271 research outputs found

    Finding high-order analytic post-Newtonian parameters from a high-precision numerical self-force calculation

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    We present a novel analytic extraction of high-order post-Newtonian (pN) parameters that govern quasi-circular binary systems. Coefficients in the pN expansion of the energy of a binary system can be found from corresponding coefficients in an extreme-mass-ratio inspiral (EMRI) computation of the change ΔU\Delta U in the redshift factor of a circular orbit at fixed angular velocity. Remarkably, by computing this essentially gauge-invariant quantity to accuracy greater than one part in 1022510^{225}, and by assuming that a subset of pN coefficients are rational numbers or products of π\pi and a rational, we obtain the exact analytic coefficients. We find the previously unexpected result that the post-Newtonian expansion of ΔU\Delta U (and of the change ΔΩ\Delta\Omega in the angular velocity at fixed redshift factor) have conservative terms at half-integral pN order beginning with a 5.5 pN term. This implies the existence of a corresponding 5.5 pN term in the expansion of the energy of a binary system. Coefficients in the pN series that do not belong to the subset just described are obtained to accuracy better than 1 part in 10265−23n10^{265-23n} at nnth pN order. We work in a radiation gauge, finding the radiative part of the metric perturbation from the gauge-invariant Weyl scalar ψ0\psi_0 via a Hertz potential. We use mode-sum renormalization, and find high-order renormalization coefficients by matching a series in L=ℓ+1/2L=\ell+1/2 to the large-LL behavior of the expression for ΔU\Delta U. The non-radiative parts of the perturbed metric associated with changes in mass and angular momentum are calculated in the Schwarzschild gauge

    Dilute, derivatise and shoot: Measurement of urinary free metanephrines and catecholamines as ethyl derivatives by LC-MSMS

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    This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (Sept 2017) in accordance with the publisher’s archiving policyBackground The measurement of catecholamines and their metabolites in either urine or plasma is an important diagnostic test used to exclude the presence of neuroendocrine tumours. Because of weak chromatographic retention and potential ion-suppression, reverse-phase LC-MSMS is not ideal for analysis of these polar molecules. Here, we investigate derivatisation by ethylation as an alternative approach. Methods A simple and rapid method involving acetaldehyde and a reducing agent was used to convert urine free metanephrines and catecholamines, and their deuterated analogues as internal standards, to mono-ethyl or diethyl- derivatives. Using an Agilent 6460 triple-quadrupole mass spectrometer, precursor and product ion mass spectra were recorded to allow comparison of multiple reaction monitoring methods for both derivatised and non-derivatised analytes under reverse-phase LC-MSMS conditions with positive electrospray ionization. Results Conversion of biogenic amines to less polar ethyl derivatives increased their mass and enhanced the intensity of their molecular ions and fragments. Ethylation also improved the chromatographic properties of the amines, with greater retention and elution from reverse-phase HPLC columns with a methanol or acetonitrile gradient. The signal response of tandem mass spectrometric detection was increased up to 50-fold for ethyl metanephrines compared to non-derivatised compounds. This increase allowed for the omission of solid-phase extraction of urine as a clean-up step prior to analysis. The ‘dilute-derivatise-shoot’ method maintained analytical performance with respect to between-run imprecision (CV < 6%) and accuracy in an external quality assurance program. Gender-related ranges for free metanephrines in early-morning spot urines, collected from adult patients, were similar using either derivatised or non-derivatised samples. Conclusions The LC-MSMS detection of free urine biogenic amines can be greatly enhanced by ethyl derivatisation, which is easy and rapid to perform. Advantages include improved chromatography and lower limits of quantitation, that negate the requirement for solid-phase clean-up of urine prior to analysis. A disadvantage is the potential toxicity of the derivatising agents used if they are not handled appropriately

    A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors

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    BACKGROUND: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. METHODS: A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. RESULTS: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3–4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3–4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. CONCLUSIONS: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00435916

    Confrontational Behavior and Escalation to War 1816-1980: A Research Plan

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    The understanding of international war, like many complex social events, may be - and has been - ap proached from a range of theoretical perspectives and via a variety of research strategies. Outside of the work of Bloch (1898), Sorokin (1936), Richardson (1941), and Wright (1942), however, there was little re search of a scientific nature until the mid-1960s. And while these past fifteen years have certainly not given us a compelling theory of international war, they have seen a steady growth in cumulative knowledge regar ding the correlates of war. These results, despite the expected mix of inconsistencies and anomalies, provide us with some sense of the factors that are most consistently associated with war over the last century and a half, along with some tentative insights into the rising and declining potency of these factors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68556/2/10.1177_002234338201900104.pd

    An integrative framework for the appraisal of coloration in nature

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    The world in color presents a dazzling dimension of phenotypic variation. Biological interest in this variation has burgeoned, due to both increased means for quantifying spectral information and heightened appreciation for how animals view the world differently than humans. Effective study of color traits is challenged by how to best quantify visual perception in nonhuman species. This requires consideration of at least visual physiology but ultimately also the neural processes underlying perception. Our knowledge of color perception is founded largely on the principles gained from human psychophysics that have proven generalizable based on comparative studies in select animal models. Appreciation of these principles, their empirical foundation, and the reasonable limits to their applicability is crucial to reaching informed conclusions in color research. In this article, we seek a common intellectual basis for the study of color in nature. We first discuss the key perceptual principles, namely, retinal photoreception, sensory channels, opponent processing, color constancy, and receptor noise. We then draw on this basis to inform an analytical framework driven by the research question in relation to identifiable viewers and visual tasks of interest. Consideration of the limits to perceptual inference guides two primary decisions: first, whether a sensory-based approach is necessary and justified and, second, whether the visual task refers to perceptual distance or discriminability. We outline informed approaches in each situation and discuss key challenges for future progress, focusing particularly on how animals perceive color. Given that animal behavior serves as both the basic unit of psychophysics and the ultimate driver of color ecology/evolution, behavioral data are critical to reconciling knowledge across the schools of color research

    Deep Investigation of Neutral Gas Origins (DINGO): HI stacking experiments with early science data

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    We present early science results from Deep Investigation of Neutral Gas Origins (DINGO), an HI survey using the Australian Square Kilometre Array Pathfinder (ASKAP). Using ASKAP sub-arrays available during its commissioning phase, DINGO early science data were taken over ∌\sim 60 deg2^{2} of the Galaxy And Mass Assembly (GAMA) 23 h region with 35.5 hr integration time. We make direct detections of six known and one new sources at z<0.01z < 0.01. Using HI spectral stacking, we investigate the HI gas content of galaxies at 0.04<z<0.090.04 < z< 0.09 for different galaxy colours. The results show that galaxy morphology based on optical colour is strongly linked to HI gas properties. To examine environmental impacts on the HI gas content of galaxies, three sub-samples are made based on the GAMA group catalogue. The average HI mass of group central galaxies is larger than those of satellite and isolated galaxies, but with a lower HI gas fraction. We derive a variety of HI scaling relations for physical properties of our sample, including stellar mass, stellar mass surface density, NUV−rNUV-r colour, specific star formation rate, and halo mass. We find that the derived HI scaling relations are comparable to other published results, with consistent trends also observed to ∌\sim0.5 dex lower limits in stellar mass and stellar surface density. The cosmic HI densities derived from our data are consistent with other published values at similar redshifts. DINGO early science highlights the power of HI spectral stacking techniques with ASKAP.Comment: 27 pages, 25 figures, 10 tables, accepted for publication in MNRA

    Deep Investigation of Neutral Gas Origins (DINGO): HI stacking experiments with early science data

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    We present early science results from Deep Investigation of Neutral Gas Origins (DINGO), an H I survey using the Australian Square Kilometre Array Pathfinder (ASKAP). Using ASKAP subarrays available during its commissioning phase, DINGO early science data were taken over ∌60 deg2 of the Galaxy And Mass Assembly (GAMA) 23 h region with 35.5 h integration time. We make direct detections of six known and one new sources at z \u3c 0.01. Using H I spectral stacking, we investigate the H I gas content of galaxies at 0.04 \u3c z \u3c 0.09 for different galaxy colours. The results show that galaxy morphology based on optical colour is strongly linked to H I gas properties. To examine environmental impacts on the H I gas content of galaxies, three subsamples are made based on the GAMA group catalogue. The average H I mass of group central galaxies is larger than those of satellite and isolated galaxies, but with a lower H I gas fraction. We derive a variety of H I scaling relations for physical properties of our sample, including stellar mass, stellar mass surface density, NUV − r colour, specific star formation rate, and halo mass. We find that the derived H I scaling relations are comparable to other published results, with consistent trends also observed to ∌0.5 dex lower limits in stellar mass and stellar surface density. The cosmic H I densities derived from our data are consistent with other published values at similar redshifts. DINGO early science highlights the power of H I spectral stacking techniques with ASKA
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