Modelling the orthographic neighbourhood for Japanese kanji

Abstract. Japanese kanji recognition experiments are typically narrowly focused, and feature only native speakers as participants. It remains unclear how to apply their results to kanji similarity applications, especially when learners are much more likely to make similarity-based confusion errors. We describe an experiment to collect authentic human similarity judgements from participants of all levels of Japanese proficiency, from non-speaker to native. The data was used to construct simple similarity models for kanji based on pixel difference and radical cosine similarity, in order to work towards genuine confusability data. The latter model proved the best predictor of human responses.

Parkinson’s disease: A review from pathophysiology to treatment

Parkinson's Disease (PD) is the second most common neurodegenerative disease in the elderly population, with a higher prevalence in men, independent of race and social class; it affects approximately 1.5 to 2.0% of the elderly population over 60 years and 4% for those over 80 years of age. PD is caused by the necrosis of dopaminergic neurons in the substantia nigra, which is the brain region responsible for the synthesis of the neurotransmitter dopamine (DA), resulting in its decrease in the synaptic cleft. The monoamine oxidase B (MAO-B) degrades dopamine, promoting the glutamate accumulation and oxidative stress with the release of free radicals, causing excitotoxicity. The PD symptoms are progressive physical limitations such as rigidity, bradykinesia, tremor, postural instability and disability in functional performance. Considering that there are no laboratory tests, biomarkers or imaging studies to confirm the disease, the diagnosis of PD is made by analyzing the motor features. There is no cure for PD, and the pharmacological treatment consists of a dopaminergic supplement with levodopa, COMT inhibitors, anticholinergics agents, dopaminergic agonists, and inhibitors of MAO-B, which basically aims to control the symptoms, enabling better functional mobility and increasing life expectancy of the treated PD patients. Due to the importance and increasing prevalence of PD in the world, this study reviews information on the pathophysiology, symptomatology as well as the most current and relevant treatments of PD patients.Laboratório de Química Farmacêutica e Medicinal (PharMedChem) Universidade Federal do AmapáFaculdade de Ciências Farmacêuticas Universidade Estadual Paulista (UNESP) Departamento de Princípios Ativos Naturais e Toxicologia, Campus AraraquaraLaboratório Computacional de Química Farmacêutica Departamento de Ciências Farmacêuticas Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São PauloDepartment of Chemistry School of Philosophy Sciences and Letters of Ribeirão Preto University of São PauloCentro Brasileiro de Pesquisas FísicasFaculdade de Ciências Farmacêuticas Universidade Estadual Paulista (UNESP) Departamento de Princípios Ativos Naturais e Toxicologia, Campus Araraquar

Theoretical Study of Monoamine Oxidase B Inhibitors as Drug Candidates for Treatment of Parkinson’s Disease

Background: Drugs used for Parkinson's disease (PD) are mainly responsible for only relieving major symptoms, but may present several side effects that are typical of such pharmacological treatment. Methods: This study aimed to use in silico methods for drug designing inhibitors of the PD therapeutic target, monoamine oxidase B (MAO-B). Thus, 20 MAO-B inhibitors from the BindingDB database were selected followed by a calculation of their descriptors at DFT B3LYP/6-31G** level of theory. Results: Statistical analysis considering a Pearson correlation matrix led to the selection of electrophilicity index as a descriptor related to the biological activity of inhibitors. Furthermore, based on the prediction of suitable ADME/Tox properties, the molecule CID 54583085 was selected as a template to carry out structural modifications to obtain 3 analogues, whereas molecules B and C showed significant improvement in mutagenicity and carcinogenicity, in relation to the template. Conclusion: Thus, it is concluded that the proposed modifications led us to satisfactory results, since there was an improvement in the toxicological properties of molecules, however, further studies must be carried out to evaluate their biological activities as possible MAO-B inhibitors for PD treatment. </jats:sec