Disseminated tumor cells (DTCs) in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form ...detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorigenicity and metastatic potential of dormant disseminated breast cancer cells (prior to activation) in the bone marrow.
Total bone marrow, isolated from mice previously injected with tumorspheres into the mammary fat pad, was injected into the mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were analyzed by H+E staining to detect metastases. The injection of bone marrow isolated from mice previously injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-injection. However, the injection of bone marrow isolated from non-injected mice did not result in tumor formation in the mammary fat pad. The DTC-derived tumors exhibited accelerated development of metastatic lesions within the lung, liver and kidney. The resultant tumors and the majority of metastatic lesions within the lung and liver exhibited a mesenchymal-like phenotype.
Dormant DTCs within the bone marrow are highly malignant upon injection into the mammary fat pad, with the accelerated development of metastatic lesions within the lung, liver and kidney. These results suggest the acquisition of a more aggressive phenotype of DTCs during metastatic latency within the bone marrow microenvironment.
Toward Empowered Design Marsden, G.
Computer (Long Beach, Calif.),
06/2008, Letnik:
41, Številka:
6
Journal Article
Recenzirano
Pragmatic design requires no radical alterations to the existing digital ecology and has successfully provided many viable solutions. Given the skills limitations within the developing world, ...however, developers also need a new design focus that views the user as designer.
The first deep blank-field 450 μm map (1σ 1.3 mJy) from the Submillimetre Common-User Bolometer Array-2 SCUBA-2 Cosmology Legacy Survey (S2CLS), conducted with the James Clerk Maxwell Telescope ...(JCMT) is presented. Our map covers 140 arcmin2 of the Cosmological Evolution Survey field, in the footprint of the Hubble Space Telescope (HST) Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey. Using 60 submillimetre galaxies detected at ≥3.75σ, we evaluate the number counts of 450-μm-selected galaxies with flux densities S
450 > 5 mJy. The 8 arcsec JCMT beam and high sensitivity of SCUBA-2 now make it possible to directly resolve a larger fraction of the cosmic infrared background (CIB, peaking at λ ∼ 200 μm) into the individual galaxies responsible for its emission than has previously been possible at this wavelength. At S
450 > 5 mJy, we resolve (7.4 ± 0.7) × 10−2 MJy sr−1 of the CIB at 450 μm (equivalent to 16 ± 7 per cent of the absolute brightness measured by the Cosmic Background Explorer at this wavelength) into point sources. A further ∼40 per cent of the CIB can be recovered through a statistical stack of 24 μm emitters in this field, indicating that the majority ( 60 per cent) of the CIB at 450 μm is emitted by galaxies with S
450 > 2 mJy. The average redshift of 450 μm emitters identified with an optical/near-infrared counterpart is estimated to be 〈z〉 = 1.3, implying that the galaxies in the sample are in the ultraluminous class (
). If the galaxies contributing to the statistical stack lie at similar redshifts, then the majority of the CIB at 450 μm is emitted by galaxies in the luminous infrared galaxy (LIRG) class with L
IR > 3.6 × 1011 L.
Sungrazing Comets Marsden, Brian G
Annual review of astronomy and astrophysics,
09/2005, Letnik:
43, Številka:
1
Journal Article
Recenzirano
▪ Abstract After centuries of speculation that the early records of observations of bright comets near the sun involved repeated returns of a single sungrazing object, there came in the 1880s the ...realization, first by Kirkwood, and then most notably by Kreutz, that the observations could be explained by the existence of a group of related comets that had separated from each other at some earlier perihelion passage. After the appearance of further bright sungrazers in the mid-twentieth century, attempts were made to understand the specific manner in which the various members of this Kreutz Group of comets had evolved from each other. Beginning in 1979, coronagraphic observations from space allowed the detection of numerous additional Kreutz members that were completely vaporized as they grazed the sun. Since 1996, the Solar and Heliospheric Observatory (SOHO) coronagraphs have revealed some 700 of these comets, giving rise to the thought that there is a constant stream of small members, much of the break-up having occurred instead near aphelion and even quite recently. Whereas consideration of break-up only near perihelion requires that the observed dispersion of the orbital parameters would take many millennia, recent calculations have shown that the evolution can be substantially sped up by allowing fragments to be rotationally spun off at heliocentric distances of many tens of AU. The SOHO observations have also allowed the recognition of three other substantial groups of sungrazing comets, as well as some pairs arriving only hours apart.
Transcriptional profiling of Campylobacter jejuni during colonization of the chick cecum identified 59 genes that were differentially expressed in vivo compared with the genes in vitro. The data ...suggest that C. jejuni regulates electron transport and central metabolic pathways to alter its physiological state during establishment in the chick cecum.
This paper reports on a study of current practice in policy transfer, and ways in which its effectiveness can be increased. A literature review identifies important factors in examining the transfer ...of policies. Results of interviews in eleven cities in Northern Europe and North America investigate these factors further.
The principal motivations for policy transfer were strategic need and curiosity. Local officials and politicians dominated the process of initiating policy transfer, and local officials were also the leading players in transferring experience.
A range of information sources are used in the search process but human interaction was the most important source of learning for two main reasons. First, there is too much information available through the Internet and the search techniques are not seen to be wholly effective in identifying the necessary information. Secondly, the information available on websites, portals and even good practice guides is not seen to be of mixed quality with risks of focussing only on successful implementation and therefore subject to some bias. Officials therefore rely on their trusted networks of peers for lessons as here they can access the ‘real implementation’ story and the unwritten lessons. Organisations which have a culture that is supportive of learning from elsewhere had strong and broad networks of external contacts and resourced their development whilst others are more insular or inward looking and reluctant to invest in policy lessons from elsewhere. Solutions to the problems identified in the evidence base are proposed.
City to city policy transfer is a very active process in the field of transport. Not enough is yet understood about its benefits or the conditions under which it is most effective. Such understandings should help to promote and accelerate the uptake of effective and well matched policies.
►the search for policy lessons from other cities is very active. ►most policy transfer is a mix of lessons learnt from several places. ►peer to peer exchange is critical in providing the context for learning. ►the organisational culture of city planners impacts on participation and learning. ►more extensive and reliable evaluations of policies could help learning.
We present maps, source catalogue and number counts of the largest, most complete and unbiased extragalactic submillimetre survey: the 850-μm SCUBA Half-Degree Extragalactic Survey (SHADES). Using ...the Submillimetre Common-User Bolometer Array (SCUBA) on the James Clerk Maxwell Telescope (JCMT), SHADES mapped two separate regions of sky: the Subaru/XMM–Newton Deep Field (SXDF) and the Lockman Hole East (LH). Encompassing 93 per cent of the overall acquired data (i.e. data taken up to 2004 February 1), these SCUBA maps cover 720 arcmin2 with a rms noise level of about 2 mJy and have uncovered >100 submillimetre galaxies. In order to ensure the utmost robustness of the resulting source catalogue, data reduction was independently carried out by four subgroups within the SHADES team, providing an unprecedented degree of reliability with respect to other SCUBA catalogues available from the literature. Individual source lists from the four groups were combined to produce a robust 120-object SHADES catalogue; an invaluable resource for follow-up campaigns aiming to study the properties of a complete and consistent sample of submillimetre galaxies. For the first time, we present deboosted flux densities for each submillimetre galaxy found in a large survey. Extensive simulations and tests were performed separately by each group in order to confirm the robustness of the source candidates and to evaluate the effects of false detections, completeness and flux density boosting. Corrections for these effects were then applied to the data to derive the submillimetre galaxy source counts. SHADES has a high enough number of detected sources that meaningful differential counts can be estimated, unlike most submillimetre surveys which have to consider integral counts. We present differential and integral source number counts and find that the differential counts are better fit with a broken power law or a Schechter function than with a single power law; the SHADES data alone significantly show that a break is required at several mJy, although the precise position of the break is not well constrained. We also find that a 850-μm survey complete down to 2 mJy would resolve 20–30 per cent of the far-infrared background into point sources.
We describe the far-infrared (far-IR; rest-frame 8-1000-μm) properties of a sample of 443 Hα-selected star-forming galaxies in the Cosmic Evolution Survey (COSMOS) and Ultra Deep Survey (UDS) fields ...detected by the High-redshift Emission Line Survey (HiZELS) imaging survey. Sources are identified using narrow-band filters in combination with broad-band photometry to uniformly select Hα (and O ii if available) emitters in a narrow redshift slice at z = 1.47 ± 0.02. We use a stacking approach in Spitzer-MIPS mid-IR, Herschel-PACS/SPIRE far-IR from the PACS Evolutionary Prove (PEP) and Herschel Multi-tiered Extragalactic Survey (HerMES) and AzTEC mm-wave images to describe their typical far-IR properties. We find that HiZELS galaxies with observed Hα luminosities of L(Hα)obs 108.1-9.1 L ( 1041.7-42.7 erg s−1) have bolometric far-IR luminosities of typical luminous IR galaxies,
L. Combining the Hα and far-IR luminosities, we derive median star formation rates (SFRs) of SFRHα, FIR = 32 ± 5 M yr−1 and Hα extinctions of A
Hα = 1.0 ± 0.2 mag. Perhaps surprisingly, little difference is seen in typical HiZELS extinction levels compared to local star-forming galaxies. We confirm previous empirical stellar mass (M
*) to A
Hα relations and the little or no evolution up to z = 1.47. For HiZELS galaxies (or similar samples) we provide an empirical parametrization of the SFR as a function of rest-frame (u − z) colours and 3.6-μm photometry - a useful proxy to aid in the absence of far-IR detections in high-z galaxies. We find that the observed Hα luminosity is a dominant SFR tracer when rest-frame (u − z) colours are 0.9 mag or when Spitzer-3.6-μm photometry is fainter than 22 mag (Vega) or when stellar masses are lower than 109.7 M. We do not find any correlation between the O ii/Hα and far-IR luminosity, suggesting that this emission line ratio does not trace the extinction of the most obscured star-forming regions, especially in massive galaxies where these dominate. The luminosity-limited HiZELS sample tends to lie above of the so-called main sequence for star-forming galaxies, especially at low stellar masses, indicating high star formation efficiencies in these galaxies. This work has implications for SFR indicators and suggests that obscured star formation is linked to the assembly of stellar mass, with deeper potential wells in massive galaxies providing dense, heavily obscured environments in which stars can form rapidly.
Solar Orbiter Müller, D.; Marsden, R. G.; St. Cyr, O. C. ...
Solar physics,
07/2013, Letnik:
285, Številka:
1-2
Journal Article
Recenzirano
Odprti dostop
The heliosphere represents a uniquely accessible domain of space, where fundamental physical processes common to solar, astrophysical and laboratory plasmas can be studied under conditions impossible ...to reproduce on Earth and unfeasible to observe from astronomical distances.
Solar Orbiter
, the first mission of ESA’s Cosmic Vision 2015 – 2025 programme, will address the central question of heliophysics: How does the Sun create and control the heliosphere? In this paper, we present the scientific goals of the mission and provide an overview of the mission implementation.
Shocks driven by fast coronal mass ejections (CMEs) are the dominant particle accelerators in large, “gradual” solar energetic particle (SEP) events. In these events, the event-integrated value of ...the iron-to-oxygen ratio (Fe/O) is typically ∼ 0.1, at least at energies of a few MeV/nucleon. However, at the start of some gradual events, when intensities are low and growing, initially Fe/O is ∼ 1. This value is also characteristic of small, “impulsive” SEP events, in which particle acceleration is due to magnetic reconnection. These observations suggested that SEPs in gradual events also include a direct contribution from the flare that accompanied the CME launch. If correct, this interpretation is of critical importance: it indicates a clear path to interplanetary space for particles from the reconnection region beneath the CME. A key issue for the flare origin is “magnetic connectedness”,
i.e.
, proximity of the flare site to the solar footpoint of the observer’s magnetic field line.
We present two large gradual events observed in 2001 by
Wind
at L1 and by
Ulysses
, when it was located at > 60
∘
heliolatitude and beyond 1.6 AU. In these events,
transient
Fe/O enhancements at 5 – 10 MeV/nucleon were seen at both spacecraft, even though one or both is not “well-connected” to the flare. These observations demonstrate that an initial Fe/O enhancement cannot be cited as evidence for a direct flare component. Instead, initial Fe/O enhancements are better understood as a transport effect, driven by the different mass-to-charge ratios of Fe and O.
We further demonstrate that the time-constant of the roughly exponential decay of the Fe/O ratio scales as
R
2
, where
R
is the observer’s radial distance from the Sun. This behavior is consistent with radial diffusion. These observations thus also provide a potential constraint on models in which SEPs reach high heliolatitudes by cross-field diffusion.
PDF
