17 research outputs found
Particle filter-based delamination shape prediction in composites subjected to fatigue loading
Modeling generic size features of delamination, such as area or length, has long been considered in the literature for damage prognosis in composites through specific models describing damage state evolution with load cycles or time. However, the delamination shape has never been considered, despite that it holds important information for damage diagnosis and prognosis, including the delamination area, its center, and perimeter, useful for structural safety evaluation. In this context, this paper develops a novel particle filter (PF)-based framework for delamination shape prediction. To this end, the delamination image is discretized by a mesh, where control points are defined as intersections between the grid lines and the perimeter of the delamination. A parametric data-driven function maps each point position as a function of the load cycles and is initially fitted on a sample test. Then, a PF is independently implemented for each node whereby to predict their future positions along the mesh lines, thus allowing delamination shape progression estimates. The new framework is demonstrated with reference to experimental tests of fatigue delamination growth in composite panels with ultrasonics C-scan monitoring
Modelling adaptive systems using plausible petri nets
One of the main challenges when analyzing and modelling complex systems using Petri nets is to deal with uncertain information, and moreover, to be able to use such uncertainty to dynamically adapt the modelled system to uncertain (changing) contextual conditions. Such self-adaptation relies on some form of learning capability of the Petri net, which can be hardly implemented using the existing Petri net formalisms. This paper shows how uncertainty management and self-adaptation can be achieved naturally using Plausible Petri Nets, a new Petri net paradigm recently developed by the authors. The methodology is exemplified using a case study about railway track asset management, where several track maintenance and inspection activities are modelled jointly with a stochastic track geometry degradation process using a Plausible Petri net. The resulting expert system is shown to be able to autonomously adapt to contextual changes coming from noisy condition monitoring data. This adaptation is carried out taking advantage of a Bayesian updating mechanism which is inherently implemented in the execution semantics of the Plausible Petri net
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
Particle Filter-Based Delamination Shape Prediction in Composites
Modelling generic size feature of delamination, like area or length, has long been considered in the literature for damage prognosis in composites through specific models describing damage state evolution with load cycles or time. However, the delamination shape has never been considered, despite that it contains more damage information like the delamination area, center, and boundary for structural safety evaluation. In this context, this paper develops a novel particle filter-based framework for delamination shape prediction. To this end, the delamination image is discretized by a mesh, where control points are defined as intersections between the grid lines and the boundary of the delamination. A parametric data-driven function maps each point position as a function of the load cycles and is initially fitted on a sample test. Then, a particle filter is independently implemented for each node whereby to predict their future positions along the mesh lines, thus allowing delamination shape progression estimates. The new framework is demonstrated with reference to experimental tests of fatigue delamination growth in composite panels with ultrasonics C-scan monitoring
Evolutionary and biogeographic history of the subfamily Neoplecostominae (Siluriformes: Loricariidae)
Freshwater fish evolution has been shaped by changes in the earth's surface involving changes in the courses of rivers and fluctuations in sea level. The main objective of this study is to improve our knowledge of the evolution of loricariids, a numerous and adaptive group of freshwater catfish species, and the role of geological changes in their evolution. We use a number of different phylogenetic methods to test the relationships among 52 representative taxa within the Neoplecostominae using 4676 bps of mitochondrial and nuclear DNA. Our analysis revealed that the subfamily Neoplecostominae is monophyletic, including Pseudotocinclus, with three lineages recognized. The first lineage is composed of part of Pareiorhina rudolphi, P. cf. rudolphi, and Pseudotocinclus; the second is composed of Isbrueckerichthys, Pareiorhaphis, Kronichthys, and the species Neoplecostomus ribeirensis; and the third is composed of Pareiorhina carrancas, P. cf. carrancas, Pareiorhina sp. 1, a new genus, and all the species of the genus Neoplecostomus, except N. ribeirensis. The relaxed molecular clock calibration provides a temporal framework for the evolution of the group, which we use for a likelihood-based historical biogeographic analysis to test relevant hypotheses on the formation of southeast Brazil. We hypothesize that headwater capture events and marine regressions have shaped the patterns of distribution within the subfamily Neoplecostominae throughout the distinct basins of southeast Brazil.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES
Molecular systematics of the armored neotropical catfish subfamily Neoplecostominae (Siluriformes: Loricariidae)
Morphological and molecular studies in the family Loricariidae have revealed that the relationships among its members are not yet well resolved, and the present study was conducted with the main objective of improving our knowledge about this highly diversified group of catfishes. Maximum parsimony and Bayesian analysis were conducted on a matrix of 53 terminal taxa and 4676 characters with partial sequences of the genes COI, CytB, 16S rRNA, 12S rRNA and F-reticulon 4. As outgroups, samples of the species Hemipsilichthys gobio and H. papillatus (subfamily Delturinae), Rineloricaria jaraguensis (subfamily Loricariinae), Hypostomus nigromaculatus (subfamily Hypostominae), Hypoptopoma inexpectatum (subfamily Hypoptopomatinae), and Corumbataia cuestae (subfamily Otothyrinae) were used. The results showed that the subfamily Neoplecostominae is monophyletic, including Pseudotocinclus, and three clades were recognized. The first one is composed of Pareiorhina rudolphi, P. cf. rudolphi and Pseudotocinclus. The second is composed of Isbrueckerichthys, Pareiorhaphis, Kronichthys and Neoplecostomus ribeirensis. The third is composed of the remaining species of the genera Neoplecostomus, except N. ribeirensis, Pareiorhina carrancas, P. cf. carrancas, Pareiorhina sp. 1 (possible new species) and an undescribed taxon referred to in this paper as new genus and species 2. In our analyses, Pareiorhina and Neoplecostomus are paraphyletic taxa.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES
Production and preliminary characterization of a thermophilic lipase from Thermomucor indicae-seudaticae N31
Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.Ministerio de Ciencia, Innovación y Universidades (MICIU) / FEDERInstituto de Salud Carlos IIIFundación Científica AECCBreast Cancer Research FoundationGeneralitat de CatalunyaCentro de Investigación Biomédica en Red (CIBERONC)Depto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasTRUEpu