Autoimmune responses against posttranslationally modified antigens are a hallmark of several autoimmune diseases. For example, antibodies against citrullinated protein antigens (ACPA) have shown ...their relevance for the prognosis and diagnosis of rheumatoid arthritis (RA), and have been implicated in disease pathogenesis. It is conceivable that other autoantibody systems, recognizing other posttranslationally modified proteins, are also present in RA. Here, we describe the presence of an autoantibody system that discriminates between citrulline- and homocitrulline-containing antigens in the sera of RA-patients. IgG antibodies recognizing carbamylated (homocitrulline-containing) antigens were present in sera of over 45% of RA-patients. Likewise, anticarbamylated protein (anti-CarP) IgA antibodies were observed in 43% of RA-sera. ACPA and anti-CarP antibodies are distinct autoantibodies because, in selected double-positive patients, the anti-CarP antibody binding to carbamylated antigens could be inhibited by carbamylated antigens, but not by control or citrullinated antigens. Similarly, ACPA-binding to citrullinated antigens could only be inhibited by citrullinated antigens. In line with this observation, 16% of ACPA-negative RA-patients, as measured by a standard ACPA assay, harbored IgG anti-CarP antibodies, whereas 30% of these patients tested positive for IgA anti-CarP antibodies. The presence of anti-CarP antibodies was predictive for a more severe disease course in ACPA-negative patients as measured by radiological progression. Taken together, these data show the presence of a unique autoantibody system recognizing carbamylated, but not citrullinated, protein antigens. These antibodies are predictive for a more severe clinical course in ACPA-negative RA-patients, indicating that anti-CarP antibodies are a unique and relevant serological marker for ACPA-negative RA.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We formulate a general framework for hp-variational physics-informed neural networks (hp-VPINNs) based on the nonlinear approximation of shallow and deep neural networks and hp-refinement via domain ...decomposition and projection onto the space of high-order polynomials. The trial space is the space of neural network, which is defined globally over the entire computational domain, while the test space contains piecewise polynomials. Specifically in this study, the hp-refinement corresponds to a global approximation with a local learning algorithm that can efficiently localize the network parameter optimization. We demonstrate the advantages of hp-VPINNs in both accuracy and training cost for several numerical examples of function approximation and in solving differential equations.
•Development of a general framework for hp-variational physics-informed neural networks•Nonlinear approximation of neural networks, projection onto space of high-order polynomials.•Domain decomposition•Comparison with other methods that use neural networks•Local and global approximations with locally/globally defined test functions.•Different loss functions based on the variational form and integration by parts.•Detailed derivation of the hp-VPINN formulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Planck cosmic microwave background temperature data are best fit with a ΛCDM model that mildly contradicts constraints from other cosmological probes. The South Pole Telescope (SPT) 2540 SPT-SZ ...survey offers measurements on sub-degree angular scales (multipoles ) with sufficient precision to use as an independent check of the Planck data. Here we build on the recent joint analysis of the SPT-SZ and Planck data in Hou et al. by comparing ΛCDM parameter estimates using the temperature power spectrum from both data sets in the SPT-SZ survey region. We also restrict the multipole range used in parameter fitting to focus on modes measured well by both SPT and Planck, thereby greatly reducing sample variance as a driver of parameter differences and creating a stringent test for systematic errors. We find no evidence of systematic errors from these tests. When we expand the maximum multipole of SPT data used, we see low-significance shifts in the angular scale of the sound horizon and the physical baryon and cold dark matter densities, with a resulting trend to higher Hubble constant. When we compare SPT and Planck data on the SPT-SZ sky patch to Planck full-sky data but keep the multipole range restricted, we find differences in the parameters ns and . We perform further checks, investigating instrumental effects and modeling assumptions, and we find no evidence that the effects investigated are responsible for any of the parameter shifts. Taken together, these tests reveal no evidence for systematic errors in SPT or Planck data in the overlapping sky coverage and multipole range and at most weak evidence for a breakdown of ΛCDM or systematic errors influencing either the Planck data outside the SPT-SZ survey area or the SPT data at .
To determine the benefit of sequential cochlear implantation after a long inter-implantation interval in children with bilateral deafness receiving their second implant between 5 and 18 years of age. ...Tertiary multicenter. 85 children with bilateral deafness and unilateral implantation receiving a contralateral cochlear implant at the age of 5 to 18 years. The primary outcomes were speech recognition in quiet and noise (CVC) scores. The secondary outcomes were language outcomes and subjective hearing abilities, all measured before and 12 months after sequential bilateral cochlear implantation. Medians of the paired data were compared using the Wilcoxon signed-rank test. Univariable linear regression analyses was used to analyze associations between variables and performance outcomes. A significant benefit was found for speech recognition in quiet (96% 89-98 vs 91% 85-96; p < 0.01) and noise (65% 57-75 vs 54% 47-71; p = 0.01) in the bilateral CI condition compared to unilateral (n = 75, excluded 10 non-users). No benefit was seen for language outcomes. The subjective sound quality score was statistically significant higher in bilateral compared to the unilateral CI condition. Pre-operative residual hearing level in the ear of the second implant, the inter-implant interval and age at time of second implantation was not significantly associated with performance scores. After 12 months of use, sequential bilateral cochlear implantation showed improved speech perception in quiet and noise and improved subjective sound quality outcomes in children despite a great inter-implantation interval (median of 8 years range 1-16 years).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a measurement of the angular power spectrum of the cosmic microwave background (CMB) using data from the South Pole Telescope (SPT). The data consist of 790 deg2 of sky observed at 150 GHz ...during 2008 and 2009. Here we present the power spectrum over the multipole range 650 < l < 3000, where it is dominated by primary CMB anisotropy. We combine this power spectrum with the power spectra from the seven-year Wilkinson Microwave Anisotropy Probe (WMAP) data release to constrain cosmological models. We find that the SPT and WMAP data are consistent with each other and, when combined, are well fit by a spatially flat, Delta *LCDM cosmological model. The SPT+WMAP constraint on the spectral index of scalar fluctuations is ns = 0.9663 ? 0.0112. We detect, at ~5 Delta *s significance, the effect of gravitational lensing on the CMB power spectrum, and find its amplitude to be consistent with the Delta *LCDM cosmological model. We explore a number of extensions beyond the Delta *LCDM model. Each extension is tested independently, although there are degeneracies between some of the extension parameters. We constrain the tensor-to-scalar ratio to be r < 0.21 (95% CL) and constrain the running of the scalar spectral index to be dns /dln k = --0.024 ? 0.013. We strongly detect the effects of primordial helium and neutrinos on the CMB; a model without helium is rejected at 7.7 Delta *s, while a model without neutrinos is rejected at 7.5 Delta *s. The primordial helium abundance is measured to be Yp = 0.296 ? 0.030, and the effective number of relativistic species is measured to be N eff = 3.85 ? 0.62. The constraints on these models are strengthened when the CMB data are combined with measurements of the Hubble constant and the baryon acoustic oscillation feature. Notable improvements include ns = 0.9668 ? 0.0093, r < 0.17 (95% CL), and N eff = 3.86 ? 0.42. The SPT+WMAP data show a mild preference for low power in the CMB damping tail, and while this preference may be accommodated by models that have a negative spectral running, a high primordial helium abundance, or a high effective number of relativistic species, such models are disfavored by the abundance of low-redshift galaxy clusters.
We report cosmic microwave background (CMB) power-spectrum measurements from the first 100 deg{sup 2} field observed by the South Pole Telescope (SPT) at 150 and 220 GHz. On angular scales where the ...primary CMB anisotropy is dominant, l {approx}< 3000, the SPT power spectrum is consistent with the standard {Lambda}CDM cosmology. On smaller scales, we see strong evidence for a point-source contribution, consistent with a population of dusty, star-forming galaxies. After we mask bright point sources, anisotropy power on angular scales of 3000 < l < 9500 is detected with a signal-to-noise ratio {approx}>50 at both frequencies. We combine the 150 and 220 GHz data to remove the majority of the point-source power and use the point-source-subtracted spectrum to detect Sunyaev-Zel'dovich (SZ) power at 2.6{sigma}. At l = 3000, the SZ power in the subtracted bandpowers is 4.2 {+-} 1.5 {mu}K{sup 2}, which is significantly lower than the power predicted by a fiducial model using WMAP5 cosmological parameters. This discrepancy may suggest that contemporary galaxy cluster models overestimate the thermal pressure of intracluster gas. Alternatively, this result can be interpreted as evidence for lower values of {sigma}{sub 8}. When combined with an estimate of the kinetic SZ contribution, the measured SZ amplitude shifts {sigma}{sub 8} from the primary CMB anisotropy derived constraint of 0.794 {+-} 0.028 down to 0.773 {+-} 0.025. The uncertainty in the constraint on {sigma}{sub 8} from this analysis is dominated by uncertainties in the theoretical modeling required to predict the amplitude of the SZ power spectrum for a given set of cosmological parameters.
We present a catalog of emissive point sources detected in the SPT-SZ survey, a contiguous 2530 square degree area surveyed with the South Pole Telescope (SPT) from 2008-2011 in three bands centered ...at 95, 150, and 220 GHz. The catalog contains 4845 sources measured at a significance of 4.5 or greater in at least one band, corresponding to detections above approximately 9.8, 5.8, and 20.4 mJy in 95, 150, and 220 GHz, respectively. The spectral behavior in the SPT bands is used for source classification into two populations based on the underlying physical mechanisms of compact, emissive sources that are bright at millimeter wavelengths: synchrotron radiation from active galactic nuclei and thermal emission from dust. The latter population includes a component of high-redshift sources often referred to as submillimeter galaxies (SMGs). In the relatively bright flux ranges probed by the survey, these sources are expected to be magnified by strong gravitational lensing. The survey also contains sources consistent with protoclusters, groups of dusty galaxies at high redshift undergoing collapse. We cross-match the SPT-SZ catalog with external catalogs at radio, infrared, and X-ray wavelengths and identify available redshift information. The catalog splits into 3980 synchrotron-dominated and 865 dust-dominated sources, and we determine a list of 506 SMGs. Ten sources in the catalog are identified as stars. We calculate number counts for the full catalog, and synchrotron and dusty components, using a bootstrap method and compare our measured counts with models. This paper represents the third and final catalog of point sources in the SPT-SZ survey.
Ferroptosis is a form of cell death that results from the catastrophic accumulation of lipid reactive oxygen species (ROS). Oncogenic signaling elevates lipid ROS production in many tumor types and ...is counteracted by metabolites that are derived from the amino acid cysteine. In this work, we show that the import of oxidized cysteine (cystine) via system x
is a critical dependency of pancreatic ductal adenocarcinoma (PDAC), which is a leading cause of cancer mortality. PDAC cells used cysteine to synthesize glutathione and coenzyme A, which, together, down-regulated ferroptosis. Studying genetically engineered mice, we found that the deletion of a system x
subunit,
, induced tumor-selective ferroptosis and inhibited PDAC growth. This was replicated through the administration of cyst(e)inase, a drug that depletes cysteine and cystine, demonstrating a translatable means to induce ferroptosis in PDAC.
We present the first three-frequency South Pole Telescope (SPT) cosmic microwave background (CMB) power spectra. The band powers presented here cover angular scales 2000 < l < 9400 in frequency bands ...centered at 95, 150, and 220 GHz. At these frequencies and angular scales, a combination of the primary CMB anisotropy, thermal and kinetic Sunyaev-Zel'dovich (SZ) effects, radio galaxies, and cosmic infrared background (CIB) contributes to the signal. We combine Planck/HFI and SPT data at 220 GHz to constrain the amplitude and shape of the CIB power spectrum and find strong evidence for nonlinear clustering. We explore the SZ results using a variety of cosmological models for the CMB and CIB anisotropies and find them to be robust with one exception: allowing for spatial correlations between the thermal SZ effect and CIB significantly degrades the SZ constraints. Neglecting this potential correlation, we find the thermal SZ power at 150 GHz and l = 3000 to be 3.65 + or - 0.69 mu K super(2), and set an upper limit on the kinetic SZ power to be less than 2.8 mu K super(2) at 95% confidence. When a correlation between the thermal SZ and CIB is allowed, we constrain a linear combination of thermal and kinetic SZ power: D super(tSZ) sub(3000) + 0.5D sub(3000) super(kSZ) = 4.60 + or - 0.63 mu K super(2), consistent with earlier measurements. We use the measured thermal SZ power and an analytic, thermal SZ model calibrated with simulations to determine sigma sub(8) = 0.807 + or - 0.016. Modeling uncertainties involving the astrophysics of the intracluster medium rather than the statistical uncertainty in the measured band powers are the dominant source of uncertainty on sigma sub(8). We also place an upper limit on the kinetic SZ power produced by patchy reionization; a companion paper uses these limits to constrain the reionization history of the universe.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted) We present measurements of secondary cosmic microwave background (CMB) anisotropies and cosmic infrared background (CIB) fluctuations ...using data from the South Pole Telescope (SPT) covering the complete 2540 deg super(2) SPT-SZ survey area. Data in the three SPT-SZ frequency bands centered at 95, 150, and 220 GHz, are used to produce six angular power spectra (three single-frequency auto-spectra and three cross-spectra) covering the multipole range 2000 < l < 11,000 (angular scales 5' > ~ straighttheta > ~ 1'). These are the most precise measurements of the angular power spectra at l > 2500 at these frequencies. The main contributors to the power spectra at these angular scales and frequencies are the primary CMB, CIB, thermal and kinematic Sunyaev-Zel'dovich effects (tSZ and kSZ), and radio galaxies. We include a constraint on the tSZ power from a measurement of the tSZ bispectrum from 800 deg super(2) of the SPT-SZ survey. We measure the tSZ power at 143 GHz to be ... mu K super(2) and the kSZ power to be ... mu K super(2). The data prefer positive kSZ power at 98.1% CL. We measure a correlation coefficient of ... between sources of tSZ and CIB power, with xi < 0 disfavored at a confidence level of 99.0%. The constraint on kSZ power can be interpreted as an upper limit on the duration of reionization. When the post-reionization homogeneous kSZ signal is accounted for, we find an upper limit on the duration Delta z < 5.4 at 95% CL.
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