Haskell Type System Analysis

Types systems of programming languages are becoming more and more sophisticated and, in some cases, they are based on concepts from Logic, Type Theory and Category Theory. Haskell is a language with a modern type system and it is often singled out as an example using such theories. This work presents a small formalization of the Haskell type system and an analysis based on the mentioned theories, including its relation with the Intuitionist Propositional Second Order Logic and its logical characteristics, if there is a category in its type system and how monads are just monoids in the category of Haskell's endofunctors

The Bauru Basin in São Paulo and its tetrapods

Funding Information: The authors thank the editors of Derbyana, especially its Editor-in-Chief Silvio T. Hiruma, for the invitation to participate in this volume dedicated to “Advances in Paleontology”. This contribution results from FAPESP grant 2020/07997-4, to which most of the authors are affiliated. We also thank the Derbyana ad-hoc reviewers, Drs. Agustin Martinelli and Fabiano Iori, for their helpful comments to the manuscript. FIGURE 6 – Cumulative chronological distribution of the tetrapod fossil record in the Bauru Basin of São Paulo (1913-2022) compared to science and technology funding metrics and events: A – For all tetrapods; grey bars indicate total records of tables 1-5; green line indicates taxonomic richness (grey lines in Tables 1-5); pink line indicates FAPESP budget in billions of reais between 1976 and 2021 (FAPESP 2022); blue line indicates CNPq, CAPES, and FINEP budget in millions of reais between 1996 and 2018 (ESCOBAR 2019). Events indicated by arrows correspond, in chronological sequence, to the foundations of USP, “Instituto Geográfico e Geológico”, FAPESP, Unicamp, UNESP, “Instituto Geológico”, and Monte Alto Museum of Paleontology, the implementations of the Qualis list, the Lattes curriculum, the CAPES Portal de Periódicos, and the CNPq “grant”, the foundation of the Marília Museum of Paleontology, the release of the first MCT/CNPq public call for “Strengthening National Paleontology”, and the foundation of “Pedro Candolo” Museum of Paleontology. B – Separately for each recorded tetrapod group, coloured lines indicate total of records in tables 1-5 of Anura = light blue, Crocodyliformes = red, Mammalia = purple, Sauropoda = green, Squamata = yellow, Testudines = orange, and Theropoda = dark blue. Publisher Copyright: Copyright © 2022 The Institute of Electronics, Information and Communication Engineers.The Bauru Basin bears one of the best sampled tetrapod paleofaunas of Brazil, with about 70% of this diversity collected from its deposits in São Paulo. Its fossils are known since the beginning of the 20th century, coming from all stratigraphic units of the Basin cropping-out in the state, i.e., Santo Anastácio, Araçatuba, Adamantina (alternatively divided into Vale do Rio do Peixe, Presidente Prudente, and São José do Rio Preto formations), and Marília formations. Identified taxa include rare anurans, mammals, and squamates, an important set of testudines, theropods (including birds), and sauropods, in addition to one of the most diverse crocodyliform faunas known worldwide. This congregates more than fifty unique taxonomic entities, including 42 formally described species. Based on biostratigraphic correlations (including tetrapods), on few absolute ages, and other sources of evidence, the Bauru Basin deposits in São Paulo seem to be chronologically restricted to the Late Cretaceous, but further investigation is much needed. Finally, the history of research with such fossils highlights the importance of public funding for research and decentralization of university education for the advancement of science.publishersversionpublishe

Limited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeuticsPM received funding from Ataxia UK Grant (Project: Pharmacologic therapy for Machado-Joseph disease: from a C. elegans drug screen to a mouse model validation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio