Ethics in Authorship: Considerations and Concerns

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Red blood cells motion in a glass microchannel

The motion of the red blood cells (RBCs) flowing in microvessels and microchannels depend on several effects, such as hematocrit (Hct), geometry, and temperature. According to our knowledge, the effect of the temperature on RBC motion was never investigated at a microscale level. Hence, the aim of the present work is to determine the effect of the temperature on the RBC’s trajectories and to investigate the best approximation of the trajectories through a nonlinear optimization. In vitro human blood was pumped through a 100 mm circular microchannel and by using a confocal micro- PTV system the RBC’s trajectories were measured at different temperatures, i.e., 25◦C and 37◦C. In this study we measured the motion of forty cells flowing in the middle of the microchannel and applied different functions to approximate its behavior.This study was supported in part by the following grants: Grant-in-Aid for Science and Technology (PTDC/SAU-BEB/108728/2008, PTDC/SAU-BEB/105650/2008 and PTDC/EME-MFE/099109/2008) from the Science and Technology Foundation (FCT) and COMPETE, Portugal

Application of the stretched simulated annealing method in the stability analysis of multicomponent systems using excess gibbs energy models

In this work, the Stretched Simulated Annealing Method was applied to identify the stationary points of the tangent plane distance function defined for the Gibbs energy. The classic excess Gibbs energy Non Random Two Liquid model was used for these studies in several multicomponent mixtures, for which specific numerical difficulties were shown. The results obtained by applying the methodology developed in this work were very satisfactory

Motion of red blood cells in a glass microchannel: a global optimization approach

Este artigo também deve ser anexado ao Departamento Tecnologia Mecânica, docente Rui Alberto Madeira Macedo Lima.In this work we characterized the behavior of red blood cell motion through a glass microchannel. In this study we consider the radial displacement of forty red blood cells and use different functions to approximate the radial displacement of each of them, by means of global optimization using stretched simulated annealing method. Some numerical results are shown

Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection

The immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responses against endogenous and exogenous insults. Disruption of these safeguard and homeostatic mechanisms can lead to unpredictable inflammatory and autoimmune responses, whereas deficiency of immune stimulatory pathways may orchestrate immunosuppressive programs that contribute to perpetuate chronic infections, but also influence cancer development and progression. Glycans have emerged as essential components of homeostatic circuits, acting as fine-tuners of immunological responses and potential molecular targets for manipulation of immune tolerance and activation in a wide range of pathologic settings. Cell surface glycans, present in cells, tissues and the extracellular matrix, have been proposed to serve as “self-associated molecular patterns” that store structurally relevant biological data. The responsibility of deciphering this information relies on different families of glycan-binding proteins (including galectins, siglecs and C-type lectins) which, upon recognition of specific carbohydrate structures, can recalibrate the magnitude, nature and fate of immune responses. This process is tightly regulated by the diversity of glycan structures and the establishment of multivalent interactions on cell surface receptors and the extracellular matrix. Here we review the spatiotemporal regulation of selected glycan-modifying processes including mannosylation, complex Nglycan branching, core 2 O-glycan elongation, LacNAc extension, as well as terminal sialylation and fucosylation. Moreover, we illustrate examples that highlight the contribution of these processes to the control of immune responses and their integration with canonical tolerogenic pathways. Finally, we discuss the power of glycans and glycan-binding proteins as a source of immunomodulatory signals that could be leveraged for the treatment of autoimmune inflammation and chronic infection.This work was supported by grants from SSP: co-funded by the European Union (ERC, GlycanSwitch, 101071386). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. The work was also co-funded by EU GlycanTrigger-grant Agreement No: 101093997. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. SSP also acknowledges funding by “2022 LRA Lupus Innovation Award” and by “European Crohn’s and Colitis Organisation (ECCO) Pioneer Award 2021”. SSP also acknowledges the US Department of Defense, US Army Medical Research Acquisition Activity, FY18 Peer Reviewed Medical Research Program Investigator-Initiated Research Award (award number W81XWH1920053) as well as grant funded by the Portuguese Foundation for Science and Technology – FCT (EXPL/MED-ONC/0496/2021). IA acknowledges FCT for funding (2022.00337.CEECIND). JG acknowledges funding from ESCMID (ESCMID Research Grant 2022), ECCO (ECCO Grant 2023) and FCT (2020.00088.CEECIND). G.A.R acknowledges grants from the Argentinean Agency for Promotion of Science, Technology and Innovation (PICT 2017-0494, PICT-FBB 620 and PICT 2020-01552). The authors are also thankful for generous support from Sales (Argentina), Bunge & Born (Argentina), Baron (Argentina), Williams (Argentina) and Richard Lounsbery (USA) Foundations, as well as donations from Ferioli-Ostry and Caraballo families to GAR

