Alkylidene malonates and acetoacetates as intermediates for the preparation of bioactive molecules

In this thesis we investigated the versatility and the potential applications of different kinds of alkylidene malonates, acetoacetates, malonamides and acetoacetoamides. Our research group devoted great attention to this kind of compounds since alkylidenes can be considered important intermediates in the synthesis of several scaffolds, to be inserted into molecules of potential biological and pharmaceutical interest. The increasing use of alkylidenes is due to their ability to react as unsaturated electrophiles and to the possibility to exploit them as intermediates for the introduction of different kind of functionalities.The preparation of alkylidene malonates, acetoacetates, malonamides and acetoacetoamides is presented in chapter 1. This section deals with different preparation methods of alkylidenes that we developed during the last few years and to the technologies involved for each synthetic protocol. The reactivity that allowed to use the alkylidenes as intermediates in the synthesis of scaffolds for biologically active compounds is shown in chapter 2. In particular, we will discuss the most important reactions used to obtain the desired molecules, and we will focus on the most interesting aspects of these latter ones. Finally, chapter 3 will illustrate the potential applications and the related syntheses of potential bioactive compounds. The synthesized molecules find application in several fields and for this reason we considered each class of compounds in its related branch of interest.

Behaviour and applications of elastic waves in structures and metamaterials

The present thesis focuses on elastic waves behaviour in ordinary structures as well as in acousto-elastic metamaterials via numerical and experimental applications. After a brief introduction on the behaviour of elastic guided waves in the framework of non-destructive evaluation (NDE) and structural health monitoring (SHM) and on the study of elastic waves propagation in acousto-elastic metamaterials, dispersion curves for thin-walled beams and arbitrary cross-section waveguides are extracted via Semi-Analytical Finite Element (SAFE) methods. Thus, a novel strategy tackling signal dispersion to locate defects in irregular waveguides is proposed and numerically validated. Finally, a time-reversal and laser-vibrometry based procedure for impact location is numerically and experimentally tested. In the second part, an introduction and a brief review of the basic definitions necessary to describe acousto-elastic metamaterials is provided. A numerical approach to extract dispersion properties in such structures is highlighted. Afterwards, solid-solid and solid-fluid phononic systems are discussed via numerical applications. In particular, band structures and transmission power spectra are predicted for 1P-2D, 2P-2D and 2P-3D phononic systems. In addition, attenuation bands in the ultrasonic as well as in the sonic frequency regimes are experimentally investigated. In the experimental validation, PZTs in a pitch-catch configuration and laser vibrometric measurements are performed on a PVC phononic plate in the ultrasonic frequency range and sound insulation index is computed for a 2P-3D phononic barrier in the sonic frequency range. In both cases the numerical-experimental results comparison confirms the existence of the numerical predicted band-gaps. Finally, the feasibility of an innovative passive isolation strategy based on giant elastic metamaterials is numerically proved to be practical for civil structures. In particular, attenuation of seismic waves is demonstrated via finite elements analyses. Further, a parametric study shows that depending on the soil properties, such an earthquake-proof barrier could lead to significant reduction of the superstructure displacement.

Valutazione della stima della traiettoria dell'elettrodo in seno coronarico in pazienti sottoposti a terapia di resincronizzazione cardiaca

La tesi tratta della mancata efficacia della terapia di resincronizzazione cardiaca e valuta un metodo per poterne predire la futura efficacia o meno. Si propone ciò studiando la traiettoria 3D dell'elettrodo in seno coronarico e analizzando se le variazioni che la caratterizzano possono essere indicative di una futura risposta positiva alla terapia. Sono inoltre state apportate alcune modifiche al programma Matlab che ricostruisce la traiettoria 3D per eliminare alcune approssimazioni.

Traduzione di un itinerario turistico: viaggio alla scoperta della Bologna dei canali

Lo scopo della seguente tesi è di presentare la traduzione di un capitolo della guida turistica “Sight-walking Bologna: Dalla parte della città”, dedicata al capoluogo emiliano. La guida propone diversi itinerari a tema, tutti inediti e di particolare interesse; quello che ho scelto è dedicato alla riscoperta dei canali sotterranei che attraversano la città ed è ricco di cenni storico-artistici e curiosità. Lo completano due ricette tipiche della cucina bolognese. A spingermi a scegliere questo tema è stato l’amore per la mia città, Bologna, e il desiderio di promuoverne ad un pubblico di lingua tedesca un aspetto che, nonostante l’impegno delle autorità e delle associazioni cittadine, è ancora poco conosciuto: il mondo sotterraneo nascosto nel suo “ventre”. Questa esperienza è stata estremamente utile e stimolante perché mi ha dato la possibilità di mettere in pratica le nozioni teoriche acquisite durante questi anni di studio nonché di migliorare la mia padronanza e naturalezza nell’uso della lingua tedesca. In secondo luogo mi ha consentito di conoscere meglio la storia della mia città e di guardarla con occhi diversi. Il mio lavoro si sviluppa in quattro capitoli. Nel primo e nel secondo capitolo vengono presentate le principali caratteristiche, rispettivamente, della guida turistica come tipo testuale e del testo specifico di cui mi sono occupata, con riferimento agli studi di Christiane Nord, Katharina Reiss e Mary Snell-Hornby. Il terzo capitolo contiene la mia proposta di traduzione e il quarto capitolo è invece dedicato all’analisi delle principali difficoltà incontrate nel processo traduttivo e alle strategie adottate per risolverle.

La traduzione audiovisiva: Teoria e pratica della sottotitolazione applicate al cortometraggio "Diez minutos"

L'elaborato consiste in una sottotitolazione, dallo spagnolo verso l'italiano, del cortometraggio spagnolo "Diez minutos". La parte pratica precede una parte teorica sulla traduzione audiovisiva in generale, con particolare attenzione alla sottotitolazione.

Presentazioni di gruppi con generatori e relazioni

La struttura di gruppo è una delle strutture algebriche più semplici e importanti della matematica. Un gruppo si può descrivere in vari modi: uno dei più interessanti è la presentazione per generatori e relazioni. Sostanzialmente presentare un gruppo per generatori e relazioni significa dire quali specifiche ”regole di calcolo” e semplificazione valgono nel gruppo in considerazione oltre a quelle che derivano dagli assiomi di gruppo. Questo porta in particolare alla definizione di gruppo libero. Un gruppo libero non ha regole di calcolo oltre quelle derivanti dagli assiomi di gruppo. Ogni gruppo è un quoziente di un gruppo libero su un appropriato insieme di generatori per un sottogruppo normale, generato dalle relazioni. In questa tesi si ricordano le definizioni più importanti ed elementari della teoria dei gruppi e si passa in seguito a discutere il gruppo libero e le presentazioni di gruppi con generatori e relazioni, dando alcuni esempi. La tesi si conclude illustrando l’algoritmo di Coxeter e Todd, per enumerare le classi laterali di un sottogruppo quando si ha un gruppo presentato per generatori e relazioni.

Step-by-step: Riqualificare per fasi l'edilizia sociale. Intervento a Bologna, quartiere pilastro

Il progetto di tesi è focalizzato sulla riqualificazione di un edificio di edilizia sociale situato nel quartiere Pilastro di Bologna. La tesi intende operare su due fronti, gli spazi chiusi e - Migliorare l’efficienza energetica dell’edificio, gli spazi aperti: considerando che la proprietà frazionata che caratterizza il contesto richiede soluzioni non unitarie ma “a pezzi” nel corso del tempo e in base alla volontà dei proprietari; - Riqualificare gli spazi esterni mettendo in relazione due registri: quello qualitativo/percettivo e quello del comfort esterno come mezzo per limitare le ricadute sugli ambienti interni agli edifici.

A musica une e ensina: o projeto DIRE FARE MUSICARE de Raffaele Maltoni

Abstract Il presente elaborato espone una proposta di traduzione in portoghese del libro DIRE FARE MUSICARE dell’autore italiano Raffaele Maltoni. Il libro contiene 15 canzoni che accompagnano varie attività musicali, motorie e ludiche. Charly, il simpatico mostro viola, guida i bambini durante il percorso musicale. All’introduzione sul genere della letteratura infantile e sull’importanza della musica nell’apprendimento, segue un analisi del testo e un commento alla traduzione. Sinopse O presente trabalho apresenta uma proposta de tradução em português do livro DIRE FARE MUSICARE do autor italiano Raffaele Maltoni. O livro contem 15 canções que acompanham atividades musicais, motoras e lúdicas. Charly, o simpático monstro violeta, acompanha as crianças ao longo do percurso musical. À introdução sobre o género da literatura infantil e sobre a importância da música na aprendizagem, segue uma analise do texto e um comentário à tradução.

Documentare gli incidenti omofobici e transfobici: Traduzione dall'inglese in italiano di un manuale informativo di ilga-europe.

The aim of this dissertation is to provide a translation from English into Italian of a handbook published online by the non-governmental organization Ilga-Europe, which aims to strengthen human rights and equality for LGBTI people at European level. Translating the whole handbook was not possible for this project, this is the reason why I decided to translate the introduction, the first chapter and one of the three appendices listed in the handbook. This work is divided into six chapters. The first one introduces the main themes of the text, i.e. what does the acronym LGBT stands for, the issue of homophobia and the measures taken against it at international and national level. The second one provides a description of the three organizations ILGA, ILGA-Europe and Arcigay, focusing on their roles and purposes. The third chapter contains the description of specialized languages, with special attention to the juridical one; moreover, it provides an analysis of the text type. The fourth chapter focuses on the resources used to translate this text. The fifth chapter includes the source text, alongside with its actual translation. Finally, the sixth and last chapter offers a detailed comment on translation difficulties and translation choices.

The role of the interplay between polymer architecture and bacterial surface properties on the microbial adhesion to polyoxazoline-based ultrathin films

Surface platforms were engineered from poly(L-lysine)-graft-poly(2-methyl-2-oxazoline) (PLL-g-PMOXA) copolymers to study the mechanisms involved in the non-specific adhesion of Escherichia coli (E. coli) bacteria. Copolymers with three different grafting densities (PMOXA chains/Lysine residue of 0.09, 0.33 and 0.56) were synthesized and assembled on niobia (Nb O ) surfaces. PLL-modified and bare niobia surfaces served as controls. To evaluate the impact of fimbriae expression on the bacterial adhesion, the surfaces were exposed to genetically engineered E. coli strains either lacking, or constitutively expressing type 1 fimbriae. The bacterial adhesion was strongly influenced by the presence of bacterial fimbriae. Non-fimbriated bacteria behaved like hard, charged particles whose adhesion was dependent on surface charge and ionic strength of the media. In contrast, bacteria expressing type 1 fimbriae adhered to the substrates independent of surface charge and ionic strength, and adhesion was mediated by non-specific van der Waals and hydrophobic interactions of the proteins at the fimbrial tip. Adsorbed polymer mass, average surface density of the PMOXA chains, and thickness of the copolymer films were quantified by optical waveguide lightmode spectroscopy (OWLS) and variable-angle spectroscopic ellipsometry (VASE), whereas the lateral homogeneity was probed by time-of-flight secondary ion mass spectrometry (ToF-SIMS). Streaming current measurements provided information on the charge formation of the polymer-coated and the bare niobia surfaces. The adhesion of both bacterial strains could be efficiently inhibited by the copolymer film only with a grafting density of 0.33 characterized by the highest PMOXA chain surface density and a surface potential close to zero.

Multiplex suspension array for human anti-carbohydrate antibody profiling

Glycan-binding antibodies form a significant subpopulation of both natural and acquired antibodies and play an important role in various immune processes. They are for example involved in innate immune responses, cancer, autoimmune diseases, and neurological disorders. In the present study, a microsphere-based flow-cytometric immunoassay (suspension array) was applied for multiplexed detection of glycan-binding antibodies in human serum. Several approaches for immobilization of glycoconjugates onto commercially available fluorescent microspheres were compared, and as the result, the design based on coupling of end-biotinylated glycopolymers has been selected. This method requires only minute amounts of glycans, similar to a printed glycan microarray. The resulting glyco-microspheres were used for detection of IgM and IgG antibodies directed against ABO blood group antigens. The possibility of multiplexing this assay was demonstrated with mixtures of microspheres modified with six different ABO related glycans. Multiplexed detection of anti-glycan IgM and IgG correlated well with singleplex assays (Pearson's correlation coefficient r = 0.95-0.99 for sera of different blood groups). The suspension array in singleplex format for A/B trisaccharide, H(di) and Le(x) microspheres corresponded well to the standard ELISA (r > 0.94). Therefore, the described method is promising for rapid, sensitive, and reproducible detection of anti-glycan antibodies in a multiplexed format.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Genome-wide association study in German patients with attention deficit/hyperactivity disorder

The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 × 10(-7)) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values ≤ 7.57 × 10(-5) ) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD.

Common obesity risk alleles in childhood attention-deficit/hyperactivity disorder

Children with attention-deficit/hyperactivity disorder (ADHD) have a higher rate of obesity than children without ADHD. Obesity risk alleles may overlap with those relevant for ADHD. We examined whether risk alleles for an increased body mass index (BMI) are associated with ADHD and related quantitative traits (inattention and hyperactivity/impulsivity). We screened 32 obesity risk alleles of single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) for ADHD based on 495 patients and 1,300 population-based controls and performed in silico analyses of the SNPs in an ADHD meta-analysis comprising 2,064 trios, 896 independent cases, and 2,455 controls. In the German sample rs206936 in the NUDT3 gene (nudix; nucleoside diphosphate linked moiety X-type motif 3) was associated with ADHD risk (OR: 1.39; P = 3.4 × 10(-4) ; Pcorr  = 0.01). In the meta-analysis data we found rs6497416 in the intronic region of the GPRC5B gene (G protein-coupled receptor, family C, group 5, member B; P = 7.2 × 10(-4) ; Pcorr  = 0.02) as a risk allele for ADHD. GPRC5B belongs to the metabotropic glutamate receptor family, which has been implicated in the etiology of ADHD. In the German sample rs206936 (NUDT3) and rs10938397 in the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) were associated with inattention, whereas markers in the mitogen-activated protein kinase 5 gene (MAP2K5) and in the cell adhesion molecule 2 gene (CADM2) were associated with hyperactivity. In the meta-analysis data, MAP2K5 was associated with inattention, GPRC5B with hyperactivity/impulsivity and inattention and CADM2 with hyperactivity/impulsivity. Our results justify further research on the elucidation of the common genetic background of ADHD and obesity.