This article presents a novel mixed-thermoelastohydrodynamic (TEHD) model for the lateral lubricating interfaces which exist between floating lateral bushings and gears in external gear machines ...(EGMs). The proposed model integrates the influence of surface asperities along with the fluid structure and thermal interaction in the interface, especially in the regions of very low film thicknesses by following a stochastic approach in modelling the mixed lubrication regime. Furthermore, the current work includes validation of the predictions of the mixed-TEHD model against experimentally measured leakages from the lateral gap and compares the performance of this model with a previously developed full film TEHD model for the lateral gaps in EGMs.
Advances in spatial proteomics and protein colocalization are a driving force in the understanding of cellular mechanisms and their influence on biological processes. New methods in the field of ...spatial proteomics call for the development of algorithms and open up new avenues of research. The newly introduced Molecular Pixelation (MPX) provides spatial information on surface proteins and their relationship with each other in single cells. This allows for in silico representation of neighborhoods of membrane proteins as graphs. In order to analyze this new data modality, we adapted local assortativity in networks of MPX single-cell graphs and created a method that is able to capture detailed information on the spatial relationships of proteins. The introduced method can evaluate the pairwise colocalization of proteins and access higher-order similarity to investigate the colocalization of multiple proteins at the same time. We evaluated the method using publicly available MPX datasets where T cells were treated with a chemokine to study uropod formation. We demonstrate that adjusted local assortativity detects the effects of the stimuli at both single- and multiple-marker levels, which enhances our understanding of the uropod formation. We also applied our method to treating cancerous B-cell lines using a therapeutic antibody. With the adjusted local assortativity, we recapitulated the effect of rituximab on the polarity of CD20. Our computational method together with MPX improves our understanding of not only the formation of cell polarity and protein colocalization under stimuli but also advancing the overall insight into immune reaction and reorganization of cell surface proteins, which in turn allows the design of novel therapies. We foresee its applicability to other types of biological spatial data when represented as undirected graphs.
Background
Malondialdehyde (MDA) is generated during lipid peroxidation as in oxidized low‐density lipoprotein, but antibodies against oxidized low‐density lipoprotein show variable results in ...clinical studies. We therefore studied the risk of cardiovascular disease (CVD) associated with IgM antibodies against MDA conjugated with human albumin (anti‐MDA).
Methods and Results
In a 5‐ to 7‐year follow‐up of 60‐year‐old men and women from Stockholm County previously screened for cardiovascular risk factors (2039 men, 2193 women), 209 incident CVD cases (defined as new events of coronary heart disease, fatal and nonfatal myocardial infarction, ischemic stroke, and hospitalization for angina pectoris) and 620 age‐ and sex‐matched controls were tested for IgM anti‐MDA by ELISA. Antibody peptide/protein characterization was done using a proteomics de novo sequencing approach. After adjustment for smoking, body‐mass index, type 2 diabetes mellitus, hyperlipidemia, and hypertension, an increased CVD risk was observed in the low IgM anti‐MDA percentiles (below 10th and 25th) (odds ratio and 95% CI: 2.0; 1.19–3.36 and 1.67; 1.16–2.41, respectively). Anti‐MDA above the 66th percentile was associated with a decreased CVD risk (odds ratio 0.68; CI: 0.48–0.98). After stratification by sex, associations were only present among men. IgM anti‐MDA levels were lower among cases (median interquartile range: 141.0 112.7–164.3 versus 147.4 123.5–169.6; P=0.0177), even more so among men (130.6 107.7–155.3 versus 143.0 120.1–165.2; P=0.001). The IgM anti‐MDA variable region profiles are distinctly different and also more homologous in their content (correlates strongly with fewer peptides) than control antibodies (not binding MDA).
Conclusions
IgM anti‐MDA is a protection marker for CVD. This finding could have diagnostic and therapeutic implications.
•A numerical model for the analysis of the compensation mechanism of an aerospace fuel delivery pump is presented.•Coupled fluid and structural effects in lubricating gaps are considered in the ...analysis.•Effect of frictional forces is shown to create a hysteresis effect on the bearing motion.•Experimental measurements are performed to validate the findings of the numerical model.
External gear pumps (EGPs) are one of the most common choices in aerospace engines as a fuel delivery pump. These units usually include a pressure compensation system that defines the lubricating gap at the lateral side of the gears. This lubricating interface is a critical design aspect, which strongly affects the reliability as well as the mechanical and volumetric efficiencies of the pump. Major challenges in designing these lubricating gaps in aero engine fuel pumps, include high operating speeds, delivery pressures and low viscosity of the working fluids. Virtual prototyping methods present a fast and efficient design tool and have the potential to improve the EGP’s reliability and efficiency. This paper presents a study on the pressure compensation system of a fuel delivery EGP and shows how the presence of frictional forces opposing the motion of the compensating element significantly affect the lubricating performance of the unit. The presence of these frictional forces produces an effect of hysteresis on the axial balance system, so that the lubricating gaps that develop within the pump at a certain operating condition depend on the previous operating state. This effect was captured in an experimental setup purposely developed for this study at Rolls-Royce. Within this work, this behavior was also reproduced numerically, through a coupled fluid structure interaction – elastohydrodynamic (EHD) model that includes the modeling of these frictional forces. After detailing the implementation of the lateral gap model, this paper presents measurements from carefully conducted experiments which correlate with the simulated predictions of the influence of frictional forces on the performance of a reference EGP design under study.
This article demonstrates how a properly designed micro-surface linear wedge added to the lateral surfaces of the gear teeth can improve the lubricating ability of external gear machines (EGMs), ...resulting in lower power losses and chance of wear during their operation. The approach of study is based on the use of a fluid structure interaction (FSI) model for the analysis of the lateral lubricating gaps developed in the authors' research team. Such a model is used to determine the best design of the wedged gear by considering the overall axial balance problem of pressure compensated EGMs for high-pressure applications. The article shows the numerical predictions along with the experimental verifications of the advantages offered by the proposed solution in terms of torque loss reduction for a particular reference pump.
This article presents a novel fluid structure interaction (FSI) model for lateral lubricating interfaces in an asymmetrically balanced external gear pump. Due to the asymmetry in the geometry of the ...floating lateral bushes responsible for sealing the displacement chambers in such machines, the lubricating interfaces on either side of the gears have been modeled as distinct but coupled lubricating films. An elastohydrodynamic (EHD) lubrication regime was modeled in all simulations and film thickness predictions for both lubricating interfaces have been achieved. The novel FSI model for the asymmetric lateral gaps is then used in an automatic optimization procedure to design the optimal axial balance in the reference external gear machine (EGM). The optimal axial balance is achieved by determining the optimal balance area on the lateral bush by considering specific design variables associated with it. The procedure aims to find the best feasible design solution that minimizes the total power losses in the lubricating interfaces while also minimizing the nonuniformities in the orientation of these gaps between two significant operating conditions of the EGM. The developed procedure highlights the potential to virtually design the axial balance in EGMs-which represent a key design aspect of pressure compensated EGM-by using an advanced FSI-EHD model.
Abs against phosphorylcholine (anti-PC) and Abs against malondialdehyde (anti-MDA) may be protective in chronic inflammation, like atherosclerosis and cardiovascular disease. It is not known how they ...develop early in life. Ab titers were measured using ELISA in healthy women (
= 105; born into life study) and their children. Plasma samples were collected from the mothers before conception and from the children at birth as well as at 1 and 2 y after birth. Extracted Abs were compared using a proteomics de novo sequencing approach. It was observed that children were born with very low levels of IgM anti-PC, whereas IgM anti-MDA was present at birth. Both IgM anti-PC and anti-MDA increased during the first 2 y of life, but IgM anti-PC in contrast to IgM anti-MDA was still significantly lower than in the mothers. IgG anti-PC decreased after 1 y but reached similar levels as mothers' after 2 y, whereas IgG anti-MDA reached similar levels as mothers' already after 1 y. Proteomics peptide sequencing analysis indicated large peptide sequence variation without specific clone expression during the early stage of life compared with the adult stage for which specific peptide sequences dominated. IgM anti-PC levels develop much slower than anti-MDA and are still relatively low at 2 y. We hypothesize that anti-PC is developed by a combination of preprogramming and exposure to the external world, in which infectious agents may play a role. For anti-MDA, preprogramming is likely to play a major role and at an earlier stage than for anti-PC.
The pathogenesis of chronic inflammation, a common denominator in cardiovascular, metabolic and systemic autoimmune diseases, is influenced by a number of genetic, metabolic and immunological risk ...factors. Oxidation of cellular membranes and lipoproteins by reactive oxygen species generates a number of complex and distinct oxidized phospholipids (OxPL) thought to be involved in this pathogenesis. Since the discovery of OxLDL in atherosclerotic lesions, research on these oxidized phospholipids and protective factors/mechanisms has expanded in recent years. As a result, oxidized phospholipids and related antigens have been characterized extensively in connection not only with cardiovascular pathogenesis, but also with related diseases that also are associated with negative cardiovascular outcomes. As a consequence, these oxidized phospholipids are now known to play a key role not only in initiating inflammation, but also in mediating deleterious consequences.In our first study, we examined the potential pro-inflammatory features of oxidized cardiolipins, phospholipids present in LDL, where they might be exposed at the surface following oxidation. Initially, we determined whether oxidized cardiolipin (OxCL) exerts pro-inflammatory effects on macrophages and neutrophils and, if so, whether Annexin-A5 can inhibit these effects. As expected, OxCL induced leukotriene production by these immune cells in a calcium-dependent manner through activation of the 5-LOX gene. Moreover, Annexin A5 bound to oxidized, but not native cardiolipin, thereby abrogating both the elevated leukotriene production and even intracellular mobilization of calcium. Annexin A5 also inhibited the expression of adhesion molecules on endothelial cells and might thus play an important role in preventing the binding of lymphocytes and monocytes to these cells and resulting inflammation around atherosclerotic plaques.In our second investigation, we characterized the clinical significance of antibodies towards malondialdehyde, an important epitope exposed at the surface of both OxLDL and apoptotic cells, in 60-year-old patients with cardiovascular disease. An assay developed to measure circulating levels of anti-MDA IgMs revealed that these patients had lower levels than ageand gender-matched controls, especially the men (130.1 107.8–155 versus 143 120–165, p=0.001), RU/mL. The odds ratio and 95% CI below the 10th 2.0; 1.19-3.36 and above the 66th percentile 0.68; 0.48-0.98 indicated that these antibodies can predict risk in such patients. Amino acid sequencing showed less variation in these antibodies than in nonspecific IgMs.To extend these findings to systemic autoimmune diseases, we next assessed the prevalence of anti-MDA and anti-PC IgM in patients with RA, SLE, SjS, SSc, MCTD, and UCTD. The levels of anti-PC, but not ant-MDA IgM were strikingly lower in the case of MCTD. Moreover, levels of both IgMs were low among those with SLE or Sjogren’s syndrome and high among patients with rheumatoid arthritis and primary phospholipid syndrome, with no difference in the case of UCTD. Furthermore, when anti-PC IgM was added exogenously, the number of immunosuppressive T cells (Tregs) increased, with no such effect with anti-MDA IgM. Finally, the amino acid sequences of these antibodies showed both certain similarities and differences.In our last study, we assessed the prevalence of anti–PC IgG1 and IgG2 in patients with SLE.
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