Predictive Controller for Refrigeration Systems Aimed to Electrical Load Shifting and Energy Storage

The need to reduce greenhouse gas emissions is leading to an increase in the use of renewable energy sources. Due to the aleatory nature of these sources, to prevent grid imbalances, smart management of the entire system is required. Industrial refrigeration systems represent a source of flexibility in this context: being large electricity consumers, they can allow large-load shifting by varying separator levels or storing surplus energy in the products and thus balancing renewable electricity production. The work aims to model and control an industrial refrigeration system used for freezing food by applying the Model Predictive Control technique. The controller was developed in Matlab® and implemented in a Model-in-the-Loop environment. Two control objectives are proposed: the first aims to minimize total energy consumption, while the second also focuses on utilizing the maximum amount of renewable energy. The results show that the innovative controller allows energy savings and better exploitation of the available renewable electricity, with a 4.5% increase in its use, compared to traditional control methods. Since the proposed software solution is rapidly applicable without the need to modify the plant with additional hardware, its uptake can contribute to grid stability and renewable energy exploitation

The Mummies in the Church of Santa Maria delle Grazie, Calascio: A New Site in the Inner Abruzzo Region, Central Italy

The inner Abruzzo region, corresponding to the province of L’Aquila, is a land of mountains and highlands in central Italy. Its environmental conditions greatly foster spontaneous mummification, and the area is well known for the human mummies found in the last decades. We present a newly discovered collection of mummified remains in the village of Calascio, located 1,210 meters above sea level, near Gran Sasso Mountain. Here, the Franciscan convent of Santa Maria delle Grazie was built in 1594. The preliminary survey of a crypt in the conventual church allowed us to observe wooden coffins with at least seven mummified bodies still in their clothes, and several bony remains. Most likely, the mummies date back to the second half of the 19th century, and belonged to laypersons. Preservation was certainly due to the cold dry environment of the crypt. The recovery of the entire series will take place through speleological techniques according to stratigraphic relationships, in order to trace a bioanthropological profile of this small community members

The masked invader strikes again: The conquest of Italy by the Northern raccoon

The Northern raccoon Procyon lotor is a species native to North and Central America, but alien populations have established in Europe, several Caribbean islands, Azerbaijan, Uzbekistan and Japan, being introduced for fur farming, hunting, or as pets/attraction in animal parks. In the introduced range, raccoons may impact on breeding birds and amphibians, exert crop damages and transmit pathologies to wild species and humans. The species has been introduced also in Italy, where the only known reproductive population is observed since 2004 in Lombardy, along the Adda river. We reconstructed the current distribution range of the Northern raccoon in Italy, collecting information from scientific papers, articles in newspapers and books, as well from experts and local reporters. A total of 53 occurrence points were collected from observation sites. Since 2008, records from Lombardy increased, and sporadic observations were reported from seven other regions. A complete lack of records from the Northernmost provinces of Lombardy (Varese, Como and Sondrio) suggests that the only Italian population does not derive from a range expansion from Switzerland, but it should be considered as an independent, new introduction. Accidental observations of single individuals possibly escaped from captivity are often ignored, and only few animals were removed from the wild. An analysis of the potential distribution of the species was performed in a species distribution modeling framework (MaxEnt). A global model was built up considering the occurrences of reproductive populations from the native range and introduced areas in Europe and Japan and then projected to Italy. The model suggested a good suitability for the plains in Central-Northern Italy and a very low suitability of the Alpine region, thus providing support to the hypothesis that the Italian population did not derive from dispersal from Switzerland. If escapes or releases of raccoons will continue, there is a risk that the species could colonize other areas, making its containment more difficult

Comparative Analysis Of Residual Factor VIII Expression from Recurrent F8 Nonsense Mutations Indicates that Localization in the B- domain Favours Readthrough- mediated Protein Output

