Whole slide image registration for the study of tumor heterogeneity

Consecutive thin sections of tissue samples make it possible to study local variation in e.g. protein expression and tumor heterogeneity by staining for a new protein in each section. In order to compare and correlate patterns of different proteins, the images have to be registered with high accuracy. The problem we want to solve is registration of gigapixel whole slide images (WSI). This presents 3 challenges: (i) Images are very large; (ii) Thin sections result in artifacts that make global affine registration prone to very large local errors; (iii) Local affine registration is required to preserve correct tissue morphology (local size, shape and texture). In our approach we compare WSI registration based on automatic and manual feature selection on either the full image or natural sub-regions (as opposed to square tiles). Working with natural sub-regions, in an interactive tool makes it possible to exclude regions containing scientifically irrelevant information. We also present a new way to visualize local registration quality by a Registration Confidence Map (RCM). With this method, intra-tumor heterogeneity and charateristics of the tumor microenvironment can be observed and quantified.Comment: MICCAI2018 - Computational Pathology and Ophthalmic Medical Image Analysis - COMPA

Reversed Janus Micro/Nanomotors with Internal Chemical Engine

Self-motile Janus colloids are important for enabling a wide variety of microtechnology applications as well as for improving our understanding of the mechanisms of motion of artificial micro- and nanoswimmers. We present here micro/nanomotors which possess a reversed Janus structure of an internal catalytic "chemical engine". The catalytic material (here platinum (Pt)) is embedded within the interior of the mesoporous silica (mSiO(2))-based hollow particles and triggers the decomposition of H2O2 when suspended in an aqueous peroxide (H2O2) solution. The pores/gaps at the noncatalytic (Pt) hemisphere allow the exchange of chemical species in solution between the exterior and the interior of the particle. By varying the diameter of the particles, we observed size-dependent motile behavior in the form of enhanced diffusion for 500 nm particles, and self-phoretic motion, toward the nonmetallic part, for 1.5 and 3 mu m ones. The direction of motion was rationalized, by a theoretical model based on self-phoresis. For the 3 mu m particles, a change in the morphology of the porous part is observed, which is accompanied by a change in the mechanism of propulsion via bubble nucleation and ejection as well as a change in the direction of motion.1128Ysciescopu

FunFOLDQA: a quality assessment tool for protein-ligand binding site residue predictions

The estimation of prediction quality is important because without quality measures, it is difficult to determine the usefulness of a prediction. Currently, methods for ligand binding site residue predictions are assessed in the function prediction category of the biennial Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment, utilizing the Matthews Correlation Coefficient (MCC) and Binding-site Distance Test (BDT) metrics. However, the assessment of ligand binding site predictions using such metrics requires the availability of solved structures with bound ligands. Thus, we have developed a ligand binding site quality assessment tool, FunFOLDQA, which utilizes protein feature analysis to predict ligand binding site quality prior to the experimental solution of the protein structures and their ligand interactions. The FunFOLDQA feature scores were combined using: simple linear combinations, multiple linear regression and a neural network. The neural network produced significantly better results for correlations to both the MCC and BDT scores, according to Kendall’s τ, Spearman’s ρ and Pearson’s r correlation coefficients, when tested on both the CASP8 and CASP9 datasets. The neural network also produced the largest Area Under the Curve score (AUC) when Receiver Operator Characteristic (ROC) analysis was undertaken for the CASP8 dataset. Furthermore, the FunFOLDQA algorithm incorporating the neural network, is shown to add value to FunFOLD, when both methods are employed in combination. This results in a statistically significant improvement over all of the best server methods, the FunFOLD method (6.43%), and one of the top manual groups (FN293) tested on the CASP8 dataset. The FunFOLDQA method was also found to be competitive with the top server methods when tested on the CASP9 dataset. To the best of our knowledge, FunFOLDQA is the first attempt to develop a method that can be used to assess ligand binding site prediction quality, in the absence of experimental data

Two distinct populations of Bovine IL-17+ T-cells can be induced and WC1+IL-17+γδ T-cells are effective killers of protozoan parasites

IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4+ and WC1+ γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17+ T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses

Galaxy and Mass Assembly (GAMA): Accurate number densities and environments of massive ultracompact galaxies at 0.02 < z < 0.3

Massive Ultracompact Galaxies (MUGs) are common at z=2-3, but very rare in the nearby Universe. Simulations predict that the few surviving MUGs should reside in galaxy clusters, whose large relative velocities prevent them from merging, thus maintaining their original properties (namely stellar populations, masses, sizes and dynamical state). We take advantage of the high-completeness, large-area spectroscopic GAMA survey, complementing it with deeper imaging from the KiDS and VIKING surveys. We find a set of 22 bona-fide MUGs, defined as having high stellar mass (>8x10^10 M_Sun) and compact size (R_e ~ 10^10 M_Sun Kpc^-2). Interestingly, a large fraction feature close companions -- at least in projection -- suggesting that many (but not all) live in the central regions of groups. Halo masses show these galaxies inhabit average-mass groups. As MUGs are found to be almost equally distributed among environments of different masses, their relative fraction is higher in more massive overdensities, matching the expectations that some of these galaxies fell in these regions at early times. However, there must be another channel leading some of these galaxies to an abnormally low merger history because our sample shows a number of objects that do not inhabit particularly dense environments. (abridged

Osmoregulators proline and glycine betaine counteract salinity stress in canola

Salt inundation leads to increased salinization of arable land in many arid and semi-arid regions. Until genetic solutions are found farmers and growers must either abandon salt-affected fields or use agronomic treatments that alleviate salt stress symptoms. Here, field experiments were carried out to study the effect of the osmoregulators proline at 200 mg L-1 and glycine betaine at 400 mg L-1 in counteracting the harmful effect of soil salinity stress on canola plants grown in Egypt. We assessed growth characteristics, yield and biochemical constituents. Results show first that all growth characters decreased with increasing salinity stress but applied osmoregulators alleviated these negative effects. Second, salinity stress decreased photosynthetic pigments, K and P contents, whilst increasing proline, soluble sugars, ascorbic acid, Na and Cl contents. Third, application of osmoregulators without salt stress increased photosynthetic pigments, proline, soluble sugars, N, K and P contents whilst decreasing Na and Cl contents. It is concluded that the exogenously applied osmoregulators glycine betaine and proline can fully or partially counteract the harmful effect of salinity stress on growth and yield of canola.© INRA and Springer-Verlag, France 2012

Consensus over Random Graph Processes: Network Borel-Cantelli Lemmas for Almost Sure Convergence

Distributed consensus computation over random graph processes is considered. The random graph process is defined as a sequence of random variables which take values from the set of all possible digraphs over the node set. At each time step, every node updates its state based on a Bernoulli trial, independent in time and among different nodes: either averaging among the neighbor set generated by the random graph, or sticking with its current state. Connectivity-independence and arc-independence are introduced to capture the fundamental influence of the random graphs on the consensus convergence. Necessary and/or sufficient conditions are presented on the success probabilities of the Bernoulli trials for the network to reach a global almost sure consensus, with some sharp threshold established revealing a consensus zero-one law. Convergence rates are established by lower and upper bounds of the $\epsilon$-computation time. We also generalize the concepts of connectivity/arc independence to their analogues from the $*$-mixing point of view, so that our results apply to a very wide class of graphical models, including the majority of random graph models in the literature, e.g., Erd\H{o}s-R\'{e}nyi, gossiping, and Markovian random graphs. We show that under $*$-mixing, our convergence analysis continues to hold and the corresponding almost sure consensus conditions are established. Finally, we further investigate almost sure finite-time convergence of random gossiping algorithms, and prove that the Bernoulli trials play a key role in ensuring finite-time convergence. These results add to the understanding of the interplay between random graphs, random computations, and convergence probability for distributed information processing.Comment: IEEE Transactions on Information Theory, In Pres

Polybrominated Diphenyl Ethers (PBDEs) and Bioaccumulative Hydroxylated PBDE Metabolites in Young Humans from Managua, Nicaragua

OBJECTIVE: Our aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected. METHODS: We assessed PBDEs in pooled serum samples obtained in 2002 from children 11-15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15-44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances. RESULTS: The children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites. CONCLUSIONS: Unexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum