INTEGRAL Observations of GW170104 Savchenko, V.; Ferrigno, C.; Bozzo, E. ...
Astrophysical journal. Letters,
09/2017, Volume:
846, Issue:
2
Journal Article
Peer reviewed
Open access
We used data from the International Gamma-Ray Astrophysics Laboratory (INTEGRAL) to set upper limits on the γ-ray and hard X-ray prompt emission associated with the gravitational-wave event GW170104, ...discovered by the Laser Interferometer Gravitational-wave Observatory (LIGO)/Virgo collaboration. The unique omnidirectional viewing capability of the instruments on board INTEGRAL allowed us to examine the full 90% confidence level localization region of the LIGO trigger. Depending on the particular spectral model assumed and the specific position within this region, the upper limits inferred from the INTEGRAL observations range from Fγ = 1.9 × 10−7 erg cm−2 to Fγ = 10−6 erg cm−2 (75 keV-2 MeV energy range). This translates into a ratio between the prompt energy released in γ-rays along the direction to the observer and the gravitational-wave energy of Eγ/EGW < 2.6 × 10−5. Using the INTEGRAL results, we cannot confirm the γ-ray proposed counterpart to GW170104 by the Astro-Rivelatore Gamma a Immagini Leggero (AGILE) team with the mini-Calorimeter (MCAL) instrument. The reported flux of the AGILE/MCAL event, E2, is not compatible with the INTEGRAL upper limits within most of the 90% LIGO localization region. There is only a relatively limited portion of the sky where the sensitivity of the INTEGRAL instruments was not optimal and the lowest-allowed fluence estimated for E2 would still be compatible with the INTEGRAL results. This region was also observed independently by Fermi/Gamma-ray Burst Monitor and AstroSAT, from which, as far as we are aware, there are no reports of any significant detection of a prompt high-energy event.
We used data from the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) to set upper-limits on the \({\gamma}\)-ray and hard X-ray prompt emission associated with the gravitational wave ...event GW170104, discovered by the LIGO/Virgo collaboration. The unique omni-directional viewing capability of the instruments on-board INTEGRAL allowed us to examine the full 90% confidence level localization region of the LIGO trigger. Depending on the particular spectral model assumed and the specific position within this region, the upper limits inferred from the INTEGRAL observations range from F\({\gamma}\)=1.9x10-7 erg cm-2 to F\({\gamma}\)=10-6 erg cm-2 (75 keV - 2 MeV energy range). This translates into a ratio between the prompt energy released in \({\gamma}\)-rays along the direction to the observer and the gravitational wave energy of E\({\gamma}\)/EGW <2.6x10-5 . Using the INTEGRAL results, we can not confirm the \({\gamma}\)-ray proposed counterpart to GW170104 by the AGILE team with the MCAL instrument. The reported flux of the AGILE/MCAL event, E2, is not compatible with the INTEGRAL upper limits within most of the 90% LIGO localization region. There is only a relatively limited portion of the sky where the sensitivity of the INTEGRAL instruments was not optimal and the lowest allowed fluence estimated for E2 would still be compatible with the INTEGRAL results. This region was also observed independently by Fermi/GBM and AstroSAT, from which, as far as we are aware, there are no reports of any significant detection of a prompt high-energy event.
Consumer acceptability of beers is influenced by product formulation and processing conditions, which impart unique sensory profiles. This study used multivariate techniques to evaluate at‐home ...consumer sensory acceptability of six commercial beers considering their style, fermentation type, and chemical composition. Samples included top‐fermented beers (American India Pale Ale and Stout) and bottom‐fermented beers (Pilsner, zero‐alcohol Pilsner, Vienna Lager, and Munich Dunkel). Beer consumers (n = 50) conducted sensory hedonic, check‐all‐that‐apply (CATA) and just‐about‐right (JAR) tests. Chemometric variables included iso‐alpha‐acids, hordenine, and volatile aromatic compounds, quantified by chromatographic methods, whereas bitterness units (IBU) were determined spectrophotometrically. Lager beers had higher acceptability than top‐fermented beer (p < .05) for all attributes. Light‐colored beers and medium‐height foams had the highest liking scores for visual sensory attributes. Higher concentrations of bitter‐tasting molecules, hordenine, and acidity decreased the liking scores of top‐fermented (Ale) beers, as a sensory penalty analysis suggested. In contrast, the most favored beers (Pilsners and Munich Dunkel) contained higher fusel alcohol esters linked to fruity aromatic notes. Although a low conversion rate of fatty acids into fruity esters was noted in nonalcoholic Pilsner, its overall liking score was not statistically different from the alcoholic version. However, consumers perceived the nonalcoholic Pilsner as less bitter than its alcoholic counterpart even when IBUs were nonsignificantly different. This study emphasized the significance of understanding beer chemometrics to comprehend consumer acceptability, highlighting the crucial role of bitter molecules. Hence, hordenine, acidity, and volatile contents provided additional and valuable insights into consumer preferences.
Most liked beers (Pilsners and Munich Dunkel) contained higher fusel alcohol esters linked to fruity aromatic notes. Consumers penalized top fermentation beers characterized by higher concentrations of bitter molecules and hordenine. Light‐colored and medium‐height foam were the highest scored sensory visual attributes.
Getting back to nature Annunziata, Maria Grazia; Apelt, Federico; Carillo, Petronia ...
Journal of experimental botany,
07/2017, Volume:
68, Issue:
16
Journal Article
Peer reviewed
Open access
Irradiance from sunlight changes in a sinusoidal manner during the day, with irregular fluctuations due to clouds, and light–dark shifts at dawn and dusk are gradual. Experiments in controlled ...environments typically expose plants to constant irradiance during the day and abrupt light–dark transitions. To compare the effects on metabolism of sunlight versus artificial light regimes, Arabidopsis thaliana plants were grown in a naturally illuminated greenhouse around the vernal equinox, and in controlled environment chambers with a 12-h photoperiod and either constant or sinusoidal light profiles, using either white fluorescent tubes or light-emitting diodes (LEDs) tuned to a sunlight-like spectrum as the light source. Rosettes were sampled throughout a 24-h diurnal cycle for metabolite analysis. The diurnal metabolite profiles revealed that carbon and nitrogen metabolism differed significantly between sunlight and artificial light conditions. The variability of sunlight within and between days could be a factor underlying these differences. Pairwise comparisons of the artificial light sources (fluorescent versus LED) or the light profiles (constant versus sinusoidal) showed much smaller differences. The data indicate that energy-efficient LED lighting is an acceptable alternative to fluorescent lights, but results obtained from plants grown with either type of artificial lighting might not be representative of natural conditions.
Objectives This study sought to investigate the technical feasibility and safety of the transaortic (TAO) transcatheter aortic valve replacement (TAVR) approach in patients not eligible for ...transfemoral (TF) access by using a device commercially available in the United States. Background A large proportion of candidates for TAVR have inadequate iliofemoral vessels for TF access. The transapical route (TAP) is the current alternative but is associated with less favorable outcomes. Other access options need to be explored. Methods Forty-four consecutive patients with inoperable, severe aortic stenosis underwent TAO TAVR in our institution. Procedural and 30-day clinical outcomes data were compared with data from 76 consecutive patients who underwent TAP TAVR at our site. Technical learning curves were assessed by comparing outcomes of the first 20 cases with the subsequent patients who underwent each procedure. Results The TAO and TAP TAVR groups were similar in terms of device success according to Valve Academic Research Consortium criteria (89% vs. 84%; p = 0.59) and rates of the 30-day combined safety endpoint of all-cause mortality, myocardial infarction, major stroke, disabling bleeding, severe acute kidney injury, and valve reintervention (20% vs. 33%; p = 0.21). The TAO approach, compared with TAP TAVR, was associated with lower combined bleeding and vascular event rate (27% vs. 46%; p = 0.05), shorter median intensive care unit length of stay (3 vs. 6 days; p = 0.01), and a favorable learning curve. Conclusions TAVR via the TAO approach is technically feasible, seems to be associated with favorable outcomes, and expands the current alternative options for access sites in patients with inoperable aortic stenosis who are ineligible for TF TAVR.
The multi-attribute method (MAM) is a liquid chromatography-mass spectrometry (LC-MS)-based method that is used to directly characterize and monitor numerous product quality attributes (PQAs) at the ...amino acid level of a biopharmaceutical product. MAM enables identity testing based on primary sequence verification, detection and quantitation of post-translational modifications and impurities. This ability to simultaneously and directly determine PQAs of therapeutic proteins makes MAM a more informative, streamlined and productive workflow than conventional chromatographic and electrophoretic assays. MAM relies on proteolytic digestion of the sample followed by reversed-phase chromatographic separation and high-resolution LC-MS analysis in two phases. First, a discovery study to determine quality attributes for monitoring is followed by the creation of a targeted library based on high-resolution retention time plus accurate mass analysis. The second aspect of MAM is the monitoring phase based on the target peptide library and new peak detection using differential analysis of the data to determine the presence, absence or change of any species that might affect the activity or stability of the biotherapeutic. The sample preparation process takes between 90 and 120 min, whereas the time spent on instrumental and data analyses might vary from one to several days for different sample sizes, depending on the complexity of the molecule, the number of attributes to be monitored and the information to be detailed in the final report. MAM is developed to be used throughout the product life cycle, from process development through upstream and downstream processes to quality control release or under current good manufacturing practices regulations enforced by regulatory agencies.
The multi-attribute method (MAM) is a liquid chromatography–mass spectrometry based method that is used to directly characterize and monitor many product quality attributes and impurities on ...biotherapeutics, most commonly at the peptide level. It utilizes high-resolution accurate mass spectral data which are analyzed in an automated fashion. MAM is a promising approach that is intended to replace or supplement several conventional assays with a single LC-MS analysis and can be implemented in a Current Good Manufacturing Practice environment. MAM provides accurate site-specific quantitation information on targeted attributes and the nontargeted new peak detection function allows to detect new peaks as impurities, modifications, or sequence variants when comparing to a reference sample. The high resolution MAM workflow was applied here for three independent case studies. First, to monitor the behavior of monoclonal antibody product quality attributes over the course of a 12-day cell culture experiment providing an insight into the behavior and dynamics of product attributes throughout the process. Second, the workflow was applied to test the purity and identity of a product through analysis of samples spiked with host cell proteins. Third, through the comparison of a drug product and a biosimilar with known sequence variants. The three case studies presented here, clearly demonstrate the robustness and accuracy of the MAM workflow that implies suitability for deployment in the regulated environment.
Peptide mapping analysis is a regulatory expectation to verify the primary structure of a recombinant product sequence and to monitor post-translational modifications (PTMs). Although proteolytic ...digestion has been used for decades, it remains a labour-intensive procedure that can be challenging to accurately reproduce. Here, we describe a fast and reproducible protocol for protease digestion that is automated using immobilised trypsin on magnetic beads, which has been incorporated into an optimised peptide mapping workflow to show method transferability across laboratories. The complete workflow has the potential for use within a multi-attribute method (MAM) approach in drug development, production and QC laboratories. The sample preparation workflow is simple, ideally suited to inexperienced operators and has been extensively studied to show global applicability and robustness for mAbs by performing sample digestion and LC-MS analysis at four independent sites in Europe. LC-MS/MS along with database searching was used to characterise the protein and determine relevant product quality attributes (PQAs) for further testing. A list of relevant critical quality attributes (CQAs) was then established by creating a peptide workbook containing the specific mass-to-charge (m/z) ratios of the modified and unmodified peptides of the selected CQAs, to be monitored in a subsequent test using LC-MS analysis. Data is provided that shows robust digestion efficiency and low levels of protocol induced PTMs.
Graphical abstract
Biosimilarity assessment requires extensive characterization and comparability exercises to investigate product quality attributes of an originator product and its potential biosimilar(s) and to ...highlight any differences between them. Performing a thorough comparison allows a shortened approval path, which also eliminates lengthy and expensive clinical trials, ensuring comparable product quality and efficacy but at lower drug prices. The wide variety of analytical methods available for biosimilar assessment ranges from biological to analytical assays, each providing orthogonal information to fully characterize biosimilar candidates. Intact native mass spectrometry (MS) has been shown to be an excellent tool for detection and monitoring of important quality attributes such as N-glycosylation, deamidation, sequence truncation and higher order structures. When combined with efficient upfront separation methods, simplification of the proteoform heterogeneity and associated complexity prior to MS analysis can be achieved. Native mass spectrometry can provide robust and accurate results within short analysis times and requires minimal sample preparation. In this study we report the use of a monodisperse strong cation exchange chromatography phase hyphenated with Orbitrap mass spectrometry (SCX-MS) to compare the best-selling biopharmaceutical product Humira® with 7 commercially approved biosimilar products. SCX-MS analysis allowed for the identification of previously described as well as so far unreported proteoforms and their relative quantitation across all samples, revealing differences in N-glycosylation and lysine truncation, as well as unique features for some products such as sialylation and N-terminal clipping. SCX-MS analysis, powered by a highly efficient separation column, enabled deep and efficient analytical comparison of biosimilar products.
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•Analytical comparability of adalimumab biosimilars was performed via SCX-MS analysis.•Monodisperse 3 µm particle column enables easy comparison of complex charge variant profiles.•Adalimumab originator was compared with 7 commercially available biosimilars.•Quantitation and identification of 42 proteoforms, including species never reported previously was accomplished.
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