A low-cost ZigBee-based wireless industrial automation system

This paper describes the development of an industrial automation system based on a ZigBee wireless sensor network, designed for the monitoring and control of multiple refrigeration equipments in an industrial area, replacing the existing cabled network, which is based on the LonWorks platform. For this purpose, ZigBee routers were used to replace the local controllers at the refrigeration equipments, while the central management controller was re-placed by a ZigBee coordinator and a PC. The proposed system was devel-oped using a hardware platform based in the CC2530 integrated circuit and the Z-Stack software. Results from experimental field tests performed in an industrial environment are provided in order to assess the performance of the developed ZigBee network.This work is supported by FCT (Fundação para a Ciência e Tecnologia) with the reference project UID/EEA/04436/2013, and by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) with the reference project POCI-01-0145-FEDER-006941

The Arabidopsis bZIP19 and bZIP23 Activity Requires Zinc Deficiency – Insight on Regulation From Complementation Lines

All living organisms require zinc as an essential micronutrient. Maintaining appropriate intracellular zinc supply, and avoiding deficiency or toxic excess, requires a tight regulation of zinc homeostasis. In Arabidopsis, bZIP19 and bZIP23 (basic-leucine zipper) transcription factors are the central regulators of the zinc deficiency response. Their targets include members of the ZIP (Zrt/Irt-like Protein) transporter family, involved in cellular zinc uptake, which are up-regulated at zinc deficiency. However, the mechanisms by which these transcription factors are regulated by cellular zinc status are not yet known. Here, to further our insight, we took advantage of the zinc deficiency hypersensitive phenotype of the bzip19 bzip23 double mutant, and used it as background to produce complementation lines of each Arabidopsis F-bZIP transcription factor, including bZIP24. On these lines, we performed complementation and localization studies, analyzed the transcript level of a subset of putative target genes, and performed elemental tissue profiling. We find evidence supporting that the zinc-dependent activity of bZIP19 and bZIP23 is modulated by zinc at protein level, in the nucleus, where cellular zinc sufficiency represses their activity and zinc deficiency is required. In addition, we show that these two transcription factors are functionally redundant to a large extent, and that differential tissue-specific expression patterns might, at least partly, explain distinct regulatory activities. Finally, we show that bZIP24 does not play a central role in the Zn deficiency response. Overall, we provide novel information that advances our understanding of the regulatory activity of bZIP19 and bZIP23.</p

Deep learning for the classification of quenched jets

An important aspect of the study of Quark-Gluon Plasma (QGP) in ultra-relativistic collisions of heavy ions is the ability to identify, in experimental data, a subset of the jets that were strongly modified by the interaction with the QGP. In this work, we propose studying deep learning techniques for this purpose. Samples of $Z+$jet events were simulated in vacuum and medium and used to train deep neural networks with the objective of discriminating between medium- and vacuum-like jets. Dedicated Convolutional Neural Networks, Dense Neural Networks and Recurrent Neural Networks were developed and trained, and their performance was studied. Our results show the potential of these techniques for the identification of jet quenching effects induced by the presence of the QGP.Fundação para a Ciência e a Tecnologiainfo:eu-repo/semantics/publishedVersio

Improving the downstream processing of interferon alfa-2b using alternative purification platforms based on ionic liquids

Improvements on human life expectancy and the lack of effective therapies has led to an increment of chronic diseases, being the application of biopharmaceuticals an efficient strategy to mitigate this scenario. Among the current available biopharmaceuticals, the role of interferon α-2b (IFNα-2b) should be highlighted, as it has been marketed over 30 years with a considerable impact on the global therapeutic proteins market (Castro et al, Vaccines, 2021). IFN manufacturing requires the use of the recombinant DNA technology, involving two main stages, the upstream and downstream stages. The first includes recombinant protein production in a suitable host microorganism, such as Escherichia coli (Castro et al, Sep. Purif. Technol., 2020), while the second comprises protein recovery, isolation, purification and polishing. Due to the high demands of the pharmaceutical industry for products with high purity and biological activity, the downstream stage is responsible for the majority of the production costs of biopharmaceuticals (50–90%), often including time-consuming and multi-step processes. Therefore, there is an immediate need to develop more efficient, cost-effective, and sustainable protein purification methodologies. In this work, two ionic-liquid-(IL)-based strategies were investigated for the purification of IFNα-2b recombinantly produced from E. coli fermentation broth, namely as adjuvants in aqueous biphasic systems or as chromatographic ligands immobilized in solid materials. Overall, the obtained results demonstrate that by tailoring IL’s chemical structures, improved protein purification processes are obtained and that the secondary structure of proteins is preserved.publishe

