370 research outputs found

    Improved metrics for comparing structures of macromolecular assemblies determined by 3D electron-microscopy

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    Recent developments in 3-dimensional electron microcopy (3D-EM) techniques and a concomitant drive to look at complex molecular structures, have led to a rapid increase in the amount of volume data available for biomolecules. This creates a demand for better methods to analyse the data, including improved scores for comparison, classification and integration of data at different resolutions. To this end, we developed and evaluated a set of scoring functions that compare 3D-EM volumes. To test our scores we used a benchmark set of volume alignments derived from the Electron Microscopy Data Bank. We find that the performance of different scores vary with the map-type, resolution and the extent of overlap between volumes. Importantly, adding the overlap information to the local scoring functions can significantly improve their precision and accuracy in a range of resolutions. A combined score involving the local mutual information and overlap (LMI_OV) performs best overall, irrespective of the map category, resolution or the extent of overlap, and we recommend this score for general use. The local mutual information score itself is found to be more discriminatory than cross-correlation coefficient for intermediate-to-low resolution maps or when the map size and density distribution differ significantly. For comparing map surfaces, we implemented two filters to detect the surface points, including one based on the ‘extent of surface exposure’. We show that scores that compare surfaces are useful at low resolutions and for maps with evident surface features. All the scores discussed are implemented in TEMPy (http://tempy.ismb.lon.ac.uk/)

    Progress and challenges to the global waste management system

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    Rapid economic growth, urbanization and increasing population have caused (materially intensive) resource consumption to increase, and consequently the release of large amounts of waste to the environment. From a global perspective, current waste and resource management lacks a holistic approach covering the whole chain of product design, raw material extraction, production, consumption, recycling and waste management. In this article, progress and different sustainability challenges facing the global waste management system are presented and discussed. The study leads to the conclusion that the current, rather isolated efforts, in different systems for waste management, waste reduction and resource management are indeed not sufficient in a long term sustainability perspective. In the future, to manage resources and wastes sustainably, waste management requires a more systems-oriented approach that addresses the root causes for the problems. A specific issue to address is the development of improved feedback information (statistics) on how waste generation is linked to consumption

    Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F(2α )Metabolite Levels

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    Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F(2α )metabolite 15-ketodihydro-PGF(2α )(PG-metabolite), progesterone and oestradiol (E(2)-17β) levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra

    Change of Diurnal Heart Rate Patterns During Pregnancy and Lactation in Dogs (Canis familiaris)

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    Pregnancy and lactation involve great demands on the cardiovascular system. The purpose of this study was to investigate how the heart rate and diurnal heart rate pattern change when dogs become pregnant or lactate. Five clinically healthy female beagle dogs were mated, and delivered three to seven healthy puppies. The heart rate was investigated with 24-h ECG (Holter) once during anoestrus, at 3, 5, 7 and 9 weeks of pregnancy, and at week 4 postpartum (lactation). However, at 9 weeks, the ECG could not be recorded for the fully 24 h in 4 of 5 dogs, because labour started and the dogs then appeared disturbed by the recordings. The results at this date are not included in the statistical comparison. The heart rate increased progressively during pregnancy and was still elevated at 4 weeks of lactation. During late pregnancy the difference in heart rates between daytime and nighttime became smaller, but the heart rate was significantly higher in daytime in all periods. In conclusion, the increased heart rates during pregnancy and lactation reflect increased demands on the cardiovascular system and may be important to consider in clinical practice

    User profiling for Pre-fetching or Caching in a Catch-Up TV Network

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    We investigate the potential of different pre-fetching and/or caching strategies for different user behaviour with respect to surfing or browsing in a catch-up-TV network. To this end we identify accounts and channels associated with strong or weak surfing or browsing respectively and study the distributions of hold times for the different types of behaviour. Finally we present results from a request prediction model and a caching simulation for the different types of behaviour and find that the results are relatively similar

    Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population

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    <div><p>Genome-wide association studies (GWAS) have identified dozens of common genetic variants associated with risk of colorectal cancer (CRC). However, the majority of CRC heritability remains unclear. In order to discover low-frequency, high-risk CRC susceptibility variants in Swedish population, we genotyped 1 515 CRC patients enriched for familial cases, and 12 108 controls. Case/control association analysis suggested eight novel variants associated with CRC risk (OR 2.0–17.6, p-value < 2.0E-07), comprised of seven coding variants in genes <i>RAB11FIP5</i>, <i>POTEA</i>, <i>COL27A1</i>, <i>MUC5B</i>, <i>PSMA8</i>, <i>MYH7B</i>, and <i>PABPC1L</i> as well as one variant downstream of <i>NEU1</i> gene. We also confirmed 27 out of 30 risk variants previously reported from GWAS in CRC with a mixed European population background. This study identified rare, coding sequence variants associated with CRC risk through analysis in a relatively homogeneous population. The segregation data suggest a complex mode of inheritance in seemingly dominant pedigrees.</p></div

    Another tool in the genome-wide association study arsenal: population-based detection of somatic gene conversion

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    The hunt for the genetic contributors to complex disease has used a number of strategies, resulting in the identification of variants associated with many of the common diseases affecting society. However most of the genetic variants detected to date are single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) and fall far short of explaining the full genetic component of any given disease. An as yet untapped genomic mechanism is somatic gene conversion and deletion, which could be complicit in disease risk but has been challenging to detect in genome-wide datasets. In a recent publication in BMC Medicine by Kenneth Ross, the author uses existing datasets to look at somatic gene conversion and deletion in human disease. Here, we describe how Ross's recent efforts to detect such occurrences could impact the field going forward
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