Implementation of 3D spatial indexing and compression in a large-scale molecular dynamics simulation database for rapid atomic contact detection

<p>Abstract</p> <p>Background</p> <p>Molecular dynamics (MD) simulations offer the ability to observe the dynamics and interactions of both whole macromolecules and individual atoms as a function of time. Taken in context with experimental data, atomic interactions from simulation provide insight into the mechanics of protein folding, dynamics, and function. The calculation of atomic interactions or contacts from an MD trajectory is computationally demanding and the work required grows exponentially with the size of the simulation system. We describe the implementation of a spatial indexing algorithm in our multi-terabyte MD simulation database that significantly reduces the run-time required for discovery of contacts. The approach is applied to the Dynameomics project data. Spatial indexing, also known as spatial hashing, is a method that divides the simulation space into regular sized bins and attributes an index to each bin. Since, the calculation of contacts is widely employed in the simulation field, we also use this as the basis for testing compression of data tables. We investigate the effects of compression of the trajectory coordinate tables with different options of data and index compression within MS SQL SERVER 2008.</p> <p>Results</p> <p>Our implementation of spatial indexing speeds up the calculation of contacts over a 1 nanosecond (ns) simulation window by between 14% and 90% (i.e., 1.2 and 10.3 times faster). For a 'full' simulation trajectory (51 ns) spatial indexing reduces the calculation run-time between 31 and 81% (between 1.4 and 5.3 times faster). Compression resulted in reduced table sizes but resulted in no significant difference in the total execution time for neighbour discovery. The greatest compression (~36%) was achieved using page level compression on both the data and indexes.</p> <p>Conclusions</p> <p>The spatial indexing scheme significantly decreases the time taken to calculate atomic contacts and could be applied to other multidimensional neighbor discovery problems. The speed up enables on-the-fly calculation and visualization of contacts and rapid cross simulation analysis for knowledge discovery. Using page compression for the atomic coordinate tables and indexes saves ~36% of disk space without any significant decrease in calculation time and should be considered for other non-transactional databases in MS SQL SERVER 2008.</p

The expanded diversity of methylophilaceae from Lake Washington through cultivation and genomic sequencing of novel ecotypes.

We describe five novel Methylophilaceae ecotypes from a single ecological niche in Lake Washington, USA, and compare them to three previously described ecotypes, in terms of their phenotype and genome sequence divergence. Two of the ecotypes appear to represent novel genera within the Methylophilaceae. Genome-based metabolic reconstruction highlights metabolic versatility of Methylophilaceae with respect to methylotrophy and nitrogen metabolism, different ecotypes possessing different combinations of primary substrate oxidation systems (MxaFI-type methanol dehydrogenase versus XoxF-type methanol dehydrogenase; methylamine dehydrogenase versus N-methylglutamate pathway) and different potentials for denitrification (assimilatory versus respiratory nitrate reduction). By comparing pairs of closely related genomes, we uncover that site-specific recombination is the main means of genomic evolution and strain divergence, including lateral transfers of genes from both closely- and distantly related taxa. The new ecotypes and the new genomes contribute significantly to our understanding of the extent of genomic and metabolic diversity among organisms of the same family inhabiting the same ecological niche. These organisms also provide novel experimental models for studying the complexity and the function of the microbial communities active in methylotrophy

The Postpartum Specific Anxiety Scale: development and preliminary validation

Perinatal symptoms of anxiety are increasingly recognised due to their high prevalence and impact. Studies using pregnancy-specific anxiety measures have found that they may predict perinatal outcomes more effectively than general measures. However, no such measure exists to assess anxieties specific to the postpartum. This study aimed to develop and validate a measure (Postpartum Specific Anxiety Scale; PSAS) that accurately represents the specific anxieties faced by postpartum women, using a four-stage methodology: (1) 51 items were generated from interviews conducted with a group of 19 postpartum women at two time points, (2) the scale was reviewed and refined by a diverse expert panel, (3) an online pilot study (n = 146) was conducted to assess comprehensibility and acceptability and (4) an online sample of 1282 mothers of infants up to 6 months old completed the PSAS against a battery of convergent measures. A subsample (n = 262) repeated the PSAS 2 weeks later. The PSAS possessed good face and content validity and was comprehensible and acceptable to postpartum women. PSAS scores were significantly correlated with other measures indicating good convergent validity. Principal component analyses (PCA) revealed a simple four-factor structure. Reliability of the overall scale and individual PSAS factors proved to be good to excellent. A preliminary receiver operating characteristic (ROC) analysis also suggested that the PSAS may be a useful screening tool. The psychometric evidence suggests that the PSAS is an acceptable, valid, and reliable research tool to assess anxieties, which are specific to the postpartum period. Next steps in the iterative validation process are considered for both research and screening purposes

Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells.

Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Δβ=13%, P<7.4 × 10(-4)) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Δβ=23%, P<9.1 × 10(-6)) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout.We thank Kerra Pearce (UCL Genomics) for array processing, and Tim Fell and Jonathan Best (CellCentric), Jason Wray (UCL) and Rosemary Drake (TAP Biosystems) for discussions. We also thank Minal Patel, Chris Kirton, Anja Kolb-Kokocinski, Willem H. Ouwehand, Richard Durbin and Fiona M. Watt on behalf of the Human Induced Pluripotent Stem Cell Initiative (HipSci) funded by grant WT098503 from the Wellcome Trust and the Medical Research Council, for sharing data and materials. This work was supported in part by a TSB/EPSRC grant (TS/H000933/1). The Vallier lab is supported by the Cambridge Hospitals National Institute for Health Research Biomedical Research Center and an ERC Starting Grant (Relieve IMDS). F.A.C.S. is funded by a PhD studentship from Fundação para a Ciência e a Tecnologia (SFRH/BD/69033/2010). The Ferguson-Smith lab is supported by grants from the MRC and Wellcome Trust, and EU-FP7 projects EPIGENESYS (257082) and BLUEPRINT (282510). The Beck lab is supported by the Wellcome Trust (084071), a Royal Society Wolfson Research Merit Award (WM100023), and EU-FP7 projects EPIGENESYS (257082) and BLUEPRINT (282510).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1045

Secondary Prevention of Suicide

Leo Sher and colleagues discuss recent research on interventions to prevent secondary suicide and discuss the additional research that is needed

Allocation of nutrients during the reproductive cycle of Ophidiaster ophidianus (Echinodermata: Asteroidea)

Copyright © 2011 Taylor & Francis.The reproductive cycle of Ophidiaster ophidianus (strictly protected status) from Sa˜o Miguel Island, in the Azorean Archipelago was studied. The reproductive strategy; the energy allocation of each sex during the reproductive cycle and the nutritional condition of the population were analyzed. Gonadal index (GI) showed a clear seasonal pattern with spawning between August and October but histological examination revealed that gamete release can occur throughout the entire year. The pyloric caeca index (PCI) showed little annual variation but with an inverse relationship with the GI. Allocation of energy to the gonads and to the pyloric caeca reflected the seasonal reproductive strategy of this species. Individuals were able to simultaneously develop gonads, pyloric caeca, and quickly regenerate lost arms. There was a major expenditure of energy by females compared to males but, sexual size dimorphism was not observed. The reproductive pattern observed in O. ophidianus combining rich food availability and seawater temperatures characteristic of a temperate zone may be the key to the success of this species in the Azorean oceanic Island.Portuguese Foundation for Science and Technology (FCT)

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

The effectiveness of a web-based self-help intervention to reduce suicidal thoughts: A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Suicide, attempted suicide and suicidal thoughts are major public health problems worldwide. Effective face-to-face treatments are Cognitive Behavioural Therapy (CBT), Dialectical Behavioural Therapy (DBT) and Problem Solving Treatment (PST). However, about two-thirds of persons who die by suicide have not been in contact with mental health care services in the preceding year, and many have never been treated. Furthermore, many patients do not disclose their suicidal thoughts to their care provider. This may be out of shame, due to fear of stigma or due to lack of trust in (mental) health care. Since many suicidal individuals seek information online, the internet provides an opportunity to reach suicidal individuals who would not be contacted otherwise. By providing a self-help intervention online, persons can anonymously learn to gain control over their suicidal thoughts. There is convincing evidence that self-help is effective for a number of mental disorders. In this study the effectiveness for suicidal thoughts is examined.</p> <p>Methods/Design</p> <p>In this study, a recently developed self-help intervention will be evaluated in a Randomized Controlled Trial. The intervention is based on Cognitive Behavioural Therapy and is aimed at subjects who experience mild to moderate suicidal thoughts. This is defined as a score between 1 and 26 on the Beck Scale for Suicidal Ideation (BSS). Higher and lower scores are excluded. In addition, severely depressed subjects are excluded. In total, 260 subjects will be randomly allocated to the intervention-condition (N = 130) or to the information-control condition (N = 130). Self-report questionnaires will be filled out at baseline, 6 weeks after baseline and 18 weeks after baseline. Primary outcome measure is the reduction in frequency and intensity of suicidal thoughts. Secondary outcome measures are the reduction of hopelessness, anxiety and depression, sleeplessness, worry and quality of life measures.</p> <p>Discussion</p> <p>This study is the first to evaluate the effectiveness of a web-based self-help intervention for suicidal thoughts. Several limitations and strengths of the design are discussed.</p> <p>Trial Registration</p> <p>Netherlands Trial Register, NTR1689</p