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The growing penetration of non-programmable renewable energy sources and the consequent fluctuations in energy prices and availability lead to the need to enhance energy system flexibility and synergies between different energy vectors. This can be reached through sector integration. Among the most relevant technologies used for this purpose, Power-to-Gas systems allow excess renewable electricity to be converted directly into fuels that can be then stored or used. A smart energy system, however, which includes these innovative solutions, requires intelligent management methods to optimize its operation. This work investigates the operational strategy of energy systems integrated with Power-to-Gas solutions for seasonal storage, by developing an optimization model for the system, formulated as Mixed-Integer Linear Programming problem. The algorithm tackles the uncertain nature of future disturbances, such as energy needs, generation and price using two-stage stochastic programming. The algorithm is tested on grid-connected and 100% renewable energy supply case studies. The novel stochastic algorithm allows a more robust optimization compared to a deterministic optimization, and system management is ensured under several future disturbances realization. Furthermore, the integration of Power-to-Gas solutions warrants the energy security of the energy systems and acts as a buffer to forestall unpredictable behavior of the disturbances.

Background: FGFR1 regulates cell–cell adhesion and extracellular matrix architecture and acts as oncogene in several cancers. Potential cancer driver mutations of FGFR1 occur in neuroblastoma (NB), a neural crest-derived pediatric tumor arising in sympathetic nervous system, but so far they have not been studied experimentally. We investigated the driver-oncogene role of FGFR1 and the implication of N546K mutation in therapy-resistance in NB cells. Methods: Public datasets were used to predict the correlation of FGFR1 expression with NB clinical outcomes. Whole genome sequencing data of 19 paired diagnostic and relapse NB samples were used to find somatic mutations. In NB cell lines, silencing by short hairpin RNA and transient overexpression of FGFR1 were performed to evaluate the effect of the identified mutation by cell growth, invasion and cologenicity assays. HEK293, SHSY5Y and SKNBE2 were selected to investigate subcellular wild-type and mutated protein localization. FGFR1 inhibitor (AZD4547), alone or in combination with PI3K inhibitor (GDC0941), was used to rescue malignant phenotypes induced by overexpression of FGFR1 wild-type and mutated protein. Results: High FGFR1 expression correlated with low relapse-free survival in two independent NB gene expression datasets. In addition, we found the somatic mutation N546K, the most recurrent point mutation of FGFR1 in all cancers and already reported in NB, in one out of 19 matched primary and recurrent tumors. Loss of FGFR1 function attenuated invasion and cologenicity in NB cells, whereas FGFR1 overexpression enhanced oncogenicity. The overexpression of FGFR1N546K protein showed a higher nuclear localization compared to wild-type protein and increased cellular invasion and cologenicity. Moreover, N546K mutation caused the failure in response to treatment with FGFR1 inhibitor by activation of ERK, STAT3 and AKT pathways. The combination of FGFR1 and PI3K pathway inhibitors was effective in reducing the invasive a

The climate change includes a decrease in seawater pH, and an increase in its temperature. It is possible that the marine fish sperm cells, which are released to the sea at spawning, can be affected by these expected changes on the water, and become unable of fulfill its role on fertilization. For that reason, different seawater pH has been tested in 3 aquaculture marine species: the European eel (Anguilla anguilla), the European seabass (Dicentrarchus labrax), and the Senegalese sole (Solea senegalensis), and their sperm motility parameters analyzed by a CASA-mot system. In the European eel, tested seawater pH, from 6.5 to 9.5, affected sperm motility and other kinetic parameters like MP, FA, VCL, VAP, LIN, STR, WOB, ALH and BFC. pH values lower than 7.8 or higher than 8.2 caused lower values of motility and the rest of kinetic parameters. The longevity was not affected by pH from 7.6 to 8.2. In other experiment a seawater pH of 7.8 caused lower motility, FA, VSL, VAP and LIN than a seawater with pH 8.2. The effect of the water temperature was tested, by comparing activation with seawater at 4 °C (our control) and at 23-24 °C. The spermatozoa beating cross frequency (BCF) was the only parameter significantly affected, being lower at 23 °C than at 4 °C. In other experiment where we combined 2 temperatures (4, 24 °C) and two pH (7.8, 8.2), a significant interaction was observed, and in general the worst results were obtained with seawater at 4 °C and at pH 7.8. Considering all these data, it seems that the seawater pH has a deeper effect on the eel sperm motility than a high temperature. Regarding European sea bass and Senegalese sole, motility and other sperm parameters were not affected by seawater temperature in the pH range from 6.5 to 9.5, thus indicating that ocean acidification would not affect their behavior. The differences found between these species, evolutively and ecologically differents, could reflect different activation mechanisms of the spermatozoa m

La grande sfida che ci pone la fragilità è la difficoltà a ricondurla a un singolo dominio perché connette le dimensioni biologica e soggettiva di perdita di resistenza e di capacità di adattamento ad eventi stressogeni, a cambiamenti, perché non è peculiare di un'unica fascia di età, anche se fortemente influenzata dall'età avanzata, perché non equivalente alla cronicità, alla politologia e non significa disabilità o non autosufficienza, di cui è però un precursore. Quindi una condizione multifattoriale nella quale intervengono fortemente molti determinanti della salute che se individuata precocemente, trattata e gestita può, in alcuni casi, regredire e/o rallentare il suo decorso. Per questi motivi il Gruppo di Lavoro Primary Health Care di SItI ha deciso, dopo la stesura del position paper La Fragilità in una prospettiva di Sanità Pubblica: principi e strumenti per un approccio "life course" orientato alla prevenzione, di dar voce, in un volume, a tutti i professionisti coinvolti e ai cittadini sui modi per definire e riconoscere la fragilità secondo un approccio multidimensionale che possa diventare guida, riflessione e formazione sulla fragilità ad ampio spettro. In particolare il progetto editoriale si rivolge agli operatori della salute per orientarli, attraverso l'acquisizione di competenze specifiche, nelle attività di prevenzione, monitoraggio, coordinamento ed integrazione dei servizi che si rivolgono a questa ampia fascia di popolazione. Si sono volutamente mantenute le posizioni diversificate degli autori per offrire, in un'unica raccolta, visioni differenti e comunque in evoluzione fra professionisti e ricercatori con estrazioni ed esperienze variegate per sottolineare la necessità di un approccio interdisciplinare ad una tematica che approda a servizi e attività che vanno dal livello territoriale a quello specialistico e "super-specialistico", ma soprattutto che coinvolgono tutta la comunità in una rete di relazioni formali ed i

Background High-risk neuroblastomas (HR-NBs) are rare, aggressive pediatric cancers characterized by resistance to therapy and relapse in more than 30% of cases, despite using an aggressive therapeutic protocol including targeting of GD2. The mechanisms responsible for therapy resistance are unclear and might include the presence of GD2neg/low NB variants and/or the expression of immune checkpoint ligands such as B7-H3. Method Here, we describe a multiparametric flow cytometry (MFC) combining the acquisition of 10 6 nucleated singlets, Syto16pos CD45neg CD56pos cells, and the analysis of GD2 and B7-H3 surface expression. 41 bone marrow (BM) aspirates from 25 patients with NB, at the onset or relapse, are analyzed, comparing results with cytomorphological analysis (CA) and/or immunohistochemistry (IHC). Spike in experiments assesses the sensitivity of MFC. Kaplan-Meier analysis on 498 primary NBs selects novel prognostic markers possibly integrating the MFC panel. Results No false positive are detected, and MFC shows high sensitivity (0.0005%). Optimized MFC identifies CD45negCD56pos NB cells in 11 out of 12 (91.6%) of BM indicated as infiltrated by CA, 7 of which coexpress high levels of GD2 and B7-H3. MFC detects CD45negCD56posGD2neg/low NB variants expressing high surface levels of B7-H3 in two patients with HR-NB (stage M) diagnosed at 53 and 139 months of age. One of them has a non-MYCN amplified tumor with unusual THpos PHOX2Bneg phenotype, which relapsed 141 months post-diagnosis with BM infiltration and a humerus lesion. All GD2neg/low NB variants are detected in patients at relapse. Kaplan-Meier analysis highlights an interesting dichotomous prognostic value of MML5, ULBPs, PVR, B7-H6, and CD47, ligands involved in NB recognition by the immune system. Conclusions Our study validates a sensitive MFC analysis providing information on GD2 and B7-H3 surface expression and allowing fast, specific and sensitive evaluation of BM tumor burden. With other routinely u

The sexual maturation of the European eel (A. anguilla) has been traditionally induced by hormonal treatments, requiring weekly handling and causing fish stress. The osmotic pumps (OP) were tested as an alternative method for induction of maturation of eel males and females. Males were divided in Control, OP-100 and OP-200 groups (n=10/group). The control group received weekly injections of recombinant hCG (1.5 IU/g fish) for 15 weeks. The induction of sexual maturation of OP groups was carried out by implanted hCGrec-loaded osmotic pumps (ALZET 1004 and 2006). Sperm samples were weekly collected by stripping and several sperm parameters were evaluated by CASA. Biometric parameters such as fin color and gonadosomatic index were evaluated as key indicators of maturation. Blood samples were taken and 11-ketotestosterone levels determined by a specific EIA. Osmotic pumps induced the maturation and spermiation in males, but without the required intensity to produce a sufficient quantity of gametes (sperm volume, density) or quality parameters (motility) for aquaculture purposes. Eel females were divided in Control (n=11) and OP-2ML4 group (n=10). The control group received weekly injections carp pituitary extract (CPE; 20 mg/kg fish) for 15-20 weeks. The OP2ML4 group was implanted with a CPE-loaded OP ALZET 2ML4. The females were weekly monitored and those riped were induced to spawn and artificial fertilization was performed. The gonadosomatic index was also evaluated. The results showed that OP evoked an unusual early maturation in some females, evidencing that this method might become a viable alternative for eel hatchery procedures.

The European eel (A. anguilla) is a valued species targeted for aquaculture production. However, it is considered a critically endangered species and its reproduction in captivity seems to be the only alternative to solve both economic and ecological problems. Although it is possible to obtain eel gametes for artificial fertilization, it requires longterm hormonal treatments. Recent studies found that cold seawater stimulates the brainpituitary-gonad axis in eel males, inducing the start of spermatogenesis. These results suggested that cold seawater could be used as a pre-treatment before the standard hormonal therapy applied to induce sexual maturation, to obtain higher sperm quantity and quality. Thus, our study evaluates the effects of cold seawater pre-treatments of different duration (1, 2 and 4-weeks) on reproductive performance of eel males. Biometric parameters from control and pre-treated fish were measured. Blood and testis samples were collected for steroid (T, 11-KT and E2) and histology analyses, respectively. Once eels were spermiating, sperm parameters were evaluated using a CASA system. Eel males pre-treated with cold temperature showed increased biometric indexes, androgens and E2 plasma levels. Males maintained at 10 ºC for 4-weeks showed a significantly higher percentage of differentiated type A spermatogonia in comparison to undifferentiated ones. However, the low sperm quality found in the pre-treated groups revealed that pretreatments followed by recombinant human chorionic gonadotropin (rechCG) treatment at high temperatures impairs spermatogenesis. Cold temperature pre-treated males had a time-dependent and fast response to rechCG treatment, but their spermiation period was shorter and sperm parameters were significantly lower. Further research is needed to study the effect of thermic pre-treatments on gene regulation controlling spermatogenesis.