Abstract: The operational model of agonism assumes that the maximum effect a particular receptor system can achieve (the Em parameter) is fixed. Em estimates are above but close to the asymptotic maximum effects of endogenous agonists. The concept of Em is contradicted by superagonists and those positive allosteric modulators that significantly increase the maximum effect of endogenous agonists. An extension of the operational model is proposed that assumes that the Em parameter does not necessarily have a single value for a receptor system but has multiple values associated to multiple active receptor conformations. The model provides a mechanistic link between active receptor conformation and agonist efficacy, which can be useful for the analysis of agonist response under different receptor scenarios.

Abstract: Vision-based bronchoscopy (VB) models require the registration of the virtual lung model with the frames from the video bronchoscopy to provide effective guidance during the biopsy. The registration can be achieved by either tracking the position and orientation of the bronchoscopy camera or by calibrating its deviation from the pose (position and orientation) simulated in the virtual lung model. Recent advances in neural networks and temporal image processing have provided new opportunities for guided bronchoscopy. However, such progress has been hindered by the lack of comparative experimental conditions.
In the present paper, we share a novel synthetic dataset allowing for a fair comparison of methods. Moreover, this paper investigates several neural network architectures for the learning of temporal information at different levels of subject personalization. In order to improve orientation measurement, we also present a standardized comparison framework and a novel metric for camera orientation learning. Results on the dataset show that the proposed metric and architectures, as well as the standardized conditions, provide notable improvements to current state-of-the-art camera pose estimation in video bronchoscopy.

Abstract: In most eukaryotes, pairing of homologous chromosomes is an essential feature of meiosis that ensures homologous recombination and segregation. However, when the pairing process begins, it is still under investigation. Contrasting data exists in Mus musculus, since both leptotene DSB-dependent and preleptotene DSB-independent mechanisms have been described. To unravel this contention, we examined homologous pairing in pre-meiotic and meiotic Mus musculus cells using a threedimensional fuorescence in situ hybridization-based protocol, which enables the analysis of the entire karyotype using DNA painting probes. Our data establishes in an unambiguously manner that 73.83% of homologous chromosomes are already paired at premeiotic stages (spermatogonia-early preleptotene spermatocytes). The percentage of paired homologous chromosomes increases to 84.60% at mid-preleptotene-zygotene stage, reaching 100% at pachytene stage. Importantly, our results demonstrate a high percentage of homologous pairing observed before the onset of meiosis; this pairing does not occur randomly, as the percentage was higher than that observed in somatic cells (19.47%) and between nonhomologous chromosomes (41.1%). Finally, we have also observed that premeiotic homologous pairing is asynchronous and independent of the chromosome size, GC content, or presence of NOR regions.

Abstract: Project-Based Learning (PBL) is an educational strategy to improve student’s learning capability that, in recent years, has had a progressive acceptance in undergraduate studies. This methodology is based on solving a problem or project in a student working group. In this way, PBL focuses on learning the necessary tools to correctly find a solution to given problems. Since the learning initiative is transferred to the student, the PBL method promotes students own abilities. This allows a better assessment of the true workload that carries out the student in the subject. It follows that the methodology conforms to the guidelines of the Bologna document, which quantifies the student workload in a subject by means of the European credit transfer system (ECTS). PBL is currently applied in undergraduate studies needing strong practical training such as medicine, nursing or law sciences. Although this is also the case in engineering studies, amazingly, few experiences have been reported. In this paper we propose to use PBL in the educational organization of the Computer Graphics subjects in the Computer Science degree. Our PBL project focuses in the development of a C++ graphical environment based on the OpenGL libraries for visualization and handling of different graphical objects. The starting point is a basic skeleton that already includes lighting functions, perspective projection with mouse interaction to change the point of view and three predefined objects. Students have to complete this skeleton by adding their own functions to solve the project. A total number of 10 projects have been proposed and successfully solved. The exercises range from human face rendering to articulated objects, such as robot arms or puppets. In the present paper we extensively report the statement and educational objectives for two of the projects: solar system visualization and a chess game. We report our earlier educational experience based on the standard classroom theoretical, problem and practice sessions and the reasons that motivated searching for other learning methods. We have mainly chosen PBL because it improves the student learning initiative. We have applied the PBL educational model since the beginning of the second semester. The student’s feedback increases in his interest for the subject. We present a comparative study of the teachers’ and students’ workload between PBL and the classic teaching approach, which suggests that the workload increase in PBL is not as high as it seems.

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.