SELECTING ADS RELEVANT TO LIVE EVENTS TO AN ONLINE AUDIENCE

If an advertiser wants to select ads for an online audience for a relevant event, the selection and audience specifications need to be manually created. Advertisers have to find the set of relevant keywords, a specified audience for the event , and an event time window, in order to create the ad campaign for their ads to show during the event. This manual process can be complex and time consuming, and advertisers may not be able to determine the right selection criteria or audience for the event. Furthermore, while some events may be identified well in advance, advertisers may not react as quickly to new events that are relevant to their ads. Additionally, advertisers may not be able to determine a proper window for presenting the ad. A search provider may be able to provide live, real-time answers for search queries related to live events that users are interested in, such as sports, weather, finance, movie show times, and more

Environmental context determines the impact of titanium oxide and silver nanoparticles on the functioning of intertidal microalgal biofilms

Coastal environments are receiving habitats for most nanoparticle (NP) waste. Coastal sediments, into which NPs accumulate, support microalgal biofilms that provide important ecosystem processes: primary production, enhanced sediment stabilisation, and nutrient recycling. We assessed the impact of realistic concentrations of titanium oxide (TiO₂) and silver (Ag) NPs on marine microalgal biofilms and associated ecosystem processes in simulated natural conditions, by exposing natural biofilms to TiO₂ and Ag-NPs for one-month periods in outdoor tidal mesocosms under three contrasted environmental contexts (seasons). Ag-NPs had no significant effects on microalgal biomass, sediment biostabilisation potential and sediment–water oxygen and nutrient fluxes, even at concentrations (25 μg l¯¹) higher than current estimated levels (25 ng l¯¹). TiO₂-NPs had no significant effect at current expected concentrations (25 μg l¯¹), but higher concentrations (25 mg l¯¹) resulted in decreased microalgal biomass; decreased ability of biofilms to biostabilise sediment, therefore limiting their coastal protection potential; reduced primary production and modified nutrient recycling. TiO₂-NPs impacts were dependent on the environmental context: most effect was seen in winter, while no toxicity on biofilms was demonstrated in early spring. Our findings demonstrate that while Ag-NPs, being liable to dissolution into Ag+ ions under the conditions tested, are not expected to have an environmental impact if current predictions of environmental loading prevail, TiO₂-NPs may have ecological consequences in coastal environments in addition to direct impacts on microbial biomass

Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood.

Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty-one patients with suspected NAFLD ingested heavy water (2 H2 O, 50-mL aliquots) two to three times daily for 3-5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on 2 H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage (F0-F4) and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic resonance elastography measurements of liver stiffness were also performed. Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g., higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis score and liver stiffness) and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR.ConclusionUsing a well-characterized cohort of patients with biopsy-proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78-88)

Pathogenic Mutations Differentially Regulate Cell-to-Cell Transmission of α-Synuclein

Recent studies suggest that the cell-to-cell spread of pathological α-synuclein (α-syn) plays important roles in the development of Parkinson’s disease (PD). PD patients who carry α-syn gene mutations often have an earlier onset and more severe clinical symptoms and pathology than sporadic PD cases who carry the wild-type (WT) α-syn gene. However, the molecular mechanism by which α-syn gene mutations promote PD remains unclear. Here, we hypothesized that pathogenic mutations facilitate the intercellular transfer and cytotoxicity of α-syn, favoring an early disease onset and faster progression. We investigated the effects of eight known pathogenic mutations in human α-syn (A18T, A29S, A30P, E46K, H50Q, G51D, A53E, and A53T) on its pathological transmission in terms of secretion, aggregation, intracellular level, cytotoxicity, seeding, and induction of neuroinflammation in SH-SY5Y neuroblastoma cells, cultured rat neurons, and microglia, and the rat substantia nigra pars compacta. We found that 2 of the 8 mutations (H50Q and A53T) significantly increased α-syn secretion while 6 mutations (A18T, A29S, A30P, G51D, A53E, and E46K) tended to enhance it. In vitroα-syn aggregation experiments showed that H50Q promoted while G51D delayed aggregation most strongly. Interestingly, 3 mutations (E46K, H50Q, and G51D) greatly increased the intracellular α-syn level when cultured cells were treated with preformed α-syn fibrils (PFFs) compared with the WT, while the other 5 had no effect. We also demonstrated that H50Q, G51D, and A53T PFFs, but not E46K PFFs, efficiently seeded in vivo and acutely induced neuroinflammation in rat substantia nigra pars compacta. Our data indicate that pathogenic mutations augment the prion-like spread of α-syn at different steps and blockade of this pathogenic propagation may serve as a promising therapeutic intervention for PD

Evolution of carnivorous traps from planar leaves through simple shifts in gene expression

Leaves vary from planar sheets and needle-like structures to elaborate cup-shaped traps. Here, we show that in the carnivorous plant Utricularia gibba, the upper leaf (adaxial) domain is restricted to a small region of the primordium that gives rise to the trap's inner layer. This restriction is necessary for trap formation, because ectopic adaxial activity at early stages gives radialized leaves and no traps. We present a model that accounts for the formation of both planar and nonplanar leaves through adaxial-abaxial domains of gene activity establishing a polarity field that orients growth. In combination with an orthogonal proximodistal polarity field, this system can generate diverse leaf forms and account for the multiple evolutionary origins of cup-shaped leaves through simple shifts in gene expression

Shaping of a three-dimensional carnivorous trap through modulation of a planar growth mechanism

Leaves display a remarkable range of forms, from flat sheets with simple outlines to cup-shaped traps. Although much progress has been made in understanding the mechanisms of planar leaf development, it is unclear whether similar or distinctive mechanisms underlie shape transformations during development of more complex curved forms. Here, we use 3D imaging and cellular and clonal analysis, combined with computational modelling, to analyse the development of cup-shaped traps of the carnivorous plant Utricularia gibba. We show that the transformation from a near-spherical form at early developmental stages to an oblate spheroid with a straightened ventral midline in the mature form can be accounted for by spatial variations in rates and orientations of growth. Different hypotheses regarding spatiotemporal control predict distinct patterns of cell shape and size, which were tested experimentally by quantifying cellular and clonal anisotropy. We propose that orientations of growth are specified by a proximodistal polarity field, similar to that hypothesised to account for Arabidopsis leaf development, except that in Utricularia, the field propagates through a highly curved tissue sheet. Independent evidence for the polarity field is provided by the orientation of glandular hairs on the inner surface of the trap. Taken together, our results show that morphogenesis of complex 3D leaf shapes can be accounted for by similar mechanisms to those for planar leaves, suggesting that simple modulations of a common growth framework underlie the shaping of a diverse range of morphologies