1,731 research outputs found

    Improved synchronous production of Plasmodium falciparum gametocytes in vitro.

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    The sexual stages of the Plasmodium falciparum life cycle are attractive targets for vaccines and transmission blocking drugs. Difficulties in culturing and obtaining large amounts of sexual stage P. falciparum parasites, particularly early stages, have often limited research progress in this area. We present a new protocol which simplifies the process of stimulating gametocytogenesis leading to improved synchronous gametocyte production. This new method can be adapted to enrich for early stage gametocytes (I and II) with a higher degree of purity than has previously been achieved, using MACS magnetic affinity columns. The protocol described lends itself to large scale culturing and harvesting of synchronous parasites suitable for biochemical assays, northern blots, flow cytometry, microarrays and proteomic analysis

    Functionalising the azobenzene motif delivers a light-responsive membrane-interactive compound with the potential for photodynamic therapy applications

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    When adorned with n-octyl chains azobenzene is able to disrupt a variety of calcein-loaded phospholipid liposomes. The levels of lysis observed are dependent both on the lipid headgroup and the conformation of the azobenzene compound. In all cases studied, it has been shown that the cis-conformer is more membrane-interactive than the trans-conformer, suggesting that this class of molecule could be optimised for photo-dynamic therapy applications against infectious pathogens

    Young Cattle Producers Conference Develops Leaders in Idaho

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    The need for young leadership in the beef industry has become a rising concern as the average age of primary operators increases. Extension educators developed a leadership conference for beef producers with the primary objective to educate and develop leadership qualities in young cattle producers. To achieve the objective participants, age 18-40 years old, had opportunities to learn all aspects of the industry through presentations, hands-on learning and industry tours. A post-conference survey revealed that participants planned to utilize what they learned and had a better understanding of the beef industry at the conclusion of the program

    C4: The New Hampshire Spherulitic Rhyolites: Rocks of Importance to Prehistoric Native Americans

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    Guidebook for field trips in Western Maine and Northern New Hampshire: New England Intercollegiate Geological Conference, p. 305-316

    Accuracy and consistency of grass pollen identification by human analysts using electron micrographs of surface ornamentation

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    • Premise of the study: Humans frequently identify pollen grains at a taxonomic rank above species. Grass pollen is a classic case of this situation, which has led to the development of computational methods for identifying grass pollen species. This paper aims to provide context for these computational methods by quantifying the accuracy and consistency of human identification. • Methods: We measured the ability of nine human analysts to identify 12 species of grass pollen using scanning electron microscopy images. These are the same images that were used in computational identifications. We have measured the coverage, accuracy, and consistency of each analyst, and investigated their ability to recognize duplicate images. • Results: Coverage ranged from 87.5% to 100%. Mean identification accuracy ranged from 46.67% to 87.5%. The identification consistency of each analyst ranged from 32.5% to 87.5%, and each of the nine analysts produced considerably different identification schemes. The proportion of duplicate image pairs that were missed ranged from 6.25% to 58.33%. • Discussion: The identification errors made by each analyst, which result in a decline in accuracy and consistency, are likely related to psychological factors such as the limited capacity of human memory, fatigue and boredom, recency effects, and positivity bias

    Invasive alien species in the food chain : advancing risk assessment models to address climate change, economics and uncertainty

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    Economic globalization depends on the movement of people and goods between countries. As these exchanges increase, so does the potential for translocation of harmful pests, weeds, and pathogens capable of impacting our crops, livestock and natural resources (Hulme 2009), with concomitant impacts on global food security (Cook et al. 2011)

    Multivariate classification with random forests for gravitational wave searches of black hole binary coalescence

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    Searches for gravitational waves produced by coalescing black hole binaries with total masses ≳25  M_⊙ use matched filtering with templates of short duration. Non-Gaussian noise bursts in gravitational wave detector data can mimic short signals and limit the sensitivity of these searches. Previous searches have relied on empirically designed statistics incorporating signal-to-noise ratio and signal-based vetoes to separate gravitational wave candidates from noise candidates. We report on sensitivity improvements achieved using a multivariate candidate ranking statistic derived from a supervised machine learning algorithm. We apply the random forest of bagged decision trees technique to two separate searches in the high mass (≳25  M_⊙) parameter space. For a search which is sensitive to gravitational waves from the inspiral, merger, and ringdown of binary black holes with total mass between 25  M_⊙ and 100  M_⊙, we find sensitive volume improvements as high as 70_(±13)%–109_(±11)% when compared to the previously used ranking statistic. For a ringdown-only search which is sensitive to gravitational waves from the resultant perturbed intermediate mass black hole with mass roughly between 10  M_⊙ and 600  M_⊙, we find sensitive volume improvements as high as 61_(±4)%–241_(±12)% when compared to the previously used ranking statistic. We also report how sensitivity improvements can differ depending on mass regime, mass ratio, and available data quality information. Finally, we describe the techniques used to tune and train the random forest classifier that can be generalized to its use in other searches for gravitational waves

    Mutation of the co-chaperone Tsc1 in bladder cancer diminishes Hsp90 acetylation and reduces drug sensitivity and selectivity

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    The molecular chaperone Heat shock protein 90 (Hsp90) is essential for the folding, stability, and activity of several drivers of oncogenesis. Hsp90 inhibitors are currently under clinical evaluation for cancer treatment, however their efficacy is limited by lack of biomarkers to optimize patient selection. We have recently identified the tumor suppressor tuberous sclerosis complex 1 (Tsc1) as a new co-chaperone of Hsp90 that affects Hsp90 binding to its inhibitors. Highly variable mutations of TSC1 have been previously identified in bladder cancer and correlate with sensitivity to the Hsp90 inhibitors. Here we showed loss of TSC1 leads to hypoacetylation of Hsp90-K407/K419 and subsequent decreased binding to the Hsp90 inhibitor ganetespib. Pharmacologic inhibition of histone deacetylases (HDACs) restores acetylation of Hsp90 and sensitizes Tsc1-mutant bladder cancer cells to ganetespib, resulting in apoptosis. Our findings suggest that TSC1 status may predict response to Hsp90 inhibitors in patients with bladder cancer, and co-targeting HDACs can sensitize tumors with Tsc1 mutations to Hsp90 inhibitors
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