Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Real-time monitoring of the interactions of transforming growth factor-beta (TGF-beta) isoforms with latency-associated protein and the ectodomains of the TGF-beta type II and III receptors reveals different kinetic models and stoichiometries of binding

Mature transforming growth factor-\u3b2 (TGF-\u3b2) is proteolytically derived from the C terminus of a precursor protein. Latency-associated protein (LAP), the N-terminal remnant of the TGF-\u3b2 precursor, is able to bind and neutralize TGF-\u3b2. Mature TGF-\u3b2 exerts its activity by binding and complexing members of two subfamilies of receptors, the type I and II receptors. In addition to these signaling receptors, TGF-\u3b2 can also interact with an accessory receptor termed the type III receptor. Using a surface plasmon resonance-based biosensor (BIAcore), we determined the mechanisms of interaction of four binding proteins (LAP, the type II and III receptor ectodomains (EDs), and a type II receptor ED/Fc chimera) with three TGF-\u3b2 isoforms, and we quantified their related kinetic parameters. Using global fitting based on a numerical integration data analysis method, we demonstrated that LAP and the type II receptor/Fc chimera interacted with the TGF-\u3b2 isoforms with a 1:1 stoichiometry. In contrast, the type II ED interactions with TGF-\u3b2 were best fit by a kinetic model assuming the presence of two independent binding sites on the ligand molecule. We also showed that the type III ED bound two TGF-\u3b2 molecules. Further experiments revealed that LAP was able to block the interactions of TGF-\u3b2 with the two EDs, but that the two EDs did not compete or cooperate with each other. Together, these results strongly support the existence of a cell-surface complex consisting of one type III receptor, two TGF-\u3b2 molecules, and four type II receptors, prior to the recruitment of the type I receptor for signal transduction. Additionally, our results indicate that the apparent dissociation rate constants are more predictive of the neutralizing potency of these TGF-\u3b2-binding proteins (LAP, the type II and III receptor EDs, and the type II receptor/Fc chimera) than the apparent equilibrium constants.NRC publication: Ye

Kinetic Analysis of the Interactions between Troponin C and the C-terminal Troponin I Regulatory Region and Validation of a New Peptide Delivery/Capture System used for Surface Plasmon Resonance

NRC publication: Ye

Kinetic Analysis of the Interactions between Troponin C and the C-terminal Troponin I Regulatory Region and Validation of a New Peptide Delivery/Capture System used for Surface Plasmon Resonance

NRC publication: Ye

Real-Time Kinetic Studies on the Interaction of Transforming Growth Factor [alpha] with the Epidermal Growth Factor Receptor Extracellular Domain Reveal a Conformational Change Model\u2020

Transforming growth factor \u3b1 (TGF-\u3b1), epidermal growth factor (EGF), and related factors mediate their biological effects by binding to the extracellular domain of the EGF receptor, which leads to activation of the receptor's cytoplasmic tyrosine kinase activity. Much remains to be determined, however, about the detailed molecular mechanism involved in this ligand-induced receptor activation. The determination of the binding mechanism and the related thermodynamic and kinetic parameters are of prime importance. To do so, we have used a surface plasmon resonance-based biosensor (the BIAcore) that allows the real-time recording of the interaction between TGF-\u3b1 and the extracellular domain of the EGF receptor. By immobilizing different biotinylated derivatives of TGF-\u3b1 on the sensor chip surface, we demonstrated that the N-terminus of TGF-\u3b1 is not directly involved in receptor binding. By optimizing experimental conditions and interpreting the biosensor results by several data analysis methods, we were able to show that the data do not fit a simple binding model. Through global analysis of the data using a numerical integration method, we tested several binding mechanisms for the TGF-\u3b1/EGF receptor interaction and found that a conformational change model best fits the biosensor data. Our results, combined with other analyses, strongly support a receptor activation mechanism in which ligand binding results in a conformation-driven exposure of a dimerization site on the receptor.NRC publication: Ye