Improvement of 3D protein models using multiple templates guided by single-template model quality assessment

Motivation: Modelling the 3D structures of proteins can often be enhanced if more than one fold template is used during the modelling process. However, in many cases, this may also result in poorer model quality for a given target or alignment method. There is a need for modelling protocols that can both consistently and significantly improve 3D models and provide an indication of when models might not benefit from the use of multiple target-template alignments. Here, we investigate the use of both global and local model quality prediction scores produced by ModFOLDclust2, to improve the selection of target-template alignments for the construction of multiple-template models. Additionally, we evaluate clustering the resulting population of multi- and single-template models for the improvement of our IntFOLD-TS tertiary structure prediction method. Results: We find that using accurate local model quality scores to guide alignment selection is the most consistent way to significantly improve models for each of the sequence to structure alignment methods tested. In addition, using accurate global model quality for re-ranking alignments, prior to selection, further improves the majority of multi-template modelling methods tested. Furthermore, subsequent clustering of the resulting population of multiple-template models significantly improves the quality of selected models compared with the previous version of our tertiary structure prediction method, IntFOLD-TS.

An experimental manipulation of responsibility in children: a test of the inflated responsibility model of obsessive-compulsive disorder

The objective of this study was to investigate whether Salkovskis (1985) inflated responsibility model of obsessive-compulsive disorder (OCD) applied to children. In an experimental design, 81 children aged 9– 12 years were randomly allocated to three conditions: an inflated responsibility group, a moderate responsibility group, and a reduced responsibility group. In all groups children were asked to sort sweets according to whether or not they contained nuts. At baseline the groups did not differ on children’s self reported anxiety, depression, obsessive-compulsive symptoms or on inflated responsibility beliefs. The experimental manipulation successfully changed children’s perceptions of responsibility. During the sorting task time taken to complete the task, checking behaviours, hesitations, and anxiety were recorded. There was a significant effect of responsibility level on the behavioural variables of time taken, hesitations and check; as perceived responsibility increased children took longer to complete the task and checked and hesitated more often. There was no between-group difference in children’s self reported state anxiety. The results offer preliminary support for the link between inflated responsibility and increased checking behaviours in children and add to the small but growing literature suggesting that cognitive models of OCD may apply to children.

Advances in sequential data assimilation and numerical weather forecasting: an Ensemble Transform Kalman-Bucy Filter, a study on clustering in deterministic Ensemble Square Root Filters, and a test of a new time stepping scheme in an atmospheric model

This dissertation deals with aspects of sequential data assimilation (in particular ensemble Kalman filtering) and numerical weather forecasting. In the first part, the recently formulated Ensemble Kalman-Bucy (EnKBF) filter is revisited. It is shown that the previously used numerical integration scheme fails when the magnitude of the background error covariance grows beyond that of the observational error covariance in the forecast window. Therefore, we present a suitable integration scheme that handles the stiffening of the differential equations involved and doesn’t represent further computational expense. Moreover, a transform-based alternative to the EnKBF is developed: under this scheme, the operations are performed in the ensemble space instead of in the state space. Advantages of this formulation are explained. For the first time, the EnKBF is implemented in an atmospheric model. The second part of this work deals with ensemble clustering, a phenomenon that arises when performing data assimilation using of deterministic ensemble square root filters in highly nonlinear forecast models. Namely, an M-member ensemble detaches into an outlier and a cluster of M-1 members. Previous works may suggest that this issue represents a failure of EnSRFs; this work dispels that notion. It is shown that ensemble clustering can be reverted also due to nonlinear processes, in particular the alternation between nonlinear expansion and compression of the ensemble for different regions of the attractor. Some EnSRFs that use random rotations have been developed to overcome this issue; these formulations are analyzed and their advantages and disadvantages with respect to common EnSRFs are discussed. The third and last part contains the implementation of the Robert-Asselin-Williams (RAW) filter in an atmospheric model. The RAW filter is an improvement to the widely popular Robert-Asselin filter that successfully suppresses spurious computational waves while avoiding any distortion in the mean value of the function. Using statistical significance tests both at the local and field level, it is shown that the climatology of the SPEEDY model is not modified by the changed time stepping scheme; hence, no retuning of the parameterizations is required. It is found the accuracy of the medium-term forecasts is increased by using the RAW filter.

Real-time multi-model decadal climate predictions

We present the first climate prediction of the coming decade made with multiple models, initialized with prior observations. This prediction accrues from an international activity to exchange decadal predictions in near real-time, in order to assess differences and similarities, provide a consensus view to prevent over-confidence in forecasts from any single model, and establish current collective capability. We stress that the forecast is experimental, since the skill of the multi-model system is as yet unknown. Nevertheless, the forecast systems used here are based on models that have undergone rigorous evaluation and individually have been evaluated for forecast skill. Moreover, it is important to publish forecasts to enable open evaluation, and to provide a focus on climate change in the coming decade. Initialized forecasts of the year 2011 agree well with observations, with a pattern correlation of 0.62 compared to 0.31 for uninitialized projections. In particular, the forecast correctly predicted La Niña in the Pacific, and warm conditions in the north Atlantic and USA. A similar pattern is predicted for 2012 but with a weaker La Niña. Indices of Atlantic multi-decadal variability and Pacific decadal variability show no signal beyond climatology after 2015, while temperature in the Niño3 region is predicted to warm slightly by about 0.5 °C over the coming decade. However, uncertainties are large for individual years and initialization has little impact beyond the first 4 years in most regions. Relative to uninitialized forecasts, initialized forecasts are significantly warmer in the north Atlantic sub-polar gyre and cooler in the north Pacific throughout the decade. They are also significantly cooler in the global average and over most land and ocean regions out to several years ahead. However, in the absence of volcanic eruptions, global temperature is predicted to continue to rise, with each year from 2013 onwards having a 50 % chance of exceeding the current observed record. Verification of these forecasts will provide an important opportunity to test the performance of models and our understanding and knowledge of the drivers of climate change.

Summertime stratospheric processes at northern mid-latitudes: comparisons between MANTRA balloon measurements and the Canadian Middle Atmosphere Model

In this paper we report on a study conducted using the Middle Atmospheric Nitrogen TRend Assessment (MANTRA) balloon measurements of stratospheric constituents and temperature and the Canadian Middle Atmosphere Model (CMAM). Three different kinds of data are used to assess the inter-consistency of the combined dataset: single profiles of long-lived species from MANTRA 1998, sparse climatologies from the ozonesonde measurements during the four MANTRA campaigns and from HALOE satellite measurements, and the CMAM climatology. In doing so, we evaluate the ability of the model to reproduce the measured fields and to thereby test our ability to describe mid-latitude summertime stratospheric processes. The MANTRA campaigns were conducted at Vanscoy, Saskatchewan, Canada (52◦ N, 107◦ W)in late August and early September of 1998, 2000, 2002 and 2004. During late summer at mid-latitudes, the stratosphere is close to photochemical control, providing an ideal scenario for the study reported here. From this analysis we find that: (1) reducing the value for the vertical diffusion coefficient in CMAM to a more physically reasonable value results in the model better reproducing the measured profiles of long-lived species; (2) the existence of compact correlations among the constituents, as expected from independent measurements in the literature and from models, confirms the self-consistency of the MANTRA measurements; and (3) the 1998 measurements show structures in the chemical species profiles that can be associated with transport, adding to the growing evidence that the summertime stratosphere can be much more disturbed than anticipated. The mechanisms responsible for such disturbances need to be understood in order to assess the representativeness of the measurements and to isolate longterm trends.

Empirical test of an agricultural landscape model: the importance of farmer preference for risk aversion and crop complexity

Developing models to predict the effects of social and economic change on agricultural landscapes is an important challenge. Model development often involves making decisions about which aspects of the system require detailed description and which are reasonably insensitive to the assumptions. However, important components of the system are often left out because parameter estimates are unavailable. In particular, measurements of the relative influence of different objectives, such as risk, environmental management, on farmer decision making, have proven difficult to quantify. We describe a model that can make predictions of land use on the basis of profit alone or with the inclusion of explicit additional objectives. Importantly, our model is specifically designed to use parameter estimates for additional objectives obtained via farmer interviews. By statistically comparing the outputs of this model with a large farm-level land-use data set, we show that cropping patterns in the United Kingdom contain a significant contribution from farmer’s preference for objectives other than profit. In particular, we found that risk aversion had an effect on the accuracy of model predictions, whereas preference for a particular number of crops grown was less important. While nonprofit objectives have frequently been identified as factors in farmers’ decision making, our results take this analysis further by demonstrating the relationship between these preferences and actual cropping patterns.

The simulation of the opposing fluxes of latent heat and CO2 over various land-use types: coupling a gas exchange model to a mesoscale atmospheric model

A mesoscale meteorological model (FOOT3DK) is coupled with a gas exchange model to simulate surface fluxes of CO2 and H2O under field conditions. The gas exchange model consists of a C3 single leaf photosynthesis sub-model and an extended big leaf (sun/shade) sub-model that divides the canopy into sunlit and shaded fractions. Simulated CO2 fluxes of the stand-alone version of the gas exchange model correspond well to eddy-covariance measurements at a test site in a rural area in the west of Germany. The coupled FOOT3DK/gas exchange model is validated for the diurnal cycle at singular grid points, and delivers realistic fluxes with respect to their order of magnitude and to the general daily course. Compared to the Jarvis-based big leaf scheme, simulations of latent heat fluxes with a photosynthesis-based scheme for stomatal conductance are more realistic. As expected, flux averages are strongly influenced by the underlying land cover. While the simulated net ecosystem exchange is highly correlated with leaf area index, this correlation is much weaker for the latent heat flux. Photosynthetic CO2 uptake is associated with transpirational water loss via the stomata, and the resulting opposing surface fluxes of CO2 and H2O are reproduced with the model approach. Over vegetated surfaces it is shown that the coupling of a photosynthesis-based gas exchange model with the land-surface scheme of a mesoscale model results in more realistic simulated latent heat fluxes.

The competition–performance relation: a meta-analytic review and test of the opposing processes model of competition and performance

What is the relation between competition and performance? The present research addresses this important multidisciplinary question by conducting a meta-analysis of existing empirical work and by proposing a new conceptual model—the opposing processes model of competition and performance. This model was tested by conducting an additional meta-analysis and 3 new empirical studies. The first meta-analysis revealed that there is no noteworthy relation between competition and performance. The second meta-analysis showed, in accord with the opposing processes model, that the absence of a direct effect is the result of inconsistent mediation via achievement goals: Competition prompts performance-approach goals which, in turn, facilitate performance; and competition also prompts performance-avoidance goals which, in turn, undermine performance. These same direct and mediational findings were also observed in the 3 new empirical studies (using 3 different conceptualizations of competition and attending to numerous control variables). Our findings provide both interpretational clarity regarding past research and conceptual guidance regarding future research on the competition–performance relation.

A GCSS model intercomparison for a tropical squall line observed during toga-coare. II: Intercomparison of single-column models and a cloud-resolving model

