ABSTRACT
Recent observations show that rings and gaps are ubiquitous in protoplanetary discs. These features are often interpreted as being due to the presence of planets; however, the effect of ...planetary migration on the observed morphology has not been investigated hitherto. In this work, we investigate whether multiwavelength mm/submm observations can detect signatures of planet migration, using 2D dusty hydrodynamic simulations to model the structures generated by migrating planets and synthesizing ALMA continuum observations at $\rm 850\, \hbox{$\mu $m}$ and $\rm 3\, mm$. We identify three possible morphologies for a migrating planet: a slowly migrating planet is associated with a single ring outside the planet’s orbit, a rapidly migrating planet is associated with a single ring inside the planet’s orbit while a planet migrating at intermediate speed generates one ring on each side of the planet’s orbit. We argue that multiwavelength data can distinguish multiple rings produced by a migrating planet from other scenarios for creating multiple rings, such as multiple planets or discs with low viscosity. The signature of migration is that the outer ring has a lower spectral index, due to larger dust grains being trapped there. Of the recent ALMA observations revealing protoplanetary discs with multiple rings and gaps, we suggest that Elias 24 is the best candidate for a planet migrating in the intermediate speed regime.
ABSTRACT
The 1.33-mm survey of protoplanetary discs in the Taurus molecular cloud found annular gaps and rings to be common in extended sources (≳ 55au), when their 1D visibility distributions were ...fit parametrically. We first demonstrate the advantages and limitations of non-parametric visibility fits for data at the survey’s 0.12-arcsec resolution. Then we use the non-parametric model in Frankenstein (frank) to identify new substructure in three compact and seven extended sources. Among the new features, we identify three trends: a higher occurrence rate of substructure in the survey’s compact discs than previously seen, underresolved (potentially azimuthally asymmetric) substructure in the innermost disc of extended sources, and a ‘shoulder’ on the trailing edge of a ring in discs with strong depletion at small radii. Noting the shoulder morphology is present in multiple discs observed at higher resolution, we postulate it is tracing a common physical mechanism. We further demonstrate how a superresolution frank brightness profile is useful in motivating an accurate parametric model, using the highly structured source DL Tau in which frank finds two new rings. Finally, we show that sparse (u, v) plane sampling may be masking the presence of substructure in several additional compact survey sources.
Functional heterogeneity within tumors presents a significant therapeutic challenge. Here we show that quiescent, therapy-resistant Sox2+ cells propagate sonic hedgehog subgroup medulloblastoma by a ...mechanism that mirrors a neurogenic program. Rare Sox2+ cells produce rapidly cycling doublecortin+ progenitors that, together with their postmitotic progeny expressing NeuN, comprise tumor bulk. Sox2+ cells are enriched following anti-mitotic chemotherapy and Smoothened inhibition, creating a reservoir for tumor regrowth. Lineage traces from Sox2+ cells increase following treatment, suggesting that this population is responsible for relapse. Targeting Sox2+ cells with the antineoplastic mithramycin abrogated tumor growth. Addressing functional heterogeneity and eliminating Sox2+ cells presents a promising therapeutic paradigm for treatment of sonic hedgehog subgroup medulloblastoma.
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•Sonic hedgehog medulloblastoma growth is driven by rare quiescent Sox2+ cells•Fate mapping and transplantation show that Sox2+ cells are tumor-propagating cells•Sox2+ medulloblastoma cells are resistant to Smoothened inhibition•Targeting Sox2+ medulloblastoma cells with mithramycin blocks tumor growth
Vanner et al. show that quiescent SOX2+ cells are SHH subtype medulloblastoma (MB)-propagating cells (MPCs) in mice and that patients having SHH MB with a high MPC signature have a poor outcome. Sox2+ cells are enriched following antimitotic or SHH pathway-targeted therapy but can be inhibited using mithramycin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Multicellular tumor spheroids (MTS) are a well-established model system for drug development and are a valuable in vitro research tool for use prior to employing animal models. These 3D-cell cultures ...are thought to display chemical gradients of oxygen and nutrients throughout their structure, giving rise to distinct microenvironments in radial layers, thus, mimicking the pathophysiological environment of a tumor. Little is known about the localized distributions of metabolites within these microenvironments. To address this, here we utilize high spectral resolution Fourier-transform ion cyclotron resonance (FT-ICR), MALDI mass spectrometry imaging (MSI) to image the distribution of endogenous metabolites in breast cancer MCF-7 spheroids. We show that known specific metabolite markers (adenosine phosphates and glutathione) indicate that the central region of these cell culture models experiences increased hypoxic and oxidative stress. By using discriminatory analysis, we have identified which m/z values localize toward the outer proliferative or central hypoxic regions of an MTS. Elemental formulae were assigned with sub-ppm mass accuracy, allowing metabolite assignment. Using this information, we have mapped these metabolites back to distinct pathways to improve our understanding of the molecular environment and biochemistry of these tumor models.
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IJS, KILJ, NUK, PNG, UL, UM
ABSTRACT
Thermal disc winds occur in many contexts and may be particularly important to the secular evolution and dispersal of protoplanetary discs heated by high energy radiation from their central ...star. In this paper, we generalize previous models of self-similar thermal winds – which have self-consistent morphology and variation of flow variables – to the case of launch from an elevated base and to non-isothermal conditions. These solutions are well-reproduced by hydrodynamic simulations, in which, as in the case of isothermal winds launched from the midplane, we find winds launch at the maximum Mach number for which the streamline solutions extend to infinity without encountering a singularity. We explain this behaviour based on the fact that lower Mach number solutions do not fill the spatial domain. We also show that hydrodynamic simulations reflect the corresponding self-similar models across a range of conditions appropriate to photoevaporating protoplanetary discs, even when gravity, centrifugal forces, or changes in the density gradient mean the problem is not inherently scale free. Of all the parameters varied, the elevation of the wind base affected the launch velocity and flow morphology most strongly, with temperature gradients causing only minor differences. We explore how launching from an elevated base affects Ne ii line profiles from winds, finding it increases (reduces) the full width at half maximum (FWHM) of the line at low (high) inclination to the line of sight compared with models launched from the disc midplane and thus weakens the dependence of the FWHM on inclination.
Abstract A correlation between proto-planetary disc radii and sub-mm fluxes has been recently reported. In this letter, we show that the correlation is a sensitive probe of grain growth processes. ...Using models of grain growth and drift, we have shown in a companion paper that the observed disc radii trace where the dust grains are large enough to have a significant sub-mm opacity. We show that the observed correlation emerges naturally if the maximum grain size is set by radial drift, implying relatively low values of the viscous α parameter ≲0.001. In this case, the relation has an almost universal normalization, while if the grain size is set by fragmentation the flux at a given radius depends on the dust-to-gas ratio. We highlight two observational consequences of the fact that radial drift limits the grain size. The first is that the dust masses measured from the sub-mm could be overestimated by a factor of a few. The second is that the correlation should be present also at longer wavelengths (e.g. 3mm), with a normalization factor that scales as the square of the observing frequency as in the optically thick case.
ABSTRACT
In this paper, we investigate whether overdensity formation via streaming instability is consistent with recent multiwavelength Atacama Large Millimeter Array (ALMA) observations in the ...Lupus star-forming region. We simulate the local action of streaming instability in 2D using the code athena, and examine the radiative properties at mm wavelengths of the resulting clumpy dust distribution by focusing on two observable quantities: the optically thick fraction ff (in ALMA band 6) and the spectral index α (in bands 3–7). By comparing the simulated distribution in the ff–α plane before and after the action of streaming instability, we observe that clump formation causes ff to drop, because of the suppression of emission from grains that end up in optically thick clumps. α, instead, can either increase or decline after the action of streaming instability; we use a simple toy model to demonstrate that this behaviour depends on the sizes of the grains whose emission is suppressed by being incorporated in optically thick clumps. In particular, the sign of evolution of α depends on whether grains near the opacity maximum at a few tenths of a mm end up in clumps. By comparing the simulation distributions before/after clump formation to the data distribution, we note that the action of streaming instability drives simulations towards the area of the plane where the data are located. We furthermore demonstrate that this behaviour is replicated in integrated disc models provided that the instability is operative over a region of the disc that contributes significantly to the total mm flux.
