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The need for decarbonization has become an urgent objective being pursued across borders and sectors. The energy sector is one example to follow, with the penetrations of renewable energy sources increasing year after year and already having an impact on carbon emissions. Despite their benefits, as these penetration levels grow, grid frequency is likely to be affected, namely in small, isolated power systems. Part of this instability is caused by the different types of connections to the grid used by most renewable energy sources. These converter-connected technologies do not contribute to the grid's inertia the same way synchronous generators do, therefore the difficulties in keeping the frequency under control. Focusing on the behaviour of the system's frequency, following some disturbances, a grid model of the Portuguese Terceira Island is created to assess the potential benefits of using hydrogen technologies (electrolysers and fuel cells) to provide grid services. In this paper, two scenarios are analyzed, the system's frequency response to large imbalances and steady-state imbalances stemming from load and wind power forecasting errors. The results reflect how the frequency behaviour is affected by the amount of the system's inertia, synchronous generators characteristics, and the presence of electrolysers and fuel cells. Hydrogen systems impact positively on the frequency containment after large disturbances, the impact related to the response to steady-state imbalances being lesser and prone to affect the stacks lifespan. • A grid model of a Portuguese island is created to assess the benefits of hydrogen to provide frequency control. • Models are developed for electrolysers, fuel cells and synchronous generators. • Two scenarios are analyzed: the response to large imbalances and steady-state imbalances (load and wind forecasting errors). • Hydrogen systems positively impact the frequency containment after large disturbances. • The impact related to the response to steady-state imbalances is lesser and prone to affect the stacks lifespan. [ABSTRACT FROM AUTHOR]

Growing renewable energy deployment worldwide has sparked a shift in the energy landscape with far-reaching geopolitical ramifications. Hydrogen's role as an energy carrier is central to this change, facilitating global trade and the decarbonisation of hard-to-abate sectors. This analysis offers a new method for optimally sizing solar/wind-to-hydrogen systems in specifically suitable locations. These locations are limited to the onshore and offshore regions of selected countries, as determined by a bespoke geospatial analysis developed to be location-agnostic. Furthermore, the research focuses on determining the best configurations for such systems that minimise the cost of producing hydrogen, with the optimisation algorithm expanding from the detailed computation of the classic levelised cost of hydrogen. One of the study's main conclusions is that the best hybrid configurations obtained provide up to 70% cost savings in some areas. Such findings represent unprecedented achievements for Italy and Portugal and can be a valuable asset for economic studies of this kind carried out by local and national governments across the globe. These results validate the optimisation model's initial premise, significantly improving the credibility of this work by constructively challenging the standard way of assessing large-scale green hydrogen projects. [Display omitted] • Identification of current locations suitable for RES-to-Hydrogen systems in Italy and Portugal. • Computation of a novel factor that enables calculation of country-wide LCOH 2 • Optimisation model for single and hybrid, onshore and offshore configurations. [ABSTRACT FROM AUTHOR]

Offshore wind energy has the potential to be associated with hydrogen production to overcome certain disadvantages, such as the high cost of electrical transmission systems. In this work, two hydrogen producing systems are modelled, one with the electrolyzer offshore, the other with the electrolyzer onshore, along with a conventional offshore wind farm. To do so, each component is individually modelled and combined to construct the systems. Furthermore, an hourly optimisation algorithm is used to control the operation of the systems and a neural network is implemented to forecast day ahead power production and electricity price, so that regulation costs could be modelled. This study extends the existing literature by modelling the regulation costs in the day ahead electricity market using neural networks to provide day ahead forecasts along with analysing the flexibility of using an electrolyzer coupled with an offshore wind farm. Furthermore, innovative floating offshore wind turbines were considered, enabling the assessment for offshore hydrogen production in deeper waters. Results show that, for the present case study, the onshore electrolyzer system is always more economically interesting than the offshore electrolyzer system, mainly due to its ability of purchasing electricity from the grid. The first has a levelized cost of hydrogen of 5.84 €/kg, 3.42 €/kg and 2.57 €/kg for 2020, 2030 and 2050, respectively, compared to 8.98 €/kg, 4.37 €/kg and 2.68 €/kg. • Coupling hydrogen production with offshore wind farms reduces costs from forecasting errors. • 2020 prices for floating offshore wind and electrolyzers result in LCOH of at least 6 €/kg. • Cost estimates for 2030 show LCOH of around 3–4 €/kg and around 2€/kg for 2050. • For the specific case study, onshore electrolyzer is always more economically attractive. [ABSTRACT FROM AUTHOR]

The European Union has been allocating funds for the energy transition to meet escalating global energy demands while minimising the environmental impact. This paper focuses on the impact of post-pandemic policies on photovoltaic technology in Italy and Portugal, specifically analysing self-consumption schemes and energy communities. A techno-economic assessment identified optimal PV systems for four families in each country, considering financial incentives. Italy offers Superbonus 110 and Ecobonus schemes, while Portugal provides access to the Environmental Fund. Profitable PV systems with storage are feasible in Italy but not in Portugal. Superbonus 110 favours smaller systems, Ecobonus supports larger ones, and Portuguese policies prioritise smaller systems. Simulations of energy communities for the same families showed that in Italy, the best configurations consist of families acting as producers with larger PV capacities and smaller batteries. In contrast, in Portugal, the policies favour smaller PV systems without batteries, resulting in optimal configurations where families are solely consumers. This research underscores diverse national approaches to post-pandemic energy policies and their nuanced impacts on PV technology in Italy and Portugal. It can be concluded that energy communities offer greater profitability than individual self-consumption schemes. This is because individual households continue to prioritise self-consumption and personal savings while selling their excess energy at a more favourable price than what they would receive from the grid. • In Italy, there are financial incentives and in Portugal, electricity cost reductions. • The models used the Net Present Value and the Internal Rate of Return as indicators. • In Italy, Superbonus 100 favours smaller systems, while Ecobonus supports larger ones. • Smaller systems without batteries for self-consumption are more profitable in Portugal. • Energy communities are more economically viable in both countries. [ABSTRACT FROM AUTHOR]

As energy system will increasingly become renewable, they will face new challenges that mainly arise due to the varying output by many renewable energy technologies. An issue that is especially prominent for countries with high shares of hydropower in their electricity generation is the varying yearly output of these technologies. This work aims to propose a techno-economically optimized energy system for such a country, using Portugal as example. For this purpose the current situation is analyzed and an energy demand model for 2050 created. The energy system is optimized for years with different outputs of hydropower to analyze the system's behavior using the simulation tool EnergyPLAN. As the tool does not possess inherent optimization capabilities it was coupled with the gray wolf optimization algorithm using Matlab. Subsequently, a system is proposed that is able to cover Portugal's expected energy demand under all circumstances. The future system will rely strongly on wind and solar power as they are expected to cover around 75% of Portugal's electricity demand. Furthermore, the analysis showed that Portugal needs to build up electrolyzer capacities of 4.2 GW and SynGas capacities of 2.4 GW as the SynGas will be used to balance supply in demand, especially in years with lower hydropower output. The system's cost will be between 22 and 35% cheaper than the created reference model. Furthermore, the primary energy demand is expected to decrease from 253 TWh to around 150 TWh while the electricity demand rises from 49 TWh to around 110 TWh. • We propose an optimized 100% renewable energy system for countries with high shares of hydropower. • The proposed system can cover Portugal's expected energy demand in 2050. • Wind and solar power are expected to cover around 75% of Portugal's electricity demand. • Portugal needs to build up electrolyzer capacities of 4.2 GW and SynGas capacities of 2.4 GW. • The system's cost will be between 22 and 35% cheaper than the created reference model. [ABSTRACT FROM AUTHOR]

The integration of intermittent renewable energy sources (RES) represents a great challenge for any energy system. In particular, islanded microgrids with a high penetration of renewables experience a strong need for technologies that allow to match demand and production at any moment. This work aims at proposing an optimised design for the energy system of Faial, an island in the Azores archipelago, featuring the highest possible renewable energy penetration that can be obtained respecting the technological and financial feasibility constraints. To this purpose, a model has been developed, using weather and electric demand measured data to combine and size optimally the components of a hybrid energy system. The model can be varied in its constraints to fit at best the multi-objective nature of the problem, where the conflicting objectives are the Net Present Value, its Renewable Energy Fraction and the Energy Index of Reliability. Once a set of possible optimal design has been determined, a system design featuring 5504 kW of geothermal installed power and 6208 kWh of BESS (Battery Energy Storage System) capacity, together with the already present thermal generators and 4250 kW of wind turbines, has been analysed more in detail. Monte Carlo simulations with synthetic time series have been performed to investigate the impact on the project of the variability in wind speed and in energy demand, highlighting the robustness of the selected design. • We propose an optimised design for the energy system of Faial, an island in the Azores archipelago. • The model features the highest possible renewable energy penetration respecting the technological and financial constraints. • Monte Carlo simulations were performed to investigate the impact of the variability in wind speed and energy demand. [ABSTRACT FROM AUTHOR]

• We investigate load modeling in an LV network with a high penetration of PV. • We use an unbalanced power flow algorithm, capable of handling load models. • Monte Carlo approach is applied for the stochastic computations. • The obtained probabilistic results are compared to the traditional load modeling. Microgeneration PV units connected to the LV distribution network is contributing to a paradigm change on the planning and operation. The proliferation of electric and electronic devices in residential houses, principally nonlinear loads, can be observed and is a result of the evolution of technology. These nonlinear devices may generate a number of harmonics, therefore disturbing and degrading the power quality of the network. This paper intends to give a contribution to the subject by investigating the static load modelling in a LV radial distribution network. For this purpose, a three-phase unbalanced power flow algorithm is used, with the capability of handling static load models variations, through the well-known concept of elasticity. The research is made by using stochastic variations, typifying the residential load segment. The Monte Carlo approach is applied for the stochastic computations, considering the uncertainty in the composition of loads. The obtained probabilistic results are compared to the typical load modelling through ZIP models. The obtained results indicate that overvoltages may occur in summer days at around noon, independently of the behaviour of the loads. On the other hand, voltages at the lower acceptable band can be expected at night during winter, when the peak load occurs. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a complex pathology in which several dysfunctions, including alterations in metabolic pathways, mitochondrial functionality and unbalanced lipid import/export, lead to lipid accumulation and progression to inflammation and fibrosis. The enzyme glycine N-methyltransferase (GNMT), the most important enzyme implicated in S-adenosylmethionine catabolism in the liver, is downregulated during NAFLD progression. We have studied the mechanism involved in GNMT downregulation by its repressor microRNA miR-873-5p and the metabolic pathways affected in NAFLD as well as the benefit of recovery GNMT expression. miR-873-5p and GNMT expression were evaluated in liver biopsies of NAFLD/NASH patients. Different in vitro and in vivo NAFLD murine models were used to assess miR-873-5p/GNMT involvement in fatty liver progression through targeting of the miR-873-5p as NAFLD therapy. We describe a new function of GNMT as an essential regulator of Complex II activity in the electron transport chain in the mitochondria. In NAFLD, GNMT expression is controlled by miR-873-5p in the hepatocytes, leading to disruptions in mitochondrial functionality in a preclinical murine non-alcoholic steatohepatitis (NASH) model. Upregulation of miR-873-5p is shown in the liver of NAFLD/NASH patients, correlating with hepatic GNMT depletion. Importantly, NASH therapies based on anti-miR-873-5p resolve lipid accumulation, inflammation and fibrosis by enhancing fatty acid β-oxidation in the mitochondria. Therefore, miR-873-5p inhibitor emerges as a potential tool for NASH treatment. GNMT participates in the regulation of metabolic pathways and mitochondrial functionality through the regulation of Complex II activity in the electron transport chain. In NAFLD, GNMT is repressed by miR-873-5p and its targeting arises as a valuable therapeutic option for treatment. Image 1 • The microRNA miR-873-5p is upregulated in human and murine NAFLD/NASH livers. • miR-873-5p upregulation downregulates GNMT in the liver. • miR-873-5p inhibition reduces liver steatosis, inflammation and fibrosis in in vivo NAFLD mouse models. • GNMT is a hepatic metabolic hub with mitochondria activity through the regulation of Complex II of the ETC. • Mitochondrial GNMT deficiency compromises ETC functionality and metabolism. [ABSTRACT FROM AUTHOR]

Excess copper causes hepatocyte death in hereditary Wilson's disease (WD). Current WD treatments by copper-binding chelators may gradually reduce copper overload; they fail, however, to bring hepatic copper close to normal physiological levels. Consequently, lifelong daily dose regimens are required to hinder disease progression. This may result in severe issues due to nonadherence or unwanted adverse drug reactions and also due to drug switching and ultimate treatment failures. This study comparatively tested bacteria-derived copper binding agents—methanobactins (MBs)—for efficient liver copper depletion in WD rats as well as their safety and effect duration. Copper chelators were tested in vitro and in vivo in WD rats. Metabolic cage housing allowed the accurate assessment of animal copper balances and long-term experiments related to the determination of minimal treatment phases. We found that copper-binding ARBM101 (previously known as MB-SB2) depletes WD rat liver copper dose dependently via fecal excretion down to normal physiological levels within 8 days, superseding the need for continuous treatment. Consequently, we developed a new treatment consisting of repetitive cycles, each of ∼1 week of ARBM101 applications, followed by months of in-between treatment pauses to ensure a healthy long-term survival in WD rats. ARBM101 safely and efficiently depletes excess liver copper from WD rats, thus allowing for short treatment periods as well as prolonged in-between rest periods. [Display omitted] In an animal model for Wilson's disease, the peptide ARBM101 drains excess liver copper down to normal levels within days, plausibly suggesting new treatment concepts for this disease. [ABSTRACT FROM AUTHOR]

PhotoVoltaic (PV) microgeneration ( μG ) located close to the end-users is gradually increasing and is expected to increase more in the future. However, a high μG penetration level may cause overvoltage issues in the Low Voltage (LV) distribution grid. On the other hand, these μG PV generators are usually placed in residential houses, composed by nonlinear loads that generate harmonics. The use of the harmonics compensation capabilities provided by modern PV systems can be an added value, as this function improves the voltage profile and reduces losses on the LV distribution network. This paper proposes an additional contribution to the subject by studying the impact of the use of PV systems harmonics compensation features to mitigate the harmonics produced by residential nonlinear loads. The assessment tool is a suitable algorithm created to compute an unbalanced three-phase power flow in the presence of harmonics. This is based on the Common Object Model (COM) interface of two software tools, MATLAB and OpenDSS. Three case-studies are proposed: harmonic compensation disabled, harmonic compensation enabled and reactive power control. The last one is introduced for comparison purposes. The assessment is made for a typical summer day, on a highly unbalanced test radial LV distribution network with high μG penetration and harmonic pollution. The obtained results allow the conclusion that the PV system harmonic compensation capability is able to attenuate the harmonics, therefore improving the voltage profile, and reducing the power losses and voltage drop on the LV distribution network. [ABSTRACT FROM AUTHOR]

Isolated power systems present high levels of Renewable Energy Sources (RES) curtailment as intermittency and isolation impose challenging difficulties regarding the integration of this energy into the electrical grid. The recent developments in electrical vehicles have decreased the kWh cost of lithium-ion batteries below a threshold value that was previously prohibitive for grid-scale applications. Therefore, the integration of RES considering the installation of a Battery Energy Storage System (BESS) into an isolated power grid is an up-to-date research topic and is assessed in this paper. The BESS is inserted into the Unit Commitment and Economic Dispatch (UC + ED) platform and regarded as another dispatchable generator. To keeps the costs down, the BESS is mainly used to provide a portion of the spinning reserve needs and secondly to alleviate the load of the thermal generators, using the free modules. The BESS configurations that maximises the economic viability and minimises the RES curtailment are presented. The results suggest that the investment in this technology may be profitable and considerably decreases the levels of RES curtailment. [ABSTRACT FROM AUTHOR]

The lack of predictability in the output of solar, wind, and small hydroelectric power plants aggravates the problem of consistently matching supply with demand on electric grids. In this paper, a database of renewable power injection, at 15-minute intervals during 2010–2014, into the Portuguese electric transmission system is analysed to characterize the variability and other patterns of renewable energy injection into the system. The system, operated by REN (Redes Energéticas Nacionais), received 20–28% of its electricity from the three renewable energy sources (RES) mentioned, with wind contributing about 90% of that amount. A strong complementarity (smoothing effect) between wind and PV was found, with correlation factors of − 0.92 and − 0.83 for typical summer and winter days, respectively. The correlation factors for different time scales decrease from annual totals (− 0.88) to hourly totals (− 0.24), as expected. The results suggest that lower wind power years correspond to sunnier ones. Moreover, the reserve regulation costs appear to decrease when the installed capacity of the three considered RES increase. [ABSTRACT FROM AUTHOR]

Coal-fired power plants with semi-dry flue gas desulfurization produce several metric tons per day of residues with 10–18%w/w of hemi-hydrated calcium sulfite. The rest of the 90–80%w/w of such residues contains silica, aluminium-silicates and calcium/magnesium carbonates, sulfates and hydroxides. This material could be added to cement, but sulfites degrade the cement quality and lead to costs of landfill disposal. To test upgrading desulfurization residues to turn it into an acceptable cement feedstock, a pilot plant was built to oxidize residues with hot air converting sulfites to sulfates. This pilot comprehends a fluidized bed reactor, an air heater, a cyclone and a heat recovery exchanger. Its operation showed that residues react favorably under fluidization. The effect of independent variables, residence time and temperature, was investigated and sulfite conversions up to 89.4% were observed. With statistical treatment of pilot experimental data, response surface of conversion of sulfites to sulfates was developed, allowing to estimate the effect of independent coordinates on conversion and the optimal oxidation conditions. Experimental data and model predictions showed agreement leading to low estimated variance. [ABSTRACT FROM AUTHOR]

A progressive implementation of renewable microgeneration, mainly small sized Photovoltaics, in low voltage distribution networks is ongoing. In this context, self-consumption with storage allows to highlight the prosumer concept, bearing in mind that this strategy may be interesting both from a technical and economical perspectives. The intelligent network environment or Smart Grid comes close to this new model and may have a critical relevance in the management of intelligent power distribution networks, in the framework of a Smart Environment. This paper intends to give an additional contribution on the subject by investigating the economic profitability of different residential PV systems configurations. These include traditional “injects all into the network/consumes all from the network”, self-consumption, storage and net-metering. The joint operation of self-consumption and battery storage is particularly focused as it presents the current trend in residential PV systems. The results of the performed economic analysis point to the conclusion that self-consumption is already attractive, but storage is not a profitable solution, because battery investment is still too high, despite the cost reduction witnessed in recent years. [ABSTRACT FROM AUTHOR]

A major development of the offshore wind energy market is being witnessed. Since the implicated costs are considerably high, it is extremely important to ensure that the energy production is maximum, so that the costs per energy unit are minimized. Thus, the turbines should be strategically positioned to extract as much energy as possible from the wind, considering wake effect losses, as well as internal grid electrical losses. In order to avoid turbines to be placed in unrealistic positions, they should be distributed according to a grid of rectangular shaped cells; each of these is divided in multiple sub-cells. The problem of finding the turbines optimal position among the pre-defined sub-cells so that maximum annual energy is produced could be addressed using a deterministic approach. However, the problem becomes unfeasible when the number of turbines and/or the number of sub-cells increase. To overcome this difficulty, optimization techniques should be used. Genetic Algorithm and Particle Swarm Optimization are approached in this paper. This paper deals with the wind park layout optimization problem. A methodology to position the turbines inside a wind park so that the annual energy production is maximum is proposed. The results proved that the meta-heuristic method is much more CPU time efficient in providing the maximum annual year production as compared to the traditional deterministic approach. [ABSTRACT FROM AUTHOR]

