Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth

The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is unknown. We show that pericyte FAK regulates tumour growth and angiogenesis in multiple mouse models of melanoma, lung carcinoma and pancreatic B-cell insulinoma and provide evidence that loss of pericyte FAK enhances Gas6-stimulated phosphorylation of the receptor tyrosine kinase, Axl with an upregulation of Cyr61, driving enhanced tumour growth. We further show that pericyte derived Cyr61 instructs tumour cells to elevate expression of the proangiogenic/protumourigenic transmembrane receptor Tissue Factor. Finally, in human melanoma we show that when 50% or more tumour blood vessels are pericyte-FAK negative, melanoma patients are stratified into those with increased tumour size, enhanced blood vessel density and metastasis. Overall our data uncover a previously unknown mechanism of tumour growth by pericytes that is controlled by pericyte FAK

Starburst Energy Feedback Seen through HCO+/HOC+ Emission in NGC 253 from ALCHEMI

Molecular abundances are sensitive to the UV photon flux and cosmic-ray ionization rate. In starburst environments, the effects of high-energy photons and particles are expected to be stronger. We examine these astrochemical signatures through multiple transitions of HCO+ and its metastable isomer HOC+ in the center of the starburst galaxy NGC 253 using data from the Atacama Large Millimeter/submillimeter Array large program ALMA Comprehensive High-resolution Extragalactic Molecular inventory. The distribution of the HOC+(1−0) integrated intensity shows its association with "superbubbles," cavities created either by supernovae or expanding H ii regions. The observed HCO+/HOC+ abundance ratios are ∼10–150, and the fractional abundance of HOC+ relative to H2 is ∼1.5 × 10−11–6 × 10−10, which implies that the HOC+ abundance in the center of NGC 253 is significantly higher than in quiescent spiral arm dark clouds in the Galaxy and the Galactic center clouds. Comparison with chemical models implies either an interstellar radiation field of G0 ≳ 103 if the maximum visual extinction is ≳5, or a cosmic-ray ionization rate of ζ ≳ 10−14 s−1 (3–4 orders of magnitude higher than that within clouds in the Galactic spiral arms) to reproduce the observed results. From the difference in formation routes of HOC+, we propose that a low-excitation line of HOC+ traces cosmic-ray dominated regions, while high-excitation lines trace photodissociation regions. Our results suggest that the interstellar medium in the center of NGC 253 is significantly affected by energy input from UV photons and cosmic rays, sources of energy feedback

Reconstructing the shock history in the CMZ of NGC 253 with ALCHEMI

Context: HNCO and SiO are well-known shock tracers and have been observed in nearby galaxies, including the nearby (D = 3.5 Mpc) starburst galaxy NGC 253. The simultaneous detection of these two species in regions where the star-formation rate is high may be used to study the shock history of the gas. // Aims: We perform a multi-line molecular study of NGC 253 using the shock tracers SiO and HNCO and aim to characterize its gas properties. We also explore the possibility of reconstructing the shock history in the central molecular zone (CMZ) of the galaxy. // Methods: Six SiO transitions and eleven HNCO transitions were imaged at high resolution 1.″6 (28 pc) with the Atacama Large Millimeter/submillimeter Array (ALMA) as part of the ALCHEMI Large Programme. Both non local thermaldynamic equilibrium (non-LTE) radiative transfer analysis and chemical modeling were performed in order to characterize the gas properties and investigate the chemical origin of the emission. // Results: The nonLTE radiative transfer analysis coupled with Bayesian inference shows clear evidence that the gas traced by SiO has different densities and temperatures than that traced by HNCO, with an indication that shocks are needed to produce both species. Chemical modeling further confirms such a scenario and suggests that fast and slow shocks are responsible for SiO and HNCO production, respectively, in most GMCs. We are also able to infer the physical characteristics of the shocks traced by SiO and HNCO for each GMC. // Conclusions: Radiative transfer and chemical analysis of the SiO and HNCO in the CMZ of NGC 253 reveal a complex picture whereby most of the GMCs are subjected to shocks. We speculate on the possible shock scenarios responsible for the observed emission and provide potential history and timescales for each shock scenario. Observations of higher spatial resolution for these two species are required in order to quantitatively differentiate between the possible scenarios

Perceptions and experiences of using a nipple shield among parents and staff - an ethnographic study in neonatal units

Background: Preterm infants have an immature sucking behavior and the capacity to be exclusively breastfed may be reduced for a period of weeks or months, depending on gestational age. Nipple shields have been used, not only as a device to help mothers with sore nipples, but also to facilitate the infant’s latch on to the breast. However, the benefits of using nipple shields have been debated. The aim of this study was to explore perceptions and experiences of using a nipple shield among parents and staff in neonatal units in Sweden and England. Methods: An ethnographic study was undertaken where observations and interviews were conducted in four neonatal units in Sweden and England. The data were analyzed using a thematic networks analysis. Result: The global theme was developed and named, ‘Nipple shield in a liminal time’. This comprised of two organizing themes: ‘Relational breastfeeding’ and ‘Progression’. ‘Relational breastfeeding’ was underpinned by the basic themes, ‘good enough breast’, ‘something in between’ and ‘tranquil moment’. ‘Progression’ was underpinned by the basic themes, ‘learning quicker’, ‘short-term solution’ and ‘rescue remedy’. Although breastfeeding was seen primarily as a nutritive transaction, the relational aspects of breastfeeding were of crucial importance. These two organizing themes show the tension between acknowledging the relational aspects of breastfeeding and yet facilitating or supporting the progression of breastfeeding in the period from tube feeding or cup feeding to breastfeeding. It is a liminal time as mothers and their infants are “in between” phases and the outcome, in terms of breastfeeding, is yet to be realized. Conclusion: This study demonstrates parents’ and staffs’ perceptions of the nipple shield as a short term solution to help initiation of breastfeeding but also as a barrier between the mother and infant. It is important that the mother and baby’s own particular needs are taken into account, in a person-centred way and on an ongoing basis. Furthermore, we need to emphasise the importance of the ‘relational’ whilst understanding the need for ‘progression’. Holding these in balance may be the key to appropriate use of the nipple shield

Geographic Variability in Access to Primary Kidney Transplantation in the United States, 1996–2005

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75057/1/j.1600-6143.2007.01785.x.pd

Multi-factor service design: identification and consideration of multiple factors of the service in its design process

Service design is a multidisciplinary area that helps innovate services by bringing new ideas to customers through a design-thinking approach. Services are affected by multiple factors, which should be considered in designing services. In this paper, we propose the multi-factor service design (MFSD) method, which helps consider the multi-factor nature of service in the service design process. The MFSD method has been developed through and used in five service design studies with industry and government. The method addresses the multi-factor nature of service for systematic service design by providing the following guidelines: (1) identify key factors that affect the customer value creation of the service in question (in short, value creation factors), (2) define the design space of the service based on the value creation factors, and (3) design services and represent them based on the factors. We provide real stories and examples from the five service design studies to illustrate the MFSD method and demonstrate its utility. This study will contribute to the design of modern complex services that are affected by varied factors

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal