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Engineered nanomaterials have been found to induce oxidative stress. Cellular oxidative stress, in turn, can result in the induction of antioxidant and detoxification enzymes which are controlled by the nuclear erythroid 2-related factor 2 (NRF2) transcription factor. Here, we present the results of a pre-validation study which was conducted within the frame of BIORIMA (“biomaterial risk management”) an EU-funded research and innovation project. For this we used an NRF2 specific chemically activated luciferase expression reporter gene assay derived from the human U2OS osteosarcoma cell line to screen for the induction of the NRF2 mediated gene expression following exposure to biomedically relevant nanobiomaterials. Specifically, we investigated Fe3O4-PEG-PLGA nanomaterials while Ag and TiO2 “benchmark” nanomaterials from the Joint Research Center were used as reference materials. The viability of the cells was determined by using the Alamar blue assay. We performed an interlaboratory study involving seven different laboratories to assess the applicability of the NRF2 reporter gene assay for the screening of nanobiomaterials. The latter work was preceded by online tutorials to ensure that the procedures were harmonized across the different participating laboratories. Fe3O4-PEG-PLGA nanomaterials were found to induce very limited NRF2 mediated gene expression, whereas exposure to Ag nanomaterials induced NRF2 mediated gene expression. TiO2 nanomaterials did not induce NRF2 mediated gene expression. The variability in the results obtained by the participating laboratories was small with mean intra-laboratory standard deviation of 0.16 and mean inter laboratory standard deviation of 0.28 across all NRF2 reporter gene assay results. We conclude that the NRF2 reporter gene assay is a suitable assay for the screening of nanobiomaterial-induced oxidative stress responses.

L’articolo è nato dalla rielaborazione di un percorso sperimentato in alcune classi di scuola secondaria di primo grado. La sperimentazione era finalizzata alla produzione del riassunto, con particolare attenzione alle diverse fasi che ne permettono la realizzazione. In fase preliminare è stato dedicato uno spazio significativo alla comprensione, presupposto fondamentale per il passaggio alla scrittura del riassunto. Il modello di Angela Ferrari e del gruppo di Basilea ha costituito il riferimento e la guida teorica principali, sia nella fase di comprensione sia in quella di scrittura; gli autori hanno riservato pertanto una particolare attenzione alla ricostruzione dell’architettura semantica del testo, alla segmentazione in unità comunicative (Movimenti testuali) e alla rielaborazione linguistica, favorendo l’individuazione di domande che mettessero in evidenza le idee centrali del testo e le connessioni per la costruzione di un riassunto coerente e coeso. Summary writing in the secondary school This article is the result of the reworking of a course held in some secondary school classes. The experimentation was aimed at the drafting of the summary, with particular attention to the different phases in its realization. During the preliminary phase, significant time was devoted to comprehension, a fundamental prerequisite for the transition to the writing of the summary. The model by Angela Ferrari and the Basel group was the main reference and theoretical guide, both during the comprehension and the writing phases; therefore, the authors paid particular attention to the reconstruction of the semantic architecture of the text, the segmentation in communicative units (Textual Movements) and linguistic re-elaboration, encouraging the identification of questions that could highlight the central ideas in the text and the connections for the construction of a coherent and cohesive summary.

Per favorire un raccordo tra Scuola superiore e Università, l’articolo propone una riflessione sulle competenze linguistiche richieste agli studenti che accedono ai corsi di laurea, in particolare a quelli della Scuola di Scienze Umane. A partire dall’analisi di due testi, l’articolo illustra l’intreccio di competenze necessarie allo studente sia in fase di lettura e comprensione sia in fase di produzione del riassunto, e intende sostenere come la comprensione richieda anche una riscrittura e come il riassunto sia profondamente condizionato dai processi di analisi e comprensione del testo. L’esperienza dell’autore, maturata nei corsi di recupero delle competenze linguistiche, ha evidenziato come la pratica del riassunto sia uno strumento essenziale per migliorare le competenze di comprensione e di produzione scritta perché costringe lo studente a confrontarsi in modo analitico con i diversi livelli del testo e ad adottare le strategie linguistiche e le forme testuali più adeguate per riprodurlo. University access skills: from text comprehension to summary writing In order to encourage a connection between the High School and University, this article proposes a reflection on the required linguistic competences for students who enroll in degree courses, in particular those in the School of Human Sciences. Starting from the analysis of two texts, the article illustrates the intertwining of skills needed by the student both in the reading-and-comprehension phase and in the summary production phase, showing how comprehension also requires rewriting and how summarizing is deeply conditioned by the processes of analysis and comprehension of the text. The author’s experience, matured in remedial language skills courses, has shown how the practice of summarizing is an essential tool to improve comprehension and written production skills because it forces the student to deal with the different levels of the text analytically and adopt the most appropriate linguistic strategies and textual forms to reproduce it.

ATTI

The epicardium has recently gained interest in the cardiovascular field due to its capacity to support heart regeneration after ischemic injury. Models to study the epicardium of large animals in vitro are limited and mainly based on epicardial cell isolation/differentiation from stem cells, followed by 2D cells culture. In this method paper, we describe the procedure to obtain and culture 3D organotypic heart slices presenting an intact epicardium, as a novel model to study the epicardial physiology and activation. Epicardial slices are obtained from porcine hearts using a high-precision vibratome and retain a healthy epicardial layer embedded in its native extracellular environment and connected with other cardiac cells (cardiomyocytes, fibroblasts, vascular cells etc.). Epicardial slices can be cultured for 72 h, providing an ideal model for studying the epicardium physiology or perform pharmacological interventions/gene therapy approaches. We also report on methods to assesses the viability and composition of the epicardial slices, and evaluate their architecture in 3D through tissue decoloration. Finally, we present a potential application for a nanomaterial-based gene transfer method for tracking of epicardial cells within the slice. Crucially, given the similarity in morphology and physiology of porcine heart with its human counterpart, our system provides a platform for translational research while providing a clinically relevant and ethical alternative to the use of small animals in this type of research.

The selective oxidation of primary alcohols into their corresponding carbonyl compounds is challenging because of the easy over oxidization to acids and esters. The traditional reaction requires large amounts of solvent and oxidant, causing serious environmental issues. Recently, several efforts have been made to transform the reaction into a more sustainable process. Here, we investigated the solvent-free oxidation of benzyl alcohol using air as a green oxidant in the presence of ruthenium supported on alumina and zirconia, thereby meeting atom economy and environmental requirements. The materials were extensively characterized and, in addition to their activity, selectivity, and reusability, the environmental sustainability of the process was assessed according to green chemistry metrics. XRD, TEM, and XPS analyses suggest that the formation of metallic Ru on the support plays a key role in the catalytic activity. Ru supported on alumina, after a reduction treatment, achieves good activity (62% conversion) and a complete selectivity in a very sustainable process (without a solvent and with air as oxidant), as indicated by the very low E-factor value. The formulation is very stable and maintains high activity after recycling.

Polyethylene terephthalate (PET) is a thermoplastic material that is widely used in many application fields, such as packaging, construction and household products. Due to the relevant contribution of PET to global yearly solid waste, the recycling of such material has become an important issue. Disposed PET does not maintain the mechanical properties of virgin material, as exposure to water and other substances can cause multiple chain scissions, with subsequent degradation of the viscoelastic properties. For this reason, chain extension is needed to improve the final properties of the recycled product. Chain extension is generally performed through reactive extrusion. As the latter involves structural modification and flow of PET molecules, rheology is a relevant asset for understanding the process and tailoring the mechanical properties of the final products. This paper briefly reviews relevant rheological studies associated with the recycling of polyethylene terephthalate through the reactive extrusion process.

The aim of this paper is to analyze to which extent wind tunnel experiments can represent the behavior of full-scale wind turbine wakes. The question is relevant because on the one hand scaled models are extensively used for wake and farm control studies, whereas on the other hand not all wake-relevant physical characteristics of a full-scale turbine can be exactly matched by a scaled model. In particular, a detailed scaling analysis reveals that the scaled model accurately represents the principal physical phenomena taking place in the outer shell of the near wake, whereas differences exist in its inner core. A large-eddy simulation actuator-line method is first validated with respect to wind tunnel measurements and then used to perform a thorough comparison of the wake at the two scales. It is concluded that, notwithstanding the existence of some mismatched effects, the scaled wake is remarkably similar to the full-scale one, except in the immediate proximity of the rotor.

ABSTRACT. There are different causes of memory complaints in the elderly, such as subjective cognitive decline (SCD), mild cognitive impairment (MCI) or dementia. Objective: 1) To characterize individuals with memory complaints in a mid-sized city in Brazil, through clinical, cognitive and functional assessment; 2) to compare SCD individuals with MCI and dementia patients in terms of clinical and cognitive variables. Methods: We consecutively included individuals aged ≥50 years, with memory complaints (spontaneous or inquired). Subjects who scored ≥25 on the Memory Complaint Questionnaire or who had spontaneous memory complaints were selected. Participants underwent a semi-structured interview, the Mini-Mental State Examination, Figure Memory Test for visual episodic memory, Clock Drawing Test, Category Fluency (Animals), Neuropsychiatric Inventory, and functional assessment. Individuals were classified as SCD, MCI or dementia. We did not include individuals with previous diagnosis of dementia. Results: The final sample consisted of 91 subjects (73.6% women; mean age 67.6±9.8 years): 14.3% had spontaneous complaints and 85.7% had inquired complaints. The most common comorbidities were hypertension (69.2%), diabetes (36.3%), and dyslipidemia (24.2%). Low levels of vitamin B12 and hypothyroidism were found in 26.4 and 16.5%, respectively. Regarding cognitive diagnosis, 16.5% of the sample were classified as SCD, 49.4% as MCI and 34.1% as dementia. MCI and dementia were identified in five (38.5%) and seven (53.4%) patients with spontaneous complaint, respectively. Conclusions: MCI and dementia are frequently underdiagnosed. Potential reversible causes of cognitive decline are common. The diagnosis of dementia is highly frequent among individuals with spontaneous memory complaints.

OBJETIVO: O objetivo foi documentar a distribuição e o padrão de comportamento deste tumor entre os nossos pacientes. MATERIAIS E MÉTODOS: Foi realizado um estudo retrospectivo dos pacientes com diagnóstico de câncer de laringe atendidos no Hospital de Clínicas de Porto Alegre entre 1990 e 1996. RESULTADOS: Foram encontrados 242 casos, a maioria da raça branca (94,2%). A divisão por faixa etária mostrou um pico do ocorrência na sétima década de vida e a proporção de homens em relação à mulheres foi de 15:1. O tipo histológico mais comum foi carcinoma epidermóide (98,76%) e o sítio mais freqüentemente acometido foi a glote (44,7%), conseqüentemente, o sintoma mais comum na apresentação foi a disfonia (76,5%). Os pacientes com tumores na supraglote apresentaram, principalmente, disfagia e, aqueles com tumores transglóticos, dispnéia. Quanto ao estadiamento, 43,2% estavam no estágio IV no momento do diagnóstico. Os tumores localizados na supraglote estão relacionados com pior prognóstico, nesta amostra 38,3% dos pacientes com câncer na supraglote estavam no estágio IV, enquanto que a maioria dos tumores glóticos (74,2%) estavam no estágio I. A cirurgia total foi o tratamento mais realizado (50,7%). CONCLUSÃO: O diagnóstico do câncer de laringe no Hospital de Clínicas de Porto Alegre é feito, em sua maior parte, em estágio avançado, tornando o prognóstico desses pacientes bastante reservado.

OBJETIVO: Estudar a epidemiologia descritiva do câncer do colo uterino no Rio Grande do Sul, no período de 1980 a 1994 e verificar a situação da prevenção secundária dessa neoplasia pela citologia. MÉTODOS: Foram construídas séries históricas com índices de mortalidade padronizados pela população mundial, a partir dos dados da Secretaria de Saúde e Meio Ambiente do Rio Grande do Sul e analisadas pelo coeficiente de correlação de Pearson para séries históricas. Os resultados foram comparados com séries anteriores publicadas na literatura e com dados do Instituto Nacional do Câncer do Brasil. RESULTADOS: A série temporal apresentou tendência ascendente (P

Routine interventions such as balloon angioplasty, result in vascular activation and remodeling, often requiring re-intervention. 2D in vitro models and small animal experiments have enabled the discovery of important mechanisms involved in this process, however the clinical translation is often underwhelming. There is a critical need for an ex vivo model representative of the human vascular physiology and encompassing the complexity of the vascular wall and the physical forces regulating its function. Vascular bioreactors for ex vivo culture of large vessels are viable alternatives, but their custom-made design and insufficient characterization often hinders the reproducibility of the experiments. The objective of the study was to design and validate a novel 3D printed cost-efficient and versatile perfusion system, capable of sustaining the viability and functionality of large porcine arteries for 7 days and enabling early post-injury evaluations. MultiJet Fusion 3D printing was used to engineer the EasyFlow insert, converting a conventional 50 ml centrifuge tube into a mini bioreactor. Porcine carotid arteries either left untreated or injured with an angioplasty balloon, were cultured under pulsatile flow for up to 7 days. Pressure, heart rate, medium viscosity and shear conditions were adjusted to resemble arterial in vivo hemodynamics. Tissue viability, cell activation and matrix remodeling were analyzed by immunohistochemistry, and vascular function was monitored by duplex ultrasound. Culture conditions in the EasyFlow bioreactor preserved endothelial coverage and smooth muscle organization and extracellular matrix structure in the vessel wall, as compared to static culture. Injured arteries presented hallmarks of early remodeling, such as intimal denudation, smooth muscle cell disarray and media/adventitia activation in flow culture. Duplex ultrasound confirmed continuous pulsatile blood flow conditions, dose-dependent vasodilator response to nitroglycerin in untreated vessels and impaired dilator response in angioplastied vessels. The scope of this work is to validate a low-cost, robust and reproducible system to explore the culture of native and injured large arteries under pulsatile flow. While the study of vascular pathology is beyond the scope of the present paper, our system enables future investigations and provides a platform to test novel therapies and devices ex vivo, in a patient relevant system.

Controlled clinical intervention studies have demonstrated that cocoa flavanols (CF) can decrease blood pressure and arterial stiffness in healthy humans, although a large variability in the effect size across trials has been reported. In this study, we evaluated the intra- and inter-individual variability of responses to CF in everyday life using a series of n-of-1 trials in healthy free-living individuals with normal blood pressure carrying personal devices. In total, eleven healthy young humans participated in a repeated crossover randomized controlled double-blind n-of-1 trial. On 8 consecutive days, each volunteer consumed on alternating days 6 CF capsules (862 mg CF) on 4 days and 6 matched placebo capsules (P, 0 mg CF/day) on another 4 days in one of the two randomized sequences (CF-P-CF-P-CF-P-CF-P or P-CF-P-CF-P-CF-P-CF). On each day, the capsules were taken at the same time in the morning with breakfast after baseline measurements. Each subject was provided with an upper arm blood pressure monitor and a finger clip that measures pulse wave velocity (PWV). Measurements of blood pressure, heart rate, and PWV were taken at least hourly over 12 h during the day by the participants. On the first 2 days, measurements were performed under supervision to provide training. The overall mixed model analysis showed that CF significantly decreased 12-h systolic blood pressure and PWV by −1.4 ± 0.3 mmHg and −0.11 ± 0.03 m/s, respectively. Peak effects were observed within the first 3 h (1.5 h SBP: −4.9 ± 2.2 mmHg, PWV: −0.32 ± 0.17 m/s) and again after 8 h post-ingestion. Large inter-individual variation in responses was found [intra-cluster correlation coefficients (ICC): 0.41, 0.41]. When analyzing single individuals’ datasets, there was also considerable between-day variation in individual responses that varied greatly between subjects (ICC: 0–0.30, 0–0.22, 0–0.45). Effect sizes inversely correlated with baseline blood pressure values both between- and within-subjects. The data confirm that cocoa can decrease blood pressure and arterial stiffness in everyday life when elevated within the normal range. The large inter- and intra-individual variation in responses calls for more personalized nutritional intervention strategies.

The yaw control of horizontal-axis wind turbines is the key point for wake redirection, which is expected to provide an improvement in the balance between wind farm production and loads. For multi-MW upwind wind turbines, there are substantially two possibilities for obtaining a desired demanded yaw angle: using yaw actuators or Individual Pitch Control (IPC). A detailed balance of the pros and cons of both approaches requires in-depth studies. On these grounds, this work is a comprehensive experimental characterization of the yaw by individual pitch control (yaw-by-IPC). The experiments are conducted at the R. Balli wind tunnel of the University of Perugia on a fully instrumented wind turbine scaled model, named G1, developed by the Technical University of Munich. The objective of the study is twofold: assessment of the performance of the yaw-by-IPC in terms of yaw tracking capabilities and impact on power, loads, and actuators usage; analysis of its impact on the shed wake. The wake has been characterized on a plane parallel to the rotor at a distance of 1.82 diameters by imposing several steady yaw references, while wind intensity measurements have been performed through a traversing system hosting a hot wire anemometer. Each target of the analysis has been characterized for the yaw-by-IPC and for the control based on yaw actuation, in order to perform a comparison. With laminar inflow, it results that the yaw-by-IPC follows very well the demanded reference, even with a slight improvement in the case of dynamic yaw reference, and no power losses are visible. Concerning the wake shed by a yawed G1 with yaw-by-IPC, a higher flow speed is observed immediately behind the windward side of the rotor than with geared yaw actuation. It results, therefore, that yaw-by-IPC applied to a yawed wind turbine may increase the available wind power at a downstream machine.

This work presents 4 open source potentiostat solutions for performing accurate measurements in cyclic voltammetry and square wave voltammetry at a low price. A very simple and easy to reproduce analogic board (c.a. 10 €) was driven either by a Teensy card from the company PJRC under an Arduino/Python software solution (39 €) or by an Analog Discovery 2 device from Digilent (less than 300 €). A smartphone Bluetooth Android interface was also created to circumvent the use of a computer. We demonstrated that our scheme is suitable for measurements in classical electrochemical conditions but also to carry out experiments with ultramicroelectrodes. We could thus reach a noise resolution of less than 1 pA. Scan rates of 8000 Vs−1 with ohmic drop compensation were also achieved. The device is suitable for teaching purposes but also for experiments in a participative science context on the ground, or countries with lower financial possibilities.

The concept of wake steering on wind farms for power maximization has gained significant popularity over the last decade. Recent field trials described in the literature not only demonstrate the real potential of wake steering on commercial wind farms but also show that wake steering does not yet consistently lead to an increase in energy production for all inflow conditions. Moreover, a recent survey among experts shows that validation of the concept currently remains the largest barrier to adoption. In response, this article presents the results of a field experiment investigating wake steering in three-turbine arrays at an onshore wind farm in Italy. This experiment was performed as part of the European CL-Windcon project. While important, this experiment excludes an analysis of the structural loads and focuses solely on the effects of wake steering on power production. The measurements show increases in power production of up to 35 % for two-turbine interactions and up to 16 % for three-turbine interactions. However, losses in power production are seen for various regions of wind directions too. In addition to the gains achieved through wake steering at downstream turbines, more interesting to note is that a significant share in gains is from the upstream turbines, showing an increased power production of the yawed turbine itself compared to baseline operation for some wind directions. Furthermore, the surrogate model, while capturing the general trends of wake interaction, lacks the details necessary to accurately represent the measurements. This article supports the notion that further research is necessary, notably on the topics of wind farm modeling and experiment design, before wake steering will lead to consistent energy gains on commercial wind farms.