Detecting Variability in Massive Astronomical Time-Series Data I: application of an infinite Gaussian mixture model

We present a new framework to detect various types of variable objects within massive astronomical time-series data. Assuming that the dominant population of objects is non-variable, we find outliers from this population by using a non-parametric Bayesian clustering algorithm based on an infinite GaussianMixtureModel (GMM) and the Dirichlet Process. The algorithm extracts information from a given dataset, which is described by six variability indices. The GMM uses those variability indices to recover clusters that are described by six-dimensional multivariate Gaussian distributions, allowing our approach to consider the sampling pattern of time-series data, systematic biases, the number of data points for each light curve, and photometric quality. Using the Northern Sky Variability Survey data, we test our approach and prove that the infinite GMM is useful at detecting variable objects, while providing statistical inference estimation that suppresses false detection. The proposed approach will be effective in the exploration of future surveys such as GAIA, Pan-Starrs, and LSST, which will produce massive time-series data.Comment: accepted for publication in MNRA

Small hive beetle, Aethina tumida , as a potential biological vector of honeybee viruses

The small hive beetle (SHB, Aethina tumida) is a parasite and scavenger of honeybee colonies. Here, we conducted laboratory experiments to investigate the potential of SHB as a vector of honeybee viruses. Using RT-PCR methods, Deformed Wing Virus (DWV) was detected in adult SHBs that: (1) were fed with dead workers with deformed wings, (2) were fed with DWV-positive brood, and (3) were associated with DWV-contaminated wax. SHB became significantly more often infected through feeding on virus infected workers, brood and the virus contaminated wax compared to pollen and the controls, where no infections were found. DWV was also detected in adult SHB after trophallaxis with infected workers. Further, among SHBs identified as DWV-positive, 40% of beetles carried negative stranded RNA of DWV, indicating virus replication. Our results suggest that SHB can be infected with honeybee viruses via food-borne transmission and have the potential of being a biological vector of honeybee viruse

Steric exclusion chromatography for the purification of recombinant baculovirus

Steric exclusion chromatography (SXC) has already proven to be a valuable tool in the purification of proteins and virus particles. An important benefit of the method is the fast and simple procedure at mild chromatography conditions as no harsh binding and elution buffers are needed. The sample is initially mixed with a polyethylene glycol (PEG) containing buffer of choice. The steric exclusion of a macromolecule from the polyethylene glycol and the stationary phase allows a selective retention of the product, depending, among others, mainly on its size as well as on the molecular weight and concentration of the PEG. Here, SXC was set up in order that smaller process contaminants, i.e. host cell proteins and DNA, did not bind to the stationary phase, in contrast to the targeted larger virus particles. These were subsequently eluted reducing the PEG concentration in the mobile phase. Regenerated cellulose was used as stationary phase to purify VSV-G pseudotyped AcMNPV baculoviruses derived from Spodoptera frugiperda cells (Sf9 cells) by SXC. The purified virus particles are used as gene transfer tools for human mesenchymal stroma cells. For this purpose, the baculovirus was clarified prior to the SXC by sequential centrifugation (4700 gmax). The SXC conditions were optimized in terms of yield and purity by a design of experiment approach considering the PEG molecular weight, its concentration and the ionic strength of the elution buffer as critical process parameters. Within the design space virus recovery was ≥70%. Without further nuclease treatment the depletion of double-stranded DNA was \u3e90% and the amount of host cell proteins were reduced \u3e90% in the virus fraction. In conclusion, SXC can drastically reduce the process development in terms of time and equipment requirements for the purification of recombinant baculoviruses, as well as for the achieved purity which is superior over classical methods

Cell-Free Microfluidic Determination of P-glycoprotein Interactions with Substrates and Inhibitors

ABSTRACT: The membrane protein P-glycoprotein (P-gp) plays key roles in the oral bioavailability of drugs, their blood brain barrier passage as well as in multidrug resistance. For new drug candidates it is mandatory to study their interaction with P-gp, according to FDA and EMA regulations. The vast majority of these tests are performed using confluent cell layers of P-gp overexpressing cell lines that render these tests laborious. In this study, we introduce a cell-free microfluidic assay for the rapid testing of drug- P-gp interactions. Cell-derived vesicles are prepared from MDCKII-MDR1 overexpressing cells and immobilized on the surface of a planar microfluidic device. The drug is delivered continuously to the vesicles and calcein accumulation is monitored by means of a fluorescence assay and total internal reflection fluorescence (TIRF) microscopy. Only small amounts of compounds (~10μl) are required in concentrations of 5, 25 and 50μM for a test that provides within 5min information on the apparent dissociation constant of the drug and P-gp. We tested 10 drugs on-chip, 9 of which are inhibitors or substrates of P-glycoprotein and one negative control. We benchmarked the measured apparent dissociation constants against an alternative assay on a plate reader and reference data from FDA. These comparisons revealed good correlations between the logarithmic apparent dissociation constants (R2 = 0.95 with ATPase assay, R2 = 0.93 with FDA data) and show the reliability of the rapid on-chip test. The herein presented assay has an excellent screening window factor (Z'-factor) of 0.8, and is suitable for high-throughput testing

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

NON-INVASIVE DETERMINATION OF THE LOCATION AND DISTRIBUTION OF FREE-PHASE DENSE NONAQUEOUS PHASE LIQUIDS (DNAPL) BY SEISMIC REFLECTION TECHNIQUES

The Earth Sciences and Resources Institute, University of South Carolina is conducting a 14 month proof of concept study to determine the location and distribution of subsurface Dense Nonaqueous Phase Liquid (DNAPL) carbon tetrachloride (CCl{sub 4}) contamination at the 216-Z-9 crib, 200 West area, Department of Energy (DOE) Hanford Site, Washington by use of two-dimensional high resolution seismic reflection surveys and borehole geophysical data. The study makes use of recent advances in seismic reflection amplitude versus offset (AVO) technology to directly detect the presence of subsurface DNAPL. The techniques proposed are a noninvasive means towards site characterization and direct free-phase DNAPL detection. This report covers the results of Task 3 and change of scope of Tasks 4-6. Task 1 contains site evaluation and seismic modeling studies. The site evaluation consists of identifying and collecting preexisting geological and geophysical information regarding subsurface structure and the presence and quantity of DNAPL. The seismic modeling studies were undertaken to determine the likelihood that an AVO response exists and its probable manifestation. Task 2 is the design and acquisition of 2-D seismic reflection data designed to image areas of probable high concentration of DNAPL. Task 3 is the processing and interpretation of the 2-D data. Task 4, 5, and 6 were designing, acquiring, processing, and interpretation of a three dimensional seismic survey (3D) at the Z-9 crib area at 200 west area, Hanford

No spatial patterns for early nectar storage in honey bee colonies

Honey bees, Apis, forage for nectar and pollen, which are subsequently stored in cells of their nests. Despite the importance of honey storage for colony survival, very little is known about decision making by honey bee workers that could optimise the transformation of nectar into honey. Here we test, using diagnostic radioentomology, whether workers use rules based on sugar concentration to optimise the spatial distribution of storage cells during nectar ripening. The data show that after the first 3 days of storing activity, various sugar concentrations were mixed in individual cells. A spatial clustering of cells with content of similar concentration was only occasionally observed. The results, therefore, suggest that at early stages of storage, spatial proximity of cells with similar sugar concentrations does not result in improved efficiency and, therefore, does not seem adaptive. The costs involved in locating particular cells probably outweighs the benefits of clustering. Alternatively, but not mutually exclusive, physiological constraints (e.g. variation in the perception of sugar concentration) might limit such optimisation behaviour. Storing behaviour can serve as a model to better understand food provisioning and complex organisation of insect societies.Partly funded by the Eva Crane Trust.http://link.springer.com/journal/402017-02-28hb2016Zoology and Entomolog