We present the spectroscopic evolution of AT 2017gfo, the optical counterpart of the first binary neutron star (BNS) merger detected by LIGO and Virgo, GW170817. While models have long predicted that ...a BNS merger could produce a kilonova (KN), we have not been able to definitively test these models until now. From one day to four days after the merger, we took five spectra of AT 2017gfo before it faded away, which was possible because it was at a distance of only 39.5 Mpc in the galaxy NGC 4993. The spectra evolve from blue (∼6400 K) to red (∼3500 K) over the three days we observed. The spectra are relatively featureless-some weak features exist in our latest spectrum, but they are likely due to the host galaxy. However, a simple blackbody is not sufficient to explain our data: another source of luminosity or opacity is necessary. Predictions from simulations of KNe qualitatively match the observed spectroscopic evolution after two days past the merger, but underpredict the blue flux in our earliest spectrum. From our best-fit models, we infer that AT 2017gfo had an ejecta mass of 0.03 M , high ejecta velocities of 0.3c, and a low mass fraction ∼10−4 of high-opacity lanthanides and actinides. One possible explanation for the early excess of blue flux is that the outer ejecta is lanthanide-poor, while the inner ejecta has a higher abundance of high-opacity material. With the discovery and follow-up of this unique transient, combining gravitational-wave and electromagnetic astronomy, we have arrived in the multi-messenger era.
Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of ...CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening.
We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry.
In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62–0.64) for men and 0.62 (95% confidence interval, 0.61–0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk.
We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies.
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Towards an Intelligent Observatory Potter, Stephen B
Anais da Academia Brasileira de Ciências,
01/2021, Letnik:
93, Številka:
suppl 1
Journal Article
Recenzirano
Odprti dostop
The Intelligent Observatory (IO) refers to the vision of the South African Astronomical Observatory (SAAO) to meet the scientific needs of both the South African and international astronomical ...communities by providing a better and more efficient service. The idea behind the IO is to harmonise the astronomical operations of all the hosted and local astronomical facilities on the Sutherland Plateau. The vision requires both upgrades to some of the telescopes and a re-design of the current Sutherland operations model. The primary science driver, for the IO, is time-domain and transient science.
Abstract
We report on SALT low-resolution optical spectroscopy and optical/IR photometry undertaken with other SAAO telescopes (MASTER-SAAO and IRSF) of the kilonova AT 2017gfo (a.k.a. SSS17a) in the ...galaxy NGC4993 during the first 10 d of discovery. This event has been identified as the first ever electromagnetic counterpart of a gravitational wave event, namely GW170817, which was detected by the LIGO and Virgo gravitational wave observatories. The event is likely due to a merger of two neutron stars, resulting in a kilonova explosion. SALT was the third observatory to obtain spectroscopy of AT 2017gfo and the first spectrum, 1.2 d after the merger, is quite blue and shows some broad features, but no identifiable spectral lines and becomes redder by the second night. We compare the spectral and photometric evolution with recent kilonova simulations and conclude that they are in qualitative agreement for post-merger wind models with proton:nucleon ratios of Ye = 0.25–0.30. The blue colour of the first spectrum is consistent with the lower opacity of the lanthanide-free r-process elements in the ejecta. Differences between the models and observations are likely due to the choice of system parameters combined with the absence of atomic data for more elements in the ejecta models.
Structural snapshots of protein/ligand complexes are a prerequisite for gaining atomic level insight into enzymatic reaction mechanisms. An important group of enzymes has been deprived of this ...analytical privilege: members of the protein tyrosine phosphatase (PTP) superfamily with catalytic WPD-loops lacking the indispensable general-acid/base within a tryptophan-proline-aspartate/glutamate context. Here, we provide the ligand/enzyme crystal complexes for one such PTP outlier: Arabidopsis thaliana Plant and Fungi Atypical Dual Specificity Phosphatase 1 (AtPFA-DSP1), herein unveiled as a regioselective and efficient phosphatase towards inositol pyrophosphate (PP-InsP) signaling molecules. Although the WPD loop is missing its canonical tripeptide motif, this structural element contributes to catalysis by assisting PP-InsP delivery into the catalytic pocket, for a choreographed exchange with phosphate reaction product. Subsequently, an intramolecular proton donation by PP-InsP substrate is posited to substitute functionally for the absent aspartate/glutamate general-acid. Overall, we expand mechanistic insight into adaptability of the conserved PTP structural elements.
Background & Aims Risk for colorectal cancer (CRC) can be greatly reduced through screening. To aid in the development of screening strategies, we refined models designed to determine risk of CRC by ...incorporating information from common genetic susceptibility loci. Methods By using data collected from more than 12,000 participants in 6 studies performed from 1990 through 2011 in the United States and Germany, we developed risk determination models based on sex, age, family history, genetic risk score (number of risk alleles carried at 27 validated common CRC susceptibility loci), and history of endoscopic examinations. The model was validated using data collected from approximately 1800 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, conducted from 1993 through 2001 in the United States. Results We identified a CRC genetic risk score that independently predicted which patients in the training set would develop CRC. Compared with determination of risk based only on family history, adding the genetic risk score increased the discriminatory accuracy from 0.51 to 0.59 ( P = .0028) for men and from 0.52 to 0.56 ( P = .14) for women. We calculated age- and sex-specific 10-year CRC absolute risk estimates based on the number of risk alleles, family history, and history of endoscopic examinations. A model that included a genetic risk score better determined the recommended starting age for screening in subjects with and without family histories of CRC. The starting age for high-risk men (family history of CRC and genetic risk score, 90%) was 42 years, and for low-risk men (no family history of CRC and genetic risk score, 10%) was 52 years. For men with no family history and a high genetic risk score (90%), the starting age would be 47 years; this is an intermediate value that is 5 years earlier than it would be for men with a genetic risk score of 10%. Similar trends were observed in women. Conclusions By incorporating information on CRC risk alleles, we created a model to determine the risk for CRC more accurately. This model might be used to develop screening and prevention strategies.
Abstract We present high-speed optical photometric observations, spanning ∼2 yr, of the recently discovered white dwarf pulsar AR Scorpii. The amplitudes of the orbital, spin, and beat modulations ...appear to be remarkably stable and repeatable over the time span of our observations. It has been suggested that the polarized and non-polarized emission from AR Scorpii is powered by the spin-down of the white dwarf. However, we find that our new data are inconsistent with the published spin-down ephemeris. Whilst our data are consistent with a constant spin period, further observations over an extended time-base are required in order to ascertain the true spin-evolution of the white dwarf. This may have implications for the various models put forward to explain the energetics and evolution of AR Scorpii.
Inositol pyrophosphates (PP−IPs) are densely phosphorylated messenger molecules involved in numerous biological processes. PP−IPs contain one or two pyrophosphate group(s) attached to a ...phosphorylated myo‐inositol ring. 5PP−IP5 is the most abundant PP−IP in human cells. To investigate the function and regulation by PP−IPs in biological contexts, metabolically stable analogs have been developed. Here, we report the synthesis of a new fluorinated phosphoramidite reagent and its application for the synthesis of a difluoromethylene bisphosphonate analog of 5PP−IP5. Subsequently, the properties of all currently reported analogs were benchmarked using a number of biophysical and biochemical methods, including co‐crystallization, ITC, kinase activity assays and chromatography. Together, the results showcase how small structural alterations of the analogs can have notable effects on their properties in a biochemical setting and will guide in the choice of the most suitable analog(s) for future investigations.
How do pyrophosphate analogs compare? The synthesis of a fluorinated analog of an inositol pyrophosphate messenger is reported. Comparison of the physicochemical and biochemical properties of a range of closely related analogs showcases that subtle modifications can distinctly influence the behavior of molecules.
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