Coating induced corrosion of coronary stents - A comparative study with clinical consequences

The clinical failsof gold (Au) and carbon (C) coated 316LSS stents have been barelyinvestigated. A comprehensive understanding of these fails maycontribute to the improvement of protocols for the development ofbetter materials and surfaces. This work elucidates the reasons ofthe clinical fails of Au and C coated 316LSS stents, demonstratesthe physical-chemical processes that leaded to these fails, reviewsthe mistaken line of thought that pushed these technologies to themost advanced clinical stages and proposes complementary techniquesto the FDA guidances for the early non-clinical engineering tests. Auand C coated 316LSS, bare-metal 316LSS and Co-Cr stents were studiedusing potentiodynamic scans according to FDA guidance protocols,image analysis and bulk elemental composition. The statisticalclinical outcome of the stents was found to correlate with the ionsrelease patterns eluted from their corresponding metallic substrates.In all cases ions release were consequence of post-passive corrosionprocesses such as pitting corrosion of 316LSS and bulk graindissolution of Co-Cr alloy. Surprisingly, the stents outcome did notcorrelate with their corresponding corrosion rates. Clinical fails ofAu and C coated 316LSS stents are explained in terms of their failsto inhibit the ions release from their 316LSS substrates. Materialsand surface improvements must be oriented to inhibit post-passivecorrosion processes of stents substrates. Potentiodynamic scanscomplemented with image analysis are strongly recommended for theevaluation of pre-clinical engineering tests.Fil: Navarro, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Gustavo Duffó. Comisión Nacional de Energía Atómica; ArgentinaFil: Vetcher, David. Bioimagen; ArgentinaFil: Moles, Victor. Unidad de Intervenciones Cardiovasculares; ArgentinaFil: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Rintoul, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Possible roles of amyloids in malaria pathophysiology

The main therapeutic and prophylactic tools against malaria have been locked for more than a century in the classical approaches of using drugs targeting metabolic processes of the causing agent, the protist Plasmodium spp., and of designing vaccines against chosen antigens found on the parasite's surface. Given the extraordinary resources exhibited by Plasmodium to escape these traditional strategies, which have not been able to free humankind from the scourge of malaria despite much effort invested in them, new concepts have to be explored in order to advance toward eradication of the disease. In this context, amyloid-forming proteins and peptides found in the proteome of the pathogen should perhaps cease being regarded as mere anomalous molecules. Their likely functionality in the pathophysiology of Plasmodium calls for attention being paid to them as a possible Achilles' heel of malaria. Here we will give an overview of Plasmodium-encoded amyloid-forming polypeptides as potential therapeutic targets and toxic elements, particularly in relation to cerebral malaria and the blood-brain barrier function. We will also discuss the recent finding that the genome of the parasite contains an astonishingly high proportion of prionogenic domains

When the optimal is not the best: parameter estimation in complex biological models

Background: The vast computational resources that became available during the past decade enabled the development and simulation of increasingly complex mathematical models of cancer growth. These models typically involve many free parameters whose determination is a substantial obstacle to model development. Direct measurement of biochemical parameters in vivo is often difficult and sometimes impracticable, while fitting them under data-poor conditions may result in biologically implausible values. Results: We discuss different methodological approaches to estimate parameters in complex biological models. We make use of the high computational power of the Blue Gene technology to perform an extensive study of the parameter space in a model of avascular tumor growth. We explicitly show that the landscape of the cost function used to optimize the model to the data has a very rugged surface in parameter space. This cost function has many local minima with unrealistic solutions, including the global minimum corresponding to the best fit. Conclusions: The case studied in this paper shows one example in which model parameters that optimally fit the data are not necessarily the best ones from a biological point of view. To avoid force-fitting a model to a dataset, we propose that the best model parameters should be found by choosing, among suboptimal parameters, those that match criteria other than the ones used to fit the model. We also conclude that the model, data and optimization approach form a new complex system, and point to the need of a theory that addresses this problem more generally

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

Key factors driving eating behavior are hunger and satiety, which are controlled by a complex interplay of central neurotransmitter systems and peripheral stimuli. The lipid-derived messenger oleoylethanolamide (OEA) is released by enterocytes in response to fat intake and indirectly signals satiety to hypothalamic nuclei. Brain histamine is released during the appetitive phase to provide a high level of arousal in anticipation of feeding, and mediates satiety. However, despite the possible functional overlap of satiety signals, it is not known whether histamine participates in OEA-induced hypophagia. Using different experimental settings and diets, we report that the anorexiant effect of OEA is significantly attenuated in mice deficient in the histamine-synthesizing enzyme histidine decarboxylase (HDC-KO) or acutely depleted of histamine via interocerebroventricular infusion of the HDC blocker α-fluoromethylhistidine (α-FMH). α-FMH abolished OEA-induced early occurrence of satiety onset while increasing histamine release in the CNS with an H3 receptor antagonist-increased hypophagia. OEA augmented histamine release in the cortex of fasted mice within a time window compatible to its anorexic effects. OEA also increased c-Fos expression in the oxytocin neurons of the paraventricular nuclei of WT but not HDC-KO mice. The density of c-Fos immunoreactive neurons in other brain regions that receive histaminergic innervation and participate in the expression of feeding behavior was comparable in OEA-treated WT and HDC-KO mice. Our results demonstrate that OEA requires the integrity of the brain histamine system to fully exert its hypophagic effect and that the oxytocin neuron-rich nuclei are the likely hypothalamic area where brain histamine influences the central effects of OEA

Extended Kalman Filter for Estimation of Parameters in Nonlinear State-Space Models of Biochemical Networks

It is system dynamics that determines the function of cells, tissues and organisms. To develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of nonlinear dynamic systems remains a challenging task. In this report, we apply extended Kalman Filter (EKF) to the estimation of both states and parameters of nonlinear state-space models. To evaluate the performance of the EKF for parameter estimation, we apply the EKF to a simulation dataset and two real datasets: JAK-STAT signal transduction pathway and Ras/Raf/MEK/ERK signaling transduction pathways datasets. The preliminary results show that EKF can accurately estimate the parameters and predict states in nonlinear state-space equations for modeling dynamic biochemical networks

J-PLUS: Detecting and studying extragalactic globular clusters. The case of NGC 1023.

Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Context. Extragalactic globular clusters (GCs) are key objects in studies of galactic histories. The advent of wide-field surveys, such as the Javalambre Photometric Local Universe Survey (J-PLUS), offers new possibilities for the study of these systems. Aims. We performed the first study of GCs in J-PLUS to recover information on the history of NGC 1023, taking advantage of wide-field images and 12 filters. Methods. We developed the semiautomatic pipeline GCFinder for detecting GC candidates in J-PLUS images, which can also be adapted to similar surveys. We studied the stellar population properties of a sub-sample of GC candidates using spectral energy distribution (SED) fitting. Results. We found 523 GC candidates in NGC 1023, about 300 of which are new. We identified subpopulations of GC candidates, where age and metallicity distributions have multiple peaks. By comparing our results with the simulations, we report a possible broad age-metallicity relation, supporting the notion that NGC 1023 has experienced accretion events in the past. With a dominating age peak at 1010 yr, we report a correlation between masses and ages that suggests that massive GC candidates are more likely to survive the turbulent history of the host galaxy. Modeling the light of NGC 1023, we find two spiral-like arms and detect a displacement of the galaxy’s photometric center with respect to the outer isophotes and center of GC distribution (~700pc and ~1600pc, respectively), which could be the result of ongoing interactions between NGC 1023 and NGC 1023A. Conclusions. By studying the GC system of NGC 1023 with J-PLUS, we showcase the power of multi-band surveys for these kinds of studies and we find evidence to support the complex accretion history of the host galaxy. © D. de Brito Silva et al. 2022.D.B.S. also acknowledges Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process number 2017J00204-6 for the financial support provided for the development of this project. P.C. acknowledges support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) under grant 310041/2018-0 and from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process number 2018J05392-8. A.C.S. acknowledges funding from CNPq and the Rio Grande do Sul Research Foundation (FAPERGS) through grants CNPq-403580/2016-1, CNPq-11153/2018-6, PqG/FAPERGS-17/2551-0001, FAPERGS/CAPES 19/2551-0000696-9 and L’Oréal UNESCO ABC Para Mulheres na Ciência and the Chinese Academy of Sciences (CAS) President’s International Fellowship Initiative (PIFI) through grant E085201009. G.B. acknowledges financial support from the National Autonomous University of México (UNAM) through grant DGAPA/PAPIIT IG100319 and from CONACyT through grant CB2015-252364. J.V. acknowledges the technical members of the UPAD for their invaluable work: Juan Castillo, Tamara Civera, Javier Hernández, Ángel López, Alberto Moreno, and David Muniesa. J.A.H.J. acknowledges Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), process number 2021J08920-8. A.E. acknowledges the financial support from the Spanish Ministry of Science and Innovation and the European Union – NextGenerationEU through the Recovery and Resilience Facility project ICTS-MRR-2021-03-CEFCA and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) under grant 313285/2020-9 D.A.F. thanks the ARC for financial assistance via DP170102344. Y.J.-T has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 898633. Y.J-T. also acknowledges financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). Based on observations made with the JAST80 telescope telescope/s at the Observatorio Astrofísico de Javalambre, in Teruel, owned, managed, and operated by the Centro de Estudios de Física del Cosmos de Aragón. We thank the Centro de Estudios de Física del Cosmos de Aragón for the allocation of the Director’s Discretionary Time to this program. We thank the OAJ Data Processing and Archiving Unit (UPAD) for reducing and calibrating the OAJ data used in this work. Funding for the J-PLUS Project has been provided by the Governments of Spain and Aragón through the Fondo de Inversiones de Teruel; the Aragón Government through the Research Groups E96, E103, and E16_17R; the Spanish Ministry of Science, Innovation, and Universities (MCIU/AEI/FEDER, UE) with grants PGC2018-097585-B-C21 and PGC2018-097585-B-C22; the Spanish Ministry of Economy and Competitiveness (MINECO) under AYA2015-66211-C2-1-P, AYA2015-66211-C2-2, AYA2012-30789, and ICTS-2009-14; and European FEDER funding (FCDD10-4E-867, FCDD13-4E-2685). The Brazilian agencies FINEP, FAPESP, and the National Observatory of Brazil have also contributed to this project. This work has made use of the computing facilities of the Laboratory of Astroinformatics (IAG/USP, NAT/Unicsul), whose purchase was made possible by the Brazilian agency FAPESP (grant 2009/54006-4) and the INCT-A.Peer reviewe

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements