386 research outputs found

    Look at that! BERT can be easily distracted from paying attention to morphosyntax

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    Syntactic knowledge involves not only the ability to combine words and phrases, but also the capacity to relate different and yet truth-preserving structural variations (e.g. passivization, inversion, topicalization, extraposition, clefting, etc.), as well as the ability to infer that these syntactic variations all adhere to common morphosyntactic rules, like subject-verb agreement. Although there is some evidence that BERT has rich syntactic knowledge, our adversarial approach suggests that it is not deployed in a robust and linguistically appropriate way. English BERT can be tricked to miss even quite simple syntactic generalizations, when compared with GPT-2, underscoring the need for stronger priors and for linguistically controlled experiments in evaluatio

    Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate derivatives: in vitro evaluation, cell cycle analysis and QSAR studies

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    Hepatocellular carcinoma (HCC) is a highly complex cancer, resistant to commonly used treatments and new therapeutic agents are urgently needed. A total of thirty-two thieno[3,2-b]pyridine derivatives of two series: methyl 3-amino-6-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates (1a-1t) and methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates (2a-2n), previously prepared by some of us, were evaluated as new potential anti-HCC agents by studying their in vitro cell growth inhibition on human HepG2 cells and hepatotoxicity using a porcine liver primary cell culture (PLP1). The presence of amino groups linked to a benzene moiety emerges as the key element for the anti-HCC activity. The methyl 3-amino-6-[(3-aminophenyl)ethynyl]thieno[3,2-b]pyridine-2-carboxylate (2f) is the most potent compound presenting GI50 values on HepG2 cells of 1.2 μM compared to 2.9 μM of the positive control ellipticine, with no observed hepatotoxicity (PLP1 GI50>125 μM against 3.3 μM of ellipticine). Moreover this compound changes the cell cycle profile of the HepG2 cells, causing a decrease in the % of cells in the S phase and a cell cycle arrest in the G2/M phase. QSAR studies were also performed and the correlations obtained using molecular and 1D descriptors revealed the importance of the presence of amino groups and hydrogen bond donors for anti-HCC activity, and hydrogen bond acceptors for hepatotoxicity. The best correlations were obtained with 3D descriptors belonging to different subcategories for anti-HCC activity and hepatotoxicity, respectively. These results point to different molecular mechanisms of action of the compounds in anti-HCC activity and hepatotoxicity. This work presents some promising thieno[3,2-b]pyridine derivatives for potential use in the therapy of HCC. These compounds can also be used as scaffolds for further synthesis of more potent analogues.FCT, FEDER/COMPETE/QREN/E

    Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis

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    Background: The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families. Methods: The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF). Sex-specific effects were assessed by genotype-by-sex interaction (GSI) models and sex-specific heritabilities. GSI effects and heterogeneity were tested in the residual environmental variance. SPSS 17 and SOLAR v. 4.1 were used in all computations. Results: The genetic component for PA and SB domains varied from low to moderate (11 % to 46 %), when analyzing both genders combined. We found GSI effects for vigorous PA (p = 0.02) and time spent watching television (WT) (p \u3c 0.001) that showed significantly higher additive genetic variance estimates in males. The heterogeneity in the residual environmental variance was significant for moderate PA (p = 0.02), vigorous PA (p = 0.006) and total PA (p = 0.001). Sex-specific heritability estimates were significantly higher in males only for WT, with a male-to-female difference in heritability of 42.5 (95 % confidence interval: 6.4, 70.4). Conclusions: Low to moderate genetic effects on PA and SB traits were found. Results from the GSI model show that there are sex-specific effects in two phenotypes, VPA and WT with a stronger genetic influence in males

    Tracking pollutants in a municipal sewage network impairing the operation of a wastewater treatment plant

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    This work provides a screening of organic contaminants and characterization of the dissolved organic matter in the sewer network until the municipal wastewater treatment plant (WWTP), identifying the network areas with a higher degree of contamination and their impact on the WWTP performance, particularly in the activated sludge reactor. Three monitoring campaigns were carried out at six selected locations of the sewage system (PVZ-1, PVZ-2, PS-F, PS-VC, CP-VC, and PS-T), influent (WWTPINF) and effluent (WWTPEFF) of the WWTP. Advanced analytical techniques were employed, namely excitation/emission matrix fluorescence-parallel factor analysis (EEM-PARAFAC), size exclusion chromatography with organic carbon detector (SEC-OCD), and liquid chromatography with high-resolution-mass spectrometric detection (LC-HRMS). EEM-PARAFAC showed higher fluorescence intensity for the protein-like component (C2), particularly at CP-VC (near seafood industries) associated with the presence of surfactants (~50 mg/L). SEC-OCD highlighted the WWTP efficiency in removing low molecular weight acids and neutrals. LC-HRMS tentatively identified 108 compounds of emerging concern (CEC) and similar detection patterns were obtained for all wastewater samples, except for PVZ-2 (lower detection), many of which occurred in the effluent. Eight CECs included on relevant Watch-Lists were detected in all WWTPEFF samples. Furthermore, 111 surfactants were detected, the classes more frequently found being alcohol ethoxylates (AEOs), nonylphenol polyethoxylates (NPEOs) and linear alkylbenzene sulphonates (LAS). The continuous presence of LAS and NPEOs allied to surfactants concentrations in the WWTPINF of 15–20 mg/L, with CP-VC location (linked with food industries) as an important contributor, explain the morphological changes in the activated sludge and high LAS content in the dewatered sludge, which may have impacted WWTP performance.i) Base-UIDB/50020/2020 and Programmatic-UIDP/50020/2020 Funding of LSRE-LCM, funded by national funds through FCT/MCTES (PIDDAC); ii) European Regional Development Fund through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014–2020 (ref. 0725_NOR_WATER_1_P); iii) Xunta de Galicia (Verónica Castro predoctoral contract: ED481A-2017/156, and ED431C2017/36), the Spanish Agencia Estatal de Investigación – MCIN/AEI/ 10.13039/501100011033 (ref. PID2020-117686RB-C32); iv) NORTE-01-0145-FEDER-000069 (Healthy Waters) co-funded by European Regional Development Fund (ERDF), through North Portugal Regional Operational Programme (NORTE2020), under the PORTUGAL 2020 Partnership Agreement. The authors also acknowledge Águas do Norte, S.A. for supporting the development of this work. Daniela F.S. Morais acknowledges her Ph.D. scholarship supported by FCT (SFRH/BD/146476/2019). Bianca M. Souza Chaves gratefully acknowledges her postdoctoral scholarship supported by CNPq through the Science Without Borders Program (Process No. 201989/2014-0). Vítor J.P. Vilar acknowledges the FCT Individual Call to Scientific Employment Stimulus 2017 (CEECIND/01317/2017)S

    Ophthalmic Complications of Bariatric Surgery

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    Obesity is increasing vastly in the world, and the number of bariatric surgeries being performed is also increasing. Patients being submitted to bariatric surgeries, especially malabsorptive procedures, have an increased risk of developing nutrient deficiencies, which can culminate in symptomatic hypovitaminosis, if supplementation is not done correctly. The eye and the optic system need an adequate level of several vitamins and minerals to perform properly, especially vitamin A, and this article wants to cover the main nutrients involved, the possible ophthalmic complications that can arise by their deficiency, and the management of those complications

    Mesial Temporal Lobe Epilepsy (MTLE) Drug-Refractoriness Is Associated With P2X7 Receptors Overexpression in the Human Hippocampus and Temporal Neocortex and May Be Predicted by Low Circulating Levels of miR-22

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    Objective: ATP-gated ionotropic P2X7 receptors (P2X7R) actively participate in epilepsy and other neurological disorders. Neocortical nerve terminals of patients with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) express higher P2X7R amounts. Overexpression of P2X7R bolsters ATP signals during seizures resulting in glial cell activation, cytokines production, and GABAergic rundown with unrestrained glutamatergic excitation. In a mouse model of status epilepticus, increased expression of P2X7R has been associated with the down-modulation of the non-coding micro RNA, miR-22. MiR levels are stable in biological fluids and normally reflect remote tissue production making them ideal disease biomarkers. Here, we compared P2X7R and miR-22 expression in epileptic brains and in the serum of patients with MTLE-HS, respectively. Methods: Quantitative RT-PCR was used to evaluate the expression of P2X7R in the hippocampus and anterior temporal lobe of 23 patients with MTLE-HS and 10 cadaveric controls. Confocal microscopy and Western blot analysis were performed to assess P2X7R protein amounts. MiR-22 expression was evaluated in cell-free sera of 40 MTLE-HS patients and 48 healthy controls. Results: Nerve terminals of the hippocampus and neocortical temporal lobe of MTLE-HS patients overexpress (p 3) anti-epileptic drug (AED) regimens. Conclusion: Data show that there is an inverse relationship between miR-22 serum levels and P2X7R expression in the hippocampus and neocortex of MTLE-HS patients, which implies that measuring serum miR-22 may be a clinical surrogate of P2X7R brain expression in the MTLE-HS. Moreover, the high area under the ROC curve (0.777; 95% CI 0.629-0.925; p = 0.001) suggests that low miR-22 serum levels may be a sensitive predictor of poor response to AEDs among MTLE-HS patients. Results also anticipate that targeting the miR-22/P2X7R axis may be a good strategy to develop newer AEDs.This research was partial funded by a BICE Tecnifar Grant. The work performed in PC-S’s Lab was partially supported by UP/Santander Totta and Fundação para a Ciência e Tecnologia (FCT, POCTI PTDC/SAU-PUB/28311/2017—EPIRaft grant and Fundo Europeu de Desenvolvimento Regional—FEDER funding and COMPETE—MedInUP projects Pest-OE/SAU/UI215/2014, UID/BIM/4308/2016, UIDB/04308/2020 and UIDP/04308/2020). Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by the Foundation for Science and Technology (FCT) Portugal (grant numbers UIDB/00215/2020 and UIDP/00215/2020) and ITR—Laboratory for Integrative and Translational Research in Population Health (LA/P/0064/2020). RM-F was in receipt of an FCT PhD studentship (SFRH/BD/137900/2018).info:eu-repo/semantics/publishedVersio
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