Modelo de Tomada de Decisão de Kortland no Delineamento de Atividade Didática para o Ensino de Bioquímica

A aplicação da metodologia de estudo de casos no ensino de ciências tem sido alvo de atenção de vários educadores nos últimos anos. No presente trabalho, relatamos a aplicação de uma atividade didática dessa natureza em disciplina de Bioquímica, oferecida no curso de Bacharelado em Química do Instituto de Química de São Carlos, da Universidade de São Paulo. Para que a atividade fosse levada a cabo fez-se necessária, inicialmente, a produção de um caso investigativo, denominado O Mal do Século, que aborda a obesidade infantil. A resolução do caso foi apresentada pelos alunos no formato de relatório, cujo roteiro foi construído com base no Modelo de Tomada de Decisão de Kortland (1996). Nessa perspectiva, os estudantes pesquisaram e analisaram múltiplas fontes de dados fazendo uso de critérios desenvolvidos por eles para solucionar o casoThe use of case-study method in science education has been the focus of attention of many educators in recent years. In this work we describe a didactic activity based on this method in a biochemistry discipline offered to undergraduate chemistry students at the São Carlos Institute of Chemistry, University of São Paulo. Thus, we developed an investigative case entitled The Plague of the Century, which addresses childhood obesity. In order to solve the case, the students wrote a formal report according to the script produced by us, based on Kortland’s Model of a Decision-making Procedure (1996). In view of this, the students researched and evaluated multiple sources of data, using criteria developed by them to solve the cas

PENGARUH HARGA DAN DESAIN PRODUK TERHADAP KEPUTUSAN PEMBELIAN MEBEL PADA UD. JEPARA INDAH KOTA PASURUAN

The purpose of this research is to examine the influence of price, and product design on furniture purchasing decision at UD. Jepara Indah Pasuruan City. This study uses multiple linier regression analysis on 100 respondents that have been determined using purposive sampling technique as a method of sampling by using questionnaires for data collection. The results of this study revealed that prices have a positive and significant effect on purchasing decision of furniture in UD. Jepara Indah and product design have a positive and significant impact on purchasing decision of furniture in UD. Jepara Indah

Characterization of an engineered human purine nucleoside phosphorylase fused to an anti-her2/neu single chain Fv for use in ADEPT

Abstract Background Antibody Directed Enzyme Prodrug Therapy (ADEPT) can be used to generate cytotoxic agents at the tumor site. To date non-human enzymes have mainly been utilized in ADEPT. However, these non-human enzymes are immunogenic limiting the number of times that ADEPT can be administered. To overcome the problem of immunogenicity, a fully human enzyme, capable of converting a non-toxic prodrug to cytotoxic drug was developed and joined to a human tumor specific scFv yielding a fully human targeting agent. Methods A double mutant of human purine nucleoside phosphorylase (hDM) was developed which unlike the human enzyme can cleave adenosine-based prodrugs. For tumor-specific targeting, hDM was fused to the human anti-HER2/neu single chain Fv (scFv), C6 MH3B1. Enzymatic activity of hDM with its natural substrates and prodrugs was determined using spectrophotomeric approaches. A cell proliferation assay was used to assess the cytotoxicity generated following conversion of prodrug to drug as a result of enzymatic activity of hDM. Affinity of the targeting scFv, C6 MH3B1 fused to hDM to Her2/neu was confirmed using affinity chromatography, surface plasmon resonance, and flow-cytometry. Results In vitro hDM-C6 MH3B1 binds specifically to HER2/neu expressing tumor cells and localizes hDM to tumor cells, where the enzymatic activity of hDM-C6 MH3B1, but not the wild type enzyme, results in phosphorolysis of the prodrug, 2-fluoro-2'-deoxyadenosine to the cytotoxic drug 2-fluoroadenine (F-Ade) causing inhibition of tumor cell proliferation. Significantly, the toxic small drug diffuses through the cell membrane of HER2/neu expressing cells as well as cells that lack the expression of HER2/neu, causing a bystander effect. F-Ade is toxic to cells irrespective of their growth rate; therefore, both the slowly dividing tumor cells and the non-dividing neighboring stromal cells that support tumor growth should be killed. Analysis of potential novel MHCII binding peptides resulting from fusion of hDM to C6 MH3B1 and the two mutations in hDM, and of the structure of hDM compared to the wild-type enzyme suggests that hDM-C6 MH3B1 should exhibit minimal immunogenicity in humans. Conclusion hDM-C6 MH3B1 constitutes a novel human based protein that addresses some of the limitations of ADEPT that currently preclude its successful use in the clinic

Manual del SoftwareIfs Construction kit para generar imágenes que representan fractales mediante sistemas de funciones iteradas

Los últimos avances en matemáticas en el campo de geometría fractal han permitido el surgimiento de una gran variedad de aplicaciones informáticas útiles para la representación de conjuntos fractales. Este trabajo pretende presentar a IFSConstruction Kit como una opción para construir fractales con base en los sistemas de funciones iteradas

Computational Modeling-Based Discovery of Novel Classes of Anti-Inflammatory Drugs That Target Lanthionine Synthetase C-Like Protein 2

Background: Lanthionine synthetase component C-like protein 2 (LANCL2) is a member of the eukaryotic lanthionine synthetase component C-Like protein family involved in signal transduction and insulin sensitization. Recently, LANCL2 is a target for the binding and signaling of abscisic acid (ABA), a plant hormone with anti-diabetic and anti-inflammatory effects. Methodology/Principal Findings: The goal of this study was to determine the role of LANCL2 as a potential therapeutic target for developing novel drugs and nutraceuticals against inflammatory diseases. Previously, we performed homology modeling to construct a three-dimensional structure of LANCL2 using the crystal structure of lanthionine synthetase component C-like protein 1 (LANCL1) as a template. Using this model, structure-based virtual screening was performed using compounds from NCI (National Cancer Institute) Diversity Set II, ChemBridge, ZINC natural products, and FDAapproved drugs databases. Several potential ligands were identified using molecular docking. In order to validate the antiinflammatory efficacy of the top ranked compound (NSC61610) in the NCI Diversity Set II, a series of in vitro and pre-clinical efficacy studies were performed using a mouse model of dextran sodium sulfate (DSS)-induced colitis. Our findings showed that the lead compound, NSC61610, activated peroxisome proliferator-activated receptor gamma in a LANCL2- and adenylate cyclase/cAMP dependent manner in vitro and ameliorated experimental colitis by down-modulating colonic inflammatory gene expression and favoring regulatory T cell responses

Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo

Neutrophilic inflammation is tightly regulated and subsequently resolves to limit tissue damage and promote repair. When the timely resolution of inflammation is dysregulated, tissue damage and disease results. One key control mechanism is neutrophil apoptosis, followed by apoptotic cell clearance by phagocytes such as macrophages. Cyclin-dependent kinase (CDK) inhibitor drugs induce neutrophil apoptosis in vitro and promote resolution of inflammation in rodent models. Here we present the first in vivo evidence, using pharmacological and genetic approaches, that CDK9 is involved in the resolution of neutrophil-dependent inflammation. Using live cell imaging in zebrafish with labelled neutrophils and macrophages, we show that pharmacological inhibition, morpholino-mediated knockdown and CRISPR/cas9-mediated knockout of CDK9 enhances inflammation resolution by reducing neutrophil numbers via induction of apoptosis after tailfin injury. Importantly, knockdown of the negative regulator La-related protein 7 (LaRP7) increased neutrophilic inflammation. Our data show that CDK9 is a possible target for controlling resolution of inflammation