653 research outputs found

    Single-Node Attack for Fooling Graph Neural Networks

    Full text link
    Graph neural networks (GNNs) have shown broad applicability in a variety of domains. Some of these domains, such as social networks and product recommendations, are fertile ground for malicious users and behavior. In this paper, we show that GNNs are vulnerable to the extremely limited scenario of a single-node adversarial example, where the node cannot be picked by the attacker. That is, an attacker can force the GNN to classify any target node to a chosen label by only slightly perturbing another single arbitrary node in the graph, even when not being able to pick that specific attacker node. When the adversary is allowed to pick a specific attacker node, the attack is even more effective. We show that this attack is effective across various GNN types, such as GraphSAGE, GCN, GAT, and GIN, across a variety of real-world datasets, and as a targeted and a non-targeted attack. Our code is available at https://github.com/benfinkelshtein/SINGLE

    Functional consequences of a rare human serotonergic 5-HT1A receptor variant

    Get PDF
    Serotonin (5-HT) plays a central role in various brain functions via the activation of a family of receptors, most of them G protein coupled receptors (GPCRs). 5-HT1A receptor, the most abundant 5-HT receptors, was implicated in many brain dysfunctions and is a major target for drug discovery. Several genetic polymorphisms within the 5-HT1A receptor gene were identified and linked to different conditions, including anxiety and depression. Here, we used Xenopus oocytes to examine the effects of one of the functional polymorphism, Arg220Leu, on the function of the receptor. We found that the mutated receptor shows normal activation of G protein and normal 5-HT binding. On the other hand, the mutated receptor shows impaired desensitization, probably due to impairment in activation of β arrestin-dependent pathway. Furthermore, while the 5-HT1A receptor was shown to exhibit voltage dependent activation by serotonin and by buspirone, the mutated receptor was voltage-independent. Our results suggest a pronounced effect of the mutation on the function of the 5-HT1A receptor and add to our understanding of the molecular mechanism of its voltage dependence. Moreover, the findings of this study may suggest a functional explanation for the possible link between this variant and brain pathologies

    “Atividades Investigativas Autênticas” para o Ensino de Razão e Proporção na Formação de Professores de Matemática para os Níveis Elementar e Médio

    Get PDF
    We present some elements related to the creation, implementation, and evaluation of the impact of “authentic investigative activities” that focus on the content as well as pedagogical knowledge and attitudes in pre-service education of elementary and high school mathematics teachers. A special learning model was developed, implemented, and tested as part of activities developed in institutions that provide pre-service teacher education in Israel. The model was developed following pilot studies investigating the change in mathematical and pedagogical knowledge of pre- and inservice mathematics teachers due to the application of “authentic investigative activities”. The conclusion of the study is that application of the model, incorporating theory and practice, leads to a dramatic positive change in the pre-service teachers’ content and pedagogical knowledge. In addition, an improvement occurred in their attitudes and beliefs towards learning and teaching mathematics in general, and ratio and proportion in particular. Keywords: Authentic Investigative Activities. Ratio and Proportion. Proportional Reasoning. Mathematics Teacher Education. Preservice Teacher Education.Neste artigo são apresentados elementos relacionados à criação, implementação e avaliação do impacto das chamadas “atividades investigativas autênticas” que focam tanto o conteúdo quanto o conhecimento pedagógico e as atitudes na formação inicial de professores de Matemática para os níveis de ensino elementar e médio. Um modelo especial de aprendizagem foi desenvolvido, implementado e testado como parte de atividades desenvolvidas em instituições israelenses voltadas à formação de professores. O modelo foi desenvolvido segundo estudos-piloto, investigando as alterações nos conhecimentos matemático e pedagógico de professores de Matemática – em formação e em atuação – ocorridas com a aplicação das “atividades investigativas autênticas”. As conclusões do estudo apontam que a aplicação do modelo – por meio do qual os professores ganham experiência e são expostos a atividades de raciocínio proporcional “autêntico”, incorporando teoria (pela leitura e análise de relevantes textos de pesquisa) e prática – produz uma alteração significativa quanto à abordagem ao conteúdo matemático e quanto ao conhecimento pedagógico. Além disso, alterações significativamente positivas ocorreram nas atitudes e crenças desses professores em relação ao ensino e à aprendizagem de Matemática, em geral e, em particular, em relação aos conceitos de razão e proporção. Palavras-chave: Atividades Investigativas Autênticas, Razão e Proporção, Raciocínio Proporcional, Formação de Professores de Matemática

    Siddur

    Get PDF
    Sichviyer Chedamh, editado por David R. Pardo en 1844Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 201

    Membrane Potentials Regulating GPCRs:Insights From Experiments and Molecular Dynamics Simulation

    Get PDF
    G-protein coupled receptors (GPCRs) form the largest class of membrane proteins in humans and the targets of most present drugs. Membrane potential is one of the defining characteristics of living cells. Recent work has shown that the membrane voltage, and changes thereof, modulates signal transduction and ligand binding in GPCRs. As it may allow differential signalling patterns depending on tissue, cell type, and the excitation status of excitable cells, GPCR voltage sensitivity could have important implications for their pharmacology. This review summarises recent experimental insights on GPCR voltage regulation and the role of molecular dynamics simulations in identifying the structural basis of GPCR voltage-sensing. We discuss the potential significance for drug design on GPCR targets from excitable and non-excitable cells

    Structural mechanisms of voltage sensing in G protein coupled receptors

    Get PDF
    G-protein-coupled receptors (GPCRs) form the largest superfamily of membrane proteins and one-third of all drug targets in humans. A number of recent studies have reported evidence for substantial voltage regulation of GPCRs. However, the structural basis of GPCR voltage sensing has remained enigmatic. Here, we present atomistic simulations on the δ-opioid and M2 muscarinic receptors, which suggest a structural and mechanistic explanation for the observed voltage-induced functional effects. The simulations reveal that the position of an internal Na+ ion, recently detected to bind to a highly conserved aqueous pocket in receptor crystal structures, strongly responds to voltage changes. The movements give rise to gating charges in excellent agreement with previous experimental recordings. Furthermore, free energy calculations show that these rearrangements of Na+ can be induced by physiological membrane voltages. Due to its role in receptor function and signal bias, the repositioning of Na+ has important general implications for signal transduction in GPCRs

    Amputation of Glans Penis: A Rare Circumcision Complication and Successful Management with Primary Anastomosis and Hyperbaric Oxygen Therapy

    Get PDF
    Penile amputation is an uncommon condition that requires immediate surgical replantation. Routine standardized procedures for dealing with this medical condition do not exist. We describe a case of complete guillotine-type glans penis amputation and review the relevant literature. We performed urethral end-to-end approximation and glanular anastomosis and then applied hyperbaric oxygen therapy postoperatively. We obtained very good cosmetic and functional results
    corecore