It is often a challenge to atomically determine the structure of large macromolecular assemblies, even if successfully crystallized, due to their weak diffraction of X-rays. Refinement algorithms that work with low-resolution diffraction data are necessary for researchers to obtain a picture of the structure from limited experimental information. Relationship between the structure and function of proteins implies that a refinement approach delivering accurate structures could considerably facilitate further research on their function and other related applications such as drug design. Here a refinement algorithm called the Deformable Complex Network is presented. Computation results revealed that, significant improvement was observed over the conventional refinement and DEN refinement, across a wide range of test systems from the Protein Data Bank, indicated by multiple criteria, including the free R value, the Ramachandran Statistics, the GDT (<1Å) score, TM-score as well as associated electron density map.

FFifteen to thirty-five percent of the population in the United States experience tinnitus, a subjective "ringing in the ears". Up to 10% of tinnitus patients report their symptoms are severe and disabling. Tinnitus was induced in FBN rats using 116 dB (SPL) unilateral octave-band sound exposures centered at 16 kHz for one hour in an anesthetized preparation. Rats were assessed behaviorally by an operant conditioning paradigm as well as a gap detection method to verify the development of tinnitus. Both young (7 mos.) and aged (30 mos.) sound exposed rats showed significant elevated auditory brainstem-evoked response (ABR) thresholds for clix and all tested frequencies immediately after the sound exposure. Eighty days post-exposure, ABR thresholds for the young exposed rats were significantly close to the initial young control values while aged exposed rats showed residual thresholds shifts relative to aged controls. Sixteen weeks following sound exposure, young exposed rats showed significantly reduced gap detection at 24 and 32 kHz, suggestive of high frequency tinnitus. Aged exposed animals showed significant tinnitus-related behavioral changes near 10 kHz by both behavior methods. Message and protein levels of &alpha1-3 glycine receptor subunits (GlyRs), gephyrin, BDNF and its receptor TrkB were assessed in dorsal cochlear nucleus (DCN) fusiform cells 4 months post exposure utilizing quantitative in situ hybridization and immunocytochemistry. Young exposed rats showed significant decreases of GlyR &alpha1 protein at middle and high frequency regions in DCN unlike the contrasting increase of their message levels. Aged exposed rats showed higher &alpha1 subunit protein levels in the same high and middle DCN frequency regions. The GlyR anchoring protein, gephyrin, was significantly increased in both young and aged exposed rats, suggesting an intracellular receptor trafficking change following acoustic trauma. BDNF and TrkB were also increased over fusiform cells in both young and aged exposed rats. [3H] strychnine binding was used to evaluate DCN GlyR pharmacology and function following sound exposure. The age-related decrease in GlyR α1 protein was reflected in the significant age-related down-regulation of GlyR (Bmax). Tinnitus-related changes in GlyR &alpha1 protein level was reflected in the decline of the GlyR (Bmax) in young exposed rats and up-regulated GlyRs in aged exposed animals. The GlyRs in DCN of young exposed animals also demonstrated an increase in affinity, further suggesting a post-exposure receptor composition change. These findings suggest that both aging and/or sound exposure/tinnitus are associated with GlyR changes capable of altering alter the output of the DCN. Detailed characterization of these GlyR modifications could advance the development of novel selective drugs for tinnitus and age-related hearing loss.

Made available in DSpace on 2017-07-20T12:40:19Z (GMT). No. of bitstreams: 1 Karine Klider.pdf: 4696661 bytes, checksum: 1625309038e6d64e39214301b4f96f7b (MD5) Previous issue date: 2016-07-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In this study, we evaluated the optical and electrochemical properties of organic compounds of different types in order to analyze their potential for application active layer in photovoltaic devices. The work was divided into three parts. The first discloses the preparation and characterization of a derivative of 1,8-naphthalimide chromophore prepared from the reaction with a benzonitrile unit (also synthesized and characterized in this work). The BID-NB compound showed optical and electrochemical properties equivalent of the chromophore with optical and electrochemical band gap of 3.41 eV and 2.19 eV. Photovoltaic devices using bilayer architecture, constructed with the compound as the active layer, reached 0.9% of power conversion efficiency (PCE) and a current density at short circuit of 5.68 mA cm-2 by using the C70 fullerene as electron acceptor layer, and 1,8-diiodoocthane as additive in the solution for active layer deposition. The second part the work described the preparation of conjugated molecules (with electron donor acceptor characteristics) from the indigo dye modification by addiction of thiophene units. It was found that increasing number of thiophene units resulted in better opto-electrochemical properties. The molecule that showed the best behavior, DHT-IND, presented optical and electrochemical band gap of 1.64 and 1.45 eV respectively. Despite the low band gap value, the bulk heterojunction (BHJ) solar cell constructed with a 1: 3 mixture of DHT-IND and PC71BM as active layer, showed PCE of 0.7% and current density at short circuit of -4.59 mA cm-2. The fill factor (FF) was 26%. In the third part of this work we evaluated the photocurrent generation by the copolymer PPV/DCN-PPV formed by DCN-PPV chains attached to PPV chain. The evaluation performed as film deposited on a glass substrate containing ITO coated, which has exposed to a LED ilumination. After irradiation the copolymer generated current of A cm-2 (unstable), and -2 A cm-2 (stable). / Neste trabalho foram avaliadas as propriedades ópticas e eletroquímicas de deferentes compostos orgânicos, e analisar suas potencialidades para aplicação como camada ativa em dispositivos fotovoltaicos. Dividiu-se o trabalho em três partes. A primeira revelou a preparação e caracterização de um derivado do cromóforo 1,8-naftalimida, preparado a partir da reação com uma unidade de benzonitrila previamente preparada e caracterizada. O composto 4-(2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-il)etoxi)-2,5-dimetilbenzonitrila, ou BID-NB, apresentou propriedades ópticas e eletroquímicas equivalentes às do cromóforo, com band gap óptico de 3,41 eV e eletroquímico de 2,19 eV. Dispositivos fotovoltaicos de bicamada foram construídos com o composto BID-NB como camada ativa, sendo que a eficiência máxima de conversão foi de 0,9% com uma densidade de corrente de curto circuito de -5,68 mA cm-2. O dispositivo que auferiu tais resultados foi construído com o fulereno elétron-aceptor C70, e com o auxilio do aditivo 1,8-diiodooctano na deposição da camada ativa. A segunda parte do trabalho consistiu da preparação de moléculas conjugadas do tipo doador/aceptor de elétrons, a partir da modificação do corante índigo com unidades de tiofenos. Constatou-se que o aumento da quantidade de unidades de tiofenos nas moléculas favoreceu suas propriedades opto-eletroquímicas. O composto 7,14-bis(3``,4`-diexil-[2,2`:5`,2``-tertiofen]-5-il)diindolo[3,2,1-de:3`,2`,1`-il][1,5]naftiridina-6,13-diona, ou DHT-IND, foi o que apresentou os menores valores de band gap óptico e eletroquímico, nos valores de 1,64 e 1,45 eV respectivamente. O dispositivo fotovoltaico de heterojunção, construído a partir da mistura 1:3 de DHT-IND e PC71BM como camada ativa, apresentou eficiência de conversão de 0,7% e densidade de corrente de -4,59 mA cm-2. Na terceira parte deste trabalho avaliou-se geração de fotocorrente em um copolímero formado por blocos de PPV ligados a blocos de DCN-PPV (PPV/DCN-PPV). A avaliação foi efetuada na forma de filme sobre um substrato de vidro contendo ITO, o qual foi exposto a iluminação de LED. O copolímero gerou corrente de até -4 A cm-2 (instável), e de -2 A cm-2 (estável) após iluminação.