Sustainable ionic-liquid-based strategies for the downstream processing of interferon α-2b from Echerichia coli

Over the last decades, society has been facing an increment of chronic diseases due to the higher human life expectancy and the lack of efficient treatments for several pathologies. In this regard, biopharmaceuticals have become one of the most effective clinical treatments for a broad range of diseases, including cancer, metabolic and neurodegenerative disorders [1]. Among biopharmaceuticals, the role of interferons, particularly interferon α-2b (IFNα-2b), should be underlined, as they have been marketed for over 30 years with a considerable impact on the global therapeutic proteins market [2]. Usually based on the recombinant DNA technology, the manufacturing process of biopharmaceuticals encompasses two main stages: the upstream and downstream stages. Typically, the upstream phase includes recombinant protein production processes in a suitable host microorganism, such as Escherichia coli [3], while the general downstream processing of biopharmaceuticals comprises four stages - recovery, isolation, purification and polishing -, which are responsible for the majority of the production costs of biopharmaceuticals (50–90%) [3]. The downstream processing is a time-consuming and multi-step process, for which the development of cost-effective purification processes is mandatory to decrease their costs and environmental impact. In this context, two ionic-liquid-(IL)-based strategies were investigated in this work for the purification of IFNα-2b recombinantly produced from E. coli fermentation broth. ILs have been used as adjuvants in aqueous two-phase systems (ATPS) and applied in supported materials as alternative ligands. The obtained results demonstrate that ILs have a tailoring ability and contribute to the development of more effective and sustainable downstream processes of biopharmaceuticals.publishe

Identification of genomic loci associated with genotypic and phenotypic variation among Pseudomonas aeruginosa clinical isolates from pneumonia

In this work, a genotype-phenotype survey of a highly diversified Pseudomonas aeruginosa collection was conducted, aiming to detail pathogen-associated scenarios that clinicians face nowadays. Genetic relation based on RAPD-PCR of 705 isolates, retrieved from 424 patients and several clinical contexts, reported an almost isolate-specific molecular-pattern. Pneumonia-associated isolates HB13 and HB15, clustered in the same RAPD-PCR group, were selected to evaluate the genomic background underlying their contrasting antibiotic resistance and virulence. The HB13 genome harbors antibiotic-inactivating enzymes-coding genes (e.g. aac(3)-Ia, arr, blaVIM-2) and single-nucleotide variations (SNVs) in antibiotic targets, likely accounting for its pan-resistance, whereas HB15 susceptibility correlated to predicted dysfunctional alleles. Isolate HB13 showed the unprecedented rhl-cluster absence and variations in other pathogen competitiveness contributors. Conversely, HB15 genome comprises exoenzyme-coding genes and SNVs linked to increased virulence. Secretome analysis identified signatures features with unknown function as potential novel pathogenic (e.g. a MATE-protein in HB13, a protease in HB15) and antibiotic resistance (a HlyD-like secretion protein in HB13) determinants. Detection of active prophages, proteases (including protease IV and alkaline metalloproteinase), a porin and a peptidase in HB15 highlights the secreted arsenal likely essential for its virulent behavior. The presented phenotype-genome association will contribute to the current knowledge on Pseudomonas aeruginosa pathogenomics.This work was supported by the strategic programme UID/BIA/0050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through FCT I.P., by ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and through a PhD grant (SFRH/BD/98558/2013) attributed to C.S.M. The facility for Biological Mass Spectrometry Isabel Moura was funded by Proteomass Scientific Society. H.M.S. is funded by the FCT 2015 Investigator Program (IF/00007/2015)

A novel multivariate STeady-state index during general ANesthesia (STAN)

The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study.The first author was supported by a scholarship from the Portuguese Foundation for Science and Technology (FCT SFRH/BD/35879/2007). The authors would also like to acknowledge the support of UISPA—System Integration and Process Automation Unit—Part of the LAETA (Associated Laboratory of Energy, Transports and Aeronautics) a I&D Unit of the Foundation for Science and Technology (FCT), Portugal. FCT support under project PEst-OE/EME/LA0022/2013.info:eu-repo/semantics/publishedVersio

Effectiveness of sacubitril–valsartan in cancer patients with heart failure

Aims Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD. Methods and results We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardiooncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirtynine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline Nterminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril–valsartan dose (low or medium/high doses). Conclusions Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.This study was funded by the Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades, Spain, and the EU—European Regional Development Fund, by means of a competitive call for excellence in research projects (PIE14/00066) as well as by the Spanish Cardiovascular Network (CIBERCV)