Background: Nonsense mutations, inserting premature termination codons (PTCs), might undergo, with low frequency (<0.01%), spontaneous suppression (readthrough) with production of full-length proteins upon amino acid insertion at the PTC. This process, dictated by nucleotide/protein sequence features, might have implications for hemophilia A (HA) patients. Aims: To investigate residual factor VIII (FVIII) expression through complementary studies in HA patients’ plasma and exploiting a sensitive in-vitro expression platform. Methods: Detection of plasma FVIII levels (ELISA, aPTT), and expression studies (HEK293 cells) with a highly-sensitive naturally-secreted luciferase (Gaussia, GL) fused to FVIII (FVIII-GL). Results: Plasma samples from HA patients affected by six nonsense mutations (p.R446X, p.R814X, p.K1289X, p.W1726X, p.R1985X, p.R2135X) revealed traces of FVIII. Strikingly, the two B-domain variants (p.R814X, p.K1289X) showed the highest FVIII levels, suggesting a position-dependent effect. Expression studies with the FVIII-GL variants showed that those of the B-domain produced the highest luciferase activity levels, thus supporting in vivo findings. Accordingly, the predicted readthrough-deriving amino acid changes (R446W, R814W, K1289Q/Y, W1726Y, R1985W, R2135W) showed a minor impact for those affecting the B-domain. To verify further our hypothesis, the panel of F8 mutations was rationally expanded to be representative of the majority of patients with nonsense mutations (60%), including the most frequent (50% of patients) in the B-domain. Through our sensitive platform we observed that all F8 nonsense variants led to detectable luciferase activity (0.4-6%). Strikingly, when categorized in two groups (B-domain, n=21; other domains, n=26), secreted luciferase activity of B-domain variants was significantly higher (p<0.0001) as compared with variants located in the other FVIII domains. Conclusions: Our findings for the first time indicate that nonsense mutations in the B-domain, known to tolerate missense changes as those potentially arising from readthrough, are favoured in terms of readthrough-mediated protein output, which might have pathophysiological implications for HA patients

Potential Use of Tea Tree Oil as a Disinfectant Agent against Coronaviruses: A Combined Experimental and Simulation Study

: The COVID-19 pandemic has highlighted the relevance of proper disinfection procedures and renewed interest in developing novel disinfectant materials as a preventive strategy to limit SARS-CoV-2 contamination. Given its widely known antibacterial, antifungal, and antiviral properties, Melaleuca alternifolia essential oil, also named Tea tree oil (TTO), is recognized as a potential effective and safe natural disinfectant agent. In particular, the proposed antiviral activity of TTO involves the inhibition of viral entry and fusion, interfering with the structural dynamics of the membrane and with the protein envelope components. In this study, for the first time, we demonstrated the virucidal effects of TTO against the feline coronavirus (FCoVII) and the human coronavirus OC43 (HCoV-OC43), both used as surrogate models for SARS-CoV-2. Then, to atomistically uncover the possible effects exerted by TTO compounds on the outer surface of the SARS-CoV-2 virion, we performed Gaussian accelerated Molecular Dynamics simulations of a SARS-CoV-2 envelope portion, including a complete model of the Spike glycoprotein in the absence or presence of the three main TTO compounds (terpinen-4-ol, γ-terpinene, and 1,8-cineole). The obtained results allowed us to hypothesize the mechanism of action of TTO and its possible use as an anti-coronavirus disinfectant agent

On the origin and propagation of the COVID-19 outbreak in the Italian Province of Trento, a tourist region of Northern Italy

15openInternationalItalian coauthor/editorBackground: Trentino is an Italian province with a tourism-based economy, bordering the regions of Lombardy and Veneto, where the two earliest and largest outbreaks of COVID-19 occurred in Italy. The earliest cases in Trentino were reported in the first week of March 2020, with most of the cases occurring in the winter sport areas in the Dolomites mountain range. The number of reported cases decreased over the summer months and was followed by a second wave in the autumn and winter of 2020. Methods: we performed high-coverage Oxford Nanopore sequencing of 253 positive SARS-CoV-2 swabs collected in Trentino between March and December 2020. Results: in this work, we analyzed genome sequences to trace the routes through which the virus entered the area, and assessed whether the autumnal resurgence could be attributed to lineages persisting undetected during summer, or as a consequence of new introductions. Conclusions: Comparing the draft genomes analyzed with a large selection of European sequences retrieved from GISAID we found that multiple introductions of the virus occurred at the early stage of the epidemics; the two epidemic waves were unrelated; the second wave was due to reintroductions of the virus in summer when traveling restrictions were upliftedopenBianco, Luca; Moser, Mirko; Silverj, Andrea; Micheletti, Diego; Lorenzin, Giovanni; Collini, Lucia; Barbareschi, Mattia; Lanzafame, Paolo; Segata, Nicola; Pindo, Massimo; Franceschi, Pietro; Rota-Stabelli, Omar; Rizzoli, Annapaola; Fontana, Paolo; Donati, ClaudioBianco, L.; Moser, M.; Silverj, A.; Micheletti, D.; Lorenzin, G.; Collini, L.; Barbareschi, M.; Lanzafame, P.; Segata, N.; Pindo, M.; Franceschi, P.; Rota-Stabelli, O.; Rizzoli, A.; Fontana, P.; Donati, C

Real and perceived feet orientation under fatiguing and non-fatiguing conditions in an immersive virtual reality environment

