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
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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.
Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has ...developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis for their properties as pests.
We find that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had accumulated up to more than 100 more members of specific detoxification and digestion gene families and more than 100 extra gustatory receptor genes, compared to other lepidopterans with narrower host ranges. The two genomes remain very similar in gene content and order, but H. armigera is more polymorphic overall, and H. zea has lost several detoxification genes, as well as about 50 gustatory receptor genes. It also lacks certain genes and alleles conferring insecticide resistance found in H. armigera. Non-synonymous sites in the expanded gene families above are rapidly diverging, both between paralogues and between orthologues in the two species. Whole genome transcriptomic analyses of H. armigera larvae show widely divergent responses to different host plants, including responses among many of the duplicated detoxification and digestion genes.
The extreme polyphagy of the two heliothines is associated with extensive amplification and neofunctionalisation of genes involved in host finding and use, coupled with versatile transcriptional responses on different hosts. H. armigera's invasion of the Americas in recent years means that hybridisation could generate populations that are both locally adapted and insecticide resistant.
With the rapidly increasing abundance and accessibility of genomic data, there is a growing interest in using population genetic approaches to characterize fine-scale dispersal of organisms, ...providing insight into biological processes across a broad range of fields including ecology, evolution and epidemiology. For sexually recombining haploid organisms such as the human malaria parasite P. falciparum, however, there have been no systematic assessments of the type of data and methods required to resolve fine scale connectivity. This analytical gap hinders the use of genomics for understanding local transmission patterns, a crucial goal for policy makers charged with eliminating this important human pathogen. Here we use data collected from four clinics with a catchment area spanning approximately 120 km of the Thai-Myanmar border to compare the ability of divergence (FST) and relatedness based on identity by descent (IBD) to resolve spatial connectivity between malaria parasites collected from proximal clinics. We found no relationship between inter-clinic distance and FST, likely due to sampling of highly related parasites within clinics, but a significant decline in IBD-based relatedness with increasing inter-clinic distance. This association was contingent upon the data set type and size. We estimated that approximately 147 single-infection whole genome sequenced parasite samples or 222 single-infection parasite samples genotyped at 93 single nucleotide polymorphisms (SNPs) were sufficient to recover a robust spatial trend estimate at this scale. In summary, surveillance efforts cannot rely on classical measures of genetic divergence to measure P. falciparum transmission on a local scale. Given adequate sampling, IBD-based relatedness provides a useful alternative, and robust trends can be obtained from parasite samples genotyped at approximately 100 SNPs.
To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales ...for Outcomes in Parkinson disease-Cognition SCOPA-COG) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks.
A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N).
Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve AUC, 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value NPV 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval CI 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%).
The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.
The Ras gene is frequently mutated in cancer, and mutant Ras drives tumorigenesis. Although Ras is a central oncogene, small molecules that bind to Ras in a well-defined manner and exert inhibitory ...effects have not been uncovered to date. Through an NMR-based fragment screen, we identified a group of small molecules that all bind to a common site on Ras. High-resolution cocrystal structures delineated a unique ligand-binding pocket on the Ras protein that is adjacent to the switch I/II regions and can be expanded upon compound binding. Structure analysis predicts that compound-binding interferes with the Ras/SOS interactions. Indeed, selected compounds inhibit SOS-mediated nucleotide exchange and prevent Ras activation by blocking the formation of intermediates of the exchange reaction. The discovery of a small-molecule binding pocket on Ras with functional significance provides a new direction in the search of therapeutically effective inhibitors of the Ras oncoprotein.
Activating mutations in KRAS and BRAF are found in more than 30% of all human tumours and 40% of melanoma, respectively, thus targeting this pathway could have broad therapeutic effects. Small ...molecule ATP-competitive RAF kinase inhibitors have potent antitumour effects on mutant BRAF(V600E) tumours but, in contrast to mitogen-activated protein kinase kinase (MEK) inhibitors, are not potent against RAS mutant tumour models, despite RAF functioning as a key effector downstream of RAS and upstream of MEK. Here we show that ATP-competitive RAF inhibitors have two opposing mechanisms of action depending on the cellular context. In BRAF(V600E) tumours, RAF inhibitors effectively block the mitogen-activated protein kinase (MAPK) signalling pathway and decrease tumour growth. Notably, in KRAS mutant and RAS/RAF wild-type tumours, RAF inhibitors activate the RAF-MEK-ERK pathway in a RAS-dependent manner, thus enhancing tumour growth in some xenograft models. Inhibitor binding activates wild-type RAF isoforms by inducing dimerization, membrane localization and interaction with RAS-GTP. These events occur independently of kinase inhibition and are, instead, linked to direct conformational effects of inhibitors on the RAF kinase domain. On the basis of these findings, we demonstrate that ATP-competitive kinase inhibitors can have opposing functions as inhibitors or activators of signalling pathways, depending on the cellular context. Furthermore, this work provides new insights into the therapeutic use of ATP-competitive RAF inhibitors.
Developed to replace organophosphate and carbamate insecticides, neonicotinoids are structurally similar to nicotine. The three main neonicotinoid insecticides, imidacloprid, clothianidin, and ...thiamethoxam, are being re-evaluated by Health Canada's Pest Management Regulatory Agency (PMRA). An important aspect of the re-evaluation is the potential for effects in non-target organisms, including aquatic organisms.
Leaching into surface waters is one of the major concerns surrounding extensive use of neonicotinoids, especially in close proximity to water bodies. The PMRA has classified IMI as ‘persistent’ with a ‘high’ leaching potential. Globally, neonicotinoids have been detected in a variety of water bodies, typically at concentrations in the low μg/L range. While IMI has been included in some monitoring exercises, there are currently very few published data for the presence of CLO and THM in Canadian water bodies.
The majority of neonicotinoid toxicity studies have been conducted with IMI due to its longer presence on the market and high prevalence of use. Aquatic insects are particularly vulnerable to neonicotinoids and chronic toxicity has been observed at concentrations of IMI below 1μg/L. Acute toxicity has been reported at concentrations below 20μg/L for the most sensitive species, including Hyalella azteca, ostracods, and Chironomus riparius.
Fish, algae, amphibians, and molluscs are relatively insensitive to IMI. However, the biological effects of THM and CLO have not been as well explored. The Canadian interim water quality guideline for IMI is 0.23μg/L, but there is currently insufficient use, fate, and toxicological information available to establish guidelines for CLO and THM.
Based on concentrations of neonicotinoids reported in surface waters in Canada and globally, there is potential for aquatic invertebrates to be negatively impacted by neonicotinoids. Therefore, it is necessary to address knowledge gaps to inform decisions around guidelines and registration status for neonicotinoid insecticides in Canada to protect our aquatic ecosystems.
•Imidacloprid, clothianidin, and thiamethoxam are under re-evaluation by PMRA.•Some fate monitoring of imidacloprid in Canada but not clothianidin or thiamethoxam•Fish, algae, amphibians, and molluscs are relatively insensitive to neonicotinoids.•Interim guideline might not be sufficiently protective of aquatic invertebrates.•Concentrations measured in Canadian waters could have impacts on aquatic organisms.
In this work, we present measurements of the E-mode (EE) polarization power spectrum and temperature-E-mode (TE) cross-power spectrum of the cosmic microwave background using data collected by ...SPT-3G, the latest instrument installed on the South Pole Telescope. This analysis uses observations of a 1500 deg2 region at 95, 150, and 220 GHz taken over a four-month period in 2018. We report binned values of the EE and TE power spectra over the angular multipole range 300≤ℓ<3000, using the multifrequency data to construct six semi-independent estimates of each power spectrum and their minimum-variance combination. These measurements improve upon the previous results of SPTpol across the multipole ranges 300 ≤ ℓ ≤ 1400 for EE and 300 ≤ ℓ ≤ 1700 for TE, resulting in constraints on cosmological parameters comparable to those from other current leading ground-based experiments. We find that the SPT-3G data set is well fit by a ΛCDM cosmological model with parameter constraints consistent with those from Planck and SPTpol data. From SPT-3G data alone, we find H0=68.8±1.5 km s-1 Mpc-1 and σ8=0.789±0.016, with a gravitational lensing amplitude consistent with the ΛCDM prediction (AL=0.98±0.12). We combine the SPT-3G and the Planck data sets and obtain joint constraints on the ΛCDM model. The volume of the 68% confidence region in six-dimensional ΛCDM parameter space is reduced by a factor of 1.5 compared to Planck-only constraints, with no significant shifts in central values. We note that the results presented here are obtained from data collected during just half of a typical observing season with only part of the focal plane operable, and that the active detector count has since nearly doubled for observations made with SPT-3G after 2018.
Superluminous supernovae (SLSNe) are very bright explosions that were only discovered recently and that show a preference for occurring in faint dwarf galaxies. Understanding why stellar evolution ...yields different types of stellar explosions in these environments is fundamental in order to both uncover the elusive progenitors of SLSNe and to study star formation in dwarf galaxies. In this paper, we present the first results of our project to study SUperluminous Supernova Host galaxIES, focusing on the sample for which we have obtained spectroscopy. We show that SLSNe-I and SLSNe-R (hydrogen-poor) often (∼50 per cent in our sample) occur in a class of galaxies that is known as Extreme Emission Line Galaxies (EELGs). The probability of this happening by chance is negligible and we therefore conclude that the extreme environmental conditions and the SLSN phenomenon are related. In contrast, SLSNe-II (hydrogen-rich) occur in more massive, more metal-rich galaxies with softer radiation fields. Therefore, if SLSNe-II constitute a uniform class, their progenitor systems are likely different from those of H-poor SLSNe. Gamma-ray bursts (GRBs) are, on average, not found in as extreme environments as H-poor SLSNe. We propose that H-poor SLSNe result from the very first stars exploding in a starburst, even earlier than GRBs. This might indicate a bottom-light initial mass function in these systems. SLSNe present a novel method of selecting candidate EELGs independent of their luminosity.
Inhaled corticosteroids (ICS) are important in reducing exacerbation frequency associated with chronic obstructive pulmonary disease (COPD). However, little is known about the risk of associated ...infections. In a post hoc analysis of the TOwards a Revolution in COPD Health (TORCH) study, we analysed and identified potential risk factors for adverse event reports of pneumonia in this randomised, double-blind trial comparing twice-daily inhaled salmeterol (SAL) 50 microg, fluticasone propionate (FP) 500 microg, and the combination (SFC) with placebo in 6,184 patients with moderate-to-severe COPD over 3 yrs. Despite a higher withdrawal rate in the placebo arm, after adjusting for time on treatment, a greater rate of pneumonia was reported in the FP and SFC treatment arms (84 and 88 per 1,000 treatment-yrs, respectively) compared with SAL and placebo (52 and 52 per 1,000 treatment-yrs, respectively). Risk factors for pneumonia were age > or =55 yrs, forced expiratory volume in 1 s <50% predicted, COPD exacerbations in the year prior to the study, worse Medical Research Council dyspnoea scores and body mass index <25 kg.m(-2). No increase in pneumonia deaths with SFC was observed; this could not be concluded for FP. Despite the benefits of ICS-containing regimens in COPD management, healthcare providers should remain vigilant regarding the possible development of pneumonia as a complication in COPD patients receiving such therapies.
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