We use absolutely calibrated data between 3 and 90 GHz from the 2006 balloon flight of the ARCADE 2 instrument, along with previous measurements at other frequencies, to constrain models of ...extragalactic emission. Such emission is a combination of the cosmic microwave background (CMB) monopole, Galactic foreground emission, the integrated contribution of radio emission from external galaxies, any spectral distortions present in the CMB, and any other extragalactic source. After removal of estimates of foreground emission from our own Galaxy, and an estimated contribution of external galaxies, we present fits to a combination of the flat-spectrum CMB and potential spectral distortions in the CMB. We find 2 Delta *s upper limits to CMB spectral distortions of Delta *m < 6 X 10--4 and |Y ff| < 1 X 10--4. We also find a significant detection of a residual signal beyond that, which can be explained by the CMB plus the integrated radio emission from galaxies estimated from existing surveys. This residual signal may be due to an underestimated galactic foreground contribution, an unaccounted for contribution of a background of radio sources, or some combination of both. The residual signal is consistent with emission in the form of a power law with amplitude 18.4 ? 2.1 K at 0.31 GHz and a spectral index of --2.57 ? 0.05.
Transient receptor potential V2 (TRPV2) has been proposed to be a high-threshold thermosensor. However, further elucidation of the channel properties and physiological role of TRPV2 have been ...hindered by the lack of selective pharmacological tools as well as by the species-dependent differences in the activation of this channel. In the present study, we have used cell-based calcium mobilization and electrophysiological assays to identify and characterize several novel cannabinoid TRPV2 agonists. Among these, cannabidiol was found to be the most robust and potent (EC(50) = 3.7 microM), followed by Delta(9)-tetrahydrocannabinol (EC(50) = 14 microM) and cannabinol (EC(50) = 77.7 microM). We also demonstrated that cannabidiol evoked a concentration-dependent release of calcitonin gene-related peptide (CGRP) from cultured rat dorsal root ganglion neurons in a cannabinoid receptor- and TRPV1-independent manner. Moreover, the cannabidiol-evoked CGRP release depended on extracellular calcium and was blocked by the nonselective TRP channel blocker, ruthenium red. We further provide evidence through the use of small interfering RNA knockdown and repetitive stimulation studies, to show that cannabidiol-evoked CGRP release is mediated, at least in part, by TRPV2. Together, these data suggest not only that TRPV2 may comprise a mechanism whereby cannabidiol exerts its clinically beneficial effects in vivo, but also that TRPV2 may constitute a viable, new drug target.
We present tensor-to-scalar ratio forecasts for GreenPol, a hypothetical ground-based B -mode experiment aiming to survey the cleanest regions of the Northern Galactic Hemisphere at five frequencies ...between 10 and 44 GHz. Its primary science goal would be to measure large-scale cosmic microwave background (CMB) polarization fluctuations at multipoles ℓ ≲ 500, and thereby constrain the primordial tensor-to-scalar ratio r . The observations for the suggested experiment would take place at the Summit Station (72 ° 34N, 38 ° 27W) on Greenland, at an altitude of 3216 m above sea level. For this paper we simulated various experimental setups, and derived limits on the tensor-to-scalar ratio after CMB component separation using a Bayesian component separation implementation called Commander. When combining the proposed experiment with Planck HFI observations for constraining polarized thermal dust emission, we found a projected limit of r < 0.02 at 95% confidence for the baseline configuration. This limit is very robust with respect to a range of important experimental parameters, including sky coverage, detector weighting, foreground priors, among others. Overall, GreenPol would have the possibility to provide deep CMB polarization measurements of the Northern Galactic Hemisphere at low frequencies.
Tropospheric clouds in Antarctica Bromwich, David H.; Nicolas, Julien P.; Hines, Keith M. ...
Reviews of geophysics,
March 2012, Letnik:
50, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Compared to other regions, little is known about clouds in Antarctica. This arises in part from the challenging deployment of instrumentation in this remote and harsh environment and from the ...limitations of traditional satellite passive remote sensing over the polar regions. Yet clouds have a critical influence on the ice sheet's radiation budget and its surface mass balance. The extremely low temperatures, absolute humidity levels, and aerosol concentrations found in Antarctica create unique conditions for cloud formation that greatly differ from those encountered in other regions, including the Arctic. During the first decade of the 21st century, new results from field studies, the advent of cloud observations from spaceborne active sensors, and improvements in cloud parameterizations in numerical models have contributed to significant advances in our understanding of Antarctic clouds. This review covers four main topics: (1) observational methods and instruments, (2) the seasonal and interannual variability of cloud amounts, (3) the microphysical properties of clouds and aerosols, and (4) cloud representation in global and regional numerical models. Aside from a synthesis of the existing literature, novel insights are also presented. A new climatology of clouds over Antarctica and the Southern Ocean is derived from combined measurements of the CloudSat and Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellites. This climatology is used to assess the forecast cloud amounts in 20th century global climate model simulations. While cloud monitoring over Antarctica from space has proved essential to the recent advances, the review concludes by emphasizing the need for additional in situ measurements.
Key Points
CloudSat‐CALIPSO data provide new insight into Antarctic cloud climatology
This data set is used to assess clouds in IPCC global climate models
Direct observations of Antarctic clouds are still limited and urgently needed
In this paper we present the Low Frequency Instrument (LFI), designed and developed as part of the Planck space mission, the ESA programme dedicated to precision imaging of the cosmic microwave ...background (CMB). Planck-LFI will observe the full sky in intensity and polarisation in three frequency bands centred at 30, 44 and 70 GHz, while higher frequencies (100–850 GHz) will be covered by the HFI instrument. The LFI is an array of microwave radiometers based on state-of-the-art indium phosphide cryogenic HEMT amplifiers implemented in a differential system using blackbody loads as reference signals. The front end is cooled to 20 K for optimal sensitivity and the reference loads are cooled to 4 K to minimise low-frequency noise. We provide an overview of the LFI, discuss the leading scientific requirements, and describe the design solutions adopted for the various hardware subsystems. The main drivers of the radiometric, optical, and thermal design are discussed, including the stringent requirements on sensitivity, stability, and rejection of systematic effects. Further details on the key instrument units and the results of ground calibration are provided in a set of companion papers.
Summary Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased ...by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31–1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29–1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40–1·66; p<0·0001) and endometrioid (1·42, 1·20–1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07–1·46, p=0·005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. Funding Medical Research Council, Cancer Research UK.
We use absolutely calibrated data from the ARCADE 2 flight in 2006 July to model Galactic emission at frequencies 3, 8, and 10 GHz. The spatial structure in the data is consistent with a ...superposition of free-free and synchrotron emission. Emission with spatial morphology traced by the Haslam 408 MHz survey has spectral index Delta *bsynch = --2.5 ? 0.1, with free-free emission contributing 0.10 ? 0.01 of the total Galactic plane emission in the lowest ARCADE 2 band at 3.15 GHz. We estimate the total Galactic emission toward the polar caps using either a simple plane-parallel model with csc |b| dependence or a model of high-latitude radio emission traced by the COBE/FIRAS map of C II emission. Both methods are consistent with a single power law over the frequency range 22 MHz to 10 GHz, with total Galactic emission toward the north polar cap T Gal = 10.12 ? 0.90 K and spectral index Delta *b = --2.55 ? 0.03 at reference frequency 0.31 GHz. Emission associated with the plane-parallel structure accounts for only 30% of the observed high-latitude sky temperature, with the residual in either a Galactic halo or an isotropic extragalactic background. The well-calibrated ARCADE 2 maps provide a new test for spinning dust emission, based on the integrated intensity of emission from the Galactic plane instead of cross-correlations with the thermal dust spatial morphology. The Galactic plane intensity measured by ARCADE 2 is fainter than predicted by models without spinning dust and is consistent with spinning dust contributing 0.4 ? 0.1 of the Galactic plane emission at 23 GHz.
Dermatomyositis (DM) is an idiopathic inflammatory myopathy that commonly manifests with proximal muscle weakness and is associated with extramuscular pathology, including characteristic skin lesions ...such as Gottron's papules and heliotrope rash, as well as lung, gastrointestinal, joint, and cardiac involvement. Systemic corticosteroids are a cornerstone of therapy, and more recently intravenous immunoglobulin (IVIG; OCTAGAM®) has been approved by the US Food and Drug Administration for the treatment of adults with DM. Both steroids and IVIG represent nonspecific anti-inflammatory therapy, and more targeted approaches are lacking. Transcriptomics has identified upregulation of interferon (IFN)-regulated genes as key features of both adult DM and juvenile DM (JDM). Accordingly, blocking IFN signalling through inhibition of the Janus kinase (JAK) pathway represents a potential treatment option for DM. Placebo-controlled trial data assessing the use of JAK inhibitors for the treatment of DM are limited; as such, a systematic literature review was undertaken to assess the evidence of JAK inhibitors in the treatment of patients with DM. Terms related to DM and JAK inhibitors were searched using PubMed, Embase, Web of Science, Scopus, and Dimensions to identify peer-reviewed publications reporting patients with DM who were treated with a JAK inhibitor. Baseline demographics, clinical characteristics, and treatment outcome data were extracted. A total of 48 publications reporting 145 unique patients (adult DM, n=84; JDM, n=61) were identified. Among cases of adult DM, 61 of 84 (73%) had refractory skin disease at baseline, and all (61 of 61) reported improvement in cutaneous symptoms. Of patients with adult DM, 16 of 84 (19%) had refractory muscle disease at baseline, and all (16 of 16) reported improvement in muscle symptoms. In patients with adult DM complicated by interstitial lung disease (ILD; n=33), 31 (94%) patients improved with JAK inhibitor treatment. Among cases of JDM with refractory skin disease at baseline (60 of 61), most patients (57 of 60; 95%) showed improvements in skin symptoms after JAK inhibitor treatment. Of patients with JDM with refractory muscle disease at baseline (36 of 61), most (30 of 36; 83%) reported improvement in muscle symptoms. Four patients with JDM and ILD experienced improvement in lung disease activity following treatment with a JAK inhibitor. Among both DM and JDM cases, all patients (17 with DM and 16 with JDM) who had elevated serum IFN and/or IFN-stimulated gene expression at baseline showed reduction in IFN or IFN gene expression. Although the conclusions that can be drawn from this analysis are limited because of the differences in assessments used across publications, overall treatment of patients with DM or JDM with a JAK inhibitor was associated with significant improvement of a wide range of DM manifestations, including skin lesions, muscle weakness, and ILD. Our systematic literature review suggests that JAK inhibitors may be a viable treatment option for DM/JDM, and randomised controlled trials are necessary to confirm these findings.
We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. ...-57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 μK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.
Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific ...risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.