1,821 research outputs found
Testing density-functional approximations on a lattice and the applicability of the related Hohenberg-Kohn-like theorem
We present a metric-space approach to quantify the performance of approximations in lattice density-functional theory for interacting many-body systems and to explore the regimes where the Hohenberg-Kohn-type theorem on fermionic lattices is applicable. This theorem demonstrates the existence of one-to-one mappings between particle densities, wave functions and external potentials. We then focus on these quantities, and quantify how far apart in metric space the approximated and exact ones are. We apply our method to the one-dimensional Hubbard model for different types of external potentials, and assess the regimes where it is applicable to one of the most used approximations in density-functional theory, the local density approximation (LDA). We find that the potential distance may have a very different behaviour from the density and wave function distances, in some cases even providing the wrong assessments of the LDA performance trends. We attribute this to the systems reaching behaviours which are borderline for the applicability of the one-to-one correspondence between density and external potential. On the contrary the wave function and density distances behave similarly and are always sensitive to system variations. Our metric-based method correctly predicts the regimes where the LDA performs fairly well and the regimes where it fails. This suggests that our method could be a practical tool for testing the efficiency of density-functional approximations
Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes
This is the final version. Available on open access from Elsevier via the DOI in this recordBACKGROUND AND AIMS: We investigated whether objectively measured sedentary time was associated with markers of inflammation in adults with newly diagnosed type 2 diabetes. METHODS AND RESULTS: We studied 285 adults (184 men, 101 women, mean age 59.0 ± 9.7) who had been recruited to the Early ACTivity in Diabetes (Early ACTID) randomised controlled trial. C-reactive protein (CRP), adiponectin, soluble intracellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and accelerometer-determined sedentary time and moderate-vigorous physical activity (MVPA) were measured at baseline and after six-months. Linear regression analysis was used to investigate the independent cross-sectional and longitudinal associations of sedentary time with markers of inflammation. At baseline, associations between sedentary time and IL-6 were observed in men and women, an association that was attenuated following adjustment for waist circumference. After 6 months of follow-up, sedentary time was reduced by 0.4 ± 1.2 h per day in women, with the change in sedentary time predicting CRP at follow-up. Every hour decrease in sedentary time between baseline and six-months was associated with 24% (1, 48) lower CRP. No changes in sedentary time between baseline and 6 months were seen in men. CONCLUSIONS: Higher sedentary time is associated with IL-6 in men and women with type 2 diabetes, and reducing sedentary time is associated with improved levels of CRP in women. Interventions to reduce sedentary time may help to reduce inflammation in women with type 2 diabetes.National Institute for Health Research (NIHR
Terrestrial exposure of a fresh Martian meteorite causes rapid changes in hydrogen isotopes and water concentrations
Determining the hydrogen isotopic compositions and H2O contents of meteorites and their components is important for addressing key cosmochemical questions about the abundance and source(s) of water in planetary bodies. However, deconvolving the effects of terrestrial contamination from the indigenous hydrogen isotopic compositions of these extraterrestrial materials is not trivial, because chondrites and some achondrites show only small deviations from terrestrial values such that even minor contamination can mask the indigenous values. Here we assess the effects of terrestrial weathering and contamination on the hydrogen isotope ratios and H2O contents of meteoritic minerals through monitored terrestrial weathering of Tissint, a recent Martian fall. Our findings reveal the rapidity with which this weathering affects nominally anhydrous phases in extraterrestrial materials, which illustrates the necessity of sampling the interiors of even relatively fresh meteorite falls and underlines the importance of sample return missions
Means and covariance functions for geostatistical compositional data: an axiomatic approach
This work focuses on the characterization of the central tendency of a sample
of compositional data. It provides new results about theoretical properties of
means and covariance functions for compositional data, with an axiomatic
perspective. Original results that shed new light on the geostatistical
modeling of compositional data are presented. As a first result, it is shown
that the weighted arithmetic mean is the only central tendency characteristic
satisfying a small set of axioms, namely continuity, reflexivity and marginal
stability. Moreover, this set of axioms also implies that the weights must be
identical for all parts of the composition. This result has deep consequences
on the spatial multivariate covariance modeling of compositional data. In a
geostatistical setting, it is shown as a second result that the proportional
model of covariance functions (i.e., the product of a covariance matrix and a
single correlation function) is the only model that provides identical kriging
weights for all components of the compositional data. As a consequence of these
two results, the proportional model of covariance function is the only
covariance model compatible with reflexivity and marginal stability
Dynamic clamp with StdpC software
Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based on a fast cycle of measuring the membrane potential of a cell, calculating the current of a desired simulated component using an appropriate model and injecting this current into the cell. Here we present a dynamic clamp protocol using free, fully integrated, open-source software (StdpC, for spike timing-dependent plasticity clamp). Use of this protocol does not require specialist hardware, costly commercial software, experience in real-time operating systems or a strong programming background. The software enables the configuration and operation of a wide range of complex and fully automated dynamic clamp experiments through an intuitive and powerful interface with a minimal initial lead time of a few hours. After initial configuration, experimental results can be generated within minutes of establishing cell recording
Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS
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Stops making sense: translational trade-offs and stop codon reassignment
Background
Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature.
Results
In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences.
Conclusions
We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants
Cost, risk, and avoidance of inbreeding in a cooperatively breeding bird
Inbreeding is often avoided in natural populations by passive processes such as sex-biased dispersal. But, in many social animals, opposite-sexed adult relatives are spatially clustered, generating a risk of incest and hence selection for active inbreeding avoidance. Here we show that, in long-tailed tits (Aegithalos caudatus), a cooperative breeder that risks inbreeding by living alongside opposite-sex relatives, inbreeding carries fitness costs and is avoided by active kin discrimination during mate choice. First, we identified a positive association between heterozygosity and fitness, indicating that inbreeding is costly. We then compared relatedness within breeding pairs to that expected under multiple mate-choice models, finding that pair relatedness is consistent with avoidance of first-order kin as partners. Finally, we show that the similarity of vocal cues offers a plausible mechanism for discrimination against first-order kin during mate choice. Long-tailed tits are known to discriminate between the calls of close kin and nonkin, and they favor first-order kin in cooperative contexts, so we conclude that long-tailed tits use the same kin discrimination rule to avoid inbreeding as they do to direct help toward kin
Has education lost sight of children?
The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating
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