Abstract: Premise of the study: Because of their limited length, xylem conduits need to connect to each other to maintain water transport from roots to leaves. Conduit spatial distribution in a cross section plays an important role in aiding this connectivity. While indices of conduit spatial distribution already exist, they are not well defined statistically. * Methods: We used point pattern analysis to derive new spatial indices. One hundred and five cross-sectional images from different species were transformed into binary images. The resulting point patterns, based on the locations of the conduit centers-of-area, were analyzed to determine whether they departed from randomness. Conduit distribution was then modeled using a spatially explicit stochastic model. * Key results: The presence of conduit randomness, uniformity, or aggregation depended on the spatial scale of the analysis. The large majority of the images showed patterns significantly different from randomness at least at one spatial scale. A strong phylogenetic signal was detected in the spatial variables. * Conclusions: Conduit spatial arrangement has been largely conserved during evolution, especially at small spatial scales. Species in which conduits were aggregated in clusters had a lower conduit density compared to those with uniform distribution. Statistically sound spatial indices must be employed as an aid in the characterization of distributional patterns across species and in models of xylem water transport. Point pattern analysis is a very useful tool in identifying spatial patterns.

Abstract: The efficiency of lung cancer screening for reducing mortality is hindered by the high rate of false positives. Artificial intelligence applied to radiomics could help to early discard benign cases from the analysis of CT scans. The available amount of data and the fact that benign cases are a minority, constitutes a main challenge for the successful use of state of the art methods (like deep learning), which can be biased, over-fitted and lack of clinical reproducibility. We present an hybrid approach combining the potential of radiomic features to characterize nodules in CT scans and the generalization of the feed forward networks. In order to obtain maximal reproducibility with minimal training data, we propose an embedding of nodules based on the statistical significance of radiomic features for malignancy detection. This representation space of lesions is the input to a feed
forward network, which architecture and hyperparameters are optimized using own-defined metrics of the diagnostic power of the whole system. Results of the best model on an independent set of patients achieve 100% of sensitivity and 83% of specificity (AUC = 0.94) for malignancy detection.

Abstract: Outlier detection is essential for optimal performance of machine learning methods and statistical predictive models. Their detection is especially determinant in small sample size unbalanced problems, since in such settings outliers become highly influential and significantly bias models. This particular experimental settings are usual in medical applications, like diagnosis of rare pathologies, outcome of experimental personalized treatments or pandemic emergencies. In contrast to population-based methods, neighborhood based local approaches compute an outlier score from the neighbors of each sample, are simple flexible methods that have the potential to perform well in small sample size unbalanced problems. A main concern of local approaches is the impact that the computation of each sample neighborhood has on the method performance. Most approaches use a distance in the feature space to define a single neighborhood that requires careful selection of several parameters, like the number of neighbors.
This work presents a local approach based on a local measure of the heterogeneity of sample labels in the feature space considered as a topological manifold. Topology is computed using the communities of a weighted graph codifying mutual nearest neighbors in the feature space. This way, we provide with a set of multiple neighborhoods able to describe the structure of complex spaces without parameter fine tuning. The extensive experiments on real-world and synthetic data sets show that our approach outperforms, both, local and global strategies in multi and single view settings.

Abstract: Two-state and operational models of both agonism and allosterism are compared to identify and characterize common pharmacological parameters. To account for the receptor-dependent basal response, constitutive receptor activity is considered in the operational models. By arranging two-state models as the fraction of active receptors and operational models as the fractional response relative to the maximum effect of the system, a one-by-one correspondence between parameters is found. The comparative analysis allows a better understanding of complex allosteric interactions. In particular, the inclusion of constitutive receptor activity in the operational model of allosterism allows the characterization of modulators able to lower the basal response of the system; that is, allosteric modulators with negative intrinsic efficacy. Theoretical simulations and overall goodness of fit of the models to simulated data suggest that it is feasible to apply the models to experimental data and constitute one step forward in receptor theory formalism.

Abstract: Chromosome territoriality is not random along the cell cycle and it is mainly governed by intrinsic chromosome factors and gene expression patterns. Conversely, very few studies have explored the factors that determine chromosome territoriality and its influencing factors during meiosis. In this study, we analysed chromosome positioning in murine spermatogenic cells using three-dimensionally fluorescence in situ hybridization-based methodology, which allows the analysis of the entire karyotype. The main objective of the study was to decipher chromosome positioning in a radial axis (all analysed germ-cell nuclei) and longitudinal axis (only spermatozoa) and to identify the chromosomal factors that regulate such an arrangement. Results demonstrated that the radial positioning of chromosomes during spermatogenesis was cell-type specific and influenced by chromosomal factors associated to gene activity. Chromosomes with specific features that enhance transcription (high GC content, high gene density and high numbers of predicted expressed genes) were preferentially observed in the inner part of the nucleus in virtually all cell types. Moreover, the position of the sex chromosomes was influenced by their transcriptional status, from the periphery of the nucleus when its activity was repressed (pachytene) to a more internal position when it is partially activated (spermatid). At pachytene, chromosome positioning was also influenced by chromosome size due to the bouquet formation. Longitudinal chromosome positioning in the sperm nucleus was not random either, suggesting the importance of ordered longitudinal positioning for the release and activation of the paternal genome after fertilisation.