Modeling stochasticity and robustness in gene regulatory networks.

MOTIVATION: Understanding gene regulation in biological processes and modeling the robustness of underlying regulatory networks is an important problem that is currently being addressed by computational systems biologists. Lately, there has been a renewed interest in Boolean modeling techniques for gene regulatory networks (GRNs). However, due to their deterministic nature, it is often difficult to identify whether these modeling approaches are robust to the addition of stochastic noise that is widespread in gene regulatory processes. Stochasticity in Boolean models of GRNs has been addressed relatively sparingly in the past, mainly by flipping the expression of genes between different expression levels with a predefined probability. This stochasticity in nodes (SIN) model leads to over representation of noise in GRNs and hence non-correspondence with biological observations. RESULTS: In this article, we introduce the stochasticity in functions (SIF) model for simulating stochasticity in Boolean models of GRNs. By providing biological motivation behind the use of the SIF model and applying it to the T-helper and T-cell activation networks, we show that the SIF model provides more biologically robust results than the existing SIN model of stochasticity in GRNs. AVAILABILITY: Algorithms are made available under our Boolean modeling toolbox, GenYsis. The software binaries can be downloaded from http://si2.epfl.ch/ approximately garg/genysis.html.

Evaluation of Health-Related Quality of Life according to Carbohydrate Metabolism Status: A Spanish Population-Based Study (Di@bet.es Study)

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12 questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2–2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26–2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma: A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study.

PURPOSE: To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. PATIENTS AND METHODS: This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150mg/m(2) followed by topotecan at 0.75mg/m(2) intravenously for five consecutive days every 28days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. RESULTS: Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median response duration of 8.5months. Tumour control rate (complete response (CR)+partial response (PR)+mixed response (MR)+stable disease (SD)) was 68% (95% CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58% respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47% of courses in 71% of patients; three patients (8%) had febrile neutropenia. CONCLUSION: Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile.

Catalogo della prima parte della biblioteca appartenuta al sig. march. Costabili di Ferrara composta di libri rari e preziosi in diverso genere : manoscritti, libri impressi in pergamena, quattrocentisti,... : Casa Silvestre, strada Bons-Enfants, 28,Parigii, 18 Febbraio 1858

[Vente. Livres. 1858-02-18. Paris]

La memoria tra pulsioni autobiografiche e rielaborazione narrativa : forme e trasformazioni del tempo nella narrativa di Giovanna Zangrandi

La tesi è imperniata sulle modalità di rappresentazione letteraria del tempo e délia memoria (dunque sulla relazione fra tempo e narratività) nella produzione narrativa ad ampio respiro délia scrittrice Giovanna Zangrandi.¦Il canone delle opere prese in esame comprende, in particolar modo, i romanzi I Brusaz (1954) e Orsola nelle stagioni (1957), la narrazione a carattere autobiografico de II campo rosso (1959) e il diario resistenziale Igiorni Veri (1963).¦Il percorso di indagine si è awalso di strumenti teorici e analitici interdisciplinari: alla critica e alla prassi letteraria è stata affiancata una strumentazione di matrice storico-filosofica, sociologica e, in misura minore, psicanalitica.¦La tesi si articola in diverse sezioni. Nella prima parte del lavoro vengono esplorati alcuni nessi fondanti del lavoro: il rapporto fra storia e memoria, la relazione fra memoria individuale e memoria collettiva, la dialettica fra ricordo e oblio e quella fra memoria e narrazione, ossia ira contenuti mnestici individuali e loro configurazione letteraria; successivamente la tesi si focalizza sul nesso individuabile, soprattutto nelle opere più scopertamente autobiografiche di Giovanna Zangrandi, tra testo letterario e meccanismi individuali del ricordo, analizzando la dialettica tra pulsione autobiografica e sua rielaborazione tematica, tra piani memoriali soggettivi e loro traduzione narrativa.¦Nell'ultima parte del percorso critico la tesi si sofferma, in particolare, sulle complesse relazioni instaurate daU'autrice, nel diario I giorni veri, fra dimensioni storico-memoriali, piani autobiografïci e sistemi letterari. A taie fine, il punto di riferimento teorico fondamentale è costituito dalla prospettiva linguististica di Harald Weinrich, applicata alio studio dei tempi verbali, in base all'assunto secondo il quale il tempo verbale non esprime necessariamente una dimensione cronologica, quanto piuttosto una condizione psicologica délia soggettività narrante.¦Soffermandosi su un aspetto flnora inesplorato nell'ambito délia produzione narrativa di Giovanna Zangrandi, il lavoro evidenzia come la dialettica memoria/oblio e la corrispondente dicotomia tra passato e présente tendano a trasformarsi nella direttrice tematica fondamentale - nonchè in uno dei tratti più interessanti e significativi - dell'opera zangrandiana.

Vectorial capacity, basic reproduction number, force of infection and all that: formal notation to complete and adjust their classical concepts and equations

A dimensional analysis of the classical equations related to the dynamics of vector-borne infections is presented. It is provided a formal notation to complete the expressions for the Ross' Threshold Theorem, the Macdonald's basic reproduction "rate" and sporozoite "rate", Garret-Jones' vectorial capacity and Dietz-Molineaux-Thomas' force of infection. The analysis was intended to provide a formal notation that complete the classical equations proposed by these authors.

Melt topology and chemistry during partial melting in contact aureoles : an experimental study and field example

This study was initiated to investigate partial melting within the high-grade metamorphic rocks beneath the Little Cottonwood contact aureole (Utah, USA), in order to understand the melt generation, melt migration, and geometry of initial melt distribution on grain scale during crustal anatexis. The emplacement of the Little Cottonwood stock produced a contact aureole in the pelitic host rocks of the Big Cottonwood formation (BC). Metamorphic isogrades in pelitic rocks range form biotite to 2nd sillimanite grade as a function of distance from the contact. Migmatites are restricted to the highest grade and resulted form partial melting of the BC formation rocks. First melt was produced by a combined muscovite/biotite dehydration reaction in the sillimanite + k-feldspar stability field. Melt extraction from the pelites resulted in restites (magnetite + cordierite + alumosilicate ± biotite) surrounded by feldspar enriched quartzite zones. This texture is the result of gradual infiltration of partial melts into the quartzite. Larger, discrete melt accumulation occurred in extensional or transpressional domains such as boudin necks, veins, and ductile shear zones. Melt composition are Si02- rich, crystallized as pegmatites, and apparently were very mobile. They were able to infiltrate the quartzite pervaisivly. These melts are similar in composition to first melts produced in the hydrothermal partial melt experiments at 2kbar between 700 - 800°C on fine grained high metamorphic rocks (andalusite-cordierited-biotite-zone) of the BC formation. The experimental melts are water rich and in disequilibrium with the melting rock. Initial melt composition is heterogeneous for short run duration, reflective a lack of chemical equilibrium between individual melt pools. Rock core scale heterogeneity decreased with time indicating partial homogenization of melt compositions. A simultaneous shift of melt composition to higher silica content with time was observed. The silica content of the melt increased due to local melt/mineral reactions. Melt textures indicate that reactive melt transport is most efficient along grain boundaries rimmed by dissimilar grains. Melt heterogeneity resulted in chemical potential gradients which are major driving forces for initial melt migration and govern melt distribution during initial melting. An additional subject of the thesis is the crystal size distributions of opaque minerals in a fine-grained, high-grade meta-pelite of the Big Cottonwood which were obtained from 3D X-ray tomography (uCT) and 2D thin section analysis. µCT delivers accurate size distributions within a restricted range (~ a factor of 20 in size in a single 3D image), while the absolute number of crystals is difficult to obtain from these sparsely distributed, small crystals on the basis of 2D images. Crystal size distributions obtained from both methods are otherwise similar. - Ce travail de recherche a été entrepris dans le but d'étudier les processus de fusion partielle dans les roches fortement métamorphiques de l'auréole de contact de Little Cottonwood (Utah, USA) et ceci afin de comprendre la génération de liquide de fusion, la migration de ces liquides et la géométrie de la distribution initiale des liquides de fusion à l'échelle du grain durant l'anatexie de la croûte. L'emplacement du petit massif intrusif de Little Cottonwood a produit une auréole de contact dans les roches pélitiques encaissantes appartenant à la Foimation du Big Cottonwood (BC). Les isogrades métamorphiques dans les roches pélitiques varient de l'isograde de la biotite à la deuxième isograde de la sillimanite en fonction de la distance par rapport au massif intrusif. Les migmatites sont restreintes aux zones montrant le plus haut degré métamorphique et résultent de la fusion partielle des roches de la Formation de BC. Le premier liquide de fusion a été produit par la réaction de déshydratation combinée de la muscovite et de la biotite dans le champ de stabilité du feldspath potassique Pt de la sillimanite. L'extraction du liquide de fusion des pélites forme des restites (magnétites + cordiérite + aluminosilicate ± biotite) entourées par des zones de quartzites enrichies en feldspath. Cette texture est le résultat de l'infiltration graduelle du liquide de fusion partielle dans les quartzites. Des accumulations distinctes et plus larges de liquide de fusion ont lieu dans des domaines d'extension ou de transpression tels que les boudins, les veines, et les zones de cisaillement ductile. La composition des liquides de fusion est similaire à celle des liquides pegmatoïdes, et ces liquides sont apparemment très mobiles et capables d'infiltrer les quartzites. Ces liquides de fusion ont la même composition que les premiers liquides produits dans les expériences hydrotheunales de fusion partielle à 2kbar et entre 700-800° C sur les roches finement grenues et hautement métamorphiques (andalousite-cordiérite-biotite zone) de la Formation de BC. Les liquides de fusion obtenus expérimentalement sont riches en eau et sont en déséquilibre avec la roche en fusion. La composition initiale des liquides de fusion est hétérogène pour les expériences de courte durée et reflète l'absence d'équilibre chimique entre les différentes zones d'accumulation des liquides de fusion. L'hétérogénéité à l'échelle du noyau s'estompe avec le temps et témoigne de l'homogénéisation de la composition des liquides de fusion. Par ailleurs, on observe parallèlement un décalage de la composition des liquides vers des compositions plus riches en silice au cours du temps. Le contenu en silice des liquides de fusion évolue vers un liquide pegmatitique en raison des réactions liquides/minéraux. Les textures des liquides de fusion indiquent que le transport des liquides est plus efficace le long des bordures de grains bordés par des grains différents. Aucun changement apparent du volume total n'est visible. L'hétérogénéité des liquides s'accompagne d'un gradient de potentiel chimique qui sert de moteur principal à la migration des liquides et à la distribution des liquides durant la fusion. Un sujet complémentaire de ce travail de thèse réside dans l'étude de la distribution de la taille des cristaux opaques dans les pélites finement grenues et fortement métamorphiques de la Formation de Big Cottonwood. Les distributions de taille ont été obtenues suite à l'analyse d'images 3D acquise par tomographie ainsi que par analyse de lames minces. La microtomographie par rayon X fournit une distribution de taille précise sur une marge restreinte (- un facteur de taille 20 dans une seule image 3D), alors que le nombre absolu de cristaux est difficile à obtenir sur la base d'image 2D en raison de la petite taille et de la faible abondance de ces cristaux. Les distributions de taille obtenues par les deux méthodes sont sinon similaire. Abstact: Chemical differentiation of the primitive Earth was due to melting and separation of melts. Today, melt generation and emplacement is still the dominant process for the growth of the crust. Most granite formation is due to partial melting of the lower crust, followed by transport of magma through the crust to the shallow crust where it is emplaced. Partial melting and melt segregation are essential steps before such a granitic magma can ascent through the crust. The chemistry and physics of partial melting and segregation is complex. Hence detailed studies, in which field observations yield critical information that can be compared to experimental observations, are crucial to the understanding of these fundamental processes that lead and are leading to the chemical stratification of the Earth. The research presented in this thesis is a combined field and experimental study of partial melting of high-grade meta-pelitic rocks of the Little Cottonwood contact aureole (Utah, USA). Contact metamorphic rocks are ideal for textural studies of melt generation, since the relatively short times of the metamorphic event prevents much of the recrystallization which plagues textural studies of lower crustal rocks. The purpose of the study is to characterize melt generation, identify melting reactions, and to constrain melt formation, segregation and migration mechanisms. In parallel an experimental study was undertaken to investigate melt in the high grade meta pelitic rocks, to confirm melt composition, and to compare textures of the partial molten rock cores in the absence of deformation. Results show that a pegmatoidal melt is produced by partial melting of the pelitic rocks. This melt is highly mobile. It is capable of pervasive infiltration of the adjacent quartzite. Infiltration results in rounded quartz grains bordered by a thin feldspar rim. Using computed micro X-ray tomography these melt networks can be imaged. The infiltrated melt leads to rheological weakening and to a decompaction of the solid quartzite. Such decompaction can explain the recent discovery of abundant xenocrysts in many magmas, since it favors the isolation of mineral grains. Pervasive infiltration is apparently strongly influenced by melt viscosity and melt-crystal wetting behavior, both of which depend on the water content of melt and the temperature. In all experiments the first melt is produced on grain boundaries, dominantly by the local minerals. Grain scale heterogeneity of a melting rock leads thus to chemical concentration gradients in the melt, which are the driving force for initial melt migration. Pervasive melt films along grain boundaries leading to an interconnected network are immediately established. The initial chemical heterogeneities in the melt diminish with time. Résumé large public: La différenciation chimique de la Terre primitive est la conséquence de la fusion des roches et de la séparation des liquides qui en résultent. Aujourd'hui, la production de liquide magmatique est toujours le mécanisme dominant pour la croissance de la croûte terrestre. Ainsi la formation de la plupart des granites est un processus qui implique la production de magma par fusion partielle de la croûte inférieure, la migration de ces magmas à travers la croûte et finalement son emplacement dans les niveaux superficielle de la croûte terrestre. Au cours de cette évolution, les processus de fusion partielle et de ségrégation sont des étapes indispensables à l'ascension des granites à travers la croûte. Les conditions physico-chimiques nécessaires à la fusion partielle et à l'extraction de ces liquides sont complexes. C'est pourquoi des études détaillées des processus de fusion partielle sont cruciales pour la compréhension de ces mécanismes fondamentaux responsables de la stratification chimique de la Terre. Parmi ces études, les observations de terrain apportent notamment des informations déterminantes qui peuvent être comparées aux données expérimentales. Le travail de recherche présenté dans ce mémoire de thèse associe études de terrain et données expérimentales sur la fusion partielle des roches pélitiques de haut degré métamorphiques provenant de l'auréole de contact de Little Cottonwood (Utah, USA). Les roches du métamorphisme de contact sont idéales pour l'étude de la folination de liquide de fusion. En effet, la durée relativement courte de ce type d'événement métamorphique prévient en grande partie la recristallisation qui perturbe les études de texture des roches dans la croûte inférieure. Le but de cette étude est de caractériser la génération des liquides de fusion, d'identifier les réactions responsables de la fusion de ces roches et de contraindre la formation de ces liquides et leur mécanisme de ségrégation et de migration. Parallèlement, des travaux expérimentaux ont été entrepris pour reproduire la fusion partielle de ces roches en laboratoire. Cette étude a été effectuée dans le but de confirmer la composition chimique des liquides, et de comparer les textures obtenues en l'absence de déformation. Les résultats montrent qu'un liquide de fusion pegmatoïde est produit par fusion partielle des roches pélitiques. La grande mobilité de ce liquide permet une infiltration pénétrative dans les quarzites. Ces infiltrations se manifestent par des grains de quartz arrondis entourés par une fine bordure de feldspath. L'utilisation de la tomography à rayons X a permis d'obtenir des images de ce réseau de liquide de fusion. L'infiltration de liquide de fusion entraîne un affaiblissement de la rhéologie de la roche ainsi qu'une décompaction des quartzites massifs. Une telle décompaction peut expliquer la découverte récente d'abondants xénocristaux dans beaucoup de magmas, puisque elle favorise l'isolation des minéraux. L'infiltration pénétrative est apparemment fortement influencée par la viscosité du fluide de fusion et le comportement de la tension superficielle entre les cristaux et le liquide, les deux étant dépendant du contenu en eau dans le liquide de fusion et de la température. Dans toutes les expériences, le premier liquide est produit sur les bordures de grains, principalement par les minéraux locaux. L'hétérogénéité à l'échelle des grains d'une roche en fusion conduit donc à un gradient de concentration chimique dans le liquide, qui sert de moteur à l'initiation de la migration du liquide. Des fines couches de liquide de fusion le long de bordures de grains formant un réseau enchevêtré s'établit immédiatement. Les hétérogénéités chimiques initiales dans le liquide s'estompent avec le temps.

Lifelong dynamics of human CD4+CD25+ regulatory T cells: insights from in vivo data and mathematical modeling.

Despite their limited proliferation capacity, regulatory T cells (T(regs)) constitute a population maintained over the entire lifetime of a human organism. The means by which T(regs) sustain a stable pool in vivo are controversial. Using a mathematical model, we address this issue by evaluating several biological scenarios of the origins and the proliferation capacity of two subsets of T(regs): precursor CD4(+)CD25(+)CD45RO(-) and mature CD4(+)CD25(+)CD45RO(+) cells. The lifelong dynamics of T(regs) are described by a set of ordinary differential equations, driven by a stochastic process representing the major immune reactions involving these cells. The model dynamics are validated using data from human donors of different ages. Analysis of the data led to the identification of two properties of the dynamics: (1) the equilibrium in the CD4(+)CD25(+)FoxP3(+)T(regs) population is maintained over both precursor and mature T(regs) pools together, and (2) the ratio between precursor and mature T(regs) is inverted in the early years of adulthood. Then, using the model, we identified three biologically relevant scenarios that have the above properties: (1) the unique source of mature T(regs) is the antigen-driven differentiation of precursors that acquire the mature profile in the periphery and the proliferation of T(regs) is essential for the development and the maintenance of the pool; there exist other sources of mature T(regs), such as (2) a homeostatic density-dependent regulation or (3) thymus- or effector-derived T(regs), and in both cases, antigen-induced proliferation is not necessary for the development of a stable pool of T(regs). This is the first time that a mathematical model built to describe the in vivo dynamics of regulatory T cells is validated using human data. The application of this model provides an invaluable tool in estimating the amount of regulatory T cells as a function of time in the blood of patients that received a solid organ transplant or are suffering from an autoimmune disease.

Prevenzione della malaria nei viaggiatori: quale antimalarico?: revisione Cochrane per il medico di famiglia.

Cet article présente les résultats de la revue systématique: Jacquerioz FA, Croft AM. Drugs for preventing malaria in travellers. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD006491. PMID: 19821371

Study and implementation of some quantitative trading models

Quantitative or algorithmic trading is the automatization of investments decisions obeying a fixed or dynamic sets of rules to determine trading orders. It has increasingly made its way up to 70% of the trading volume of one of the biggest financial markets such as the New York Stock Exchange (NYSE). However, there is not a signi cant amount of academic literature devoted to it due to the private nature of investment banks and hedge funds. This projects aims to review the literature and discuss the models available in a subject that publications are scarce and infrequently. We review the basic and fundamental mathematical concepts needed for modeling financial markets such as: stochastic processes, stochastic integration and basic models for prices and spreads dynamics necessary for building quantitative strategies. We also contrast these models with real market data with minutely sampling frequency from the Dow Jones Industrial Average (DJIA). Quantitative strategies try to exploit two types of behavior: trend following or mean reversion. The former is grouped in the so-called technical models and the later in the so-called pairs trading. Technical models have been discarded by financial theoreticians but we show that they can be properly cast into a well defined scientific predictor if the signal generated by them pass the test of being a Markov time. That is, we can tell if the signal has occurred or not by examining the information up to the current time; or more technically, if the event is F_t-measurable. On the other hand the concept of pairs trading or market neutral strategy is fairly simple. However it can be cast in a variety of mathematical models ranging from a method based on a simple euclidean distance, in a co-integration framework or involving stochastic differential equations such as the well-known Ornstein-Uhlenbeck mean reversal ODE and its variations. A model for forecasting any economic or financial magnitude could be properly defined with scientific rigor but it could also lack of any economical value and be considered useless from a practical point of view. This is why this project could not be complete without a backtesting of the mentioned strategies. Conducting a useful and realistic backtesting is by no means a trivial exercise since the \laws" that govern financial markets are constantly evolving in time. This is the reason because we make emphasis in the calibration process of the strategies' parameters to adapt the given market conditions. We find out that the parameters from technical models are more volatile than their counterpart form market neutral strategies and calibration must be done in a high-frequency sampling manner to constantly track the currently market situation. As a whole, the goal of this project is to provide an overview of a quantitative approach to investment reviewing basic strategies and illustrating them by means of a back-testing with real financial market data. The sources of the data used in this project are Bloomberg for intraday time series and Yahoo! for daily prices. All numeric computations and graphics used and shown in this project were implemented in MATLAB^R scratch from scratch as a part of this thesis. No other mathematical or statistical software was used.

Stochastic optimal bid to electricity markets with environmental risk constraints

There are many factors that influence the day-ahead market bidding strategies of a generation company (GenCo) in the current energy market framework. Environmental policy issues have become more and more important for fossil-fuelled power plants and they have to be considered in their management, giving rise to emission limitations. This work allows to investigate the influence of both the allowances and emission reduction plan, and the incorporation of the derivatives medium-term commitments in the optimal generation bidding strategy to the day-ahead electricity market. Two different technologies have been considered: the coal thermal units, high-emission technology, and the combined cycle gas turbine units, low-emission technology. The Iberian Electricity Market and the Spanish National Emissions and Allocation Plans are the framework to deal with the environmental issues in the day-ahead market bidding strategies. To address emission limitations, some of the standard risk management methodologies developed for financial markets, such as Value-at-Risk (VaR) and Conditional Value-at-Risk (CVaR), have been extended. This study offers to electricity generation utilities a mathematical model to determinate the individual optimal generation bid to the wholesale electricity market, for each one of their generation units that maximizes the long-run profits of the utility abiding by the Iberian Electricity Market rules, the environmental restrictions set by the EU Emission Trading Scheme, as well as the restrictions set by the Spanish National Emissions Reduction Plan. The economic implications for a GenCo of including the environmental restrictions of these National Plans are analyzed and the most remarkable results will be presented.

