599 research outputs found

    Diversity in parasitic nematode genomes: the microRNAs of Brugia pahangi and Haemonchus contortus are largely novel

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    <b>BACKGROUND:</b> MicroRNAs (miRNAs) play key roles in regulating post-transcriptional gene expression and are essential for development in the free-living nematode Caenorhabditis elegans and in higher organisms. Whether microRNAs are involved in regulating developmental programs of parasitic nematodes is currently unknown. Here we describe the the miRNA repertoire of two important parasitic nematodes as an essential first step in addressing this question. <b>RESULTS:</b> The small RNAs from larval and adult stages of two parasitic species, Brugia pahangi and Haemonchus contortus, were identified using deep-sequencing and bioinformatic approaches. Comparative analysis to known miRNA sequences reveals that the majority of these miRNAs are novel. Some novel miRNAs are abundantly expressed and display developmental regulation, suggesting important functional roles. Despite the lack of conservation in the miRNA repertoire, genomic positioning of certain miRNAs within or close to specific coding genes is remarkably conserved across diverse species, indicating selection for these associations. Endogenous small-interfering RNAs and Piwi-interacting (pi)RNAs, which regulate gene and transposon expression, were also identified. piRNAs are expressed in adult stage H. contortus, supporting a conserved role in germline maintenance in some parasitic nematodes. <b>CONCLUSIONS:</b> This in-depth comparative analysis of nematode miRNAs reveals the high level of divergence across species and identifies novel sequences potentially involved in development. Expression of novel miRNAs may reflect adaptations to different environments and lifestyles. Our findings provide a detailed foundation for further study of the evolution and function of miRNAs within nematodes and for identifying potential targets for intervention

    Prestrain relaxation in non-covalently modified ethylene-vinyl acetate | PyChol | multiwall carbon nanotube nanocomposites

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    Effects of aging on chemical structure and molecular dynamic behaviour of strained thermally active ethylene-vinyl acetate | multiwall carbon nanotube (EVA|MWCNT) composites were investigated by spectroscopy and microscopy techniques. Aged composites showed spatial inhomogeneity due to system relaxation. Inhomogeneity is attributed to segregation of non-covalently linked cholestryl 1-pyrenecarboxylate, acting as MWCNT dispersant and polymer compatibilizer. Analysis of molecular interplay between filler and matrix upon in situ temperature variation showed a lack of synchronicity, which had been observed in fresh composites. Reduced synchronous interplay allowed quantification of degraded π-π interactions, promoting PyChol unlatching as a result of both sonication and strained-derived π-π degradation

    Quantum state merging and negative information

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    We consider a quantum state shared between many distant locations, and define a quantum information processing primitive, state merging, that optimally merges the state into one location. As announced in [Horodecki, Oppenheim, Winter, Nature 436, 673 (2005)], the optimal entanglement cost of this task is the conditional entropy if classical communication is free. Since this quantity can be negative, and the state merging rate measures partial quantum information, we find that quantum information can be negative. The classical communication rate also has a minimum rate: a certain quantum mutual information. State merging enabled one to solve a number of open problems: distributed quantum data compression, quantum coding with side information at the decoder and sender, multi-party entanglement of assistance, and the capacity of the quantum multiple access channel. It also provides an operational proof of strong subadditivity. Here, we give precise definitions and prove these results rigorously.Comment: 23 pages, 3 figure

    Comparison of submicron particle counting methods with a heat stressed monoclonal antibody: effect of electrolytes and implications on sample preparation

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    Within this study, the performance and limitations of tunable resistive pulse sensing (TRPS) was evaluated to characterize submicron particles in unstressed and heat stressed monoclonal antibody (mAb) solutions. These were compared with microfluidic resistive pulse sensing (MRPS), resonant mass measurement (RMM), and nanoparticle tracking analysis (NTA). For TRPS and MRPS measurements, an adjustment of ionic strength was required to achieve suitable measurement conditions. The addition of electrolytes is potentially critical for protein formulations and therefore the effect of salt concentration and pH on submicron particle levels was further investigated. Heat stress caused a sharp increase in particle levels between 250-900 nm, observable by all four techniques. Due to reduced colloidal stability, indicated by increased attractive forces and reduced aggregation onset temperatures in the presence of sodium chloride, protein aggregation was observed in heat stressed mAb only after the addition of sodium chloride. Achieving adequate ionic strength by replacing sodium chloride with other electrolytes similarly resulted in reduced colloidal stability and protein aggregation. It is recommended that protein samples prone for aggregation in the presence of high ionic strength should not be analyzed by RPS measurements after the addition of electrolytes. However, protein samples containing already required ionic strength can be analyzed by any of the four techniques.Drug Delivery Technolog

    Pharmacokinetics of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Terminally Ill Adult Patients

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    Background and Objective: Morphine dosing can be challenging in terminally ill adult patients due to the heterogeneous nature of the population and the difficulty of accurately assessing pain during sedation. To determine the pharmacokinetics of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in this population, and to find clinically relevant parameters for dose individualisation, we performed a population pharmacokinetic analysis. Methods: Blood samples were randomly collected from 47 terminally ill patients in both the pre-terminal and terminal phases. Nonlinear mixed-effects modelling (NONMEM) was used to develop a population pharmacokinetic model and perform covariate analysis. Results: The data were accurately described by a two-compartment model for morphine with two one-compartment models for both its metabolites. Typical morphine clearance was 48 L/h and fell exponentially by more than 10 L/h in the last week before death. Decreased albumin levels and a decreased estimated glomerular filtration rate (eGFR) resulted in lower metabolite clearance. Between-subject variability in clearance was 52 % (morphine), 75 % (M3G) and 79 % (M6G), and changed to 53, 29 and 34 %, respectively, after inclusion of the covariates. Conclusions: Our results show that morphine clearance decreased up to the time of death, falling by more than 10 L/h (26 %) in the last week before death, and that M3G and M6G accumulated due to decreased renal function. Further studies are warranted to determine whether dose adjustment of morphine is required in terminally ill patients

    A Compact Beam Stop for a Rare Kaon Decay Experiment

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    We describe the development and testing of a novel beam stop for use in a rare kaon decay experiment at the Brookhaven AGS. The beam stop is located inside a dipole spectrometer magnet in close proximity to straw drift chambers and intercepts a high-intensity neutral hadron beam. The design process, involving both Monte Carlo simulations and beam tests of alternative beam-stop shielding arrangements, had the goal of minimizing the leakage of particles from the beam stop and the resulting hit rates in detectors, while preserving maximum acceptance for events of interest. The beam tests consisted of measurements of rates in drift chambers, scintilation counter hodoscopes, a gas threshold Cherenkov counter, and a lead glass array. Measurements were also made with a set of specialized detectors which were sensitive to low-energy neutrons, photons, and charged particles. Comparisons are made between these measurements and a detailed Monte Carlo simulation.Comment: 39 pages, 14 figures, submitted to Nuclear Instruments and Method

    Vismigratie en lozingspluimen: Samenvattend rapport

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    Zeewaarts migrerende schieralen laten een gedragsverandering zien wanneer zij geconfronteerd worden met een lozingspluim van rwzi-effluent. Ruim de helft van de vissen verandert van zwemrichting en tracht langs de rand van de pluim te passeren. Het risico dat een permanente migratie-barrière ontstaat is bij de meeste rwzi’s niet groot door het dynamische karakter van de lozingspluim. Bij rwzi’s die lozen op wateren met een beperkt afvoerdebiet kunnen wel migratie-barrières ontstaan, maar met relatief eenvoudige aanpassingen kan de kans daarop worden verkleind. De onderzoeksresultaten geven aan dat rwzi-effluentpluimen potentie hebben om te worden ingezet voor de geleiding van stroomafwaarts migrerende vissen naar een veilige route langs gevaarlijke situaties zoals koelwaterinlaten, gemalen en waterkrachtcentrales

    Один из способов управления технологическим процессом дуговой сталеплавильной печи

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    В статье приводится описание комплексной математической модели, используемой для рационального управления работой дуговых электросталеплавильных печей.In article the description of the complex mathematical model used for rational management by work of arc electrosteel-smelting furnaces is resulted
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