This paper presents single-column model (SCM) simulations of a tropical squall-line case observed during the Coupled Ocean-Atmosphere Response Experiment of the Tropical Ocean/Global Atmosphere Programme. This case-study was part of an international model intercomparison project organized by Working Group 4 ‘Precipitating Convective Cloud Systems’ of the GEWEX (Global Energy and Water-cycle Experiment) Cloud System Study. Eight SCM groups using different deep-convection parametrizations participated in this project. The SCMs were forced by temperature and moisture tendencies that had been computed from a reference cloud-resolving model (CRM) simulation using open boundary conditions. The comparison of the SCM results with the reference CRM simulation provided insight into the ability of current convection and cloud schemes to represent organized convection. The CRM results enabled a detailed evaluation of the SCMs in terms of the thermodynamic structure and the convective mass flux of the system, the latter being closely related to the surface convective precipitation. It is shown that the SCMs could reproduce reasonably well the time evolution of the surface convective and stratiform precipitation, the convective mass flux, and the thermodynamic structure of the squall-line system. The thermodynamic structure simulated by the SCMs depended on how the models partitioned the precipitation between convective and stratiform. However, structural differences persisted in the thermodynamic profiles simulated by the SCMs and the CRM. These differences could be attributed to the fact that the total mass flux used to compute the SCM forcing differed from the convective mass flux. The SCMs could not adequately represent these organized mesoscale circulations and the microphysicallradiative forcing associated with the stratiform region. This issue is generally known as the ‘scale-interaction’ problem that can only be properly addressed in fully three-dimensional simulations. Sensitivity simulations run by several groups showed that the time evolution of the surface convective precipitation was considerably smoothed when the convective closure was based on convective available potential energy instead of moisture convergence. Finally, additional SCM simulations without using a convection parametrization indicated that the impact of a convection parametrization in forced SCM runs was more visible in the moisture profiles than in the temperature profiles because convective transport was particularly important in the moisture budget.

Does the PMSP connectionist model of single word reading learn to read in the same way as a child?

The Plaut, McClelland, Seidenberg and Patterson (1996) connectionist model of reading was evaluated at two points early in its training against reading data collected from British children on two occasions during their first year of literacy instruction. First, the network’s non-word reading was poor relative to word reading when compared with the children. Second, the network made more non-lexical than lexical errors, the opposite pattern to the children. Three adaptations were made to the training of the network to bring it closer to the learning environment of a child: an incremental training regime was adopted; the network was trained on grapheme– phoneme correspondences; and a training corpus based on words found in children’s early reading materials was used. The modifications caused a sharp improvement in non-word reading, relative to word reading, resulting in a near perfect match to the children’s data on this measure. The modified network, however, continued to make predominantly non-lexical errors, although evidence from a small-scale implementation of the full triangle framework suggests that this limitation stems from the lack of a semantic pathway. Taken together, these results suggest that, when properly trained, connectionist models of word reading can offer insights into key aspects of reading development in children.

Development of a wind gust model to estimate gust speeds and their return periods

Spatially dense observations of gust speeds are necessary for various applications, but their availability is limited in space and time. This work presents an approach to help to overcome this problem. The main objective is the generation of synthetic wind gust velocities. With this aim, theoretical wind and gust distributions are estimated from 10 yr of hourly observations collected at 123 synoptic weather stations provided by the German Weather Service. As pre-processing, an exposure correction is applied on measurements of the mean wind velocity to reduce the influence of local urban and topographic effects. The wind gust model is built as a transfer function between distribution parameters of wind and gust velocities. The aim of this procedure is to estimate the parameters of gusts at stations where only wind speed data is available. These parameters can be used to generate synthetic gusts, which can improve the accuracy of return periods at test sites with a lack of observations. The second objective is to determine return periods much longer than the nominal length of the original time series by considering extreme value statistics. Estimates for both local maximum return periods and average return periods for single historical events are provided. The comparison of maximum and average return periods shows that even storms with short average return periods may lead to local wind gusts with return periods of several decades. Despite uncertainties caused by the short length of the observational records, the method leads to consistent results, enabling a wide range of possible applications.

