Transferable neural networks for enhanced sampling of protein dynamics

Variational auto-encoder frameworks have demonstrated success in reducing complex nonlinear dynamics in molecular simulation to a single non-linear embedding. In this work, we illustrate how this non-linear latent embedding can be used as a collective variable for enhanced sampling, and present a simple modification that allows us to rapidly perform sampling in multiple related systems. We first demonstrate our method is able to describe the effects of force field changes in capped alanine dipeptide after learning a model using AMBER99. We further provide a simple extension to variational dynamics encoders that allows the model to be trained in a more efficient manner on larger systems by encoding the outputs of a linear transformation using time-structure based independent component analysis (tICA). Using this technique, we show how such a model trained for one protein, the WW domain, can efficiently be transferred to perform enhanced sampling on a related mutant protein, the GTT mutation. This method shows promise for its ability to rapidly sample related systems using a single transferable collective variable and is generally applicable to sets of related simulations, enabling us to probe the effects of variation in increasingly large systems of biophysical interest.Comment: 20 pages, 10 figure

Massless Scalar Field Propagator in a Quantized Space-Time

We consider in detail the analytic behaviour of the non-interacting massless scalar field two-point function in H.S. Snyder's discretized non-commuting spacetime. The propagator we find is purely real on the Euclidean side of the complex $p^2$ plane and goes like $1/p^2$ as $p^2\to 0$ from either the Euclidean or Minkowski side. The real part of the propagator goes smoothly to zero as $p^2$ increases to the discretization scale $1/a^2$ and remains zero for $p^2>1/a^2$. This behaviour is consistent with the termination of single-particle propagation on the ultraviolet side of the discretization scale. The imaginary part of the propagator, consistent with a multiparticle-production branch discontinuity, is finite and continuous on the Minkowski side, slowly falling to zero when $1/a^2<p^2<\infty$. Finally, we argue that the spectral function for the multiparticle states appears to saturate as $p^2$ probes just beyond the $1/a^2$ discretization scale. We speculate on the cosmological consequences of such a spectral function.Comment: 6 pages, 1 eps figure embedded in manuscrip

Combining PPB and marker-assisted selection: strategies and experiences with rice

Participatory plant breeding should not preclude the use of modern biotechnological techniques

Variation between European eel Anguilla anguilla (L.) stocks in five marshes of the Thames Estuary (United Kingdom)

The European eel (Anguilla anguilla, L.) was historically widely distributed throughout the United Kingdom, in coastal waters, lakes, rivers and wetlands. Recruitment has declined in recent decades and the species is now listed as ‘Critically Endangered’ on the International Union for Conservation of Nature and Natural Resources (IUCN) Red List. Management of suitable wetland habitats may contribute to species recovery; however, little is known about the stocks in these areas. In this study, yellow (adult stage > 300 mm) eels were sampled in ditches in five marshes bordering the Thames Estuary in England, UK. Ecological variables, including ditch characteristics, invertebrate abundance and water quality parameters were measured. Habitat features were also observed and recorded, including access, land use and water management regimes. Eels were found in all marshes, but at varying catch-per-unit-effort (CPUE). There were no significant correlations between CPUE and the ecological variables, except ditch width. However, a significant difference in CPUE was found between two of the marshes, which may be explained by variations in local habitat management. Mean lengths showed a high proportion of females and mean body condition of four of the marshes was also found to be greater than in three rivers in the same region. These findings suggest that the marshes are potentially favourable eel habitats and that factors influencing habitat quality, such as land use and water management, may affect eel abundance, production of females and body condition. Effective management of such wetlands may therefore contribute to the conservation of European eel

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence

This study was part funded by an unrestricted educational grant provided by Schering-Plough, a grant by an anonymous trust and the Scottish Mental Health Research Network.Background: Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. Method: The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). Results: Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain–thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. Conclusions: Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.Publisher PDFPeer reviewe

Assessing changes in the internal worlds of early- and late-adopted children using the Story Stem Assessment Profile (SSAP)

A growing body of literature has consistently shown how adopted children often have previous history of trauma and neglect, and in turn develop negative representations of the self and others. This study assesses the internal representations of three groups of children, as measured by the Story Stem Assessment Profile (SSAP). These were: (1) a maltreated, late-adopted (MLA) sample (n = 63); (2) a non-maltreated, early-adopted (EA) sample (n = 48); and (3) a non-maltreated community sample (COMM) (n = 80). In addition, it examined whether MLA and EA adopted children’s attachment and internal representations changed over time. Results showed that children in the MLA sample significantly displayed more disorganised, avoidant and negative representations and fewer representations characteristic of ‘secure’ attachment when compared with EA and, especially, COMM children. Longitudinal follow-up of both MLA and EA samples demonstrated significant changes over a two-year period in SSAP representation; secure representations increased while the avoidant and disorganised ones diminished. These findings are discussed and the limitations and implications of the study presented