Orientadora: Profa. Dra. Káthia Maria Honório / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Ciência e Tecnologia/Química, Santo André, 2018. / Um dos alvos biologicos relacionado ao controle da glicemia e a enzima dipeptidil peptidase-IV (DPP-IV); ela esta associada com a estimulacao do pancreas na producao de insulina, sendo, portanto, um alvo de interesse da pesquisa e da industria farmaceutica para o tratamento do diabetes tipo 2. O diabetes e uma doenca cronica que se caracteriza por um aumento da glicemia causando uma serie de complicacoes fisiologicas com destaque para as doencas cardiacas como a aterosclerose; estima-se que 425 milhoes de pessoas sejam portadoras da doenca. Estudos indicam que inibidores da DPP-IV tambem podem apresentar acao sobre a FAP¿¿, uma enzima que esta relacionada com reparacao de tecidos e crescimento de tumores. Este trabalho consiste em utilizar metodos de modelagem molecular, como a construcao e analise de modelos de HQSAR (Hologram Quantitative Structure-Activity) e de CoMFA (analise comparativa de campos de interacao molecular); acoplamento molecular (docking), analise de propriedades eletronicas e deteccao e caracterizacao de sitios de ligacao da enzima FAP¿¿, com intuito de compreender as principais caracteristicas de ambas as enzimas, assim como a interacao das mesmas com uma serie de compostos bioativos. Os modelos CoMFA construidos apresentaram significativos valores de validacao interna (0,768) e externa (0,986); o alinhamento obtido utilizando a tecnica de acoplamento molecular e complementada com o uso da tecnica BINANA delineou as principais interacoes das enzimas com o conjunto de ligantes; identificou-se tres sitios de ligacao da enzima FAP¿¿ utilizando os servidores FTSite e FTMap. Desta forma, com informacoes sobre ambos os alvos e as interacoes estabelecidas com os ligantes, sera possivel propor com maior seguranca modificacoes moleculares para tais compostos candidatos a farmacos mais seguros para o tratamento do diabetes tipo 2. / One of the biological targets related to glycemic control is the dipeptidyl peptidase IV (DPP-IV) enzyme; it is associated with stimulation of the pancreas in insulin production and it is a target of interest for the researches related to the treatment of type 2 diabetes. Diabetes is a chronic disease characterized by an increase in blood glucose causing a series of physiological complications such as atherosclerosis, it is estimated that 425 million people have this disease. Studies have indicated that DPP-IV inhibitors may also have action on FAPá, an enzyme that is related to tissue repair and tumor growth. This work consists of using molecular modeling methods, such as the construction and analysis of HQSAR (Hologram Quantitative Structure-Activity) and CoMFA (comparative analysis of molecular interaction fields) models; molecular docking, analysis of electronic properties, detection and characterization of FAPá enzyme binding sites, and pharmacokinetic and pharmacodynamic properties studies; in order to understand the main characteristics of both enzymes, as well as their interaction with a series of bioactive compounds. The CoMFA models presented significant values of internal validation (0,768) and external (0,986) and the alignment obtained using the molecular docking technique outlined the main interactions of the enzymes with the set of ligands. With information on both targets and the interactions established with the ligands, it will be possible to more safely propose molecular modifications for such safer drug candidates for the treatment of type 2 diabetes.

The researcher investigated the management of multi-grade teaching for optimal learning in Gauteng West primary schools. Ten participants, including school principals, heads of departments and educators participated in individual and focus group interviews and in observation of multi-grade classroom contexts. Findings revealed that educators involved in multi-grade teaching feel overwhelmed by challenging work conditions pertaining to large learner numbers and a lack of adequate didactical resources. This is exacerbated by a lack of professional development by means of tailor-made training for multi-grade teaching and the presumption that educators teaching such classes must merely change the monograde teaching format of the curriculum themselves for applicable implementation in a multi-grade teaching context. This leaves educators socially, emotionally and professionally isolated. Recommendations include the involvement of seasoned educators with expert knowledge and experience of multi-grade teaching to present training sessions constituting advice and support to inexperienced educators involved in said teaching. / Die navorser het die bestuur van meergraadonderrig by laerskole in Wes-Gauteng vir optimale leer ondersoek. Afgesien van individuele en fokusgroeponderhoude met skoolhoofde, departementshoofde en opvoeders, is waarneming in meergraadklaskamers gedoen. Volgens die bevindings bemoeilik groot klasse en ʼn gebrek aan didaktiese hulpmiddels meergraadopvoeders se taak. Meergraadopvoeders voel hulle geensins opgewasse teen hierdie werksomstandighede nie. ʼn Gebrek aan opleiding in meergraadonderrig en die veronderstelling dat opvoeders die eengraadformaat van die kurrikulum in ʼn meergraadformaat kan omskakel, vererger sake. Opvoeders is van mening dat hulle maatskaplik, emosioneel en professioneel in die steek gelaat word. Daar word aanbeveel dat gesoute opvoeders met kennis van en ervaring in meergraadonderrig onervare opvoeders oplei en adviseer. / Monyakisisi o dirile dinyakisiso ka ga go ruta dikereiti tse fapanego go fihlelela bokgoni le tsebo tikologong ya go thekga dinyakwa tsa baithuti dikolong tsa phoraemari go la Gauteng Bodikela. Batseakarolo ba lesome, go akaretswa dihlogo tsa dikolo, dihlogo tsa dikgoro le barutisi ba tseere karolo ditherisanong ka botee le dihlopha tseo di nepisitswego gape le temogo dikemong tsa diphaposi tsa dikereiti tse di fapanego. Dikhwetso di utollotse gore barutisi bao ba rutago dikereiti tse fapanego ba imelwa ke maemo a modiro wo o nyakago gore ba ntshe bokgoni bja bona ka moka ka lebaka la dipalo tse ntsi tsa baithuti le tlhokego ya dithusi tsa thuto tse di lekanego. Se se thatafiswa ke tlhokego ya tlhabollo ya profesene ye ka go fa tlhahlo yeo e lebanego ya go ruta dikreiti tse fapanego le kgopolo ya go re barutisi bao ba rutago ba swanela go no fetola popego ya lenaneothuto la kereiti e tee ka bobona go re ba le dirise kemong ya go ruta dikereiti tse fapanego. Se se dira gore barutisi ba ikhwetse ba se na kgokagano le setshaba leagong, ba hloka bao ba ka llelago go bona le go se be le bao ba nago le kgahlego go profesene ya bona. Ditshisinyo di akaretsa go ba gona ga barutisi bao e lego kgale ba ruta ba nago le maitemogelo le botsebi go ruta dikereiti tse fapanego go hlagisa dipaka tsa tlhahlo tseo di fago maele le thuso go barutisi bao ba se nago maitemogelo. / Educational Management and Leadership / M. Ed. (Education Management)