the increase in TGD occurred under both normoxic and hypoxic conditions suggests that anti-VEGF mAb treatment can compensate for the resistance to radiation induced by hypoxia.

High local polyamine concentrations may suppress cell growth of primary prostatic carcinomas. When cell growth assays were conducted in defined serum-free medium, spermine inhibited the growth of poorly metastatic rat prostate carcinoma cells, causing cell cycle arrest in the G1 phase. In contrast, highly metastatic prostate carcinoma cells were resistant to the growth inhibitory activity of spermine. Ornithine decarboxylase antizyme levels, measured by Western blotting, were elevated 1-2 h after spermine treatment of spermine-sensitive cells but not spermine-resistant cells. Spermine uptake was similar in both the sensitive and resistant cell lines. These results suggest that failure to induce antizyme correlates with spermine resistance in prostate carcinoma.

The maturation of chondrocytes is essential for endochondral bone formation. The Indian Hedgehog (Ihh) gene is expressed in prehypertropic chondrocytes and has been proposed to regulate chondrocyte maturation. While such secretary factors as PTHrP and BMP are thought to be involved in Ihh expression, the mechanism of the restricted expression of Ihh is not clear.Using primary chondrocytes, we have developed here a modified micromass culture (MM-C) system that allows the formation of concentration gradients of secreted factors, expressed either endogenously or retrovirally, from each of plural micromass cultures on a single plate. Using this system, we determined that chondrocytes create the inhibitory micro-environment, partly dependent on PTHrP secretion, for the Ihh expression. We also showed that retrovirally induced BMP-2 induces the expression of both Ihh and Noggin (encoding the BMP-inactivating protein), and we further present evidence that a negative-feedback loop involving Noggin might account for the precise localization of BMP signalling for Ihh induction.These results suggest that the expression of the Ihh gene in cartilage is regulated by several mechanisms that include the secretion of inhibitory factors (including PTHrP) and the negative-feed back loop formed by BMPs and Noggin.

To elucidate the behavior of various metastatic tumor cells with different characteristics in the blood flow, we have developed a system to investigate real-time trafficking using positron emission tomography. In this study, positron-labeled cells, i.e., lung-metastatic B16BL6 melanoma and two sublines of liver-metastatic RAW117 large cell lymphoma, were injected i.v., and the trafficking of these cells was noninvasively determined. All sublines tested accumulated in the lungs immediately after injection, presumably because the lungs were the first organ passed through after i.v. injection. The elimination of RAW117 cells from the lungs, however, was fast compared with that of B16BL6 cells. The latter showed a release rate from the lungs of less than 1%/min, whereas that of RAW117 cells was greater than 2%/min. Reflecting the elimination from lungs, RAW117 cells accumulated in the liver in a time-dependent manner. Biodistribution of metastatic cells was also analyzed by whole-body autoradiography after injection of 5-[125I]iodo-2'-deoxyuridine-labeled cells, using a bioimaging analyzer system. The method is invasive; however, it enables a precise determination of the biodistribution of metastatic cells. Bioimaging analyzer system analysis also showed the organ-specific accumulation of these metastatic cells. Furthermore, colonized distribution of B16BL6 cells in the lungs and that of RAW117 cells in the liver were observed. The present data suggest that the trafficking of metastatic tumor cells greatly influences the organ specificity of cancer metastasis.

The existence of silica within several debris disks has been suggested. Data on both the spectroscopy and annealing conditions of the various polymorphs of silica need to be investigated, as these data are lacking and incomplete in the literature. We investigate the annealing conditions of silica and prepare various types of silica, including α-cristobalite, α-quartz, coesite, stishovite, and fused quartz, which are natural, synthetic, or commercial samples. This paper presents a new study of both the spectroscopy of relevant silica polymorphs and the conditions under which they form. We compare the results to previous studies and find that there are discrepancies. The interesting result of features similar to those of forsterite should be highlighted, where α-cristobalite and coesite showed similar peaks at 16, 33, and 69 μm as forsterite. The 69 μm band for α-cristobalite is especially very broad and strong and shifts largely to a shorter wavelengths under cooling to low temperatures. The band for coesite, however, is very sharp and shifts only a small amount to longer wavelengths under cooling to low temperatures. We discuss the possibility of silica detection around debris disks.

To solve the chronic donor organ shortage, the pig is considered to be a possible donor candidate for human transplantation. However, hyperacute rejection occurs due to the activation of the complement cascade. Therefore, the introduction of human complement inhibitors into animal cells has been proposed as a means to prevent such exologous complement activation. To investigate the extent to which complement inhibitors are resistant to human sera in discordant animals, we established transgenic mice lines which expressed either human decay-accelerating factor (DAF) and/or homologous restriction factor 20 (HRF20) using microinjection methods. Human sera were injected into (a) 10 control mice, (b) 10 DAF-transgenic mice, (c) 10 HRF20-transgenic mice, and (d) 10 DAF and HRF20-transgenic mice. The results showed that all the mice in groups a, b, and c died immediately after injection. Three of the mice in group d died, while seven survived but showed hyperpnea and low activity. The pathological findings of groups a, b, and c included severe coagulation; however, the survivors of group d showed less severe symptoms. The above findings thus suggest that both DAF and HRF20 tend to prevent complement activation to some extent; however, its effectiveness is not considered to be sufficient for clinical use in transplantation.

For the success of xenotransplantation, hyperacute rejection must be controlled. Hyperacute rejection is induced by the activation of complement system via alternative pathway and/or classical pathway. Complement regulatory factors can inhibit activation of complement system via the both pathways. To overcome hyperacute rejection in organ xenotransplantation, gene engineering in the establishment of xeno-endothelial cells and transgenic animals (mouse and pig) using human complement regulatory factors are studied. In the near future, transgenic pig using human complement regulatory factor genes can be used as a potential donor in organ xenotransplantation.

Organ-specific colonization of metastatic tumor cells is regulated through complex interactions of specific adhesion molecules on the tumor cell surface with organ specific microvascular endothelium. The present paper shows the real time tumor cell trafficking under the actual blood flow, which became able to be determined using a new technology, positron emission tomography. This technology would be useful to evaluate the interaction of characteristic tumor cells with various organs in vivo. High and low metastatic rat mammary adenocarcinoma cell variants, MTLn3 and MTC, respectively, were labeled with [2-18F]2-fluoro-2-deoxy-D-glucose in vitro. The labeled cells preferentially accumulated in the lungs, in which the disposition was more intense for MTLn3 than for MTC cells especially for the first 2-10 min after injection, apparently reflecting the organ specific interaction of metastatic tumor cells which may lead to metastasis. Such a short time change of cell disposition is easily determined in a living animal by this new technique. Furthermore, sialidase treatment of MTLn3 cells suppressed the accumulation of these cells in lungs, suggesting that some sialyl glycoconjugates on the MTLn3 cell surface play an important role in cell adhesion to lung endothelium. Positron emission tomography scanning thus enables the noninvasive study of the interaction of characteristic tumor cells with specific endothelium in a living animal.