Benchmarks for Pir\'a 2.0, a Reading Comprehension Dataset about the Ocean, the Brazilian Coast, and Climate Change

Pir\'a is a reading comprehension dataset focused on the ocean, the Brazilian coast, and climate change, built from a collection of scientific abstracts and reports on these topics. This dataset represents a versatile language resource, particularly useful for testing the ability of current machine learning models to acquire expert scientific knowledge. Despite its potential, a detailed set of baselines has not yet been developed for Pir\'a. By creating these baselines, researchers can more easily utilize Pir\'a as a resource for testing machine learning models across a wide range of question answering tasks. In this paper, we define six benchmarks over the Pir\'a dataset, covering closed generative question answering, machine reading comprehension, information retrieval, open question answering, answer triggering, and multiple choice question answering. As part of this effort, we have also produced a curated version of the original dataset, where we fixed a number of grammar issues, repetitions, and other shortcomings. Furthermore, the dataset has been extended in several new directions, so as to face the aforementioned benchmarks: translation of supporting texts from English into Portuguese, classification labels for answerability, automatic paraphrases of questions and answers, and multiple choice candidates. The results described in this paper provide several points of reference for researchers interested in exploring the challenges provided by the Pir\'a dataset.Comment: Accepted at Data Intelligence. Online ISSN 2641-435

Genetic comparison of sickle cell anaemia cohorts from Brazil and the United States reveals high levels of divergence

Genetic analysis of admixed populations raises special concerns with regard to study design and data processing, particularly to avoid population stratification biases. The point mutation responsible for sickle cell anaemia codes for a variant hemoglobin, sickle hemoglobin or HbS, whose presence drives the pathophysiology of disease. Here we propose to explore ancestry and population structure in a genome-wide study with particular emphasis on chromosome 11 in two SCA admixed cohorts obtained from urban populations of Brazil (Pernambuco and Sao Paulo) and the United States (Pennsylvania). Ancestry inference showed different proportions of European, African and American backgrounds in the composition of our samples. Brazilians were more admixed, had a lower African background (43% vs. 78% on the genomic level and 44% vs. 76% on chromosome 11) and presented a signature of positive selection and Iberian introgression in the HbS region, driving a high differentiation of this locus between the two cohorts. The genetic structures of the SCA cohorts from Brazil and US differ considerably on the genome-wide, chromosome 11 and HbS mutation locus levels9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP8367/2011-1; 150398/2013-1; 304455/2012-1; 310938/2014-7; 305218/2017-48367/2011-1; 150398/2013-1; 304455/2012-1; 310938/2014-7; 305218/2017-42008/57441-0; 2014/00984-3; 2012/06438-5; 2015/13152-9; 2008/10596-

Full elucidation of the transmembrane anion transport mechanism of squaramides using in silico investigations

A comprehensive experimental and theoretical investigation of the transmembrane chloride transport promoted by four series of squaramide derivatives, with different degrees of fluorination, number of convergent N-H binding units and conformational shapes, is reported. The experimental chloride binding and transport abilities of these small synthetic molecules in liposomes were rationalised with quantum descriptors and molecular dynamics simulations in POPC bilayers. The tripodal tren-based compounds, with three squaramide binding motifs, have high chloride affinity, isolating the anion from water molecules within the membrane model and preventing its release to the aqueous phase, in agreement with the absence of experimental transport activity. In contrast, the symmetrical monosquaramides, with moderate chloride binding affinity, are able to bind and release chloride either in the aqueous phase or at the membrane interface level, in line with experimentally observed high transport activity. The PMF profiles associated with the diffusion of these free transporters and their chloride complexes across phospholipid bilayers show that the assisted chloride translocation is thermodynamically favoured

Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins

Inhibition of human transthyretin aggregation by non-steroidal anti-inflammatory compounds: a structural and thermodynamic analysis

Transthyretin (TTR) is a homotetrameric protein that circulates in plasma and cerebral spinal fluid (CSF) whose aggregation into amyloid fibrils has been associated with at least two different amyloid diseases: senile systemic amyloidosis (SSA) and familial amyloid polyneuropathy (FAP). In SSA aggregates are composed of WT-TTR, while in FAP more than 100 already-described variants have been found in deposits. Until now, TTR-related diseases have been untreatable, although a new drug called Tafamidis has been approved only in Europe to specifically treat V30M patients. Thus, new strategies are still necessary to treat FAP caused by other variants of TTR. TTR has two channels in the dimer interface that bind to the hormone thyroxin and that have been used to accommodate anti-amyloidogenic compounds. These compounds stabilize the tetramers, rendering TTR less amyloidogenic. Here, we investigated the effects of three non-steroidal anti-inflammatory compounds-sulindac (SUL), indomethacin (IND) and lumiracoxib (LUM)-as tetramer stabilizers and aggregation inhibitors. WT-TTR and the very aggressive TTR variant L55P were used as models. These compounds were able to stabilize TTR against high hydrostatic pressure (HHP), increasing the ΔGf by several kcal. They were also effective in inhibiting WT-TTR and L55P acid- or HHP-induced aggregation; in particular, LUM and IND were very effective, inhibiting almost 100% of the aggregation of both proteins under certain conditions. The species formed when aggregation was performed in the presence of these compounds were much less toxic to cells in culture. The crystal structures of WT-TTR bound to the three compounds were solved at high resolution, allowing the identification of the relevant protein:drug interactions. We discuss here the ligand-binding features of LUM, IND and SUL to TTR, emphasizing the critical interactions that render the protein more stable and less amyloidogenic.CAPESCNPqInstituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem (INBEB)FAPERJFAPES

Association of Chlamydia trachomatis, C. pneumoniae, and IL-6 and IL-8 Gene Alterations With Heart Diseases

Atherosclerosis is a progressive disease characterized by chronic inflammation of the arterial walls, associated with genetic and infectious factors. The present study investigated the involvement of Chlamydia trachomatis and Chlamydia pneumoniae infections and immunological markers (C-reactive protein, CRP, TNF-α, IL-6, IL-8, and IL-10) in the process of atherosclerosis. The evaluation included 159 patients for surgical revascularization (CAD) and 71 patients for surgical heart valve disease (HVD) at three hospitals in Belém, Brazil. The control group (CG) comprised 300 healthy individuals. Blood samples collected before surgery were used for antibodies detection (enzyme immunoassay), CRP (immunoturbidimetry) and IL-6 levels (enzyme immunoassay). Tissue fragments (atheroma plaque, heart valve and ascending aorta) were collected during surgery and subjected to qPCR for detection of bacterial DNA. Promoter region polymorphisms of each marker and relative quantification of TNF-α, IL-8, and IL-10 gene expression were performed. Demography and social information were similar to the general population involved with both diseases. Antibody prevalence to C. trachomatis was 30.6, 20.3, and 36.7% (in the CAD, HVD, and CG, respectively) and to C. pneumoniae was 83.6, 84.5, and 80.3% (in the CAD, HVD, and CG, respectively). C. trachomatis cryptic plasmid DNA was detected in 7.4% of the samples. Frequency of IL6−174G>C polymorphism was higher in CAD and HVD than in CG regardless of previous exposure to Chlamydia. Previous C. trachomatis infection showed involvement in HVD and CAD. Significant association between disease and previous C. pneumoniae infection was found only among HVD. GG genotype of IL6−174G>C is apparently a risk factor for heart disease, whereas AT genotype of IL8−251A>T was mainly involved in valvulopathies, including patients with prior exposure to C. pneumoniae