2,318 research outputs found

    A reflective characterisation of occasional user

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    This work revisits established user classifications and aims to characterise a historically unspecified user category, the Occasional User (OU). Three user categories, novice, intermediate and expert, have dominated the work of user interface (UI) designers, researchers and educators for decades. These categories were created to conceptualise user's needs, strategies and goals around the 80s. Since then, UI paradigm shifts, such as direct manipulation and touch, along with other advances in technology, gave new access to people with little computer knowledge. This fact produced a diversification of the existing user categories not observed in the literature review of traditional classification of users. The findings of this work include a new characterisation of the occasional user, distinguished by user's uncertainty of repetitive use of an interface and little knowledge about its functioning. In addition, the specification of the OU, together with principles and recommendations will help UI community to informatively design for users without requiring a prospective use and previous knowledge of the UI. The OU is an essential type of user to apply user-centred design approach to understand the interaction with technology as universal, accessible and transparent for the user, independently of accumulated experience and technological era that users live in

    Ground States for Diffusion Dominated Free Energies with Logarithmic Interaction

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    Replacing linear diffusion by a degenerate diffusion of porous medium type is known to regularize the classical two-dimensional parabolic-elliptic Keller-Segel model. The implications of nonlinear diffusion are that solutions exist globally and are uniformly bounded in time. We analyse the stationary case showing the existence of a unique, up to translation, global minimizer of the associated free energy. Furthermore, we prove that this global minimizer is a radially decreasing compactly supported continuous density function which is smooth inside its support, and it is characterized as the unique compactly supported stationary state of the evolution model. This unique profile is the clear candidate to describe the long time asymptotics of the diffusion dominated classical Keller-Segel model for general initial data.Comment: 30 pages, 2 figure

    On the singularity formation and relaxation to equilibrium in 1D Fokker-Planck model with superlinear drift

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    We consider a class of Fokker--Planck equations with linear diffusion and superlinear drift enjoying a formal Wasserstein-like gradient flow structure with convex mobility function. In the drift-dominant regime, the equations have a finite critical mass above which the measure minimising the associated entropy functional displays a singular component. Our approach, which addresses the one-dimensional case, is based on a reformulation of the problem in terms of the pseudo-inverse distribution function. Motivated by the structure of the equation in the new variables, we establish a general framework for global-in-time existence, uniqueness and regularity of monotonic viscosity solutions to a class of nonlinear degenerate (resp. singular) parabolic equations, using as a key tool comparison principles and maximum arguments. We then focus on a specific equation and study in more detail the regularity and dynamics of solutions. In particular, blow-up behaviour, formation of condensates (i.e. Dirac measures at zero) and long-time asymptotics are investigated. As a consequence, in the mass-supercritical case, solutions will blow up in L∞ in finite time and---understood in a generalised, measure sense---they will eventually have condensate. We further show that the singular part of the measure solution does in general interact with the density and that condensates can be transient. The equations considered are motivated by a model for bosons introduced by Kaniadakis and Quarati (1994), which has a similar entropy structure and a critical mass if d≥3

    Interspecific Introgression in Cetaceans: DNA Markers Reveal Post-F1 Status of a Pilot Whale

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    Visual species identification of cetacean strandings is difficult, especially when dead specimens are degraded and/or species are morphologically similar. The two recognised pilot whale species (Globicephala melas and Globicephala macrorhynchus) are sympatric in the North Atlantic Ocean. These species are very similar in external appearance and their morphometric characteristics partially overlap; thus visual identification is not always reliable. Genetic species identification ensures correct identification of specimens. Here we have employed one mitochondrial (D-Loop region) and eight nuclear loci (microsatellites) as genetic markers to identify six stranded pilot whales found in Galicia (Northwest Spain), one of them of ambiguous phenotype. DNA analyses yielded positive amplification of all loci and enabled species identification. Nuclear microsatellite DNA genotypes revealed mixed ancestry for one individual, identified as a post-F1 interspecific hybrid employing two different Bayesian methods. From the mitochondrial sequence the maternal species was Globicephala melas. This is the first hybrid documented between Globicephala melas and G. macrorhynchus, and the first post-F1 hybrid genetically identified between cetaceans, revealing interspecific genetic introgression in marine mammals. We propose to add nuclear loci to genetic databases for cetacean species identification in order to detect hybrid individuals.

    Tailored functionalized magnetic nanoparticles to target breast cancer cells including cancer stem-like cells

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    Nanotechnology-based approaches hold substantial potential to avoid chemoresistance and minimize side effects. In this work, we have used biocompatible iron oxide magnetic nanoparticles (MNPs) called MF66 and functionalized with the antineoplastic drug doxorubicin (DOX) against MDA-MB-231 cells. Electrostatically functionalized MNPs showed effective uptake and DOX linked to MNPs was more efficiently retained inside the cells than free DOX, leading to cell inactivation by mitotic catastrophe, senescence and apoptosis. Both effects, uptake and cytotoxicity, were demonstrated by different assays and videomicroscopy techniques. Likewise, covalently functionalized MNPs using three different linkers—disulfide (DOX-S-S-Pyr, called MF66-S-S-DOX), imine (DOX-I-Mal, called MF66-I-DOX) or both (DOX-I-S-S-Pyr, called MF66-S-S-I-DOX)—were also analysed. The highest cell death was detected using a linker sensitive to both pH and reducing environment (DOX-I-S-S-Pyr). The greatest success of this study was to detect also their activity against breast cancer stem-like cells (CSC) from MDA-MB-231 and primary breast cancer cells derived from a patient with a similar genetic profile (triple-negative breast cancer). In summary, these nanoformulations are promising tools as therapeutic agent vehicles, due to their ability to produce efficient internalization, drug delivery, and cancer cell inactivation, even in cancer stem-like cells (CSCs) from patientsThis research was funded by the European Seventh Framework Program (grant agreement number 262943); the European Union’s Horizon 2020 research and innovation programme (grant agreement number 685795); Ministerio de Economía y Competitividad, Spain (grants CTQ2016-78454-C2-2-R, BIO2016-77367-C2-1-R and SAF2017-87305-R); Basque Government Elkartek KK- 2017/00008; Comunidad de Madrid (IND2017/IND-7809; S2017/BMD-3867 RENIM-CM and S2018/NMT-4321 NANOMAGCOST-CM); NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007) and Breast Cancer Now (MAN-Q2); co-financed by European Structural Cancers 2020, 12, 1397 17 of 19 and Investment Fund, Asociación Española Contra el Cáncer (Singulares 2014) and IMDEA Nanociencia. CIC biomaGUNE acknowledges Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (Grant MDM-2017-0720). IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686

    Caspase-8 inhibition represses initial human monocyte activation in septic shock model

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    In septic patients, the onset of septic shock occurs due to the over-activation of monocytes. We tested the therapeutic potential of directly targeting innate immune cell activation to limit the cytokine storm and downstream phases. We initially investigated whether caspase-8 could be an appropriate target given it has recently been shown to be involved in microglial activation. We found that LPS caused a mild increase in caspase-8 activity and that the caspase-8 inhibitor IETD-fmk partially decreased monocyte activation. Furthermore, caspase-8 inhibition induced necroptotic cell death of activated monocytes. Despite inducing necroptosis, caspase-8 inhibition reduced LPS-induced expression and release of IL-1β and IL-10. Thus, blocking monocyte activation has positive effects on both the pro and anti-inflammatory phases of septic shock. We also found that in primary mouse monocytes, caspase-8 inhibition did not reduce LPS-induced activation or induce necroptosis. On the other hand, broad caspase inhibitors, which have already been shown to improve survival in mouse models of sepsis, achieved both. Thus, given that monocyte activation can be regulated in humans via the inhibition of a single caspase, we propose that the therapeutic use of caspase-8 inhibitors could represent a more selective alternative that blocks both phases of septic shock at the source.Unión Europea, Ministerio de Economía y Competitividad SAF2012-39029Unión Europea, Ministerio de Economía y Competitividad SAF2015-64171REspaña,Junta de Andalucía P10-CTS-649

    Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease Virus Nonstructural Protein 2B

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    Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains

    Eficacia de la pelmatoscopia a través de capacitación especializada e implementación de oficinas pelmatoscópicas en el hospital “Hermilio Valdizán Medrano” y el centro de salud “Carlos Showing Ferrari”. Huánuco, mayo 2003 – abril 2004

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    The study demonstrated that the techniques used for the taking of plantar impression are not the suitable ones, the same ones that do not guarantee reliability from the legal medical point of view; on the other hand, the process of identification of new born is not fulfilled efficiently, so this process is left unfinished, fulfilling only with the first stage consisting of the capture of the plantar impression on the part of the personnel of health and his corresponding file in clinical history; the expert's report is not realized on the part of the police personnel in the moment of the discharge of the patient; steps that must be realized according to the stipulated thing in the Manual of Proceeding of Personal Identification. Opposite to this problems, it was tried to demonstrated the effectiveness of the pelmatoscopía by means of the use of the suitable skills and the processing logistic resources through a specializing training and the office implementation pelmatoscópicas in the institutions in study. The type and level of investigation are descriptive-explanatory and transversal. Between the main results it was obtained that 100% of the samples picked up (15 pelmatoscópicas sheets) of the personnel who received the training, and at the same time they have the requirements established by the effective norms for a good taking of papiloscópicas impressions; therefore, there is a team of obstetricians professionals that are in the capacity to assume the taking of plantar impression in the identification of the neonatus.El en estudio se demostró que las técnicas utilizadas para la toma de impresión plantar no son las adecuadas, las mismas que no garantizan confiabilidad desde el punto de vista médico legal; por otro lado, el proceso de identificación del recién nacido no se cumple eficientemente, pues este proceso se deja inconcluso, cumpliendo solamente con la primera fase, consistente en la toma de la impresión plantar por parte del personal de salud y su correspondiente archivo en la historia clínica; sin realizarse el peritaje por parte del personal policial en el momento del alta del paciente; pasos que deben ser realizados de acuerdo a lo estipulado en el Manual de Procedimientos de Identificación Personal. Frente a esta problemática, se pretendió demostrar la eficacia de la pelmatoscopía mediante el uso de las técnicas adecuadas y el procesamiento de los recursos logísticos a través de una capacitación especializada y la implementación de oficinas pelmatoscópicas en las instituciones en estudio. El tipo y nivel de investigación es el descriptivo explicativo y transversal. Entre los principales resultados se obtuvo que el 100 % de las muestras recogidas (15 hojas pelmatoscópicas) del personal que recibió la capacitación cumplen con los requisitos establecidos por las normas vigentes para una buena toma de impresiones papiloscópicas; por tanto, existe un equipo de profesionales de obstetricia que está en la capacidad de asumir la toma de impresión plantar en la identificación del neonato

    Diabetes-related excess mortality in Mexico: a comparative analysis of National Death Registries between 2017-2019 and 2020

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    OBJECTIVE: To estimate diabetes-related mortality in Mexico in 2020 compared with 2017-2019 after the onset of the coronavirus disease 2019 (COVID-19) pandemic. RESEARCH DESIGN AND METHODS: This retrospective, state-level study used national death registries of Mexican adults aged ≥20 years for the 2017-2020 period. Diabetes-related death was defined using ICD-10 codes listing diabetes as the primary cause of death, excluding certificates with COVID-19 as the primary cause of death. Spatial and negative binomial regression models were used to characterize the geographic distribution and sociodemographic and epidemiologic correlates of diabetes-related excess mortality, estimated as increases in diabetes-related mortality in 2020 compared with average 2017-2019 rates. RESULTS: We identified 148,437 diabetes-related deaths in 2020 (177 per 100,000 inhabitants) vs. an average of 101,496 deaths in 2017-2019 (125 per 100,000 inhabitants). In-hospital diabetes-related deaths decreased by 17.8% in 2020 versus 2017-2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes (130 per 100,000 inhabitants). Compared with 2018-2019 data, hyperglycemic hyperosmolar state and diabetic ketoacidosis were the two contributing causes with the highest increase in mortality (128% and 116% increase, respectively). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, rates of COVID-19 hospitalization, and prevalence of HbA1c ≥7.5%. CONCLUSIONS: Diabetes-related deaths increased among Mexican adults by 41.6% in 2020 after the onset of the COVID-19 pandemic, occurred disproportionately outside the hospital, and were largely attributable to type 2 diabetes and hyperglycemic emergencies. Disruptions in diabetes care and strained hospital capacity may have contributed to diabetes-related excess mortality in Mexico during 2020

    Similarities between the lipid proile of Mexican patients with lupus and the general population

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    Premature cardiovascular events have been observed in systemic lupus erythematosus (SLE) patients, but the reason for this accelerated process is still debatable; although traditional risk factors are more prevalent in such patients than in the general population, the do not seem to fully explain that enhanced risk. One of the most important conditions is a proatherogenic lipid proile. There is not enough data about it in Mexican SLE patients. Objective: To establish the differences in the lipid proiles between Mexican patients with SLE and the general population. Material and methods: Observational, transversal, descriptive and comparative study, between SLE patients and age-sex-matched healthy volunteers. We performed a full lipid proile (by spectrophotometry) 14 hours of fast. The results obtained were analyzed by the statistical program SPSS® Statistics version 17. Results: We studied the full lipid proiles of 138 subjects, 69 with a diagnosis of SLE and 69 agesex- matched healthy volunteers; 95.7% were females and 4.3% males. Average age was 30 years; average body mass index (BMI) 25.96 ± 5.96 kg/m² in SLE patients and 26.72 ± 4.36 kg/m² in the control group (p = 0.396). Average of total cholesterol 156 mg/dl in the SLE patients and 169.4 mg/dl in the control group (p =0.028); average of low density lipoprotein (LDL) cholesterol 85.27 mg/dl in the SLE patients and 97.57 mg/dl in the control group (p = 0.023). Conclusions: We did not ind statistical differences in the lipid proiles among patients and healthy volunteers, which could explain increased cardiovascular morbidity and mortality observed in SLE patient
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