Analysis and Design of Lubricating Interfaces in External Gear Machines for High and Low Viscous Working Fluids

Lubricating interfaces represent a significant design constituent which contribute to the reliability and efficiency of many modern designs of gap compensated external gear machines (EGMs). However, the complex nature of the influence of fluid behavior in these interfaces on the structural and thermal effects of the solid components involved in the lubricating gap makes their design quite challenging. Moreover, the extensive range of applications currently available for EGMs warrant designs which can perform efficiently at extended range of operating conditions as well as with a comprehensive variety of working fluids. In order to improve the understanding of the physics in these lubricating gaps especially in gap compensated units, and thereby achieve virtual prototyping design tools for these conditions, the principal goal of this research is to extend the capabilities of the state of art numerical models for the lubricating interfaces in EGMs. The present research addresses the design and analysis of the lateral lubricating interface between the lateral bushing and the gears in EGMs for critical operating points as well as for reference working fluids with significant differences in their viscosities which challenge the lubricating ability of the thin film interface. A novel mixed film-TEHD (Thermo-Elastohydrodynamic) model for the lateral lubricating gap was developed as a part of this research to capture the effects of such widely varying design parameters. Two different instances of experimental validation of this mixed film lubrication model were carried out for the reference cases of conventional oil based EGMs, namely with measured torque losses and drain leakage measurements. Furthermore, the capabilities of the lateral gap model are utilized in studying the impact of the variations in surface finishes on the performance of a commercially available EGM chosen for this study, by considering lateral plate designs of varying surface roughness. Additional contributions have also been made to the modeling of lateral gaps in EGMs to extend their capabilities, which include consideration of frictional contact forces between the lateral bushing and the housing for the first time. This research demonstrates the significance of considering the effect of friction on the performance of the lubricating gaps in gear pumps by using a reference case of an asymmetrically balanced EGM used for aerospace fuel injection applications. In addition, a mass conserving cavitation algorithm to account for the cavitating conditions in the lubricating interface was also integrated with the mixed lubrication model to improve the stability of the numerical predictions of the pressures in the lubricating gap. Leveraging the design potential of the numerical tool developed in this research, designs to improve the lubrication performance of EGMs are presented in this work, which include surface shaping on the gears as well as achieving an optimal balance configuration in the lateral gap. These unique modifications along with the mixed lubrication model are then applied to a reference EGM case with water as its working fluid where the low viscosity of a fluid further adds to complexity in designing the lateral lubricating interface. A novel water based EGM prototype which can work at high pressures is thus proposed in this work, to implement and validate the proposed design approaches for the reference low viscous fluid. Furthermore, the present work also proposes certain unique variations to the common designs of oil-EGMs that need to be implemented in the prototype water hydraulic EGM to facilitate its practical implementation especially at high pressure operating conditions. The methodologies and models developed in this research along with their proven fidelity using experiments could potentially serve as a design tool to formulate new efficient EGM designs for an extensive range of applications and working fluids

Phospholipid related antigens and protective mechanisms : implications for cardiovascular diseases, human autoimmunity and inflammation

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. Low levels of IgG1 proved to be indicators of risk, whereas higher concentrations were protective. In addition, exposure of macrophages to monoclonal antibodies against phosphorylcholine (developed in-house) improved the efficiency of phagocytosis by these cells in a manner dependent on complement, which might explain why higher levels of these antibodies in patients with SLE appear to be protective. Overall, the clinical and experimental evidence we provide here confirms the relevance of anti-PC and anti-MDA IgMs in connection with cardiovascular and autoimmune diseases. Both these natural protective antibodies and Annexin A5 could serve as prognostic markers and potentially be of value in treating inflammatory and autoimmune conditions

A numerical procedure to design the optimal axial balance in external gear machines and its potential in formulating novel efficient design solutions

A novel numerical procedure to design the optimal axial balance in external gear machines (EGMs) has been formulated and developed in the present study. Lateral lubricating interfaces exist between the lateral bushes and the rotating gears in pressure compensated designs of EGMs and play a significant role in minimizing power losses arising from fluid shear stress and leakages from the gap. Moreover, lateral bushes in pressure compensated designs of EGMs perform significant functions of sealing the tooth space volumes while they transfer fluid from the inlet to the outlet port. ^ The losses from the lateral gap from these two opposing sources can be minimized by designing an optimal balance area on the side of the lateral bushes which do not face the gears, while simultaneously ensuring that proper pressure is established at the high pressure port of the EGM. This condition is termed as the \u27axial balance\u27 of the machine, which is significant in improving its reliability and reducing wear in the EGM under consideration. ^ To determine the optimal axial balance which minimizes the power losses associated with the lubricating gap in all operating conditions, all the static and hydrodynamic forces acting on the lateral bushes have to be considered. This delicate aspect of external gear units design is usually addressed through empirical procedures which rely heavily on experience, expertise and expensive experimental trial and error. ^ In this research, the proposed method is fully automatic and leverages the previous work of modeling the lateral lubricating interface between gears and lateral bushes in the author\u27s research group at Purdue. The developed procedure has a significant potential to virtually design the axial balance in a variety of EGM designs, results for which are presented in the current study. Furthermore, the possibilities of using the developed procedure to design new efficient solutions is demonstrated in this research by applying this method to design a micro surface shaping effect, by introducing a linear sloping wedge on either side of the gear teeth. Optimal axial balance configurations are determined for these effects which further improves the efficiency of the reference EGM chosen for the purpose of this study

IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases

IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sjögren's syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test) = 0.0037). IgM low levels were more prevalent in MCTD, SLE, SjS, SSc and UCTD. IgM anti-PC variable region profiles were different from and more homologous than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, anti-MDA did not promote polarization of Tregs. Taken together, Anti-PC is decreased in MCTD and also in SLE, SjS and SSc but not in other studied diseases. Anti-PC may thus differentiate between these. In contrast, anti-MDA did not show these differences between diseases studied. Anti-PC level is negatively correlated with CV in the patient group cohort. In contrast to anti-PC, anti-MDA did not promote Treg polarization. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC in some rheumatic conditions

IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases

IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sjögren's syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test) = 0.0037). IgM low levels were more prevalent in MCTD, SLE, SjS, SSc and UCTD. IgM anti-PC variable region profiles were different from and more homologous than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, anti-MDA did not promote polarization of Tregs. Taken together, Anti-PC is decreased in MCTD and also in SLE, SjS and SSc but not in other studied diseases. Anti-PC may thus differentiate between these. In contrast, anti-MDA did not show these differences between diseases studied. Anti-PC level is negatively correlated with CV in the patient group cohort. In contrast to anti-PC, anti-MDA did not promote Treg polarization. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC in some rheumatic conditions

IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases

IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sjögren's syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test) = 0.0037). IgM low levels were more prevalent in MCTD, SLE, SjS, SSc and UCTD. IgM anti-PC variable region profiles were different from and more homologous than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, anti-MDA did not promote polarization of Tregs. Taken together, Anti-PC is decreased in MCTD and also in SLE, SjS and SSc but not in other studied diseases. Anti-PC may thus differentiate between these. In contrast, anti-MDA did not show these differences between diseases studied. Anti-PC level is negatively correlated with CV in the patient group cohort. In contrast to anti-PC, anti-MDA did not promote Treg polarization. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC in some rheumatic conditions.PRECISESADS Clinical Consortium Members: Te research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115565, resources of which are composed of fnancial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies in kind contribution. Swedish Heart Lung foundation and Swedish Rheumatism Association also contributed to fnancing. Open access funding provided by Karolinska Institute.Ye

Insights From Liver-Humanized Mice on Cholesterol Lipoprotein Metabolism and LXR-Agonist Pharmacodynamics in Humans

Background and Aims Genetically modified mice have been used extensively to study human disease. However, the data gained are not always translatable to humans because of major species differences. Liver-humanized mice (LHM) are considered a promising model to study human hepatic and systemic metabolism. Therefore, we aimed to further explore their lipoprotein metabolism and to characterize key hepatic species-related, physiological differences. Approach and Results Fah(-/-), Rag2(-/-), and Il2rg(-/-) knockout mice on the nonobese diabetic (FRGN) background were repopulated with primary human hepatocytes from different donors. Cholesterol lipoprotein profiles of LHM showed a human-like pattern, characterized by a high ratio of low-density lipoprotein to high-density lipoprotein, and dependency on the human donor. This pattern was determined by a higher level of apolipoprotein B100 in circulation, as a result of lower hepatic mRNA editing and low-density lipoprotein receptor expression, and higher levels of circulating proprotein convertase subtilisin/kexin type 9. As a consequence, LHM lipoproteins bind to human aortic proteoglycans in a pattern similar to human lipoproteins. Unexpectedly, cholesteryl ester transfer protein was not required to determine the human-like cholesterol lipoprotein profile. Moreover, LHM treated with GW3965 mimicked the negative lipid outcomes of the first human trial of liver X receptor stimulation (i.e., a dramatic increase of cholesterol and triglycerides in circulation). Innovatively, LHM allowed the characterization of these effects at a molecular level. Conclusions LHM represent an interesting translatable model of human hepatic and lipoprotein metabolism. Because several metabolic parameters displayed donor dependency, LHM may also be used in studies for personalized medicine.Peer reviewe

Mixed Lubrication Effects in the Lateral Lubricating Interfaces of External Gear Machines: Modelling and Experimental Validation

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

Mixed Lubrication Effects in the Lateral Lubricating Interfaces of External Gear Machines: Modelling and Experimental Validation

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