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- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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- Scelo, Ghislaine, et al.
(författare)
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Exploring Definitions and Predictors of Response to Biologics for Severe Asthma
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Ingår i: Journal of Allergy and Clinical Immunology: In Practice. - 2213-2198.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. Objective: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. Methods: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. Results: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. Conclusions: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed. © 2024 The Authors
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- Acharya, B., et al.
(författare)
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Corrections to nucleon capture cross sections computed in truncated Hilbert spaces
- 2017
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 95:3
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Tidskriftsartikel (refereegranskat)abstract
- Nucleon capture cross sections enter various astrophysical processes. The measurement of proton capture on nuclei at astrophysically relevant lowenergies is a challenge, and theoretical computations in this long-wavelength regime are sensitive to the long-distance asymptotics of thewave functions. Atheoretical foundation for estimating and correcting errors introduced in capture cross sections due to Hilbert space truncation has so far been lacking. We derive extrapolation formulas that relate the infrared regularized capture amplitudes to the infinite basis limit and demonstrate their efficacy for proton-proton fusion. Our results are thus relevant to current calculations of few-body capture reactions such as proton-proton fusion or proton capture on the deuteron, and they also open the way for the use of ab initio many-body wave functions represented in finite Hilbert spaces in precision calculations of nucleon capture on heavier nuclei.
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- Pines, A, et al.
(författare)
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PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1
- 2012
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 199:2, s. 235-249
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Tidskriftsartikel (refereegranskat)abstract
- The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how DDB2 promotes NER in chromatin is poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated factor. We demonstrate that DDB2 facilitated poly(ADP-ribosyl)ation of UV-damaged chromatin through the activity of PARP1, resulting in the recruitment of the chromatin-remodeling enzyme ALC1. Depletion of ALC1 rendered cells sensitive to UV and impaired repair of UV-induced DNA lesions. Additionally, DDB2 itself was targeted by poly(ADP-ribosyl)ation, resulting in increased protein stability and a prolonged chromatin retention time. Our in vitro and in vivo data support a model in which poly(ADP-ribosyl)ation of DDB2 suppresses DDB2 ubiquitylation and outline a molecular mechanism for PARP1-mediated regulation of NER through DDB2 stabilization and recruitment of the chromatin remodeler ALC1.
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- Abramowski, A., et al.
(författare)
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TeV gamma-ray observations of the young synchrotron-dominated SNRs G1.9+0.3 and G330.2+1.0 with HESS
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 441:1, s. 790-799
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Tidskriftsartikel (refereegranskat)abstract
- The non-thermal nature of the X-ray emission from the shell-type supernova remnants (SNRs) G1.9+0.3 and G330.2+1.0 is an indication of intense particle acceleration in the shock fronts of both objects. This suggests that the SNRs are prime candidates for very-high-energy (VHE; E > 0.1 TeV) gamma-ray observations. G1.9+0.3, recently established as the youngest known SNR in the Galaxy, also offers a unique opportunity to study the earliest stages of SNR evolution in the VHE domain. The purpose of this work is to probe the level of VHE gamma-ray emission from both SNRs and use this to constrain their physical properties. Observations were conducted with the H. E. S. S. (High Energy Stereoscopic System) Cherenkov Telescope Array over a more than six-year period spanning 2004-2010. The obtained data have effective livetimes of 67 h for G1.9+0.3 and 16 h for G330.2+1.0. The data are analysed in the context of the multiwavelength observations currently available and in the framework of both leptonic and hadronic particle acceleration scenarios. No significant gamma-ray signal from G1.9+0.3 or G330.2+1.0 was detected. Upper limits (99 per cent confidence level) to the TeV flux from G1.9+0.3 and G330.2+1.0 for the assumed spectral index Gamma = 2.5 were set at 5.6 x 10(-1)3 cm(-2) s(-1) above 0.26 TeV and 3.2 x 10(-12) cm(-2) s(-1) above 0.38 TeV, respectively. In a one-zone leptonic scenario, these upper limits imply lower limits on the interior magnetic field to B-G1.9 greater than or similar to 12 mu G for G1.9+0.3 and to B-G330 greater than or similar to 8 mu G for G330.2+1.0. In a hadronic scenario, the low ambient densities and the large distances to the SNRs result in very low predicted fluxes, for which the H.E.S.S. upper limits are not constraining.
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- Rolinska, Monika, 1996-, et al.
(författare)
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Revisiting the applications of the extraction replica sample preparation technique for analysis of precipitates in engineering alloys
- 2022
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Ingår i: Materials Characterization. - : Elsevier BV. - 1044-5803 .- 1873-4189. ; 189, s. 111978-
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Tidskriftsartikel (refereegranskat)abstract
- The extraction replica technique is a useful sample preparation method to fabricate transmission electron microscopy samples for subsequent studies of small particles, such as precipitates, in different types of alloys. With other sample preparation methods, such as thin foil fabrication, the surrounding matrix might influence compositional or crystallographic analysis in the TEM. The extraction replica technique omits that problem, as the precipitates are extracted onto a thin, amorphous film (most commonly carbon) and the influence of the matrix is thus eliminated. The replica can be produced in a direct manner, by a two stage-method or in certain cases by the oxide replica method. A variety of precipitates from common engineering alloys including carbides, nitrides, oxides and various intermetallic phases in steels, nickel-, zirconium-, aluminium-, copper-, and magnesium-based alloys, can be extracted and the techniques are summarized in this work. The choice of etchant is crucial for the end result, as is also showcased experimentally in this work. Furthermore, the direct replica and two-stage replica method are directly compared with each other by new experiments on a low alloyed steel and a zirconium alloy. There are indications that the direct method has a greater particle extraction efficiency of smaller particles compared to the two-stage method. Moreover, the direct method also facilitates the analysis of other features, such as grain boundaries, in special cases.
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