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The social, political and economic transformations that Brazil has undergone in the last years and obviously with repercussions in all areas of society are great. In school education, the training field of individuals, these changes are "proposed" through legislation that regulates teaching and presents a discourse to meet new social demands. In the whole legislation on teacher education in Basic Education, the New National Curriculum Guidelines for Undergraduate Courses for Teachers were approved and homologated in 2015. This document proposes a policy of formation and valorization of teaching in a political and economic context that contradicts the legislation itself and, therefore, a discursive analysis of the document and the senses produced from its publication is pertinent. Thus, this research has as main objective to unveil the senses present in the functioning of the teacher training discourse in the DCN using the theoretical instrumentation of the French AD. We use as a theoretical contribution Pêcheux (1990, 2010, 2014, 2015), which bases the theory of non-subjective reading and supports discourse as a historical materiality accessed through texts; Althusser (1998); Orlandi (2000, 2014, 2015); Foucault (2007), as well as studies that involve the field of education, aimed at teacher education and the bases that support the educational legislation in force, arranged by Libâneo (2010, 2012) and other authors, whose critics contribute to the elaboration of the our work. We select as an object of analysis the discourse about teacher education, present in the New National Curricular Guidelines. In order to meet the objective of our research, we use the qualitative research methodology whose objective is to understand the functioning of the discourses in the object already mentioned. In order to meet the objective of our research, we selected as corpus the discursive sequences contained in CNE / CP Resolution 2 of July 1, 2015 and elaborated the following questions to guide our analysis, namely: a) How the proposal is presented teacher training in the new guidelines? b) In what context were these DCN been / are being presented? c) What are the subject positions occupied by the interlocutors? d) What discursive / ideological formations are involved in these proposals? e) What effects of meaning present in the proposals / policies of the current teacher conception? We have seen the resumption of "already said" in proposals that are presented as a solution to meet the new social demands of the teaching profession and that are related to other discourses strongly influenced by the conception of the neoliberal politics of capital, manifested by the discursive formation of the market occupied by the position -subject that holds the power to institute the norms of teaching and discipline the individuals. / São grandes as transformações sociais, políticas e econômicas pelas quais o Brasil tem passado nos últimos anos e obviamente com reflexos em todas as áreas da sociedade. Na educação escolar, campo de formação dos indivíduos, essas mudanças são “propostas” através da legislação que regulamenta o ensino e apresenta um discurso de atendimento às novas demandas sociais. No conjunto da legislação sobre formação de professor na Educação Básica, foram aprovadas e homologadas em 2015 as novas Diretrizes Curriculares Nacionais para as Licenciaturas. Esse documento propõe uma política de formação e de valorização do magistério em um contexto político e econômico que contradiz a própria legislação e, por isso, é pertinente uma análise discursiva do documento e dos sentidos produzidos a partir da sua publicação. Assim, essa pesquisa tem como objetivo principal desvelar os sentidos presentes no funcionamento do discurso da formação de professores nas DCN utilizando a instrumentação teórica da AD francesa. Utilizamos como aporte teórico Pêcheux (1990, 2010, 2014, 2015), que funda a teoria de leitura não subjetiva e alicerça o discurso como materialidade histórica acessada através dos textos; Althusser (1998); Orlandi (2000, 2014, 2015); Foucault (2007) como também os estudos que envolvem o campo da educação, voltados para formação do professor e para as bases que fundamentam a legislação educacional em vigor, dispostos por Libâneo (2010, 2012) e outros autores, cujas críticas contribuem para elaboração do nosso trabalho. Selecionamos como objeto de análise o discurso sobre a formação do professor, presente nas Novas Diretrizes Curriculares Nacionais. Para atender ao objetivo de nossa pesquisa, utilizamos a metodologia de pesquisa qualitativa cujo objetivo é compreender o funcionamento dos discursos no objeto já citado. Para atender ao objetivo de nossa pesquisa, selecionamos como corpus as sequências discursivas contidas na Resolução CNE/CP nº 2, de 1º de julho de 2015 e elaboramos as questões a seguir para nortear nossa análise, quais sejam: a) Como se apresenta a proposta de formação de professores nas novas diretrizes? b) Em que contexto essas DCN foram/estão sendo apresentadas? c) Quais são as posições-sujeito ocupadas pelos interlocutores? d) Que formações discursivas/ideológicas estão envolvidas nessas propostas? e) Quais efeitos de sentido presentes nas propostas/políticas da concepção atual de docente? Constatamos a retomada de “já ditos” em propostas que se colocam como solução para atender às novas demandas sociais da profissão docente e que se relacionam a outros discursos fortemente influenciados pela concepção da política neoliberal do capital, manifestos pela formação discursiva de mercado ocupada pela posição-sujeito que detém o poder para instituir as normativas do ensino e disciplinar os indivíduos. / São Cristóvão, SE