Reactive processing of polymers:melt grafting of glycidyl methacrylate on ethylene propylene copolymer in the presence of a coagent

Glycidyl methacrylate (GMA) was grafted on ethylene-propylene copolymer during melt processing with peroxide initiation in the presence and absence of a more reactive comonomer (coagent), trimethylolpropane triacrylate (Tris). The characteristics of the grafting systems in terms of the grafting reaction yield and the nature and extent of the competing side reactions were examined. The homopolymers of GMA (Poly-GMA) and Tris (Poly-Tris) and the GMA-Tris copolymer (GMA-co-Tris) were synthesized and characterized. In the absence of the coagent, high levels of poly-GMA, which constituted the major competing reaction, was formed, giving rise to low GMA grafting levels. Further, this grafting system resulted in a high extent of gel formation and polymer crosslinking due to the high levels of peroxide needed to achieve optimum GMA grafting and a consequent large drop in the melt index (increased viscosity) of the polymer. In the presence of the coagent, however, the grafting system required much lower peroxide concentration, by almost an order of magnitude, to achieve the optimum grafting yield. The coagent-containing GMA-grafting system has also resulted in a drastic reduction in the extent of all competing reactions, and in particular, the GMA homopolymerization, leading to improved GMA grafting efficiency with no detectable gel or crosslinking. The mechanisms of the grafting reactions, in the presence and absence of Tris, are proposed.

Binding of small molecules to DNA junctions

Previous results in our laboratory suggest that the (CG) 4 segments whether present in a right-handed or a left-handed conformation form distinctive junctions with adjacent random sequences. These junctions and their associated sequences have unique structural and thermodynamic properties that may be recognized by DNA-binding molecules. This study probes these sequences by using the following small ligands: actinomycin D, 1,4-bis(((di(aminoethyl)amino)ethyl)amino)anthracene-9,10-dione, ametantrone, and tris(phenanthroline)ruthenium (II). These ligands may recognize the distinctive features associated to the (CG)4 segment and its junctions and thus interact preferentially near these sequences. Restriction enzyme inhibition assays were used to determine whether or not binding interactions took place, and to approximate locations of these interactions. These binding studies are first carried out using two small synthetic oligomers BZ-III and BZ-IV. The (5meCG)4 segment present in BZ-III adopts the Z-conformation in the presence of 50 m M Co(NH3)63+. In BZ-IV, the unmethylated (CG)4 segment changes to a non-B conformation in the presence of 50 m M Co(NH3)63+. BZ-IV, containing the (CG)4 segment, was inserted into a clone plasmid then digested with the restriction enzyme Hinf I to produce a larger fragment that contains the (CG)4 segment. The results obtained on the small oligomers and on the larger fragment for restriction enzyme Mbo I indicate that 1,4-bis(((di(aminoethyl)amino)ethyl)amino)anthracene-9,10-dione binds more efficiently at or near the (CG)4 segment. Restriction enzymes EcoRV, Sac I and Not I with cleavage sites upstream and downstream of the (CG)4 insert were used to further localize binding interactions in the vicinity of the (CG)4 insert. RNA polymerase activity was studied in a plasmid which contained the (CG)4 insert downstream from the promoter sites of SP6 and T7 RNA polymerases. Activities of these two polymerases were studied in the presence of each one of the ligands used throughout the study. Only actinomycin D and spider, which bind at or near the (CG)4 segment, alter the activities of SP6 and T7 RNA polymerases. Surprisingly, enhancement of polymerase activity was observed in the presence of very low concentrations of actinomycin D. These results suggest that the conformational features of (CG) segments may serve in regulatory functions of DNA. ^

Functionalized carbon nanotube nanoelectrodes for biomolecular recognition

The objective of this research is to develop nanoscale ultrasensitive transducers for detection of biological species at molecular level using carbon nanotubes as nanoelectrodes. Rapid detection of ultra low concentration or even single DNA molecules are essential for medical diagnosis and treatment, pharmaceutical applications, gene sequencing as well as forensic analysis. Here the use of functionalized single walled carbon nanotubes (SWNT) as nanoscale detection platform for rapid detection of single DNA molecules is demonstrated. The detection principle is based on obtaining electrical signal from a single amine terminated DNA molecule which is covalently bridged between two ends of an SWNT separated by a nanoscale gap. The synthesis, fabrication, chemical functionalization of nanoelectrodes and DNA attachment were optimized to perform reliable electrical characterization these molecules. Using this detection system fundamental study on charge transport in DNA molecule of both genomic and non genomic sequences is performed. We measured an electrical signal of about 30 pA through a hybridized DNA molecule of 80 base pair in length which encodes a portion of sequence of H5N1 gene of avian Influenza A virus. Due the dynamic nature of the DNA molecules the local environment such as ion concentration, pH and temperature significantly influence its physical properties. We observed a decrease in DNA conductance of about 33% in high vacuum conditions. The counterion variation was analyzed by changing the buffer from sodium acetate to tris(hydroxymethyl) aminomethane, which resulted in a two orders of magnitude increase in the conductivity of the DNA. The fabrication of large array of identical SWNT nanoelectrodes was achieved by using ultralong SWNTs. Using these nanoelectrode array we have investigated the sequence dependent charge transport in DNA. A systematic study performed on PolyG - PolyC sequence with varying number of intervening PolyA - PolyT pairs showed a decrease in electrical signal from 180 pA (PolyG - PolyC) to 30 pA with increasing number of the PolyA - PolyT pairs. This work also led to the development of ultrasensitive nanoelectrodes based on enzyme functionalized vertically aligned high density multiwalled CNTs for electrochemical detection of cholesterol. The nanoelectrodes exhibited selectively detection of cholesterol in the presence of common interferents found in human blood.

New organogermanium substrates for palladium-catalyzed cross-coupling reactions. Application of organogermanes towards the synthesis of carbon-5 modified uridine analogues

The diverse biological properties exhibited by uridine analogues modified at carbon-5 of the uracil base have attracted special interest to the development of efficient methodologies for their synthesis. This study aimed to evaluate the possible application of vinyl tris(trimethylsilyl)germanes in the synthesis of conjugated 5-modified uridine analogues via Pd-catalyzed cross-coupling reactions. The stereoselective synthesis of 5-[(2-tris(trimethylsilyl)germyl)ethenyl]uridine derivatives was achieved by the radical-mediated hydrogermylation of the protected 5-alkynyluridine precursors with tris(trimethylsilyl)germane [(TMS)3GeH]. The hydrogermylation with Ph3GeH afforded in addition to the expected 5-vinylgermane, novel 5-(2-triphenylgermyl)acetyl derivatives. Also, the treatment with Me3GeH provided access to 5-vinylgermane uridine analogues with potential biological applications. Since the Pd-catalyzed cross-coupling of organogermanes has received much less attention than the couplings involving organostannanes and organosilanes, we were prompted to develop novel organogermane precursors suitable for transfer of aryl and/or alkenyl groups. The allyl(phenyl)germanes were found to transfer allyl groups to aryl iodides in the presence of sodium hydroxide or tetrabutylammonium fluoride (TBAF) via a Heck arylation mechanism. On the other hand, the treatment of allyl(phenyl)germanes with tetracyanoethylene (TCNE) effectively cleaved the Ge-C(allyl) bonds and promoted the transfer of the phenyl groups upon fluoride activation in toluene. It was discovered that the trichlorophenyl,- dichlorodiphenyl,- and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of TBAF in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two or three phenyl groups from the organogermane precursors. The methodology shows that organogermanes can render a coupling efficiency comparable to the more established stannane and silane counterparts. Our coupling methodology (TBAF/moist toluene) was also found to promote the transfer of multiple phenyl groups from analogous chloro(phenyl)silanes and stannanes.

Covalent protein adduction of nitrogen mustards and related compounds

Chemical warfare agents continue to pose a global threat despite the efforts of the international community to prohibit their use in warfare. For this reason, improvement in the detection of these compounds remains of forensic interest. Protein adducts formed by the covalent modification of an electrophilic xenobiotic and a nucleophilic amino acid may provide a biomarker of exposure that is stable and specific to compounds of interest (such as chemical warfare agents), and have the capability to extend the window of detection further than the parent compound or circulating metabolites. This research investigated the formation of protein adducts of the nitrogen mustard chemical warfare agents mechlorethamine (HN-2) and tris(2-chloroethyl)amine (HN-3) to lysine and histidine residues found on the blood proteins hemoglobin and human serum albumin. Identified adducts were assessed for reproducibility and stability both in model peptide and whole protein assays. Specificity of these identified adducts was assessed using in vitro assays to metabolize common therapeutic drugs containing nitrogen mustard moieties. Results of the model peptide assays demonstrated that HN-2 and HN-3 were able to form stable adducts with lysine and histidine residues under physiological conditions. Results for whole protein assays identified three histidine adducts on hemoglobin, and three adducts (two lysine residues and one histidine residue) on human serum albumin that were previously unknown. These protein adducts were determined to be reproducible and stable at physiological conditions over a three-week analysis period. Results from the in vitro metabolic assays revealed that adducts formed by HN-2 and HN-3 are specific to these agents, as metabolized therapeutic drugs (chlorambucil, cyclophosphamide, and melphalan) did not form the same adducts on lysine or histidine residues as the previously identified adducts formed by HN-2 and HN-3. Results obtained from the model peptide and full protein work were enhanced by comparing experimental data to theoretical calculations for adduct formation, providing further confirmatory data. This project was successful in identifying and characterizing biomarkers of exposure to HN-2 and HN-3 that are specific and stable and which have the potential to be used for the forensic determination of exposure to these dangerous agents.

Novel approaches for the synthesis of C-5 modified pyrimidine nucleosides

The antiviral or anticancer activities of C-5 modified pyrimidine nucleoside analogues validate the need for the development of their syntheses. In the first half of this dissertation, I explore the Pd-catalyzed cross-coupling reaction of allylphenylgermanes with aryl halides in the presence of SbF 5/TBAF to give various biaryls by transferring multiple phenyl groups, which has also been applied to the 5-halo pyrimidine nucleosides for the synthesis of 5-aryl derivatives. To avoid the use of organometallic reagents, I developed Pd-catalyzed direct arylation of 5-halo pyrimidine nucleosides. It was discovered that 5-aryl pyrimidine nucleosides could be synthesized by Pd-catalyzed direct arylation of N3-free 5-halo uracil and uracil nucleosides with simple arenes or heteroaromatics in the presence of TBAF within 1 h. Both N3-protected and N3-free uracil and uracil nucleosides could undergo base-promoted Pd-catalyzed direct arylation, but only with electron rich heteroaromatics. ^ In the second half of this dissertation, 5-acetylenic uracil and uracil nucleosides have been employed to investigate the hydrogermylation, hydrosulfonylation as well as hydroazidation for the synthesis of various functionalized 5-vinyl pyrimidine nucleosides. Hydrogermylation of 5-alkynyl uracil analogues with trialkylgermane or tris(trimethylsilyl)germane hydride gave the corresponding vinyl trialkylgermane, or tris(trimethylsilyl)germane uracil derivatives. During the hydrogermylation with triphenylgermane, besides the vinyl triphenylgermane uracil derivatives, 5-[2-(triphenylgermyl)acetyl]uracil was also isolated and characterized and the origin of the acetyl oxygen was clarified. Tris(trimethylsilyl)germane uracil derivatives were coupled to aryl halides but with decent yield. Iron-mediated regio- and stereoselective hydrosulfonylation of the 5-ethynyl pyrimidine analogues with sulfonyl chloride or sulfonyl hydrazine to give 5-(1-halo-2-tosyl)vinyluracil nucleoside derivatives has been developed. Nucleophilic substitution of the 5-(β-halovinyl)sulfonyl nucleosides with various nucleophiles have been performed to give highly functionalized 5-vinyl pyrimidine nucleosides via the addition-elimination mechanism. The 5-(β-keto)sulfonyluracil derivative has also been synthesized via the aerobic difunctionalization of 5-ethynyluracil analogue with sulfinic acid in the presence of catalytic amount of pyridine. Silver catalyzed hydroazidation of protected 2'-deoxy-5-ethynyluridine with TMSN3 in the presence of catalytic amount of water to give 5-(α-azidovinyl)uracil nucleoside derivatives was developed. Strain promoted Click reaction of the 5-(α-azidovinyl)uracil with cyclooctyne provide the corresponding fully conjugated triazole product.^

New Organogermanium Substrates for Palladium-Catalyzed Cross-Coupling Reactions. Application of Organogermanes towards the Synthesis of Carbon-5 Modified Uridine Analogues

The diverse biological properties exhibited by uridine analogues modified at carbon-5 of the uracil base have attracted special interest to the development of efficient methodologies for their synthesis. This study aimed to evaluate the possible application of vinyl tris(trimethylsilyl)germanes in the synthesis of conjugated 5-modified uridine analogues via Pd-catalyzed cross-coupling reactions. The stereoselective synthesis of 5-[(2-tris(trimethylsilyl)germyl)ethenyl]uridine derivatives was achieved by the radical-mediated hydrogermylation of the protected 5-alkynyluridine precursors with tris(trimethylsilyl)germane [(TMS)3GeH]. The hydrogermylation with Ph3GeH afforded in addition to the expected 5-vinylgermane, novel 5-(2-triphenylgermyl)acetyl derivatives. Also, the treatment with Me3GeH provided access to 5-vinylgermane uridine analogues with potential biological applications. Since the Pd-catalyzed cross-coupling of organogermanes has received much less attention than the couplings involving organostannanes and organosilanes, we were prompted to develop novel organogermane precursors suitable for transfer of aryl and/or alkenyl groups. The allyl(phenyl)germanes were found to transfer allyl groups to aryl iodides in the presence of sodium hydroxide or tetrabutylammonium fluoride (TBAF) via a Heck arylation mechanism. On the other hand, the treatment of allyl(phenyl)germanes with tetracyanoethylene (TCNE) effectively cleaved the Ge-C(allyl) bonds and promoted the transfer of the phenyl groups upon fluoride activation in toluene. It was discovered that the trichlorophenyl,- dichlorodiphenyl,- and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of TBAF in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two or three phenyl groups from the organogermane precursors. The methodology shows that organogermanes can render a coupling efficiency comparable to the more established stannane and silane counterparts. Our coupling methodology (TBAF/moist toluene) was also found to promote the transfer of multiple phenyl groups from analogous chloro(phenyl)silanes and stannanes.

Program notes and translations for a graduate voice recital

"Ghi ii sole dal Gange" "O cessate dipiagarmi" "Spesso vibra per suo gioco" Alessandro Scarlatti (1660-1725) "Must the winter come so soon"? from Vanessa Samuel Barber (1910-1981) Two Songs from Mirabai Songs "It's True I Went to the Market" "Don t Go, Don t Go" John Harbison (b.1938) El amor brujo "Cancidn del amor dolido" "Cancidn delfuegofatuo" "Danza del juego del amor" "Las campanas del amanecer " Manuel de Falla (18 76-1946) INTERMISSION "Standchen" from Leise flehen meine Lieder "Du bist die Ruh" D776 "Gretchen am Spinnrade" D257 Franz Schubert (1797-1828) "Una voce pocofa" from Il barbiere di Siviglia Gioachino Rossini (1792-1868) La Regata Veneziana - Three songs in Venetian dialect "Anzoleta avanti la regata" "Anzoleta co passa la regata" "Anzoleta dopo la regata"

Definizione e validazione di uno strumento per la misurazione dell'impatto delle variabili redazionali di un item matematico sulla performance degli studenti

Questa tesi descrive la ricerca condotta tra l'autunno e l'inverno di quest'anno da un gruppo di ricercatori in didattica della matematica relativamente all'influenza che le variazioni redazionali di un quesito matematico hanno sulle performance degli studenti. Lo scopo della ricerca è quella di strutturare e validare una metodologia e uno strumento che permettano di individuare e quantificare l'influenza delle variazioni del testo sulle prestazioni dello studente. Si è sentita l'esigenza di condurre uno studio di questo tipo poichè è sempre più evidente il profondo legame tra il linguaggio e l'apprendimento della matematica. La messa a punto di questo strumento aprirebbe le porte a una serie di ricerche più approfondite sulle varie tipologie di variazioni numeriche e/o linguistiche finora individuate. Nel primo capitolo è presentato il quadro teorico di riferimento relativo agli studi condotti fino ad ora nell'ambito della didattica della matematica, dai quali emerge la grossa influenza che la componente linguistica ha sulla comprensione e la trasmissione della matematica. Si farà quindi riferimento alle ricerche passate volte all'individuazione e alla schematizzazione delle variazioni redazionali dei Word Problems. Nel secondo capitolo, invece si passerà alla descrizione teorica relativa allo strumento statistico utilizzato. Si tratta del modello di Rasch appartenente alla famiglia dei modelli statistici dell'Item Response Theory, particolarmente utilizzato nella ricerca in didattica. Il terzo capitolo sarà dedicato alla descrizione dettagliata della sperimentazione svolta. Il quarto capitolo sarà il cuore di questa tesi; in esso infatti verrà descritta e validata la nuova metodologia utilizzata. Nel quinto sarà eseguita un analisi puntuale di come lo strumento ha messo in evidenza le differenze per ogni item variato. Infine verranno tratte le conclusioni complessive dello studio condotto.

Matematica e DSA: analisi delle consegne per una formulazione adeguata

Scopo di questa tesi è verificare se, testi di matematica modificati da un punto di vista grafico e senza variazioni a livello di competenze matematiche richieste, possano facilitare i ragazzi con Disturbi Specifici di Apprendimento (DSA). Aspetti non legati alla matematica, come la difficoltà a leggere il testo troppo lungo, a ricordare o sapere il significato di alcune parole, a non avere una immagine di riferimento, bloccano il ragazzo impedendo all’insegnante una corretta valutazione. Viene presentata dapprima una parte teorica sui disturbi e sulle leggi che tutelano i ragazzi, in seguito viene analizzata nel dettaglio la parte sperimentale, riportando un’analisi di quanto emerso da interviste semi-strutturate e questionari posti a ragazzi DSA di diverse associazioni.

Gamification e rilevazione di barriere architettoniche: un caso di studio con applicazioni mobili

Questo volume di tesi descrive lo sviluppo di un'applicazione cross-platform per la raccolta dati sull'accessibilità urbana. E' stato creato un Pervasive GWAP strutturato in modo tale da raccogliere, tramite un gioco in mixed-reality, dati sulla geolocalizzazione delle barriere/facility architettoniche in ambiente urbano, in modo da mappare il territorio. Il gioco è rivolto a bambini accompagnati da insegnanti/genitori e prevede l'utilizzo di dispositivi mobili quali tablet e smartphone con sistema operativo Andoid. E' stata utilizzata la funzione GPS dei dispositivi per la geolocalizzazione dei giocatori e delle barriere/facility segnalate e la CAMERA per lo scan dei Qr-Code utilizzati come incentivo per intrattenere gli utenti. L'applicazione è scritta utilizzando tecnologie web quali HTML, CSS, JavaScript, PHP, JSON e grazie all'utilizzo del framework Apache Cordova è stato possibile lo sviluppo multipiattaforma. Questo strumento permette di utilizzare tecnologie web per lo sviluppo di applicazioni mobile, generando codice nativo supportato da sistemi operativi quali Android, iOS, BlackBerry.

L'insegnamento della Trigonometria nella Scuola Secondaria

Lo scopo di questa tesi è quello di verificare il livello di conoscenza riguardo alla trigonometria negli studenti del 4 anno della Scuola Secondaria di II grado e in quelli iscritti al primo anno del corso di studi in Matematica. Per analizzare al meglio le conoscenze che dovrebbero avere gli studenti, è stato osservato come affrontano questo argomento i libri di testo della scuola e quelli universitari. Sono stati osservati anche gli esercizi proposti dai libri, gli obiettivi di apprendimento e le indicazioni nazionali previste dal ministero.

Valutazione formativa in matematica. Strumenti di rilevazione delle abilità in matematica nei video del progetto FAMT&L

Questa tesi espone il mio lavoro all'interno del progetto di ricerca del FAMT&L, progetto sviluppato dal dipartimento di Matematica e dal dipartimento di Scienze dell'Educazione sulla valutazione formativa in matematica, finanziato dall'Unione Europea e svolto in collaborazione con Francia, Svizzera, Olanda e Cipro. Questo progetto di ricerca è centrato sulla formazione degli insegnanti alla valutazione formativa. L'obiettivo è quello di formare gli insegnanti a fare valutazione formativa in matematica. Lo strumento scelto è quello di lavorare su video di situazioni in classe. Il mio lavoro di tesi è consistito nell'analizzare le situazioni dei video per trovare delle categorie relative ai contenuti, alle competenze matematiche e alle caratteristiche dell'apprendimento della matematica. Questi materiali saranno utilizzati come materiale nella formazione insegnanti.

Discalculia: includere attraverso la didattica in classe

Perché uno studente, con quoziente intellettivo nella media, che ha buoni voti in tutte le materie, colleziona insuccessi in matematica? Si può trattare di difficoltà di apprendimento passeggere su un dato argomento, può essere un atteggiamento negativo nei confronti della materia o può trattarsi di discalculia. L'insegnante di matematica deve essere preparato ad individuare le possibili cause dell'insuccesso scolastico degli studenti e ad attuare le strategie didattiche che migliorino il più possibile il suo percorso scolastico. Nel mio elaborato ho riportato una sintesi delle leggi che hanno condotto la scuola italiana ad orientarsi in una prospettiva sempre più inclusiva. In particolare ho riportato la legge 170 del 2010, la prima che definisce i disturbi dell'apprendimento, e la direttiva Bes del 2012, che amplia ancora di più l'area delle problematiche scolastiche. Partendo da una distinzione tra disturbo e difficoltà nell'apprendimento, ho trattato poi in particolare la discalculia, dal punto di vista didattico e riportando le sue definizioni nel corso del tempo. Tra le difficoltà ho citato invece la Matofobia o Math Anxiety. Una paura della matematica ereditata, un'eredità trasmessa però attraverso l'ambiente in cui si cresce e non dai geni. Infine ipotizzando delle lezioni in una classe di seconda superiore in cui sono presenti studenti con discalculia, ho realizzato un'unità didattica dal titolo "Le rette nel piano cartesiano". Per la sua realizzazione ho pensato all'utilizzo del software geogebra e del lavoro in gruppi, per promuovere l'apprendimento attraverso la scoperta e il ragionamento logico, piuttosto che la memorizzazione di formule e la loro mera applicazione. Ho concluso il mio elaborato riportando delle riflessioni su come i docenti si attivano in presenza di uno studente con certificazione di dsa e sul rapporto tra scuola e famiglie, riflessioni tratte da alcune interviste fatte ai referenti per i dsa in diverse scuole della Romagna.

Valutazione delle performance di un algoritmo per la quantificazione della pressione portale epatica da ecografia con mezzo di contrasto

La misurazione del gradiente pressorio venoso (HVPG) viene utilizzata per diagnosticare la gravità della malattia del fegato ma si tratta di una pratica invasiva e che non può essere effettuata in tutti i pazienti. Per questo motivo sono state studiate nuove metodiche per riuscire ad analizzare la cirrosi, una tra le quali l’indagine ecografica. Un progetto in fase di svolgimento (progetto CLEVER) è stato avviato per riuscire a sviluppare, validare e trasferire nella pratica clinica un nuovo sistema basato sull'analisi di immagini ecografiche con mezzo di contrasto al fine di valutare la gravità della degenerazione della rete vascolare causata dalla cirrosi. L'obiettivo principale della ricerca è quello di sviluppare uno strumento completamente automatico per l'analisi in tempo reale della rete vascolare del fegato in grado di valutare la connettività vascolare e quantificare il grado di squilibrio della rete.