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NRC publication: Yes

NRC publication: Yes

We present the design, implementation and performance of a digital backend constructed for the Canadian Hydrogen Intensity Mapping Experiment (CHIME) that uses accelerated computing to observe radio pulsars and transient radio sources. When operating, the CHIME correlator outputs 10 independent streams of beamformed data for the CHIME/Pulsar backend that digitally track specified celestial positions. Each of these independent streams are processed by the CHIME/Pulsar backend system which can coherently dedisperse, in real-time, up to dispersion measure values of 2500 pc/cm\\(^{-3}\\) . The tracking beams and real-time analysis system are autonomously controlled by a priority-based algorithm that schedules both known sources and positions of interest for observation with observing cadences as small as one day. Given the distribution of known pulsars and radio-transient sources, the CHIME/Pulsar system can monitor up to 900 positions once per sidereal day and observe all sources with declinations greater than \\(-20^\\circ\\) once every \\(\\sim\\)2 weeks. We also discuss the science program enabled through the current modes of data acquisition for CHIME/Pulsar that centers on timing and searching experiments.

Fast radio bursts (FRBs) are bright, millisecond-duration radio transients originating from extragalactic distances. Their origin is unknown. Some FRB sources emit repeat bursts, ruling out cataclysmic origins for those events. Despite searches for periodicity in repeat burst arrival times on time scales from milliseconds to many days, these bursts have hitherto been observed to appear sporadically, and though clustered, without a regular pattern. Here we report the detection of a \\(16.35\\pm0.15\\) day periodicity (or possibly a higher-frequency alias of that periodicity) from a repeating FRB 180916.J0158+65 detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project (CHIME/FRB). In 38 bursts recorded from September 16th, 2018 through February 4th, 2020, we find that all bursts arrive in a 5-day phase window, and 50% of the bursts arrive in a 0.6-day phase window. Our results suggest a mechanism for periodic modulation either of the burst emission itself, or through external amplification or absorption, and disfavour models invoking purely sporadic processes.

Magnetars are highly magnetized young neutron stars that occasionally produce enormous bursts and flares of X-rays and gamma-rays. Of the approximately thirty magnetars currently known in our Galaxy and Magellanic Clouds, five have exhibited transient radio pulsations. Fast radio bursts (FRBs) are millisecond-duration bursts of radio waves arriving from cosmological distances. Some have been seen to repeat. A leading model for repeating FRBs is that they are extragalactic magnetars, powered by their intense magnetic fields. However, a challenge to this model has been that FRBs must have radio luminosities many orders of magnitude larger than those seen from known Galactic magnetars. Here we report the detection of an extremely intense radio burst from the Galactic magnetar SGR 1935+2154 using the Canadian Hydrogen Intensity Mapping Experiment (CHIME) FRB project. The fluence of this two-component bright radio burst and the estimated distance to SGR 1935+2154 together imply a 400-800 MHz burst energy of \\(\\sim 3 \\times 10^{34}\\) erg, which is three orders of magnitude brighter than those of any radio-emitting magnetar detected thus far. Such a burst coming from a nearby galaxy would be indistinguishable from a typical FRB. This event thus bridges a large fraction of the radio energy gap between the population of Galactic magnetars and FRBs, strongly supporting the notion that magnetars are the origin of at least some FRBs.

NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy.

Nicotinamide adenine dinucleotide (NAD + ) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD + precursors to augment NAD + bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD + precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD + metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group. Declining NAD + levels have been linked to aging-associated pathologies. Here the authors present results of a double-blind, randomized crossover trial on 30 healthy middle-aged individuals to show that nicotinamide riboside effectively elevates NAD + levels in humans, appears to be well tolerated, and may have potential to improve cardiovascular parameters.

Tree decline is a global concern and the primary cause is often unknown. Complex interactions between fluctuations in nitrogen (N) and acidifying compounds have been proposed as factors causing nutrient imbalances and decreasing stress tolerance of oak trees. Microorganisms are crucial in regulating soil N available to plants, yet little is known about the relationships between soil N-cycling and tree health. Here, we combined high-throughput sequencing and qPCR analysis of key nitrification and denitrification genes with soil chemical analyses to characterise ammonia-oxidising bacteria (AOB), archaea (AOA) and denitrifying communities in soils associated with symptomatic (declining) and asymptomatic (apparently healthy) oak trees ( Quercus robur and Q. petraea ) in the United Kingdom. Asymptomatic trees were associated with a higher abundance of AOB that is driven positively by soil pH. No relationship was found between AOA abundance and tree health. However, AOA abundance was driven by lower concentrations of NH 4 + , further supporting the idea of AOA favouring lower soil NH 4 + concentrations. Denitrifier abundance was influenced primarily by soil C:N ratio, and correlations with AOB regardless of tree health. These findings indicate that amelioration of soil acidification by balancing C:N may affect AOB abundance driving N transformations, reducing stress on declining oak trees.

Background Mosquito-borne diseases exert a huge impact on both animal and human populations, posing substantial health risks. The behavioural and fitness traits of mosquitoes, such as locomotion and fecundity, are crucial factors that influence the spread of diseases. In existing egg-counting tools, each image requires separate processing with adjustments to various parameters such as intensity threshold and egg area size. Furthermore, accuracy decreases significantly when dealing with clustered or overlapping eggs. To overcome these issues, we have developed EggCountAI, a Mask Region-based Convolutional Neural Network (RCNN)-based free automatic egg-counting tool for Aedes aegypti mosquitoes. Methods The study design involves developing EggCountAI for counting mosquito eggs and comparing its performance with two commonly employed tools—ICount and MECVision—using 10 microscopic and 10 macroscopic images of eggs laid by females on a paper strip. The results were validated through manual egg counting on the strips using ImageJ software. Two different models were trained on macroscopic and microscopic images to enhance egg detection accuracy, achieving mean average precision, mean average recall, and F1-scores of 0.92, 0.90, and 0.91 for the microscopic model, and 0.91, 0.90, and 0.90 for the macroscopic model, respectively. EggCountAI automatically counts eggs in a folder containing egg strip images, offering adaptable filtration for handling impurities of varying sizes. Results The results obtained from EggCountAI highlight its remarkable performance, achieving overall accuracy of 98.88% for micro images and 96.06% for macro images. EggCountAI significantly outperformed ICount and MECVision, with ICount achieving 81.71% accuracy for micro images and 82.22% for macro images, while MECVision achieved 68.01% accuracy for micro images and 51.71% for macro images. EggCountAI also excelled in other statistical parameters, with mean absolute error of 1.90 eggs for micro, 74.30 eggs for macro, and a strong correlation and R -squared value (0.99) for both micro and macro. The superior performance of EggCountAI was most evident when handling overlapping or clustered eggs. Conclusion Accurate detection and counting of mosquito eggs enables the identification of preferred egg-laying sites and facilitates optimal placement of oviposition traps, enhancing targeted vector control efforts and disease transmission prevention. In future research, the tool holds the potential to extend its application to monitor mosquito feeding preferences. Graphical Abstract

Mosquitoes of the Culex genus are responsible for a large burden of zoonotic virus transmission globally. Collectively, they play a significant role in the transmission of medically significant diseases such as Japanese encephalitis virus and West Nile virus. Climate change, global trade, habitat transformation and increased urbanisation are leading to the establishment of Culex mosquitoes in new geographical regions. These novel mosquito incursions are intensifying concerns about the emergence of Culex-transmitted diseases and outbreaks in previously unaffected areas. New mosquito control methods are currently being developed and deployed globally. Understanding the complex interaction between pathogens and mosquitoes is essential for developing new control strategies for Culex species mosquitoes. This article reviews the role of Culex mosquitos as vectors of zoonotic disease, discussing the transmission of viruses across different species, and the potential use of Wolbachia technologies to control disease spread. By leveraging the insights gained from recent successful field trials of Wolbachia against Aedes-borne diseases, we comprehensively discuss the feasibility of using this technique to control Culex mosquitoes and the potential for the development of next generational Wolbachia-based control methods.