ABSTRACT Atacama Large Millimetre/submillimetre Array (ALMA) observations of the thermal emission from protoplanetary disc dust have revealed a wealth of substructures that could evidence embedded ...planets, but planet-driven spirals, one of the more compelling lines of evidence, remain relatively rare. Existing works have focused on detecting these spirals using methods that operate in image space. Here, we explore the planet detection capabilities of fitting planet-driven spirals to disc observations directly in visibility space. We test our method on synthetic ALMA observations of planet-containing model discs for a range of disc/observational parameters, finding it significantly outperforms image residuals in identifying spirals in these observations and is able to identify spirals in regions of the parameter space in which no gaps are detected. These tests suggest that a visibility-space fitting approach warrants further investigation and may be able to find planet-driven spirals in observations that have not yet been found with existing approaches. We also test our method on six discs in the Taurus molecular cloud observed with ALMA at 1.33 mm, but find no evidence for planet-driven spirals. We find that the minimum planet masses necessary to drive detectable spirals range from ≈0.03 to $0.5 \, M_{\text{Jup}}$ over orbital radii of 10–100 au, with planet masses below these thresholds potentially hiding in such disc observations. Conversely, we suggest that planets ≳0.5–1 MJup can likely be ruled out over orbital radii of ≈20–$60 \, \text{au}$ on the grounds that we would have detected them if they were present.
Summary Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any ...effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification. Methods In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. We obtained individual participant datasets that included 49 621 participants in all 13 such trials (ten trials of folic acid for prevention of cardiovascular disease n=46 969 and three trials in patients with colorectal adenoma n=2652). All these trials were evenly randomised. The main outcome was incident cancer (ignoring non-melanoma skin cancer) during the scheduled treatment period (among participants who were still free of cancer). We compared those allocated folic acid with those allocated placebo, and used log-rank analyses to calculate the cancer incidence rate ratio (RR). Findings During a weighted average scheduled treatment duration of 5·2 years, allocation to folic acid quadrupled plasma concentrations of folic acid (57·3 nmol/L for the folic acid groups vs 13·5 nmol/L for the placebo groups), but had no significant effect on overall cancer incidence (1904 cancers in the folic acid groups vs 1809 cancers in the placebo groups, RR 1·06, 95% CI 0·99–1·13, p=0·10). There was no trend towards greater effect with longer treatment. There was no significant heterogeneity between the results of the 13 individual trials (p=0·23), or between the two overall results in the cadiovascular prevention trials and the adenoma trials (p=0·13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast, or any other specific site. Interpretation Folic acid supplementation does not substantially increase or decrease incidence of site-specific cancer during the first 5 years of treatment. Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials. Funding British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The NSA report Clarke, Richard A; Clarke, Richard A; Morell, Michael J ...
2014., 20140331, 2014, 2014-03-31
eBook
"We cannot discount the risk, in light of the lessons of our own history, that at some point in the future, high-level government officials will decide that this massive database of extraordinarily ...sensitive private information is there for the plucking. Americans must never make the mistake of wholly 'trusting' our public officials."--The NSA Report
This is the official report that is helping shape the international debate about the unprecedented surveillance activities of the National Security Agency. Commissioned by President Obama following disclosures by former NSA contractor Edward J. Snowden, and written by a preeminent group of intelligence and legal experts, the report examines the extent of NSA programs and calls for dozens of urgent and practical reforms. The result is a blueprint showing how the government can reaffirm its commitment to privacy and civil liberties--without compromising national security.
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