Despite the fact that the current level of energy supply security in Europe is quite satisfactory, new challenges present a potential risk of jeopardising the current state of affairs. Among others, key challenges are related to the strengthening of the market framework (in the context of deregulation and unbundling as imposed by EU directives) and the increasing penetration of renewable energy sources in the generation mix (with inherently greater variability). Under these circumstances, assessing the value of lost load (VoLL) is useful to support energy decision-making, including benefit-cost analysis and the design of suitable regulatory frameworks. This paper develops VoLL estimation using a macroeconomic technique, namely the production-function approach. The VoLL determines the foregone value added due to electricity outage. The production-function method is applied to the Portuguese case and an average VoLL of 5.12 €/kWh is found. The paper also presents the VoLL results obtained for various economic sectors as well as households. Moreover, the temporal variation of the VoLL along typical weekdays and weekend, in winter and in summer, and for the most relevant sectors (manufacturing, retail services, and households) is demonstrated and discussed. [ABSTRACT FROM AUTHOR]

This study aims to explore the impact of light-duty passenger (LdP) electric vehicle (EV) charging on the Portuguese national load profile (LP) in 2030. The goal is to identify EV charging strategies that enable a sustainable configuration of the Portuguese LP under different potential levels of LdP EV penetration in 2030. The research offers Portuguese utilities and policymakers information regarding potential threats and solutions of different EV charging strategies on the national grid infrastructure in 2030. Furthermore, it proposes a methodology that can also be adopted in other countries to analyse similar problems. Low, medium, and high penetration scenarios were designated based on the number of LdP EVs. The low and medium penetration scenarios indicate that an intelligent grid is not necessary to perform charging activities. However, coordinating EV charging in the evening via a smart grid (SG) is imperative in the high penetration scenario, as unsustainable levels of power demand will otherwise be reached, compared with the current production and distribution capacity. Moreover, morning charging sessions must also be addressed, as they may induce new peaks of daily consumption given the significant amount of charging activity taking place within that period. • The impact of light-duty passenger EV charging on the Portuguese load profile (LP) in 2030 is explored. • EV charging strategies enabling a sustainable LP for different levels of penetration are identified. • Three scenarios of EV penetration: low, medium, and high. • An intelligent grid is not required to perform EV charging for low and medium penetration. • EV charging in the morning and evening through a Smart-Grid is imperative for high penetration. [ABSTRACT FROM AUTHOR]

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of stages from simple steatosis to non-alcoholic steatohepatitis (NASH). However, disease pathogenesis remains largely unknown. microRNA (miRNA or miR) expression has recently been reported to be altered in human NASH, and modulated by ursodeoxycholic acid (UDCA) in the rat liver. Here, we aimed at evaluating the miR-34a/Sirtuin 1(SIRT1)/p53 pro-apoptotic pathway in human NAFLD, and to elucidate its function and modulation by UDCA in the rat liver and primary rat hepatocytes. Methods: Liver biopsies were obtained from NAFLD morbid obese patients undergoing bariatric surgery. Rat livers were collected from animals fed a 0.4% UDCA diets. Primary rat hepatocytes were incubated with bile acids or free fatty acids (FFAs) and transfected with a specific miRNA-34a precursor and/or with a p53 overexpression plasmid. p53 transcriptional activity was assessed by ELISA and target reporter constructs. Results: miR-34a, apoptosis and acetylated p53 increased with disease severity, while SIRT1 diminished in the NAFLD liver. UDCA inhibited the miR-34a/SIRT1/p53 pathway in the rat liver in vivo and in primary rat hepatocytes. miR-34a overexpression confirmed its targeting by UDCA, which prevented miR-34a-dependent repression of SIRT1, p53 acetylation, and apoptosis. Augmented apoptosis by FFAs in miR-34a overexpressing cells was also inhibited by UDCA. Finally, p53 overexpression activated miR-34a/SIRT1/p53, which in turn was inhibited by UDCA, via decreased p53 transcriptional activity. Conclusions: Our results support a link between liver cell apoptosis and miR-34a/SIRT1/p53 signaling, specifically modulated by UDCA, and NAFLD severity. Potential endogenous modulators of NAFLD pathogenesis may ultimately provide new tools for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Abstract: In the European Union, promotion of renewable energies, in particular wind energy, has become a fundamental vector of the strategy to tackle the challenges associated with the growing awareness of environmental matters. All over Europe, aggressive incentive schemes, e.g. feed-in tariffs, came into force to promote renewable technologies. In Portugal, those tariffs are applicable for a definite period of the project’s lifecycle, typically 15–20years, after which the legislation establishes a remuneration method based on market prices. This work’s purpose is to examine, from a technical and economical perspective, the operation of a wind producer when, in the future, he will be forced to compete into the electricity market. Accordingly, a simulator of a day-ahead market is implemented using a market splitting model and the economic outcome of a wind farm is assessed, considering various strategies. The results gathered show its great dependency on market prices volatility, production forecast accuracy, balancing prices and liquidity and frequency of intraday markets. A few actions are identified to mitigate some drawbacks associated with the wind farm operation in a market environment. [Copyright &y& Elsevier]

The interplay between p53 and apoptosis in diseases such as cancer, neurodegeneration, ischemia and atherosclerosis underscores the need to understand the complexity of p53 networks. Here, we highlight recent studies of p53-induced apoptosis in human diseases, with a focus on the modulation of liver cell apoptosis. In addition, recent work has provided new insights into mechanisms underlying the antiapoptotic functions of the endogenous bile acid ursodeoxycholic acid (UDCA), suggesting that the finely tuned, complex control of p53 by Mdm2 is a key step in the UDCA modulation of deregulated, p53-triggered apoptosis. The effect of targeting cell death signaling proteins has been established in preclinical models of human diseases. Finally, we review recent therapeutic strategies and clinical applications of targeted agents, with a particular emphasis on the potential use of UDCA. [Copyright &y& Elsevier]

This study identifies the optimal operating strategy of storage systems in the electricity markets, from the perspective of a market participant with a renewables' portfolio. The energy storage system provides a balancing service for renewable sources, while also performing energy arbitrage at the considered three short-term markets. A Long Short-Term Memory (LSTM) model is developed to forecast spot price and renewable generation which are used to guide the bidding decision-making process to maximise the agents' economic profit. Additionally, the designed decision support models consider market rules and the technical constraints in the operation of the storage system. The influence of storage systems in the optimal operation, regulation costs and revenues are analysed on a daily and yearly basis. The Iberian electricity market has been utilised as a case study. It was shown that the use of forecasting techniques and battery implementation reduce daily and yearly regulation costs up to 100% and 53%, respectively and that acting in the balancing market increases the expected profit of the storage system between 21% and 36%. Additionally, the economic viability evaluation in 2018 and 2025, for several battery types, shows that only the lithium-ion battery is a profitable investment. [ABSTRACT FROM AUTHOR]

p53 plays an important role in regulating expression of genes that mediate cell cycle progression and/or apoptosis. In addition, we have previously shown that the hydrophilic bile acid ursodeoxycholic acid (UDCA) prevents transforming growth factor β1-induced p53 stabilization and apoptosis in primary rat hepatocytes. Therefore, we hypothesized that p53 may represent an important target in bile acid-induced modulation of apoptosis and cell survival. In this study we demonstrated that UDCA reduces p53 transcriptional activity, thereby preventing its ability to induce Bax expression, mitochondrial translocation, cytochrome c release, and apoptosis in primary rat hepatocytes. More importantly, bile acid inhibition of p53-induced apoptosis was associated with decreased p53 DNA binding activity. Subcellular localization of p53 was also altered by UDCA. Both events appear to be related with increased association between p53 and its direct repressor, Mdm-2. In conclusion, these results further clarify the antiapoptotic mechanism of UDCA and suggest that modulation of Mdm-2/p53 interaction is a prime target for this bile acid. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of treatment with peginterferon alpha-2b and ribavirin on liver histology in patients with chronic hepatitis C (CHC) with or without HIV infection.Methods: Patients received peginterferon alpha-2b (1.5 micro/kg/week during the first 4 weeks; 1.0 micro/kg/week thereafter) plus ribavirin (800-1200 mg/day, adjusted for weight) for 24 (genotypes 2/3) or 48 weeks (genotypes 1/4). Paired liver biopsy specimens were obtained at baseline and at the end of follow-up.Results: 108 paired biopsy specimens were available: 67 from HCV-monoinfected and 41 from co-infected patients. At the end of follow-up, necroinflammatory activity (NIA) was significantly reduced (P<0.001), and fibrosis scores improved by > or = 1 point (Ishak et al criteria) in 65.7% of HCV-monoinfected patients. In co-infected patients, NIA was significantly reduced (P<0.001), and fibrosis scores improved by > or = 1 point in 42.5% of cases. In both groups, results were better for patients who attained sustained virological response (SVR). HCV RNA was undetectable in the second biopsy specimens of all patients who attained SVR.Conclusion: Liver fibrosis is reduced significantly after a course of therapy in patients with chronic hepatitis C. Reduction of fibrosis is more significant in patients who are monoinfected with HCV and in those who attained SVR. [ABSTRACT FROM AUTHOR]

The Polish coal-based power system faces the necessity of a pressing transition. Partially, the challenge may be addressed by floating photovoltaics. Since there is no analysis covering the implementation of this technology in Polish conditions, in this paper the design process of a 1 MWp floating photovoltaic system and its technical and economic assessment were performed. To find the best solution different floating assemblies were considered. Floating systems were compared with the reference ground mounted system and, based on simulations conducted in PVsyst, economic study with sensitivity analysis was carried out. The results revealed that even in case of the best performing floating system the extra yield cannot compensate the higher CAPEX. Currently, in Polish market conditions, this technology is not as profitable as the ground-mounted systems and higher product maturity stage need to be achieved for it to be considered as competitive. [ABSTRACT FROM AUTHOR]

This study aims to analyse whether the Australian commitment to the Paris Agreement in 2016 and national energy policies will have a visible effect in decreasing the historical dependence of the NEM (National Electricity Market) on fossil fuels by 2030 and consequently decreasing the carbon emissions generated. In this paper, we model the 2030 electricity mix in the NEM in Australia. EnergyPlan , which is the modelling tool adopted for this study, is described and a reference model is conceived and calibrated based on the 2018 electricity situation on the NEM. The simulations are implemented considering three different supply scenarios and three potential electricity demands, to evaluate how different variables can influence the NEM electricity mix by 2030. This study concludes that by 2030 wind and solar power (including rooftop-PV systems) will be the major renewable energy contributors in the NEM, as opposed to 2018 where hydropower represented the main renewable energy source. Nonetheless, the electricity system in 2030 will continue to rely on fossil fuels, which will account for more than 50% of the final energy mix in every scenario, depicting that new efforts will still be needed beyond 2030. • We foresee the electricity mix in Australia by 2030. • We study three generation and three demand scenarios. • Fossil fuels will still account for more than 50% of the final electricity mix. • We expect a visible CO2 emissions reduction, due to the bet in RES in recent years. [ABSTRACT FROM AUTHOR]

Offshore wind farms, while strategically positioned to maximise wind energy capture, are exposed to harsh environments, impacting their reliability and accessibility. Low reliability and accessibility in turn translate into high Operation and Maintenance (O&M) costs, which represent approximately 30% of the total lifetime costs of the project. One approach to reduce O&M costs is to improve maintenance planning decisions. The present paper presents a novel O&M scheduling methodology for offshore wind farm operations based on wind and wave forecasts. The methodology forecasts farm yield considering farm wake effects to identify optimal operation schedules, vessel routing, and turbine maintenance sequences that minimise costs and revenue losses due to downtime. Weather forecast uncertainty is modelled and integrated into the decision-making process to minimise weather risks. A case study inspired by the WindFloat Atlantic floating wind project was used to demonstrate the optimisation potential. Results suggest that adopting the proposed methodology over business-as-usual scheduling significantly boosts offshore wind farm operational profits during the forecasted period, with increases ranging from 2% to 24%, depending on the scenario considered. It was found that integrating the wind farm wake losses into the scheduling decisions can improve the optimal scheduling solution and further minimise total operation costs. • A novel O&M planning methodology for offshore wind farm operation is proposed. • Model generates optimal maintenance schedules based on weather forecasts. • Model integrates weather forecast uncertainty and farm wake effects into planning. • The WindFloat Atlantic floating wind project was used as a case study. • Factoring in wake effects enhances maintenance scheduling and reduces energy losses. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) comprises a heterogeneous group of malignant tumors associated with dismal prognosis. Alterations in post-translational modifications (PTMs), including NEDDylation, result in abnormal protein dynamics, cell disturbances and disease. Herein, we investigate the role of NEDDylation in CCA development and progression. Levels and functions of NEDDylation, together with response to pevonedistat (NEDDylation inhibitor) or CRISPR/Cas9 against NAE1 were evaluated in vitro , in vivo and/or in patients with CCA. The development of preneoplastic lesions in Nae1 +/- mice was investigated using an oncogene-driven CCA model. The impact of NEDDylation in CCA cells on tumor-stroma crosstalk was assessed using CCA-derived cancer-associated fibroblasts (CAFs). Proteomic analyses were carried out by mass-spectrometry. The NEDDylation machinery was found overexpressed and overactivated in human CCA cells and tumors. Most NEDDylated proteins found upregulated in CCA cells, after NEDD8-immunoprecipitation and further proteomics, participate in the cell cycle, proliferation or survival. Genetic (CRISPR/Cas9- NAE1) and pharmacological (pevonedistat) inhibition of NEDDylation reduced CCA cell proliferation and impeded colony formation in vitro. NEDDylation depletion (pevonedistat or Nae1 +/- mice) halted tumorigenesis in subcutaneous, orthotopic, and oncogene-driven models of CCA in vivo. Moreover, pevonedistat potentiated chemotherapy-induced cell death in CCA cells in vitro. Mechanistically, impaired NEDDylation triggered the accumulation of both cullin RING ligase and NEDD8 substrates, inducing DNA damage and cell cycle arrest. Furthermore, impaired NEDDylation in CCA cells reduced the secretion of proteins involved in fibroblast activation, angiogenesis, and oncogenic pathways, ultimately hampering CAF proliferation and migration. Aberrant protein NEDDylation contributes to cholangiocarcinogenesis by promoting cell survival and proliferation. Moreover, NEDDylation impacts the CCA-stroma crosstalk. Inhibition of NEDDylation with pevonedistat may represent a potential therapeutic strategy for patients with CCA. Little is known about the role of post-translational modifications of proteins in cholangiocarcinoma development and progression. Herein, we show that protein NEDDylation is upregulated and hyperactivated in cholangiocarcinoma, promoting tumor growth. Pharmacological inhibition of NEDDylation halts cholangiocarcinogenesis and could be an effective therapeutic strategy to tackle these tumors. [Display omitted] • NAE1-dependent protein NEDDylation is increased in human cholangiocarcinoma. • NEDDylation contributes to cholangiocarcinogenesis favoring pro-survival mechanisms. • Abnormal NEDDylation alters the cholangiocarcinoma secretome, impacting on the stroma crosstalk. • Molecular and pharmacological targeting of NAE1 halts experimental tumor growth. • NAE1 inhibition with pevonedistat is a promising therapy for patients with cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

The paper describes the integration between what used to be a passive element of the energy value chain – the grid – and both upstream and downstream elements. The evolution of communications among the elements has permitted a more robust and adaptable structure that already is being implemented: the Smart Grid. The paper relates the evolution of EU policy concerning both the development and the rolling-out of solutions to exploit the potential of the Smart Grid concept and describes what has been done by the regulators of three countries that share the same goal but seek to attain it via distinct paths. The article starts with a justification of the need for more integrated networks and a definition of the Smart Grid. A second part covers the risks and difficulties of implementation within an established network, introducing the role of the regulator. The third part describes EU policy response and three different approaches by regulators in the UK, Italy and Portugal, showing how in each case policy is influenced by characteristics of their respective national electricity markets in terms of competition dynamics. [ABSTRACT FROM AUTHOR]

Transforming growth factor β1 (TGF-β1)-induced hepatocyte apoptosis is associated with activation of E2F transcription factors and p53 stabilization through Mdm-2, thus potentially modulating a number of target genes. In previous studies, we have shown that ursodeoxycholic acid (UDCA) prevents TGF-β1-induced hepatocyte apoptosis by inhibiting the mitochondrial pathway of cell death. In this study we examined the role of p53 in the induction of apoptosis by TGF-β1, and identified additional antiapoptosis targets for UDCA. Our data show a significant transcriptional activation of E2F-1 in primary rat hepatocytes incubated with TGFβ1, as well as a 5-fold increase in p53 and a 2-fold decrease in its inhibitor, Mdm-2 (p < 0.05). In addition, bax mRNA expression was significantly induced at 36 h (p < 0.01), resulting in increased levels of Bax protein. In contrast, Bcl-2 transcript and protein levels were decreased at all time points (p < 0.01). Notably, UDCA inhibited E2F-1 transcriptional activation, p53 stabilization and Bcl-2 family expression (p < 0.05), in part, through a caspase-independent mechanism. Moreover, in the absence of TGF-β1, UDCA prevented induction of p53 and Bax by overexpression of E2F-1 and p53, respectively (p < 0.05). In addition, UDCA inhibited TGF-β1 induced degradation of nuclear factor κB (NF-κB) and its inhibitor IκB (p < 0.05). In conclusion, these results demonstrate that UDCA inhibits E2F-1 transcriptional activation of hepatocyte apoptosis, thus modulating p53 stabilization, NF-κB degradation, and expression of Bcl-2 family members. [ABSTRACT FROM AUTHOR]

Highlights • A high prevalence of non-AIDS-related comorbidities (NARC) was found in Portuguese HIV-infected patients ≥50 years old. • The most common NARC were metabolic, cardiovascular, and psychological conditions. • Lipid-lowering and antihypertensive agents were the most common co-medications. • Age and duration of HIV infection were modestly associated with the number of NARC. Abstract Objective To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC. Methods This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC. Results Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B = 0.032, 95% confidence interval 0.015–0.049; p = 0.0003) and between the duration of HIV-1 infection and NARC (B = 0.039, 95% confidence interval 0.017–0.059; p = 0.0005). Conclusions A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population. [ABSTRACT FROM AUTHOR]

• Design of a non-intrusive device to intelligently control electric water heaters. • Development of a machine-learning tool to forecast residential hot water demand. • Details and results of a six-month pilot study where the device was implemented. • Heating demand reduced by an average of 26.43% and cost saving of 35.54% per device. • Device is cost-effective and can reduce the need for imported fossil-fuel generation. Water heating accounts for approximately 25% of household energy use in developed countries. Therefore, the optimal control of water heating through the deployment of intelligent residential Electric Water Heaters (EWH) brings significant benefits. This paper presents an innovative design and implementation of an easy-to-use device for intelligent residential water heating. The device relied upon machine learning techniques to forecast a consumer's hot water demand and optimize the operation of an EWH using a novel data collection process that relied on non-intrusive vibration data alone. The device was deployed in a six-month pilot project on the island of São Miguel, Portugal. The major difficulties were the novel use of vibration data to forecast the volume of hot water used and the uncertain behavior of the consumers. The challenges of only using vibration data were solved by careful data collection and artificial intelligence methods. To tackle the issue of uncertain consumer behavior, an innovative 'heat now' function was incorporated into the device to override the novel control framework. Results show that the device could accurately forecast hot water demand and optimally operate the EWH to meet this demand. The results showed an average reduction of 1.33 kWh/day per consumer, which equates to an average decrease of 35.5% in water heating costs. Calculations show that these devices can reduce the total energy used by 2832 kWh daily or 0.21% of total electricity generated. Furthermore, a fleet of these devices could reduce thermal generation by 0.37%, reducing emissions by 693.31 tons of CO 2 per year. The results from the consumer survey show that the device did not affect the consumer's comfort, validating the benefits and efficacy of the proposed device. Hence, the paper shows that a simple-to-use, novel device using an innovative forecasting algorithm based on non-intrusive vibration data brings numerous quantifiable benefits to actual consumers and electrical utilities. [ABSTRACT FROM AUTHOR]