Preliminary safety assessment of a membrane-bound delta 9 desaturase candidate protein for transgenic oilseed crops

AbstractA gene encoding delta 9 desaturase (D9DS), an integral membrane protein, is being considered for incorporation into oilseed crops to reduce saturated fatty acids and thus improve human nutritional value. Typically, a safety assessment for transgenic crops involves purifying heterologously produced transgenic proteins in an active form for use in safety studies. Membrane-bound proteins have been very difficult to isolate in an active form due to their inherent physicochemical properties. Described here are methods used to derive enriched preparations of the active D9DS protein for use in early stage safety studies. Results of these studies, in combination with bioinformatic results and knowledge of the mode of action of the protein, along with a history of safe consumption of related proteins, provides a weight of evidence supporting the safety of the D9DS protein in food and feed

LoCuSS: A Comparison of Sunyaev-Zel'dovich Effect and Gravitational Lensing Measurements of Galaxy Clusters

We present the first measurement of the relationship between the Sunyaev-Zel'dovich effect signal and the mass of galaxy clusters that uses gravitational lensing to measure cluster mass, based on 14 X-ray luminous clusters at z~0.2 from the Local Cluster Substructure Survey. We measure the integrated Compton y-parameter, Y, and total projected mass of the clusters (M_GL) within a projected clustercentric radius of 350 kpc, corresponding to mean overdensities of 4000-8000 relative to the critical density. We find self-similar scaling between M_GL and Y, with a scatter in mass at fixed Y of 32%. This scatter exceeds that predicted from numerical cluster simulations, however, it is smaller than comparable measurements of the scatter in mass at fixed T_X. We also find no evidence of segregation in Y between disturbed and undisturbed clusters, as had been seen with T_X on the same physical scales. We compare our scaling relation to the Bonamente et al. relation based on mass measurements that assume hydrostatic equilibrium, finding no evidence for a hydrostatic mass bias in cluster cores (M_GL = 0.98+/-0.13 M_HSE), consistent with both predictions from numerical simulations and lensing/X-ray-based measurements of mass-observable scaling relations at larger radii. Overall our results suggest that the Sunyaev-Zel'dovich effect may be less sensitive than X-ray observations to the details of cluster physics in cluster cores.Comment: Minor changes to match published version: 2009 ApJL 701:114-11

Joint analysis of X-ray and Sunyaev Zel'dovich observations of galaxy clusters using an analytic model of the intra-cluster medium

We perform a joint analysis of X-ray and Sunyaev Zel'dovich (SZ) effect data using an analytic model that describes the gas properties of galaxy clusters. The joint analysis allows the measurement of the cluster gas mass fraction profile and Hubble constant independent of cosmological parameters. Weak cosmological priors are used to calculate the overdensity radius within which the gas mass fractions are reported. Such an analysis can provide direct constraints on the evolution of the cluster gas mass fraction with redshift. We validate the model and the joint analysis on high signal-to-noise data from the Chandra X-ray Observatory and the Sunyaev-Zel'dovich Array for two clusters, Abell 2631 and Abell 2204.Comment: ApJ in pres

LoCuSS: The Sunyaev-Zel'dovich Effect and Weak Lensing Mass Scaling Relation

We present the first weak-lensing-based scaling relation between galaxy cluster mass, M_wl, and integrated Compton parameter Y_sph. Observations of 18 galaxy clusters at z~0.2 were obtained with the Subaru 8.2-m telescope and the Sunyaev-Zel'dovich Array. The M_wl-Y_sph scaling relations, measured at Delta=500, 1000, and 2500 rho_c, are consistent in slope and normalization with previous results derived under the assumption of hydrostatic equilibrium (HSE). We find an intrinsic scatter in M_wl at fixed Y_sph of 20%, larger than both previous measurements of M_HSE-Y_sph scatter as well as the scatter in true mass at fixed Y_sph found in simulations. Moreover, the scatter in our lensing-based scaling relations is morphology dependent, with 30-40% larger M_wl for undisturbed compared to disturbed clusters at the same Y_sph at r_500. Further examination suggests that the segregation may be explained by the inability of our spherical lens models to faithfully describe the three-dimensional structure of the clusters, in particular, the structure along the line-of-sight. We find that the ellipticity of the brightest cluster galaxy, a proxy for halo orientation, correlates well with the offset in mass from the mean scaling relation, which supports this picture. This provides empirical evidence that line-of-sight projection effects are an important systematic uncertainty in lensing-based scaling relations.Comment: Accepted versio

Comparison of Pressure Profiles of Massive Relaxed Galaxy Clusters using Sunyaev-Zel'dovich and X-ray Data

We present Sunyaev-Zel'dovich (SZ) effect observations of a sample of 25 massive relaxed galaxy clusters observed with the Sunyaev-Zel'dovich Array (SZA), an 8-element interferometer that is part of the Combined Array for Research in Millimeter-wave Astronomy (CARMA). We perform an analysis of new SZA data and archival Chandra observations of this sample to investigate the integrated pressure -- a proxy for cluster mass -- determined from X-ray and SZ observations, two independent probes of the intra-cluster medium. This analysis makes use of a model for the intra-cluster medium introduced by Bulbul (2010) which can be applied simultaneously to SZ and X-ray data. With this model, we estimate the pressure profile for each cluster using a joint analysis of the SZ and X-ray data, and using the SZ data alone. We find that the integrated pressures measured from X-ray and SZ data are consistent. This conclusion is in agreement with recent results obtained using WMAP and Planck data, confirming that SZ and X-ray observations of massive clusters detect the same amount of thermal pressure from the intra-cluster medium. To test for possible biases introduced by our choice of model, we also fit the SZ data using the universal pressure profile proposed by Arnaud (2010), and find consistency between the two models out to r500 in the pressure profiles and integrated pressures.Comment: Accepted for New Journal of Physics, Focus Issue on Galaxy Cluster

The linear multiplet and ectoplasm

In the framework of the superconformal tensor calculus for 4D N=2 supergravity, locally supersymmetric actions are often constructed using the linear multiplet. We provide a superform formulation for the linear multiplet and derive the corresponding action functional using the ectoplasm method (also known as the superform approach to the construction of supersymmetric invariants). We propose a new locally supersymmetric action which makes use of a deformed linear multiplet. The novel feature of this multiplet is that it corresponds to the case of a gauged central charge using a one-form potential not annihilated by the central charge (unlike the standard N=2 vector multiplet). Such a gauge one-form can be chosen to describe a variant nonlinear vector-tensor multiplet. As a byproduct of our construction, we also find a variant realization of the tensor multiplet in supergravity where one of the auxiliaries is replaced by the field strength of a gauge three-form.Comment: 31 pages; v3: minor corrections and typos fixed, version to appear in JHE

Safety and Feasibility of a Novel Sparse Optical Coherence Tomography Device for Patient-Delivered Retina Home Monitoring

Purpose To study a novel and fast optical coherence tomography (OCT) device for home-based monitoring in age-related macular degeneration (AMD) in a small sample yielding sparse OCT (spOCT) data and to compare the device to a commercially available reference device. Methods In this prospective study, both eyes of 31 participants with AMD were included. The subjects underwent scanning with an OCT prototype and a spectral-domain OCT to compare the accuracy of the central retinal thickness (CRT) measurements. Results Sixty-two eyes in 31 participants (21 females and 10 males) were included. The mean age was 79.6 years (age range, 69-92 years). The mean difference in the CRT measurements between the devices was 4.52 μm (SD ± 20.0 μm; range, -65.6 to 41.5 μm). The inter- and intrarater reliability coefficients of the OCT prototype were both >0.95. The laser power delivered was <0.54 mW for spOCT and <1.4 mW for SDOCT. No adverse events were reported, and the visual acuity before and after the measurements was stable. Conclusion This study demonstrated the safety and feasibility of this home-based OCT monitoring under real-life conditions, and it provided evidence for the potential clinical benefit of the device. Translational Relevance The newly developed spOCT is a valid and readily available retina scanner. It could be applied as a portable self-measuring OCT system. Its use may facilitate the sustainable monitoring of chronic retinal diseases by providing easily accessible and continuous retinal monitoring

Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81-0·84 for cutaneous only vs 0·84, 0·82-0·85 for antibody only vs 0·84, 0·83-0·86 for combined) or for progression-free survival (0·70, 0·69-0·71 vs 0·71, 0·70-0·72 vs 0·71, 0·70-0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46-0·71 for antibody only vs 0·29, 0·19-0·39 for cutaneous only) and disease progression (0·36, 0·29-0·46 vs 0·21, 0·14-0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70-0·74 for antibody only vs 0·66, 0·64-0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75-0·77 vs 0·71, 0·70-0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P &lt; 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P &lt; 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P &lt; 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P &lt; 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P &lt; 0.001; OR(BP) = 2.4, P &lt; 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P &lt; 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P &lt; 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality