The impact of users’ cognitive function on evaluator perceptions of usability

To explore the association between the user’s cognitive function and usability reported by the evaluator. A cross-sectional study was conducted with a community-based sample. Data about participants’ age, sex, education, sleep quantity, subjective memory complaints, and cognitive function were collected. A usability session was conducted to evaluate a digital solution called Brain on Track. Independent linear-regression analyses were used to explore univariable and multivariable associations between evaluator-reported usability assessment and the users’ cognitive function, age, sex, education, sleep quantity, and subjective memory complaints. A total of 238 participants entered this study, of which 161 (67.6%) were females and the mean age was 42 (SD 12.9) years old. All variables (age, education, sleep quantity, subjective memory complaints and cognitive function) except sex were significantly associated with evaluator-reported usability in the univariable analysis (p < 0.05). Cognitive function, age, education, and subjective memory complaints remained significant in the multivariable model (F = 38.87, p < 0.001) with an adjusted R2 of 0.391. Cognition scores alone showed an adjusted R2 of 0.288. This work suggests that cognitive function impacts evaluator reported usability, alongside other users’ characteristics and needs to be considered in the usability evaluation. © 2022, The Author(s).This study was partially supported by the Águeda City Council as part of a community cognitive screening program

Targeting Aquaporin Function:Potent Inhibition of Aquaglyceroporin-3 by a Gold-Based Compound

Aquaporins (AQPs) are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III) complexes screened on human red blood cells (hRBC) and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC(50) = 0.8±0.08 µM in hRBC). Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III) to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III) complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range) together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development

The variation of G in a negatively curved space-time

Scalar-tensor (ST) gravity theories provide an appropriate theoretical framework for the variation of Newton's fundamental constant, conveyed by the dynamics of a scalar-field non-minimally coupled to the space-time geometry. The experimental scrutiny of scalar-tensor gravity theories has led to a detailed analysis of their post-newtonian features, and is encapsulated into the so-called parametrised post-newtonian formalism (PPN). Of course this approach can only be applied whenever there is a newtonian limit, and the latter is related to the GR solution that is generalized by a given ST solution under consideration. This procedure thus assumes two hypothesis: On the one hand, that there should be a weak field limit of the GR solution; On the other hand that the latter corresponds to the limit case of given ST solution. In the present work we consider a ST solution with negative spatial curvature. It generalizes a general relativistic solution known as being of a degenerate class (A) for its unusual properties. In particular, the GR solution does not exhibit the usual weak field limit in the region where the gravitational field is static. The absence of a weak field limit for the hyperbolic GR solution means that such limit is also absent for comparison with the ST solution, and thus one cannot barely apply the PPN formalism. We therefore analyse the properties of the hyperbolic ST solution, and discuss the question o defining a generalised newtonian limit both for the GR solution and for the purpose of contrasting it with the ST solution. This contributes a basic framework to build up a parametrised pseudo-newtonian formalism adequate to test ST negatively curved space-times.Comment: 7 pages, 5 figures. Contribution to the Joint European and National Astronomy Meeting (JENAM) 2010; based on a talk given by JPM in the "From Varying Couplings to Fundamental Physics" Symposiu

Ultrahard carbon film from epitaxial two-layer graphene

Atomically thin graphene exhibits fascinating mechanical properties, although its hardness and transverse stiffness are inferior to those of diamond. To date, there hasn't been any practical demonstration of the transformation of multi-layer graphene into diamond-like ultra-hard structures. Here we show that at room temperature and after nano-indentation, two-layer graphene on SiC(0001) exhibits a transverse stiffness and hardness comparable to diamond, resisting to perforation with a diamond indenter, and showing a reversible drop in electrical conductivity upon indentation. Density functional theory calculations suggest that upon compression, the two-layer graphene film transforms into a diamond-like film, producing both elastic deformations and sp2-to-sp3 chemical changes. Experiments and calculations show that this reversible phase change is not observed for a single buffer layer on SiC or graphene films thicker than 3 to 5 layers. Indeed, calculations show that whereas in two-layer graphene layer-stacking configuration controls the conformation of the diamond-like film, in a multilayer film it hinders the phase transformation.Comment: Published online on Nature Nanotechnology on December 18, 201

Trypanosoma rangeli is phylogenetically closer to Old World trypanosomes than to Trypanosoma cruzi.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T. cruzi and bat-restricted trypanosomes, and Tra[Tve-Tco] formed by T. rangeli, Trypanosoma vespertilionis and Trypanosoma conorhini clades. Tve comprises European T. vespertilionis and African T. vespertilionis-like of bats and bat cimicids characterised in the present study and Trypanosoma sp. Hoch reported in monkeys and herein detected in bats. Tco included the triatomine-transmitted tropicopolitan T. conorhini from rats and the African NanDoum1 trypanosome of civet (carnivore). Consistent with their very close relationships, Tra[Tve-Tco] species shared highly similar Spliced Leader RNA structures that were highly divergent from those of Schizotrypanum. In a plausible evolutionary scenario, a bat trypanosome transmitted by cimicids gave origin to the deeply rooted Tra[Tve-Tco] and Schizotrypanum lineages, and bat trypanosomes of diverse genetic backgrounds jumped to new hosts. A long and independent evolutionary history of T. rangeli more related to Old World trypanosomes from bats, rats, monkeys and civets than to Schizotrypanum spp., and the adaptation of these distantly related trypanosomes to different niches of shared mammals and vectors, is consistent with the marked differences in transmission routes, life-cycles and host-parasite interactions, resulting in T. cruzi (but not T. rangeli) being pathogenic to humans.This study was supported by grants awarded to MMGT and EPC from CNPq (National Council for Scientific and Technological Development) PROAFRICA, PROSUL and UNIVERSAL programs, CAPES (Coordination for the Improvement of Higher Education Personnel) PNIPB, PNPD and PROTAX programs, and FAPESP (São Paulo Research Foundation; process 2016/07487-0). Genome sequencing was supported by the Assembling the Tree of Life (ATOL) Project of the National Science Foundation, USA (NSF DEB-0830056), and TCC-USP (Trypanosomatid Culture Collection of the University of São Paulo) projects. OEA received PhD fellowships from CNPq (PROTAX) and COLCIENCIAS (Administrative Department of Science, Technology and Innovation, Colombia); PAO is a postdoctoral fellow of CAPES (PNPD); LL and AGCM are supported by a postdoctoral fellowship from CAPES (PROTAX)

Ancient coins: cluster analysis applied to find a correlation between corrosion process and burial soil characteristics

Although it is well known that any material degrades faster when exposed to an aggressive environment as well as that "aggressive" cannot be univocally defined as depending also on the chemical-physical characteristics of material, few researches on the identification of the most significant parameters influencing the corrosion of metallic object are available

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited