Influence of HAART on Alternative Reading Frame Immune Responses over the Course of HIV-1 Infection

Background: Translational errors can result in bypassing of the main viral protein reading frames and the production of alternate reading frame (ARF) or cryptic peptides. Within HIV, there are many such ARFs in both sense and the antisense directions of transcription. These ARFs have the potential to generate immunogenic peptides called cryptic epitopes (CE). Both antiretroviral drug therapy and the immune system exert a mutational pressure on HIV-1. Immune pressure exerted by ARF CD8(+) T cells on the virus has already been observed in vitro. HAART has also been described to select HIV-1 variants for drug escape mutations. Since the mutational pressure exerted on one location of the HIV-1 genome can potentially affect the 3 reading frames, we hypothesized that ARF responses would be affected by this drug pressure in vivo. Methodology/Principal findings: In this study we identified new ARFs derived from sense and antisense transcription of HIV-1. Many of these ARFs are detectable in circulating viral proteins. They are predominantly found in the HIV-1 env nucleotide region. We measured T cell responses to 199 HIV-1 CE encoded within 13 sense and 34 antisense HIV-1 ARFs. We were able to observe that these ARF responses are more frequent and of greater magnitude in chronically infected individuals compared to acutely infected patients, and in patients on HAART, the breadth of ARF responses increased. Conclusions/Significance: These results have implications for vaccine design and unveil the existence of potential new epitopes that could be included as vaccine targets.

Aesthetic analysis of an implant-supported denture at the cleft area

Objective: To evaluate the aesthetics of an implant-supported denture at the cleft area, comparing the peri-implant tissues and prosthetic crown with the contralateral tooth. Settings: Hospital for Rehabilitation of Craniofacial Anomalies, Bauru, São Paolo, Brazil. Patients: A total of 39 individuals of both genders, with complete unilateral cleft lip and palate, who received secondary alveolar bone graft and were rehabilitated with single implant-supported dentures at the area of the missing maxillary lateral incisor after completion of orthodontic treatment. Interventions: The following parameters were analyzed in follow-up sessions: length and width of prosthetic crown and contralateral tooth, characteristics of implants, filling of interproximal space by the papilla, and smile height of the patients. Results: The implant-supported prosthetic crowns were longer than the contralateral tooth (p < .001). Among the 78 papillae analyzed, 29 (37.17%) received a score of 3; 32 (41.02%) papillae had a score of 2; and 17 (21.79%) received a score of 1. Concerning the smile height, among the 39 patients analyzed, 23 (56.41%) had a medium smile, 15 (38.46%) had a high smile, and two (5.12%) presented a low smile. Conclusion: The use of dental implants to rehabilitate the edentulous cleft area is an excellent option. However, adequate evaluation of the bone quantity and quality, positioning and shape of adjacent teeth, smile height, and patient expectations should be considered to achieve success and avoid aesthetic deformities such as elongated teeth and absence of gingival papillae.

Análise do conforto térmico na obra de João Filgueiras Lima, Lelé: Hospitais Sarah de Salvador e do Rio de Janeiro

Estratégias passivas de projeto reduzem significativamente o uso de ar condicionado e melhoram o conforto térmico dos usuários. Isto pode ser ilustrado através dos hospitais da Rede Sarah Kubitschek projetados pelo arquiteto João Filgueiras Lima, Lelé, cujas soluções além de propiciarem ambientes mais agradáveis e salubres, evitam o uso de sistemas mecânicos de resfriamento, reduzindo o consumo de energia elétrica. Deste modo, o presente artigo tem como objetivo avaliar o conforto térmico dos hospitais Sarah de Salvador e do Rio de Janeiro, através de medições in loco da temperatura do ar, umidade relativa do ar e velocidade do ar. A análise dos resultados foi baseada em leituras de projeto, na norma ASHRAE Standard 55/2004 e em parâmetros adquiridos na literatura especializada. Os resultados demonstram a preocupação de Lelé na incorporação de aspectos bioclimáticos nos projetos. No Sarah - Salvador, alguns ambientes permaneceram fora da zona de conforto no período do meio dia, devido ao ganho de calor pela cobertura. No entanto, o uso da ventilação natural auxilia no efeito de resfriamento, melhorando o conforto térmico nos espaços internos. Já no Sarah - Rio, todos os ambientes permanecem dentro da zona de conforto proposta pela ASHRAE 55.

Minori rumeni tra percorsi migratori e rappresentazioni. Nè soli, nè accompagnati a Bologna

The thesis deals with the heterogenous category of the “unaccompanied minors”, concentrating the scientific work on those who migrate from Romania to the Italian city of Bologna. Between different migratory routes that include Romanian minors, I chose to explore the ones linked with the underground and illegal contexts. In order to analyse the reasons and the morphology of their migratory career, I used the multisituated field research which allowed me to consider the social policies in both the Romanian and the Italian environment. The main debate on the situation of the “unaccompanied children” refers to the extent to which these minors leave their country of origin “accompanied” by different adult figures and it also involves the role played by these adults. The first chapter is dedicated to a brief theoretical and methodological introduction to the main arguments of the thesis such as Romanian migration to Italy, trafficking in human beings, transnationality of migrant’s migration and decentered cooperation as a means of contrasting illegal migration and trafficking. Each field of research is characterized by a specific methodological approach, but they are all linked by the anthropological perspective I adopted throughout the entire work. The Romanian context, analized from a diachronic and a synchronic perspective represents the object of the second chapter. Some aspects of the Regime policies and other characteristics of the Romanian poscomunist period of “transition” are useful frameworks that become a background of the migration flows outside the country. The third chapter focuses on the Romanian patterns of migration. The reconstruction of some past attitudes that Romanians adopted towards migration are relevant in order to reveal the continuity with the present migratory practices. A consistent part is dedicated to a concrete example based on a field research in Bologna on a group of Romanian roma migrating from the south of Romania. The contact with these persons opened a debate on the limits between legal and illegal migration practices among the Romanians. The conclusion is that minors’ migration to Italy follows the adult patterns and flows. The nucleus of the field researches is included in the fourth and the fifth chapter. Before presenting the settings and the itineraries of the field researches, some deconstructive reflections are made on the representations that common sense and social sciences create on concepts as “child”, “minor” and “childhood”. A first perspective on the Romanian migrant minors emerges from a research concentrated on a group of roma teenagers engaged in Bologna in activities like windscreen washing, pocket-picking, begging and street prostitution. The aim of the research was to gain access to their daily life, to observe their relationship with the adults who “accompany” them and the strategies they activate in order to take some material profit out of their migratory experience. A parallel field research focuses on the Romanian minors who are part of the roma group coming from the south of Romania. Most of them are reunited with their family in Bologna, but according to the Italian law, they are all living as illegal migrants. Others are only temporary sheltered by these families and they meanwhile dedicate to illegal survviving practices. An interesting point of my participant observation was to reveal the motivations that these minors give when asked about the refusal to start a legal career inside the local Centres dedicated to the “non accompanied minors”. Their autoreflexivity brings some light on the controversy regarding the adequacy of the local and national care system and the migratory projects the minors have. In this respect, a small part of the research is dedicated to the phenomena of minors’ street prostitution in Bologna, as a useful contribution to the fragmented vision researchers have on the “unaccompanied” or “separated” children. The last chapter focuses on a decentered cooperation project that emerged as an alternative response the local administration from Bologna had chosen for facing the presence of numerous migrants coming from the south of Romania. The group of Romanian roma who was also the object of my field research became the starting point for the cooperation proposals between the city of Bologna and the city of Craiova. Although there are three projects involving the two administrations, throughout a period of stage in the Romanian city of Craiova I chose to analyse, only the one dedicated to the “urgent measures” requested in order to contrast the illegal migration and the trafficking in minors. This final part of the thesis highlightens the possible contribution that such a project might bring to the study of a complex and in some parts contradictory phenomena as that of the “unaccompanied” migrant minors.

Analysis of ion channel stochastic signals for biosensing

In biological world, life of cells is guaranteed by their ability to sense and to respond to a large variety of internal and external stimuli. In particular, excitable cells, like muscle or nerve cells, produce quick depolarizations in response to electrical, mechanical or chemical stimuli: this means that they can change their internal potential through a quick exchange of ions between cytoplasm and the external environment. This can be done thanks to the presence of ion channels, proteins that span the lipid bilayer and act like switches, allowing ionic current to flow opening and shutting in a stochastic way. For a particular class of ion channels, ligand-gated ion channels, the gating processes is strongly influenced by binding between receptive sites located on the channel surface and specific target molecules. These channels, inserted in biomimetic membranes and in presence of a proper electronic system for acquiring and elaborating the electrical signal, could give us the possibility of detecting and quantifying concentrations of specific molecules in complex mixtures from ionic currents across the membrane; in this thesis work, this possibility is investigated. In particular, it reports a description of experiments focused on the creation and the characterization of artificial lipid membranes, the reconstitution of ion channels and the analysis of their electrical and statistical properties. Moreover, after a chapter about the basis of the modelling of the kinetic behaviour of ligand gated ion channels, a possible approach for the estimation of the target molecule concentration, based on a statistical analysis of the ion channel open probability, is proposed. The fifth chapter contains a description of the kinetic characterisation of a ligand gated ion channel: the homomeric α2 isoform of the glycine receptor. It involved both experimental acquisitions and signal analysis. The last chapter represents the conclusions of this thesis, with some remark on the effective performance that may be achieved using ligand gated ion channels as sensing elements.

Transformation von Osteospermum ecklonis mit Konstrukten zur Induktion von Virusresistenz und Blühverfrühung

Für die Etablierung einer Transformationsmethode züchterisch relevanter Sorten von Osteospermum ecklonis (Kapmargerite) wurde zunächst ein geeignetes Protokoll für die Regeneration adventiver Sprosse aus vegetativem Gewebe entwickelt. Anschließend wurden Transformationen von Markergenen durch Kokultur mit Agrobacterium tumefaciens durchgeführt. Hierzu wurden Konstrukte verwendet, die das Gen für ß-D-Glucuronidase (GUS) enthielten und deren Expression in transgenen Pflanzen histochemisch nachgewiesen werden konnte. Kanamycinresistenz erwies sich als geeigneter Selektionsmarker für die Transformation. Es konnten von verschiedenen O. ecklonis Sorten GUS-transgene, nicht-chimäre Pflanzen regeneriert werden.Zur Erzeugung transgener Pflanzen mit dem Ziel der Resistenz gegen LMV (lettuce mosaic potyvirus, Salat Mosaik Virus) wurden drei Konstrukte verwendet. Das erste enthält die kodierende Sequenz der Virusproteine VPg, Pro und 6K2. Durch PCR-Mutation wurde die Proteinase-Schnittstelle zwischen 6K2 und VPg zerstört, sowie Start- und Stopcodon eingeführt. Die anderen LMV-abgeleiteten Konstrukte enthalten nicht translatierbare Fragmente des coat protein Gens in sense und antisense Orientierung.Außerdem wurde O. ecklonis noch mit dem Gen des mutmaßlichen Transkriptionsfaktor SPL3 aus Arabidopsis thaliana unter der Kontrolle eines konstitutiven Promotors transformiert. SPL3 ist an der Regulierung der Blüteninduktion in A. thaliana beteiligt.Regenerierte O. ecklonis wurden durch PCR mit konstruktspezifischen Primern auf Anwesenheit des Transgens und Kontamination durch A. tumefaciens überprüft.

Mixed Mode Fracture Behaviour of Piezoelectric Materials

Piezoelectrics present an interactive electromechanical behaviour that, especially in recent years, has generated much interest since it renders these materials adapt for use in a variety of electronic and industrial applications like sensors, actuators, transducers, smart structures. Both mechanical and electric loads are generally applied on these devices and can cause high concentrations of stress, particularly in proximity of defects or inhomogeneities, such as flaws, cavities or included particles. A thorough understanding of their fracture behaviour is crucial in order to improve their performances and avoid unexpected failures. Therefore, a considerable number of research works have addressed this topic in the last decades. Most of the theoretical studies on this subject find their analytical background in the complex variable formulation of plane anisotropic elasticity. This theoretical approach bases its main origins in the pioneering works of Muskelishvili and Lekhnitskii who obtained the solution of the elastic problem in terms of independent analytic functions of complex variables. In the present work, the expressions of stresses and elastic and electric displacements are obtained as functions of complex potentials through an analytical formulation which is the application to the piezoelectric static case of an approach introduced for orthotropic materials to solve elastodynamics problems. This method can be considered an alternative to other formalisms currently used, like the Stroh’s formalism. The equilibrium equations are reduced to a first order system involving a six-dimensional vector field. After that, a similarity transformation is induced to reach three independent Cauchy-Riemann systems, so justifying the introduction of the complex variable notation. Closed form expressions of near tip stress and displacement fields are therefore obtained. In the theoretical study of cracked piezoelectric bodies, the issue of assigning consistent electric boundary conditions on the crack faces is of central importance and has been addressed by many researchers. Three different boundary conditions are commonly accepted in literature: the permeable, the impermeable and the semipermeable (“exact”) crack model. This thesis takes into considerations all the three models, comparing the results obtained and analysing the effects of the boundary condition choice on the solution. The influence of load biaxiality and of the application of a remote electric field has been studied, pointing out that both can affect to a various extent the stress fields and the angle of initial crack extension, especially when non-singular terms are retained in the expressions of the electro-elastic solution. Furthermore, two different fracture criteria are applied to the piezoelectric case, and their outcomes are compared and discussed. The work is organized as follows: Chapter 1 briefly introduces the fundamental concepts of Fracture Mechanics. Chapter 2 describes plane elasticity formalisms for an anisotropic continuum (Eshelby-Read-Shockley and Stroh) and introduces for the simplified orthotropic case the alternative formalism we want to propose. Chapter 3 outlines the Linear Theory of Piezoelectricity, its basic relations and electro-elastic equations. Chapter 4 introduces the proposed method for obtaining the expressions of stresses and elastic and electric displacements, given as functions of complex potentials. The solution is obtained in close form and non-singular terms are retained as well. Chapter 5 presents several numerical applications aimed at estimating the effect of load biaxiality, electric field, considered permittivity of the crack. Through the application of fracture criteria the influence of the above listed conditions on the response of the system and in particular on the direction of crack branching is thoroughly discussed.

Strukturelle und funktionelle Untersuchungen zur Bedeutung der endogenen retroviralen Insertion HERV-K(C4) im C4-Gen des Menschen

Der Längenpolymorphismus des C4-Gens beruht auf der An- oder Abwesenheit einer 6.4 kb langen Insertion im Intron 9. Es handelt sich dabei um einen eigenständigen bisher noch nicht beschriebenen Virus-Typ, der alle Sequenzmerkmale der Familie der humanen endogenen Retroviren (HERV) trägt und zu den HERV-K Viren gehört. Der Provirus wurde als HERV-K(C4) bezeichnet. Die Orientierung dieses retroviralen Elements ist entgegengesetzt zu der Transkriptionsrichtung des C4-Gens. Mittels RT-PCR, RNase Protection Assays und Northern-Blot Analysen konnte der Nachweis von HERV-K(C4)-Antisense mRNA-Transkripten in verschiedenen humanen Zellinien und Geweben erbracht werden. Die retroviralen Transkripte schlossen am 5'- und 3'-Ende Sequenzen des C4-Exon 9 und Exon 10 ein, so daß diese wahrscheinlich "readthrough" Transkripte darstellen, die durch einen 5' des LTR2 gelegenen Promotor initiiert oder im Zusammenhang mit der C4-Expression transkribiert und reguliert werden. Weiterhin konnten insgesamt 4 HERV-K(C4)-mRNA Spezies, einschließlich einer Vollängen-RNA detektiert werden. Die drei subgenomischen mRNAs werden vermutlich durch einfaches und mehrfaches Spleißen generiert. Die quantitative Analyse in verschiedenen humanen Zellinien ergab, daß HERV-K(C4) durchschnittlich mit einer Kopienanzahl zwischen ca.1 bis 100 Transkripten in einer Zelle vorkommt, so daß es sich um low abundance mRNAs handelt. Mittels eines Reportergen-System konnte eine Aktivität des LTR2-Promotors in der Sense-Orientierung des Retrovirus nachgewiesen werden, die nach Stimulation mit IFN- signifikant abnahm. Ein humanes Modell-Systems wurde etabliert, um die Theorie einer Antisense-Abwehr gegen exogene Retroviren in HepG2-Zellen zu überprüfen. Die Theorie basiert auf dem Nachweis von HERV-K(C4)-Antisense-Transkripten, die über eine Heteroduplexbildung mit der Sense-mRNA von verwandten, infektiösen Retroviren eine mögliche Blockierung deren Translation erwirken könnten. Es konnte eine signifikante Abnahme der retroviralen Expression von bis zu 45% nach steigenden Dosen an IFN- in HepG2-Zellen nachgewiesen werden. Der funktionell aktive 3'-LTR-Sense Promotor sowie der Nachweis von HERV-K(C4)-Antisense Transkripten sprechen für die bedeutende Rolle von HERV-K(C4) bei der Genregulation und Schutz gegen exogene Retroviren, wodurch eine Selektion stattgefunden hat.

Der implizite Bewußtseinsinhalt in der Phänomenologie und der analytischen Philosophie

Die vorliegende Arbeit wurde durch die Erkenntnis motiviert, daß die Theorie der Intentionalität ohne eine Theorie der impliziten Intentionalität unvollständig ist. Die Anlage einer solchen Theorie gründet in der Annahme, daß die impliziten ("ergänzenden oder "mit-bewußten") Erfahrungsinhalte Inhalte intentional wirksam sind: daß sie zur "Konstitution" der intentionalen Objekte – im Sinne vom Husserl und Gurwitsch – beitragen. Die Bedingungen und Umstände dieser Wirksamkeit herauszuarbeiten, ist das Hauptziel der vorliegenden Untersuchungen. Dazu wurde (1) eine phänomenologische Theorie des impliziten Inhalts kritisch expliziert, und (2) diese anhand einiger aktueller Ansätze der analytischen Philosophie auf die Probe gestellt. Im phänomenologischen Teil der Arbeit wurden zuerst die methodologischen Voraussetzungen von Gurwitschs gestalttheoretischer Neuformulierung des Husserlschen Projekts unter Berücksichtigung der sogenannten Konstanzannahme kritisch untersucht. Weiterhin wurden Husserls Noema-Konzeption und seine Horizontlehre aus der Perspektive von Gurwitschs Feldtheorie des Bewußtseins expliziert, und in der Folge Gurwitschs dreifache Gliederung des Bewußtseinsfeldes – das Kopräsenz-Kohärenz-Relevanz-Schema – um die phänomenologischen Begriffe "Potentialität", "Typik" und "Motivation" erweitert. Die Beziehungen, die diesen Begriffen zugrunde liegen, erwiesen sich als "mehr denn bloß kontigent, aber als weniger denn logisch oder notwendig" (Mulligan). An Beispielen aus der analytischen Philosphie der Wahrnehmung (Dretske, Peacocke, Dennett, Kelly) und der Sprache (Sperber, Wilson, Searle) wurde das phänomenologische Konzept des impliziten Inhalts kritisch beurteilt und weiterentwickelt. Hierbei wurde(n) unter anderem (1) der Zusammenhang zwischen dem phänomenologischen Begriff "vorprädikativer Inhalt" und dem analytischen Begriff "nichtkonzeptueller Inhalt" aufgezeigt und (2) Kriterien für die Zuschreibung impliziter Überzeugungen in den typischen Fällen der prädikativen Intentionalität zusammengetragen und systematisiert.

La salute detenuta: tra diritto e sicurezza”. Un’ indagine nella Casa Circondariale di Rimini.

The survey approachs the issue of health and the problem of its effective protection in a context of deprivation of liberty and coercion, which is the prison. The theoretical reflection born from the reform of the Legislative Decree 230/99 which marked the transition from an employee by the Prison Health within prison a fully integrated in the National Health Service. The comparison between an institution of health promotion and institution of punishment which may operate on the same subject held produces multiple attrits, making their relationship problematic. The work shows the daily difficulties in the management of prison health within the institution, physician-patient between different health care roles, and between the latter and prison workers. The coexistence, in fact, is not always harmonious though quite often it is common sense and the willingness of operators to reduce barriers: overcrowding, limited resources and insufficient staff make the application of the rule and therefore the right to goal a difficult to be pursued. It is designed for a scheme of semi-structured interview essay is divided into 3 sections covering: "staff and its functions", "health reform" and "health of the prisoner"; questions were directed to doctors, nurses and psychologists engaged inside the prison of Rimini with the specific aim of examining the ambivalent relationship between the demand for health care in prisons and the need for security and a clear - albeit partial - point of view. We tried to reconstruct the situation of prison health care through the perception of prison operators, capturing the problematic issues that deal on both issues is instrumental to the experience of persons detained by analyzing, in terms of operators , what happens inside of a prison institution in everyday health care.

Chitosan based hydrogels for transmucosal drug delivery

The aim of this thesis was the formulation of new chitosan based delivery systems for transmucosal drug administration. Transmucosal routes, such as buccal, vaginal and nasal routes, allow the circumvention of the hepatic first pass metabolism and avoid the gastrointestinal chemical and enzymatic degradations. Moreover, transmucosal drug administration can allow to avoid pain or discomfort caused by injections, when drugs are administered through parenteral routes, thus increasing patient compliance. On the other side, the major disadvantage of transmucosal drug administration is represented by the presence of biological fluids and mucus that can remove drug systems from the application site, thus reducing the contact time between drug and mucosa and consequently, decreasing drug bioavailability. For this reason, in this study, the investigation of chitosan delivery systems as mucoadhesive formulations able to increase drugs residence time and to improve their bioavailability, was taken into account. In the paper 1, buccal films based on chitosan-gelatin complexes were prepared and loaded with propranolol hydrochloride. The complexes were characterized and studied in order to evaluate their physical- chemical properties and their ability to release the drug and to allow its permeation through buccal mucosa. In the paper 2, vaginal inserts based on chitosan/alginate complexes were formulated for local delivery of chlorhexidine digluconate. Tests to evaluate the interaction between the polymers and to study drug release properties were performed, as well as the determination of antimicrobial activity against the patogens responsible of vaginitis and candidosis. In the project 3, chitosan based nanoparticles containing cyclodextrin and other excipients, with the capacity to modify insulin bioavailabity were formulated for insulin nasal delivery. Nanoparticles were characterized in terms of size, stability and drug release. Moreover, in vivo tests were performed in order to study the hypoglycemic reduction in rats blood samples.

Ricostruzione mandibolare con tecnologia CAD-CAM

L’obbiettivo di una ricostruzione micro vascolare di mandibola è quello di assicurare al paziente il miglior risultato estetico e funzionale auspicabile. Ciò può essere conseguito utilizzando il lembo microvascolare di perone/cresta iliaca e una placca ricostruttiva in titanio che funga da guida nella fase di modellamento del lembo per ricreare un contorno parabolico il più possibile simile al profilo mandibolare originario del paziente. Il modellamento manuale ed artigianale intraoperatorio di una placca ricostruttiva è operatore dipendente ed anche in mani molto abili o ricorrendo a modelli anatomici stereolitografici non sempre risulta preciso quanto voluto e spesso non porta ai risultati postoperatori attesi e desiderati. Obbiettivo del nostro studio è stato pertanto, sfruttando le moderne tecnologie CAD-CAM, la produzione di placche ricostruttive “custom -made” progettate direttamente al computer ricreanti il profilo osseo originale del paziente.

Procedimento legislativo e qualita' della legislazione. Criticita' e prospettive

La tesi riprende un tema che è stato oggetto in passato di studi anche molto approfonditi; oggi sembra essere tornato alla ribalta grazie ad alcuni contributi che hanno nuovamente stimolato la dottrina a confrontarsi su aspetti così delicati anche alla luce della crisi economica. E'stato da sempre rilevato che la buona scrittura delle norme è un fattore fondamentale per il rilancio dell’economia del paese, per la semplificazione e per garantire ordine, coerenza e chiarezza all’ordinamento giuridico. La prima parte è incentrata su una ricostruzione storica e giuridica delle fonti che hanno disciplinato le “regole per la qualità delle regole”, oltre ad una panoramica della dottrina che si è occupata in passato del tema. Segue l’individuazione specifica di quali sono le regole formali e sostanziali di drafting. In particolare, una parte è dedicata alla giurisprudenza costituzionale per comprendere se esiste o meno un aggancio per la Corte Costituzionale da permetterle il sindacato sulle “regole oscure” e dichiararle illegittime. La seconda parte analizza le pressai, in particolare si è scelto di analizzare il rapporto tra Governo e Parlamento nelle problematiche principali che attengono al procedimento legislativo e alla cornice entro la quale viene esplicato in relazione alla decretazione d’urgenza, maxiemendamenti, questione di fiducia, istruttoria in commissione, gruppi di pressione. Ciò che è stato rilevato, è una scarsa aderenza ai principi e ai criteri di better regulation, peraltro difficilmente giustiziabili da parte della Corte costituzionale e sottratti al controllo di chi, al contrario, ha competenza in questo settore, ossia il Comitato per la legislazione e il DAGL. Le conclusioni, pertanto, prendono le mosse da una serie di criticità rilevate e tentano di tracciare una strada da percorrere che sia rispettosa dei canoni della “better regulation” anche alla luce delle riforme costituzionali e dei regolamenti parlamentari in corso di approvazione.

Integration of a simulation platform for electrical mobility within the arrowhead interoperability framework

This dissertation document deals with the development of a project, over a span of more than two years, carried out within the scope of the Arrowhead Framework and which bears my personal contribution in several sections. The final part of the project took place during a visiting period at the university of Luleå. The Arrowhead Project is an European project, belonging to the ARTEMIS association, which aims to foster new technologies and unify the access to them into an unique framework. Such technologies include the Internet of Things phe- nomenon, Smart Houses, Electrical Mobility and renewable energy production. An application is considered compliant with such framework when it respects the Service Oriented Architecture paradigm and it is able to interact with a set of defined components called Arrowhead Core Services. My personal contribution to this project is given by the development of several user-friendly API, published in the project's main repository, and the integration of a legacy system within the Arrowhead Framework. The implementation of this legacy system was initiated by me in 2012 and, after many improvements carried out by several developers in UniBO, it has been again significantly modified this year in order to achieve compatibility. The system consists of a simulation of an urban scenario where a certain amount of electrical vehicles are traveling along their specified routes. The vehicles are con-suming their battery and, thus, need to recharge at the charging stations. The electrical vehicles need to use a reservation mechanism to be able to recharge and avoid waiting lines, due to the long recharge process. The integration with the above mentioned framework consists in the publication of the services that the system provides to the end users through the instantiation of several Arrowhead Service Producers, together with a demo Arrowhead- compliant client application able to consume such services.

Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists

Despite the fact that consensus guidelines recommend long-term dopamine agonist (DA) therapy as a first-line approach to the treatment of small prolactinoma, some patients continue to prefer a primary surgical approach. Concerns over potential adverse effects of long-term medical therapy and/or the desire to become pregnant and avoid long-term medication are often mentioned as reasons to pursue surgical removal. In this retrospective study, 34 consecutive patients (30 female, 4 male) preferably underwent primary pituitary surgery without prior DA treatment for small prolactinomas (microprolactinoma 1-10 mm, macroprolactinoma 11-20 mm) at the Department of Neurosurgery, University of Bern, Switzerland. At the time of diagnosis, 31 of 34 patients (91%) presented with symptoms. Patients with microprolactinomas had significantly lower preoperative prolactin (PRL) levels compared to patients with macroprolactinomas (median 143 μg/l vs. 340 μg/l). Ninety percent of symptomatic patients experienced significant improvement of their signs and symptoms upon surgery. The postoperative PRL levels (median 3.45 μg/l) returned to normal in 94% of patients with small prolactinomas. There was no mortality and no major morbidities. One patient suffered from hypogonadotropic hypogonadism after surgery despite postoperative normal PRL levels. Long-term remission was achieved in 22 of 24 patients (91%) with microprolactinomas, and in 8 of 10 patients (80%) with macroprolactinomas after a median follow-up period of 33.5 months. Patients with small prolactinomas can safely consider pituitary surgery in a specialized centre with good chance of long-term remission as an alternative to long-term DA therapy.