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•Membranes are essential components ofin vitrotissue barrier models.•FEA parametric sweeps of fluid flow, shear stress and molecular transport are presented.•Single channel perfusion, ...provide control over fluid flow and molecular transport.•Parallel perfusion influences the steady state concentration distribution in channels.•Experimental barrier model verifies the key finding of the modelling parameters.
Following the rapid growth of Organ-on-a-Chip (OoaC) technology, porous membranes have become essential components for in vitro tissue barrier models. Nonetheless, literature highlights lacking knowledge on their integration and effect on microfluidic devices. Therefore, we conducted finite element modelling (FEM) to characterize the influence of membrane, channel geometry, flow and diffusion parameters, in modelling flow rate, shear stress, transient transport and steady state molecular concentration. This analysis was performed for four different conditions based on single channel (SCP) and parallel perfusion (PP). It was found that membrane and geometry parameters are crucial in determining flow and shear for SCP. However, for PP, flow and shear are predominantly governed by the inlet flow rate. Although the transient behaviour is well-controlled within SCP and PP, only PP allows modelling the steady state concentration distribution. It is highlighted that: (1) the pore radius has great influence on flow and shear; (2) a shallow cell channel and a long membrane are capable of establishing different levels of shear on opposing surfaces of the same channel; (3) the membrane thickness, membrane length, height of the cell and flow channels, and inlet flow rate provide good control over transient transport; (4) the membrane length and inlet flow rate enable changing the concentration from a uniform distribution to a complete heterogeneous state across the device. Experimental assays were performed to support the FEM and evidence its significance for OoaC applications. Ultimately, extensive, and systematic guidelines are provided on designing future OoaC devices with integrated porous membranes.
Neutron stars are among of the most exotic objects in the universe and constitute a unique laboratory to study nuclear matter above the nuclear saturation density. In this work, we study the equation ...of state (EoS) of the nuclear matter within a relativistic model subject to a strong magnetic field. We then apply this EoS to study and describe some of the physical characteristics of neutron stars, especially the mass–radius relation and chemical compositions. To study the influence of the magnetic field and the hyperons in the stellar interior, we consider altogether four solutions: two different magnetic field to obtain a weak and a strong influence; and two configurations: a family of neutron stars formed only by protons, electrons, and neutrons and a family formed by protons, electrons, neutrons, muons, and hyperons. The limit and the validity of the results found are discussed with some care. In all cases, the particles that constitute the neutron star are in
β
equilibrium and zero total net charge. Our work indicates that the effect of a strong magnetic field has to be taken into account in the description of magnetars, mainly if we believe that there are hyperons in their interior, in which case the influence of the magnetic field can increase the mass by more than 10 %. We have also seen that although a magnetar can reach 2.48
M
⊙
, a natural explanation of why we do not know pulsars with masses above 2.0
M
⊙
arises. We also discuss how the magnetic field affects the strangeness fraction in some standard neutron star masses, and to conclude our paper, we revisit the direct Urca process related to the cooling of the neutron stars and show how it is affected by the hyperons and the magnetic field.
To investigate smoking trajectories and their association with pulmonary function (PF) and respiratory symptoms at age 22.
Data from a population-based cohort study of 3350 individuals and their ...spirometries were analysed. The outcomes were: forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at the mid expiratory phase (FEF25–75 %), FEV1/FVC and FEF25–75/FVC ratio. Smoking data were collected at perinatal follow-up (gestational exposure) and 15, 18 and 22 years. Group-based trajectory model was applied.
Four groups were identified: no exposure (NE), gestational (GE), gestational and adulthood (GAE) and continuous (CE) exposure. Both CE and GAE trajectories were associated with lower values of FEV1/FVC (−1.77pp; p = 0.01 and −1.58 pp; p<0.001 respectively) and FEF25–75/FVC ratio (−7.27pp; p = 0.019 and −6.04pp; p<0.001 respectively) compared to the NE trajectory. Lower FEV1 and FEF25–75 % values were also related to the GAE trajectory (−68 ml; p = 0.03 and −253 ml/s;p<0.001 respectively). Compared to those who never smoked, individuals who smoked 10 or more cigarettes daily presented a reduction in the FEV1/FVC ratio by 1.37pp (p<0.001), FEF25–75 % by 126 ml (p = 0.012) and FEF25–75 %/FVC ratio by 3.62pp (p = 0.011). CE trajectory showed higher odds of wheezing (OR 4.14; p<0.001) and cough (OR 2.39; p = 0.002) compared to the non-exposed group.
The in-uterus exposure to maternal smoking reduces PF later in life. However, the perpetuation of smoking behaviour throughout adolescence and early adulthood is determinant for PF main reduction and the emergence of respiratory-related symptoms.
