Improving sequence-based fold recognition by using 3D model quality assessment

Motivation: The ability of a simple method (MODCHECK) to determine the sequence–structure compatibility of a set of structural models generated by fold recognition is tested in a thorough benchmark analysis. Four Model Quality Assessment Programs (MQAPs) were tested on 188 targets from the latest LiveBench-9 automated structure evaluation experiment. We systematically test and evaluate whether the MQAP methods can successfully detect native-likemodels. Results: We show that compared with the other three methods tested MODCHECK is the most reliable method for consistently performing the best top model selection and for ranking the models. In addition, we show that the choice of model similarity score used to assess a model's similarity to the experimental structure can influence the overall performance of these tools. Although these MQAP methods fail to improve the model selection performance for methods that already incorporate protein three dimension (3D) structural information, an improvement is observed for methods that are purely sequence-based, including the best profile–profile methods. This suggests that even the best sequence-based fold recognition methods can still be improved by taking into account the 3D structural information.

Daily precipitation statistics in regional climate models: evaluation and intercomparison for the European Alps

An evaluation is undertaken of the statistics of daily precipitation as simulated by five regional climate models using comprehensive observations in the region of the European Alps. Four limited area models and one variable-resolution global model are considered, all with a grid spacing of 50 km. The 15-year integrations were forced from reanalyses and observed sea surface temperature and sea ice (global model from sea surface only). The observational reference is based on 6400 rain gauge records (10–50 stations per grid box). Evaluation statistics encompass mean precipitation, wet-day frequency, precipitation intensity, and quantiles of the frequency distribution. For mean precipitation, the models reproduce the characteristics of the annual cycle and the spatial distribution. The domain mean bias varies between −23% and +3% in winter and between −27% and −5% in summer. Larger errors are found for other statistics. In summer, all models underestimate precipitation intensity (by 16–42%) and there is a too low frequency of heavy events. This bias reflects too dry summer mean conditions in three of the models, while it is partly compensated by too many low-intensity events in the other two models. Similar intermodel differences are found for other European subregions. Interestingly, the model errors are very similar between the two models with the same dynamical core (but different parameterizations) and they differ considerably between the two models with similar parameterizations (but different dynamics). Despite considerable biases, the models reproduce prominent mesoscale features of heavy precipitation, which is a promising result for their use in climate change downscaling over complex topography.

Evaluation of water and energy budgets in regional climate models applied over Europe

This study presents a model intercomparison of four regional climate models (RCMs) and one variable resolution atmospheric general circulation model (AGCM) applied over Europe with special focus on the hydrological cycle and the surface energy budget. The models simulated the 15 years from 1979 to 1993 by using quasi-observed boundary conditions derived from ECMWF re-analyses (ERA). The model intercomparison focuses on two large atchments representing two different climate conditions covering two areas of major research interest within Europe. The first is the Danube catchment which represents a continental climate dominated by advection from the surrounding land areas. It is used to analyse the common model error of a too dry and too warm simulation of the summertime climate of southeastern Europe. This summer warming and drying problem is seen in many RCMs, and to a less extent in GCMs. The second area is the Baltic Sea catchment which represents maritime climate dominated by advection from the ocean and from the Baltic Sea. This catchment is a research area of many studies within Europe and also covered by the BALTEX program. The observed data used are monthly mean surface air temperature, precipitation and river discharge. For all models, these are used to estimate mean monthly biases of all components of the hydrological cycle over land. In addition, the mean monthly deviations of the surface energy fluxes from ERA data are computed. Atmospheric moisture fluxes from ERA are compared with those of one model to provide an independent estimate of the convergence bias derived from the observed data. These help to add weight to some of the inferred estimates and explain some of the discrepancies between them. An evaluation of these biases and deviations suggests possible sources of error in each of the models. For the Danube catchment, systematic errors in the dynamics cause the prominent summer drying problem for three of the RCMs, while for the fourth RCM this is related to deficiencies in the land surface parametrization. The AGCM does not show this drying problem. For the Baltic Sea catchment, all models similarily overestimate the precipitation throughout the year except during the summer. This model deficit is probably caused by the internal model parametrizations, such as the large-scale condensation and the convection schemes.

Considering user attitude and behaviour in persuasive systems design: the 3D-RAB model

As in any technology systems, analysis and design issues are among the fundamental challenges in persuasive technology. Currently, the Persuasive Systems Development (PSD) framework is considered to be the most comprehensive framework for designing and evaluation of persuasive systems. However, the framework is limited in terms of providing detailed information which can lead to selection of appropriate techniques depending on the variable nature of users or use over time. In light of this, we propose a model which is intended for analysing and implementing behavioural change in persuasive technology called the 3D-RAB model. The 3D-RAB model represents the three dimensional relationships between attitude towards behaviour, attitude towards change or maintaining a change, and current behaviour, and distinguishes variable levels in a user’s cognitive state. As such it provides a framework which could be used to select appropriate techniques for persuasive technology.

Novel polyvinylpyrrolidones to improve delivery of poorly-water soluble drugs; from design to synthesis and evaluation

Polyvinylpyrrolidone is a widely used in tablet formulations with the linear form acting as a wetting agent and disintegrant whereas the cross-linked form is a super-disintegrant. We have previously reported that simply mixing the commercial cross-linked polymer with ibuprofen disrupted drug crystallinity with consequent improvements in drug dissolution behavior. In this study, we have designed and synthesized novel cross-linking agents containing a range of oligoether moieties which have then be polymerized with vinylpyrrolidone to generate a suite of novel excipients with enhanced hydrogen-bonding capabilities. The polymers have a porous surface and swell in most common solvents and in water; properties which suggest their value as disintegrants. The polymers were evaluated in simple physical mixtures with ibuprofen as a model poorly-water soluble drug. The results show that the novel PVPs induce the drug to become “X-ray amorphous”, which increased dissolution to a greater extent than that seen with commercial cross-linked PVP. The polymers stabilize the amorphous drug with no evidence for recrystallization seen after 20 weeks storage.

Likelihood-free estimation of model evidence

Statistical methods of inference typically require the likelihood function to be computable in a reasonable amount of time. The class of “likelihood-free” methods termed Approximate Bayesian Computation (ABC) is able to eliminate this requirement, replacing the evaluation of the likelihood with simulation from it. Likelihood-free methods have gained in efficiency and popularity in the past few years, following their integration with Markov Chain Monte Carlo (MCMC) and Sequential Monte Carlo (SMC) in order to better explore the parameter space. They have been applied primarily to estimating the parameters of a given model, but can also be used to compare models. Here we present novel likelihood-free approaches to model comparison, based upon the independent estimation of the evidence of each model under study. Key advantages of these approaches over previous techniques are that they allow the exploitation of MCMC or SMC algorithms for exploring the parameter space, and that they do not require a sampler able to mix between models. We validate the proposed methods using a simple exponential family problem before providing a realistic problem from human population genetics: the comparison of different demographic models based upon genetic data from the Y chromosome.

Evaluation and management of the impact of land use change on the nitrogen and phosphorus load delivered to surface waters: the export coefficient modelling approach

A manageable, relatively inexpensive model was constructed to predict the loss of nitrogen and phosphorus from a complex catchment to its drainage system. The model used an export coefficient approach, calculating the total nitrogen (N) and total phosphorus (P) load delivered annually to a water body as the sum of the individual loads exported from each nutrient source in its catchment. The export coefficient modelling approach permits scaling up from plot-scale experiments to the catchment scale, allowing application of findings from field experimental studies at a suitable scale for catchment management. The catchment of the River Windrush, a tributary of the River Thames, UK, was selected as the initial study site. The Windrush model predicted nitrogen and phosphorus loading within 2% of observed total nitrogen load and 0.5% of observed total phosphorus load in 1989. The export coefficient modelling approach was then validated by application in a second research basin, the catchment of Slapton Ley, south Devon, which has markedly different catchment hydrology and land use. The Slapton model was calibrated within 2% of observed total nitrogen load and 2.5% of observed total phosphorus load in 1986. Both models proved sensitive to the impact of temporal changes in land use and management on water quality in both catchments, and were therefore used to evaluate the potential impact of proposed pollution control strategies on the nutrient loading delivered to the River Windrush and Slapton Ley

Liquid-vapour homogenisation of fluid inclusions in stalagmites: Evaluation of a new thermometer for paleoclimate research

We present a new approach to determine palaeotemperatures (mean annual surface temperatures) based on measurements of the liquid–vapour homogenisation temperature of fluid inclusions in stalagmites. The aim of this study is to explore the potential and the limitations of this new palaeothermometer and to develop a reliable methodology for routine applications in palaeoclimate research. Therefore, we have investigated recent fluid inclusions from the top part of actively growing stalagmites that have formed at temperatures close to the present-day cave air temperature. A precondition for measuring homogenisation temperatures of originally monophase inclusions is the nucleation of a vapour bubble by means of single ultra-short laser pulses. Based on the observed homogenisation temperatures (Th(obs)) and measurements of the vapour bubble diameter at a known temperature, we calculated stalagmite formation temperatures (Tf) by applying a thermodynamic model that takes into account the effect of surface tension on liquid–vapour homogenisation. Results from recent stalagmite samples demonstrate that calculated stalagmite formation temperatures match the present-day cave air temperature within ± 0.2 °C. To avoid artificially induced changes of the fluid density we defined specific demands on the selection, handling and preparation of the stalagmite samples. Application of the method is restricted to stalagmites that formed at cave temperatures greater than ~ 9–11 °C.

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.

Evaluation of water and energy budgets in regional climate models applied over Europe

Abstract This study presents a model intercomparison of four regional climate models (RCMs) and one variable resolution atmospheric general circulation model (AGCM) applied over Europe with special focus on the hydrological cycle and the surface energy budget. The models simulated the 15 years from 1979 to 1993 by using quasi-observed boundary conditions derived from ECMWF re-analyses (ERA). The model intercomparison focuses on two large atchments representing two different climate conditions covering two areas of major research interest within Europe. The first is the Danube catchment which represents a continental climate dominated by advection from the surrounding land areas. It is used to analyse the common model error of a too dry and too warm simulation of the summertime climate of southeastern Europe. This summer warming and drying problem is seen in many RCMs, and to a less extent in GCMs. The second area is the Baltic Sea catchment which represents maritime climate dominated by advection from the ocean and from the Baltic Sea. This catchment is a research area of many studies within Europe and also covered by the BALTEX program. The observed data used are monthly mean surface air temperature, precipitation and river discharge. For all models, these are used to estimate mean monthly biases of all components of the hydrological cycle over land. In addition, the mean monthly deviations of the surface energy fluxes from ERA data are computed. Atmospheric moisture fluxes from ERA are compared with those of one model to provide an independent estimate of the convergence bias derived from the observed data. These help to add weight to some of the inferred estimates and explain some of the discrepancies between them. An evaluation of these biases and deviations suggests possible sources of error in each of the models. For the Danube catchment, systematic errors in the dynamics cause the prominent summer drying problem for three of the RCMs, while for the fourth RCM this is related to deficiencies in the land surface parametrization. The AGCM does not show this drying problem. For the Baltic Sea catchment, all models similarily overestimate the precipitation throughout the year except during the summer. This model deficit is probably caused by the internal model parametrizations, such as the large-scale condensation and the convection schemes.

Predictability and uncertainty in a regional climate model

The evaluation of the quality and usefulness of climate modeling systems is dependent upon an assessment of both the limited predictability of the climate system and the uncertainties stemming from model formulation. In this study a methodology is presented that is suited to assess the performance of a regional climate model (RCM), based on its ability to represent the natural interannual variability on monthly and seasonal timescales. The methodology involves carrying out multiyear ensemble simulations (to assess the predictability bounds within which the model can be evaluated against observations) and multiyear sensitivity experiments using different model formulations (to assess the model uncertainty). As an example application, experiments driven by assimilated lateral boundary conditions and sea surface temperatures from the ECMWF Reanalysis Project (ERA-15, 1979–1993) were conducted. While the ensemble experiment demonstrates that the predictability of the regional climate varies strongly between different seasons and regions, being weakest during the summer and over continental regions, important sensitivities of the modeling system to parameterization choices are uncovered. In particular, compensating mechanisms related to the long-term representation of the water cycle are revealed, in which summer dry and hot conditions at the surface, resulting from insufficient evaporation, can persist despite insufficient net solar radiation (a result of unrealistic cloud-radiative feedbacks).

Characteristics of high-resolution versions of the Met Office unified model for forecasting convection over the United Kingdom

With many operational centers moving toward order 1-km-gridlength models for routine weather forecasting, this paper presents a systematic investigation of the properties of high-resolution versions of the Met Office Unified Model for short-range forecasting of convective rainfall events. The authors describe a suite of configurations of the Met Office Unified Model running with grid lengths of 12, 4, and 1 km and analyze results from these models for a number of convective cases from the summers of 2003, 2004, and 2005. The analysis includes subjective evaluation of the rainfall fields and comparisons of rainfall amounts, initiation, cell statistics, and a scale-selective verification technique. It is shown that the 4- and 1-km-gridlength models often give more realistic-looking precipitation fields because convection is represented explicitly rather than parameterized. However, the 4-km model representation suffers from large convective cells and delayed initiation because the grid length is too long to correctly reproduce the convection explicitly. These problems are not as evident in the 1-km model, although it does suffer from too numerous small cells in some situations. Both the 4- and 1-km models suffer from poor representation at the start of the forecast in the period when the high-resolution detail is spinning up from the lower-resolution (12 km) starting data used. A scale-selective precipitation verification technique implies that for later times in the forecasts (after the spinup period) the 1-km model performs better than the 12- and 4-km models for lower rainfall thresholds. For higher thresholds the 4-km model scores almost as well as the 1-km model, and both do better than the 12-km model.

Are clinical documents optimised for patient safety? A critical analysis of patient safety outcomes using the EDA error model

Iatrogenic errors and patient safety in clinical processes are an increasing concern. The quality of process information in hardcopy or electronic form can heavily influence clinical behaviour and decision making errors. Little work has been undertaken to assess the safety impact of clinical process planning documents guiding the clinical actions and decisions. This paper investigates the clinical process documents used in elective surgery and their impact on latent and active clinical errors. Eight clinicians from a large health trust underwent extensive semi- structured interviews to understand their use of clinical documents, and their perceived impact on errors and patient safety. Samples of the key types of document used were analysed. Theories of latent organisational and active errors from the literature were combined with the EDA semiotics model of behaviour and decision making to propose the EDA Error Model. This model enabled us to identify perceptual, evaluation, knowledge and action error types and approaches to reducing their causes. The EDA error model was then used to analyse sample documents and identify error sources and controls. Types of knowledge artefact structures used in the documents were identified and assessed in terms of safety impact. This approach was combined with analysis of the questionnaire findings using existing error knowledge from the literature. The results identified a number of document and knowledge artefact issues that give rise to latent and active errors and also issues concerning medical culture and teamwork together with recommendations for further work.

Assessing the spatial and temporal variation in the skill of precipitation forecasts from an NWP model

It is becoming increasingly important to be able to verify the spatial accuracy of precipitation forecasts, especially with the advent of high-resolution numerical weather prediction (NWP) models. In this article, the fractions skill score (FSS) approach has been used to perform a scale-selective evaluation of precipitation forecasts during 2003 from the Met Office mesoscale model (12 km grid length). The investigation shows how skill varies with spatial scale, the scales over which the data assimilation (DA) adds most skill, and how the loss of that skill is dependent on both the spatial scale and the rainfall coverage being examined. Although these results come from a specific model, they demonstrate how this verification approach can provide a quantitative assessment of the spatial behaviour of new finer-resolution models and DA techniques.

Stratospheric climate and variability from a general circulation model and observations

The climate and natural variability of the large-scale stratospheric circulation simulated by a newly developed general circulation model are evaluated against available global observations. The simulation consisted of a 30-year annual cycle integration performed with a comprehensive model of the troposphere and stratosphere. The observations consisted of a 15-year dataset from global operational analyses of the troposphere and stratosphere. The model evaluation concentrates on the simulation of the evolution of the extratropical stratospheric circulation in both hemispheres. The December–February climatology of the observed zonal mean winter circulation is found to be reasonably well captured by the model, although in the Northern Hemisphere upper stratosphere the simulated westerly winds are systematically stronger and a cold bias is apparent in the polar stratosphere. This Northern Hemisphere stratospheric cold bias virtually disappears during spring (March–May), consistent with a realistic simulation of the spring weakening of the mean westerly winds in the model. A considerable amount of monthly interannual variability is also found in the simulation in the Northern Hemisphere in late winter and early spring. The simulated interannual variability is predominantly caused by polar warmings of the stratosphere, in agreement with observations. The breakdown of the Northern Hemisphere stratospheric polar vortex appears therefore to occur in a realistic way in the model. However, in early winter the model severely underestimates the interannual variability, especially in the upper troposphere. The Southern Hemisphere winter (June–August) zonal mean temperature is systematically colder in the model, and the simulated winds are somewhat too strong in the upper stratosphere. Contrary to the results for the Northern Hemisphere spring, this model cold bias worsens during the Southern Hemisphere spring (September–November). Significant discrepancies between the model results and the observations are therefore found during the breakdown of the Southern Hemisphere polar vortex. For instance, the simulated Southern Hemisphere stratosphere westerly jet continuously decreases in intensity more or less in situ from June to November, while the observed stratospheric jet moves downward and poleward.