Tracing tumorigenesis in a solid tumor model at single-cell resolution

Characterizing the complex composition of solid tumors is fundamental for understanding tumor initiation, progression and metastasis. While patient-derived samples provide valuable insight, they are heterogeneous on multiple molecular levels, and often originate from advanced tumor stages. Here, we use single-cell transcriptome and epitope profiling together with pathway and lineage analyses to study tumorigenesis from a developmental perspective in a mouse model of salivary gland squamous cell carcinoma. We provide a comprehensive cell atlas and characterize tumor-specific cells. We find that these cells are connected along a reproducible developmental trajectory: initiated in basal cells exhibiting an epithelial-to-mesenchymal transition signature, tumorigenesis proceeds through Wnt-differential cancer stem cell-like subpopulations before differentiating into luminal-like cells. Our work provides unbiased insights into tumor-specific cellular identities in a whole tissue environment, and emphasizes the power of using defined genetic model systems

Present Effects of Past Wildfires on Leaf Litter Breakdown in Stream Ecosystems

We investigated the present effects from a 10-year-old wildfire on leaf litter breakdown rates in 3 headwater streams in central Idaho. These systems experienced a massive debris flow one year after the fire. Based on soil instability and burn patterns, we identified 3 stream conditions: unburned, burned only, and burned/scoured. We placed leaf bags containing willow leaves (Salix sp.) in each stream type and removed bags at various time intervals until all bags were collected 100 days after their introduction. Leaf material was dried and weighed, and decay rate coefficients were calculated. Macroinvertebrates colonizing the bags were enumerated and identified, and selected taxa were placed into trophic groups. We found that the unburned stream had the fastest leaf litter breakdown rate, the lowest level of incident light reaching the stream, and the largest amount of benthic organic matter. The burned/scoured stream was nearly opposite in all respects. Numbers of 2 detritivore invertebrate taxa, Serratella tibialis and Zapada oregonensis, were highest in the unburned stream but lowest in the burned/scoured stream. A third taxon, Baetis sp., showed the opposite relationship. Presence of predatory invertebrates did not affect detritivore abundance or leaf decay rate in the bags. Our research suggests that recovery response variables of some stream systems may not have returned to prefire levels even a decade after the initial wildfire. In this study, the recovery of our streams appears to be connected to the return of the riparian zone, though fire-induced debris flows may slow or alter final recovery of the stream system

An overlooked play? Structure, stratigraphy and hydrocarbon prospectivity of the Carboniferous in the East Irish Sea–North Channel basin complex

Seismic mapping of key Paleozoic surfaces in the East Irish Sea–North Channel region has been incorporated into a review of hydrocarbon prospectivity. The major Carboniferous basinal and inversion elements are identified, allowing an assessment of the principal kitchens for hydrocarbon generation and possible migration paths. A Carboniferous tilt-block is identified beneath the central part of the (Permian–Mesozoic) East Irish Sea Basin (EISB), bounded by carbonate platforms to the south and north. The importance of the Bowland Shale Formation as the key source rock is reaffirmed, the Pennine Coal Measures having been extensively excised following Variscan inversion and pre-Permian erosion. Peak generation from the Bowland source coincided with maximum burial of the system in late Jurassic–early Cretaceous time. Multiphase Variscan inversion generated numerous structural traps whose potential remains underexplored. Leakage of hydrocarbons from these into the overlying Triassic Ormskirk Sandstone reservoirs is likely to have occurred on a number of occasions, but currently unknown is how much resource remains in place below the Base Permian Unconformity. Poor permeability in the Pennsylvanian strata beneath the Triassic fields is a significant risk; the same may not be true in the less deeply buried marginal areas of the EISB, where additional potential plays are present in Mississippian carbonate platforms and latest Pennsylvanian clastic sedimentary rocks. Outside the EISB, the North Channel, Solway and Peel basins also contain Devonian and/or Carboniferous rocks. There have, however, been no discoveries, largely a consequence of the absence of a high-quality source rock and a regional seal comparable to the Mercia Mudstone Group and Permian evaporites of the Cumbrian Coast Group in the EISB

VERITAS: the Very Energetic Radiation Imaging Telescope Array System

The Very Energetic Radiation Imaging Telescope Array System (VERITAS) represents an important step forward in the study of extreme astrophysical processes in the universe. It combines the power of the atmospheric Cherenkov imaging technique using a large optical reflector with the power of stereoscopic observatories using arrays of separated telescopes looking at the same shower. The seven identical telescopes in VERITAS, each of aperture 10 m, will be deployed in a filled hexagonal pattern of side 80 m; each telescope will have a camera consisting of 499 pixels with a field of view of 3.5 deg VERITAS will substantially increase the catalog of very high energy (E > 100GeV) gamma-ray sources and greatly improve measurements of established sources.Comment: 44 pages, 16 figure

Comparing research priority-setting partnerships for older adults across international health care systems: a systematic review

OBJECTIVES: Priority setting partnerships (PSPs) attempt to shape the research agenda to address the needs of local populations of interest. We reviewed the PSPs for older adults, with a focus on exemplar health care systems: United Kingdom (UK; publicly funded), United States (private health insurance-based), South Korea (national health insurance-based), and Africa (out-of-pocket). DESIGN: Systematic review. SETTING AND PARTICIPANTS: We searched databases and sources (January 2011-October 202l; updated in February 2023) for PSPs of older adults' health care. METHODS: Based on the British geriatric medicine curriculum, we extracted and categorized the PSP topics by areas and the research priorities by themes, and generated evidence maps depicting and comparing the research gaps across the systems. We evaluated PSP quality using the Nine Common Themes of Good Clinical Practice. RESULTS: We included 32 PSPs (United Kingdom: n = 25; United States: n = 7; South Korea and Africa: n = 0) and identified priorities regarding 27 conditions or service arrangements in the United Kingdom and 9 in the United States (predominantly in neurology/psychiatry). The UK priorities focused on treatments and interventions whereas the US on prognostic/predictive factors. There were notable research gaps within the existing PSPs, including common geriatric conditions like continence and frailty. The PSP quality evaluation revealed issues around lacking inclusion of ethnic minorities. CONCLUSIONS AND IMPLICATIONS: Research priorities for older adult health care vary internationally, but certain health care systems/countries have no available PSPs. Where PSPs are available, fundamental aspects of geriatric medicine have not been included. Future researchers should conduct prioritizations in different countries, focus on core geriatric syndromes, and ensure the inclusion of all relevant stakeholder groups

Kepler-22b: A 2.4 Earth-radius Planet in the Habitable Zone of a Sun-like Star

A search of the time-series photometry from NASA's Kepler spacecraft reveals a transiting planet candidate orbiting the 11th magnitude G5 dwarf KIC 10593626 with a period of 290 days. The characteristics of the host star are well constrained by high-resolution spectroscopy combined with an asteroseismic analysis of the Kepler photometry, leading to an estimated mass and radius of 0.970 +/- 0.060 MSun and 0.979 +/- 0.020 RSun. The depth of 492 +/- 10ppm for the three observed transits yields a radius of 2.38 +/- 0.13 REarth for the planet. The system passes a battery of tests for false positives, including reconnaissance spectroscopy, high-resolution imaging, and centroid motion. A full BLENDER analysis provides further validation of the planet interpretation by showing that contamination of the target by an eclipsing system would rarely mimic the observed shape of the transits. The final validation of the planet is provided by 16 radial velocities obtained with HIRES on Keck 1 over a one year span. Although the velocities do not lead to a reliable orbit and mass determination, they are able to constrain the mass to a 3{\sigma} upper limit of 124 MEarth, safely in the regime of planetary masses, thus earning the designation Kepler-22b. The radiative equilibrium temperature is 262K for a planet in Kepler-22b's orbit. Although there is no evidence that Kepler-22b is a rocky planet, it is the first confirmed planet with a measured radius to orbit in the Habitable Zone of any star other than the Sun.Comment: Accepted to Ap

Carboniferous petroleum systems around the Mid North Sea High, UK

The existence of an extensive, prospective Visean–Namurian Carboniferous petroleum system in and around the hitherto under-explored Mid North Sea High is documented. Evidence is drawn from integrated analysis of over 50,000 line kilometres of seismic data and well data, together with regional source rock screening, reservoir analysis and basin modelling. Visean-Namurian marine and non-marine mudstones and coal source rocks are interbedded within fluvial and marine reservoir sandstones within a stacked succession up to 5 km thick. Source rocks are dominantly gas-prone with oil-prone intervals, and have reached oil to gas maturity levels dependent on location. Burial/thermal history modelling indicates a kitchen area on the southern margin of the Mid North Sea High with northwest and northeastwards migration of gas and oil during Mesozoic and Cenozoic times. A variety of structural and stratigraphic traps are possible, including intraformational Carboniferous traps, with a regional seal at Permian (Zechstein) level. Synthesis of many previously unpublished datasets demonstrates the Visean–Namurian play south of the Mid North Sea High as part of an extensive petroleum system from the East Irish Sea, across onshore to offshore UK and into The Netherlands sector of the North Sea. The purpose of this synthesis is to highlight future exploration opportunities beneath and northwards of the productive Westphalian Southern North Sea gas basin, and to begin to de-risk the petroleum systems that are exemplified by the lower Carboniferous Breagh Field in a frontier area of the mature North Sea province

Rescattering and chiral dynamics in B\to \rho\pi decay

We examine the role of B^0(\bar B^0) \to \sigma \pi^0 \to \pi^+\pi^- \pi^0 decay in the Dalitz plot analysis of B^0 (\bar B^0) \to \rho\pi \to \pi^+\pi^-\pi^0 decays, employed to extract the CKM parameter \alpha. The \sigma \pi channel is significant because it can break the relationship between the penguin contributions in B\to\rho^0\pi^0, B\to\rho^+\pi^-, and B\to\rho^-\pi^+ decays consequent to an assumption of isospin symmetry. Its presence thus mimics the effect of isospin violation. The \sigma\pi^0 state is of definite CP, however; we demonstrate that the B\to\rho\pi analysis can be generalized to include this channel without difficulty. The \sigma or f_0(400-1200) ``meson'' is a broad I=J=0 enhancement driven by strong \pi\pi rescattering; a suitable scalar form factor is constrained by the chiral dynamics of low-energy hadron-hadron interactions - it is rather different from the relativistic Breit-Wigner form adopted in earlier B\to\sigma\pi and D\to\sigma\pi analyses. We show that the use of this scalar form factor leads to an improved theoretical understanding of the measured ratio Br(\bar B^0 \to \rho^\mp \pi^\pm) / Br(B^-\to \rho^0 \pi^-).Comment: 26 pages, 8 figs, published version. typos fixed, minor change

A Virtual Agent as Vocabulary Trainer: Iconic Gestures Help to Improve Learners’ Memory Performance

An important and often laborious task in foreign language acquisition is vocabulary learning. Research has repeatedly demonstrated that performing iconic gestures together with novel words has a beneficial effect on learning performance. Can these findings be transferred onto virtual agents applied in gesture-supported vocabulary training? We present a study investigating whether iconic gestures performed by a virtual agent and imitated by learners have an impact on verbal memory for words in a foreign language. In a within-subject design we compared participants’ memory performance achieved with the help of a virtual agent and those achieved with the help of a human trainer regarding both short-term learning effects and long-term decay effects. The overall results demonstrate improved memory scores when participants learned with a virtual agent. Especially high performers could profit from gesture-supported training with a virtual agent