Mixture models of nucleotide sequence evolution that account for heterogeneity in the substitution process across sites and across lineages

Molecular phylogenetic studies of homologous sequences of nucleotides often assume that the underlying evolutionary process was globally stationary, reversible, and homogeneous (SRH), and that a model of evolution with one or more site-specific and time-reversible rate matrices (e.g., the GTR rate matrix) is enough to accurately model the evolution of data over the whole tree. However, an increasing body of data suggests that evolution under these conditions is an exception, rather than the norm. To address this issue, several non-SRH models of molecular evolution have been proposed, but they either ignore heterogeneity in the substitution process across sites (HAS) or assume it can be modeled accurately using the distribution. As an alternative to these models of evolution, we introduce a family of mixture models that approximate HAS without the assumption of an underlying predefined statistical distribution. This family of mixture models is combined with non-SRH models of evolution that account for heterogeneity in the substitution process across lineages (HAL). We also present two algorithms for searching model space and identifying an optimal model of evolution that is less likely to over- or underparameterize the data. The performance of the two new algorithms was evaluated using alignments of nucleotides with 10 000 sites simulated under complex non-SRH conditions on a 25-tipped tree. The algorithms were found to be very successful, identifying the correct HAL model with a 75% success rate (the average success rate for assigning rate matrices to the tree's 48 edges was 99.25%) and, for the correct HAL model, identifying the correct HAS model with a 98% success rate. Finally, parameter estimates obtained under the correct HAL-HAS model were found to be accurate and precise. The merits of our new algorithms were illustrated with an analysis of 42 337 second codon sites extracted from a concatenation of 106 alignments of orthologous genes encoded by the nuclear genomes of Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, S. castellii, S. kluyveri, S. bayanus, and Candida albicans. Our results show that second codon sites in the ancestral genome of these species contained 49.1% invariable sites, 39.6% variable sites belonging to one rate category (V1), and 11.3% variable sites belonging to a second rate category (V2). The ancestral nucleotide content was found to differ markedly across these three sets of sites, and the evolutionary processes operating at the variable sites were found to be non-SRH and best modeled by a combination of eight edge-specific rate matrices (four for V1 and four for V2). The number of substitutions per site at the variable sites also differed markedly, with sites belonging to V1 evolving slower than those belonging to V2 along the lineages separating the seven species of Saccharomyces. Finally, sites belonging to V1 appeared to have ceased evolving along the lineages separating S. cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus, implying that they might have become so selectively constrained that they could be considered invariable sites in these species.

Susceptibility to social engineering in social networking sites: The case of Facebook

Past research has suggested that social engineering poses the most significant security risk. Recent studies have suggested that social networking sites (SNSs) are the most common source of social engineering attacks. The risk of social engineering attacks in SNSs is associated with the difficulty of making accurate judgments regarding source credibility in the virtual environment of SNSs. In this paper, we quantitatively investigate source credibility dimensions in terms of social engineering on Facebook, as well as the source characteristics that influence Facebook users to judge an attacker as credible, therefore making them susceptible to victimization. Moreover, in order to predict users’ susceptibility to social engineering victimization based on their demographics, we investigate the effectiveness of source characteristics on different demographic groups by measuring the consent intentions and behavior responses of users to social engineering requests using a role-play experiment.

PocketMatch: A new algorithm to compare binding sites in protein structures

Recognizing similarities and deriving relationships among protein molecules is a fundamental requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison. Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. A comparison with other site matching algorithms is also presented. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless combined with chemical nature of amino acids. Conclusion: A new algorithm has been developed to compare binding sites in accurate, efficient and high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250(th) second for one comparison on a single processor. A parallel version on BlueGene has also been implemented.

Waste not want not: Applying an old adage to the modern issue of pharmaceutical waste

Our predecessors taught us, ‘waste not, want not’ – if we did not waste anything we would always have enough. Unfortunately, we did not heed their sage advice. Over the last three centuries, human kind’s wastefulness, or lack of respect for the finite resources of this planet, has contributed to climate change and negatively impacted on ‘ecosystem services’ with a significant, irreversible loss of biodiversity...

Micro-scale anaerobic digestion of point source components of organic fraction of municipal solid waste

The fermentation characteristics of six specific types of the organic fraction of municipal solid waste (OFMSW) were examined, with an emphasis on properties that are needed when designing plug-flow type anaerobic bioreactors. More specifically, the decomposition patterns of a vegetable (cabbage), fruits (banana and citrus peels), fresh leaf litter of bamboo and teak leaves, and paper (newsprint) waste streams as feedstocks were studied. Individual OFMSW components were placed into nylon mesh bags and subjected to various fermentation periods (solids retention time, SRT) within the inlet of a functioning plug-flow biogas fermentor. These were removed at periodic intervals, and their composition was analyzed to monitor decomposition rates and changes in chemical composition. Components like cabbage waste, banana peels, and orange peels fermented rapidly both in a plug-flow biogas reactor (PFBR) as well as under a biological methane potential (BMP) assay, while other OFMSW components (leaf litter from bamboo and teak leaves and newsprint) fermented slowly with poor process stability and moderate biodegradation. For fruit and vegetable wastes (FVW), a rapid and efficient removal of pectins is the main cause of rapid disintegration of these feedstocks, which left behind very little compost forming residues (2–5%). Teak and bamboo leaves and newsprint decomposed only to 25–50% in 30 d. These results confirm the potential for volatile fatty acids accumulation in a PFBR’s inlet and suggest a modification of the inlet zone or operation of a PFBR with the above feedstocks.

Perception of ultraviolet light by crab spiders and its role in selection of hunting sites

The perception of ultraviolet (UV) light by spiders has so far been only demonstrated in salticids. Crab spiders (Thomisidae) hunt mostly on flowers and need to find appropriate hunting sites. Previous studies have shown that some crab spiders that reflect UV light use UV contrast to enhance prey capture. The high UV contrast can be obtained either by modulation of body colouration or active selection of appropriate backgrounds for foraging. We show that crab spiders (Thomisus sp.)hunting on Spathiphyllum plants use chromatic contrast, especially UV contrast, to make themselves attractive to hymenopteran prey. Apart from that, they are able to achieve high UV contrast by active selection of non-UV reflecting surfaces when given a choice of UV-reflecting and non-UV reflecting surfaces in the absence of odour cues. Honeybees (Apis cerana) approached Spathiphyllum plants bearing crab spiders on which the spiders were high UV-contrast targets with greater frequency than those plants on which the UV-contrast of the spiders was low. Thus, crab spiders can perceive UV and may use it to choose appropriate backgrounds to enhance prey capture, by exploiting the attraction of prey such as honeybees to UV.

Cholinergic Muscarinic Receptors in Human Fetal Brain: Ontogeny of [3H]Quinuclidinyl Benzilate Binding Sites in Corpus Striatum, Brainstem, and Cerebellum

The ontogeny of muscarinic receptors was studied in human fetal striatum, brainstem, and cerebellum to investigate general principles of synaptogenesis as well as the physiological balance between various chemical synapses during development in a given region of the brain. [3H]Quinuclidinyl benzilate ([-'H]QNB) binding was assayed in total particulate fraction (TPF) from various parts of brain. In the corpus striatum, QNB binding sites are present at 16 weeks of gestation (average concentration 180 fmol/mg protein of TPF), slowly increase up to 24 weeks (average concentration 217 fmol/mg protein), and rapidly increase during the third trimester to 480 fmol/mg protein of TPF. In contrast, dopaminergic receptors exist as two subpopulations. one with low affinity and the other with high affinity up to the 24th week of gestation; all of them acquire the highaffinity characteristic during the third trimester. In brainstem, the muscarinic receptors show maximum concentration by 16 weeks of age (360 fmolimg protein of TPF). Subsequently the muscarinic receptor concentration shows a gradual decline in the brainstem. In cerebellum, except for a slight increase at 24 weeks (average concentration 90 fmol/mg protein of TPF), the receptor concentration remained nearly constant at about 60-70 fmolimg protein of TPF throughout fetal life. This study demonstrates that the ontogeny of muscarinic receptors varies among the different regions, and the patterns observed suggest that receptor formation occurs principally in the third trimester. Also noteworthy is the finding that the QNB binding sites decreased in all regions of the human brain during adult life. Key Words: Cholinergic muscarinic receptors-Quinuclidinyl benzilate-Corpus striaturn-Brainstem-Cerebellum. Ravikumar B. V. and Sastry P. S. Cholinergic muscarinic receptors in human fetal brain: Ontogeny of [3H]quinuclidinyl benzilate binding sites in corpus striatum, brainstem, and cerebellum. J. Neurochem. 45, 1948- 1950 (1985).

A large-scale analysis of genetic variants within putative miRNA binding sites in prostate cancer

Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3' untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P<2.3×10(-5)) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. SIGNIFICANCE Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk.

An overview of land application of pig effluent-P using soil P chemistry and mass balance calculations.

Attention is directed at land application of piggery effluent (containing urine, faeces, water, and wasted feed) as a potential source of water resource contamination with phosphorus (P). This paper summarises P-related properties of soil from 0-0.05 m depth at 11 piggery effluent application sites, in order to explore the impact that effluent application has had on the potential for run-off transport of P. The sites investigated were situated on Alfisol, Mollisol, Vertisol, and Spodosol soils in areas that received effluent for 1.5-30 years (estimated effluent-P applications of 100-310000 kg P/ha in total). Total (PT), bicarbonate extractable (PB), and soluble P forms were determined for the soil (0-0.05 m) at paired effluent and no-effluent sites, as well as texture, oxalate-extractable Fe and Al, organic carbon, and pH. All forms of soil P at 0-0.05 m depth increased with effluent application (PB at effluent sites was 1.7-15 times that at no-effluent sites) at 10 of the 11 sites. Increases in PB were strongly related to net P applications (regression analysis of log values for 7 sites with complete data sets: 82.6 % of variance accounted for, p <0.01). Effluent irrigation tended to increase the proportion of soil PT in dilute CaCl2-extractable forms (PTC: effluent average 2.0 %; no-effluent average 0.6%). The proportion of PTC in non-molybdate reactive forms (centrifuged supernatant) decreased (no-effluent average, 46.4 %; effluent average, 13.7 %). Anaerobic lagoon effluent did not reliably acidify soil, since no consistent relationship was observed for pH with effluent application. Soil organic carbon was increased in most of the effluent areas relative to the no-effluent areas. The four effluent areas where organic carbon was reduced had undergone intensive cultivation and cropping. Current effluent management at many of the piggeries failed to maximise the potential for waste P recapture. Ten of the case-study effluent application areas have received effluent-P in excess of crop uptake. While this may not represent a significant risk of leaching where sorption retains P, it has increased the risk of transport of P by run-off. Where such sites are close to surface water, run-off P loads should be managed.

Fluorescent labelling of strychnine: A novel approach for recognition of strychnine binding sites on neuronal membrane

trychnine was coupled to fluorescein isothiocyanate to mark strychnine binding sites in spinal cord of rat. Specific binding of strychnine could be demonstrated in synaptosomal fraction. Addition of glycine to the strychninised membrane led to a decrease in fluorescence indicating same receptor loci.

Comparison of sampling sites and detection methods for Haemophilus parasuis

Objective To improve the isolation rate and identification procedures for Haemophilus parasuis from pig tissues. Design Thirteen sampling sites and up to three methods were used to confirm the presence of H. parasuis in pigs after experimental challenge. Procedure Colostrum-deprived, naturally farrowed pigs were challenged intratracheally with H parasuis serovar 12 or 4. Samples taken during necropsy were either inoculated onto culture plates, processed directly for PCR or enriched prior to being processed for PCR. The recovery of H parasuis from different sampling sites and using different sampling methods was compared for each serovar. Results H parasuis was recovered from several sample sites for all serovar 12 challenged pigs, while the trachea was the only positive site for all pigs following serovar 4 challenge. The method of solid medium culture of swabs, and confirmation of the identity of cultured bacteria by PCR, resulted in 38% and 14% more positive results on a site basis for serovars 12 and 4, retrospectively, than direct PCR on the swabs. This difference was significant in the serovar 12 challenge. Conclusion Conventional culture proved to be more effective in detecting H parasuis than direct PCR or PCR on enrichment broths. For subacute (serovar 4) infections, the most successful sites for culture or direct PCR were pleural fluid, peritoneal fibrin and fluid, lung and pericardial fluid. For acute (serovar 12) infections, the best sites were lung, heart blood, affected joints and brain. The methodologies and key sampling sites identified in this study will enable improved isolation of H parasuis and aid the diagnosis of Glässer's disease.

Ways and Means for Disposal of Surplus Water in Storage Reservoirs and other Irrigation and Flood Protective Works

In the paper new way of classifying spillways have been suggested. The various types, merits and demerits or existing spillway devices have been discussed. The considerations governing the choice of a design of a spillway have been mention. A criteria for working out the economics of spillway design has been suggested. An efficient surplus sing device has next been described and compared with other devices. In conclusion it has been suggested that the most efficient and at the same time economical arrangement will be a combination of devices. In conclusion it has been suggested will be a combination of crest gate, volute siphons and high head gates. The appendix gives a list of devices used in dams in various parts of the world.

Minimizing overprocessing waste in business processes via predictive activity ordering

Overprocessing waste occurs in a business process when effort is spent in a way that does not add value to the customer nor to the business. Previous studies have identied a recurrent overprocessing pattern in business processes with so-called "knockout checks", meaning activities that classify a case into "accepted" or "rejected", such that if the case is accepted it proceeds forward, while if rejected, it is cancelled and all work performed in the case is considered unnecessary. Thus, when a knockout check rejects a case, the effort spent in other (previous) checks becomes overprocessing waste. Traditional process redesign methods propose to order knockout checks according to their mean effort and rejection rate. This paper presents a more fine-grained approach where knockout checks are ordered at runtime based on predictive machine learning models. Experiments on two real-life processes show that this predictive approach outperforms traditional methods while incurring minimal runtime overhead.

Selecting replacements for invasive plants to support frugivores in highly modified sites: a case study focusing on Lantana camara

Invasive plants are regarded as a major threat to biodiversity worldwide. Yet, in some cases, invasive plants now perform important ecological functions. For example, fleshy-fruited invasive plants provide food that supports indigenous frugivore populations. How can the disparate goals of conservation versus invasive weed control be managed? We suggest using the fruit characteristics of the invasive plant to select replacement indigenous plants that are functionally similar from the perspective of frugivores. These could provide replacement food resources at sites where plants with these characteristics are part of the goal plant community and where such plants would not otherwise regenerate. Replacement plants could also redirect seed dispersal processes to favour indigenous, rather than invasive, plant species. We investigated the utility of this approach by ranking all indigenous fleshy-fruited plant species from a region using a simple model that scored species based upon measures of fruit phenology, morphology, conspicuousness and accessibility relative to a target invasive species, Lantana (Lantana camara). The model successfully produced high scores for indigenous plant species that were used by more of the frugivores of Lantana than a random selection of plants, suggesting that this approach warrants further investigation.