Dissertations / Theses on the topic 'NMSC'

Non-melanoma skin cancer (NMSC) is the most common malignant tumor, representing more than a third of all malignant tumors combined and the incidence is increasing every year. Ultraviolet (UV) radiation from the sun is the most dominant factor contributing to tumor initiation and progression. The condition is most prevalent in populations with lighter skin and older age. Current pharmaceutical molecular research targets the inhibition of the Epidermal Growth Factor Receptor (EGFR), a receptor which is commonly over-expressed or dysregulated in skin malignancies. This study evaluates the content and location of the damage marker p21 within keratinocytes that were incubated in sphingomyelin (SM) and later exposed to UV. Confocal microscopy and automated image processing provided the tools to assess large populations of keratinocytes in the effort to accurately identify the photoprotective qualities of sphingomyelin. Classification of individual cells into subpopulations yielded results suggesting SM may be involved in the inhibition of EGFR, and could potentially be a more naturally derived treatment.

Thesis advisor: Junona Moroianu
Some non melanoma skin cancers (NMSC) have been associated with human papillomavirus (HPV) pathogenesis, like epidermodysplasia verruciformis (EV) and squamous cell carcinoma (SCC). EV is a genetically inherited skin disease that develops when the individuals are infected with cutaneous HPV types belonging to the β-genus, especially types 5 and 8. Transgenic mouse lineages expressing all early genes of cutaneous HPV8 develop papillomas, dysplasias and SCC after UV irradiation and this correlates with enhanced HPV8 oncogenes expression. We have previously discovered that the nuclear localization of mucosal HPV16 E7 and HPV11 E7 proteins is mediated by their zinc-binding domain via a Ran-dependent pathway and independent of nuclear import receptors and that a patch of hydrophobic residues within the zinc-binding domain of HPV16 E7 and HPV11 E7 proteins is responsible for their nuclear import via hydrophobic interactions with FG nucleoporins. Here we investigated the nucleocytoplasmic traffic of cutaneous HPV8 E7 protein using confocal microscopy to analyze the intracellular localization of EGFP-8E7, its subdomains and its mutants after transient transfections. We also investigated the nuclear import ability of GST-8E7, its subdomains and mutants using in vitro nuclear import assays in digitonin-permeabilized HeLa cells. In addition, we performed isolation assays to study the direct interaction between HPV8 E7 and two FG nucleoporins, Nup62 and Nup153 or the nuclear export receptor, CRM1. We found that the nuclear import of cutaneous HPV8 E7 is mediated by a nuclear localization signal (NLS) located within its zinc-binding domain. Furthermore, we determined that the hydrophobic residues within the 65LRLFV69 patch are responsible for the nuclear import and nuclear localization of HPV8 E7 via direct hydrophobic interactions with FG nucleoporins, Nup62 and Nup153, whereas the positively charged arginine 66 plays no significant role in the function of the NLS. In addition, we examined the nuclear export mechanism of cutaneous HPV8 E7 protein and showed that it has a leucine-rich nuclear export signal (NES) in its C-terminal domain that is recognized by the CRM1 nuclear export receptor. These studies are essential for understanding the nucleocytoplasmic traffic of cutaneous HPV8 E7 protein
Thesis (PhD) — Boston College, 2014
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology

Non Melanoma Skin Cancer (NMSC) affects 3.3 million Americans each year and results from Ultra Violet Radiation (UVR) damage to DNA in the form of pyrimidine dimers and photoproducts [1]–[5]. Cells directly detect the damage and initiate apoptosis, cell cycle arrest, or DNA repair by modulating p53 and p21 levels [6]–[9]. Current methods of photoprotection include sunscreen, but controversy over safety of some active ingredients necessitates research into more natural alternatives [10]–[12]. In particular, 24 hour incubation with bovine milk sphingomyelin (BSM) has demonstrated photoprotective potential by reducing p21 and p53 levels in keratinocytes (KRTs) after UV radiation [13], [14]. This thesis aims to expand on past BSM research by exploring the mechanism for photoprotection. Normally, sphingomyelin (SM) is metabolically degraded to ceramide which then leads to cell apoptosis [6]. The goals of this thesis were to characterize a fluorescent SM (FSM) to assess changes in intracellular fluorescence distribution after various incubation and post-UV exposure times. FSM was deemed functionally equivalent to BSM by reducing levels of p21 after UV. Furthermore, quantification demonstrated that FSM trafficking and intracellular fluorescence were independent of continuous incubation time, warranting further investigation into shorter timepoints like 1 hour. Across several post-UV timepoints, the 1 hour incubation had a consistently higher average cytoplasmic mean gray value compared to 24 hour incubation. In addition, the no UV control was significantly lower compared to the 24 hour and 12 hour post-UV timepoints. No post-UV differences were observed for the 24 hour incubation, suggesting future work is necessary for the 1 hour incubation, which potentially streamlines future experiments. Two immunofluorescence stains for endogenous SM (lysenin) and ceramide were also optimized for preliminary fluorescence distribution studies and colocalization with FSM. Finally, a 3T3 fibroblast spheroid model was utilized as proof-of-concept for future 3D KRT cultures and depth of dye penetration quantification methods. These findings suggest FSM is an appropriate model for BSM trafficking, a shorter FSM incubation time could potentially be adopted in future studies, dual immunofluorescence staining for SM and ceramide is viable, and spheroids provide a promising model for future 3D KRT studies.

I carcinomi spinocellulari (o a cellule squamose) sono le malattie umane più comuni che si verificano negli adulti di carnagione chiara e rappresentano circa il 30% dei tumori totali nel mondo. L'eziologia di questo tipo di cancro è multifattoriale, dal momento che fattori genotipici, fenotipici e/ o ambientali possono essere coinvolti nel suo sviluppo. Diversi studi hanno messo in evidenza che l'esposizione ai raggi ultravioletti (UVB) rappresenta un fattore di rischio chiave nello sviluppo del cancro della pelle. Inoltre, gli agenti infettivi potrebbero costituire un ulteriore fattore di rischio, ipotesi sostenuta dal fatto che i pazienti immunocompromessi, quali ad esempio i soggetti che hanno subito un trapianto di organo (OTR), mostrano un rischio più elevato di sviluppare carcinomi spinocellulari rispetto agli individui immunocompetenti. Molti agenti infettivi sono in grado di colonizzare la pelle e in particolare un sottogruppo di beta papillomavirus umani a tropismo cutaneo (β-HPV) è considerato il fattore eziologico più probabile nello sviluppo del carcinoma a cellule squamose. In particolare, la presenza di β-HPV è stata riportata nei pazienti affetti da un raro difetto dell’immunità cellulo-mediata, chiamato epidermodisplasia verruciformis (EV), che causa un’elevata suscettibilità allo sviluppo del carcinoma a cellule squamose della pelle (SCC). Questo costituisce la prova iniziale secondo la quale gli agenti infettivi, come β-HPV, rappresenterebbero un potenziale fattore di rischio supplementare nello sviluppo dei tumori spinocellulari. Diversi studi hanno dimostrato le proprietà trasformanti delle oncoproteine virali, E6 e E7, sia in modelli sperimentali in vitro che in vivo. Entrambe le proteine, alterando le funzioni di proteine cellulari, quali p53 e pRb, sono in grado di deregolare diversi eventi cellulari chiave, come il ciclo cellulare, la riparazione del danno del DNA, l'apoptosi e la senescenza. Sulla base di questi risultati in vitro, il nostro gruppo ha generato un modello animale di topi transgenici (Tg) che esprimono le proteine virali E6 e E7 di HPV38 nello strato basale della pelle e nella mucosa epiteliale. Questi topi hanno mostrato un’elevata suscettibilità alla radiazione UV; infatti, la loro esposizione ai raggi UVB causa lo sviluppo di lesioni attiniche simili alla cheratosi che sono considerati come precursori del carcinoma a cellule squamose della pelle nell'uomo, e alcune settimane dopo hanno sviluppato il carcinoma conclamato. Al contrario, i topi wild-type non hanno sviluppato alcun tipo di lesioni cutanee quando sono stati esposti alla stessa dose di radiazioni UV. Tuttavia, il meccanismo della cooperazione tra UV e HPV38 non è stato ancora chiarito e l’obiettivo di questo lavoro di tesi è stato quello di esaminare i meccanismi molecolari di tale sinergismo. A tale scopo, abbiamo valutato se l'espressione degli oncogeni virali negli animali transgenici potesse alterare l'espressione genica indotta dalle radiazioni UV. L'analisi dell'intero trascrittoma ha rilevato che più di 300 geni sono deregolati nei topi transgenici dopo l'esposizione ai raggi UVB, rispetto agli animali wild-type. In particolare, le oncoproteine E6 e E7 sono in grado di deregolare l'espressione di proteine coinvolte nella formazione dei complessi dell’inflammosoma o dei loro effettori a valle, come IL-18. È interessante notare che molti studi condotti su linee cellulari di cheratinociti hanno dimostrato che le radiazioni UV attivano l’inflammosoma, portando alla secrezione di specifiche citochine pro-infiammatorie, come IL-1β e IL-18. I risultati ottenuti tramite RT-qPCR hanno confermato i dati dell’analisi del trascrittoma, mostrando che l'espressione dell’IL-18 è regolata nei topi wild-type dopo l'esposizione a UV, mentre è fortemente inibita nei topi transgenici. Successivamente, utilizzando i cheratinociti umani primari (HPKs) come modello sperimentale, abbiamo analizzato i meccanismi coinvolti nell'espressione dell’IL-18 indotta dai raggi UV, nonché il ruolo di HPV38 nella deregolazione di questi eventi. I cheratinociti primari umani in seguito all’irradiazione con raggi UV mostravano un aumento dei livelli di espressione di mRNA dell’IL-18 e di altri componenti chiave dei complessi dell’inflammosoma, quali AIM2 e ASC; al contrario, la presenza delle proteine virali E6 e E7 riduceva fortemente l’espressione dell’IL-18 sia a livello di espressione di mRNA che di secrezione. L’utilizzo di cheratinociti esprimenti il gene della telomerasi umano (hTERT), al fine di prolungare il ciclo vitale delle cellule, quale modello sperimentale in vitro alternativo, ha messo in evidenza un elevalto livello basale di mRNA di IL-18 rispetto ai cheratinociti primari; inoltre, la presenza di E6 e E7 svolge un ruolo inibitorio su tale espressione. L’espressione transiente di un vettore contenente il promotore isolato dell’IL-18 clonato davanti al gene reporter della luciferasi, in cheratinociti esprimenti il gene hTERT, ha confermato la capacità di E6 e E7 di HPV38 di reprimere l'attività del promotore dell’Interleuchina 18. Inoltre, l'analisi del promotore dell’ IL-18, mediante l’utilizzo del programma bioinformatico TFBIND, ha rivelato la presenza di 15 putativi siti di legame per p53, classicamente attivato dalle radiazioni UV. Eseguendo test di immunoprecipitazione della cromatina (CHIP), abbiamo dimostrato che p53 viene reclutato in due distinte regioni del promotore dell’IL-18, che comprendono quattro elementi responsivi per p53. Le proteine E6 e E7 di HPV38 impediscono in modo efficace il reclutamento di p53 su queste regioni del promotore dell’IL-18. Questi risultati corroborano la nostra ipotesi circa la possibilità che β-HPV38 svolga un ruolo importante nell'inibizione della risposta dell’inflammosoma indotta dai raggi UV; in particolare, il virus potrebbe alterare l'espressione genica e la produzione di proteine coinvolte nella formazione del complesso dell’inflammosoma così come di citochine specifiche (quali ad esempio IL-18). Altresì, la riduzione della regolazione dell’IL-18 potrebbe compromettere la capacità dei cheratinociti di reclutare le cellule del sistema immunitario nell'area esposta ai raggi UV, causando un difetto nell'eliminazione delle cellule che hanno subito un danno al DNA. In conclusione, tutte queste alterazioni potrebbero determinare l'accumulo di danni al DNA indotti dall’esposizione ai raggi UV e allo sviluppo del cancro a cellule squamose della pelle.
Non-melanoma skin cancers (NMSC) are the most common human malignancies occurring in fair-skinned adult population, representing approximately 30% of total cancer. The etiology of this cancer is multifactorial, since genotypic, phenotypic and/or environmental factors can be involved in its development. Several studies have reported that the exposure to ultraviolet irradiation (UVB) represents a key risk factor in the development of skin cancer. Furthermore, infectious agents could be an additional risk factor and this hypothesis is supported by the evidence that immunocompromised people, e.g. organ transplant recipients (OTRs), show a higher risk of developing NMSC compared with immunocompetent individuals. Several infectious agents are able to colonize the skin and especially a subgroup of beta cutaneous human papillomavirus (HPV) is considered the most likely additional etiological factors of NMSC. In particular, the presence of β-HPV has been reported in patients with a rare cell-mediated immunity disorder, called epidermodysplasia verruciformis (EV), which causes high rates of susceptibility to develop skin squamous cell carcinoma (SCC) on sun-exposed areas. Thus, it provided the initial clues about infectious agents, such as β HPV, as potential additional risk factor for NMSC. Several studies have demonstrated the transforming properties of the viral oncoproteins, E6 and E7, in in vitro and in vivo experimental models. Both proteins, altering the functions of tumour suppressor gene products, e.g. p53 and retinoblastoma (pRb), are able to deregulate key cellular events, such as cell cycle, DNA repair, apoptosis and senescence. Based on these in vitro results, our group has generated a transgenic (Tg) mouse model that express E6 and E7 oncogenes from beta HPV38 in the basal level of the skin and mucosal epithelia. Those mice were highly susceptible to UV-radiation; in fact, the exposure of HPV38 E6/E7 Tg mice to UVB caused the development of actinic keratosis-like lesions that are considered as precursors of SCC in humans and a few week later SCC. Conversely, the wild-type mice did not develop any type of skin lesions when exposed to the same dose of UV radiations. However, the mechanism of the UV/HPV38 cooperation has not been elucidated yet. The aim of this work thesis was to dissect the molecular mechanisms of such cooperation. We have first determined whether the expression of the viral oncogenes in the Tg animals alters the pattern of gene expression induced by UV radiation. The analysis of the entire transcriptome pointed out that more than 300 genes are deregulated in the Tg mice after UVB exposure, compared to the wild type animals. In particular, the HPV38 E6 and E7 oncoproteins were able to down regulate the expression of proteins involved in the inflammasome complexes or the downstream effectors, such as IL-18. Interestingly, many studies in keratinocyte cell lines provided evidence that UV radiation activate the inflammasome pathway, leading the secretion of specific pro-inflammatory cytokines, like IL-1β and IL-18. RT-qPCR experiments confirmed the transcriptome findings, showing that IL-18 expression is up-regulated in wild-type mice after UV exposure, while it is strongly inhibited in HPV38 E6/E7 Tg mice. Using primary human keratinocytes (HPKs) as experimental models, we dissected the mechanisms involved in the UV-induced IL-18 expression as well as the role of HPV38 in the deregulation of these events. RT-qPCR analysis showed an UV-induced upregulation of IL-18 mRNA expression as well as some key inflammasome components, like AIM2 and ASC, in HPKs cells; conversely, the presence of E6 and E7 oncoproteins strongly down regulated IL-18 both at the expression and secretion levels. Using another in vitro experimental model, such as keratinocytes expressing the human telomerase reverse transcriptase gene (hTERT), in order to prolong the life span of the cells, we found that this cell line presents a higher basal level of IL-18 compared to HPKs and the presence of E6 and E7 plays an inhibitory role. Transient transfection experiments in hTERT HPKs using a vector containing the isolated IL-18 promoter cloned in front the luciferase reporter gene confirmed the ability of HPV38 E6 and E7 to repress the IL-18 promoter activity. The analysis of IL-18 promoter by TFBIND bioinformatics tool revealed the presence of 15 putative binding sites for p53, which is well known to be activated by UV radiation. Performing chromatin immunoprecipitation assays (CHIP), we showed that p53 is recruited to two distinct regions of the IL-18 promoters that includes four p53 responsive elements. Importantly, HPV38 E6 and E7 efficiently prevent p53 recruitment to these IL-18 promoter regions. Together these results corroborated our hypothesis that beta HPV38 play an important role in the inhibition UV-induce inflammasome response, by altering the gene expression and the production of proteins involved in the inflammasome pathways as well as of specific cytokines (e.g. IL-18). Most likely, the down regulation of IL-18 may impair the ability of the keratinocytes to recruit the immune cell population at the UV-exposed area, causing a defect in the elimination of cells harboring DNA damage. In conclusion, all these alterations may lead to the accumulation of UV-induced DNA damage and development of non-melanoma skin cancer.

The purpose of this study was to examine the trends, attrition and retention rates of National Merit Finalists at the University of Central Florida between the years of 1997 to 2005. This study was intended to provide information for higher education practitioners, faculty, and administrators to help them better understand the expectations and current trends of National Merit Finalists. The problem was to determine how to increase recruitment and retention while decreasing the attrition rates of these highly desirable students. The importance of this study includes identifying trends that may aid in future recruitment efforts for National Merit Finalists; finding the causes of dissatisfaction towards the University among these students; and identifying specific areas in which to alleviate those dissatisfactions. The results will hopefully provide insight into specific recruitment, services, and programming options for these students. The study examined data that was collected from the University of Central Florida's Burnett Honors College database known as FileMaker 8.0. The data examined characteristics such as grade point averages (high school and college); valedictorian and salutatorian status; test scores (SAT and ACT); Honors in the Major (undergraduate thesis) students; Honors and university status (withdrawn, probation, removed, disqualified, enrolled, graduated); Honors college attrition; university attrition; ethnicity; gender ratios; majors; and, prestigious scholarships awarded in college (such as the Rhodes, Truman, Marshall). The actual size of the sample was one hundred ninety-eight National Merit Finalists. Data was also collected from a survey given to all University of Central Florida National Merit Finalists. Descriptive statistics were reported for each of the components examined. This data examined the types of scholarship packages that National Merit Finalists were offered; the reasons students chose the University of Central Florida over other universities; the college recruitment process; hours studied for the PSAT; siblings; perceptions on being a National Merit Finalist; the number of times students changed their majors; job status; transportation; computer attainment; disabilities; and the potential disadvantages of being labeled as a National Merit Finalist. The data could be utilized to examine the trends of our National Merit Finalists, in order to see what is working and what is not in terms or recruitment and retention; and also to further examine what these students want from their institutions. Findings indicated that problems exist in regard to the following: the recruitment of female and minority National Merit Finalists; males historically score higher on the SAT than females; decreasing the attrition rates of this population at the University of Central Florida; the majority of National Merit Finalists at the University of Central Florida come from Florida; the majority of National Merit Finalists at the University of Central Florida do not tend to be high school salutatorians or valedictorians; high school counselors seem to be the least effective tool for recruiting National Merit Finalists at the University of Central Florida; and the majority of National Merit Finalists at the University of Central Florida did not study at all for the PSAT test. However, the University of Central Florida is extremely competitive with other institutions of higher education with regard to scholarship packages. Results also revealed the following: the SAT is a more widely accepted tool for determining NMSC status as opposed to the ACT; the majority of National Merit Finalists have a GPA between 3.600 and 3.999 at the University of Central Florida; the University of Central Florida is succeeding in making its National Merit Finalists feel special during the recruitment process; the most influential reason that National Merit Finalists are choosing UCF is based upon the financial scholarship packages they are offered; and the majority of National Merit Finalists at the University of Central Florida do not feel that there are disadvantages toward being labeled as such. This data provides a basis for further research on National Merit Finalists trends, attrition, and retention. Practical considerations are revealed in the data that will influence future recruitment methods and lead to higher retention rates and increased student satisfaction. Several other recommendations are made to conduct further research studies on the trends, attrition, and retention rates of National Merit Finalists.
Ed.D.
Department of Educational Research, Technology and Leadership
Education
Educational Leadership

In den letzen Jahren gab es durch epidemiologische und molekularbiologische Studien vermehrt Hinweise, dass kutane humane Papillomviren (HPV) ursächlich an der Entstehung nicht-melanozytärer Hauttumore (engl. NMSC) beteiligt sind. Ziel der vorliegenden Arbeit war die Identifizierung molekularer Mechanismen der viralen Proteine E6 und E7 kutaner HPV-Typen. Die E6 oder E7 Gene der verschiedenen HPV-Typen 1, 4, 5, 8, 20, 38 und RTRX7 wurden untersucht. Natürliche Wirtszellen dieser Viren, humane primäre Keratinozyten (HPK) der Haut, wurden mit rekombinanten, für E6 oder E7 kodierenden Retroviren infiziert. Die Analysen erfolgten in Monolayer-Kultur (undifferenzierte Keratinozyten) oder in organotypischen Hautmodellen (Induktion der Keratinozytendifferenzierung). Die Expression von E6 oder E7 führte in Monolayer-HPK zu einer Verlängerung der Lebensspanne und zu einer deutlich erhöhten Verdoppelungsrate. Eine Telomeraseaktivierung, die charakteristisch für immortale Zellen ist, wurde nur in HPV 8 E6 positiven HPK nachgewiesen. In organotypischen Hautmodellen induzierte das E7 Protein von HPV 1, 4 und 38 starke Veränderungen in der Differenzierung sowie eine Zunahme der Proliferation. Weiterhin wurde eine Aufhebung der normalen Zellzykluskontrolle in suprabasalen HPV 5 E7 oder HPV 8 E7 beobachtet. Hinweise auf ein starkes invasives Potential von E7-infizierten HPK wurden für HPV 8 E7 bestätigt und für HPV 4 E7, HPV 38 E7 und RTRX7 E7 erweitert. Molekulare Mechanismen der viralen Gene E6 und E7 kutaner HPV unterscheiden sich von mukosalen Typen. Das Mehrstufenmodell der Karzinogenese beinhaltet eine Reihe fundamentaler Zelltransformationen, die für eine Tumorgenese nötig sind. In dieser Arbeit beschriebene Mechanismen der Modulation der Zelldifferenzierung und Zellproliferation durch die kutanen HPV-Typen 4, 5, 8 und 38 können unter Umständen zur Induktion und Progression früher Stadien von Plattenepithelkarzinomen (SCC) beitragen.
In the last years epidemiologic and molecular biological studies accumulated increasing evidence that cutaneous human papillomaviruses are etiologically involved in the formation of non-melanoma skin cancer (NMSC). The presented work aims to identify the underlying molecular mechanisms of the viral proteins E6 and E7 of cutaneous HPV types. The E6 and E7 genes of the different HPV types 1, 4, 5, 8, 20, and RTRX7, which are in vivo associated with cutaneous benign or malignant lesions, were studied. Natural host cells of these viruses, human primary keratinocyts (HPK) of the skin, were infected with recombinant E6 and E7 encoding retroviruses. The following analyses were performed in monolayer culture (non-differentiated keratinocytes) or in organotypic skin culture (induction of keratinocyte differentiation). The expression of E6 and E7 elongated the life span of monolayer HPK and significantly increased the doubling rate. An activation of the telomerase, characteristic for immortalized cells, was only detected in HPV 8 E6 positive cells. In organotypic skin cultures E7 of HPV 1, 4 and 38 induced drastic changes in differentiation and proliferation. Additionally an impairment of the normal cell cycle control in suprabasale HPV 5 E7 and 8 E7 cultures was seen. Hints for a strong invasive potential of E7 infected HPK were proven for HPV 8 E7 and expanded to HPV 4 E7, HPV 38 E7 and RTRX E7. The viral E6 and E7 genes of cutaneous and mucosal HPV types exhibit different molecular mechanisms. The multistep model of carcinogenesis includes a series of fundamental cell transformations necessary for tumorigenesis. Mechanisms for the modulation of cell differentiation and proliferation by cutaneous HPV types 4, 5, 8 and 38 described in this work could potentially contribute to the induction and progression of early stages of squamous cell carcinoma.

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior
A sociedade tem passado por um conjunto de transformaÃÃes em sua estrutura. Um dos aspectos mais interessantes dessa transformaÃÃo à observar como a juventude passa por tais mudanÃas de maneira rÃpida, mas nem sempre guiada pelo aspecto qualitativo desse processo. A juventude, principalmente da periferia, està sendo vÃtima de uma ordem social que se estrutura na Ãtica da desumanizaÃÃo. Tendo como base essa premissa, a presente pesquisa tem como objetivo compreender o papel formativo do Movimento Nacional dos Meninos e Meninas de Rua (MNMMR) na Comunidade do Lagamar atravÃs da perspectiva dos participantes, observando esse processo dentro de uma experiÃncia de construÃÃo da resiliÃncia e do empoderamento. Para compreender esse processo formativo (MACEDO, 2010), utilizei da construÃÃo das histÃrias de vida (DELORY-MOMBERGER, 2008; FERRAROTTI, 1996; NÃVOA & FINGER, 2010; PINEAU, 2006, 2012), de acordo com os procedimentos da entrevista narrativa (JOVCHELOVITCH & BAUER, 2002) buscando compor traÃos identitÃrios importantes do MNMMR do Cearà que acaba por completar 30 anos de histÃria em 2015. A categoria da resiliÃncia (ANTUNES, 2011; ASSIS, 2006; CYRULNIK, 2004, 2012; MELILLO & OJEDA, 2005; POLETTI, 2013; YUNES, 2003) e do empoderamento forjado no processo de lutas e conquistas sociais (FREIRE, 1983, 1986, 2006; LOBO, 2011; SAWAIA, 2008) ajudam a compreender esse processo de exclusÃo social e de tomada de consciÃncia crÃtica frente Ãs adversidades sociais. Nas histÃrias de vida, fica evidenciado a importÃncia social do MNMMR, tornando-se um movimento social importante para a Comunidade do Lagamar por atuar com os sujeitos em situaÃÃo de rua. A relevÃncia mostra que as dimensÃes de resiliÃncia e do empoderamento, podem servir de significados para a melhoria de uma formaÃÃo humana propiciada pelo prÃprio MNMMR. O presente trabalho investigativo traz à tona um diÃlogo formativo, que contempla tambÃm um processo educativo, uma aÃÃo educativa construÃda no seio da rua, tendo como protagonista a juventude da periferia da cidade de Fortaleza.

Für die Entstehung nicht-melanozytärer Hauttumore sind mehrere Risikofaktoren verantwortlich: UV-Exposition, Pigmentierung, Alter, Immunsuppression und möglicherweise Humane Papillomviren (HPV). Die molekularen Mechanismen der Tumorgenese des kutanen Plattenepithelkarzinoms (SCC) sowie der Präkanzerose Aktinische Keratose (AK) sind nur lückenhaft bekannt. Fokus dieser Arbeit ist die Untersuchung von SCC-Genexpressionsprofilen sowie der Einfluss kutaner HPV-Typen während der Karzinogenese bei immunkompetenten und immunsupprimierten, organtransplantierten Patienten. Durch Genexpressionsanalyse kutaner SCC, AK und normaler Haut konnten 118 differenziell exprimierte Gene in SCC mittels cDNA-Microarrays identifiziert werden. Bestätigt wurde die Expression von 11 aus 13 ausgewählten Genen (85%) mittels quantitativer real-time RT-PCR (qPCR), dabei konnte eine Korrelation der Genexpression mit der Progression der AK zum SCC für 3 Gene nachgewiesen werden. Dazu zählen das Gen Metalloproteinase-1, kodierend für ein Enzym, das in den Umbau von extrazellulärer Matrix involviert ist, das Protoonkogen RAB31 und das Tenascin-C (Tn-C) kodierende Gen Tn-C. Tn-C war im SCC-Gewebe an der Invasionsfront in Basalzellen sowie Keratinozyten im Stratum papillare und retikulare als Protein nachweisbar, nicht aber in normaler Haut. Die im Rahmen dieser Arbeit erstmalig nachgewiesene 2243 bp-Spleißvariante von Tn-C könnte aufgrund der primären Expression in SCC–Gewebe als diagnostischer Marker für SCC dienen. Diese Daten zeigen, dass simultane, multifaktorielle Dysregulationen von Genexpression und DNA-Reparatur, Zellzyklus und Proliferation, proteolytischen Enzymen und Adhäsionsmolekülen in SCC vorliegen. Ferner wurde die Expression von HPV in SCC und damit der kausale Zusammenhang einer HPV-Infektion mit der Hauttumorgenese untersucht. Das Infektionsmuster von SCC-Gewebe und normaler Haut mit spezifischen HPV-Typen erfolgte durch den Nachweis typenspezifischer HPV-DNA. Virale E6/E7-mRNA-Transkripte der kutanen HPV-Typen 8, 9 und 15 wurden in AK und SCC nachgewiesen. Dagegen konnten in HPV-DNA positiver, gesunder Haut oder Warzen keine HPV-Transkripte gefunden werden. Die Variantenanalyse des offenen Leserahmens von E6 identifizierte eine einzelne, bislang nicht beschriebene Punktmutation mit nicht bekannter Veränderung der Proteinstruktur. Die virale Aktivität der Onkogene E6 und E7 einiger kutaner Typen in AK und SCC weisen auf eine mögliche Rolle von HPV bei der kutanen Hautkarzinogenese hin.
During development of non-melanoma skin cancer, several risk factors are involved: UV-exposition, pigmentation, age, and potentially human papilloma virus (HPV). The molecular mechanisms underlying tumourgenesis in squamous cell carcinoma (SCC) and its pre-cancerosis actinic keratosis (AK) are not fully understood. In this study, the gene expression profile and HPV-infection status were analysed in SCC from immunocompetent and organ transplanted, immunocompromised patients.By global transcriptome analysis from cutaneous SCC, AK and healthy skin, 118 genes were identified differentially expressed in a cDNA-microarray. The expression of 11 out of 13 selected genes (85%) was investigated by real-time RT-PCR (qPCR) and the expression of three genes remarkably induced in SCC correlated with the progression to AK until SCC. These genes encoded for Metalloproteinase-1, which is involved in the remodelling of extracellular matrix, and the protooncogene RAB31 and Tenascin-C (Tn-C). Tn-C protein is expressed in SCC-tissue at the invasion front in basal cells and in keratinocytes in the Stratum papillare and retikulare, but not in healthy skin. This study, the 2243 bp Tn-C-specific splice-variant has for the first time detected in SCC, but not in normal skin. Thus it might serve as diagnostic marker of SCC progression. The data of the transcriptome analysis indicates that a simultaneous dysregulation of oncogene expression and DNA-repair, cell-cycle and proliferation, proteolysis and adhesion molecules exists in SCC. Additionally, the expression of HPV in SCC and thus the causal relationship between HPV-infection and tumourgenesis of SCC in immunocompromised patients was investigated. The HPV-infection pattern in SCC-tissue and normal skin was assessed by detection of DNA from cutaneous HPV-types. Viral E6/E7-mRNA-transcripts of the cutaneous HPV-types 8, 9, 15 were expressed selectively in AK and SCC. In contrast, no HPV-specific mRNA was present in HPV-DNA positive normal skin. The analysis of the open reading frame from the respective E6-protein genes unravelled one single pointmutation, which is not been characterized so far in terms of e.g. its impact on protein structure. The viral activity of the oncogenes E6 and E7 of cutaneous HPV-types indicates a potential function of HPV in the tumourgenesis of SCC in immunocompromised individuals.

Genetic changes are hallmarks of cancer development involving the activation and/or inactivation of oncogenes and tumour suppressor genes, respectively. In non-melanoma skin cancer (NMSC) development, the initiation of genetic mutations results from exposure to solar ultraviolet radiation. Non-melanoma skin cancers are comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Several related cutaneous lesions also exist, of which solar keratoses (SK) are widely accepted as a precursor dysplasia to SCC development. The study of recurrent genetic changes present within NMSC and SK should help reveal causative mutations in skin cancer development. Such analysis could also elucidate links in the genetic similarity of these dysplasia. The rapid screening of numerical changes in DNA sequence copy number throughout the entire genome has been made possible by the advent of comparative genomic hybridisation (CGH). This technique enables the identification of net gains and loss of genetic material within a tumour DNA sample. Chromosomal regions of recurrent gain or loss identify loci containing putative oncogenes and tumour suppressor genes, respectively with potential roles in NMSC tumourigenesis. Used in conjunction with tissue microdissection and universal degenerate PCR techniques this can enable the elucidation of aberrations in small histologically distinct regions of tumour. Such a technique can utilize archival material such as paraffin embedded tissue, which is the major source of neoplastic material available for cancer research. This study used the CGH technique to investigate aberrations in BCC, SCC and SK samples. The screening of copy number abnormalities (CNAs) in BCC revealed that although these tumours were close to diploid and generally genetically stable, they did contain several recurrent aberrations. The loss of genetic material at 9q was identified in a third of BCC tumours studied. This is characteristic of inactivation of the PTCH tumour suppressor gene, a known attribute in some sporadic BCC development. Validation of this loss was performed via loss of heterozygosity, demonstrating good concordance with the CGH data. In addition the over-representation of the 6p chromosome arm was revealed in 47% of biopsies. This novel CNA is also commonly observed in other cutaneous neoplasias, including Merkel cell carcinoma and malignant melanoma. This suggests a possible common mechanism in development and or promotion in these cutaneous dysplasias, the mechanisms of which have yet to be clearly defined. In contrast to BCC, numerical genetic aberrations in SCC and SK were much more frequent. Several regions of recurrent gain were commonly shared between both dysplasias including gain of 3q, 4p, 5p, 8q, 9q, 14q, 17p, 17q and 20q. Common chromosomal regions of loss included 3p, 8p, 9p, 11p, 13q and 17p. In addition loss of chromosome 18 was significantly observed in SCC in comparison to SK, a possible defining event in SK progression to SCC. The identification of shared genetic aberrations suggests a clonal and genetic relationship between the two lesions. This information further supports the notion for re-classification of SK to an SCC in situ or superficial SCC. Finally, the CNAs detected have been similarly observed in other squamous cell-derived tumours, for example cervical and head and neck SCC. This provides further evidence to common mechanisms involved in the initiation, development and progression of SCC neoplasia. This study has identified a number of recurrent chromosomal regions, some of which are novel in NMSC development. The further delineation of these loci should provide additional evidence of their significance and degree of involvement in NMSC tumourigenesis. The identification of the cancer-causing genes mapped to these loci will further demarcate the genetic mechanisms of BCC and SCC progression. An understanding of the events involved in skin cancer formation and progression should shed additional light on molecular targets for diagnostics, management and therapeutic treatment.

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Nesta tese propõe-se o projeto e o desenvolvimento de controladores de formação descentralizados para robôs móveis de diferentes tipos. As soluções baseiam-se na utilização de controladores preditivos não lineares NMPC de tempo contínuo para o cálculo das referências de pose e velocidade para cada robô da formação acoplados via função objetivo ou estados. A tarefa definida para os robôs em formação é o seguimento de caminhos espaciais, pré definidos ou adquiridos através de informações visuais, caso em que o controle é realizado diretamente no plano da imagem, através da utilização de características visuais simplificadas. Para o tratamento de formações e caminhos variantes no tempo, propõe-se uma abordagem para garantia de factibilidade recursiva sem demasiado aumento da complexidade algorítmica dos controladores locais. Tal abordagem baseia-se no relaxamento das restrições do problema de otimização sem penalização explícita na função objetivo. São apresentadas duas propostas para o controle de formação utilizando informações visuais, uma baseia-se num novo conceito de câmeras e caminhos virtuais e a outra implementa a estratégia líder seguidor tradicional. Decorrente da não linearidade dos modelos obtidos, surgem limitações nos horizontes de predição e controle, interferindo diretamente nos requisitos de estabilidade. Neste caso, a estabilidade é garantida através da adição de um custo terminal às funções objetivo e uma zona terminal para as restrições. Resultados simulados e experimentais são apresentados para demonstrar o desempenho das estratégias propostas em diversas situações.
This thesis proposes the design and the development of decentralized formation controllers for di erent types of mobile robots. The solutions are based on the use of continuous time non-linear model predictive formation controllers NMPC for the calculus of references of poses and velocity. The task de ned for the robots in formation are to track spacial paths, pre-speci ed or acquired through visual information, in wich case the control is accomplished direct from the image plane. For the handling of time-varying formations and paths, an approach is proposed to guarantee recursive feasibility without too much increase of the algorithmic complexity of the local controllers. Such an approach is based on the constraints relaxation of the optimization problem without any explicit penalty in the objective function. Two approaches are presented for Formation control using visual information, one based on a new concept of virtual cameras and paths and the other one implements the traditional Leader-Follower strategy. Due to the non-linearity of the obtained models, limitations on prediction and control horizons arise, directly interfering on the stability requirements. Simulated and experimental results are shown to demonstrate the good performance of the proposed strategies in di erent situations.

The thesis work intends to provide an architecture for discovery and monitoring of nodes in a network with improved performance and security. The proposed work addresses limitations identified within the scope of this thesis. The limitations are identified by analyzing some of the better existing monitoring tools in the market with the use of different protocols. The proposed work use different protocols depending on the situation of the problem that exists in a network. Analyze the existing network monitoring tools, by performing metrics and overcoming the limitations. We proposed a new architecture motivated from traditional network monitoring tools with subtle changes. Proposed architecture is also conceptually evaluated for its viability.
0045-31272355, basasrinu@yahoo.co.in,ji_nav@yahoo.co.in

Cryptographic hash functions are an important tool in cryptography to achieve certain security goals such as authenticity, digital signatures, digital time stamping, and entity authentication. They are also strongly related to other important cryptographic tools such as block ciphers and pseudorandom functions. The standard and widely used hash functions such as MD5 and SHA-1 follow the design principle of Merkle-Damgard iterated hash function construction which was presented independently by Ivan Damgard and Ralph Merkle at Crypto'89. It has been established that neither these hash functions nor the Merkle-Damgard construction itself meet certain security requirements. This thesis aims to study the attacks on this popular construction and propose schemes that offer more resistance against these attacks as well as investigating alternative approaches to the Merkle-Damgard style of designing hash functions. This thesis aims at analysing the security of the standard hash function Cellular Authentication and Voice Encryption Algorithm (CAVE) used for authentication and key-derivation in the second generation (2G) North American IS-41 mobile phone system. In addition, this thesis studies the analysis issues of message authentication codes (MACs) designed using hash functions. With the aim to propose some efficient and secure MAC schemes based on hash functions. This thesis works on three aspects of hash functions: design, cryptanalysis and applications with the following significant contributions: * Proposes a family of variants to the Damgard-Merkle construction called 3CG for better protection against specific and generic attacks. Analysis of the linear variant of 3CG called 3C is presented including its resistance to some of the known attacks on hash functions. * Improves the known cryptanalytical techniques to attack 3C and some other similar designs including a linear variant of GOST, a Russian standard hash function. * Proposes a completely novel approach called Iterated Halving, alternative to the standard block iterated hash function construction. * Analyses provably secure HMAC and NMAC message authentication codes (MACs) based on weaker assumptions than stated in their proofs of security. Proposes an efficient variant for NMAC called NMAC-1 to authenticate short messages. Proposes a variant for NMAC called M-NMAC which offers better protection against the complete key-recovery attacks than NMAC. As well it is shown that M-NMAC with hash functions also resists side-channel attacks against which HMAC and NMAC are vulnerable. Proposes a new MAC scheme called O-NMAC based on hash functions using just one secret key. * Improves the open cryptanalysis of the CAVE algorithm. * Analyses the security and legal implications of the latest collision attacks on the widely used MD5 and SHA-1 hash functions.

Cryptographic hash functions are an important tool in cryptography to achieve certain security goals such as authenticity, digital signatures, digital time stamping, and entity authentication. They are also strongly related to other important cryptographic tools such as block ciphers and pseudorandom functions. The standard and widely used hash functions such as MD5 and SHA-1 follow the design principle of Merkle-Damgard iterated hash function construction which was presented independently by Ivan Damgard and Ralph Merkle at Crypto'89. It has been established that neither these hash functions nor the Merkle-Damgard construction itself meet certain security requirements. This thesis aims to study the attacks on this popular construction and propose schemes that offer more resistance against these attacks as well as investigating alternative approaches to the Merkle-Damgard style of designing hash functions. This thesis aims at analysing the security of the standard hash function Cellular Authentication and Voice Encryption Algorithm (CAVE) used for authentication and key-derivation in the second generation (2G) North American IS-41 mobile phone system. In addition, this thesis studies the analysis issues of message authentication codes (MACs) designed using hash functions. With the aim to propose some efficient and secure MAC schemes based on hash functions. This thesis works on three aspects of hash functions: design, cryptanalysis and applications with the following significant contributions: * Proposes a family of variants to the Damgard-Merkle construction called 3CG for better protection against specific and generic attacks. Analysis of the linear variant of 3CG called 3C is presented including its resistance to some of the known attacks on hash functions. * Improves the known cryptanalytical techniques to attack 3C and some other similar designs including a linear variant of GOST, a Russian standard hash function. * Proposes a completely novel approach called Iterated Halving, alternative to the standard block iterated hash function construction. * Analyses provably secure HMAC and NMAC message authentication codes (MACs) based on weaker assumptions than stated in their proofs of security. Proposes an efficient variant for NMAC called NMAC-1 to authenticate short messages. Proposes a variant for NMAC called M-NMAC which offers better protection against the complete key-recovery attacks than NMAC. As well it is shown that M-NMAC with hash functions also resists side-channel attacks against which HMAC and NMAC are vulnerable. Proposes a new MAC scheme called O-NMAC based on hash functions using just one secret key. * Improves the open cryptanalysis of the CAVE algorithm. * Analyses the security and legal implications of the latest collision attacks on the widely used MD5 and SHA-1 hash functions.

With this paper we intended to simplify deployment and management of monitoring agents for a Network Monitoring System. We found interest on the subject since the time consumed to deploy and manage agents was found to be very inefficient. During a lecture with the Swedish based company Op5 AB at the Linnaeus University in Kalmar, Sweden, we presented the complex of problem. The lecturer showed great interest in a solution on the subject and we found it to be a great thesis subject for the Bachelor degree in Computer Science. By the year of 2016 it is expected that the number of network connected devices will grow threefold, there will be four times as much IP traffic and the data storage demand will increase tenfold. [8] This growing demand will also affect the requirement on the Network Monitoring System and in turn the monitoring agents. In this paper we created a baseline, which consisted of a timing regarding the time consumption for manual deployment, configuration and management of the monitoring agents. We also developed an automated way for deployment, configuration and management of monitoring agents by integrating a Content Management Software called Puppet, combined with several scripts. To simplify the management and deployment furthermore a widget was developed for Op5’s Web based User Interface called Ninja. The developed solution was measured against the baseline and a result regarding time consumption was presented. The result fell into a discussion on the subject of automatization and the time savings that it may result in due to less frequent human errors and a less repetitive work processes.

Thesis (Ph. D.)--Earth and Atmospheric Sciences, Georgia Institute of Technology, 2006.
Davis, Douglas, Committee Chair ; Cunnold, Derek, Committee Member ; Mulholland, James, Committee Member ; Wang, Yuhang, Committee Member ; Wine, Paul, Committee Member. Vita. Includes bibliographical references.

Esta tese tem por objetivo a obtenção de modelos que apresentem melhor desempenho quando utilizados em controladores preditivos baseados em modelo (Model-based Predictive Control, MPC). Ao longo dos últimos 25 anos diversos trabalhos propuseram métodos baseados na minimização de uma função de predição múltiplos passos à frente, que se caracteriza por ser uma função não linear. Estes métodos foram denominados MPC Relevent Identification (MRI). A maioria destes artigos propõe técnicas para a obtenção de modelos lineares. Ao longo dos últimos 5 anos, alguns métodos, também baseados na minimização da função de predição múltiplos passos à frente, foram propostos para a identificação de modelos não lineares. Estes trabalhos são baseados na minimização direta da função de custo não linear, para obter com estrutura NARMAX (Nonlinear Autoregressive Moving Average with exogenous inputs). Entretanto, estruturas simplificadas de controladores MPC não lineares podem ser obtidas utilizando modelos com estruturas de Wiener e de Hammerstein. Esta tese apresenta novos resultados teóricos que permitem a obtenção de algoritmos de identificação MRI para modelos com estrutura de Wiener e Hammerstein, sem a necessidade de minimizar a função de custo não linear. Além da demonstração dos resultados teóricos, novos algoritmos são propostos tendo a sua capacidade de predição, propriedades estatísticas e aplicação em controladores MPC não lineares avaliadas.
This thesis focuses on obtaining models that may produce a better performance of Model-based Predictive Controllers (MPC). Several papers published in the last 25 years have proposed methods based on the minimization of multi-step ahead prediction functions, which are inherently nonlinear. These methods have been called MPC Relevant Identification (MRI). Most of the papers focused on obtaining linear models. In the last 5 years, some methods have been proposed to obtain nonlinear models based on the minimization of the same cost function. These papers were based on the direct minimization of the nonlinear cost function to produce models with NARMAX (nonlinear Autoregressive Moving Average with exogenous inputs) structure. However, simplified MPC schemes may be obtained using models with Wiener and Hammerstein structures. This thesis presents new theoretical results which allow the development of MRI identification algorithms for models with Wiener and Hammerstein structures, without the need to perform the minimization of the nonlinear cost function. Besides the proof of theoretical results, new algorithms are developed and have their prediction capability statistical properties and performance in nonlinear MPC controllers evaluated.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Earth, Atmospheric, and Planetary Sciences, 1998.
Includes bibliographical references (p. 169-180).
by John J. Graham, Jr.
Ph.D.

Thesis: S.B., Massachusetts Institute of Technology, Department of Earth, Atmospheric, and Planetary Sciences, 2000.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 21-22).
Under the auspices of NASA's Global Tropospheric Experiment (GTE), the Pacific Exploratory Missions (PEM) have collected numerous air samples of many regions of the troposphere. Data from PEM-West B (February 7 to March 15, 1994), and PEM-Tropics A (August 15 to October 5, 1996) have been used here to study non-methane hydrocarbon (NMHC) ratios and to compare pollution transport by large scale convection and subsidence, as well as horizontal transport across the Pacific. For PEM-Tropics A, 7 cases are studied, each involving different aspects of transport. Persistent circulation features in the South Pacific played a significant role in NIMHC ratio distribution and processing. For PEM-West B, sources of a large pollution region are studied and compared to equatorial transport. NMHC ratios were found to be useful tracers of pollution distribution through the troposphere. The contrasts of these ratios across relatively small distances, particularly on either side of the South Pacific Convergence Zone in PEM-Tropics A, suggest that convection shapes pollution transport and distribution, particularly in the South Pacific.
This work was supported by the NASA GTE program under grant NAG1-1758 and NAG1-2173
by Christopher Chay Casso.
S.B.

Cette thèse traite de la synthèse et de la mise en œuvre en temps réel (RT) de schémas de contrôle prédictif non linéaire paramétré (pNMPC) pour les systèmes de suspension semi-active des automobiles. Le schéma pNMPC est basé sur une technique d'optimisation par simulation en boîte noire. Le point essentiel de la méthode est de paramétrer finement le profil d'entrée et de simuler le système pour chaque entrée paramétrée et d'obtenir la valeur approximative de l'objectif et de la violation des contraintes pour le problème pNMPC. Avec les résultats obtenus de la simulation, l'entrée admissible (si elle existe) ayant la valeur objective minimale ou, à défaut, la valeur de violation de contrainte la plus faible est sélectionnée et injectée dans le système et ceci est répété indéfiniment à chaque période de décision. La méthode a été validée expérimentalement sur dSPACE MicroAutoBoX II (MABXII) et les résultats montrent de bonnes performances de l'approche proposée. La méthode pNMPC a également été étendue à une méthode pNMPC parallélisée et la méthode proposée a été mise en œuvre pour le contrôle du système de suspension semi-active d'un demi-véhicule. Cette méthode a été mise en œuvre grâce à des unités de traitement graphique (GPU) qui servent de plate-forme modèle pour la mise en œuvre d'algorithmes parallèles par le biais de ses processeurs multi-cœurs. De plus, une version stochastique de la méthode pNMPC parallélisée est proposée sous le nom de schéma pNMPC à Scénario-Stochastique (SS-pNMPC). Cette méthode a été mise en œuvre et testée sur plusieurs cartes NVIDIA embarquées pour valider la faisabilité de la méthode proposée pour le contrôle du système de suspension semi-active d'un demi-véhicule. En général, les schémas pNMPC parallélisés offrent de bonnes performances et se prêtent bien à un large espace de paramétrage en entrée. Enfin, la thèse propose un outil logiciel appelé "pNMPC - A code generation software tool for implementation of derivative free pNMPC scheme for embedded control systems". L'outil logiciel de génération de code (S/W) a été programmé en C/C++ et propose également une interface avec MATLAB/Simulink. Le logiciel de génération de code a été testé pour divers exemples, tant en simulation que sur du matériel embarqué en temps réel (MABXII), et les résultats semblent prometteurs et viables pour la mise en œuvre de la RT pour des applications réelles. L'outil de génération de code S/W comprend également une fonction de génération de code GPU pour une mise en œuvre parallèle. Pour conclure, la thèse a été menée dans le cadre du projet EMPHYSIS et les objectifs du projet s'alignent sur cette thèse et les méthodes pNMPC proposées sont compatibles avec la norme eFMI
This thesis discusses the synthesis and real-time (RT) implementation of parameterized Nonlinear Model Predictive Control (pNMPC) schemes for automotive semi-active suspension systems. The pNMPC scheme uses a black-box simulation-based optimization method. The crux of the method is to finitely parameterize the input profile and simulate the system for each parameterized input and obtain the approximate objective and constraint violation value for the pNMPC problem. With the obtained results from the simulation, the input with minimum objective value or the least constraint violation value is selected and injected into the system and this is repeated in a receding horizon fashion. The method was experimentally validated on dSPACE MicroAutoBoX II (MABXII) and the results display good performance of the proposed approach. The pNMPC method was also augmented to parallelized pNMPC and the proposed method was implemented for control of semi-active suspension system for a half car vehicle. This method was implemented by virtue of Graphic Processing Units (GPUs) which serves as a paragon platform for implementation of parallel algorithms through its multi-core processors. Also, a stochastic version of the parallelized pNMPC method is proposed which is termed as Scenario-Stochastic pNMPC (SS-pNMPC) scheme and the method was implemented and tested on several NVIDIA embedded boards to verify and validate the RT feasibility of the proposed method for control of semi-active suspension system for a half car vehicle. In general, the parallelized pNMPC schemes provide good performance and also, fares well for large input parameterization space. Finally, the thesis proposes a software tool termed “pNMPC – A code generation software tool for implementation of derivative free pNMPC scheme for embedded control systems”. The code generation software (S/W) tool was programmed in C/C++ and also, provides interface to MATLAB/Simulink. The S/W tested for variety of examples both in simulation as well as on RT embedded hardware (MABXII) and the results looks promising and viable for RT implementation for real world applications. The code generation S/W tool also includes GPU code generation feature for parallel implementation. To conclude, the thesis was conducted under the purview of the EMPHYSIS project and the goals of the project align with this thesis and the proposed pNMPC methods are amenable with eFMI standard

The objective of this report was to implement battery cycling and an intermittent current interruption (ICI) method for determining battery resistance into a simple lithium-ion battery model in the finite element methods (FEM) program COMSOL Multiphysics, andevaluate how accurately the model reflects the behaviour of voltage and internal resistance with respect to experimental results. The ICI technique consists of repeating the steps of first having a longer charging period and then having a short current interruption, where the internal resistance is calculated from the voltage drop that occurs when the current is turned off. The model was evaluated against measurements, made with the same technique (ICI), on assembled NMC-graphite batteries. Codes written in the statistical programming language “R” were used to process the data from both COMSOL and the experiments. Both the batteries and the model were constructed with a reference electrode, to enable measurement of each electrode by itself. The results as documented in this report show that it is possible to simulate the measurement technique in COMSOL, but that both the resistance and voltage profiles differed quite a lot from the behaviour of the tested batteries. The resistance of the positive electrode did however give good results and it was possible to improve the model by changing some parameters. The magnitude of the resistance, which was already quite close, could be improved by changing the porosity and particle size, and the voltage profiles were improved when using voltage-data achieved from the real measurements.

Disturbing sound sometimes should be cancelled when music has been recorded. In this thesis, MATLAB was used as a tool. System identification was a main method used to find the unknown system. By subtracting the simulated output, disturbing sound was cancelled. Two different systems were identified with both linear (ARX) model and nonlinear (Parallel Hammerstein) model. The quality of these models was measured and compared using different methods. Possibility to implement this work on hardware was also discussed.

Ageing mechanisms of graphite/NMC Li-ion batteries have been studied using computational methods. The purpose of the project was to investigate solid electrolyte interphase (SEI) formation and growth during cycling of the battery. The SEI layer formation was considered to be a reason for capacity fade of the battery. Irreversible consumption of cyclable Li-ions and increased resistance in the layer was considered to be the result of solid electrolyte layer formation and these two effects were studied more closely using cell modelling. The battery cycled with three cases of fast charge rates (2C, 4C and 6C) and the same discharge rate (1C) showed a thick film formation on the anode side and a higher film resistance when compared to the battery cycled with the same charge/discharge rate (1C). All investigated batteries were affected by the studied ageing mechanism, and in the case of batteries cycled with fast charge rates, the ageing was even more pronounced. The report includes a general description of Li-ion battery functionality, a summary of ageing mechanisms and a mathematical description of the electrochemistry governing the battery and implemented in the software.

La inestabilidad microsatélite (MSI) es una característica de los pacientes HNPCC. En estos tumores la perdida del sistema de reparación MMR tiene como consecuencia una acumulación progresiva de mutaciones. Hasta la actualidad no esta claro, como se acumulan estas alteraciones. Sin embargo, la MSI se puede detectar en los pacientes HNPCC antes del diagnóstico del tumor. Uno de nuestros objetivo fue evaluar la presencia de inestabilidad genética en sangre periférica de 2 familias HNPCC tanto portadores como no portadores de una mutación germinal en los genes MLH1 y MSH2. Hemos realizado un análisis extensivo de la distribución alélica de BAT26 meditante una técnica basada en PCR-clonación de esta secuencia. En los pacientes no portadores de la mutación, la distribución alelica de BAT26 sigue una distribución de campana de Gauss sin ningún alelo por debajo de 21Adeninas, mientras que todos los portadores de la mutación demuestran alelos inestables con una frecuencia de 5,6%. Por lo tanto sugerimos que la baja inestabilidad caracteriza los portadores de mutaciones en MMR. Estas observaciones sugieren que las mutaciones somáticas se acumulan antes del diagnostico del tumor, aunque no esta claro si estas acumulación de mutaciones se debe a la pérdida de MMR en un porcentaje pequeño de células o a la haploinsuficiencia del MMR. La detección de estos alelos inestables posiblemente nos puede ayudar en la identificación de portadores asintomáticos que pertenecen a familias con mutaciones germinales no detectables en MMR.
Además del defecto en MMR, las alteraciones de los microsatélites en zonas no codificantes podrían tener otras causas. Por este motivo, hemos utilizado un modelo alternativo (DNA mitocondrial) para evaluar si estas alteraciones dependerán solamente del MMR como se ha postulado anteriormente. Las mutaciones somáticas en la secuencia D310 mitocondrial se ha asociado con la progresión tumoral. La inserción o la deleción de nucleótidos se ha encontrado en varios tipos de tumores. La frecuencia de mutaciones en tumores de colon, estómago u endometrio es de 23, 17 y 11%, respectivamente, que es paralelo al grado relativo de MSI observado en tumores con deficiencia en MMR (colon > estómago > endometrio, ratio relativo 10:8:4). Los tumores de colon con mutaciones de +1 nucleótido se ha observado en tumores de estadios avanzados de progresión. Se han identificado dos tumores con una mutación de T > C que restauró una repetición homoplasmica, con deleciones de secuencias de 4 y 6 nucleótidos. Estos resultados demuestran que el incremento mutacional de la secuencia repetitiva mitocondrial depende de la estructura repetitiva del DNA y no es resultado del proceso selectivo durante la tumorogénesis. Estos resultados sugieren que D310 se podría utilizar como reloj molecular para evaluar la historia replicativa de los tumores.
La última parte de este estudio se concentra en el análisis de los microsatélites en zonas codificantes y el efecto que podría tener en el proceso tumorogénico. Estas alteraciones podrían cambiar el comportamiento de varias vías donde están implicados estos genes.
El mantenimiento de la estabilidad genómica depende de una respuesta celular apropiada al daño y la integridad del sistema de reparación del DNA. Hemos analizado varios genes diana implicados en estas 2 vías en tumores con MSI. Hemos encontrado una alta frecuencia de mutaciones en los genes ATR (21%), MED1 (43%), hMSH3 (56%) y hMSH6 (43%). También se ha detectado una baja frecuencia en CHK1 (9% de los tumores). Estos resultados confirman que ATR, MED1 y CHK1 son genes diana en el proceso tumoral de estómago, y también sugiere que MED1 junto con hMSH3 y hMSH6 aumentan la inestabilidad genómica considerándolos como mutadores segundarios. Además, estos resultados sugieren la inhibición de la vía de respuesta de daño genómico que depende de ATR y CHK1 y que probablemente está implicada en el proceso tumoral en tumores gástricos con MSI.
Microsatellite instability (MSI) characterizes tumors arising in patients with HNPCC syndrome. In these tumors, the loss of MMR compromises the genome integrity, allowing the progressive accumulation of mutations and the establishment of a mutator phenotype in a recessive manner. It is not clear, however, whether MSI can be detected in HNPCC carriers before tumor diagnosis. The aim of this study was to evaluate the presence of genetic instability in MMR gene carriers in peripheral blood lymphocytes of carriers and non-carriers members of two HNPCC families harboring a germline MLH1 and MSH2 mutation, respectively. An extensive analysis of the allelic distribution of single molecules of the polyA tract bat26 was performed using a highly sensitive PCR-cloning approach. In non-carriers, the allelic distribution of single bat26 molecules followed a gaussian distribution with no bat26 alleles shorter than (A)21. All mutation carriers showed unstable alleles with an overall frequency of 5.6%. We therefore suggest that low levels of genomic instability characterize MMR mutation carriers. These observations suggest that somatic mutations accumulate well before tumor diagnosis. Even though it is not clear whether this is due to the presence of a small percentage of cells with lost MMR or due to MMR haploinsufficiency, detection of these short unstable alleles might help in the identification of asymptomatic carriers belonging to families with no detectable MMR gene mutations.
In addition to the defect in MMR, alterations of microsatellites in no- coding regions may have other causes. For this reason we have used an alternative model (mitocondrial DNA) to evaluate if these alterations depend only on the defects of the MMR, as previously thought. Somatic mutations at a mitochondrial noncoding polycytidine D310 repeat have been associated with tumor progression. We analyzed whether these alterations are due to the inherent mutability of repeated sequences. Insertion and deletion mutations were found in colon, stomach, endometrium, breast, lung, and prostate tumors. The mutation frequency in colon, gastric, and endometrial tumors was 23, 17, and 11% respectively, which paralleled the relative extent of microsatellite instability in long mononucleotide repeats observed in tumors with mismatch repair deficiency (colon > stomach > endometrium, relative ratio 10:8:4). Colon tumors with mutations of more than one nucleotide were more advanced in tumor progression. Further, two tumors showing a T > C mutation that restored the homopolymeric repeat, harbored sequential deletion mutations of 4 and 6 nucleotides. These results illustrate that the increased mutability of repeated mitochondrial sequences is dependent on the repetitive structure of the DNA molecule and suggest that mutations in the D310, whether homoplasmic or not, and by extrapolation, mitochondrial mutations in general, are not the result of selective pressure during tumorigenesis. We also suggest that the D310 may be used as an universal molecular clock to estimate the relative mitotic history of tumors.
The last part of this thesis concentrates in studying the alterations of microsatellites in coding regions and the effect that these will have in tumorogenesis process. Alteration in these genes sequences may be change the behaviour comportment of several pathways..
Maintenance of genomic stability depends on the appropriate cellular responses to DNA damage and the integrity of the DNA repair systems. We analyzed stomach tumors with MSI for frameshift mutations in several potential targets of the mutator phenotype involved in DNA damage-response pathways, and DNA repair system. High frequency of mutations was found within ATR (21%), MED1 (43%), hMSH3 (56%) and hMSH6 (43%) genes. Also, a low frequency of mutations within the CHK1 gene was detected in 9% of tumors. These results confirm ATR, MED1 and CHK1 as targets of the mutator pathway in stomach tumorigenesis, and also suggest a potential role of MED1 increasing, together with hMSH3 and hMSH6, the genomic instability in the mutator pathway as a secondary mutator. Furthermore, these results suggest that the inhibition of the ATR-CHK1 DNA damage-response pathway might be involved in the tumorigenesis of gastric cancer with MSI.

In the future autonomous vehicles are expected to navigate independently and manage complex traffic situations. This thesis is one of two theses initiated with the aim of researching which methods could be used within the field of autonomous vehicles. The purpose of this thesis was to investigate how Model Predictive Control could be used in the field of autonomous vehicles. The tasks to generate a safe and economic path, to re-plan to avoid collisions with moving obstacles and to operate the vehicle have been studied. The algorithm created is set up as a hierarchical framework defined by a high and a low level planner. The objective of the high level planner is to generate the global route while the objectives of the low level planner are to operate the vehicle and to re-plan to avoid collisions. Optimal Control problems have been formulated in the high level planner for the use of path planning. Different objectives of the planning have been investigated e.g. the minimization of the traveled length between the start and the end point. Approximations of the static obstacles' forbidden areas have been made with circles. A Quadratic Programming framework has been set up in the low level planner to operate the vehicle to follow the high level pre-computed path and to locally re-plan the route to avoid collisions with moving obstacles. Four different strategies of collision avoidance have been implemented and investigated in a simulation environment.

Rapporten beskriver arbetet och resultaten av en jämförelse mellan Sensu och op5 Monitor, vilka är verktyg som används för att övervaka enheter i nätverk, så kallade network monitoring systems. Arbetet har utförts för att utbudet av nätverksövervakningsverktyg ständigt växer och det ansågs värdefullt att jämföra en ny aktör med ett äldre verktyg som är byggd på ett annat tankesätt. Det som ansågs intressant att testa var hur dessa verktyg hanterade de rapporter som skapades och samlades in, om det slutgiltiga resultatet från detta skulle skilja sig åt eller inte. För att testa detta sattes en virtuell testmiljö upp, där Sensu och op5 Monitor rullade parallellt med varandra och övervakade samma system och använde sig utav samma plugin för övervakningen. Experimenten utfördes på två stycken tjänster, BIND9 samt Apache2, i och med att de två pluginen som användes var uppbyggda på olika sätt konstruerades även olika experiment. Under dessa experiment samlades information in om hur de två övervakningsverktygen hanterade de rapporter de fick in, vilket sedan sammanställdes och analyserades. Slutsatsen av det hela var att Sensu och op5 Monitor hanterar sina insamlade rapporter på ett likvärdigt sätt, de rapporterade resultaten blev i samtliga fall detsamma, således fungerade de två övervakningsverktygen på ett jämgott vis.
The report describes the work and results of a comparison between Sensu and op5 Monitor, which are both tools used to monitor devices in a network, more commonly known as network monitoring systems. The subject was chosen due to the fact that there is such a wide range of network monitoring systems, and it is constantly expanding. It was considered valuable to compare a newcomer with an older tool that is built with a different mindset. It was considered interesting to test how these tools handled the reports created and collected by them, to see if the final results from this would differ or not. To test this a virtual testing environment was built, where Sensu and op5 Monitor were run in parallel to each other and monitored the same systems and used the same set of plugins. The experiments were conducted on two services, BIND9 and Apache2, since the plugins were constructed in different ways, so were the various experiments. In these experiments information was gathered about how the two monitoring tools handled the reports they received, which was then compiled and analysed. The conclusion of it all was that Sensu and op5 Monitor handles the collected information in a similar manner. The reported results were in all cases the same, thus the two monitoring tools behave in the same fashion.

L’électrification des véhicules se base aujourd’hui sur l’utilisation de batteries Lithium-ion utilisant des oxydes lamellaires de nickel, manganèse et cobalt (NMC) comme matériaux d’électrode positive. Au niveau industriel, la production de matériaux riches en nickel est désormais privilégiée pour satisfaire la demande de meilleures autonomies de la batterie de la part des consommateurs. Cependant, ces matériaux sont affectés par un fort dégagement gazeux pendant le cyclage en batterie. Plusieurs études ont été conduites pour définir les principales causes de ce dégazage et trouver les meilleures solutions pour le réduire. En revanche, la plus grande partie de ces recherches se concentre exclusivement sur une observation des matériaux pendant le cyclage. Pour répondre au besoin d’une caractérisation systématique du NMC riche en Ni dans son état initial, les surfaces de plusieurs échantillons industriels ont été observées à l’aide de différentes techniques d’analyse. 7Li MAS-NMR, XPS, STEM-EELS et SEM-FIB ont été combinées pour obtenir une description complète des matériaux et de leurs surfaces. Les limites et complémentarités de chaque technique sont discutées et les résultats obtenus comparés et exploités de façon synergique. Il a donc été possible de décrire en détail la surface du matériau dans son état initial à l’échelle nanométrique et d’évaluer ensuite l’influence des conditions de stockage, ainsi que des étapes de mise en forme en électrode. Le mode opératoire ainsi défini a pu être utilisé par la suite pour analyser la surface de matériaux issus de différentes méthodes de synthèse
The electrification of vehicles is currently based on the use of Lithium-ion batteries using lamellar oxides of nickel, manganese and cobalt (NMC) as positive electrode materials. At the industrial level, the production of nickel-rich materials is now the main focus in order to satisfy the need for longer range battery performances demanded by consumers. However, these materials are affected by strong outgassing during battery cycling. Several studies have been conducted to define the main factors contributing to this outgassing and to find the best solutions to reduce it. The majority of this research, though, focuses exclusively on observing the materials during cycling. To address the necessity of a systematic characterisation of Ni rich NMC in its initial state, the surfaces of several industrial samples were observed using different analytical techniques. 7Li MAS-NMR, XPS, STEM-EELS and SEM-FIB were used to obtain a thorough description of the materials and their surfaces. The limitations and complementarities of each technique are discussed and the results obtained compared and exploited in a synergistic way. It was thus possible to describe in detail the surface of the material in its initial state at the nanometric scale and to evaluate the influence of the storage conditions, as well as the electrode preparation steps. The procedure thus defined could then be used to analyse the surface of materials from different synthesis methods

Rapporten tar upp en kartläggning av nätverksövervakningssystem (NMS) som används för att övervaka nätverkstjänster och noder på ett nätverk. De egenskaper för NMS som utvärderas är vilket stöd systemen har för att övervaka ett flertal tjänster, hur god prestandan är för varje system samt hur god användbarheten i gränssnittet är. Resultatet visar att Nagios, OpenNMS samt Argus hade stöd för samtliga tjänster medan Munin inte hade stöd för nätverksenheter och Cacti endast stöd att övervaka SNMP. Det visar även att Nagios och OpenNMS generellt hade möjlighet att larma vid fler händelser samt att dessa två system var markant snabbare än Cacti och Munin. Användbarheten visade relativt stor skillnad i olika system. OpenNMS hade högst totalpoäng, men Nagios presterade något bättre i vad Sundström (2005) kallar för interaktion. Munin och Argus fick samma resultat med låg funktionalitet och högre struktur medan Cacti hade god funktionalitet och interaktion men väldigt låg struktur.

This thesis deals with the design of a robust and safe control algorithm to aim at an artificial pancreas. More precisely we will be interested in controlling the stabilizing part of a classical cure. To meet this objective, the design of a robust nonlinear model predictive controller based on the solution of a saddle point optimization problem is considered. Also, to test the controller performances in a realistic case, numerical simulations on a FDA validated testing platform are envisaged.In a first part, we present an extension of the usual nonlinear model predictive controller designed to robustly control, in a sampled-data framework, systems described by nonlinear ordinary differential equations. This controller, which computes the best control input by considering the solution of a constrained saddle point optimization problem, is called saddle point model predictive controller (SPMPC). Using this controller, it is proved that the closed-loop is Ultimately Bounded and, with some assumptions on the problem structure, Input-to State practically Stable. Then, we are interested in numerically solving the corresponding control problem. To do so, we propose an algorithm inspired from the augmented Lagrangian technique and which makes use of adjoint model.In a second part, we consider the application of this controller to the problem of artificial blood glucose control. After a modeling phase, two models are retained. A simple one will be used to design the controller and a complex one will be used to simulate realistic virtual patients. This latter is needed to validate our control approach. In order to compute a good control input, the SPMPC controller needs the full state value. However, the sensors can only provide the value of blood glucose. That is why the design of an adequate observer is envisaged. Then, numerical simulations are performed. The results show the interest of the approach. For all virtual patients, no hypoglycemia event occurs and the time spent in hyperglycemia is too short to induce damageable consequences. Finally, the interest of extending the SPMPC approach to consider the control of time delay systems in a sampled-data framework is numerically explored.

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The purpose of this study is to adapt and embed a navigation system and control of mobile robots, based on NMPC, in a low-cost board existent on the market, to provide sufficient com-putational resources so that the robot is able to converge, without losing performance, using the same horizons applied in a Laptop. The obtained results demonstrate the proposed scenario according with the experiments, proving that it is possible to use low cost boards, to a navigation system and control of mobile robots, based on NMPC, using the same predictive and control horizons applied in a Laptop.
A proposta desse trabalho é adaptar e embarcar um sistema de navegação e controle de robôs móveis, baseado em NMPC, em uma placa de baixo custo já existente no mercado, que dispo-nibilize recursos computacionais suficientes para que o Robô seja capaz de convergir, sem perda de desempenho e utilizando os mesmos horizontes aplicados em um Laptop. Os Resulta-dos obtidos demonstram todo o cenário proposto e de acordo com os experimentos realizados, comprovou-se que é possível o uso de placas de baixo custo, para controle de robôs móveis, baseado em NMPC, utilizando os mesmos horizontes de predição e controle aplicados em uma Laptop.

The focus of this Thesis has been to evaluate different monitoring systems and processes that are used by the Network Operations Center at TDC Sverige AB. The problem formulation involves (i) how the monitoring systems are used, (ii) how these work together, (iii) what processes are involved and (iv) how the systems and processes can be improved to benefit the Network Operations Center. Processes involved in TDC’s work follows the Information Technology Infrastructure Library. To be able to answer the problem formulation, the current documentation is browsed and together with meetings with key figures within the company; such as managers, project managers, technicians and system administrators; information is gathered to give a comprehensive view of the current state of the monitoring systems, and the whole process leading to handover to the Network Operations Center. TDC Network as a Service is a concept that includes different networking solutions in which LAN and WLAN as a Service offers standardized networking solutions for LAN and WLAN. The Network Management System is described, which includes HP Network Node Manager i, Network Performance Servers and incident ticket systems. The process of how incident tickets can be created, both manually and automatically, is described as well as the whole process of how new customers are added to the monitoring and how customers are registered in the different Service Asset and Configuration Management applications. It is discussed how new nodes are added to the monitoring, and which systems are involved in this process, including Network Node Manager i, VisionApp, NetMRI and incident ticket systems. The regular monitoring process of the Network Operations Center is presented in this Thesis. It is suggested that the improvements include involving the Network Operations Center at an earlier stage during the selling and implementation process, and devised a better transition to the Service Operation phase. TDC would benefit from fewer Service Asset and Configuration Management applications and incident ticket systems and there should be better routines regarding documentation.

Thesis advisor: John Ebel
The New Madrid Seismic Zone (NMSZ) is well known for producing some of the largest intra-cratonic earthquakes within the North American Plate. The common hypothesis for the geological structure within the NMSZ is that stress is released across three major faults: the Cottonwood Grove Fault, the New Madrid North Fault, and the Reelfoot Thrust Fault. Evidence exists that would suggest an alternative model of geologic deformation in the area: that stress is being released across more than these three faults. A geologic and geophysical investigation was done to investigate a hypothetical fault west of Dyersburg, TN to test the alternative multi-fault hypothesis. A seismically created sand blow was logged in close proximity to the fault projection. Weathering of the sand blow indicated that the age of the sand blow came from a seismic event prior to the 1811-1812 earthquakes. There was no evidence to confirm this sand blow was created by a hypothetical fault in close proximity. A seismic exploration of the area was done across four seismic lines, primarily mapping Quaternary-age Mississippi River flood plain deposits. These seismic surveys yielded no evidence to suggest the presence of an additional fault. Across all surveys no evidence was found to conclusively support any existing theory on fault movement in the NMSZ
Thesis (MS) — Boston College, 2014
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Earth and Environmental Sciences

Poor prognosis for high-risk neuroblastoma patients makes it necessary to find novel treatmentstrategies. This work aims to understand the cell cycle behavior of various high-riskneuroblastoma cell lines following chemotherapy treatment. Here, we mapped the expressionof cell cycle dependent proteins, p21 and p27, in seven high-risk neuroblastoma celllines. All cell lines showed an overall impaired growth following doxorubicin treatment.However, regrowth was observed in all cell lines between day 6 to 15 by forming colonies.The expression of p21 and p27 was measured in all cell lines showing an upregulationof p21 in 3 out of 5 p53 mutated cell lines while it was downregulated in the 2 cell lineswith a p53 wild type. Furthermore, inhibition assays using inhibitors of CHK1/2, p21 ,andSKP2 were performed. The results were promising as the CHK1/2 inhibitor reduced cellviability in all tested cell lines, while the p21 inhibitor had an effect in 3 out of 6 testedcell lines and the SKP2 inhibitor in 4 out of 6 tested cell lines. Confluency measurementover 15 days showed impaired growth following treatment with the CHK1/2 inhibitor for3 out of 6 tested cell lines and p21 inhibitor in 1 out of 6 tested cell lines. The obtainedresults were encouraging and might aid in finding a novel treatment strategy preventingresistance and relapse in neuroblastoma. However, further studies are needed in order tovalidate the efficacy and safety of these promising drugs in neuroblastoma patients.
Dålig prognos för högrisk neuroblastompatienter gör det nödvändigt att hitta nya behandlingsstrategier.Detta arbete syftar till att förstå cellcykelbeteendet hos olika högrisk neuroblastomcellinjerefter kemoterapibehandling. I denna studie kartlades uttrycket av cellcykelberoendeproteinerna, p21 och p27, i sju högrisk neuroblastomcellinjer. Alla cellinjervisade en total nedsatt tillväxt efter doxorubicinbehandling. Återväxt observerades emellertidmellan dag 6 och 15 genom bildandet av kolonier. Uttrycket av p21 och p27 mättesi alla cellinjer. Resultaten visade en uppreglering av p21 i 3 av 5 p53-muterade cellinjermedans det nedreglerades i de två cellinjerna med en p53-vildtyp. Vidare utfördes inhiberingsanalysermed användning av hämmare mot CHK1/2, p21 eller, SKP2. Resultatenär lovande då CHK1/2-hämmaren reducerade cellviabiliteten i alla testade cellinjer, medanp21-hämmaren hade en effekt i 3 av 6 testade cellinjer och SKP2 i 4 av 6 testadecellinjer. Konfluensmätning under 15 dagar visade nedsatt tillväxt efter behandling medCHK1/2-hämmaren för 3 av 6 testade cellinjer och p21-hämmare i 1 av 6 testade cellinjer.De erhållna resultaten är lovande och kan hjälpa till att hitta en ny behandlingsstrategi somförhindrar resistens och återfall i neuroblastom. Ytterligare studier behövs emellertid föratt validera effektiviteten och säkerheten för dessa lovande läkemedel hos neuroblastompatienter.

"A ¡°mixed cathodes¡± LIB recycling process was first proposed and developed in the CR3 center at Worcester Polytechnic Institute. This process can efficiently and economically recover all the valuable metal elements in LIB waste. In the end of the recovery process, lithium, nickel, manganese, and cobalt ions will be recovered in the leaching solution. The objective of this work is to utilize the leaching solution to synthesis NixMnyCoz(OH)2 precursors and their corresponding LiNixMnyCozO2 cathode materials. The synthesized cathode materials can be used to build new LIBs, allowing the overall process to be a ¡°closed loop¡±. "

This thesis focuses on the possibilities of application of nonlinear model predictive control for electric drives. Specifically, for drives with a permanent magnet synchronous motor. The thesis briefly describes the properties of this type of drive and presents its mathematical model. After that, a nonlinear model of predictive control and methods of nonlinear optimization, which form the basis for the controller output calculation, are described. As it is used in the proposed algorithm, the Active set method is described in more detail. The thesis also includes simulation experiments focusing on the choice of the objective function on the ability to control the drive. The same effect is examined for the different choices of the length of the prediction horizon. The end of the thesis is dedicated to the comparison between the proposed algorithm and commonly used field oriented control. The computational demands of the proposed algorithm are also measured and compared to the used sampling time.

De nouveaux électrolytes à base de N-methyl sydnone (NMS) et de carbonates d'alkyle dissymétriques (ACS) ont été étudiés en vue de leur utilisation dans les accumulateurs à ion- lithium. Chacune de ces nouvelles molécules synthétisées présente une propriété intéressante pour cette application. En l'occurrence, la NMS possède une constante diélectrique particulièrement élevée, quant aux ACS, leur température de fusion est très basse, ce qui leur confère la propriétés de rester à l'état liquide sur un large domaine de température. L'étude des propriétés physico-chimiques de ces solvants et de leurs mélanges avec d'autres carbonates usuellement utilisés dans les batteries tels le carbonate d'éthylène (EC) et le carbonate de diméthyle (DMC) ont été déterminées. La constante diélectrique, la viscosité, la conductivité d'un sel de lithium (en particulier LiPF 6) et le produit de Walden ont été quelques uns des paramètres considérés. Les performances électrochimiques ont également fait l'objet de cette étude. La détermination du potentiel de réduction et du potentiel d'oxydation ont contribué à mettre en évidence le domaine d'électroactivité. Le comportement électrochimique d'une électrode de graphite (cote anodique de l'accumulateur) et d'une électrode d'oxyde de cobalt (cote cathodique) ont été étudiés. Les différentes capacités, le comportement en cyclage et le vieillissement ont été évalués au cours de cette étude.

Le but de cette thèse était d'étudier et de mieux comprendre les mécanismes d'interaction entre protéines laitières (caséines micellaires natives NMC et protéines de lactosérum natives WPI) sous forme de poudres dispersées (5% p/v) dans des milieux fortement ionisés par des sels (NaCl, CaCl2). D'une manière générale notre étude a été organisée en trois parties. Premièrement, nous avons étudié l'influence des milieux ioniques (eau distillé, solution de NaCl, solution de CaCl2) sur la réhydratation de protéines laitières. Dans une seconde partie nous avons caractérisé les dispersions en milieux ionisés par les études respectives de la structure secondaire des protéines, de la taille et de la morphologie des particules en cours de dispersion et de l'hydrophobicité des protéines. Dans la troisième et dernière partie nous nous sommes intéressés aux propriétés fonctionnelles des protéines du lactosérum par l'effet combiné de la température (30 - 90°C) et de la concentration en NaCl (0,75 - 3%). La réhydratation des protéines du lait a montré deux comportements distincts en fonction du type de sel d'une part (NaCl, CaCl2) et de la concentration d'autre part (0 - 12%). Dans les dispersions de NMC, avec l'ajout et l'augmentation de la concentration de NaCl on observe (DLS, TEM), une désintégration des micelles de taille 150 nm en petites micelles de 20-30 nm qui sont plus ou moins agrégées. En définitive, les propriétés fonctionnelles des protéines du WPI dépendent en même temps de la concentration en sel et de la température appliquée
The overall objective of this work was to investigate the mechanisms of protein-salt interactions and linkage between milk proteins powders and milk proteins dispersions (5% w/v) mainly NMC and WPI under various ranges of ionic environments (distilled water, NaCl solution and CaCl2 solution. In the first phase, we investigated the influence of the ionic environments on milk proteins powders rehydration profiles. The second phase of this study includes the characterization of milk proteins dispersions in an aqueous ionic environment regarding changes in the protein: secondary structure (ß-sheet, alpha-helix, ß-turns and unordered structures), size, morphological features and surface hydrophobicity by using FTIR, TEM, and DLS with other complimentary techniques. In the last part, the functionality of whey proteins was studied by the combined effect of heat and different ratios of salts. For this purpose, the study was exclusively focalized in an aqueous ionic medium composed of NaCl (0.75-3%) at different temperatures (30-90°C). The results obtained from the first part showed two distinct rehydration behaviors depending on the salts type and concentration. For the NMC dispersions under salt increase, spherical micelles with an average size around 150 nm disintegrated in sub-micelles around 20-30 nm and more or less aggregated were observed by DLS and TEM. WPI dispersions in water were composed of well separated proteins by a spherical shape with two populations around 6 and 70 nm. Salt increase resulted in an aggregation of the proteins and the formation of denser aggregates. Moreover, a combined salt/heat resulted showed a stabilizing effect on the secondary structural elements of both Amide I and III bands and higher denaturation temperatures observed by FTIR and µDSC respectively. A size and morphological investigation showed a transition from spherical/compact protein aggregates to linear ones. Finally, this work demonstrated that whey protein functional properties depend on both salt and how heat treatment is applied

En raison de leur faible pression de vapeur et de leur stabilité électrochimique (5~6 V) et thermique, les dinitriles N≡C-(CH2)n-C≡N sont proposés comme solvants d’électrolytes alternatifs aux carbonates d’alkyles habituellement utilisés dans les batteries Li-ion. L’objectif de cette thèse est d’étudier le comportement physico-chimique de ces électrolytes alternatifs (viscosité, conductivité ionique, comportement thermique, propriétés volumétriques, etc.) et leur compatibilité avec une application dans les batteries Li-ion. Deux systèmes de batteries sont étudiés en utilisant une électrode positive d’oxyde lamellaire (LiNi1/3Mn1/3Co1/3O2) associée à une électrode négative à bas potentiel (graphite) ou à plus haut potentiel (Li4Ti5O12). La cyclabilité des électrodes en demi-pile et en pile complète est étudiée en fonction de la composition de l’électrolyte et de la nature du dinitrile utilisé. Les techniques de caractérisations suivantes : spectroscopie d’impédance électrochimique, microscopie électronique et spectroscopie de photoélectrons aux rayons X, sont utilisées pour suivre le processus de passivation des électrodes par formation d’une interface solide (SEI). L’effet de la présence d’additifs favorisant la formation de la couche de passivation a été étudié et leur efficacité est ainsi clairement mise en évidence
Due to their low vapor pressure as well as their electrochemical (5~6 V) and thermal stability, dinitriles N≡C-(CH2)n-C≡N are proposed as alternative electrolyte solvents to alkyl carbonates commonly used in Li- ion batteries. The objective of this thesis is to study the physico-chemical behavior of these alternative electrolytes (viscosity, ionic conductivity, thermal behavior, volumetric properties, etc.) and their use in Li-ion batteries. Two battery systems are studied using a lamellar oxide (LiNi1/3Mn1/3Co1/3O2) as positive electrode associated with graphite or Li4Ti5O12 as negative electrodes. The cyclability of electrodes in half-cell and full-cell is studied according to the electrolyte composition and the nature of the dinitrile used. Characterization techniques like: electrochemical impedance spectroscopy, electron microscopy and X-Ray photoelectrons spectroscopy, are used to study the passivation of the negative electrode and the stability of the positive electrode. The effect of adding specific solid electrolyte interphase (SEI) builders is investigated and their efficiency is hence clearly demonstrated

This thesis deals with description of preparation and use of monomers and copolymers for gel polymer electrolytes usable in electrochemical power sources. This thesis is divided in theoretical and experimental part. The theoretical part describes electrolytes focused on gel polymer electrolytes, measuring methods and materials used for experiments. The experimental part deals with calculation of composition of polymer electrolytes, method of preparation and evaluation of measured results. The method of applying GPE to a negative LTO electrode and a positive NMC electrode is described too. Linear Sweep Voltammetry (LSV) and Potentiostatic Electrochemical Impedance Spectroscopy (PEIS), Cyclic Voltammetry (CV) and Galvanostatic Cycling with Potential Limitation (GCPL) were chosen for measurement of properties.

For the last 9,000-10,000 years the Central Hardwood Region (CHR) has been primarily composed of a mosaic of mesophytic communities in climax and communities of successional forest types dominated by oak (Quercus Linnaeus) and hickory (Carya Nuttall). Shade intolerant oak/hickory dominated forest types have been maintained by natural disturbance processes in synergy with anthropogenic causes, resulting in a large composition of communities which are neither at climatic nor edaphic climax. Reduction in fire events, thinning, forest grazing, and other disturbance processes over the last 80-100 years have coincided with decreased regeneration of shade intolerant species due to lack of adequate light availability and recruitment of shade tolerant species of communities dominated by American beech (Fagus grandifolia L.) and maple (Acer saccharum L.) into the overstory of forests typically dominated by oak/hickory. Forest inventory data at Trail of Tears State Forest was analyzed across two separate time events (1980 and 2014) to determine compositional and structural changes which have occurred. Density, basal area, and community patterns via ordination were compared across six Ecological Land Types (ELTs) to determine topography’s effect on composition. Community trends were analyzed via NMS Ordination and between ELTs by a Mantel Test. A Multi-Response Permutation Procedures (MRRP) was also used as a nonparametric method for assessing differences between ELTs examined in the NMS. Density and basal area between years for species, ELT, and species*ELT interactions were compared. Across all ELTs, between 1980 and 2014, overstory density decreased from 218 trees/ac in 1980 to 180 trees/ac in 2014 and basal area increased from 98 ft2/ac in 1980 to 106 ft2/ac in 2014. Maple basal area increased from 5 ft2/ac to 12 ft2/ac while beech increased from 1 ft2/ac to 8ft2/ac, signifying progression of these species from the understory up into the canopy. The component of soft masting species within the forest has also decreased sharply in the last 34 years. MRPP analysis of overstory compositional gradients reported distinct species compositions between ELTs, however the trend was weak (MRPP: p < 0.001, A = 0.038). NMDS ordination graphs confirmed MRPP showing little separation among ELTs. The final stress was 18.71146 and instability was < 0.01 after 212 iterations (Table 6). Our research at TTSF is a clear example of oak/hickory succession to beech maple on an upland site among species community types as delineated by topographic moisture gradient (ELTs) within the CHR. Expansion of beech and maple onto xeric ELTs suggests a breakdown of edaphic barriers that have previously been thought to be resistant to encroachment from mesophytic species. Currently oak decline induced by lack of management is likely the number one forest health issue resulting in loss of oak/hickory and other soft masting species.