Far infrared mapping of three Galactic star forming regions : W3(OH), S 209 & S 187

Three Galactic star forming regions associated with W3(OH), S209 and S187 have been simultaneously mapped in two trans-IRAS far infrared (FIR) bands centered at ~ 140 and 200 micron using the TIFR 100 cm balloon borne FIR telescope. These maps show extended FIR emission with structures. The HIRES processed IRAS maps of these regions at 12, 25, 60 & 100 micron have also been presented for comparison. Point-like sources have been extracted from the longest waveband TIFR maps and searched for associations in the other five bands. The diffuse emission from these regions have been quantified, which turns out to be a significant fraction of the total emission. The spatial distribution of cold dust (T < 30 K) for two of these sources (W3(OH) & S209), has been determined reliably from the maps in TIFR bands. The dust temperature and optical depth maps show complex morphology. In general the dust around S209 has been found to be warmer than that in W3(OH) region.Comment: Accepted for publication in Journal of Astrophysics and Astronomy (20 pages including 8 figures & 3 tables

A multi-wavelength census of stellar contents in the young cluster NGC 1624

We present a comprehensive multi-wavelength analysis of the young cluster NGC 1624 associated with the H II region Sh2-212 using optical UBVRI photometry, optical spectroscopy and GMRT radio continuum mapping along with the near-infrared (NIR) JHK archival data. Reddening E(B-V) and distance to the cluster are estimated to be 0.76 - 1.00 mag and 6.0 +/- 0.8 kpc, respectively. Present analysis yields a spectral class of O6.5V for the main ionizing source of the region. The distribution of YSOs in (J-H)/ (H-K) NIR colour-colour diagram shows that a majority of them have A_V $\le$ 4 mag. Based on the NIR excess characteristics, we identified 120 probable candidate YSOs in this region which yield a disk frequency of ~ 20%. These YSOs are found to have an age spread of ~ 5 Myr with a median age of ~ 2-3 Myr and a mass range of ~ 0.1 - 3.0 $M_\odot$. A significant number of YSOs are located close to the cluster centre and we detect an enhanced density of reddened YSOs located/projected close to the molecular clumps at the periphery of NGC 1624. This indicates that the YSOs located within the cluster core are relatively older in comparison to those located/projected near the clumps. From the radio continuum flux, spectral class of the ionizing source of the ultra-compact H II region at the periphery of Sh2-212 is estimated to be ~ B0.5V. From optical data, slope of the mass function (MF) $\Gamma$, in the mass range $1.2 \le M/M_{\odot}<27$ can be represented by a single power law with a slope -1.18 +/- 0.10, whereas the NIR data in the mass range $0.65 \le M/M_{\odot}<27$ yields $\Gamma$ = -1.31 +/- 0.15. The slope of the K-band luminosity function (KLF) for the cluster is found to be 0.30 +/- 0.06 which is in agreement with the values obtained for other young clusters.Comment: Accepted for publication in MNRA

An excess of emission in the dark cloud LDN 1111 with the Arcminute Microkelvin Imager

We present observations of the Lynds' dark nebula LDN 1111 made at microwave frequencies between 14.6 and 17.2 GHz with the Arcminute Microkelvin Imager (AMI). We find emission in this frequency band in excess of a thermal free--free spectrum extrapolated from data at 1.4 GHz with matched uv-coverage. This excess is > 15 sigma above the predicted emission. We fit the measured spectrum using the spinning dust model of Drain & Lazarian (1998a) and find the best fitting model parameters agree well with those derived from Scuba data for this object by Visser et al. (2001).Comment: accepted MNRA

Somatic p16INK4a loss accelerates melanomagenesis

Loss of p16INK4a–RB and ARF–p53 tumor suppressor pathways, as well as activation of RAS–RAF signaling, is seen in a majority of human melanomas. Although heterozygous germline mutations of p16INK4a are associated with familial melanoma, most melanomas result from somatic genetic events: often p16INK4a loss and N-RAS or B-RAF mutational activation, with a minority possessing alternative genetic alterations such as activating mutations in K-RAS and/or p53 inactivation. To generate a murine model of melanoma featuring some of these somatic genetic events, we engineered a novel conditional p16INK4a-null allele and combined this allele with a melanocyte-specific, inducible CRE recombinase strain, a conditional p53-null allele and a loxP-stop-loxP activatable oncogenic K-Ras allele. We found potent synergy between melanocyte-specific activation of K-Ras and loss of p16INK4a and/or p53 in melanomagenesis. Mice harboring melanocyte-specific activated K-Ras and loss of p16INK4a and/or p53 developed invasive, unpigmented and nonmetastatic melanomas with short latency and high penetrance. In addition, the capacity of these somatic genetic events to rapidly induce melanomas in adult mice suggests that melanocytes remain susceptible to transformation throughout adulthood

Genetically Engineered Cancer Models, But Not Xenografts, Faithfully Predict Anticancer Drug Exposure in Melanoma Tumors

Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The usefulness of xenograft models for efficacy testing, however, has been questioned, whereas genetically engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may offer some advantages for efficacy assessment. A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human patients has not been performed

Alterations of LKB1 and KRAS and risk of brain metastasis: Comprehensive characterization by mutation analysis, copy number, and gene expression in non-small-cell lung carcinoma

Brain metastases are one of the most malignant complications of lung cancer and constitute a significant cause of cancer related morbidity and mortality worldwide. Recent years of investigation suggested a role of LKB1 in NSCLC development and progression, in synergy with KRAS alteration. In this study, we systematically analyzed how LKB1 and KRAS alteration, measured by mutation, gene expression (GE) and copy number (CN), are associated with brain metastasis in NSCLC

High resolution optical spectroscopy of an LBV-candidate inside the CygOB2 association

For the first time, we obtained the high-resolution (R=15000 and 60000) optical spectra for the extremely luminous star No.12, associated with the IR-source IRAS20308+4104, a member of the CygOB2 association. We have found about 200 spectral features in range 4552-7939AA, including the interstellar NaI, KI lines and numerous DIBs, which are the strongest absorption lines in the spectrum, along with the HeI, CII, and SiII lines. A two-dimensional spectral classification indicates that the spectral type is B5+/-0.5 Ia+. Our analysis of the Vr data shows the presence of a Vr gradient in the stellar atmosphere, caused by the infall of matter onto the star. The strong Halpha emission displays broad Thompson wings and time-variable core absorption, providing evidence that the stellar wind is inhomogeneous, and a slightly blue-shifted PCyg type absorption profile. We concluded that the wind is variable in time.Comment: 20 pages, 5 figures, 2 table

p16INK4A Positively Regulates Cyclin D1 and E2F1 through Negative Control of AUF1

/pRB/E2F pathway, a key regulator of the critical G1 to S phase transition of the cell cycle, is universally disrupted in human cancer. However, the precise function of the different members of this pathway and their functional interplay are still not well defined. -dependent manner, and several of these genes are also members of the AUF1 and E2F1 regulons. We also present evidence that E2F1 mediates p16-dependent regulation of several pro- and anti-apoptotic proteins, and the consequent induction of spontaneous as well as doxorubicin-induced apoptosis. is also a modulator of transcription and apoptosis through controlling the expression of two major transcription regulators, AUF1 and E2F1

An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2−/− γc−/− mouse

The occurrence of metastases is a critical determinant of the prognosis for breast cancer patients. Effective treatment of breast cancer metastases is hampered by a poor understanding of the mechanisms involved in the formation of these secondary tumor deposits. To study the processes of metastasis, valid in vivo tumor metastasis models are required. Here, we show that increased expression of the EGF receptor in the MTLn3 rat mammary tumor cell-line is essential for efficient lung metastasis formation in the Rag mouse model. EGFR expression resulted in delayed orthotopic tumor growth but at the same time strongly enhanced intravasation and lung metastasis. Previously, we demonstrated the critical role of NK cells in a lung metastasis model using MTLn3 cells in syngenic F344 rats. However, this model is incompatible with human EGFR. Using the highly metastatic EGFR-overexpressing MTLn3 cell-line, we report that only Rag2−/−γc−/− mice, which lack NK cells, allow efficient lung metastasis from primary tumors in the mammary gland. In contrast, in nude and SCID mice, the remaining innate immune cells reduce MTLn3 lung metastasis formation. Furthermore, we confirm this finding with the orthotopic transplantation of the 4T1 mouse mammary tumor cell-line. Thus, we have established an improved in vivo model using a Rag2−/− γc−/− mouse strain together with MTLn3 cells that have increased levels of the EGF receptor, which enables us to study EGFR-dependent tumor cell autonomous mechanisms underlying lung metastasis formation. This improved model can be used for drug target validation and development of new therapeutic strategies against breast cancer metastasis formation