Summary Background Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum , but ...containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand–Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5–2·7) in 2001, to 3·7 h (3·6–3·8) in 2010, compared with a mean of 5·5 h (5·2–5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand–Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2–6 years. Funding The Wellcome Trust and National Institutes of Health.
Summary Background Artemisinin-resistant Plasmodium falciparum has been reported in Pailin, western Cambodia, detected as a slow parasite clearance rate in vivo. Emergence of this phenotype in ...western Thailand and possibly elsewhere threatens to compromise the effectiveness of all artemisinin-based combination therapies. Parasite genetics is associated with parasite clearance rate but does not account for all variation. We investigated contributions of both parasite genetics and host factors to the artemisinin-resistance phenotype in Pursat, western Cambodia. Methods Between June 19 and Nov 28, 2009, and June 26 and Dec 6, 2010, we enrolled patients aged 10 years or older with uncomplicated falciparum malaria, a density of asexual parasites of at least 10 000 per μL of whole blood, no symptoms or signs of severe malaria, no other cause of febrile illness, and no chronic illness. We gave participants 4 mg/kg artesunate at 0, 24, and 48 h, 15 mg/kg mefloquine at 72 h, and 10 mg/kg mefloquine at 96 h. We assessed parasite density on thick blood films every 6 h until undetectable. The parasite clearance half-life was calculated from the parasite clearance curve. We genotyped parasites with 18 microsatellite markers and patients for haemoglobin E, α-thalassaemia, and a mutation of G6PD , which encodes glucose-6-phosphate dehydrogenase. To account for the possible effects of acquired immunity on half-life, we used three surrogates for increased likelihood of exposure to P falciparum : age, sex, and place of residence. This study is registered with ClinicalTrials.gov , number NCT00341003. Findings We assessed 3504 individuals from all six districts of Pursat province seeking treatment for malaria symptoms. We enrolled 168 patients with falciparum malaria who met inclusion criteria. The geometric mean half-life was 5·85 h (95% CI 5·54–6·18) in Pursat, similar to that reported in Pailin (p=0·109). We identified two genetically different parasite clone groups: parasite group 1 (PG1) and parasite group 2 (PG2). Non-significant increases in parasite clearance half-life were seen in patients with haemoglobin E (0·55 h; p=0·078), those of male sex (0·96 h; p=0·064), and in 2010 (0·68 h; p=0·068); PG1 was associated with a significant increase (0·79 h; p=0·033). The mean parasite heritability of half-life was 0·40 (SD 0·17). Interpretation Heritable artemisinin resistance is established in a second Cambodian province. To accurately identify parasites that are intrinsically susceptible or resistant to artemisinins, future studies should explore the effect of erythrocyte polymorphisms and specific immune responses on half-life variation. Funding Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Evolving resistance to arte misi ni n-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, ...but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10⁻⁶ to 10⁻¹²) with slow CRs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits.
We report the detection of an ultra-bright fast radio burst (FRB) from a modest, 3.4-day pilot survey with the Australian Square Kilometre Array Pathfinder. The survey was conducted in a wide-field ...fly's-eye configuration using the phased-array-feed technology deployed on the array to instantaneously observe an effective area of 160 deg2, and achieve an exposure totaling 13200 deg2 hr . We constrain the position of FRB 170107 to a region in size (90% containment) and its fluence to be 58 6 Jy ms. The spectrum of the burst shows a sharp cutoff above 1400 MHz, which could be due to either scintillation or an intrinsic feature of the burst. This confirms the existence of an ultra-bright ( Jy ms) population of FRBs.
Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most ...commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research.
The tidal disruption of a star by a supermassive black hole leads to a short-lived thermal flare. Despite extensive searches, radio follow-up observations of known thermal stellar tidal disruption ...flares (TDFs) have not yet produced a conclusive detection. We present a detection of variable radio emission from a thermal TDF, which we interpret as originating from a newly launched jet. The multiwavelength properties of the source present a natural analogy with accretion-state changes of stellar mass black holes, which suggests that all TDFs could be accompanied by a jet. In the rest frame of the TDF, our radio observations are an order of magnitude more sensitive than nearly all previous upper limits, explaining how these jets, if common, could thus far have escaped detection.
The detection of gravitational waves by Advanced LIGO and Advanced Virgo provides an opportunity to test general relativity in a regime that is inaccessible to traditional astronomical observations ...and laboratory tests. We present four tests of the consistency of the data with binary black hole gravitational waveforms predicted by general relativity. One test subtracts the best-fit waveform from the data and checks the consistency of the residual with detector noise. The second test checks the consistency of the low- and high-frequency parts of the observed signals. The third test checks that phenomenological deviations introduced in the waveform model (including in the post-Newtonian coefficients) are consistent with 0. The fourth test constrains modifications to the propagation of gravitational waves due to a modified dispersion relation, including that from a massive graviton. We present results both for individual events and also results obtained by combining together particularly strong events from the first and second observing runs of Advanced LIGO and Advanced Virgo, as collected in the catalog GWTC-1. We do not find any inconsistency of the data with the predictions of general relativity and improve our previously presented combined constraints by factors of 1.1 to 2.5. In particular, we bound the mass of the graviton to be mg≤4.7×10−23 eV/c2 (90% credible level), an improvement of a factor of 1.6 over our previously presented results. Additionally, we check that the four gravitational-wave events published for the first time in GWTC-1 do not lead to stronger constraints on alternative polarizations than those published previously.
The Ground State Electronic Energy of Benzene Eriksen, Janus J; Anderson, Tyler A; Deustua, J. Emiliano ...
The journal of physical chemistry letters,
10/2020, Letnik:
11, Številka:
20
Journal Article
Recenzirano
Odprti dostop
We report on the findings of a blind challenge devoted to determining the frozen-core, full configuration interaction (FCI) ground-state energy of the benzene molecule in a standard ...correlation-consistent basis set of double-ζ quality. As a broad international endeavor, our suite of wave function-based correlation methods collectively represents a diverse view of the high-accuracy repertoire offered by modern electronic structure theory. In our assessment, the evaluated high-level methods are all found to qualitatively agree on a final correlation energy, with most methods yielding an estimate of the FCI value around −863 mE H. However, we find the root-mean-square deviation of the energies from the studied methods to be considerable (1.3 mE H), which in light of the acclaimed performance of each of the methods for smaller molecular systems clearly displays the challenges faced in extending reliable, near-exact correlation methods to larger systems. While the discrepancies exposed by our study thus emphasize the fact that the current state-of-the-art approaches leave room for improvement, we still expect the present assessment to provide a valuable community resource for benchmark and calibration purposes going forward.
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