1,011 research outputs found

    The Refractive Index of Curved Spacetime II: QED, Penrose Limits and Black Holes

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    This work considers the way that quantum loop effects modify the propagation of light in curved space. The calculation of the refractive index for scalar QED is reviewed and then extended for the first time to QED with spinor particles in the loop. It is shown how, in both cases, the low frequency phase velocity can be greater than c, as found originally by Drummond and Hathrell, but causality is respected in the sense that retarded Green functions vanish outside the lightcone. A "phenomenology" of the refractive index is then presented for black holes, FRW universes and gravitational waves. In some cases, some of the polarization states propagate with a refractive index having a negative imaginary part indicating a potential breakdown of the optical theorem in curved space and possible instabilities.Comment: 62 pages, 14 figures, some signs corrected in formulae and graph

    Rapid modification of the bone microenvironment following short-term treatment with Cabozantinib in vivo

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    Introduction: Bone metastasis remains incurable with treatment restricted to palliative care. Cabozantinib (CBZ) is targeted against multiple receptor tyrosine kinases involved in tumour pathobiology, including hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR-2). CBZ has demonstrated clinical activity in advanced prostate cancer with resolution of lesions visible on bone scans, implicating a potential role of the bone microenvironment as a mediator of CBZ effects. We characterised the effects of short-term administration of CBZ on bone in a range of in vivo models to determine how CBZ affects bone in the absence of tumour. Methods: Studies were performed in a variety of in vivo models including male and female BALB/c nude mice (age 6– 17-weeks). Animals received CBZ (30 mg/kg, 5× weekly) or sterile H2O control for 5 or 10 days. Effects on bone integrity (ÎŒCT), bone cell activity (PINP, TRAP ELISA), osteoblast and osteoclast number/mm trabecular bone surface, area of epiphyseal growth plate cartilage, megakaryocyte numbers and bone marrow composition were assessed. Effects of longer-term treatment (15-day & 6-week administration) were assessed in male NOD/SCID and beige SCID mice. Results: CBZ treatment had significant effects on the bone microenvironment, including reduced osteoclast and increased osteoblast numbers compared to control. Trabecular bone structure was altered after 8 administrations. A significant elongation of the epiphyseal growth plate, in particular the hypertrophic chondrocyte zone, was observed in all CBZ treated animals irrespective of administration schedule. Both male and female BALB/c nude mice had increased megakaryocyte numbers/mm2 tissue after 10-day CBZ treatment, in addition to vascular ectasia, reduced bone marrow cellularity and extravasation of red blood cells into the extra-vascular bone marrow. All CBZinduced effects were transient and rapidly lost following cessation of treatment. Conclusion: Short-term administration of CBZ induces rapid, reversible effects on the bone microenvironmentin vivo highlighting a potential role in mediating treatment responses

    Functional and molecular analysis of proprioceptive sensory neuron excitability in mice

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    Neurons located in dorsal root ganglia (DRG) are crucial for transmitting peripheral sensations such as proprioception, touch, temperature, and nociception to the spinal cord before propagating these signals to higher brain structures. To date, difficulty in identifying modality-specific DRG neurons has limited our ability to study specific populations in detail. As the calcium-binding protein parvalbumin (PV) is a neurochemical marker for proprioceptive DRG cells we used a transgenic mouse line expressing green fluorescent protein (GFP) in PV positive DRGs, to study the functional and molecular properties of putative proprioceptive neurons. Immunolabeled DRGs showed a 100% overlap between GFP positive (GFP+) and PV positive cells, confirming the PVeGFP mouse accurately labeled PV neurons. Targeted patch-clamp recording from isolated GFP+ and GFP negative (GFP−) neurons showed the passive membrane properties of the two groups were similar, however, their active properties differed markedly. All GFP+ neurons fired a single spike in response to sustained current injection and their action potentials (APs) had faster rise times, lower thresholds and shorter half widths. A hyperpolarization-activated current (Ih) was observed in all GFP+ neurons but was infrequently noted in the GFP− population (100% vs. 11%). For GFP+ neurons, Ih activation rates varied markedly, suggesting differences in the underlying hyperpolarization-activated cyclic nucleotide-gated channel (HCN) subunit expression responsible for the current kinetics. Furthermore, quantitative polymerase chain reaction (qPCR) showed the HCN subunits 2, 1, and 4 mRNA (in that order) was more abundant in GFP+ neurons, while HCN 3 was more highly expressed in GFP− neurons. Likewise, immunolabeling confirmed HCN 1, 2, and 4 protein expression in GFP+ neurons. In summary, certain functional properties of GFP+ and GFP− cells differ markedly, providing evidence for modality-specific signaling between the two groups. However, the GFP+ DRG population demonstrates considerable internal heterogeneity when hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel) properties and subunit expression are considered. We propose this heterogeneity reflects the existence of different peripheral receptors such as tendon organs, muscle spindles or mechanoreceptors in the putative proprioceptive neuron population

    A Bayesian view of the current status of dark matter direct searches

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    Bayesian statistical methods offer a simple and consistent framework for incorporating uncertainties into a multi-parameter inference problem. In this work we apply these methods to a selection of current direct dark matter searches. We consider the simplest scenario of spin-independent elastic WIMP scattering, and infer the WIMP mass and cross-section from the experimental data with the essential systematic uncertainties folded into the analysis. We find that when uncertainties in the scintillation efficiency of Xenon100 have been accounted for, the resulting exclusion limit is not sufficiently constraining to rule out the CoGeNT preferred parameter region, contrary to previous claims. In the same vein, we also investigate the impact of astrophysical uncertainties on the preferred WIMP parameters. We find that within the class of smooth and isotropic WIMP velocity distributions, it is difficult to reconcile the DAMA and the CoGeNT preferred regions by tweaking the astrophysics parameters alone. If we demand compatibility between these experiments, then the inference process naturally concludes that a high value for the sodium quenching factor for DAMA is preferred.Comment: 37 pages, 14 figures and 7 tables. Replacement for matching the version accepted for publicatio

    Nonequilibrium wetting

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    When a nonequilibrium growing interface in the presence of a wall is considered a nonequilibrium wetting transition may take place. This transition can be studied trough Langevin equations or discrete growth models. In the first case, the Kardar-Parisi-Zhang equation, which defines a very robust universality class for nonequilibrium moving interfaces, with a soft-wall potential is considered. While in the second, microscopic models, in the corresponding universality class, with evaporation and deposition of particles in the presence of hard-wall are studied. Equilibrium wetting is related to a particular case of the problem, it corresponds to the Edwards-Wilkinson equation with a potential in the continuum approach or to the fulfillment of detailed balance in the microscopic models. In this review we present the analytical and numerical methods used to investigate the problem and the very rich behavior that is observed with them.Comment: Review, 36 pages, 16 figure

    Multi-Wavelength Observations of a Flux Rope Failed in the Eruption and Associated M-Class Flare from NOAA AR 11045

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    We present the multi-wavelength observations of a flux rope that was trying to erupt from NOAA AR 11045 and the associated M-class solar flare on 12 February 2010 using space and ground based observations from TRACE, STEREO, SOHO/MDI, Hinode/XRT and BBSO. While the flux rope was rising from the active region, an M1.1/2F class flare was triggered nearby one of its footpoints. We suggest that the flare triggering was due to the reconnection of a rising flux rope with the surrounding low-lying magnetic loops. The flux rope reached a projected height of ~0.15 Rs with a speed of ~90 km/s while the soft X-ray flux enhanced gradually during its rise. The flux rope was suppressed by an overlying field and the filled plasma moved towards the negative polarity field to the west of its activation site. We find the first observational evidence of the initial suppression of a flux rope due to a remnant filament visible both at chromospheric and coronal temperatures that evolved couple of days before at the same location in the active region. SOHO/MDI magnetograms show the emergence of a bipole ~12 h prior to the flare initiation. The emerged negative polarity moved towards the flux rope activation site, and flare triggering near the photospheric polarity inversion line (PIL) took place. The motion of the negative polarity region towards PIL helped in the build-up of magnetic energy at the flare and flux rope activation site. This study provides a unique observational evidence of a rising flux rope that failed to erupt due to a remnant filament and overlying magnetic field, as well as associated triggering of an M-class flare.Comment: 20 pages, 11 figures, Sol. Phy

    The Imaging Magnetograph eXperiment (IMaX) for the Sunrise balloon-borne solar observatory

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    The Imaging Magnetograph eXperiment (IMaX) is a spectropolarimeter built by four institutions in Spain that flew on board the Sunrise balloon-borne telesocope in June 2009 for almost six days over the Arctic Circle. As a polarimeter IMaX uses fast polarization modulation (based on the use of two liquid crystal retarders), real-time image accumulation, and dual beam polarimetry to reach polarization sensitivities of 0.1%. As a spectrograph, the instrument uses a LiNbO3 etalon in double pass and a narrow band pre-filter to achieve a spectral resolution of 85 mAA. IMaX uses the high Zeeman sensitive line of Fe I at 5250.2 AA and observes all four Stokes parameters at various points inside the spectral line. This allows vector magnetograms, Dopplergrams, and intensity frames to be produced that, after reconstruction, reach spatial resolutions in the 0.15-0.18 arcsec range over a 50x50 arcsec FOV. Time cadences vary between ten and 33 seconds, although the shortest one only includes longitudinal polarimetry. The spectral line is sampled in various ways depending on the applied observing mode, from just two points inside the line to 11 of them. All observing modes include one extra wavelength point in the nearby continuum. Gauss equivalent sensitivities are four Gauss for longitudinal fields and 80 Gauss for transverse fields per wavelength sample. The LOS velocities are estimated with statistical errors of the order of 5-40 m/s. The design, calibration and integration phases of the instrument, together with the implemented data reduction scheme are described in some detail.Comment: 17 figure

    A systematic review and recommendations for prom instruments for older people with frailty in emergency care

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    Introduction The current service metrics used to evaluate quality in emergency care do not account for specific healthcare outcome goals for older people living with frailty. These have previously been classified under themes of ‘Autonomy’ and ‘Functioning’. There is no person-reported outcome measure (PROM) for older people with frailty and emergency care needs. This study aimed to identify and co-produce recommendations for instruments potentially suitable for use in this population. Methods In this systematic review, we searched six databases for PROMs used between 2010 and 2021 by older people living with frailty receiving acute hospital care. Studies were reviewed against predefined eligibility criteria and appraised for quality using the COSMIN Risk of Bias checklist. Data were extracted to map instrument constructs against an existing framework of acute healthcare outcome goals. Instrument face and content validity were assessed by lay collaborators. Recommendations for instruments with potential emergency care suitability were formed through co-production. Results Of 9392 unique citations screened, we appraised the full texts of 158 studies. Nine studies were identified, evaluating nine PROMs. Quality of included studies ranged from ‘doubtful’ to ‘very good’. Most instruments had strong evidence for measurement properties. PROMs mainly assessed ‘Functioning’ constructs, with limited coverage of ‘Autonomy’. Five instruments were considered too burdensome for the emergency care setting or too specific for older people living with frailty. Conclusions Four PROMs were recommended as potentially suitable for further validation with older people with frailty and emergency care needs: COOP/WONCA charts, EuroQol, McGill Quality of Life (Expanded), and Palliative care Outcome Scale
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