Least-Squares Filtering Algorithm in Sensor Networks with Noise Correlation and Multiple Random Failures in Transmission

This paper addresses the least-squares centralized fusion estimation problem of discrete-time random signals from measured outputs, which are perturbed by correlated noises. These measurements are obtained by different sensors, which send their information to a processing center, where the complete set of data is combined to obtain the estimators. Due to random transmission failures, some of the data packets processed for the estimation may either contain only noise (uncertain observations), be delayed (randomly delayed observations), or even be definitely lost (random packet dropouts). These multiple random transmission uncertainties are modelled by sequences of independent Bernoulli random variables with different probabilities for the different sensors. By an innovation approach and using the last observation that successfully arrived when a packet is lost, a recursive algorithm is designed for the filtering estimation problem. The proposed algorithm is easily implemented and does not require knowledge of the signal evolution model, as only the first- and second-order moments of the processes involved are used. A numerical simulation example illustrates the feasibility of the proposed estimators and shows how the probabilities of the multiple random failures influence their performance

Integration of CLIP experiments of RNAbinding proteins: a novel approach to predict context-dependent splicing factors from transcriptomic data

Background: Splicing is a genetic process that has important implications in several diseases including cancer. Deciphering the complex rules of splicing regulation is crucial to understand and treat splicing-related diseases. Splicing factors and other RNA-binding proteins (RBPs) play a key role in the regulation of splicing. The specific binding sites of an RBP can be measured using CLIP experiments. However, to unveil which RBPs regulate a condition, it is necessary to have a priori hypotheses, as a single CLIP experiment targets a single protein. Results: In this work, we present a novel methodology to predict context-specific splicing factors from transcriptomic data. For this, we systematically collect, integrate and analyze more than 900 CLIP experiments stored in four CLIP databases: POSTAR2, CLIPdb, DoRiNA and StarBase. The analysis of these experiments shows the strong coherence between the binding sites of RBPs of similar families. Augmenting this information with expression changes, we are able to correctly predict the splicing factors that regulate splicing in two gold-standard experiments in which specific splicing factors are knocked-down. Conclusions: The methodology presented in this study allows the prediction of active splicing factors in either cancer or any other condition by only using the information of transcript expression. This approach opens a wide range of possible studies to understand the splicing regulation of different conditions. A tutorial with the source code and databases is available at https://gitlab.com/fcarazo.m/sfprediction

Graphic Classes in the Worldwide Classroom: A Comparison of Two MOOC Experiences

Graphics are present in the day-to-day professional practice of architects and engineers, not only to receive and transmit information, but also to design and create. Students who are accepted on university courses have varied curriculum vitae, and some may initially lack skills. Consequently, engineering schools have developed a Massive Open Online Course (MOOC) entitled “The Language of Engineering” (ELI), which reviews basic geometry concepts and develops spatial intelligence, among others. The Barcelona School of Architecture has produced “From reality to design. From design to augmented reality” (RA), which covers topics including traditional architectural representation and the latest techniques. The goal of this study was to explain and analyse the main characteristics and learning strategies of these two MOOC (strengths, weaknesses and opportunities for improvement). The results show that although strategies vary depending on the subjects, the contents and exercises should be practical and adapted to students (interests, level, time availability and aesthetics), always considering motivation as a key point (gamification). These topics have been found to have a considerable influence on the success of a MOOC. Therefore, the conclusions should be considered in subsequent versions of these courses and other MOOCs.Postprint (author's final draft

Spatial Memory Training Counteracts Hippocampal GIRK Channel Decrease in the Transgenic APPSw,Ind J9 Alzheimer's Disease Mouse Model

This work was supported by grants BFU2017-82494-P, PID2020-115823-GB100 funded by MCIN/AEI/10.13039/501100011033, and SBPLY/21/180501/000150 funded by JCCM and ERDF A way of making Europe, to LJD and JDNL; and grant PID2019-106615RB-I00 and Instituto de Salud Carlos III (CIBERNED CB06/05/0042) to CAS. AC held a Margarita Salas Postdoctoral Research Fellow funded by European Union NextGenerationEU/PRTR.G-protein-gated inwardly rectifying potassium (GIRK) channels are critical determinants of neuronal excitability. They have been proposed as potential targets to restore excitatory/inhibitory balance in acute amyloidosis models, where hyperexcitability is a hallmark. However, the role of GIRK signaling in transgenic mice models of Alzheimer's disease (AD) is largely unknown. Here, we study whether progressive amyloid-β (Aβ) accumulation in the hippocampus during aging alters GIRK channel expression in mutant β-amyloid precursor protein (APP J9) transgenic AD mice. Additionally, we examine the impact of spatial memory training in a hippocampal-dependent task, on protein expression of GIRK subunits and Regulator of G-protein signaling 7 (RGS7) in the hippocampus of APP J9 mice. Firstly, we found a reduction in GIRK2 expression (the main neuronal GIRK channels subunit) in the hippocampus of 6-month-old APP J9 mice. Moreover, we found an aging effect on GIRK2 and GIRK3 subunits in both wild type (WT) and APP J9 mice. Finally, when 6-month-old animals were challenged to a spatial memory training, GIRK2 expression in the APP J9 mice were normalized to WT levels. Together, our results support the evidence that GIRK2 could account for the excitatory/inhibitory neurotransmission imbalance found in AD models, and training in a cognitive hippocampal dependent task may have therapeutic benefits of reversing this effect and lessen early AD deficits

Comparison of molecular dynamics and superfamily spaces of protein domain deformation

<p>Abstract</p> <p>Background</p> <p>It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space).</p> <p>Results</p> <p>Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases.</p> <p>Conclusion</p> <p>Theoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or <it>ab initio </it>protein folding.</p

Elastofibroma Dorsi

Se realiza un estudio clínico-patológico de dos casos, mujeres de 57 y 45 años, de "elastofibroma dorsi" intervenidos quirúrgicamente. En una enferma apareció como una tumoracion asintomática y en otra asociada a dolor en el hombro irradiado a miembro superior derecho. Se describen las particularizadas clínicas, las exploraciones complementarias, los hallazgos quirúrgicos y las características histológicas de estos tumores de partes blandas cuyo origen debe referirse a una alteración del tejido fibroelástico. Se confronta nuestra experiencia con los casos anteriormente publicados confirmándose su aparición en mujeres adultas o añosas dedicadas a trabajos manuales rutinarios, que parecen estar implicados en la patogenia del elastofibroma dorsi. En uno de los casos, aunque localizado en el espacio anatómico escápulo-torácico, su situación era supraescapular frente a la típicamente infraescapular del elastofibroma dorsi, y la consideramos la primera observación de la literatura.A clinical-pathological study of two cases of elastofibroma dorsi was carried out. Both patients were female, 57 and 45 years old, and underwent surgical operation. One patients was sympton-free, while the other complained of pain in the shoulder which spread to the upper right arm. The autors describe the clinical details, the diagnostic methods employed, the results of surgery and the histopathological features of these tumours which must have originated in a modification of conective tissue, especially in elastic fibres. We compare our findings with those of previously published cases and can confirm the appearence of these tumours in adults or middle-aged women who carry out rutinary manual work, which seems to be connected with the pathogeny of the elastofibroma dorsi. These are normally found adjacent to the vertebral border of the escapula at its inferior angle, but in one case ot was located in the supra-escapular region and we believe this is the first evidence of this kind in the literature

TranscriptAchilles: a genome-wide platform to predict isoform biomarkers of gene essentiality in cancer

Background Aberrant alternative splicing plays a key role in cancer development. In recent years, alternative splicing has been used as a prognosis biomarker, a therapy response biomarker, and even as a therapeutic target. Next-generation RNA sequencing has an unprecedented potential to measure the transcriptome. However, due to the complexity of dealing with isoforms, the scientific community has not sufficiently exploited this valuable resource in precision medicine. Findings We present TranscriptAchilles, the first large-scale tool to predict transcript biomarkers associated with gene essentiality in cancer. This application integrates 412 loss-of-function RNA interference screens of >17,000 genes, together with their corresponding whole-transcriptome expression profiling. Using this tool, we have studied which are the cancer subtypes for which alternative splicing plays a significant role to state gene essentiality. In addition, we include a case study of renal cell carcinoma that shows the biological soundness of the results. The databases, the source code, and a guide to build the platform within a Docker container are available at GitLab. The application is also available online. Conclusions TranscriptAchilles provides a user-friendly web interface to identify transcript or gene biomarkers of gene essentiality, which could be used as a starting point for a drug development project. This approach opens a wide range of translational applications in cancer