In the epididymis, epithelial cells work in a concerted manner to create a luminal environment for sperm maturation, transport, and storage. However, the cell functions may be affected by ...anthropogenic factors, causing negative impacts on male fertility. In our study, we describe the pattern of protein expression in the epithelium and luminal fluid from epididymis of
Oligoryzomys nigripes,
a South American sigmodontine rodent whose reproductive biology has been little studied. Nine animals were captured from a preserved area of Atlantic Forest, where the exposure to anthropogenic influences is minimal. Epididymides were processed for histological analysis under light and epifluorescence microscopy, in which we used cell-specific markers aquaporin 9 (AQP9), vacuolar H
+
-ATPase (V-ATPase), and cytokeratin 5 (KRT5). Other samples were assessed for protein expression using shotgun proteomics. Similar to laboratory rodents, principal cells expressed AQP9 in their stereocilia. Basal cells, identified by KRT5 labeling, presented lateral body projections and a few axiopodia going toward the lumen. Clear cells expressed V-ATPase in their sub-apical vesicles and microplicae, and showed different shapes along the duct. Shotgun proteomics detected 51 proteins from epididymal supernatant. Most of them have been previously described in other species, indicating that they are well conserved. Twenty-three proteins detected in
O. nigripes
have not been described in epididymis from other South American sigmodontine rodents, confirming that the secretion pattern is species-specific. Our findings in
O. nigripes
from a protected area may help to create a baseline for studies investigating the effects of anthropogenic factors on functionality of the epididymal epithelium.
Most yield criteria possess a point-symmetry with respect to its center, meaning that a stress state and its reverse state have the same absolute value. However, this can be an unrealistic ...approximation, even for cubic metals (both face-centered cubic and body center cubic)), which can present a small asymmetry between the yield stress in tension and compression, i.e. a strength differential (SD) effect. This work analyzes the influence of taking or not into account the SD effect in the modeling of the sheet orthotropic behavior in the numerical simulation of a cylindrical cup drawing process. The yield criterion adopted is the CPB06 1, including its version with two linear transformations 2, allowing a better fitting of the experimental data available. The material analyzed presents a quite small tension-compression ratio of 0.963. However, this small SD effect leads to a slightly higher punch force during the bending dominated stage, resulting in a very small influence on the springback prediction. The influence on the thickness evolution during the process is negligible.
Over recent years, human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have been associated with monophasic and relapsing central nervous system demyelination involving the ...optic nerves, spinal cord, and brain. While the clinical relevance of MOG Ab detection is becoming increasingly clear as therapeutic and prognostic differences from multiple sclerosis are acknowledged, an in-depth characterization of human MOG Ab is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we investigated the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults (n = 287 patients at baseline, 130 longitudinal samples, and 22 cerebrospinal fluid samples). MOG extracellular domain was also immobilized to determine the affinity of MOG Ab. MOG Ab response was of immunoglobulin G1 isotype, and was of peripheral rather than intrathecal origin. High affinity MOG Ab were detected in 15% paediatric and 18% adult sera. More than 75% of paediatric and adult MOG Ab targeted a dominant extracellular antigenic region around Proline42. MOG Ab titers fluctuated over the progression of disease, but affinity and reactivity to Proline42 remained stable. Adults with a relapsing course intrinsically presented with a reduced immunoreactivity to Proline42 and had a more diverse MOG Ab response, a feature that may be harnessed for predicting relapse. Higher titers of MOG Ab were observed in more severe phenotypes and during active disease, supporting the pathogenic role of MOG Ab. Loss of MOG Ab seropositivity was observed upon conformational changes to MOG, and this greatly impacted the sensitivity of the detection of relapsing disorders, largely considered as more severe. Careful consideration of the binding characteristics of autoantigens should be taken into account when detecting disease-relevant autoantibodies.
Abstract
Background
Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF ...is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46–60 days after YF symptom onset.
Methods
Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017–2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post–symptom onset.
Results
From 46 to 60 days post–symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF.
Conclusions
These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.
Late-relapsing hepatitis after yellow fever is a clinical picture described around 60 days after the acute yellow fever phase, presenting with nonspecific symptoms, such as fatigue and rebound in aminotransferases, alkaline phosphatase, and total bilirubin values, with a benign final outcome.
In this work, we revisit the study published in Dutra et al., Chinese Physics C 42, 064105 (2018) where 34 consistent relativistic mean-field models were analyze at the nuclear matter constraints in ...relation to the role of short-range correlations in the calculation of the symmetry energy and its consequence on the value of the gamma parameter.