Chandra Study of the Cepheus B Star Forming Region: Stellar Populations and the Initial Mass Function

Cepheus B (Cep B) molecular cloud and a portion of the nearby Cep OB3b OB association, one of the most active regions of star formation within 1 kpc, has been observed with the ACIS detector on board the Chandra X-ray Observatory. We detect 431 X-ray sources, of which 89% are confidently identified as clustered pre-main sequence stars. Two main results are obtained. First, we provide the best census to date for the stellar population of the region. We identify many members of two rich stellar clusters: the lightly obscured Cep OB3b association, and the deeply embedded cluster in Cep B whose existence was previously traced only by a handful of radio sources and T Tauri stars. Second, we find a discrepancy between the X-ray Luminosity Functions of the Cep OB3b and the Orion Nebula Cluster. This may be due to different Initial Mass Functions of two regions (excess of ~0.3 solar mass stars), or different age distributions. Several other results are obtained. A diffuse X-ray component seen in the field is attributed to the integrated emission of unresolved low mass PMS stars. The X-ray emission from HD 217086 (O7n), the principle ionizing source of the region, follows the standard model involving many small shocks in an unmagnetized radiatively accelerated wind. The X-ray source #294 joins a number of similar superflare PMS stars where long magnetic structures may connect the protoplanetary disk to the stellar surface.Comment: 72 pages, 31 figures, 8 tables. Accepted for publication in Ap

Chandra observations of SN 1987A: the soft X-ray light curve revisited

We report on the present stage of SN 1987A as observed by the Chandra X-ray Observatory. We reanalyze published Chandra observations and add three more epochs of Chandra data to get a consistent picture of the evolution of the X-ray fluxes in several energy bands. We discuss the implications of several calibration issues for Chandra data. Using the most recent Chandra calibration files, we find that the 0.5-2.0 keV band fluxes of SN 1987A have increased by ~6 x 10 ^-13 erg s^-1 cm^-2 per year since 2009. This is in contrast with our previous result that the 0.5-2.0 keV light curve showed a sudden flattening in 2009. Based on our new analysis, we conclude that the forward shock is still in full interaction with the equatorial ring.Comment: Accepted for publication by ApJ, 7 pages, 5 figure

Global X-ray properties of the O and B stars in Carina

The key empirical property of the X-ray emission from O stars is a strong correlation between the bolometric and X-ray luminosities. In the framework of the Chandra Carina Complex Project, 129 O and B stars have been detected as X-ray sources; 78 of those, all with spectral type earlier than B3, have enough counts for at least a rough X-ray spectral characterization. This leads to an estimate of the Lx/Lbol ratio for an exceptional number of 60 O stars belonging to the same region and triples the number of Carina massive stars studied spectroscopically in X-rays. The derived log(Lx/Lbol) is -7.26 for single objects, with a dispersion of only 0.21dex. Using the properties of hot massive stars listed in the literature, we compare the X-ray luminosities of different types of objects. In the case of O stars, the Lx/Lbol ratios are similar for bright and faint objects, as well as for stars of different luminosity classes or spectral types. Binaries appear only slightly harder and slightly more luminous in X-rays than single objects; the differences are not formally significant (at the 1% level), except for the Lx/Lbol ratio in the medium (1.0--2.5keV) energy band. Weak-wind objects have similar X-ray luminosities but they display slightly softer spectra compared to "normal" O stars with the same bolometric luminosity. Discarding three overluminous objects, we find a very shallow trend of harder emission in brighter objects. The properties of the few B stars bright enough to yield some spectral information appear to be different overall (constant X-ray luminosities, harder spectra), hinting that another mechanism for producing X-rays, besides wind shocks, might be at work. However, it must be stressed that the earliest and X-ray brightest amongst these few detected objects are similar to the latest O stars, suggesting a possibly smooth transition between the two processes.Comment: 30 pages, 9 figures. Accepted for the ApJS Special Issue on the Chandra Carina Complex Project (CCCP), scheduled for publication in May 2011. All 16 CCCP Special Issue papers are available at http://cochise.astro.psu.edu/Carina_public/special_issue.html through 2011 at leas

Diffuse Thermal X-Ray Emission in the Core of the Young Massive Cluster Westerlund 1

We present an analysis of the diffuse hard X-ray emission in the core of the young massive Galactic cluster Westerlund 1 based on a 48 ks XMM-Newton observation. Chandra results for the diffuse X-ray emission have indicated a soft thermal component together with a hard component that could be either thermal or non-thermal. We seek to resolve this ambiguity regarding the hard component exploiting the higher sensitivity of XMM-Newton to diffuse emission. Our new X-ray spectra from the central (2' radius) diffuse emission are found to exhibit He-like Fe 6.7 keV line emission, demonstrating that the hard emission in the cluster core is predominantly thermal in origin. Potential sources of this hard component are reviewed, namely an unresolved Pre-Main Sequence population, a thermalized cluster wind and Supernova Remnants interacting with stellar winds. We find that the thermalized cluster wind likely contributes the majority of the hard emission with some contribution from the Pre-Main Sequence population. It is unlikely that Supernova Remnants are contributing significantly to the Wd1 diffuse emission at the current epoch

HIF-1 alpha-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion

© 2014 Landes Bioscience. PTK6/Brk is a non-receptor tyrosine kinase overexpressed in cancer. Here we demonstrate that cytosolic PTK6 is rapidly and robustly induced in response to hypoxic conditions in a HIF-1-independent manner. Furthermore, a proportion of hypoxic PTK6 subsequently re-localized to the cell membrane. We observed that the rapid stabilization of PTK6 is associated with a decrease in PTK6 ubiquitylation and we have identified c-Cbl as a putative PTK6 E3 ligase in normoxia. The consequences of hypoxia-induced PTK6 stabilization and subcellular re-localization to the plasma membrane include increased cell motility and invasion, suggesting PTK6 targeting as a therapeutic approach to reduce hypoxia-regulated metastatic potential. This could have particular significance for breast cancer patients with triple negative disease

Non-invasive assessment of murine PD-L1 levels in syngeneic tumor models by nuclear imaging with nanobody tracers

Blockade of the inhibitory PD-1/PD-L1 immune checkpoint axis is a promising cancer treatment. Nonetheless, a significant number of patients and malignancies do not respond to this therapy. To develop a screen for response to PD-1/PD-L1 inhibition, it is critical to develop a non-invasive tool to accurately assess dynamic immune checkpoint expression. Here we evaluated non-invasive SPECT/CT imaging of PD-L1 expression, in murine tumor models with varying PD-L1 expression, using high affinity PD-L1-specific nanobodies (Nbs). We generated and characterized 37 Nbs recognizing mouse PD-L1. Among those, four Nbs C3, C7, E2 and E4 were selected and evaluated for preclinical imaging of PD-L1 in syngeneic mice. We performed SPECT/CT imaging in wild type versus PD-L1 knock-out mice, using Technetium-99m (99mTc) labeled Nbs. Nb C3 and E2 showed specific antigen binding and beneficial biodistribution. Through the use of CRISPR/Cas9 PD-L1 knock-out TC-1 lung epithelial cell lines, we demonstrate that SPECT/CT imaging using Nb C3 and E2 identifies PD-L1 expressing tumors, but not PD-L1 non-expressing tumors, thereby confirming the diagnostic potential of the selected Nbs. In conclusion, these data show that Nbs C3 and E2 can be used to non-invasively image PD-L1 levels in the tumor, with the strength of the signal correlating with PD-L1 levels. These findings warrant further research into the use of Nbs as a tool to image inhibitory signals in the tumor environment

The Spectra and Variability of X-ray Sources in a Deep Chandra Observation of the Galactic Center

We examine the X-ray spectra and variability of the sample of X-ray sources with L_X = 10^{31}-10^{33} erg s^{-1} identified within the inner 9' of the Galaxy. Very few of the sources exhibit intra-day or inter-month variations. We find that the spectra of the point sources near the Galactic center are very hard between 2--8 keV, even after accounting for absorption. When modeled as power laws the median photon index is Gamma=0.7, while when modeled as thermal plasma we can only obtain lower limits to the temperature of kT>8 keV. The combined spectra of the point sources is similarly hard, with a photon index of Gamma=0.8. Strong line emission is observed from low-ionization, He-like, and H-like Fe, both in the average spectra and in the brightest individual sources. The line ratios of the highly-ionized Fe in the average spectra are consistent with emission from a plasma in thermal equilibrium. This line emission is observed whether average spectra are examined as a function of the count rate from the source, or as a function of the hardness ratios of individual sources. This suggests that the hardness of the spectra may in fact to due local absorption that partially-covers the X-ray emitting regions in the Galactic center systems. We suggest that most of these sources are intermediate polars, which (1) often exhibit hard spectra with prominent Fe lines, (2) rarely exhibit either flares on short time scales or changes in their mean X-ray flux on long time scales, and (3) are the most numerous hard X-ray sources with comparable luminosities in the Galaxy.Comment: 27 pages, including 13 figures. To appear in ApJ, 1 October 2004, v613 issue. An electronic version of table 2 is on http://astro.ucla.edu/~mmuno/sgra/table2_electronic.txt and reduced data files for each source are available on http://www.astro.psu.edu/users/niel/galcen-xray-data/galcen-xray-data.htm

The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2

Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2