The first real-time worldwide ionospheric predictions network: an advance in support of spaceborne experimentation, on-line model validation, and space weather

We report on the first realtime ionospheric predictions network and its capabilities to ingest a global database and forecast F-layer characteristics and "in situ" electron densities along the track of an orbiting spacecraft. A global network of ionosonde stations reported around-the-clock observations of F-region heights and densities, and an on-line library of models provided forecasting capabilities. Each model was tested against the incoming data; relative accuracies were intercompared to determine the best overall fit to the prevailing conditions; and the best-fit model was used to predict ionospheric conditions on an orbit-to-orbit basis for the 12-hour period following a twice-daily model test and validation procedure. It was found that the best-fit model often provided averaged (i.e., climatologically-based) accuracies better than 5% in predicting the heights and critical frequencies of the F-region peaks in the latitudinal domain of the TSS-1R flight path. There was a sharp contrast however, in model-measurement comparisons involving predictions of actual, unaveraged, along-track densities at the 295 km orbital altitude of TSS-1R In this case, extrema in the first-principle models varied by as much as an order of magnitude in density predictions, and the best-fit models were found to disagree with the "in situ" observations of Ne by as much as 140%. The discrepancies are interpreted as a manifestation of difficulties in accurately and self-consistently modeling the external controls of solar and magnetospheric inputs and the spatial and temporal variabilities in electric fields, thermospheric winds, plasmaspheric fluxes, and chemistry.

Improving power and accuracy of genome-wide association studies via a multi-locus mixed linear model methodology

Genome-wide association studies (GWAS) have been widely used in genetic dissection of complex traits. However, common methods are all based on a fixed-SNP-effect mixed linear model (MLM) and single marker analysis, such as efficient mixed model analysis (EMMA). These methods require Bonferroni correction for multiple tests, which often is too conservative when the number of markers is extremely large. To address this concern, we proposed a random-SNP-effect MLM (RMLM) and a multi-locus RMLM (MRMLM) for GWAS. The RMLM simply treats the SNP-effect as random, but it allows a modified Bonferroni correction to be used to calculate the threshold p value for significance tests. The MRMLM is a multi-locus model including markers selected from the RMLM method with a less stringent selection criterion. Due to the multi-locus nature, no multiple test correction is needed. Simulation studies show that the MRMLM is more powerful in QTN detection and more accurate in QTN effect estimation than the RMLM, which in turn is more powerful and accurate than the EMMA. To demonstrate the new methods, we analyzed six flowering time related traits in Arabidopsis thaliana and detected more genes than previous reported using the EMMA. Therefore, the MRMLM provides an alternative for multi-locus GWAS.

Evaluation of a polynya flux model by means of thermal infrared satellite estimates

We test the ability of a two-dimensional flux model to simulate polynya events with narrow open-water zones by comparing model results to ice-thickness and ice-production estimates derived from thermal infrared Moderate Resolution Imaging Spectroradiometer (MODIS) observations in conjunction with an atmospheric dataset. Given a polynya boundary and an atmospheric dataset, the model correctly reproduces the shape of an 11 day long event, using only a few simple conservation laws. Ice production is slightly overestimated by the model, owing to an underestimated ice thickness. We achieved best model results with the consolidation thickness parameterization developed by Biggs and others (2000). Observed regional discrepancies between model and satellite estimates might be a consequence of the missing representation of the dynamic of the thin-ice thickening (e.g. rafting). We conclude that this simplified polynya model is a valuable tool for studying polynya dynamics and estimating associated fluxes of single polynya events.

CMB and LSS constraints on a single-field model of inflation

A new inflationary scenario whose exponential potential V (Phi) has a quadratic dependence on the field Phi in addition to the standard linear term is confronted with the five-year observations of the Wilkinson-Microwave Anisotropy Probe and the Sloan Digital Sky Survey data. The number of e-folds (N), the ratio of tensor-to-scalar perturbations (r), the spectral scalar index of the primordial power spectrum (n(s)) and its running (dn(s)/d ln k) depend on the dimensionless parameter a multiplying the quadratic term in the potential. In the limit a. 0 all the results of the exponential potential are fully recovered. For values of alpha not equal 0, we find that the model predictions are in good agreement with the current observations of the Cosmic Microwave Background (CMB) anisotropies and Large-Scale Structure (LSS) in the Universe. Copyright (C) EPLA, 2008.