Explanation-by-Example Based on Item Response Theory

Intelligent systems that use Machine Learning classification algorithms are increasingly common in everyday society. However, many systems use black-box models that do not have characteristics that allow for self-explanation of their predictions. This situation leads researchers in the field and society to the following question: How can I trust the prediction of a model I cannot understand? In this sense, XAI emerges as a field of AI that aims to create techniques capable of explaining the decisions of the classifier to the end-user. As a result, several techniques have emerged, such as Explanation-by-Example, which has a few initiatives consolidated by the community currently working with XAI. This research explores the Item Response Theory (IRT) as a tool to explaining the models and measuring the level of reliability of the Explanation-by-Example approach. To this end, four datasets with different levels of complexity were used, and the Random Forest model was used as a hypothesis test. From the test set, 83.8% of the errors are from instances in which the IRT points out the model as unreliable.Comment: 15 pages, 5 figures, 3 tables, submitted for the BRACIS'22 conferenc

LPS Induces mTORC1 and mTORC2 Activation During Monocyte Adhesion

Monocyte adhesion is a crucial step in transmigration and can be induced by lipopolysaccharide (LPS). Here, we studied the role of mammalian target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, and PKC in this process. We used THP-1 cells, a human monocytic cell line, to investigate monocyte adhesion under static and flow conditions. We observed that 1.0 μg/mL LPS increased PI3K/mTORC2 pathway and PKC activity after 1 h of incubation. WYE-354 10−6 M (mTORC2/mTORC1 inhibitor) and 10−6 M wortmannin avoided monocyte adhesion in culture plates. In addition, WYE also blocked LPS-induced CD11a expression. Interestingly, rapamycin and WYE-354 blocked both LPS-induced monocyte adhesion in a cell monolayer and actin cytoskeleton rearrangement, confirming mTORC1 involvement in this process. Once activated, PKC activates mTORC1/S6K pathway in a similar effect observed to LPS. Activation of the mTORC1/S6K pathway was attenuated by 10−6 M U0126, an MEK/ERK inhibitor, and 10−6 M calphostin C, a PKC inhibitor, indicating that the MEK/ERK/TSC2 axis acts as a mediator. In agreement, 80 nM PMA (a PKC activator) mimicked the effect of LPS on the activation of the MEK/ERK/TSC2/mTORC1/S6K pathway, monocyte adhesion to ECV cells and actin cytoskeleton rearrangement. Our findings show that LPS induces activation of mTOR complexes. This signaling pathway led to integrin expression and cytoskeleton rearrangement resulting in monocyte adhesion. These results describe a new molecular mechanism involved in monocyte adhesion in immune-based diseases

Methods of assessment of the post-exercise cardiac autonomic recovery: A methodological review

The analysis of post-exercise cardiac autonomic recovery is a practical clinical tool for the assessment of cardiovascular health. A reduced heart rate recovery-an indicator of autonomic dysfunction-has been found in a broad range of cardiovascular diseases and has been associated with increased risks of both cardiac and all-cause mortality. For this reason, over the last several years, non-invasive methods for the assessment of cardiac autonomic recovery after exercise - either based on heart rate recovery or heart rate variability indices-have been proposed. However, for the proper implementation of suchmethods in daily clinical practice, the discussion of their clinical validity, physiologic meaning, mathematical formulation and reproducibility should be better addressed. Therefore, the aim of this methodological review is to present some of the most employed methods of post-exercise cardiac autonomic recovery in the literature and comprehensively discuss their strengths and weaknesses. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Univ Sao Paulo, Sch Phys Educ & Sport, Av Prof Mello Moraes,65 Cidade Univ, BR-05508030 Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Biomed Engn Program COPPE, BR-21941 Rio De Janeiro, BrazilUniv Fed Sao Paulo, Dept Physiol, Grad Program Translat Med, Sao Paulo, BrazilUniv Exeter, Childrens Hlth & Exercise Res Ctr, Exeter, Devon, EnglandUniv Miami, Miller Sch Med, Miami, FL 33136 USAUniv Fed Sao Paulo, Dept Physiol, Grad Program Translat Med, Sao Paulo, BrazilWeb of Scienc

Peripheral Chemoreflex Regulates Post-exercise Cardiac Vagal Reactivation in Healthy Humans and Patients with Pulmonary Arterial Hypertension

Sao Paulo Research Foundation, FAPESPUniv Fed Sao Paulo, Div Pulm Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, BrazilUniv Alberta, Div Pulm Med, Edmonton, AB, CanadaUniv Fed Sao Paulo, Div Pulm Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, BrazilFAPESP: 2014/24294-6FAPESP: 2015/22198-2Web of Scienc

Pathogenic Mycobacterium bovis strains differ in their ability to modulate the proinflammatory activation phenotype of macrophages

Abstract Background Tuberculosis, caused by Mycobacterium tuberculosis or Mycobacterium bovis, remains one of the leading infectious diseases worldwide. The ability of mycobacteria to rapidly grow in host macrophages is a factor contributing to enhanced virulence of the bacteria and disease progression. Bactericidal functions of phagocytes are strictly dependent on activation status of these cells, regulated by the infecting agent and cytokines. Pathogenic mycobacteria can survive the hostile environment of the phagosome through interference with activation of bactericidal responses. To study the mechanisms employed by highly virulent mycobacteria to promote their intracellular survival, we investigated modulating effects of two pathogenic M. bovis isolates and a reference M. tuberculosis H37Rv strain, differing in their ability to multiply in macrophages, on activation phenotypes of the cells primed with major cytokines regulating proinflammatory macrophage activity. Results Bone marrow- derived macrophages obtained from C57BL/6 mice were infected by mycobacteria after a period of cell incubation with or without treatment with IFN-γ, inducing proinflammatory type-1 macrophages (M1), or IL-10, inducing anti-inflammatory type-2 cells (M2). Phenotypic profiling of M1 and M2 was then evaluated. The M. bovis strain MP287/03 was able to grow more efficiently in the untreated macrophages, compared with the strains B2 or H37Rv. This strain induced weaker secretion of proinflammatory cytokines, coinciding with higher expression of M2 cell markers, mannose receptor (MR) and arginase-1 (Arg-1). Treatment of macrophages with IFN-γ and infection by the strains B2 and H37Rv synergistically induced M1 polarization, leading to high levels of inducible nitric oxide synthase (iNOS) expression, and reduced expression of the Arg-1. In contrast, the cells infected with the strain MP287/03 expressed high levels of Arg-1 which competed with iNOS for the common substrate arginine, leading to lower levels of NO production. Conclusions The data obtained demonstrated that the strain, characterized by increased growth in macrophages, down- modulated classical macrophage activation, through induction of an atypical mixed M1/M2 phenotype