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33rd European Photovoltaic Solar Energy Conference and Exhibition; 2485-2491, On regional scale, the estimation of the solar power generation from the environmental conditions and the solar power forecast is essential for Distribution System Operators, Transmission System Operator, energy traders, and aggregators. Indeed, high photovoltaic penetration results in a stochastic variability of the electric demand that could compromise the stability of the grid, increase the amount of energy reserve and the energy imbalance cost. In this context, two upscaling methods and several models were developed and used for estimation and forecast of the photovoltaic distributed generation in a small area of Italy with high photovoltaic penetration. The upscaling methods are based on chains of data-driven models (k-mean clustering, principal component analysis and ensemble of neural networks) that use as inputs satellite derived irradiance and numerical weather prediction. These models allow a complete assessment of the accuracy of the regional power forecast at different horizons, from 0 hour ahead (power estimation) to 48 hours ahead. The power estimation model provided a RMSE of 3% of installed capacity. Intra-day forecast (from 1 to 4 hours) obtained a RMSE of 5% - 7% and a skill score with respect to the clear sky persistence from -8% to 33.6%. The one and two days ahead forecast achieved a RMSE of 7% and 7.5% and a skill score of 39.2% and 45.7%. The ensemble smoothing effect on cluster scale was also studied. It was proved that the RMSE reduction achieved on cluster scale due to the ensemble smoothing follows the same exponential law found for single systems. In this case the smoothing effect reduces the RMSE of day-ahead forecast of 12% with respect to the mean single cluster value. It was also shown that the skill score increases linearly with the size of the region with a rate of 0.1% for km. Furthermore, a method to estimate the forecast error was also developed. It was based on an ensemble neural network model coupled with a probabilistic correction. It can provide a highly reliable computation of the prediction intervals.

32nd European Photovoltaic Solar Energy Conference and Exhibition; 1475-1481, This work aims to compare several data-driven models using different Numerical Weather Prediction (NWP) input data and then to build up an outperforming Multi-Model Ensemble (MME) and its prediction intervals. Statistic, stochastic and hybrid machine-learning algorithms were developed and the NWP data from IFS and WRF models were used as input. It was found that the same machine learning algorithm differs in performance even if it make use of NWP data with comparable accuracy. This apparent inconsistency depends on the capability of the machine learning model to correct the bias error of the input data. The stochastic and the hybrid model using the same WRF input, as well as the stochastic and the non-linear statistic models using the same IFS input, produce very similar results. The MME resulting from the averaging of the best data-driven forecasts, improves the accuracy of the outperforming member of the ensemble, bringing the skill score from 42% to 46%. To reach this performance, the ensemble should include forecasts with similar accuracy but generated with the higher variety of different data-driven technology and NWP input.

CONTEXT: In Italy, the surveillance of congenital hypothyroidism (CH) is performed by the Italian National Registry of Infants with CH (INRICH). Up to now, about 3600 infants with CH are recorded in the INRICH, and a high number of twins are included. OBJECTIVE: Our objective was to estimate the risk of CH in multiple and single deliveries and to compare neonatal features of CH twins with twins from the general population. DESIGN: The Italian population of CH infants recorded in the INRICH from 1989-2000 was investigated. RESULTS: A more than 3-fold higher frequency of twins was found in the CH population than in the general population, and for the first time, it was possible to estimate the CH incidence in multiple (10.1 in 10,000) and single deliveries (3.2 in 10,000 live births). Significantly higher frequencies of in situ gland as well as lower TSH mean level at screening were found in twin than in singleton CH babies. The concordance rate for permanent CH was very low (4.3%) and due to only three concordant couples. However, a high recurrence risk for CH was estimated in siblings of affected babies recorded in the INRICH, including twins considered as siblings. CONCLUSIONS: The high CH incidence observed in twins is worthy of interest for the high number of induced pregnancies in Italy as well as in other Western countries. Moreover, the low concordance rate for CH among twins together with a high recurrence risk for the disease among siblings indicates that environmental risk factors may act as a trigger on a susceptible genetic background in the etiology of the disease

An application of Evolution Strategies (ESs) to the dynamic identification of hybrid seismic isolation systems is presented. It is shown how ESs are highly effective for the optimisation of the test problem defined in previous work for methodology validation. The acceleration records of a number of dynamic tests performed on a seismically isolated building are used as reference data for the parameter identification. The application of CMA-ES to a previously existing model considerably improves previous results but at the same time reveals limitations of the model. To investigate the problem three new mechanical models with higher number of parameters are developed. The application of CMA-ES to the best designed model allows improvements of up to 79% compared to the solutions previously available in literature. © Springer-Verlag Berlin Heidelberg 2013.

CCTs (Italian Treasury credit certificates) were first introduced in 1977 in order to meet the need for more effective management of the public debt. The CCT was accepted in the market as a `centaur': a short-term security in its yield and risk features, but with a long maturity. However, in terms of techniques of financial analysis and portfolio management, the methodological approach to CCTs appears to be generally confused. JEL: G20, PSL Quarterly Review, V. 46, N. 185 (1993)

BACKGROUND: Organogenesis of the thyroid gland requires the Pax8 protein. Absence or reduction of Pax8 results in congenital hypothyroidism in animal models and humans, respectively. This study aims at elucidating the regulatory mechanism leading to the expression of Pax8 in thyroid cells. METHODS: The murine Pax8 gene promoter was functionally dissected by mutagenesis and transfection in the thyroid cell line FRTL-5. Nuclear factors important for thyroid-specific gene expression were identified by DNA-binding assays. RESULTS: We show that Pax8 binds to and controls the expression of its own promoter. Furthermore, we identify a novel, thyroid-specific, DNA-binding activity (denominated nTTF [for novel Thyroid Transcription Factor]) that recognizes a specific region of the Pax8 promoter. CONCLUSIONS: The Pax8 promoter appears to be autoregulated, a feature that might be responsible for the haploinsufficiency displayed by this gene.

BACKGROUND: Mucosal infections are a major global health problem and it is generally accepted that mucosal vaccination strategies, able to block infection at their entry site, would be preferable with respect to other prevention approaches. However, there are still relatively few mucosal vaccines available, mainly because of the lack of efficient delivery systems and of mucosal adjuvants. Recombinant bacterial spores displaying a heterologous antigen have been shown to induce protective immune responses and, therefore, proposed as a mucosal delivery system. A non-recombinant approach has been recently developed and tested to display antigens and enzymes. RESULTS: We report that the binding subunit of the heat-labile toxin (LTB) of Escherichia coli efficiently adsorbed on the surface of Bacillus subtilis spores. When nasally administered to groups of mice, spore-adsorbed LTB was able to induce a specific immune response with the production of serum IgG, fecal sIgA and of IFN-gamma in spleen and mesenteric lympho nodes (MLN) of the immunized animals. Dot blotting experiments showed that the non-recombinant approach was more efficient than the recombinant system in displaying LTB and that the efficiency of display could be further increased by using mutant spores with an altered surface. In addition, immunofluorescence microscopy experiments showed that only when displayed on the spore surface by the non-recombinant approach LTB was found in its native, pentameric form. CONCLUSION: Our results indicate that non-recombinant spores displaying LTB pentamers can be administered by the nasal route to induce a Th1-biased, specific immune response. Mutant spores with an altered coat are more efficient than wild type spores in adsorbing the antigen, allowing the use of a reduced number of spores in immunization procedures. Efficiency of display, ability to display the native form of the antigen and to induce a specific immune response propose this non-recombinant delivery system as a powerful mucosal vaccine delivery approach.

Background Applications of bacteriocins as food preservatives have been so far limited, principally because of their low antimicrobial activity in foods. Nisin is the only bacteriocin of significant use, but applications are restricted principally because of its very low activity at neutral or alkaline pH. Thus the isolation of new bacteriocins active in foods is desirable. Results We isolated a Bacillus licheniformis thermophilic strain producing a bacteriocin with some novel features, named here bacillocin 490. This bacteriocin was inactivated by pronase E and proteinase K and was active against closely related Bacillus spp. both in aerobic and in anaerobic conditions. Bactericidal activity was kept during storage at 4°C and was remarkably stable in a wide pH range. The bacteriocin was partially purified by elution after adhesion to cells of the food-isolated strain Bacillus smithii and had a rather low mass (2 KDa). Antimicrobial activity against B. smithii was observed also when this organism was grown in water buffalo milk. Conclusions Bacillocin 490 is a novel candidate as a food anti-microbial agent since it displays its activity in milk, is stable to heat treatment and during storage, is active in a wide pH range and has bactericidal activity also at high temperature. These features may allow the use of bacillocin 490 during processes performed at high temperature and as a complementary antimicrobial agent of nisin against some Bacillus spp. in non-acidic foods. The small size suggests its use on solid foods.

Despite advances in our understanding of basic mechanisms driving post-surgical pain, treating incision-induced pain remains a major clinical challenge. Moreover, surgery has been implicated as a major cause of chronic pain conditions. Hence, more efficacious treatments are needed to inhibit incision-induced pain and prevent the transition to chronic pain following surgery. We reasoned that activators of AMP-activated protein kinase (AMPK) may represent a novel treatment avenue for the local treatment of incision-induced pain because AMPK activators inhibit ERK and mTOR signaling, two important pathways involved in the sensitization of peripheral nociceptors.

Cadherin-16 was originally identified as a tissue-specific cadherin present exclusively in kidney. Only recently, Cadherin-16 has been detected also on the plasma membrane of mouse thyrocytes. This last finding prompted us to note that the expression profile of Cadherin-16 resembles that of the transcription factor Pax8, a member of the Pax (paired-box) gene family, predominantly expressed in the developing and adult kidney and thyroid. Pax8 has been extensively characterized in the thyroid and shown to be a master gene for thyroid development and differentiation. In this study, we determined the role of the transcription factor Pax8 in the regulation of Cadherin-16 expression. We demonstrate that the Cadherin-16 minimal promoter is transcriptionally active in thyroid cells as well as in kidney cells, that Pax8 is able to activate transcription from a Cadherin-16 promoter reporter construct, and more importantly, that indeed Pax8 is able to bind in vivo the Cadherin-16 promoter region. In addition, by means of Pax8 RNA interference in thyroid cells and by analyzing Pax8 null mice, we demonstrate that Pax8 regulates also in vivo the expression of Cadherin-16. Finally, we reveal that the expression of Cadherin-16 is TSH dependent in FRTL-5 thyroid cells and significantly reduced in mouse thyroid carcinomas. Therefore, we conclude that Cadherin-16 is a novel downstream target of the transcription factor Pax8, likely since the early steps of thyroid development, and that its expression is associated with the fully differentiated state of the thyroid cell.

Fe65 interacts with the cytosolic domain of the Alzheimer amyloid precursor protein (APP). The functions of the Fe65 are still unknown. To address this point we generated Fe65 knockout (KO) mice. These mice do not show any obvious phenotype; however, when fibroblasts (mouse embryonic fibroblasts), isolated from Fe65 KO embryos, were exposed to low doses of DNA damaging agents, such as etoposide or H2O2, an increased sensitivity to genotoxic stress, compared with wild type animals, clearly emerged. Accordingly, brain extracts from Fe65 KO mice, exposed to non-lethal doses of ionizing radiations, showed high levels of gamma-H2AX and p53, thus demonstrating a higher sensitivity to X-rays than wild type mice. Nuclear Fe65 is necessary to rescue the observed phenotype, and few minutes after the exposure of MEFs to DNA damaging agents, Fe65 undergoes phosphorylation in the nucleus. With a similar timing, the proteolytic processing of APP is rapidly affected by the genotoxic stress: in fact, the cleavage of the APP COOH-terminal fragments by gamma-secretase is induced soon after the exposure of cells to etoposide, in a Fe65-dependent manner. These results demonstrate that Fe65 plays an essential role in the response of the cells to DNA damage.

Bacillus subtilis spores displaying the tetanus toxin fragment C (TTFC) on their surface have been previously shown to induce the production of specific IgG and secretory IgA in mice immunized through the oral or nasal route. Aim of this study was to analyze whether these spores were also able to induce cellular immunity, and whether such immune response was dependent on spore germination in the animal gastro-intestinal tract (GIT). We first developed a germination defective strain of B. subtilis unable to produce viable cells inside the mouse GIT. Germination-defective and congenic wild-type spores both expressing TTFC on their surface were then used to orally immunize Balb/C mice. Both types of spores induced spleen and mesenteric lymph nodes cell proliferation as well as production of IFNgamma but not of IL-4 and IL-10 in both districts. Our results indicate that recombinant spores preferentially induce a strong cell-mediated immune response with a Th1 phenotype, independently from their ability to germinate in the GIT.

Bacillus subtilis spores displaying the tetanus toxin fragment C (TTFC) on their surface have been previously shown to induce the production of specific IgG and secretory IgA in mice immunized through the oral or nasal route. Aim of this study was to analyze whether these spores were also able to induce cellular immunity, and whether such immune response was dependent on spore germination in the animal gastro-intestinal tract (GIT). We first developed a germination defective strain of B. subtilis unable to produce viable cells inside the mouse GIT. Germination-defective and congenic wild-type spores both expressing TTFC on their surface were then used to orally immunize Balb/C mice. Both types of spores induced spleen and mesenteric lymph nodes cell proliferation as well as production of IFNgamma but not of IL-4 and IL-10 in both districts. Our results indicate that recombinant spores preferentially induce a strong cell-mediated immune response with a Th1 phenotype, independently from their ability to germinate in the GIT.