Cell-free layer (CFL) analysis in a glass capillary: comparison between a manual and automatic method

In this study, in vitro blood flowing through a 100 m glass capillary was studied. The images were captured using a confocal system and post-processed using Image J and MatLab. The aim of the present work, was to measure the trajectories of the cell-free layer (CFL) by using two different methods, i. e., a manual method (MM) and an automatic method (AM). For theMM we have used amanual tracking plugin (MTrackJ) from Image J to track labeled red blood cells (RBCs) flowing around the boundary of the RBCs core. For the AM we have used a MatLab scripts to measure automatically the CFL trajectories. The preliminary numerical results suggest that the CFL trajectories follow a polynomial function for both methods.The authors acknowledge the financial support provided by: PTDC/SAU-BEB/108728/2008, PTDC/SAU-BEB/105650/2008, PTDC/EME-MFE/099109/2008 and PTDC/SAU-ENB/116929/2010 from the FCT (Science and Technology Foundation) and COMPETE, Portugal

Label-free multi-step microfluidic device for mechanical characterization of blood cells: Diabetes type II

The increasing interest to establish significant correlations between blood cell mechanical measurements and blood diseases, has led to the promotion of microfluidic devices as attractive clinical tools for potential use in diagnosis. A multi-step microfluidic device able to separate red and white blood cells (RBCs and WBCs) from plasma and simultaneously measure blood cells deformability (5 and 20% of hematocrit) is presented in this paper. The device employs passive separation based on the cross-flow filtration principle, introduced at each daughter channel. At the outlets, hyperbolic geometries allow single-cell deformability analysis. The device was tested with blood from five healthy and fifteen diabetic type II voluntary donors. The results have shown that WBCs have lower deformability than RBCs, and no significant differences were observed in WBCs from healthy and pathological blood samples. In contrast, RBCs have shown significant differences, with pathological cells exhibiting lower deformability. Shear rheology has shown that blood from patients with type II diabetes has higher viscosity than blood from healthy donors. This microfluidic device has demonstrated the ability to reduce cell concentration at the outlets down to 1%, an ideal cell concentration for assessing the blood cells deformability, under healthy and pathological conditions. The results provide new insights and quantitative information about the hemodynamics of in vitro type II diabetes mellitus RBCs. Thus, such device can be a promising complement in clinical diagnosis and biological research as part of an integrated blood-on-a-chip system.This work was supported by Projects NORTE-01-0145-FEDER- 028178, NORTE-01-0145-FEDER-029394, NORTE-01-0145-FEDER- 030171 funded by COMPETE2020, NORTE2020, PORTUGAL2020, and FEDER. This work was also supported by Fundação para a Ciência e a Tecnologia (FCT) under the strategic grants UIDB/04077/2020 and UIDB/00532/2020. D. Pinho and V. Faustino acknowledge the Ph.D. scholarships SFRH/BD/89077/2012 and SFRH/BD/99696/2014, respectively, both provided by FCT. Susana Catarino thanks FCT for her contract funding provided through 2020.00215.CEECIND. F. T. Pinho is thankful to FCT for financial support through projects LA/P/0045/2020 of the Associate Laboratory in Chemical Engineering (ALiCE) and projects UIDB/00532/2020 and UIDP/00532/2020 of Centro de Estudos de Fenómenos de Transporte.info:eu-repo/semantics/publishedVersio

Steady and unsteady laminar flows of newtonian and generalized newtonian fluids in a planar T-junction

An investigation of laminar steady and unsteady flows in a two-dimensional T-junction was carried out for Newtonian and a non-Newtonian fluid analogue to blood. The flow conditions considered are of relevance to hemodynamical applications and the localization of coronary diseases, and the main objective was to quantify the accuracy of the predictions and to provide benchmark data that are missing for this prototypical geometry. Under steady flow, calculations were performed for a wide range of Reynolds numbers and extraction flow rate ratios, and accurate data for the recirculation sizes were obtained and are tabulated. The two recirculation zones increased with Reynolds number, but the behaviour was non-monotonic with the flow rate ratio. For the pulsating flows a periodic instability was found, which manifests itself by the breakdown of the main vortex into two pieces and the subsequent advection of one of them, while the secondary vortex in the main duct was absent for a sixth of the oscillating period. Shear stress maxima were found on the walls opposite the recirculations, where the main fluid streams impinge onto the walls. For the blood analogue fluid, the recirculations were found to be 10% longer but also short lived than the corresponding Newtonian eddies, and the wall shear stresses are also significantly different especially in the branch duct