Using bi-clustering algorithm for analyzing online users activity in a virtual campus

Data mining algorithms have been proved to be useful for the processing of large data sets in order to extract relevant information and knowledge. Such algorithms are also important for analyzing data collected from the users' activity users. One family of such data analysis is that of mining of log files of online applications that register the actions of online users during long periods of time. A relevant objective in this case is to study the behavior of online users and feedback the design processes of online applications to provide better usability and adaption to users' preferences. The context of this work is that of a virtual campus in which thousands of students and tutors carry out the learning and teaching activity using online applications. The information stored in log files of virtual campuses tend to be large, complex and heterogeneous in nature. Hence, their mining requires both efficient and intelligent processing and analysis of user interaction data during long-term learning activities. In this paper, we present a bi-clustering algorithm for processing large log data sets from the online daily activity of students in a real virtual campus. Our approach is useful to extract relevant knowledge about user activity such as navigation patterns, activities performed as well as to study time parameters related to such activities. The extracted information can be useful not only to students and tutors to stimulate and improve their experience when interacting with the system but also to the designers and developers of the virtual campus in order to better support the online teaching and learning.Peer ReviewedPostprint (published version

Membrane protein detection and morphological analysis of red blood cells in hereditary spherocytosis by confocal laser scanning microscopy

In hereditary spherocytosis (HS), genetic mutations in the cell membrane and cytoskeleton proteins cause structural defects in red blood cells (RBCs). As a result, cells are rigid and misshapen, usually with a characteristic spherical form (spherocytes), too stiff to circulate through microcirculation regions, so they are prone to undergo hemolysis and phagocytosis by splenic macrophages. Mild to severe anemia arises in HS, and other derived symptoms like splenomegaly, jaundice, and cholelithiasis. Although abnormally shaped RBCs can be identified under conventional light microscopy, HS diagnosis relies on several clinical factors and sometimes on the results of complex molecular testing. It is specially challenging when other causes of anemia coexist or after recent blood transfusions. We propose two different approaches to characterize RBCs in HS: (i) an immunofluorescence assay targeting protein band 3, which is affected in most HS cases and (ii) a three-dimensional morphology assay, with living cells, staining the membrane with fluorescent dyes. Confocal laser scanning microscopy (CLSM) was used to carry out both assays, and in order to complement the latter, a software was developed for the automated detection of spherocytes in blood samples. CLSM allowed the precise and unambiguous assessment of cell shape and protein expression.This publication is part of the project PID2020-112527RBI00, funded by CIN/AEI/10.13039/501100011033. Laura Rey-Barroso thanks the Ministry of Science, Innovation and Universities for the PhD (FPI) grant she has received (DPI2017-89414-R). The current study has been funded by the Spanish National Agency of Investigation (AEI).Peer ReviewedPostprint (published version

Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation

Gasdermin B (GSDMB) over-expression promotes poor prognosis and aggressive behavior in HER2 breast cancer by increasing resistance to therapy. Decoding the molecular mechanism of GSDMB-mediated drug resistance is crucial to identify novel effective targeted treatments for HER2/GSDMB aggressive tumors. Different in vitro approaches (immunoblot, qRT-PCR, flow cytometry, proteomic analysis, immunoprecipitation, and confocal/electron microscopy) were performed in HER2 breast and gastroesophageal carcinoma cell models. Results were then validated using in vivo preclinical animal models and analyzing human breast and gastric cancer samples. GSDMB up-regulation renders HER2 cancer cells more resistant to anti-HER2 agents by promoting protective autophagy. Accordingly, the combination of lapatinib with the autophagy inhibitor chloroquine increases the therapeutic response of GSDMB-positive cancers in vitro and in zebrafish and mice tumor xenograft in vivo models. Mechanistically, GSDMB N-terminal domain interacts with the key components of the autophagy machinery LC3B and Rab7, facilitating the Rab7 activation during pro-survival autophagy in response to anti-HER2 therapies. Finally, we validated these results in clinical samples where GSDMB/Rab7/LC3B co-expression associates significantly with relapse in HER2 breast and gastric cancers. Our findings uncover for the first time a functional link between GSDMB over-expression and protective autophagy in response to HER2-targeted therapies. GSDMB behaves like an autophagy adaptor and plays a pivotal role in modulating autophagosome maturation through Rab7 activation. Finally, our results provide a new and accessible therapeutic approach for HER2/GSDMB + cancers with adverse clinical outcome. The online version contains supplementary material available at 10.1186/s13046-022-02497-w

Projecte científico tècnic de definició de subunitats paisatgístiques del Parc Natural de l'Alt Pirineu

La identificació i caracterització de subunitats de paisatge per al Parc Natural de l'Alt Pirineu (PNAP) s'ha fet en base a la Llei 8/2005, de 8 de juny, de Protecció, Gestió i Ordenació del Paisatge la qual estableix que "els catàlegs del paisatge són els documents de carácter descriptiu i prospectiu que determinen la tipologia dels paisatges de Catalunya, identifiquen llurs valors i llur estat de conservació i proposen els objectius de qualitat que han de complir" (Article 10). Igualment, la Llei ha previst que la responsabilitat dels catàlegs sigui de l'Observatori del Paisatge que "és una entitat de suport i col·laboració amb l'Administració de la Generalitat en totes les qüestions relacionades amb l'elaboració, l'aplicació i la gestió de les polítiques de paisatge" (Article 13). Per això, aquest treball es basarà en els criteris establerts per l'Observatori del Paisatge (document de referència pels grups de treball, Olot i Barcelona, maig de 2005) i les bases conceptuals, metodològiques i procedimentals que han elaborat per a la realització dels Catàlegs del Paisatge de Catalunya que s'han recollit en un document anomenat Prototipus de Catàleg de Paisatge (PCP). Com que en l'actualitat aquests paràmetres estan en fase de desenvolupament, aquest Projecte Científico Tècnic de Definició de Subunitats Paisatgístiques per al Parc Natural de l'Alt Pirineu s'ha inspirat en aquest document adaptant-se a les necessitats del Parc i desenvolupant les metodologies proposades. El document que es presenta recull la Primera Fase del treball, que s'ha destinat al tractament i adequació de la informació existent (cartogràfica i escrita) per a la delimitació i definició posterior de les diferents subunitats de paisatge

Evaluación de la microscopía confocal como herramienta de diagnóstico en enfermedades de los glóbulos rojos

La esferocitosis hereditaria (EH) provoca mutaciones en las proteínas de la membrana de los glóbulos rojos (GRs) que hacen que las células se deformen y se vuelvan demasiado rígidas para poder viajar a través de los vasos sanguíneos. Estas células anormales se destruyen masivamente en el bazo, lo que provoca anemia grave y esplenomegalia además de ictericia y cálculos biliares. El diagnóstico de la EH requiere la realización de complejas pruebas moleculares en la mayoría de casos. Para evitar la realización de dichas pruebas, la microscopía confocal espectral podría utilizarse en el diagnóstico de estas y otras enfermedades. En este estudio, se tiñó la membrana de los GRs con tintes de color e inmunomarcadores, y, bajo un microscopio Leica TCS8, se analizaron los posibles defectos de membrana expresados como diferencias en color y forma en pacientes con EH

Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes

Background: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients. Methods: This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes. Results: Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening

From vineyards to feedlots: a fund-flow scanning of sociometabolic transition in the Vallès County (Catalonia) 1860-1956-1999

We analyse the changes to agricultural metabolism in four municipalities of Vallès County (Catalonia, Iberia) by accounting for their agroecosystemfunds and flows during the socioecological transition from organic to industrial farming between the late nineteenth and twentieth centuries. The choice of three different stages in this transition allows us to observe the transformation of its funds and flows over time, the links established between them and the effect on their energy profiles.We emphasize the relevance of the integration and consistency of agroecosystem funds for energy efficiency in agriculture and their role as underlying historical drivers of this socioecological transition. While readjustment to market conditions and availability and affordability of external inputs are considered the main drivers of the transition, we also highlight the role of societal energy and nutritional transitions. An analysis of advanced organic agriculture c. 1860 reveals the great effort required to reproduce soil fertility and livestock from the internal recirculation of biomass. Meanwhile, a balance between land produce and livestock densities enabled the integration of funds, with a positive impact on energy performance. The adoption of fossil fuels and synthetic fertilizers c. 1956 reduced somewhat the pressure exerted on the land by overcoming the former dependence on local biomass flows to reproduce the agroecosystem. Yet external inputs diminished sustainability. Partial dependence on external markets existed congruently with internal crop diversity and the predominance of organic over industrial farm management. A shift towards animal production and consumption led to a new specialization process c. 1999 that resulted in crop homogenization and agroecological landscape disintegration. The energy returns of this linear feed-food livestock bioconversion declined compared to earlier mixed farming. Huge energy flows driven by a globalized economy ran through this agroecosystem, provoking deep impacts at both a local and external scale

Langmuir probe electronics upgrade on the tokamak a configuration variable

A detailed description of the Langmuir probe electronics upgrade for TCV (Tokamak a Configuration Variable) is presented. The number of amplifiers and corresponding electronics has been increased from 48 to 120 in order to simultaneously connect all of the 114 Langmuir probes currently mounted in the TCV divertor and main-wall tiles. Another set of 108 amplifiers is ready to be installed in order to connect 80 new probes, built in the frame of the TCV divertor upgrade. Technical details of the amplifier circuitry are discussed as well as improvements over the first generation of amplifiers developed at SPC (formerly CRPP) in 1993/1994 and over the second generation developed in 2012/2013. While the new amplifiers have been operated successfully for over a year, it was found that their silicon power transistors can be damaged during some off-normal plasma events. Possible solutions are discussed. (C) 2019 Author(s)

Overview of the TCV tokamak experimental programme

The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with \u27small\u27 (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations

Real-time plasma state monitoring and supervisory control on TCV

In ITER and DEMO, various control objectives related to plasma control must be simultaneously achieved by the plasma control system (PCS), in both normal operation as well as off-normal conditions. The PCS must act on off-normal events and deviations from the target scenario, since certain sequences (chains) of events can precede disruptions. It is important that these decisions are made while maintaining a coherent prioritization between the real-time control tasks to ensure high-performance operation. In this paper, a generic architecture for task-based integrated plasma control is proposed. The architecture is characterized by the separation of state estimation, event detection, decisions and task execution among different algorithms, with standardized signal interfaces. Central to the architecture are a plasma state monitor and supervisory controller. In the plasma state monitor, discrete events in the continuous-valued plasma state are modeled using finite state machines. This provides a high-level representation of the plasma state. The supervisory controller coordinates the execution of multiple plasma control tasks by assigning task priorities, based on the finite states of the plasma and the pulse schedule. These algorithms were implemented on the TCV digital control system and integrated with actuator resource management and existing state estimation algorithms and controllers. The plasma state monitor on TCV can track a multitude of plasma events, related to plasma current, rotating and locked neoclassical tearing modes, and position displacements. In TCV experiments on simultaneous control of plasma pressure, safety factor profile and NTMs using electron cyclotron heating (ECH) and current drive (ECCD), the supervisory controller assigns priorities to the relevant control tasks. The tasks are then executed by feedback controllers and actuator allocation management. This work forms a significant step forward in the ongoing integration of control capabilities in experiments on TCV, in support of tokamak reactor operation