deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data

Gene fusions created by somatic genomic rearrangements are known to play an important role in the onset and development of some cancers, such as lymphomas and sarcomas. RNA-Seq (whole transcriptome shotgun sequencing) is proving to be a useful tool for the discovery of novel gene fusions in cancer transcriptomes. However, algorithmic methods for the discovery of gene fusions using RNA-Seq data remain underdeveloped. We have developed deFuse, a novel computational method for fusion discovery in tumor RNA-Seq data. Unlike existing methods that use only unique best-hit alignments and consider only fusion boundaries at the ends of known exons, deFuse considers all alignments and all possible locations for fusion boundaries. As a result, deFuse is able to identify fusion sequences with demonstrably better sensitivity than previous approaches. To increase the specificity of our approach, we curated a list of 60 true positive and 61 true negative fusion sequences (as confirmed by RT-PCR), and have trained an adaboost classifier on 11 novel features of the sequence data. The resulting classifier has an estimated value of 0.91 for the area under the ROC curve. We have used deFuse to discover gene fusions in 40 ovarian tumor samples, one ovarian cancer cell line, and three sarcoma samples. We report herein the first gene fusions discovered in ovarian cancer. We conclude that gene fusions are not infrequent events in ovarian cancer and that these events have the potential to substantially alter the expression patterns of the genes involved; gene fusions should therefore be considered in efforts to comprehensively characterize the mutational profiles of ovarian cancer transcriptomes

Sporangiospore Size Dimorphism Is Linked to Virulence of Mucor circinelloides

Mucor circinelloides is a zygomycete fungus and an emerging opportunistic pathogen in immunocompromised patients, especially transplant recipients and in some cases otherwise healthy individuals. We have discovered a novel example of size dimorphism linked to virulence. M. circinelloides is a heterothallic fungus: (+) sex allele encodes SexP and (−) sex allele SexM, both of which are HMG domain protein sex determinants. M. circinelloides f. lusitanicus (Mcl) (−) mating type isolates produce larger asexual sporangiospores that are more virulent in the wax moth host compared to (+) isolates that produce smaller less virulent sporangiospores. The larger sporangiospores germinate inside and lyse macrophages, whereas the smaller sporangiospores do not. sexMΔ mutants are sterile and still produce larger virulent sporangiospores, suggesting that either the sex locus is not involved in virulence/spore size or the sexP allele plays an inhibitory role. Phylogenetic analysis supports that at least three extant subspecies populate the M. circinelloides complex in nature: Mcl, M. circinelloides f. griseocyanus, and M. circinelloides f. circinelloides (Mcc). Mcc was found to be more prevalent among clinical Mucor isolates, and more virulent than Mcl in a diabetic murine model in contrast to the wax moth host. The M. circinelloides sex locus encodes an HMG domain protein (SexP for plus and SexM for minus mating types) flanked by genes encoding triose phosphate transporter (TPT) and RNA helicase homologs. The borders of the sex locus between the three subspecies differ: the Mcg sex locus includes the promoters of both the TPT and the RNA helicase genes, whereas the Mcl and Mcc sex locus includes only the TPT gene promoter. Mating between subspecies was restricted compared to mating within subspecies. These findings demonstrate that spore size dimorphism is linked to virulence of M. circinelloides species and that plasticity of the sex locus and adaptations in pathogenicity have occurred during speciation of the M. circinelloides complex

Optimum Layouts of a Cluster of Heaving Point Absorbers in front of a Wall

In this paper, we determine optimum layouts of a cluster of oblate spheroidal heaving point absorbers in front of a wall, that maximize the annual averaged power absorbed by the cluster, while satisfying specific spatial constraints. An iterative optimization process is developed by coupling a hydrodynamic model with a genetic algorithms solver. Optimization is performed for three near-shore sites in the Aegean Sea, Greece. Optimum layouts are obtained considering part of or the whole wall length, available for the PAs’ sitting. The effect of the incident wave direction on the optimum layouts’ formation and the absorbed power is also assessed. Finally, the dependence of the maximized absorbed power upon the deployment site is illustrated

Effects of metocean conditions on selecting optimal location for wave energy production

Wave Energy Converters (WEC) have seen a wide variety of innovations capable to harness the vast untapped energy source of the seas. This wide range of WECs often has varied applicability and power production capabilities, making the selection of a device overwhelming. These uncertainties are increased whenconsidering the interactions and suitability of the device with local metocean conditions, and the impacts to long-term reliable operation. The study focuses on the Mediterranean region and presents a comprehensive approachin selecting a WEC, using a novel Selection Index for Wave Energy Deployments (SIWED), which accounts for resource, extreme events, power production capabilities, reducing uncertainties and biases. As a case study ourapproach explores: (i) the viability of WECs at milder resource (ii) the use of SIWED to select the “optimal” location and (iii) an approach to optimise considering the multi-faceted resource impacts. The study providesa comprehensive assessment of the “hidden” benefits of wave energy in the Mediterranean and its methodology is universally replicable. Finally, a discussion and overview on the importance of this interdisciplinary method for WECdeployments is underlined

Optimum Layouts of a Cluster of Heaving Point Absorbers in front of a Wall

In this paper, we determine optimum layouts of a cluster of oblate spheroidal heaving point absorbers in front of a wall, that maximize the annual averaged power absorbed by the cluster, while satisfying specific spatial constraints. An iterative optimization process is developed by coupling a hydrodynamic model with a genetic algorithms solver. Optimization is performed for three near-shore sites in the Aegean Sea, Greece. Optimum layouts are obtained considering part of or the whole wall length, available for the PAs’ sitting. The effect of the incident wave direction on the optimum layouts’ formation and the absorbed power is also assessed. Finally, the dependence of the maximized absorbed power upon the deployment site is illustrated.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Offshore Engineerin

Load assessment of optimally-arranged point absorbers arrays in front of a vertical wall

In this paper, we assess numerically the loads applied on PAs of optimally-arranged linear arrays in front of a bottom-mounted vertical wall of finite length under normal operating conditions. The arrays, maximizing the yearly absorbed energy, consist of five, identical, oblate spheroidal heaving PAs and are deployed at three near-shore sites in the Aegean Sea, Greece. The PAs are assumed to be attached on the wall via connection configurations restraining all rigid-body modes except heave. A spectral analysis is performed to quantify loads. The corresponding transfer functions are obtained from a frequency-based hydrodynamic model that solves the diffraction/radiation problem of the multi-body arrangement in the presence of the wall. Results, focusing on surge and sway restraining loads, are, initially, presented for regular waves and, then, for normal operating conditions (irregular waves), highlighting the effect of the arrays’ layouts and of the local wave conditions on the restraining loads. Comparison is also made with equally-spaced arrays to reveal potential positive effects of optimum layouts on structural integrity related issues.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Offshore Engineerin

Simultaneous Treatment of Agro-Industrial and Industrial Wastewaters: Case Studies of Cr(VI)/Second Cheese Whey and Cr(VI)/Winery Effluents

Hexavalent chromium (Cr(VI)) was co-treated either with second cheese whey (SCW) or winery effluents (WE) using pilot-scale biological trickling filters in series under different operating conditions. Two pilot-scale filters in series using plastic support media were used in each case. The first filter (i.e., Cr-SCW-filter or Cr-WE-filter) aimed at Cr(VI) reduction and the partial removal of dissolved chemical oxygen demand (d-COD) from SCW or WE and was inoculated with indigenous microorganisms originating from industrial sludge. The second filter in series (i.e., SCW-filter or WE-filter) aimed at further d-COD removal and was inoculated with indigenous microorganisms that were isolated from SCW or WE. Various Cr(VI) (5–100 mg L−1) and SCW or WE (d-COD, 1000–25,000 mg L−1) feed concentrations were tested. Based on the experimental results, the sequencing batch reactor operating mode with recirculation of 0.5 L min−1 proved very efficient since it led to complete Cr(VI) reduction in the first filter in series and achieved high Cr(VI) reduction rates (up to 36 and 43 mg L−1 d−1, for SCW and WW, respectively). Percentage d-COD removal for SCW and WE in the first filter was rather low, ranging from 14 to 42.5% and from 4 to 29% in the Cr-SCW-filter and Cr-WE-filter, respectively. However, the addition of the second filter in series enhanced total d-COD removal to above 97% and 90.5% for SCW and WE, respectively. The above results indicate that agro-industrial wastewater could be used as a carbon source for Cr(VI) reduction, while the use of two trickling filters in series could effectively treat both industrial and agro-industrial wastewaters with very low installation and operational costs

House Fly (<i>Musca domestica</i> L.) Attraction to Insect Honeydew

<div><p>House flies are of major concern as vectors of food-borne pathogens to food crops. House flies are common pests on cattle feedlots and dairies, where they develop in and feed on animal waste. By contacting animal waste, house flies can acquire human pathogenic bacteria such as <i>Escherichia coli</i> and <i>Salmonella</i> spp., in addition to other bacteria, viruses, or parasites that may infect humans and animals. The subsequent dispersal of house flies from animal facilities to nearby agricultural fields containing food crops may lead to pre-harvest food contamination with these pathogens. We hypothesized that odors from honeydew, the sugary excreta produced by sucking insects feeding on crops, or molds and fungi growing on honeydew, may attract house flies, thereby increasing the risk of food crop contamination. House fly attraction to honeydew-contaminated plant material was evaluated using a laboratory bioassay. House flies were attracted to the following plant-pest-honeydew combinations: citrus mealybug on squash fruit, pea aphid on faba bean plants, whitefly on navel orange and grapefruit leaves, and combined citrus mealybug and cottony cushion scale on mandarin orange leaves. House flies were not attracted to field-collected samples of lerp psyllids on eucalyptus plants or aphids on crepe myrtle leaves. Fungi associated with field-collected honeydews were isolated and identified for further study as possible emitters of volatiles attractive to house flies. Two fungal species, <i>Aureobasidium pullulans</i> and <i>Cladosporium cladosporioides</i>, were repeatedly isolated from field-collected honeydew samples. Both fungal species were grown in potato dextrose enrichment broth and house fly attraction to volatiles from these fungal cultures was evaluated. House flies were attracted to odors from <i>A</i>. <i>pullulans</i> cultures but not to those of <i>C</i>. <i>cladosporioides</i>. Identification of specific honeydew odors that are attractive to house flies could be valuable for the development of improved house fly baits for management of this pest species.</p></div