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Anomaly detection when observing a large number of data streams is essential in a variety of applications, ranging from epidemiological studies to monitoring of complex systems. High-dimensional scenarios are usually tackled with scan-statistics and related methods, requiring stringent modeling assumptions for proper calibration. In this work we take a nonparametric stance, and propose a permutation-based variant of the higher criticism statistic not requiring knowledge of the null distribution. This results in an exact test in finite samples which is asymptotically optimal in the wide class of exponential models. We demonstrate the power loss in finite samples is minimal with respect to the oracle test. Furthermore, since the proposed statistic does not rely on asymptotic approximations it typically performs better than popular variants of higher criticism that rely on such approximations. We include recommendations such that the test can be readily applied in practice, and demonstrate its applicability in monitoring the content uniformity of an active ingredient for a batch-produced drug product. for this article are available online. [ABSTRACT FROM AUTHOR]

Despite the widespread usage of high-voltage alternating current (HVAC) for the connection of offshore wind farms (OWF), its use to power-from-shore (PFS) offshore oil and gas (O&G) production sites is often not feasible. Its limitations for long-distance subsea transmission are usually found at 50–70 km from shore and might be even shorter when compared commercially to a direct-current (DC) alternative or conventional generation. Therefore, this research paper aims to address the standardization of offshore transmission with a particular focus on the high-voltage direct current (HVDC) alternative. While the distance is typically not a limiting factor when using DC, and the voltages used are rather standard, the concept of power envelopes can be quite useful in addressing the high variability of offshore site power requirements and setting a design baseline that would lead to improved lead time. In this article, a full back and front-end genetic optioneering model purposely built from the ground up in Python language is used to #1 define up to three DC power envelopes that would cater to most of the candidate's requirements and #2 provide the lowest cost variance. The results will demonstrate that this can be achieved at a minor overall cost expense. [ABSTRACT FROM AUTHOR]

The world is facing many challenges to keep up with growing energy demand and greenhouse gas and pollutant emissions. A possible solution is to integrate renewable energy sources (RESs) into residences and create energy management systems (EMSs) that reduce consumption and relieve the main grid in critical hours. This paper is focused on analyzing different EMSs using solar photovoltaic (PV) modules and three energy storage systems (ESSs) to increase savings without affecting the user's needs, with thirty-three power consumption profiles and three energy tariffs over a 25-year investment to compare which solution presents the best economic result in each of the 297 analyzed scenarios. The results show that the higher the overall daily consumption values, the greater the profits for all EMSs. The lowest demand profiles lead to the best self-consumption and self-sufficiency results. PV-only systems with a tri-hourly tariff have the best overall results. In the case of battery operation, each case should be carefully analyzed in order to choose the correct technologies and tariff. The results also allowed us to verify that even though having more PV modules generates more energy, it can make a project less economically desirable. [ABSTRACT FROM AUTHOR]

Although the current literature describes significant advances in biocatalytic ester syntheses, few industrial plants worldwide are currently producing esters using biocatalysts. Green and sustainable esters can be obtained via a biocatalytic route, including some operational advantages over conventional syntheses. An analysis of the literature revealed that most articles neglect or describe the economic issues generically, without quantitative information. Scaling-up studies are also scarce in this field. The main disadvantage of biocatalysis using immobilized lipases—their cost—has not been studied at the same level of depth as other technical aspects. This gap in the literature is less intense in enzymatic biodiesel production studies and, despite the lack of a strict correlation, enzymatic biodiesel commercial plants are relatively more common. Preliminary techno-economic assessments are crucial to identify and circumvent the economic drawbacks of biocatalytic ester syntheses, opening the way to broader application of this technology in a large-scale context. [ABSTRACT FROM AUTHOR]

In recent years, there has been a significant increase in investment in renewable energy sources, leading to the decarbonization of the electricity sector. Accordingly, a key concern is the influence of this process on future electricity market prices, which are expected to decrease with the increasing generation of renewable power. This is important for both current and future investors, as it can affect profitability. To address these concerns, a long-term analysis is proposed here to examine the influence of the future electricity mix on Iberian electricity prices in 2030. In this study, we employed artificial intelligence forecasting models that incorporated the main electricity price-driven components of MIBEL, providing accurate predictions for the real operation of the market. These can be extrapolated into the future to predict electricity prices in a scenario with high renewable power penetration. The results, obtained considering a framework featuring an increase in the penetration of renewables into MIBEL of up to 80% in 2030, showed that electricity prices are expected to decrease by around 50% in 2030 when compared to 2019, and there will be a new pattern of electricity prices throughout the year due to the uneven distribution of renewable electricity. The study's findings are relevant for ongoing research on the unique challenges of energy markets with high levels of renewable generation. [ABSTRACT FROM AUTHOR]

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]

Every country has objectives for climate change, and public policies are implemented to achieve those commitments. This paper aims to review the different public policies used to promote the integration of photovoltaic technology into smart grids, taking the case of Portugal as reference. An analysis of previous supporting policies is performed both in Portugal and some European countries; these policies consist of feed-in tariffs, feed-in premiums, green certificates, electricity compensation, direct capital subsidies, and tax credits. The policies currently in force in Portugal no longer aim to support the technology; instead, they intend to promote it. Energy communities, local markets, and solar auctions are examples of public policies that are currently being used, not only to promote PV power but also the development of microgrids. Finally, the Portuguese solar auctions of 2019 and 2020 are analyzed and compared. It is concluded that auctions are a very effective way of expanding the installed capacity of the PV technology in the country and have more weight on promoting the technology than other promoting policies currently being used. [ABSTRACT FROM AUTHOR]

Hydrogen technologies have been rapidly developing in the past few decades, pushed by governments' road maps for sustainability and supported by a widespread need to decarbonize the global energy sector. Recent scientific progress has led to better performances and higher efficiencies of hydrogen-related technologies, so much so that their future economic viability is now rarely called into question. This article intends to study the integration of hydrogen systems in both gas and electric distribution networks. A preliminary analysis of hydrogen's physical storage methods is given, considering both the advantages and disadvantages of each one. After examining the preeminent ways of physically storing hydrogen, this paper then contemplates two primary means of using it: integrating it in Power-to-Gas networks and utilizing it in Power-to-Power smart grids. In the former, the primary objective is the total replacement of natural gas with hydrogen through progressive blending procedures, from the transmission pipeline to the domestic burner; in the latter, the set goal is the expansion of the implementation of hydrogen systems—namely storage—in multi-microgrid networks, thus helping to decarbonize the electricity sector and reducing the impact of renewable energy's intermittence through Demand Side Management strategies. The study concludes that hydrogen is assumed to be an energy vector that is inextricable from the necessary transition to a cleaner, more efficient, and sustainable future. [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]

Significant price spikes occurred as early as 2021, initially driven by low gas storage levels, a post-pandemic economic rebound and then exacerbated by the Russian invasion of Ukraine. The situation had a range of wide-ranging consequences, from rising inflation, increasing energy poverty, food insecurity, business bankruptcies and recession. A well-known tool to protect energy consumers from energy price spikes, while at the same time contributing to the development of sustainable technologies, is Power Purchase Agreements. PPAs are long-term bilateral contracts for the purchase and sale of a certain amount of electricity, usually generated from renewable sources. The primary goal of this paper is to assess how the risk associated with PPAs has evolved between 2020 and 2023. It aims to examine whether, after the events in 2022, PPAs remain a robust solution that protects the off-taker from energy price spikes, ensures greater energy budget stability and enables savings. To achieve this, the probability of PPA prices being higher than market prices is evaluated, considering the changing market landscape. Furthermore, this paper intends to gain a thorough understanding of each risk related to PPAs and the best strategies for mitigating it, to maximize the protection of the off-taker. [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]

Introduction: Surveillance of Lynch syndrome (LS) is recommended to reduce cancer-risk. There is an increased awareness that cancer-risk may vary with mismatch-repair mutation and family history. However, gene-specific and family-specific surveillance are not recommended. Therefore, we aimed to estimate the cumulative incidence of lesions and to assess the cancer-risk by family history and mismatch-repair mutation (MMR). Methods: Single-centre retrospective cohort of all individuals (n = 241) in a specialized institution was conducted. Results: Forty-eight percent of individuals inherited MSH2 mutations, 32% MLH1, 15% MSH6 and 5% PMS2. The calculated cumulative incidence for any cancer increased with age. By age 70, the cumulative incidence for low-risk, high-risk adenomas and CRC was estimated at 66.6%, 57.7% and 25.7%, respectively. By age 70, the cumulative incidence of endometrial cancer (EC), gastric cancer and urinary tract cancer was estimated at 17.3%, 3.3% and 12.6%, respectively. MLH1 and MSH2 mutation carriers had lower mean age of CRC diagnosis than MSH6 and PMS2 [MLH1:44(CI95% 38–50); MSH2:43(CI95% 40–47); MSH6:52(CI95% 45–59); PMS2:46(CI95% 35–57)]. The risk of EC was higher when family history was present (RR = 2.39, CI95%[1.3;4.6]). MSH6 mutation carriers had higher risk of EC comparative to other MMR mutation carriers (RR = 1.9, p =.09). The risk of urinary tract cancer was higher with MSH2 (RR = 8.4, CI95%[2.7;25.9]) and positive family history (RR = 10.8, CI95%[1.4;82.8]). Conclusion: This cohort demonstrates the effectiveness of LS surveillance and suggests possible tailored surveillance strategies by gene mutation and family history. [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 significant public health concern, owing to its high prevalence, progressive nature and lack of effectivemedical therapies. NAFLD is a complex and multifactorial disease involving the progressive and concerted action of factors that contribute to the development of liver inflammation and eventually fibrosis. Here, we summarize fundamental molecular mechanisms underlying the pathogenesis of non-alcoholic steatohepatitis (NASH), how they are interrelated and possible translation to clinical applications. We focus on processes triggering and exacerbating apoptotic signalling in the liver of NAFLD patients and their metabolic and pathological implications. Indeed, liver injury and inflammation are cardinal histopathological features of NASH, a duo in which derailment of apoptosis is of paramount importance. In turn, the liver houses a very high number of mitochondria, crucial metabolic unifiers of both extrinsic and intrinsic signals that converge in apoptosis activation. The role of lifestyle options is also dissected, highlighting the management of modifiable risk factors, such as obesity and harmful alcohol consumption, influencing apoptosis signalling in the liver and ultimately NAFLD progression. Integrating NAFLD-associated pathologic mechanisms in the cell death context could provide clues for a more profound understating of the disease and pave the way for novel rational therapies. [ABSTRACT FROM AUTHOR]

Background and aims: An endoscopic grading system (EGGIM) using narrow-band-imaging (NBI) has shown to accurately identify patients with extensive gastric intestinal metaplasia (GIM). However, description with alternative systems such as blue-light-imaging (BLI) is limited. The aim of this study is to determine the reliability and accuracy of BLI-bright regarding diagnosis and staging of GIM. Methods: Reliability of WLE (white-light-endoscopy) and BLI among 6 observers was assessed using a standard classification based on endoscopic images. Afterward, 37 patients were submitted to gastroscopy using FujifilmEG-760Z and endoscopists had to determine EGGIM score using BLI-bright and to perform gastric biopsies for operative-link-of-gastric-intestinal-metaplasia (OLGIM) calculation. BLI-bright accuracy was determined by comparing results with prior EGGIM scores with NBI and current OLGIM. Results: Compared with WLE, the interobserver reliability between observers was substantially better with BLI (Weighted Kappa: 0.8 vs 0.41). There was an 84% agreement between BLI and NBI assessing EGGIM intervals (EGGIM 0-4vs5-10). The area under the ROC curve was 0.90 (95%CI: 0.79–1.0) using the cut-off of EGGIM > 4 to determine advanced GIM, with a sensitivity of 100% (95%CI: 88–100%). Discussion: BLI-bright is reliable for the diagnosis of gastric intestinal metaplasia and agrees significantly with NBI evaluation. Preliminary data suggests high sensitivity for identifying patients with increased risk of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: For the correct staging of chronic atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) at least 4 biopsies are recommended: 2 from the antrum/incisura and 2 from the body sent in two different vials. As virtual chromoendoscopy with narrow-band-imaging (NBI) is valid both in the diagnosis and staging of GIM, it is reasonable to question the need to separate biopsy samples in all procedures. Aims: To evaluate if biopsy samples can be placed in the same vial without implications in the diagnosis and follow-up of the patient, if during gastroscopy no typical endoscopic pattern of GIM with NBI is observed. Methods: Multicentre prospective study of a consecutive sample of patients (n = 183) submitted to gastroscopy using NBI with no superficial neoplastic lesions and no suggestive areas of GIM. Biopsies of both antrum/incisure and body were performed in all patients and samples were placed in the same vial for histologic assessment [according to OLGA (operative link for gastritis assessment) and OLGIM (operative link for gastric intestinal metaplasia)], blinded to endoscopic features. Results: In all patients, OLGA and OLGIM calculation was possible as the pathologists could distinguish biopsy samples from antrum/incisure from those of gastric body. The negative predictive value was 100% for advanced stages of GIM or AG as 179 (98%) patients presented OLGIM 0 and only 4 (2%) presented OLGIM I. Regarding AG, 150 (82%) presented OLGA 0, 23 (13%) OLGA I and 10 (6%) OLGA II. Conclusion: In the absence of a typical endoscopic pattern of GIM using NBI, it is effective to place biopsies' specimens in the same vial (for Helicobacter pylori diagnosis) or even to abstain from biopsies as no single patient with significant changes seems to be missed. This change in clinical practice can have a significant impact on endoscopy costs. [ABSTRACT FROM AUTHOR]

The scan statistic is by far the most popular method for anomaly detection, being popular in syndromic surveillance, signal and image processing, and target detection based on sensor networks, among other applications. The use of the scan statistics in such settings yields a hypothesis testing procedure, where the null hypothesis corresponds to the absence of anomalous behavior. If the null distribution is known, then calibration of a scan-based test is relatively easy, as it can be done by Monte Carlo simulation. When the null distribution is unknown, it is less straightforward. We investigate two procedures. The first one is a calibration by permutation and the other is a rank-based scan test, which is distribution-free and less sensitive to outliers. Furthermore, the rank scan test requires only a one-time calibration for a given data size making it computationally much more appealing. In both cases, we quantify the performance loss with respect to an oracle scan test that knows the null distribution. We show that using one of these calibration procedures results in only a very small loss of power in the context of a natural exponential family. This includes the classical normal location model, popular in signal processing, and the Poisson model, popular in syndromic surveillance. We perform numerical experiments on simulated data further supporting our theory and also on a real dataset from genomics. Supplementary materials for this article are available online. [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]

This paper investigates the problem of recovering the support of structured signals via adaptive compressive sensing. We examine several classes of structured support sets, and characterize the fundamental limits of accurately recovering such sets through compressive measurements, while simultaneously providing adaptive support recovery protocols that perform near optimally for these classes. We show that by adaptively designing the sensing matrix, we can attain significant performance gains over non-adaptive protocols. These gains arise from the fact that adaptive sensing can: 1) better mitigate the effects of noise and 2) better capitalize on the structure of the support sets. [ABSTRACT FROM PUBLISHER]

The article focuses on hepatological studies about a definite mouse model of prevalence of non-alcoholic fatty liver disease (NAFLD), which is estimated to be 24% and continues to rise significantly due to the growth in obesity and other metabolic disorders. Other information about the use of mouse models is presented.

The main objective of this paper is to study the implementation of a battery energy storage system (BESS) in order to improve the dynamic behaviour of an offshore wind farm. Special attention is given to the frequency excursions limitation in the sequence of a fault on the onshore grid. This goal is accomplished by setting up a case study in which an offshore wind farm is connected to an onshore grid through a high voltage direct current line commutated converter (HVDC-LCC) link. The Power System Simulator for Engineering (PSS/E) simulation tool is used to implement the whole system, including the onshore and offshore grids and the load flow and dynamic models of the conventional generators, the wind turbine generators (WTGs), the HVDC-LCC link and the BESS. With the BESS out of service, some protective actions of the DC link lead to the uncontrolled frequency increase of the WTG, which are consequently tripped out. The BESS proves to be essential, as it allows the offshore wind farm to keep running by maintaining the frequency of the WTG at acceptable levels and therefore bringing the entire system to a steady state operating point. [ABSTRACT FROM PUBLISHER]

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]

Photovoltaic microgeneration (μG) located near the domestic consumers is expected to increase more in the future. Known issues regarding high μG penetration are voltage rise and reverse power flow. The concept of selfconsumption and storage is emerging as a way to improve network power supply quality and to facilitate the integration of small renewable energy sources in low voltage networks. This paper intends to give a further contribution by assessing the improvements provided by allowing domestic clients to consume and store the energy they produce. The tool at hand to study the situation is the unbalanced three-phase load flow algorithm, based on the power summation technique, improved with the capability of explicitly compute the neutral voltages. The behaviour of a test radial distribution grid is assessed in different operating conditions, namely winter/summer, μG penetration level and μG operating mode. Voltage profile, active power flow in the service transformer and losses are monitored. The results suggest that self-consumption with storage operating mode is a promising solution. Voltage excursions above normal grid voltage operating limits were not observed, the situation of reverse active power flow does not occur and the power losses are reduced. [ABSTRACT FROM AUTHOR]

Photovoltaic microgeneration (μG) located near the domestic consumers is expected to increase more in the future. Known issues regarding high μG penetration are voltage rise and reverse power flow. The concept of self‐consumption and storage is emerging as a way to improve network power supply quality and to facilitate the integration of small renewable energy sources in low voltage networks. This paper intends to give a further contribution by assessing the improvements provided by allowing domestic clients to consume and store the energy they produce. The tool at hand to study the situation is the unbalanced three‐phase load flow algorithm, based on the power summation technique, improved with the capability of explicitly compute the neutral voltages. The behaviour of a test radial distribution grid is assessed in different operating conditions, namely winter/summer, μG penetration level and μG operating mode. Voltage profile, active power flow in the service transformer and losses are monitored. The results suggest that self‐consumption with storage operating mode is a promising solution. Voltage excursions above normal grid voltage operating limits were not observed, the situation of reverse active power flow does not occur and the power losses are reduced. [ABSTRACT FROM AUTHOR]

The major concern of power utilities is to maintain, in all situations, the supply of electrical power to all its customers without any failure. However, because of a recent phenomenon such as demand power increase, insufficient power generation and other economical and environmental factors, most power system utilities operate with its equipment very close to their limits. This situation implies that events such as voltage instability and voltage collapse become more likely to occur. The static synchronous compensator, a shunt-connected Flexible AC Transmission Systems device capable of regulating the voltage level, is an important tool in order to prevent these occurrences from happening. In this paper, an approach to the problem of where these devices have to be inserted and what size should they have in order to enhance the voltage stability margin to a specified level is introduced in the form of metaheuristic approach. The approach was developed using the continuation power flow method to calculate the point of maximum loadability of the power system and using the particle swarm optimization concept to find the optimal combination of locations and sizes of a group of static synchronous compensator units. This is a known approach to the problem, but a new design of the objective function, which seeks to attain a pre-specified desired voltage stability margin, instead of maximizing it, is presented as an original contribution of the paper. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The incorporation of clean energy sources in the power system is a topic of discussion almost everywhere. After the "wind (farms) of change", small, dispersed, urban photovoltaic (PV) generators are being installed in the roofs of the buildings, connected to the local Low Voltage (LV) grid. A boost in this type of renewable micro generation is expected in the near future. Due to the domestic loads, LV grids are inherently unbalanced, its analysis requiring the use of three-phase load flow methods. This same methodology is used in this paper to assess the problem of the concurrent unbalanced generation and load and to cope with the presence of both single and three-phase equipment in the same grid. A review of existent models for three-phase equipment is performed. The issue of modelling three-phase loads (isolated star and delta connected) and singlephase PV generators and associated power electronics is given special attention. Finally, a case-study is presented, enabling to draw some conclusions regarding the impacts on the Medium Voltage (MV) grid and the behaviour of the system facing different climacteric conditions. [ABSTRACT FROM AUTHOR]

In many practical settings one can sequentially and adaptively guide the collection of future data, based on information extracted from data collected previously. These sequential data collection procedures are known by different names, such as sequential experimental design, active learning, or adaptive sensing/sampling. The intricate relation between data analysis and acquisition in adaptive sensing paradigms can be extremely powerful, and often allows for reliable signal estimation and detection in situations where nonadaptive sensing would fail dramatically. In this paper, we investigate the problem of estimating the support of a structured sparse signal from coordinate-wise observations under the adaptive sensing paradigm. We present a general procedure for support set estimation that is optimal in a variety of cases and shows that through the use of adaptive sensing one can: 1) mitigate the effect of observation noise when compared with nonadaptive sensing and 2) capitalize on structural information to a much larger extent than possible with nonadaptive sensing. In addition to a general procedure to perform adaptive sensing in structured settings, we present both performance upper bounds, and corresponding lower bounds for both sensing paradigms. [ABSTRACT FROM AUTHOR]

The problem of detecting correlations from samples of a high-dimensional Gaussian vector has recently received a lot of attention. In most existing work, detection procedures are provided with a full sample. However, following common wisdom in experimental design, the experimenter may have the capacity to make targeted measurements in an on-line and adaptive manner. In this paper, we investigate such adaptive sensing procedures for detecting positive correlations. It is shown that, using the same number of measurements, adaptive procedures are able to detect significantly weaker correlations than their nonadaptive counterparts. We also establish minimax lower bounds that show the limitations of any procedure. [ABSTRACT FROM AUTHOR]

During the past years, governments throughout the world have been encouraging the installation of renewable energy systems to cope with environmental goals. In this framework, there has been a significant increase in the number of energy producers on the consumers' side, majorly due to photovoltaic and wind energy microgeneration. This has brought some concerns in voltage control on buses far away from the substation. The present paper analyses the impact of these microgeneration systems on the low voltage grid, namely in what concerns over voltage issues. For this purpose, both stochastic models to predict solar irradiance and wind speed and a three-phase power flow algorithm to compute voltages on the buses of a test network are used. The probabilistic power flow study, carried on using Monte Carlo methods, reveals the possibility of over voltage problems. A solution based on batteries attached to the micro generators is proposed to cope with this issue. The obtained results show the effectiveness of the solution, as a way to decrease over voltages, while preserving the producers' revenues. [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]

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]

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]

Cognitive radios process their sensed information collectively in order to opportunistically identify and access underutilized spectrum segments (spectrum holes). Due to the transient and rapidly varying nature of the spectrum occupancy, the cognitive radios (secondary users) must be agile in identifying the spectrum holes in order to enhance their spectral efficiency. We propose a novel adaptive procedure to reinforce the agility of the secondary users for identifying multiple spectrum holes simultaneously over a wide spectrum band. This is accomplished by successively exploring the set of potential spectrum holes and progressively allocating the sensing resources to the most promising areas of the spectrum. Such exploration and resource allocation results in conservative spending of the sensing resources and translates into very agile spectrum monitoring. The proposed successive and adaptive sensing procedure is in contrast to the more conventional approaches that distribute the sampling resources equally over the entire spectrum. Besides improved agility, the adaptive procedure requires less-stringent constraints on the power of the primary users to guarantee that they remain distinguishable from the environment noise and renders more reliable spectrum hole detection. [ABSTRACT FROM AUTHOR]

Adaptive sampling results in significant improvements in the recovery of sparse signals in white Gaussian noise. A sequential adaptive sampling-and-refinement procedure called Distilled Sensing (DS) is proposed and analyzed. DS is a form of multistage experimental design and testing. Because of the adaptive nature of the data collection, DS can detect and localize far weaker signals than possible from non-adaptive measurements. In particular, reliable detection and localization (support estimation) using non-adaptive samples is possible only if the signal amplitudes grow logarithmically with the problem dimension. Here it is shown that using adaptive sampling, reliable detection is possible provided the amplitude exceeds a constant, and localization is possible when the amplitude exceeds any arbitrarily slowly growing function of the dimension. [ABSTRACT FROM AUTHOR]

Abstract: p53/Mdm-2 interaction is a prime target of ursodeoxycholic acid (UDCA) for regulating apoptosis in primary rat hepatocytes. Here, we further explored the role of UDCA in downregulating p53 by Mdm-2. UDCA reduced the stability of p53 by decreasing protein half-life. Although proteasomal activity was slightly increased with UDCA, the effect was also observed for other bile acids. More importantly, immunoprecipitation assays revealed that UDCA promoted p53 ubiquitination, therefore leading to increased p53 degradation. In this regard, proteasome inhibition after UDCA pre-treatment resulted in accumulation of ubiquitinated p53, which in turn was prevented in cells overexpressing a mutated form of p53 that does not undergo Mdm-2 ubiquitination. The involvement of Mdm-2 in UDCA-mediated response was further confirmed by siRNA-mediated gene silencing experiments. Finally, the protective effect of UDCA against p53-induced apoptosis was abolished after inhibition of proteasome activity and prevention of p53 ubiquitination by Mdm-2. These findings suggest that UDCA protects cells from p53-mediated apoptosis by promoting its degradation via the Mdm-2-ubiquitin-proteasome pathway. [ABSTRACT FROM AUTHOR]

New gene regulation study tools such as microRNA (miRNA or miR) analysis may provide unique insights into the remarkable ability of the liver to regenerate. In addition, we have previously shown that ursodeoxycholic acid (UDCA) modulates mRNA levels during liver regeneration. Bile acids are also homeotrophic sensors of functional hepatic capacity. The present study was designed to determine whether miRNAs are modulated in rats following 70% partial hepatectomy (PH) and elucidate the role of UDCA in regulating miRNA expression during liver regeneration (LR). Total RNA was isolated from livers harvested at 3-72 h following 70% PH or sham operations, from both 0.4% (wt/wt) UDCA and control diet-fed animals. By using a custom microarray platform we found that several miRNAs are significantly altered alter PH by > 1.5-fold, including some previously described as modulators of cell proliferation, differentiation, and death. In particular, expression of miR-21 was increased after PH. Functional modulation of miR-21 in primary rat hepatocytes increased cell proliferation and viability. Importantly, UDCA was a strong inducer of miR-21 both during LR and in cultured HepG2 cells. In fact, UDCA feeding appeared to induce a sustained increase of proliferative miRNAs observed at early time points after PH. In conclusion, miRNAs, in particular miR-21, may play a significant role in modulating proliferation and cell cycle progression genes after PH. miR-21 is additionally induced by UDCA in both regenerating rat liver and in vitro, which may represent a new mechanism behind UDCA biological functions. [ABSTRACT FROM AUTHOR]

As the onshore wind resource is running shorter, wind power promoters are paying attention to the offshore resources. As in most cases there is no load offshore, wind power must be transmitted to the main land. To do so, two options are available: HVAC and HVDC transmission systems. In this paper, the two options are analysed from a power flow point of view. The influence in the voltage regulation of the onshore connection busbar is investigated in a 57 bus test power system. The simulation results obtained for each one of the above mentioned transmission system configurations allow the conclusion that HVAC solution is limited by the distance to shore and by the wind transmitted power. HVDC options do not show these limitations, but are more expensive and more delicate to deal with, because there is a lack of operational experience, so far. [ABSTRACT FROM AUTHOR]

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 paper analyzes the potential advantages and theoretical challenges of "active learning" algorithms. Active learning involves sequential sampling procedures that use information gleaned from previous samples in order to focus the sampling and accelerate the learning process relative to "passive learning" algorithms, which are based on nonadaptive (usually random) samples. There are a number of empirical and theoretical results suggesting that in certain situations active learning can be significantly more effective than passive learning. However, the fact that active learning algorithms are feedback systems makes their theoretical analysis very challenging. This paper aims to shed light on achievable limits in active learning. Using minimax analysis techniques, we study the achievable rates of classification error convergence for broad classes of distributions characterized by decision boundary regularity and noise conditions. The results clearly indicate the conditions under which one can expect significant gains through active learning. Furthermore, we show that the learning rates derived are tight for "boundary fragment" classes in d-dimensional feature spaces when the feature marginal density is bounded from above and below. [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]

Ursodeoxycholic (UDCA) and tauroursodeoxycholic (TUDCA) acids modulate apoptosis and regulate cell-cycle effectors, including cyclin D1. In contrast, deoxycholic acid (DCA) induces cell death and cyclin D1. In this study, we explored the role of cyclin D1 in DCA-induced toxicity and further elucidated the antiapoptotic function of UDCA and TUDCA in primary rat hepatocytes. Cells were incubated with DCA and with or without UDCA or TUDCA for 8-30 h. In addition, hepatocytes were transfected with either an adenovirus expressing cyclin D1 or with a cyclin D1 reporter plasmid with or without bile acids. Finally, cells were cotransfected with short interfering RNA targeting p53. Unlike DCA, both UDCA and TUDCA reduced cyclin D1 expression and transcriptional activation, confirming our previous DNA microarray data. Furthermore, UDCA and TUDCA prevented DCA-induced cyclin D1 and cell death. Cyclin D1 overexpression increased DCA-induced Bax translocation, cytochrome c release, and apoptosis. However, UDCA and TUDCA were less efficient at decreasing cyclin D1 levels as well as DCA-induced changes with overexpression. Finally, after p53 silencing, the effects of cyclin D1 overexpression were almost completely abrogated, whereas UDCA and TUDCA cytoprotective potential was reestablished. In conclusion, cyclin D1 is a relevant player in modulating apoptosis by bile acids, in part through a p53-dependent mechanism. [ABSTRACT FROM AUTHOR]

Background/Aims: Ursodeoxycholic acid (UDCA) and its taurine-conjugated derivative, TUDCA, modulate cell death and cell cycle regulators, such as E2F-1 and p53. However, precise pathways underlying UDCA''s effects are not fully understood. The aim of this study was to identify specific cellular targets of UDCA. Methods: The expression profile of primary rat hepatocytes incubated with UDCA was determined using Affymetrix GeneChip Rat 230A arrays. Hybridization data were processed to identify genes with significant expression changes. RT-PCR and immunoblot analyses of a selected target confirmed microarray data. Results: The results showed that >440 genes were modulated with UDCA by >1.5-fold; ∼25% were significantly different from controls. Genes affected by UDCA included new regulatory molecules, such as Apaf-1. RT-PCR and immunoblotting confirmed a decrease in Apaf-1. Other altered genes were directly involved in cell cycle (cyclin D1, cadherin 1, HMG-box containing protein 1) and apoptosis (prothymosin-α) events. The E2F-1/p53/Apaf-1 pathway appears to be targeted by UDCA. Finally, transcripts for proteins with kinase activity and transcription factors were specifically modulated by TUDCA. Conclusions: This study expands our knowledge of the biological effects of UDCA in hepatocytes. Most of the identified genes represent novel potential targets of UDCA, which may ultimately explain its therapeutic properties. [Copyright &y& Elsevier]

This paper develops a new method for hierarchical clustering. Unlike other existing clustering schemes, our method is based on a generative, tree-structured model that represents relationships between the objects to be clustered, rather than directly modeling properties of objects themselves. In certain problems, this generative model naturally captures the physical mechanisms responsible for relationships among objects, for example, in certain evolutionary tree problems in genetics and communication net- work topology identification. The paper examines the networking problem in some detail to illustrate the new clustering method. More broadly, the generative model may not reflect actual physical mechanisms, but it nonetheless provides a means for dealing with errors in the similarity matrix, simultaneously promoting two desirable features in clustering: intraclass similarity and interclass dissimilarity. [ABSTRACT FROM AUTHOR]

We have recently shown that both ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) prevent transforming growth factor β (TGF-β1)-induced hepatocyte apoptosis by modulating the E2F- l/p53/Bax pathway. In addition, activation of glucocorticoid (GR) and mineralocorticoid receptors (MR) inhibits apoptosis in various systems. UDCA induces a ligand-independent activation of the GR, thus potentially regulating a number of targets. In this study, we investigated the role of GR and MR during TGF-β1-induced hepatocyte apoptosis, and identified additional antiapoptotic targets for UDCA. Our results showed that in primary hepatocytes, TGF-β1 induced 40-50% decreases in gr and mr mRNA expression (p < 0.01), together with up to 10-fold reductions in their protein levels (p < 0.01). Notably, pretreatment with UDCA resulted in a significant upregulation of nuclear steroid receptors (p < 0.05), which coincided with 2- and 3-fold increases in the level of GR and MR nuclear translocation, respectively, when compared with that of TGF-β1 alone (p < 0.05). Similarly, TUDCA induced GR and MR nuclear translocations (p < 0.05) and markedly prevented MR protein changes associated with TGF-β1 (p < 0.05) without affecting GR protein levels. Moreover, when interference RNA was used to inhibit GR and MR, UDCA no longer protected hepatocytes against TGF-β 1-induced apoptosis. In fact, the protective effect of UDCA in TGF-β1-associated caspase activation decreased from 65 to <10% when GR or MR function was blocked. Finally, the TGF-β1-induced E2F-1/Mdm-2/p53 apoptotic pathway, normally inhibited by UDCA, was not regulated by the bile acid after GR or MR silencing. These results demonstrate that UDCA protects against apoptosis through an additional pathway that involves nuclear receptors GR and MR as key factors. Further, the E2F- l/Mdm-2/p53 apoptotic pathway appears to be a prime target for UDCA-induced steroid receptor activation. [ABSTRACT FROM AUTHOR]

Presents a study which addressed the issue of the capacity credit provided by wind energy conversion systems. Method of the study; Results and discussion; Conclusion.