31,246 research outputs found
Maria Bersani
No full textLa voce illustra la biografia e l'apporto letterario dato da Maria Bersani alla letteratura per l'infanziaThe headword explains the biography and the contribution of the author Maria Bersani to the children's literatur
Structural insights into the immune subversion of coronaviruses and identification of potent small molecule inhibitors using computational approaches
No full text학위논문(박사)--아주대학교 일반대학원 :분자과학기술학과,2020. 8CHAPTER 1 1
Introduction 1
1.1 Overview of Coronaviruses 2
1.2 Entry and replication of viruses 3
1.3 Potential therapeutic targets 6
CHAPTER 2 9
Methods 9
2.1 Protein modeling and interface analysis 10
2.2 Alanine scanning mutagenesis 10
2.3 Virtual screening and molecular docking 11
2.4 Molecular dynamic simulations 12
2.5 Principal component analysis 15
2.6 Free energy landscape 15
2.7 MMPBSA 16
2.8 Data analysis and visualization 17
CHAPTER 3 18
Results and Discussion 1 18
Structural insights into the Middle East respiratory syndrome coronavirus 4a protein and its dsRNA binding mechanism 19
3.1 Summary 20
3.2 3D modeling of p4a-dsRNA complex and interface analyses 20
3.3 Identification of hotspot residues and their influence on p4a-dsRNA binding mechanism 23
3.4 Investigation of impact of hotspot residues on p4a-dsRNA complex through structural dynamics 24
3.5 Interactions analysis between p4a-dsRNA wild type complex and mutants 27
3.6 Dynamic motions of MERS-CoV p4a mutants 27
3.7 Transition of proteins from unfolded to native state 31
3.8 Binding free energy calculation 32
3.9 Discussion 33
CHAPTER 4 36
Results and Discussion 2 36
Discovery of potential inhibitors to block MERS-CoV evasion from the host immune system by targeting a non-structural accessory protein 37
4.1 Summary 38
4.2 Understanding of dynamic behavior and stability of p4a 38
4.3 Identification of potential compound to block p4a-dsRNA interaction 39
4.4 Identification of physicochemical and pharmacokinetic properties 45
4.5 Discussion 46
CHAPTER 5 48
Results and Discussion 3 48
Structural insights into the behavior of the catalytic site of SARS-CoV-2 main protease 49
5.1 Summary 50
5.2 Analysis of apo-3CL protease behavior via MD simulations 50
5.3 Dynamic behavior of 3CL protease with different ligands 52
5.4 The behavior of 3CL protease catalytic site in the presence of ligands 58
5.5 The binding energy of ligands toward 3CL protease 60
5.6 Discussion 61
Bibliography 64
Appendix 1 74
Appendix 2 75
Appendix 3 76DoctoralThe recent occurrence of COVID-19 pandemic causing fever, respiratory illness, and pneumonia, has drawn the attention across the globe and has been declared a global health emergency. Among humans, coronaviruses were not believed to be pathogenic until the severe acute respiratory syndrome (SARS) epidemic occurred in late 2002. Ten years later in 2012, a new coronavirus epidemic named as Middle East respiratory syndrome (MERS) emerged in Asian and Middle Eastern countries. Several studies have been published to understand the cell entry, replication, and protein structures of virus. The genomic organization of SARS and MERS is similar, comprising an enveloped, positive-sense, single-stranded RNA genome that translates into various structural and non-structural proteins (nsps). After viral entry into the host cell, virus releases its RNA into the cytoplasm where it is translated into polyproteins pp1a and pp1ab. These polyproteins are cleaved by proteases that produce 16 nsps. The viral genome is translated, replicated, and assembled in the cytoplasm which is then released via exocytosis.
To combat with the coronavirus diseases, it is important to block viral infection or replication. Therefore, two potential target proteins were selected for the drug development. The first target is an accessory protein 4a of MERS-CoV which has been proved through in vitro and in vivo studies that it is involved in inhibition of IFN production which influences the viral pathogenicity. 3D structure of protein 4a was modeled followed by structural validation and computational alanine mutagenesis. Residues N8, K27, W45, K63, and K67 were selected based on the dStability and dAffinity values. The mutant and wild type complexes were simulated for 200 ns each. The MD simulation results revealed that K27, W45, K63, and K67 are key residues that play crucial role in RNA binding. Thus, suggesting that blocking these residual interactions could destabilize the 4a-RNA complex. Furthermore, considering these residues a part of binding site, virtual screening of
antiviral as well as druglike and leadlike compounds from ZINC database is conducted using the most stable confirmation extracted from MD simulations. The ten compounds from both datasets were selected based on binding affinity scores and their binding pose. The interactions were analyzed in detail along with the free binding energy calculations. Most of the selected compounds possess antiviral properties. These compounds can be tested through in vitro and in vivo experiments.
The 3CL protease is another potential target due to its proteolytic activity that cleaves the polyprotein. Many drugs have been repositioned, and a few ligands are cocrystalized with SARS-CoV-2 3CL protease. The flexibility of the catalytic site leads to the conformational changes that influences the ligand binding. Thus, it is necessary to probe the flexibility and rigidity of protein’s active site. 100 ns MD simulations were performed for apo form of 3CL protease and its complexes with different cocrystalized ligands. The trajectory analysis and binding free energy calculation revealed that the ligand that can break the catalytic dyad bond in the active site would be a potential candidate to block the proteolytic activity. The alpha-keto group present in the inhibitor of 6LU7 make strong bonds with both residues Cys and His of catalytic dyad. Therefore, addition of such chemical groups that break the bond between Cys and His would be important to block the functional 3CL protease.
Conclusively, both target proteins 4a and 3CL protease are important for viral pathogenicity and replication, respectively. Therefore, understanding of structure dynamics and insights into the binding site is crucial for development of an efficient drug molecule. 3CL protease is structurally and functionally conserved protein among all three coronaviruses. Thus, targeting this protein would be a hope to combat all coronavirus diseases
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Optical properties of ZnS and effect of doping with transition elements
No full textBy the help of density functional theory for a Cu doped ZnS compound the charge density,
Fermi surface and electronic structure have been examined. We have used (FP-LAPW)
method, to deal with interchange relationship potential for solving of kohn-sham equations.
We apply generalized gradient approximation (GGA), local density approximation (LDA)
and Engel-Vosko GGA (EVGGA). Cu doped ZnS compound confirms that nature of
material is metallic and Fermi energy (EF) is obtained by the overlapping of Cu-p and Zn-
d state. At Fermi energy (EF) calculated density of states is 51.932, 18.655 and 13.235
states/ev, and low-temperature electronic specific heat co-efficient (γ) is found to be
9.008mJ/mol-K2 for GGA, 3.236mJ/mol-K2 for LDA, and it was 2.295mJ/mol-K2 for
EVGGA respectively. The thermal properties and optical constant were also discussed and
calculated
O curso de licenciatura em educação física da Universidade Federal de Santa Catarina: suas concepções de ensino e de educação física
No full textDissertação (mestrado) - Universidade Federal de Santa Maria. Centro de Educação Fisica e Desporto
Erratum: Lack of immunity against rubella among Italian young adults. [BMC Infect Dis., 17, (2017) (199)] Doi: 10.1186/s12879-017-2295-y
No full textAfter publication of this article [1], the authors noted that the given names and family names of all authors had been inverted, and are therefore incorrect in the original article. In the original article, the author names appear as the following: Gallone Maria Serena, Gallone Maria Filomena, Larocca Angela Maria Vittoria, Germinario Cinzia and Tafuri Silvio. However, this is incorrect, and the author names should appear as per the below: Maria Serena Gallone, Maria Filomena Gallone, Angela Maria Vittoria Larocca, Cinzia Germinario, Silvio Tafuri. The author names have been corrected in the author list and the citation for this Erratum
Imagens de Otto Maria Carpeaux: esboço de biografia
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Programa de Pós-Graduação em História, Florianópolis, 2015.Este esboço de biografia procura citar algumas imagens de Otto Maria Carpeaux: construções biográficas de naturezas múltiplas, elaboradas em contextos, por atores e sob condições igualmente díspares. Está constituído a partir de uma visão crítica da História, o que permite que ?outras imagens?, fragmentárias e não monumentais, também tenham espaço. Em diálogo com o princípio da montagem, este esboço apresenta-se em duas partes. Na primeira, Imagens possíveis, estão citadas as imagens elaboradas em vida e post mortem acerca do austríaco-brasileiro que nasceu em Viena em 1900, se exilou no Brasil em 1939 e morreu no Rio de Janeiro, em 1978. Na segunda, Montagens possíveis, apresentam-se duas possibilidades de exercício biográfico: pela leitura alegórica do documentário O velho e o Novo (Otto Maria Carpeaux), entendido como instrumento de intervenção no contexto ditatorial brasileiro e de uma reelaboração biográfica concernentes às suas experiências europeias; e pelo Caderno de imagens críticas, registro dos encontros em Carpeaux pelo meio de imagens críticas produzidas a partir da cesura do presente.Abstract : This biographical sketch attempts to quote some images of Otto Maria Carpeaux: various types of biographical constructions, carried out in different contexts by disparate authors under conditions just as distinct. It stems from a critical view of history, allowing for ?other images? fragmented and non-monumental ? to share the space.In dialogue with the montage principle, this sketch has two parts. The first, Possible Images, quotes the images produced during and after the life of the Austrian-Brazilian, who was born in Vienna in 1900, went to Brazil in exile in 1939 and died in Rio de Janeiro in 1978. The second part, Possible Montages, presents two possibilities of a biographical exercise: through the allegorical reading of documentary O Velho e o Novo (Otto Maria Carpeaux), understood as an instrument of intervention in the Brazilian dictatorship context and as a biographical retelling of the author?s European experiences; and through my Scrapbook of Critical Images, a record of the encounters in Carpeaux through critical images produced from the caesura of the present
Maria José ao encontro de Tchekov
No full text“A Carta da Corcunda para o Serralheiro” (“Letter from the Hunchback Girl to the Metalworker”), signed by Maria José, was first performed in a theatre show in 1988 (by actress-director Maria do Céu Guerra), two years before the typescript was published in book form for the first time by Teresa Rita Lopes. The evidence upon which this article is built is that it was the theatre that revealed the dramatic destination of this singular epistle of the only female heteronym that Fernando Pessoa invented, which was also the last heteronym to be created by the author. The dramatic construction of Maria José can be approximated to the character-building strategies in Anton Chekhov’s realist dramaturgy, in a way that differs from Pessoa’s other dramaturgical experiences. The analysis of Chekhov’s ascendancy over Stanislavski’s research, as well as the importance of Schopenhauer’s conception of the tragicomic, which is simultaneously projected onto Chekhov’s theatre and Maria José’s profile, are favourable lines of reading for this rapprochement between Pessoa and the Russian fiction writer and playwright. Pessoa’s readings of Chekhov’s texts (such as the play Uncle Vania and the short story “Vanka”) provide relevant data for assessing the magnitude of this encounter.“A Carta da Corcunda para o Serralheiro”, assinada por Maria José, começou por ser difundida num espectáculo de teatro em 1988 (pela actriz-encenadora Maria do Céu Guerra) dois anos antes de o dactiloscrito se ver publicado em livro, pela primeira vez, por Teresa Rita Lopes. Parte-se da evidência de ter sido o teatro a revelar a destinação dramática da epístola singular do único heterónimo mulher que Fernando Pessoa inventou, que terá sido também o último a ser criado pelo autor. A construção dramática de Maria José pode ser aproximada às estratégias de construção de personagem na dramaturgia realista de Anton Tchekov, de um modo que se distingue de outras experiências dramatúrgicas de Pessoa. A análise do ascendente de Tchekov sobre as pesquisas de Stanislavski, bem como a importância da concepção de tragicómico em Schopenhauer, que se projecta em simultâneo sobre o teatro de Tchekov e sobre o perfil de Maria José, são linhas de leitura propícias para esta aproximação entre Pessoa e o ficcionista e dramaturgo russo. As leituras de textos de Tchekov por parte de Pessoa (como o caso da peça Tio Vânia e o conto “Vanka”) fornecem dados relevantes para avaliar a magnitude deste encontro
O negro como personagem na literatura infantil, na obra de Maria Rita Py
No full textTried to when analyzing the works of Coleção História da Vó Preta, of the Santa Mariense author Maria Rita Py, the representation of black people, showing how the issues surrounding it in society, his yearnings, sorrows, lived since last century , are present in contemporary children's literature. The literature has shown an increasing concern in presenting a cultural identity that expresses the relationship of social inclusion. The Brazilian reality shows that the black, after the liberations of slaves, and most recently with the growth of the black movement, assumed a new vision, creating a new discourse in this literature, when passing to be personage of the transformation of black spirit (sense). It is in this context that the black literature of Maria Rita Py inserts, dedicated to child audience, search for solutions to solve the problems of this personage such as frustration, rejection, desire to be white, doubts and anxieties of children black in society, affect self-esteem and identityProcurou-se ao analisar nas obras da Coleção História da Vó Preta, da autora santa-mariense Maria Rita Py, a representação do negro, demonstrando como as questões que o envolvem na sociedade, seus anseios, mágoas, vividas desde o século passado, estão presentes na literatura infantil contemporânea. A literatura tem evidenciado uma preocupação cada vez maior em apresentar uma identidade cultural que expresse as relações de inclusão social. A realidade brasileira mostra que o negro, após a libertação dos escravos, e mais recentemente com o crescimento do movimento negro assumiu uma nova visão, criando um novo discurso nessa literatura, quando passa a ser personagem da transformação da consciência negra. Neste contexto que se insere a literatura negra de Maria Rita, dedicadas ao público infantil, destaca-se a preocupação em buscar soluções para resolver os problemas dos seus personagens tais como: frustração, rejeição, desejo de ser branco, dúvidas e os anseios de crianças negras na sociedade, mas que afetam a auto-estima e a sua identidade
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