CU Comae: a new field double-mode RR Lyrae, the most metal poor discovered to date

We report the discovery of a new double-mode RR Lyrae variable (RRd) in the field of our Galaxy: CU Comae. CU Comae is the sixth such RRd identified to date and is the most metal-poor RRd ever detected. Based on BVI CCD photometry spanning eleven years of observations, we find that CU Comae has periods P0=0.5441641 +/-0.0000049d and P1=0.4057605 +/-0.0000018d. The amplitude of the primary (first-overtone) period of CU Comae is about twice the amplitude of the secondary (fundamental) period. The combination of the fundamental period of pulsation P0 and the period ratio of P1/P0=0.7457 places the variable on the metal-poor side of the Petersen diagram, in the region occupied by M68 and M15 RRd's. A mass of 0.83 solar masses is estimated for CU Comae using an updated theoretical calibration of the Petersen diagram. High resolution spectroscopy (R=30,000) covering the full pulsation cycle of CU Comae was obtained with the 2.7 m telescope of the Mc Donald Observatory, and has been used to build up the radial velocity curve of the variable. Abundance analysis done on the four spectra taken near minimum light (phase: 0.54 -- 0.71) confirms the metal poor nature of CU Comae, for which we derive [Fe/H]=-2.38 +/-0.20. This value places this new RRd at the extreme metal-poor edge of the metallicity distribution of the RR Lyrae variables in our Galaxy.Comment: 21 pages including 8 Tables, Latex, 11 Figures. Accepted for publication in The Astronomical Journal, October 2000 issu

A multi-Lorentzian timing study of the atoll sources 4U 0614+09 and 4U 1728-34

We present the results of a multi-Lorentzian fit to the power spectra of two kilohertz QPO sources; 4U 0614+09 and 4U 1728-34. This work was triggered by recent results of a similar fit to the black-hole candidates (BHCs) GX 339-4 and Cyg X-1 by Nowak in 2000. We find that one to six Lorentzians are needed to fit the power spectra of our two sources. The use of exactly the same fit function reveals that the timing behaviour of 4U 0614+09 and 4U 1728-34 is almost identical at luminosities which are about a factor 5 different. As the characteristic frequency of the Lorentzians we use the frequency, nu_max, at which each component contributes most of its variance per log frequency as proposed by Belloni, Psaltis & van der Klis in 2001. When using nu_max instead of the centroid frequency of the Lorentzian, the recently discovered hectohertz Lorentzian is practically constant in frequency. We use our results to test the suggestions by, respectively, Psaltis Belloni and van der Klis in 1999 and Nowak in 2000 that the two Lorentzians describing the high-frequency end of the broad-band noise in BHCs in the low state can be identified with the kilohertz QPOs in the neutron star low mass X-ray binaries. We find, that when the two kilohertz QPOs are clearly present, the low-frequency part of the power spectrum is too complicated to draw immediate conclusions from the nature of the components detected in any one power spectrum. However, the relations we observe between the characteristic frequencies of the kilohertz QPOs and the band-limited noise, when compared to the corresponding relations in BHCs, hint towards the identification of the second-highest frequency Lorentzian in the BHCs with the lower kilohertz QPO. They do not confirm the identification of the highest-frequency Lorentzian with the upper kilohertz QPO.Comment: 30 pages, 35 figures, ApJ accepted; changed name of BLN QPO into very low-frequency Lorentzian, removed table 4 and figure 8 from previous versio

Hierarchical information clustering by means of topologically embedded graphs

We introduce a graph-theoretic approach to extract clusters and hierarchies in complex data-sets in an unsupervised and deterministic manner, without the use of any prior information. This is achieved by building topologically embedded networks containing the subset of most significant links and analyzing the network structure. For a planar embedding, this method provides both the intra-cluster hierarchy, which describes the way clusters are composed, and the inter-cluster hierarchy which describes how clusters gather together. We discuss performance, robustness and reliability of this method by first investigating several artificial data-sets, finding that it can outperform significantly other established approaches. Then we show that our method can successfully differentiate meaningful clusters and hierarchies in a variety of real data-sets. In particular, we find that the application to gene expression patterns of lymphoma samples uncovers biologically significant groups of genes which play key-roles in diagnosis, prognosis and treatment of some of the most relevant human lymphoid malignancies.Comment: 33 Pages, 18 Figures, 5 Table

Direct Evidence that Bevacizumab, an Anti-VEGF Antibody, Up-regulates SDF1 , CXCR4, CXCL6, and Neuropilin 1 in Tumors from Patients with Rectal Cancer

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy

Modeling dust mineralogical composition: sensitivity to soil mineralogy atlases and their expected climate impacts

Soil dust aerosols are a key component of the climate system, as they interact with short- and long-wave radiation, alter cloud formation processes, affect atmospheric chemistry and play a role in biogeochemical cycles by providing nutrient inputs such as iron and phosphorus. The influence of dust on these processes depends on its physicochemical properties, which, far from being homogeneous, are shaped by its regionally varying mineral composition. The relative amount of minerals in dust depends on the source region and shows a large geographical variability. However, many state-of-the-art Earth system models (ESMs), upon which climate analyses and projections rely, still consider dust mineralogy to be invariant. The explicit representation of minerals in ESMs is more hindered by our limited knowledge of the global soil composition along with the resulting size-resolved airborne mineralogy than by computational constraints. In this work we introduce an explicit mineralogy representation within the state-of-the-art Multiscale Online Nonhydrostatic AtmospheRe CHemistry (MONARCH) model. We review and compare two existing soil mineralogy datasets, which remain a source of uncertainty for dust mineralogy modeling and provide an evaluation of multiannual simulations against available mineralogy observations. Soil mineralogy datasets are based on measurements performed after wet sieving, which breaks the aggregates found in the parent soil. Our model predicts the emitted particle size distribution (PSD) in terms of its constituent minerals based on brittle fragmentation theory (BFT), which reconstructs the emitted mineral aggregates destroyed by wet sieving. Our simulations broadly reproduce the most abundant mineral fractions independently of the soil composition data used. Feldspars and calcite are highly sensitive to the soil mineralogy map, mainly due to the different assumptions made in each soil dataset to extrapolate a handful of soil measurements to arid and semi-arid regions worldwide. For the least abundant or more difficult-to-determine minerals, such as iron oxides, uncertainties in soil mineralogy yield differences in annual mean aerosol mass fractions of up to ∼ 100 %. Although BFT restores coarse aggregates including phyllosilicates that usually break during soil analysis, we still identify an overestimation of coarse quartz mass fractions (above 2 µm in diameter). In a dedicated experiment, we estimate the fraction of dust with undetermined composition as given by a soil map, which makes up ∼ 10 % of the emitted dust mass at the global scale and can be regionally larger. Changes in the underlying soil mineralogy impact our estimates of climate-relevant variables, particularly affecting the regional variability of the single-scattering albedo at solar wavelengths or the total iron deposited over oceans. All in all, this assessment represents a baseline for future model experiments including new mineralogical maps constrained by high-quality spaceborne hyperspectral measurements, such as those arising from the NASA Earth Surface Mineral Dust Source Investigation (EMIT) mission.</p

PDGF-C Induces Maturation of Blood Vessels in a Model of Glioblastoma and Attenuates the Response to Anti-VEGF Treatment

Recent clinical trials of VEGF inhibitors have shown promise in the treatment of recurrent glioblastomas (GBM). However, the survival benefit is usually short-lived as tumors escape anti-VEGF therapies. Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy.We first showed that PDGF-C is present in human GBMs. Then, we overexpressed or downregulated PDGF-C in a human GBM cell line, U87MG, and grew them in cranial windows in nude mice to assess vessel structure and function using intravital microscopy. PDGF-C overexpressing tumors had smaller vessel diameters and lower vascular permeability compared to the parental or siRNA-transfected tumors. Furthermore, vessels in PDGF-C overexpressing tumors had more extensive coverage with NG2 positive perivascular cells and a thicker collagen IV basement membrane than the controls. Treatment with DC101, an anti-VEGFR-2 antibody, induced decreases in vessel density in the parental tumors, but had no effect on the PDGF-C overexpressing tumors.These results suggest that PDGF-C plays an important role in glioma vessel maturation and stabilization, and that it can attenuate the response to anti-VEGF therapy, potentially contributing to escape from vascular normalization

現地観測に基づく河川流の乱流特性に関する研究

博士（工学）神戸大

Multiorgan Metastasis of Human HER-2+ Breast Cancer in Rag2−/−;Il2rg−/− Mice and Treatment with PI3K Inhibitor

In vivo studies of the metastatic process are severely hampered by the fact that most human tumor cell lines derived from highly metastatic tumors fail to consistently metastasize in immunodeficient mice like nude mice. We describe a model system based on a highly immunodeficient double knockout mouse, Rag2−/−;Il2rg−/−, which lacks T, B and NK cell activity. In this model human metastatic HER-2+ breast cancer cells displayed their full multiorgan metastatic potential, without the need for selections or additional manipulations of the system. Human HER-2+ breast cancer cell lines MDA-MB-453 and BT-474 injected into Rag2−/−;Il2rg−/− mice faithfully reproduced human cancer dissemination, with multiple metastatic sites that included lungs, bones, brain, liver, ovaries, and others. Multiorgan metastatic spread was obtained both from local tumors, growing orthotopically or subcutaneously, and from cells injected intravenously. The problem of brain recurrencies is acutely felt in HER-2+ breast cancer, because monoclonal antibodies against HER-2 penetrate poorly the blood-brain barrier. We studied whether a novel oral small molecule inhibitor of downstream PI3K, selected for its penetration of the blood-brain barrier, could affect multiorgan metastatic spread in Rag2−/−; Il2rg−/− mice. NVP-BKM120 effectively controlled metastatic growth in multiple organs, and resulted in a significant proportion of mice free from brain and bone metastases. Human HER-2+ human breast cancer cells in Rag2−/−;Il2rg−/− mice faithfully reproduced the multiorgan metastatic pattern observed in patients, thus allowing the investigation of metastatic mechanisms and the preclinical study of novel antimetastatic agents