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.

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.

In vitro assessment of the bioaccessibility of brominated flame retardants in indoor dust using a colon extended model of the human gastrointestinal tract

An in vitro colon extended physiologically based extraction test (CEPBET) which incorporates human gastrointestinal tract (GIT) parameters (including pH and chemistry, solid-to-fluid ratio, mixing and emptying rates) was applied for the first time to study the bioaccessibility of brominated flame retardants (BFRs) from the 3 main GIT compartments (stomach, small intestine and colon) following ingestion of indoor dust. Results revealed the bioaccessibility of γ-HBCD (72%) was less than that for α- and β-isomers (92% and 80% respectively) which may be attributed to the lower aqueous solubility of the γ-isomer (2 μg L−1) compared to the α- and β-isomers (45 and 15 μg L−1 respectively). No significant change in the enantiomeric fractions of HBCDs was observed in any of the studied samples. However, this does not completely exclude the possibility of in vivo enantioselective absorption of HBCDs, as the GIT cell lining and bacterial flora – which may act enantioselectively – are not included in the current CE-PBET model. While TBBP-A was almost completely (94%) bioaccessible, BDE-209 was the least (14%) bioaccessible of the studied BFRs. Bioaccessibility of tri-hepta BDEs ranged from 32–58%. No decrease in the bioaccessibility with increasing level of bromination was observed in the studied PBDEs.

Assessment of a 1 hour gridded precipitation dataset to drive a hydrological model: a case study of the summer 2007 floods in the Upper Severn, UK

In this study a gridded hourly 1-km precipitation dataset for a meso-scale catchment (4,062 km2) of the Upper Severn River, UK was constructed using rainfall radar data to disaggregate a daily precipitation (rain gauge) dataset. The dataset was compared to an hourly precipitation dataset created entirely from rainfall radar data. Results found that when assessed against gauge readings and as input to the Lisflood-RR hydrological model, the rain gauge/radar disaggregated dataset performed the best suggesting that this simple method of combining rainfall radar data with rain gauge readings can provide temporally detailed precipitation datasets for calibrating hydrological models.

Assessment of temperature, trace species, and ozone in chemistry-climate model simulations of the recent past

Simulations of the stratosphere from thirteen coupled chemistry-climate models (CCMs) are evaluated to provide guidance for the interpretation of ozone predictions made by the same CCMs. The focus of the evaluation is on how well the fields and processes that are important for determining the ozone distribution are represented in the simulations of the recent past. The core period of the evaluation is from 1980 to 1999 but long-term trends are compared for an extended period (1960–2004). Comparisons of polar high-latitude temperatures show that most CCMs have only small biases in the Northern Hemisphere in winter and spring, but still have cold biases in the Southern Hemisphere spring below 10 hPa. Most CCMs display the correct stratospheric response of polar temperatures to wave forcing in the Northern, but not in the Southern Hemisphere. Global long-term stratospheric temperature trends are in reasonable agreement with satellite and radiosonde observations. Comparisons of simulations of methane, mean age of air, and propagation of the annual cycle in water vapor show a wide spread in the results, indicating differences in transport. However, for around half the models there is reasonable agreement with observations. In these models the mean age of air and the water vapor tape recorder signal are generally better than reported in previous model intercomparisons. Comparisons of the water vapor and inorganic chlorine (Cly) fields also show a large intermodel spread. Differences in tropical water vapor mixing ratios in the lower stratosphere are primarily related to biases in the simulated tropical tropopause temperatures and not transport. The spread in Cly, which is largest in the polar lower stratosphere, appears to be primarily related to transport differences. In general the amplitude and phase of the annual cycle in total ozone is well simulated apart from the southern high latitudes. Most CCMs show reasonable agreement with observed total ozone trends and variability on a global scale, but a greater spread in the ozone trends in polar regions in spring, especially in the Arctic. In conclusion, despite the wide range of skills in representing different processes assessed here, there is sufficient agreement between the majority of the CCMs and the observations that some confidence can be placed in their predictions.

A digital ecosystems model of assessment feedback on student learning

The term ecosystem has been used to describe complex interactions between living organisms and the physical world. The principles underlying ecosystems can also be applied to complex human interactions in the digital world. As internet technologies make an increasing contribution to teaching and learning practice in higher education, the principles of digital ecosystems may help us understand how to maximise technology to benefit active, self-regulated learning especially among groups of learners. Here, feedback on student learning is presented within a conceptual digital ecosystems model of learning. Additionally, we have developed a Web 2.0-based system, called ASSET, which incorporates multimedia and social networking features to deliver assessment feedback within the functionality of the digital ecosystems model. Both the digital ecosystems model and the ASSET system are described and their implications for enhancing feedback on student learning are discussed.

Sequential variations of phytoplankton growth and mortality in an NPZ model: a remote-sensing-based assessment

Radiometric data in the visible domain acquired by satellite remote sensing have proven to be powerful for monitoring the states of the ocean, both physical and biological. With the help of these data it is possible to understand certain variations in biological responses of marine phytoplankton on ecological time scales. Here, we implement a sequential data-assimilation technique to estimate from a conventional nutrient–phytoplankton–zooplankton (NPZ) model the time variations of observed and unobserved variables. In addition, we estimate the time evolution of two biological parameters, namely, the specific growth rate and specific mortality of phytoplankton. Our study demonstrates that: (i) the series of time-varying estimates of specific growth rate obtained by sequential data assimilation improves the fitting of the NPZ model to the satellite-derived time series: the model trajectories are closer to the observations than those obtained by implementing static values of the parameter; (ii) the estimates of unobserved variables, i.e., nutrient and zooplankton, obtained from an NPZ model by implementation of a pre-defined parameter evolution can be different from those obtained on applying the sequences of parameters estimated by assimilation; and (iii) the maximum estimated specific growth rate of phytoplankton in the study area is more sensitive to the sea-surface temperature than would be predicted by temperature-dependent functions reported previously. The overall results of the study are potentially useful for enhancing our understanding of the biological response of phytoplankton in a changing environment.

A semi-distributed ntegrated itrogen model for multiple source assessment in tchments (INCA): Part I — model structure and process equations

A new model has been developed for assessing multiple sources of nitrogen in catchments. The model (INCA) is process based and uses reaction kinetic equations to simulate the principal mechanisms operating. The model allows for plant uptake, surface and sub-surface pathways and can simulate up to six land uses simultaneously. The model can be applied to catchment as a semi-distributed simulation and has an inbuilt multi-reach structure for river systems. Sources of nitrogen can be from atmospheric deposition, from the terrestrial environment (e.g. agriculture, leakage from forest systems etc.), from urban areas or from direct discharges via sewage or intensive farm units. The model is a daily simulation model and can provide information in the form of time series at key sites, or as profiles down river systems or as statistical distributions. The process model is described and in a companion paper the model is applied to the River Tywi catchment in South Wales and the Great Ouse in Bedfordshire.

A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment

Risk assessment for mammals is currently based on external exposure measurements, but effects of toxicants are better correlated with the systemically available dose than with the external administered dose. So for risk assessment of pesticides, toxicokinetics should be interpreted in the context of potential exposure in the field taking account of the timescale of exposure and individual patterns of feeding. Internal concentration is the net result of absorption, distribution, metabolism and excretion (ADME). We present a case study for thiamethoxam to show how data from ADME study on rats can be used to parameterize a body burden model which predicts body residue levels after exposures to LD50 dose either as a bolus or eaten at different feeding rates. Kinetic parameters were determined in male and female rats after an intravenous and oral administration of 14C labelled by fitting one-compartment models to measured pesticide concentrations in blood for each individual separately. The concentration of thiamethoxam in blood over time correlated closely with concentrations in other tissues and so was considered representative of pesticide concentration in the whole body. Body burden model simulations showed that maximum body weight-normalized doses of thiamethoxam were lower if the same external dose was ingested normally than if it was force fed in a single bolus dose. This indicates lower risk to rats through dietary exposure than would be estimated from the bolus LD50. The importance of key questions that should be answered before using the body burden approach in risk assessment, data requirements and assumptions made in this study are discussed in detail.

Precipitation diurnal cycle and summer climatology assessment over South America: An evaluation of Regional Climate Model version 3 simulations

Regional Climate Model version 3 (RegCM3) simulations of 17 summers (1988-2004) over part of South America south of 5 degrees S were evaluated to identify model systematic errors. Model results were compared to different rainfall data sets (Climate Research Unit (CRU), Climate Prediction Center (CPC), Global Precipitation Climatology Project (GPCP), and National Centers for Environmental Prediction (NCEP) reanalysis), including the five summers mean (1998-2002) precipitation diurnal cycle observed by the Tropical Rainfall Measuring Mission (TRMM)-Precipitation Radar (PR). In spite of regional differences, the RegCM3 simulates the main observed aspects of summer climatology associated with the precipitation (northwest-southeast band of South Atlantic Convergence Zone (SACZ)) and air temperature (warmer air in the central part of the continent and colder in eastern Brazil and the Andes Mountains). At a regional scale, the main RegCM3 failures are the underestimation of the precipitation in the northern branch of the SACZ and some unrealistic intense precipitation around the Andes Mountains. However, the RegCM3 seasonal precipitation is closer to the fine-scale analyses (CPC, CRU, and TRMM-PR) than is the NCEP reanalysis, which presents an incorrect north-south orientation of SACZ and an overestimation of its intensity. The precipitation diurnal cycle observed by TRMM-PR shows pronounced contrasts between Tropics and Extratropics and land and ocean, where most of these features are simulated by RegCM3. The major similarities between the simulation and observation, especially the diurnal cycle phase, are found over the continental tropical and subtropical SACZ regions, which present afternoon maximum (1500-1800 UTC) and morning minimum (0900-1200 UTC). More specifically, over the core of SACZ, the phase and amplitude of the simulated precipitation diurnal cycle are very close to the TRMM-PR observations. Although there are amplitude differences, the RegCM3 simulates the observed nighttime rainfall in the eastern Andes Mountains, over the Atlantic Ocean, and also over northern Argentina. The main simulation deficiencies are found in the Atlantic Ocean and near the Andes Mountains. Over the Atlantic Ocean the convective scheme is not triggered; thus the rainfall arises from the grid-scale scheme and therefore differs from the TRMM-PR. Near the Andes, intense (nighttime and daytime) simulated precipitation could be a response of an incorrect circulation and topographic uplift. Finally, it is important to note that unlike most reported bias of global models, RegCM3 does not trigger the moist convection just after sunrise over the southern part of the Amazon.

Flood Risk Assessment in Coastal Drainage Basins through a Multivariate Analysis within a GIS-Based Model

This paper presents a GIS-based multicriteria flood risk assessment and mapping approach applied to coastal drainage basins where hydrological data are not available. It involves risk to different types of possible processes: coastal inundation (storm surge), river, estuarine and flash flood, either at urban or natural areas, and fords. Based on the causes of these processes, several environmental indicators were taken to build-up the risk assessment. Geoindicators include geological-geomorphologic proprieties of Quaternary sedimentary units, water table, drainage basin morphometry, coastal dynamics, beach morphodynamics and microclimatic characteristics. Bioindicators involve coastal plain and low slope native vegetation categories and two alteration states. Anthropogenic indicators encompass land use categories properties such as: type, occupation density, urban structure type and occupation consolidation degree. The selected indicators were stored within an expert Geoenvironmental Information System developed for the State of Sao Paulo Coastal Zone (SIIGAL), which attributes were mathematically classified through deterministic approaches, in order to estimate natural susceptibilities (Sn), human-induced susceptibilities (Sa), return period of rain events (Ri), potential damages (Dp) and the risk classification (R), according to the equation R=(Sn.Sa.Ri).Dp. Thematic maps were automatically processed within the SIIGAL, in which automata cells (""geoenvironmental management units"") aggregating geological-geomorphologic and land use/native vegetation categories were the units of classification. The method has been applied to the Northern Littoral of the State of Sao Paulo (Brazil) in 32 small drainage basins, demonstrating to be very useful for coastal zone public politics, civil defense programs and flood management.

Towards an assessment of character interdependence in avian RNA phylogenetics: A general secondary structure model for the avian mitochondrial 16S rRNA

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Inference and local influence assessment in skew-normal null intercept measurement error model

In this article, we discuss inferential aspects of the measurement error regression models with null intercepts when the unknown quantity x (latent variable) follows a skew normal distribution. We examine first the maximum-likelihood approach to estimation via the EM algorithm by exploring statistical properties of the model considered. Then, the marginal likelihood, the score function and the observed information matrix of the observed quantities are presented allowing direct inference implementation. In order to discuss some diagnostics techniques in this type of models, we derive the appropriate matrices to assessing the local influence on the parameter estimates under different perturbation schemes. The results and methods developed in this paper are illustrated considering part of a real data set used by Hadgu and Koch [1999, Application of generalized estimating equations to a dental randomized clinical trial. Journal of Biopharmaceutical Statistics, 9, 161-178].

Metabolomic assessment with CE-MS of the nutraceutical effect of Cystoseira spp extracts in an animal model

There is a need of scientific evidence of claimed nutraceutical effects, but also there is a social movement towards the use of natural products and among them algae are seen as rich resources. Within this scenario, the development of methodology for rapid and reliable assessment of markers of efficiency and security of these extracts is necessary. The rat treated with streptozotocin has been proposed as the most appropriate model of systemic oxidative stress for studying antioxidant therapies. Cystoseira is a brown alga containing fucoxanthin and other carothenes whose pressure-assisted extracts were assayed to discover a possible beneficial effect on complications related to diabetes evolution in an acute but short-term model. Urine was selected as the sample and CE-TOF-MS as the analytical technique to obtain the fingerprints in a non-target metabolomic approach. Multivariate data analysis revealed a good clustering of the groups and permitted the putative assignment of compounds statistically significant in the classification. Interestingly a group of compounds associated to lysine glycation and cleavage from proteins was found to be increased in diabetic animals receiving vehicle as compared to control animals receiving vehicle (N6, N6, N6-trimethyl-L-lysine, N-methylnicotinamide, galactosylhydroxylysine, L-carnitine, N6-acetyl-N6-hydroxylysine, fructose-lysine, pipecolic acid, urocanic acid, amino-isobutanoate, formylisoglutamine. Fructoselysine significantly decreased after the treatment changing from a 24% increase to a 19% decrease. CE-MS fingerprinting of urine has provided a group of compounds different to those detected with other techniques and therefore proves the necessity of a cross-platform analysis to obtain a broad view of biological samples.

Integration and Assessment of Information Literacy in an Undergraduate Biology Program: a Sustainable and Transferrable Model

This presentation was offered as part of the CUNY Library Assessment Conference, Reinventing Libraries: Reinventing Assessment, held at the City University of New York in June 2014.