Lower limbs position sense is a complex yet poorly understood mechanism, influenced by many factors. Hence, we investigated the position sense of lower limbs through feet orientation with the use of Immersive Virtual Reality (IVR). Participants had to indicate how they perceived the real orientation of their feet by orientating a virtual representation of the feet that was shown in an IVR scenario. We calculated the angle between the two virtual feet (α-VR) after a high-knee step-in-place task. Simultaneously, we recorded the real angle between the two feet (α-R) (T1). Hence, we assessed whether the acute fatigue impacted the position sense. The same procedure was repeated after inducing muscle fatigue (T2) and after 10 min from T2 (T3). Finally, we also recorded the time needed to confirm the perceived position before and after the acute fatigue protocol. Thirty healthy adults (27.5 ± 3.8: 57% women, 43% men) were immersed in an IVR scenario with a representation of two feet. We found a mean difference between α-VR and α-R of 20.89° [95% CI: 14.67°, 27.10°] in T1, 16.76° [9.57°, 23.94°] in T2, and 16.34° [10.00°, 22.68°] in T3. Participants spent 12.59, 17.50 and 17.95 s confirming the perceived position of their feet at T1, T2, T3, respectively. Participants indicated their feet as forwarding parallel though divergent, showing a mismatch in the perceived position of feet. Fatigue seemed not to have an impact on position sense but delayed the time to accomplish this task

LKB1 Down-Modulation by miR-17 Identifies Patients With NSCLC Having Worse Prognosis Eligible for Energy-Stress–Based Treatments

Abstract Introduction Preclinical models recently unveiled the vulnerability of LKB1/KRAS comutated NSCLC to metabolic stress-based treatments. Because miR-17 is a potential epigenetic regulator of LKB1, we hypothesized that wild-type LKB1 (LKB1WT) NSCLC with high miR-17 expression may be sensitive to an energetic stress condition, and eligible for metabolic frailties-based therapeutic intervention. Methods We took advantage of NSCLC cell lines with different combinations of KRAS mutation and LKB1 deletion and of patient-derived xenografts (PDXs) with high (LKB1WT/miR-17 high) or low (LKB1WT/miR-17 low) miR-17 expression. We evaluated LKB1 pathway impairment and apoptotic response to metformin. We retrospectively evaluated LKB1 and miR-17 expression levels in tissue specimens of patients with NSCLC and PDXs. In addition, a lung cancer series from The Cancer Genome Atlas data set was analyzed for miR-17 expression and potential correlation with clinical features. Results We identified miR-17 as an epigenetic regulator of LKB1 in NSCLC and confirmed targeting of miR-17 to LKB1 3′ untranslated region by luciferase reporter assay. We found that miR-17 overexpression functionally impairs the LKB1/AMPK pathway. Metformin treatment prompted apoptosis on miR-17 overexpression only in LKB1WT cell lines, and in LKB1WT/miR-17 high PDXs. A retrospective analysis in patients with NSCLC revealed an inverse correlation between miR-17 and LKB1 expression and highlighted a prognostic role of miR-17 expression in LKB1WT patients, which was further confirmed by The Cancer Genome Atlas data analysis. Conclusions We identified miR-17 as a mediator of LKB1 expression in NSCLC tumors. This study proposes a miR-17 expression score potentially exploitable to discriminate LKB1WT patients with NSCLC with impaired LKB1 expression and poor outcome, eligible for energy-stress-based treatments

A novel de novo HCN1 loss-of-function mutation in genetic generalized epilepsy causing increased neuronal excitability

Abstract The causes of genetic epilepsies are unknown in the majority of patients. HCN ion channels have a widespread expression in neurons and increasing evidence demonstrates their functional involvement in human epilepsies. Among the four known isoforms, HCN1 is the most expressed in the neocortex and hippocampus and de novo HCN1 point mutations have been recently associated with early infantile epileptic encephalopathy. So far, HCN1 mutations have not been reported in patients with idiopathic epilepsy. Using a Next Generation Sequencing approach, we identified the de novo heterozygous p.Leu157Val (c.469C > G) novel mutation in HCN1 in an adult male patient affected by genetic generalized epilepsy (GGE), with normal cognitive development. Electrophysiological analysis in heterologous expression model (CHO cells) and in neurons revealed that L157V is a loss-of-function, dominant negative mutation causing reduced HCN1 contribution to net inward current and responsible for an increased neuronal firing rate and excitability, potentially predisposing to epilepsy. These data represent the first evidence that autosomal dominant missense mutations of HCN1 can also be involved in GGE, without the characteristics of epileptic encephalopathy reported previously. It will be important to include HCN1 screening in patients with GGE, in order to extend the knowledge of the genetic causes of idiopathic epilepsies, thus paving the way for the identification of innovative therapeutic strategies