Ynamides are among the most powerful building blocks in organic synthesis and have become invaluable starting materials for the construction of multifunctional compounds and challenging architectures ...that would be difficult to prepare otherwise. The rapidly growing popularity originates from the unique reactivity and ease of manipulation of the polarized ynamide triple bond, the advance of practical methods for making them, and the simplicity of storage and handling. These attractive features and the demonstration of numerous synthetic applications have spurred the development of intriguing asymmetric reaction strategies during the last decade. An impressive variety of chemo-, regio- and stereoselective carbon-carbon and carbon-heteroatom bond forming reactions with ynamides have been developed and now significantly enrich the toolbox of synthetic chemists. This review provides a comprehensive overview of asymmetric ynamide chemistry since 2010 with a focus on the general scope, current limitations, stereochemical reaction control and mechanistic aspects.
The diversity, utility and mechanistic aspects of asymmetric synthesis with ynamides developed during the last decade is discussed.
Abstract
We compute the spherically averaged power spectrum from four seasons of data obtained for the Epoch of Reionization (EoR) project observed with the Murchison Widefield Array (MWA). We ...measure the EoR power spectrum over k = 0.07–3.0 h Mpc−1 at redshifts $z$ = 6.5–8.7. The largest aggregation of 110 h on EoR0 high band (3340 observations), yields a lowest measurement of (43 mK)2 = 1.8 × 103 mK2 at k = 0.14 h Mpc−1 and $z$ = 6.5 (2σ thermal noise plus sample variance). Using the Real-Time System to calibrate and the CHIPS pipeline to estimate power spectra, we select the best observations from the central five pointings within the 2013–2016 observing seasons, observing three independent fields and in two frequency bands. This yields 13 591 2-min snapshots (453 h), based on a quality assurance metric that measures ionospheric activity. We perform another cut to remove poorly calibrated data, based on power in the foreground-dominated and EoR-dominated regions of the two-dimensional power spectrum, reducing the set to 12 569 observations (419 h). These data are processed in groups of 20 observations, to retain the capacity to identify poor data, and used to analyse the evolution and structure of the data over field, frequency, and data quality. We subsequently choose the cleanest 8935 observations (298 h of data) to form integrated power spectra over the different fields, pointings, and redshift ranges.
Nonionic surfactant excipients (NISEs) are commonly added to biologics formulations to mitigate the effects of stress incurred by the active biotherapeutic during manufacturing, transport, and ...storage. During manufacturing, NISEs are added by dilution of a stock solution directly into a protein formulation, and their accurate addition is critical in maintaining the quality and integrity of the drug product and thus ensuring patient safety. This is especially true for the common NISEs, polysorbates 20 and 80 (PS20 and PS80, respectively) and poloxamer 188 (P188). With the increasing diversity of biologic modalities within modern pharmaceutical pipelines, there is thus a critical need to develop and deploy convenient and user-accessible analytical techniques that can rapidly and reliably quantify these NISEs under biopharmaceutically relevant conditions. We thus pursued 60 MHz benchtop quantitative NMR (qNMR) as a nondestructive and user-friendly analytical technique for the quantification of PS20, PS80, and P188 under such conditions. We demonstrated the ability of benchtop qNMR (1) to quantify simulated PS20, PS80, and P188 stock solutions representative of those used during the drug substance (DS) formulation step in biomanufacturing and (2) to quantify these NISEs at and below their target concentrations (≤0.025% w/v) directly in biologics formulations containing histidine, sucrose, and one of three biotherapeutic modalities (monoclonal antibody, antibody-drug conjugate, and Fc-fusion protein). Our results demonstrate that benchtop qNMR offers a fit-for-purpose, reliable, user-friendly, and green analytical route by which NISE of interest to the biopharmaceutical industry may be readily and reliably quantified. We conclude that benchtop qNMR has the potential to be applied to other excipient formulation components in the presence of various biological modalities as well as the potential for routine integration within analytical and QC laboratories across pharmaceutical development and manufacturing sites.
A generally useful palladium-catalyzed method for the asymmetric allylic amination with a large variety of isatins, sulfonamides, imides, amines, and N-heterocycles is introduced. A single protocol ...with a readily available catalyst accomplishes this reaction at room temperature with high yields and enantioselectivities often exceeding 90%, which is demonstrated with 31 examples.
Root and rhizosphere microbial communities can affect plant health, but it remains undetermined how plant domestication may influence these bacterial and fungal communities.
We grew 33 sunflower ...(Helianthus annuus) strains (n = 5) that varied in their extent of domestication and assessed rhizosphere and root endosphere bacterial and fungal communities. We also assessed fungal communities in the sunflower seeds to investigate the degree to which root and rhizosphere communities were influenced by vertical transmission of the microbiome through seeds.
Neither root nor rhizosphere bacterial communities were affected by the extent of sunflower domestication, but domestication did affect the composition of rhizosphere fungal communities. In particular, more modern sunflower strains had lower relative abundances of putative fungal pathogens. Seed-associated fungal communities strongly differed across strains, but several lines of evidence suggest that there is minimal vertical transmission of fungi from seeds to the adult plants.
Our results indicate that plant-associated fungal communities are more strongly influenced by host genetic factors and plant breeding than bacterial communities, a finding that could influence strategies for optimizing microbial communities to improve crop yields.
The compact configuration of Phase II of the Murchison Widefield Array (MWA) consists of both a redundant subarray and pseudo-random baselines, offering unique opportunities to perform sky-model and ...redundant interferometric calibration. The highly redundant hexagonal cores give improved power spectrum sensitivity. In this paper, we present the analysis of nearly 40 hr of data targeting one of the MWA's epoch of reionization (EoR) fields observed in 2016. We use both improved analysis techniques presented in Barry et al. and several additional techniques developed for this work, including data quality control methods and interferometric calibration approaches. We show the EoR power spectrum limits at redshift 6.5, 6.8, and 7.1 based on our deep analysis on this 40 hr data set. These limits span a range in k-space of 0.18 h Mpc−1 < k < 1.6 h Mpc−1, with a lowest measurement of Δ2 ≤ 2.39 × 103 mK2 at k = 0.59 h Mpc−1 and z = 6.5.
A radio counterpart to a neutron star merger Hallinan, G.; Corsi, A.; Mooley, K. P. ...
Science (American Association for the Advancement of Science),
12/2017, Letnik:
358, Številka:
6370
Journal Article
Recenzirano
Odprti dostop
Gravitational waves have been detected from a binary neutron star merger event, GW170817. The detection of electromagnetic radiation from the same source has shown that the merger occurred in the ...outskirts of the galaxy NGC 4993, at a distance of 40 megaparsecs from Earth. We report the detection of a counterpart radio source that appears 16 days after the event, allowing us to diagnose the energetics and environment of the merger. The observed radio emission can be explained by either a collimated ultrarelativistic jet, viewed off-axis, or a cocoon of mildly relativistic ejecta. Within 100 days of the merger, the radio light curves will enable observers to distinguish between these models, and the angular velocity and geometry of the debris will be directly measurable by very long baseline interferometry.
GW170817 was the first gravitational-wave detection of a binary neutron-star merger. It was accompanied by radiation across the electromagnetic spectrum and localized to the galaxy NGC 4993 at a ...distance of 40 megaparsecs. It has been proposed that the observed γ-ray, X-ray and radio emission is due to an ultra-relativistic jet being launched during the merger (and successfully breaking out of the surrounding material), directed away from our line of sight (off-axis). The presence of such a jet is predicted from models that posit neutron-star mergers as the drivers of short hard-γ-ray bursts. Here we report that the radio light curve of GW170817 has no direct signature of the afterglow of an off-axis jet. Although we cannot completely rule out the existence of a jet directed away from the line of sight, the observed γ-ray emission could not have originated from such a jet. Instead, the radio data require the existence of a mildly relativistic wide-angle outflow moving towards us. This outflow could be the high-velocity tail of the neutron-rich material that was ejected dynamically during the merger, or a cocoon of material that breaks out when a jet launched during the merger transfers its energy to the dynamical ejecta. Because the cocoon model explains the radio light curve of GW170817, as well as the γ-ray and X-ray emission (and possibly also the ultraviolet and optical emission), it is the model that is most consistent with the observational data. Cocoons may be a ubiquitous phenomenon produced in neutron-star mergers, giving rise to a hitherto unidentified population of radio, ultraviolet, X-ray and γ-ray transients in the local Universe.
Illuminating gravitational waves Kasliwal, M. M.; Nakar, E.; Singer, L. P. ...
Science (American Association for the Advancement of Science),
12/2017, Letnik:
358, Številka:
6370
Journal Article
Recenzirano
Odprti dostop
Merging neutron stars offer an excellent laboratory for simultaneously studying strong-field gravity and matter in extreme environments. We establish the physical association of an electromagnetic ...counterpart (EM170817) with gravitational waves (GW170817) detected from merging neutron stars. By synthesizing a panchromatic data set, we demonstrate that merging neutron stars are a long-sought production site forging heavy elements by r-process nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared, and the delayed radio and x-ray emission. We posit that all neutron star mergers may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful jet and sometimes by a choked jet.
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