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Genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly important to monitor the transmission and adaptive evolution of the virus. The accessibility of high-throughput methods and polymerase chain reaction (PCR) has facilitated a growing ecosystem of protocols. Two differing protocols are tiling multiplex PCR and bait capture enrichment. Each method has advantages and disadvantages but a direct comparison with different viral RNA concentrations has not been performed to assess the performance of these approaches. Here we compare Liverpool amplification, ARTIC amplification, and bait capture using clinical diagnostics samples. All libraries were sequenced using an Illumina MiniSeq with data analyzed using a standardized bioinformatics workflow (SARS-CoV-2 Illumina GeNome Assembly Line; SIGNAL). One sample showed poor SARS-CoV-2 genome coverage and consensus, reflective of low viral RNA concentration. In contrast, the second sample had a higher viral RNA concentration, which yielded good genome coverage and consensus. ARTIC amplification showed the highest depth of coverage results for both samples, suggesting this protocol is effective for low concentrations. Liverpool amplification provided a more even read coverage of the SARS-CoV-2 genome, but at a lower depth of coverage. Bait capture enrichment of SARS-CoV-2 cDNA provided results on par with amplification. While only two clinical samples were examined in this comparative analysis, both the Liverpool and ARTIC amplification methods showed differing efficacy for high and low concentration samples. In addition, amplification-free bait capture enriched sequencing of cDNA is a viable method for generating a SARS-CoV-2 genome sequence and for identification of amplification artifacts.

The precise origins of fast radio bursts (FRBs) remain unknown. Multiwavelength observations of nearby FRB sources can provide important insights into the enigmatic FRB phenomenon. Here we present results from a sensitive, broadband X-ray and radio observational campaign of FRB 20200120E, the closest known extragalactic repeating FRB source (located 3.63 Mpc away in an ~10-Gyr-old globular cluster). We place deep limits on the persistent and prompt X-ray emission from FRB 20200120E, which we use to constrain possible origins for the source. We compare our results with various classes of X-ray sources, transients and FRB models. We find that FRB 20200120E is unlikely to be associated with ultraluminous X-ray bursts, magnetar-like giant flares or an SGR 1935+2154-like intermediate flare. Although other types of bright magnetar-like intermediate flares and short X-ray bursts would have been detectable from FRB 20200120E during our observations, we cannot entirely rule them out as a class. We show that FRB 20200120E is unlikely to be powered by an ultraluminous X-ray source or a young extragalactic pulsar embedded in a Crab-like nebula. We also provide new constraints on the compatibility of FRB 20200120E with accretion-based FRB models involving X-ray binaries. These results highlight the power of multiwavelength observations of nearby FRBs for discriminating between FRB models. Deep X-ray limits are placed on the source of the closest fast radio burst, FRB 20200120E, ruling out an ultraluminous X-ray source or a young extragalactic pulsar embedded in a Crab-like nebula as its origin.

The incorporation of sequencing technologies in frontline and public health healthcare settings was vital in developing virus surveillance programs during the Coronavirus Disease 2019 (COVID-19) pandemic caused by transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, increased data acquisition poses challenges for both rapid and accurate analyses. To overcome these hurdles, we developed the SARS-CoV-2 Illumina GeNome Assembly Line (SIGNAL) for quick bulk analyses of Illumina short-read sequencing data. SIGNAL is a Snakemake workflow that seamlessly manages parallel tasks to process large volumes of sequencing data. A series of outputs are generated, including consensus genomes, variant calls, lineage assessments and identified variants of concern (VOCs). Compared to other existing SARS-CoV-2 sequencing workflows, SIGNAL is one of the fastest-performing analysis tools while maintaining high accuracy. The source code is publicly available (github.com/jaleezyy/covid-19-signal) and is optimized to run on various systems, with software compatibility and resource management all handled within the workflow. Overall, SIGNAL illustrated its capacity for high-volume analyses through several contributions to publicly funded government public health surveillance programs and can be a valuable tool for continuing SARS-CoV-2 Illumina sequencing efforts and will inform the development of similar strategies for rapid viral sequence assessment.

NRC publication: Yes

Fast radio bursts (FRBs) are microsecond-to-millisecond-duration radio transients 1 that originate mostly from extragalactic distances. The FRB emission mechanism remains debated, with two main competing classes of models: physical processes that occur within close proximity to a central engine 2 , 3 – 4 ; and relativistic shocks that propagate out to large radial distances 5 , 6 , 7 – 8 . The expected emission-region sizes are notably different between these two types of models 9 . Here we present the measurement of two mutually coherent scintillation scales in the frequency spectrum of FRB 20221022A 10 : one originating from a scattering screen located within the Milky Way, and the second originating from its host galaxy or local environment. We use the scattering media as an astrophysical lens to constrain the size of the observed FRB lateral emission region 9 to ≲3 × 10 4  kilometres. This emission size is inconsistent with the expectation for the large-radial-distance models 5 , 6 , 7 – 8 , and is more naturally explained by an emission process that operates within or just beyond the magnetosphere of a central compact object. Recently, FRB 20221022A was found to exhibit an S-shaped polarization angle swing 10 , most likely originating from a magnetospheric emission process. The scintillation results presented in this work independently support this conclusion, while highlighting scintillation as a useful tool in our understanding of FRB emission physics and progenitors. The detection of scintillation caused by inhomogeneous plasma near a fast radio burst indicates an emission process that occurs within or just beyond the magnetosphere of a compact object.

Fast radio bursts (FRBs) are millisecond-duration flashes of radio waves that are visible at distances of billions of light years. The nature of their progenitors and their emission mechanism remain open astrophysical questions. Here we report the detection of the multicomponent FRB 20191221A and the identification of a periodic separation of 216.8(1) ms between its components, with a significance of 6.5σ. The long (roughly 3 s) duration and nine or more components forming the pulse profile make this source an outlier in the FRB population. Such short periodicity provides strong evidence for a neutron-star origin of the event. Moreover, our detection favours emission arising from the neutron-star magnetosphere, as opposed to emission regions located further away from the star, as predicted by some models.

Fast radio bursts (FRBs) last for milliseconds and arrive at Earth from cosmological distances. Although their origins and emission mechanisms are unknown, their signals bear similarities with the much less luminous radio emission generated by pulsars within our Miky Way Galaxy 1 , with properties suggesting neutron star origins 2 , 3 . However, unlike pulsars, FRBs typically show minimal variability in their linear polarization position angle (PA) curves 4 . Even when marked PA evolution is present, their curves deviate significantly from the canonical shape predicted by the rotating vector model (RVM) of pulsars 5 . Here we report on FRB 20221022A, detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst project (CHIME/FRB) and localized to a nearby host galaxy (about 65 Mpc), MCG+14-02-011. This FRB shows a notable approximately 130° PA rotation over its about 2.5 ms burst duration, resembling the characteristic S-shaped evolution seen in many pulsars and some radio magnetars. The observed PA evolution supports magnetospheric origins 6 , 7 – 8 over models involving distant shocks 9 , 10 – 11 , echoing similar conclusions drawn from tempo-polarimetric studies of some repeating FRBs 12 , 13 . The PA evolution is well described by the RVM and, although we cannot determine the inclination and magnetic obliquity because of the unknown period or duty cycle of the source, we exclude very short-period pulsars (for example, recycled millisecond pulsars) as the progenitor. FRB 20221022A, detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst project, shows a pronounced change in polarization during the burst, providing important clues into the nature of the source.

Donor-acceptor cyclopropanes are unique strained compounds that have been studied extensively toward the synthesis of valuable heterocyclic compounds. We investigated a two-step sequence to spirocyclic heterocycles involving an initial cycloaddition of an alkylidene cyclopropane followed by Lewis acid catalyzed annulation of the cyclopropane with an array of electrophiles. Secondly, the potential for α-keto esters to serve as acceptor groups in donor-acceptor cyclopropane annulations was explored. This led to the development of a copper-(II) catalyzed annulation of these cyclopropanes with aromatic aldehydes that proceeded with good diastereoselectivity.An asymmetric dearomatization of benzenoid compound was achieved by an enantioselective arene cyclopropanation using α-cyanodiazoacetates under the action of Rh2[(S)-PTTL]4 as a catalyst. The enantioenriched norcaradienes were subsequently functionalized via cycloadditions with a multitude of dienophiles and direct diene functionalization via dihydroxylation. Benzene norcaradienes were desymmetrized by epoxidation and the products elaborated to complex cyclohexanes with high stereocomplexity. A rhodium-(I) catalyzed addition of arylboronic acids to silyl glyoxylates was developed. Direct addition followed by enolate protonation/deuteration afforded mandelate products in good yield. Both racemic and asymmetric three-component couplings of arylboronic acids, silyl glyoxylates and aldehydes were developed, representing a rare instance of intermolecular three-component reactions where two carbon-carbon bonds are formed in a controlled sequence.

Extragalactic fast radio bursts (FRBs) are a new class of astrophysical transients with unknown origins that have become a main focus of radio observatories worldwide. FRBs are highly energetic (\\(\\sim 10^{36}\\)-\\(10^{42}\\) ergs) flashes that last for about a millisecond. Thanks to its broad bandwidth (400-800 MHz), large field of view (\\(\\sim\\)200 sq. deg.), and massive data rate (1500 TB of coherently beamformed data per day), the Canadian Hydrogen Intensity Mapping Experiment / Fast Radio Burst (CHIME/FRB) project has increased the total number of discovered FRBs by over a factor 10 in 3 years of operation. CHIME/FRB observations are hampered by the constant exposure to radio frequency interference (RFI) from artificial devices (e.g., cellular phones, aircraft), resulting in \\(\\sim\\)20% loss of bandwidth. In this work, we describe our novel technique for mitigating RFI in CHIME/FRB real-time intensity data. We mitigate RFI through a sequence of iterative operations, which mask out statistical outliers from frequency-channelized intensity data that have been effectively high-pass filtered. Keeping false positive and false negative rates at very low levels, our approach is useful for any high-performance surveys of radio transients in the future.

When applied to the non-linear matter distribution of the universe, neural networks have been shown to be very statistically sensitive probes of cosmological parameters, such as the linear perturbation amplitude \\(\\sigma_8\\). However, when used as a \"black box\", neural networks are not robust to baryonic uncertainty. We propose a robust architecture for constraining primordial non-Gaussianity \\(f_{NL}\\), by training a neural network to locally estimate \\(\\sigma_8\\), and correlating these local estimates with the large-scale density field. We apply our method to N-body simulations, and show that \\(\\sigma(f_{NL})\\) is 3.5 times better than the constraint obtained from a standard halo-based approach. We show that our method has the same robustness property as large-scale halo bias: baryonic physics can change the normalization of the estimated \\(f_{NL}\\), but cannot change whether \\(f_{NL}\\) is detected.