Il Discorso dell'amore verso la patria (1631) di Ludovico Zuccolo

Scopo di questo studio è la disamina e la divulgazione dei pregi letterari e del valore concettualmente innovativo del Discorso dell 'amore verso la patria di Ludovico Zuccolo. L'analisi dei contenuti dell'opera, unitamente alla puntualizzazione delle sue caratteristiche formali e stilistiche, permette di vedere come questo scrittore proponga, utilizzando la forma letteraria del discorso politico, una riuscita codificazione della tematica dei diritti e dei doveri dei cittadini verso la patria; operazione in cui si sostanzia, a mio avviso, l'apporto innovativo dello Zuccolo. Dopo l'iniziale riscoperta, da parte di Benedetto Croce, del capitolo delle Considerazioni sulla Ragion di Stato, l`opera dello Zuccolo ha generato un certo interesse critico fra gli studiosi di letteratura politica del "900" senza tuttavia divenire oggetto di contributi esaustivi malgrado, a nostro parere, la presenza di elementi di originalità di pensiero nel Discorso dell 'amore verso la patria. Inoltre, l'opinione degli specialisti non è mai stata unanime riguardo al valore e ai contenuti delle opere di questo autore. Se per il Croce, ne << La Critica >> del 1926, egli appare come colui che ha prodotto, «Lo scritto più acuto e originale sull'argomento [della Ragion di Stato], composto in quel seco1o.>> (p. 301), per altri egli si presenta come un dotto estensore di trattati politici nei quali sfoggia abilmente la sua erudizione classica e Luigi Firpo arriva a suggerire addirittura che lo Zuccolo sia colpevole di plagio proprio laddove tratta il tema della Ragion di Stato : Al punto in cui siamo, una cosa è certa, e cioè che i conti non tornano : non riesco a credere che uno scrittore inzeppi centinaia e centinaia di pagine di luoghi comuni, di erudizione d"accatto, di oziosità accademiche, e poi un bel mattino, morso dalla tarantola o baciato in fronte da Minerva, metta in carta il piccolo capolavoro, le pagine meditate e profonde, e perciò lungamente soffeite, che pure gli appartengono per una paternità incontestata e certa. Dico questo, perché in un caso del genere, non al miracolo s"avrebbe da credere, ma, semmai, al plagio. (1). Catherine Pitiot, nel suo saggio La retorica politica nell 'opera utopica di Ludovico Zuccolo, coglie invece in questo autore unicamente l"utopista che << lntende allontanarsi dalla realtà contemporanea per modificarla, correggerla e presentare un'in1magine che sia fondamentalmente diversa, a livello strutturale. >> (2). Di parere diametralmente opposto Rodolfo de Mattei, che attribuisce allo Zuccolo lo status di anti-utopista per eccellenza, tipico di uno scrittore che, Non ha voluto usufruire della facile libertà della fantasia per sovvertire l'ordine storico e per alterare arbitrariamente la natura umana, cioé per proporre un ordinamento mirante ad una radicale trasformazione della società e quindi di assai dubbia realizzazione. (3). Altri studiosi, fra cui Bruno Nediani, si sono dedicati alla descrizione della personalità dello Zuccolo, attingendo alle sue lettere - che lo stesso Nediani ha riscoperto - oltre che ai brevi accermi che di sé fa lo Zuccolo negli scritti. Dal saggio del Nediani, La personalità di Ludovico Zuccolo (1969), emerge la figura di un uomo tormentato e insoddisfatto, ossessionato dal sospetto dell"autorità ecclesiastica, costretto a procacciarsi impieghi inadeguati presso i potenti, all'inseguimento dell'obiettivo di una carriera che, comunque, finisce con il risultargli sempre, prima o poi, insopportabile. Più recentemente, Sergio Bertelli, nel suo contributo alla Storia della letteratura di Cecchi e Sapegno, ha aperto una nuova prospettiva sullo Zuccolo proponendolo come colui che, Spezza finalmente il cerchio moralistico costruito dal Botero attorno al pensiero machiavelliano e la ragion di stato cessa di essere giudicata vera o falsa, buona o malvagia, interessando in sé e per sé, cioé nei suoi presupposti e nei suoi fini esclusivamente politici. (4).