Real-time experimental implementation of predictive control schemes in a small-scale pasteurization plant

Model predictive control (MPC) is one of the most used optimization-based control strategies for large-scale systems, since this strategy allows to consider a large number of states and multi-objective cost functions in a straightforward way. One of the main issues in the design of multi-objective MPC controllers, which is the tuning of the weights associated to each objective in the cost function, is treated in this work. All the possible combinations of weights within the cost function affect the optimal result in a given Pareto front. Furthermore, when the system has time-varying parameters, e.g., periodic disturbances, the appropriate weight tuning might also vary over time. Moreover, taking into account the computational burden and the selected sampling time in the MPC controller design, the computation time to find a suitable tuning is limited. In this regard, the development of strategies to perform a dynamical tuning in function of the system conditions potentially improves the closed-loop performance. In order to adapt in a dynamical way the weights in the MPC multi-objective cost function, an evolutionary-game approach is proposed. This approach allows to vary the prioritization weights in the proper direction taking as a reference a desired region within the Pareto front. The proper direction for the prioritization is computed by only using the current system values, i.e., the current optimal control action and the measurement of the current states, which establish the system cost function over a certain point in the Pareto front. Finally, some simulations of a multi-objective MPC for a real multi-variable case study show a comparison between the system performance obtained with static and dynamical tuning.Peer ReviewedPostprint (author's final draft

Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor β signaling

BACKGROUND: Transforming growth factor-βs (TGF-βs), bone morphogenetic proteins (BMPs) and activins are important regulators of developmental cell growth and differentiation. Signaling by these factors is mediated chiefly by the Smad family of latent transcription factors. RESULTS: There are a large number of uncharacterized cDNA clones that code for novel proteins with homology to known signaling molecules. We have identified a novel molecule from the HUGE database that is related to a previously known molecule, AMSH (associated molecule with the SH3 domain of STAM), an adapter shown to be involved in BMP signaling. Both of these molecules contain a coiled-coil domain located within the amino-terminus region and a JAB (Domain in Jun kinase activation domain binding protein and proteasomal subunits) domain at the carboxy-terminus. We show that this novel molecule, which we have designated AMSH-2, is widely expressed and its overexpression potentiates activation of TGF-β-dependent promoters. Coimmunoprecipitation studies indicated that Smad7 and Smad2, but not Smad3 or 4, interact with AMSH-2. We show that overexpression of AMSH-2 decreases the inhibitory effect of Smad7 on TGF-β signaling. Finally, we demonstrate that knocking down AMSH-2 expression by RNA interference decreases the activation of 3TP-lux reporter in response to TGF-β. CONCLUSIONS: This report implicates AMSH and AMSH-2 as a novel family of molecules that positively regulate the TGF-β signaling pathway. Our results suggest that this effect could be partially explained by AMSH-2 mediated decrease of the action of Smad7 on TGF-β signaling pathway

Community composition and habitat characterization of a rock sponge aggregation (Porifera, Corallistidae) in the Cantabrian Sea.

Deep-sea sponge-dominated communities are complex habitats considered hotspots of biodiversity and ecosystem functioning. They are classified as Vulnerable Marine Ecosystem and are listed as threatened or declining as a result of anthropogenic activities. Yet, studies into the distribution, community structure and composition of these habitats are scarce, hampering the development of appropriate management measures to ensure their conservation. In this study we describe a diverse benthic community, dominated by a lithistid sponge, found in two geomorphological features of important conservation status —Le Danois Bank and El Corbiro Canyon— of the Cantabrian Sea. Based on the analyses of visual transects using a photogrammetric towed vehicle and samples collected by rock dredge, we characterize the habitat and the associated community in detail. This deep-sea sponge aggregation was found on bedrock. It is dominated by one lithistid sponge, Neoschrammeniella aff. bowerbankii (0.2 ind./m2) and further composed of various sponge species as well as of other benthic invertebrates such as cnidarians, bryozoans and crustaceans. Using a non-invasive methodology (SfM – Structure from Motion) and empirical relationships of individuals size and biomass/volume obtained in laboratory for N. aff. bowerbankii, we were able to estimate a total biomass of 41 kg and volume of 39 l of this species in the surveyed area. This approach allows a fine tune methodology for estimating biomass and volume by image-based-observed area avoiding destructive techniques for this species.Postprin

Scope for growth and dietary needs of Mediteranean Pinnids maintained in captivity

Abstract Background: The measurement of the energy available for growth (scope of growth, SFG) can be used in bivalves to make a long-term prediction in a short-term experiment of the condition of the individual. In order to tackle the best conditions for captive maintenance of Mediterranean Pinnids, a SFG study was conducted using Pinna rudis as a model species. Three diets were examined to test the viability of live microalgae and commercial products: i) a control diet using 100% of live microalgae based on the species Isochrysis galbana (t-ISO), ii) a 100% of commercial microalgae diet based on the product Shellfish Diet 1800®, and iii) a 50/50% mix diet of I. galbana (t-ISO) and Shellfish Diet 1800®. Results: SFG results showed significant differences among diets in the physiological functions measured and suggested lower acceptability and digestibility of the commercial product. Negative SFG values were obtained for the commercial diet which indicates that it should be rejected for both Pinnid maintenance. The mixed diet showed improved physiological performance compared to the commercial diet, resulting in a higher SFG that had no significant differences with the control diet. However, in the long-term, the lower digestibility of the mixed diet compared to the control diet could lead to a deterioration of individuals’ conditions and should be considered cautiously. Conclusions: This work represents the first case study of SFG in Pinna spp. and provides fundamental data on dietary needs for the critically endangered species, P. nobilis.En prens

Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin

Background Human pigmentation is a polygenic quantitative trait with high heritability. In addition to genetic factors, it has been shown that pigmentation can be modulated by oestrogens and androgens via up- or down-regulation of melanin synthesis. Our aim was to identify possible sex differences in pigmentation phenotype as well as in melanoma association in a melanoma case-control population of Spanish origin. Methods Five hundred and ninety-nine females (316 melanoma cases and 283 controls) and 458 males (234 melanoma cases and 224 controls) were analysed. We genotyped 363 polymorphisms (single nucleotide polymorphisms (SNPs)) from 65 pigmentation gene regions. Results When samples were stratified by sex, we observed more SNPs associated with dark pigmentation and good sun tolerance in females than in males (107 versus 75; P = 2.32 × 10−6), who were instead associated with light pigmentation and poor sun tolerance. Furthermore, six SNPs in TYR, SILV/CDK2, GPR143, and F2RL1 showed strong differences in melanoma risk by sex (P < 0.01). Conclusions We demonstrate that these genetic variants are important for pigmentation as well as for melanoma risk, and also provide suggestive evidence for potential differences in genetic effects by sex.We thank the Madrid College of Lawyers and all patients from the different contributing Hospitals. We would like to thank Tais Moreno, M. Rosario Alonso, and Guillermo Pita for their expert technical assistance with Illumina genotyping, performed at the Spanish National Genotyping Centre (CeGen, Madrid). MI-V is funded by the “Ministry of Health Carlos III” under a Sara Borrell contract (CD15/00153). ML-C is funded by a Prometeo contract (2015/005). SSO is funded by the “ Ministry of Education, Culture and Sport” under a FPU fellowship (FPU13/04976). GR is funded by the “Ministry of Health Carlos III” under a Miquel Servet II contract (CPII14-00013). This work has also been partly funded by a research project from the Spanish Ministry of Economy and Competitiveness (CGL2014-58526-P), whose principal investigator is S

Mapping the habitats of a complex circalittoral rocky shelf in the Cantabrian Sea (south Bay of Biscay)

This work focuses on the study of habitats and communities of a high structural complexity area at different levels and scales. This gives us a better understanding of an area from an ecological point of view and at the same time provides us with tools that will facilitate management measures. It was developed in a complex circalittoral rocky platform of the central Cantabrian Sea (Bay of Biscay). The sampling was carried out using a towed photogrammetric vehicle and a rock dredge, which was used for the identification of the species. The first level of the study was the abiotic characterization of the area and the analysis of the communities. These analysis were developed using the unsupervised k-means classification method. For abiotic characterization we used the variables directly associated with the composition and morphology of the ground, such as backscatter, BPI (Bathymetric Position Index), roughness and slope. Depth was also included to discriminate between the circalittoral and bathyal zones. We obtained 5 different classes, which we related to the ground types observed by photogrammetry. In the analysis of the communities, the cluster was based on the sampling units extracted from the images (~10 m), from which 5 assemblages were obtained, providing information on the most abundant species of each class supplied by the abiotic study. The second level was carried out considering a management approach and was based on the modeling of the area at lower resolution, more suitable for the analysis of the habitat-fisheries interactions. Thus, the main habitat-forming species (HFS) of the entire circalittoral area were used to perform delta models based on GAMs (Generalize Additive Models). Obtaining the predictions of presence/absence and combining it with the predictions of densities, we got the zero inflated values density-based model. As all the identified habitats have vulnerable benthic species of a certain size settled on rocky bottoms, they can all be considered to belong to the designation 1170 reefs of the Habitats Directive

Germline cdh1 g212e missense variant: Combining clinical, in vitro and in vivo strategies to unravel disease Burden

E-cadherin, encoded by CDH1, is an essential molecule for epithelial homeostasis, whose loss or aberrant expression results in disturbed cell–cell adhesion, increased cell invasion and metas-tasis. Carriers of CDH1 germline mutations have a high risk of developing diffuse gastric cancer and lobular breast cancer, associated with the cancer syndrome Hereditary Diffuse Gastric Cancer (HDGC). The ubiquitous availability of cancer panels has led to the identification of an increasing amount of “incidental” CDH1 genetic variants that pose a serious clinical challenge. This has sparked intensive research aiming at an accurate classification of the variants and consequent validation of their clinical relevance. The present study addressed the significance of a novel CDH1 variant, G212E, identified in an unusually large pedigree displaying strong aggregation of diffuse gastric cancer. We undertook a comprehensive pipeline encompassing family data, in silico predictions, in vitro assays and in vivo strategies, which validated the deleterious phenotype induced by this genetic alteration. In particular, we demonstrated that the G212E variant affects the stability and localization, as well as the adhesive and anti-invasive functions of E-cadherin, triggering epithelial disruption and disorganization. Our findings illustrate the clinical implication of a complementary approach for effective variant categorization and patient management.This work was financed by FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE 2020), Programa Operacional de Competitividade e Inter-nacionalização (POCI) and Programa Operacional Regional do Norte (Norte 2020); and by National Funds through the Portuguese Foundation for Science and Technology (FCT) in the frame-work of the projects PTDC/MED-GEN/30356/2017, PTDC/BTM-SAL/30383/2017, PTDC/BIM-ONC/0281/2014, NORTE-01-0145-FEDER-000029, as well as doctoral grants SFRH/BD/108009/2015-S.M. and SFRH/BD/130708/2017-M.G. E.M.S. is funded by the “FCT Scientific Employment Stimulus—Individual Call” program (CEECIND/00622/2017). We acknowledge the American Association of Patients with Hereditary Gastric Cancer “No Stomach for Cancer” for funding Seruca’s and Figueiredo’s research

The European Transdisciplinary Assessment of Climate Engineering (EuTRACE): Removing Greenhouse Gases from the Atmosphere and Reflecting Sunlight away from Earth

The European Transdisciplinary Assessment of Climate Engineering (EuTRACE): Removing Greenhouse Gases from the Atmosphere and Reflecting Sunlight away from Eart

Recovery of eutrophized marine ecosystems using the European flat oyster, Ostrea edulis

The development of tourism and intensification of agriculture has released large amounts of nitrogen and phosphorus into the Mar Menor coastal lagoon in South-east Spain, resulting in a phytoplankton bloom in 2016. This bloom turned the clear and transparent waters turbid and greenish, and killed approximately 85% of benthic macrophytes. Nutrient bioextraction by flat oysters, Ostrea edulis, has been proposed for remediation of these eutrophication events and water quality recovery. This research aims to quantify the clearance rate and investigate the genetic origin of Mar Menor oysters under eutrophized conditions for potential applications to bioremediation projects. Oligotrophic and eutrophic conditions were replicated in the laboratory, and oyster feeding behaviour (i.e. clearance rates, ingestion rates, absorption efficiency and absorption rates) were studied using a flow-through system. The genetic characterization of oysters showed no significant difference between individuals from the Mar Menor and individuals collected from a nearby Mediterranean bed (Tabarca Island). Based on the physiological results observed, oysters were grouped into high-feeder (HF) and low-feeder (LF) categories according to their clearance rate, that was 3-fold higher in the HF group. Different responses in feeding behaviour were observed under eutrophic conditions in both oyster groups. Constraints in the absorption capacity of LF oysters seemed to be related to their reduced filtering activity. Lower body condition of LF oysters was evidenced by their negative scope for growth value. From this work, several conclusions can be drawn for future restoration/bioextraction actions: (i) the recovery of half of the oyster population that existed in the past would act as an effective top-down control on the phytoplankton community; (ii) using clearance rate measurements is recommended to select oysters as broodstock; and (iii) Mediterranean oysters could be used as broodstock in the event that Mar Menor oysters fail to reproduce.We appreciate the work done by Francisco Gomez in the maintenance and feeding of the oyster and support on the physiological measurements. We also appreciate the technical assistance of Susana Sánchez with the genetic analyses. English has been reviewed by Selby Clarke (PhD student, Dalhousie University, Canada). This research has been performed in the scope of the RemediOS Project, developed with the collaboration of the Biodiversity Foundation (Spanish Ministry for Ecological Transition and the Demographic Challenge), through the Pleamar Program, co-financed by the European Maritime and Fisheries Fund (EMFF). Genetic analyses have been financed by the General Direction of the Mar Menor from the Murcia Regional Government (Reference 2021/009284).Peer reviewe

The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets