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Yes / Here in, we describe a non-covalent (ionic interlocking and hydrogen bonding) strategy of self-healing in a covalently crosslinked organic-inorganic hybrid 15 nanocomposite hydrogel, with special emphasize on it's improved mechanical stability. The hydrogel was prepared via in-situ free radical polymerization of sodium acrylate (SA) and successive crosslinking in the presence of poly(2-(methacryloyloxy)ethyl trimethyl ammonium chloride) (PMTAC) grafted cationically armed starch and organically modified montmorillonite (OMMT). This hydrogel shows stimuli triggered self-healing following damage in both neutral and acidic solutions (pH=7.4 and pH=1.2). This was elucidated by tensile strength and rheological analyses of the hydrogel segments joined at their fractured points. Interestingly this hydrogel can show water based shape memory effects. It was observed that the ultimate tensile strength (UTS) of the self-healed hydrogel at pH = 7.4 was comparable to extensor digitorum longus (EDL) muscle of the New Zealand white rabbit. The as synthesized self-healable hydrogel was found to be non-cytotoxic against NIH 3T3 fibroblast cells. / Medical Research Council (MRC (MR/N501888/2))

Yes / The Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer. / This work was supported by the EPSRC (RCUK Academic Fellowship and Grant EP/H002626/1 to H.M.S.) and Prostate Cancer UK (Pilot Grant PA10-01). F.O.F.O.A-S.. was funded by the Public Authority for Applied Education and Training, Kuwait (PhD studentship).

Ceria is a lanthanide series element that can exist as Ce3+ or Ce4+. Cerium oxide nanostructures are being developed for use in industry as catalysts. Nanostructures often behave differently from their corresponding macrostructures and these new behaviors can result in novel and important biological and chemical properties. The free radical theory of aging suggests that free radicals many of which are reactive oxygen species, damage cellular macromolecules. This damage can contribute to degenerative diseases, cancer and aging. Recent research has shown that ceria oxide nanoparticles protected cells from UV and radiation damage as well as decrease intracellular reactive oxygen species in primary cell cultures. The enzyme superoxide dismutase (SOD) protects the cell from free radicals by reacting with superoxide, a reactive oxygen species. Chemicals that catalyze the same reaction as SOD are referred to as SOD mimetics. Another biologically significant free radical is nitric oxide, a reactive nitrogen species. Nitric oxide is an important signaling molecule in both the cardiovascular and nervous system; however it can also cause damage to proteins through nitrosylation. When superoxide and nitric oxide react with each other they form the highly potent free radical, peroxynitrite. This reaction naturally occurs in the phagolysosome of the macrophage and is utilized by the immune system to kill pathogens. Nanoceria was tested for activity against superoxide, nitric oxide and peroxynitrite. The results presented in this work show that ceria oxide nanoparticles exhibit SOD mimetic activity and reduce protein nitrosylation in vitro.

In 1972, with the publication of Violence and the Sacred, René Girard makes the stunning assertion that violence is the foundation of culture. Humanity’s innate urges for competition and rivalry entrap us in cycles of violence, which left alone would find no resolution. Girard calls the cause of this rivalry “mimetic desire”, and the only way out of this deeply embedded vengeance is to create a scapegoat to take the blame, reconciling the conflicting parties. Girard asserts that the biblical texts uniquely reveal the mechanisms of mimetic rivalry and scapegoating, and even demystify sacrificial rituals as nothing more than sacrilized “good” violence to keep a fragile peace. This revelation, according to Girard, can finally allow us to remove violence from the sacred. Much scholarship has been devoted to Girard’s theory, in particular how it offers a viable alternative to the still-dominant sacrificial theology of the cross. But there is little scholarship on the connection between Girard and Judaism; and Girard’s own work leaves us with a picture of Judaism that is at best incomplete, and at worst unable to find an answer to disturbing violence permeating the scriptures. This dissertation brings the Hebrew Bible into dialogue with Girard’s ideas in a systematic fashion to assert, contra Girard, that the Jewish revelation is a full, effective and even practical expression of his theory. After an overview of Girard’s work in the first chapter, the dissertation examines three Jewish “vaccines” to the mimetic disease as follows: the Birkhat ha-Banim (“The Blessing of the Children”); the reading of the Book of Esther on Purim; and the reading of Jonah on Yom Kippur. The conclusion to the dissertation asserts, drawing on these three demonstrations, the following points: 1) Rene Girard gives an important and clarifying lens to aid us in finding a new way to talk about, understand, and unify Jewish scripture and ritual; 2) a Jewish perspective can help flesh out what a different “revelation” of Girard’s mimetic desire looks like—even providing prescriptions to curtail this desire; and 3) positive mimesis is possible, and there are Hebrew examples of it free of originary violence. The final chapter addresses certain challenges in reconciling Girard with Judaism, moving toward a sincere Jewish Girardianism that will harmonize with the central views of the tradition.

Das Ovarialkarzinom ist eines der tödlichsten Malignome in der Gynäkologie und birgt eine große therapeutische Herausforderung. Trotz Platin und Taxan haltiger Chemotherapie liegt die Rezidivrate des Ovarialkarzinoms bei 70%. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gilt aufgrund seiner Eigenschaft spezifisch in Krebszellen Apoptose zu induzieren ohne normalen Körperzellen zu schaden in der Krebsforschung als vielversprechendes Therapeutikum. Seit einiger Zeit ist jedoch ersichtlich, dass 50% der Zelllinien und die Mehrheit aller primären humanen Krebszellen resistent für TRAIL induzierte Apoptose sind (Koschny, Walczak et al. 2007) und zunächst sensitiviert werden müssen. In dieser Studie konnte gezeigt werden, dass primäre Ovarialkarzinomzellen die mit Hilfe von EpCAM Dynabeads aus der Aszites von Krebspatientinnen isoliert wurden, sowohl mit Bortezomib (Proteasominhibitor) als auch mit PIK75 (PI3K- Inhibitor)spezifisch für TRAIL induzierte Apoptose sensitiviert werden konnten. Desweiteren konnte gezeigt werden, dass diese Kombinationstherapie normale hämatopoietische Zellen nicht beschädigt. Dies bekräftigt vor allem die Eigenschaft von TRAIL, krebszellspezifisch Apoptose zu induzieren. Wichtig ist vor allem, dass diese Kombinationstherapie sogar Chemotherapie resistente primäre Ovarialkarzinomzellen in Apoptose führen konnte.

The Mimetic Theory (MT) of René Girard promises a new landscape for the humanities. In this paper I will outline MT, giving a brief overview of the terrain and how the theory works, defend MT against criticisms made against it, and argue that MT ought to be evaluated by a wider academic audience. / Thesis (Master, Philosophy) -- Queen's University, 2013-06-03 14:15:30.176

Becoming a young woman amid the foothills and valleys of the Appalachian Mountains has fulfilled me with an awareness that I am not from "around these parts" that I now find myself in. As I navigated my way across the mountains, to the southern slopes of the east coast, I began to realize the life I was leaving behind through the process of photography, film, and the act of making a recording. This document speaks about the ideas and persistent energy that drive my process of creation while focusing on three important bodies of work that exhibit what I believe to be a method of engagement between the body and the camera. Out of my experiences, I want to make record of the blips and intonations, and of the in-between spaces where language is displaced and the visual speaks for itself.

Made available in DSpace on 2016-04-25T20:21:12Z (GMT). No. of bitstreams: 1 Silvia Maria Carbone.pdf: 9290034 bytes, checksum: 1d06740e586db906924ebaeba33e0ed3 (MD5) Previous issue date: 2014-06-04 / Conversations with René Girard proposes understanding of the work of Girard in all its complexity. The thesis focuses on analyzing the theory of mimetic desire, the relationship between violence and the sacred, and the need for a scapegoat. Three interwoven, united themes surround all the work of Girard, explained for the first time in the Violence and the Sacred essay considered as one of the pillars of Girardian thought. According to Girard, violence intrinsic to humanity, is the desire to control the violence that establishes the passage of the state of nature to the state of culture. The channeling of violence is vital to the existence of societies - archaic and modern. Girard shows us that the way to control violence is possible only by the institution of the sacred, that is through the atoning sacrifice of the victim. For the author, the desire is always mimetic desire : what is desired by the other subject, which raises the rivalry and consequently the violence that needs to be contained / Conversações com René Girard propõe o entendimento da obra de Girard em toda sua complexidade. A tese concentra a análise sobre a teoria do desejo mimético, a relação da violência com o sagrado e a necessidade do bode expiatório. Três temas entrelaçados, uníssonos que circundam toda a obra de Girard, explicitados pela primeira vez em A violência e o Sagrado, ensaio considerado como um dos pilares do pensamento girardiano. Para Girard, a violência é intrínseca à humanidade, é o controle do desejo de violência que estabelece a passagem do estado de natureza para o estado de cultura. A canalização da violência é vital para a existência das sociedades arcaicas e modernas. Girard nos mostra que a forma de controle da violência só é possível pela instituição do sagrado, que o faz por meio dos sacrifícios da vítima expiatória. Para o autor, o desejo é sempre mimético, desejamos aquilo que é desejado por outro sujeito, o que suscita a rivalidade e, consequentemente, a violência que precisa ser contida

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-06-21T19:19:10Z No. of bitstreams: 1 AnaDias.pdf: 3102283 bytes, checksum: 6eb4c0bb2a542e274e68001ba7b1b766 (MD5) / Made available in DSpace on 2017-06-21T19:19:10Z (GMT). No. of bitstreams: 1 AnaDias.pdf: 3102283 bytes, checksum: 6eb4c0bb2a542e274e68001ba7b1b766 (MD5) Previous issue date: 2016-06-21 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) / Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Apoio à Pequisa (FUNAPE) / Leishmaniasis is a neglected and endemic disease in Brazil, especially in the Northeast, caused by over 20 species of the Leishmania protozoan. Diagnosis includes epidemiological, clinical, and laboratory aspects. Despite the existence of various diagnostic techniques that can be used, none has 100% sensitivity and specificity. Hence, this study aimed to validate three recombinant mimetic peptides (LC1, LC2, and LT) obtained by Phage display, for the development of a specific, sensitive, rapid low-cost immunological diagnosis. Sera for detection of IgG from 223 individuals were used (123 with visceral leishmaniasis (VL), 45 with cutaneous leishmaniasis (CL) and 55 with LV-HIV coinfection). For cross-reaction tests, we used samples of patients with Chagas' disease (n = 60) and Malaria (n=65), and control group (n= 75 sera from newborns). The peptides were also tested in saliva from patients with LV (n = 65), with LT (n = 40), and healthy individuals from an endemic area were used as control (n =35). Diagnostic tests using the mimetic LC1 and LC2 peptides were carried out in serum of 15 asymptomatic subjects; 13 healed individuals and 15 healthy subjects. To test the ability of the mimetic peptides to improve the immune response against Leishmania, murine macrophages C57BL/6 were treated in vitro with peptides LC1, LC2, and LT (0,6μM; 1,25μM; 2,5μM; 5μM, 10μM) and infected with L. infantum chagasi and L. amazonensis for invasion and multiplication assays. We also evaluated the potential protective action of mimetic peptide in mice infected with L. amazonensis. Therefore, animals were immunized and the parasite load, expression of cytokines, lesion size, and protein analysis binders were evaluated. The immunoassays showed that both serum and saliva of the patients exhibited a highly significant difference (p < 0.0001) compared to their controls, with 100% sensitivity and 100%specificity. Peptides were able to detect infection in asymptomatic subjects and showed no cross-reactivity to either Chagas’ disease or malaria, as well as co-infection LV-HIV did not interfere with responsiveness to LV antibodies, therefore being a promising tool for monitoring regions where these diseases occur. Tests using macrophages showed a highly significant reduction in the number of infected cells and of internalized parasites. A further reduction of parasites with increasing concentration of peptide was observed. Furthermore, it was observed that immunization of mice was able to induce high levels of IFN-γ, IL-12, GM-CSF and IL-10, while IL-4 did not change compared to the control. Additionally, immunized animals showed a reduction in parasitic load in all organs (spleen, lymph node, liver, and bone marrow), a decrease in paw lesion in which parasites were inoculated and phosphorylation of ERK1/2, JNK and p65/RelA. Western Blot assay identified two proteins to L. amazonensis (42 KDa) and two to Leishmania infantum chagasi (26 KDa). Thus, our results demonstrate that mimetic peptides act as antigens of L. infantum chagasi and L. amazonensis, being good immune markers for a simple and fast diagnosis with high sensitivity and specificity. Finally, data in murine macrophages in vitro and in vivo open perspectives for their use as a vaccine tool. / Leishmaniose é uma doença negligenciada e endêmica no Brasil, especialmente na região Nordeste, sendo causada por cerca de 20 espécies do protozoário Leishmania. O diagnóstico abrange aspectos epidemiológicos, clínicos e laboratoriais. Apesar de existir várias técnicas diagnósticas que podem ser utilizadas, nenhum dos testes disponíveis apresenta 100% de sensibilidade e especificidade. Baseado nisto, este trabalho se propôs a validar três peptídeos recombinantes miméticos (LC1, LC2 e LT) obtidos por Phage display, para o desenvolvimento de um diagnóstico imunológico rápido, específico, sensível e de baixo custo. Foram utilizados soros para detecção de IgG em 223 indivíduos, sendo 123 com leishmaniose visceral (LV), 45 com leishmaniose tegumentar (LT) e 55 com coinfecção LV-HIV. Para testes de reação cruzada, foram utilizadas amostras de pacientes com Doença de Chagas (n = 60) e com Malária (n = 65) e, como grupo controle, foram utilizados soros de 75 de recém-nascidos. Os peptídeos também foram testados em amostras de saliva de 65 pacientes com LV e 40 pacientes com LT, tendo como grupo controle 35 indivíduos saudáveis de área endêmica. Foram realizados também testes diagnósticos utilizando os peptídeos miméticos LC1 e LC2 em soro de 15 indivíduos assintomáticos; 13 indivíduos curados e 15 indivíduos sadios. Com a finalidade vacinal, macrófagos murinos C57BL/6 foram tratados in vitro com peptídeos LC1, LC2 e LT (0,6μM; 1,25μM; 2,5μM; 5μM; 10μM) e infectados com L. infantum chagasi e L. amazonensis para ensaio de invasão e multiplicação. Foram também realizados ensaios para testar o potencial protetor do peptídeo mimético em camundongos infectados por L. amazonensis. Para tanto, os animais foram imunizados e avaliada a carga parasitária, expressão de citocinas, tamanho da lesão, e análise protéica de ligantes. Os ensaios imunoenzimáticos mostraram que tanto soro quanto saliva dos pacientes apresentaram diferença altamente significativa (p < 0,0001) em relação a seus controles, apresentando sensibilidade de 100% e especificidade de 100% para todos os peptídeos, tanto em soro quanto em saliva. Os peptídeos foram capazes de detectar infecção em indivíduos assintomáticos e não apresentaram reação cruzada com Doença de Chagas e Malária, bem como a coinfecção com HIV não interfere na reatividade com os anticorpos para L. infantum chagasi, sendo, portanto, uma promissora ferramenta para monitoramento da infecção em regiões endêmicas. Os ensaios com macrófagos mostraram uma redução altamente significativa no número de células infectadas e do número de parasitas internalizados. Observou-se maior redução de parasitas com o aumento da concentração dos peptídeos. Foi observado que a imunização de camundongos foi capaz de induzir níveis elevados de IFN-γ, IL-12 e GM-CSF, enquanto os níveis de IL-4 e IL-10 foram reduzidos. Além disso, os animais imunizados apresentaram uma redução da carga parasitária em todos os órgãos (baço, linfonodo, fígado e medula óssea), uma diminuição da lesão da pata na qual os parasitas foram inoculados e fosforilação das proteínas ERK1/2, JNK e p65/RelA. O ensaio Western Blot identificou duas proteínas de L. amazonensis (42 kDa) e duas para Leishmania infantum chagasi (26 kDa). Assim, os resultados demonstram que os peptídeos sintéticos mimetizam antígenos de L. amazonensis e L. infantum chagasi, revelando-se bons marcadores para diagnóstico imunológico de uso rápido, simples e, principalmente, com alta sensibilidade e especificidade. Finalmente, os dados em macrófagos murinos in vitro e in vivo abrem perspectivas para o uso desses peptídeos como ferramenta vacinal.