Learning probabilistic models of hydrogen bond stability from molecular dynamics simulation trajectories

Hydrogen bonds (H-bonds) play a key role in both the formation and stabilization of protein structures. H-bonds involving atoms from residues that are close to each other in the main-chain sequence stabilize secondary structure elements. H-bonds between atoms from distant residues stabilize a protein’s tertiary structure. However, H-bonds greatly vary in stability. They form and break while a protein deforms. For instance, the transition of a protein from a nonfunctional to a functional state may require some H-bonds to break and others to form. The intrinsic strength of an individual H-bond has been studied from an energetic viewpoint, but energy alone may not be a very good predictor. Other local interactions may reinforce (or weaken) an H-bond. This paper describes inductive learning methods to train a protein-independent probabilistic model of H-bond stability from molecular dynamics (MD) simulation trajectories. The training data describes H-bond occurrences at successive times along these trajectories by the values of attributes called predictors. A trained model is constructed in the form of a regression tree in which each non-leaf node is a Boolean test (split) on a predictor. Each occurrence of an H-bond maps to a path in this tree from the root to a leaf node. Its predicted stability is associated with the leaf node. Experimental results demonstrate that such models can predict H-bond stability quite well. In particular, their performance is roughly 20 % better than that of models based on H-bond energy alone. In addition, they can accurately identify a large fraction of the least stable H-bonds in a give

Strategies, methods and tools for managing nanorisks in construction

This paper presents a general overview of the work carried out by European project SCAFFOLD (GA 280535) during its 30 months of life, with special emphasis on risk management component. The research conducted by SCAFFOLD is focused on the European construction sector and considers 5 types of nanomaterials (TiO2, SiO2, carbon nanofibres, cellulose nanofibers and nanoclays), 6 construction applications (Depollutant mortars, selfcompacting concretes, coatings, self-cleaning coatings, fire resistant panels and insulation materials) and 26 exposure scenarios, including lab, pilot and industrial scales. The document focuses on the structure, content and operation modes of the Risk Management Toolkit developed by the project to facilitate the implementation of "nano-management" in construction companies. The tool deploys and integrated approach OHSAS 18001 - ISO 31000 and is currently being validated on 5 industrial case studies.Research carried out by project SCAFFOLD was made possible thanks to funding from the European Commission, through the Seventh Framework Programme (GA 280535

User Experiences of Development of Dependence on the Synthetic Cannabinoids, 5f-AKB48 and 5F-PB-22, and Subsequent Withdrawal Syndromes

Emergence of synthetic cannabinoids (SCBs) in herbal smoking mixtures is a public health concern. New SCB’s such as 5f-AKB48 and 5F-PB-22 have been detected in French seizures and in sudden death post mortems in the US. The aim was to describe development of dependence on herbal smoking mixtures containing the SCB’s, 5f-AKB48 and 5F-PB-22 and subsequent withdrawal syndromes. Dependent users of herbal smoking mixtures known to contain the SCB’s 5f-AKB48 and 5F-PB-22 with an average Severity of Dependence Score (SDS) of 13 were interviewed using a structured guide (three males/three females). Narratives were analysed using the Empirical Phenomenological Psychological (EPP) five step method. Six themes with 68 categories emerged from the analysis. Themes are illustrated as 1) Networks and Product Availability; 2) Drivers and Motives for Use; 3) Effect and Pathways toward Dependence; 4) Poly Substance Use and Comparisons to Natural Cannabis; 5) Dependence and Withdrawal and 6) Self-detoxification Attempts. Two higher levels of abstraction above these theme-levels emerged from the data, with sole use of herbal smoking mixtures containing 5f-AKB48 and 5F-PB-22 centering on the interplay between intense cravings, compulsive all-consuming seeking, use and re-dose behaviours, and fear of the psychiatric and self-harms caused when in withdrawal. This is the first study describing dependence and withdrawal experiences in users dependent on 5f-AKB48 and 5F-PB-22. Given the potential for adverse psychiatric and physical consequences of dependent use, further development of specific clinical responses and clinical research around toxicity and withdrawal severity are warranted

Large-scale climatic phenomena drive fluctuations in macroinvertebrate assemblages in lowland tropical streams, Costa Rica: The importance of ENSO events in determining long-term (15y) patterns

Understanding how environmental variables influence the distribution and density of organisms over relatively long temporal scales is a central question in ecology given increased climatic variability (e.g., precipitation, ENSO events). The primary goal of our study was to evaluate long-term (15y time span) patterns of climate, as well as environmental parameters in two Neotropical streams in lowland Costa Rica, to assess potential effects on aquatic macroinvertebrates. We also examined the relative effects of an 8y whole-stream P-enrichment experiment on macroinvertebrate assemblages against the backdrop of this long-term study. Climate, environmental variables and macroinvertebrate samples were measured monthly for 7y and then quarterly for an additional 8y in each stream. Temporal patterns in climatic and environmental variables showed high variability over time, without clear inter-annual or intra-annual patterns. Macroinvertebrate richness and abundance decreased with increasing discharge and was positively related to the number of days since the last high discharge event. Findings show that fluctuations in stream physicochemistry and macroinvertebrate assemblage structure are ultimately the result of large-scale climatic phenomena, such as ENSO events, while the 8y P-enrichment did not appear to affect macroinvertebrates. Our study demonstrates that Neotropical lowland streams are highly dynamic and not as stable as is commonly presumed, with high intra- and inter-annual variability in environmental parameters that change the structure and composition of freshwater macroinvertebrate assemblages.This study was financed by National Science Foundation (DEB 1122389) to Catherine M. Pringle. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR

A storage manager for the hypernode model

Book synopsis: The theme of this book is the potential of new advanced database systems. The volume presents the proceedings of the 10th British National Conference on Databases, held in Aberdeen, Scotland, in July 1992. The volume contains two invited papers, one on the promise of distributed computing andthe challenges of legacy systems by M.L. Brodie, and the other on object-oriented requirements capture and analysis and the Orca project by D.J.L. Gradwell. The following four parts each contain three submitted papers selected from a total of 36 submissions. The parts are entitled: - Object-oriented databases - Parallel implementationsand industrial systems - Non-relational data models - Logic programming and database

Implementation of a graph-based data model for complex objects

We have developed a graph-based data model called the Hypernode Model whose single data structure is the hypernode, a directed graph whose nodes may themselves reference further directed graphs. A prototype database system supporting this model is being developed at London University as part of a project whose aims are threefold: (i) to ascertain the expressiveness and flexibility of the hypernode model, (ii) to experiment with various querying paradigms for this model, and (iii) to investigate the suitability of the directed graph as a data structure supported throughout all levels of the implementation. The purpose of this paper is to report upon our findings to date