Feature Gradient Flow for Interpreting Deep Neural Networks in Head and Neck Cancer Prediction

This paper introduces feature gradient flow, a new technique for interpreting deep learning models in terms of features that are understandable to humans. The gradient flow of a model locally defines nonlinear coordinates in the input data space representing the information the model is using to make its decisions. Our idea is to measure the agreement of interpretable features with the gradient flow of a model. To then evaluate the importance of a particular feature to the model, we compare that feature's gradient flow measure versus that of a baseline noise feature. We then develop a technique for training neural networks to be more interpretable by adding a regularization term to the loss function that encourages the model gradients to align with those of chosen interpretable features. We test our method in a convolutional neural network prediction of distant metastasis of head and neck cancer from a computed tomography dataset from the Cancer Imaging Archive

Influence of Linker Length and Composition on Enzymatic Activity and Ribosomal Binding of Neomycin Dimers

The human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by AMEs also showed increased bacterial A site binding, with one compound (compound 14) even showing substantially reduced human A site binding. The urea-linked dimers showed a substantial decrease in activity by AMEs when a conformationally restrictive phenyl linker was introduced. The information learned herein advances our understanding of the importance of the linker length and composition for the generation of dimeric aminoglycoside antibiotics capable of avoiding the action of AMEs and selective binding to the bacterial rRNA over binding to the human rRNA

Designing multiplayer games to facilitate emergent social behaviours online

This paper discusses an exploratory case study of the design of games that facilitate spontaneous social interaction and group behaviours among distributed individuals, based largely on symbolic presence 'state' changes. We present the principles guiding the design of our game environment: presence as a symbolic phenomenon, the importance of good visualization and the potential for spontaneous self-organization among groups of people. Our game environment, comprising a family of multiplayer 'bumper-car' style games, is described, followed by a discussion of lessons learned from observing users of the environment. Finally, we reconsider and extend our design principles in light of our observations

Interaction of eddies and mean zonal flow on Jupiter as inferred from Voyager 1 and 2 images

Voyager 1 and 2 narrow-angle frames were used to obtain displacements of features at resolutions of 130 km over time intervals of 1 Jovian rotation. The zonal velocity ū was constant to 1.5% during the 4 months between the Voyager 1 and 2 encounters. The latitudes of the zonal jet maxima (extrema of ū) are the same as inferred from earth-based observations extending over the past 80 years. The curvature of the velocity profile d²ū/dy² varies with latitudinal coordinate y in the range from −3β to +2β, where β is the planetary vorticity gradient. The barotropic stability criterion is violated at about 10 latitudes between ±60°. The eddy momentum flux variation with latitude (u'ν')(overbar) is positively correlated with dū/dy for both Voyager 1 and 2 data. The rate of conversion {K'K(overbar)} of eddy kinetic energy into zonal mean kinetic energy is in the range 1.5–3.0 Wm^(−2), for a layer 2.5 bar deep. The time constant for resupply of zonal mean kinetic energy by eddies is in the range 2–4 months, less than the interval between Voyager encounters. The rate of energy conversion is more than 10% of the total infrared heat flux for Jupiter, in contrast with earth where it is only 0.1% of the infrared heat flux. This hundred-fold difference suggests that the thermomechanical energy cycles are very different on the two planets

Molecular and evolutionary basis of O-antigenic polysaccharide-driven phage sensitivity in environmental pseudomonads.

Pseudomonas protegens CHA0, a bacterial strain able to suppress plant pathogens as well as efficiently kill lepidopteran pest insects, has been studied as a biocontrol agent to prevent ensuing agricultural damage. However, the success of this method is dependent on efficient plant colonization by the bacterial inoculant, while it faces competition from the resident microbiota as well as predators such as bacteriophages. One of these naturally occurring phages, ΦGP100, was found to drastically reduce the abundance of CHA0 once inoculated into plant microcosms, resulting in the loss of plant protection effect against a phytopathogen. Here, we investigated the molecular determinants implicated in the interaction between CHA0 and the phage ΦGP100 using a high-density transposon-sequencing approach. We show that lipopolysaccharide cell surface decorations, specifically the longer OBC3-type O-antigenic polysaccharide (O-PS, O-antigen) of the two dominant O-PS of CHA0, are essential for the attachment and infection of ΦGP100. Moreover, when exploring the distribution of the OBC3 cluster in bacterial genomes, we identified several parts of this gene cluster that are conserved in phylogenetically distant bacteria. Through heterologous complementation, we integrated an OBC3-type gene copy from a phylogenetically distant bacterium and were able to restore the phage sensitivity of a CHA0 mutant which lacked the ability to form long O-PS. Finally, we evidence that the OBC3 gene cluster of CHA0 displays a high genomic plasticity and likely underwent several horizontal acquisitions and genomic rearrangements. Collectively, this study underlines the complexity of phage-bacteria interactions and the multifunctional aspect of bacterial cell surface decorations. IMPORTANCE The application of plant-beneficial microorganisms to protect crop plants is a promising alternative to the usage of chemicals. However, biocontrol research often faces difficulties in implementing this approach due to the inconsistency of the bacterial inoculant to establish itself within the root microbiome. Beneficial bacterial inoculants can be decimated by the presence of their natural predators, notably bacteriophages (also called phages). Thus, it is important to gain knowledge regarding the mechanisms behind phage-bacteria interactions to overcome this challenge. Here, we evidence that the major long O-antigenic polysaccharide (O-PS, O-antigen) of the widely used model plant-beneficial bacterium Pseudomonas protegens CHA0 is the receptor of its natural predator, the phage ΦGP100. We examined the distribution of the gene cluster directing the synthesis of this O-PS and identified signatures of horizontal gene acquisitions. Altogether, our study highlights the importance of bacterial cell surface structure variation in the complex interplay between phages and their Pseudomonas hosts

North America’s oldest boreal trees are more efficient water users due to increased [CO2], but do not grow faster

Due to anthropogenic emissions and changes in land use, trees are now exposed to atmospheric levels of [CO2] that are unprecedented for 650,000 y [Lüthi et al. (2008) Nature 453:379–382] (thousands of tree generations). Trees are expected to acclimate by modulating leaf–gas exchanges and alter water use efficiency which may result in forest productivity changes. Here, we present evidence of one of the strongest, nonlinear, and unequivocal postindustrial increases in intrinsic water use efficiency (iWUE) ever documented (+59%). A dual-isotope tree-ring analysis (δ13C and δ18O) covering 715 y of growth of North America’s oldest boreal trees (Thuja occidentalis L.) revealed an unprecedented increase in iWUE that was directly linked to elevated assimilation rates of CO2 (A). However, limited nutrient availability, changes in carbon allocation strategies, and changes in stomatal density may have offset stem growth benefits awarded by the increased iWUE. Our results demonstrate that even in scenarios where a positive CO2 fertilization effect is observed, other mechanisms may prevent trees from assimilating and storing supplementary anthropogenic emissions as above-ground biomass. In such cases, the sink capacity of forests in response to changing atmospheric conditions might be overestimated

The Response of the Honey Bee Gut Microbiota to Nosema ceranae Is Modulated by the Probiotic Pediococcus acidilactici and the Neonicotinoid Thiamethoxam.

The honey bee Apis mellifera is exposed to a variety of biotic and abiotic stressors, such as the highly prevalent microsporidian parasite Nosema (Vairimorpha) ceranae and neonicotinoid insecticides. Both can affect honey bee physiology and microbial gut communities, eventually reducing its lifespan. They can also have a combined effect on the insect's survival. The use of bacterial probiotics has been proposed to improve honey bee health, but their beneficial effect remains an open question. In the present study, western honey bees were experimentally infected with N. ceranae spores, chronically exposed to the neonicotinoid thiamethoxam, and/or supplied daily with the homofermentative bacterium Pediococcus acidilactici MA18/5M thought to improve the honey bees' tolerance to the parasite. Deep shotgun metagenomic sequencing allowed the response of the gut microbiota to be investigated with a taxonomic resolution at the species level. All treatments induced significant changes in honey bee gut bacterial communities. Nosema ceranae infection increased the abundance of Proteus mirabilis, Frischella perrara, and Gilliamella apicola and reduced the abundance of Bifidobacterium asteroides, Fructobacillus fructosus, and Lactobacillus spp. Supplementation with P. acidilactici overturned some of these alterations, bringing back the abundance of some altered species close to the relative abundance found in the controls. Surprisingly, the exposure to thiamethoxam also restored the relative abundance of some species modulated by N. ceranae. This study shows that stressors and probiotics may have an antagonistic impact on honey bee gut bacterial communities and that P. acidilactici may have a protective effect against the dysbiosis induced by an infection with N. ceranae

Flow fields within Jupiter's great red spot and white oval BC

Using sequences of Voyager 1 high-resolution images of Jupiter's Great Red Spot (GRS) and White Oval BC we map the flow fields within the GRS and Oval BC. We compute relative vorticity within these features as a function of semi-major axis length and position angle in a coordinate system consisting of concentric ellipses of equal eccentricity. Both the velocity and the relative vorticity profiles are nearly identical for Oval BC and the outer portion of the GRS. Wind speeds of 110–120 m/s are observed near the outer edges of both features. Along their minor axes relative vorticity profiles reach a maximum of ∼6 × 10^(−5) s^(−1). This is several times greater than the ambient 1.5 × 10^(−5) s^(−1) meridional shear of zonal winds at the latitudes of the GRS and Oval BC. Maximum Rossby numbers of 0.36 are computed for flows within both the GRS and the Oval BC. Generally, the Rossby numbers within these features are much lower, indicating strongly geostrophic constraints on the flow. The difference in streamline curvature within the GRS and the Oval BC is found to compensate for the difference in planetary vorticity at the respective latitudes of the features. Motions within the central region of the GRS are much slower and more random than around the spot’s outer portion

The double-edged sword of CRISPR-Cas systems

A recent paper gives the details on how specific small RNAs can program a protein to cleave an undesired piece of DNA and to provide immunity to a microbial cell