78 research outputs found

    Experimental Investigation of the Effect of Radial Gap and Impeller Blade Exit on Flow-Induced Vibration at the Blade-Passing Frequency in a Centrifugal Pump

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    It has been recognized that the pressure pulsation excited by rotor-stator interaction in large pumps is strongly influenced by the radial gap between impeller and volute diffusers/tongues and the geometry of impeller blade at exit. This fluid-structure interaction phenomenon, as manifested by the pressure pulsation, is the main cause of flow-induced vibrations at the blade-passing frequency. In the present investigation, the effects of the radial gap and flow rate on pressure fluctuations, vibration, and pump performance are investigated experimentally for two different impeller designs. One impeller has a V-shaped cut at the blade's exit, while the second has a straight exit (without the V-cut). The experimental findings showed that the high vibrations at the blade-passing frequency are primarily raised by high pressure pulsation due to improper gap design. The existence of V-cut at blades exit produces lower pressure fluctuations inside the pump while maintaining nearly the same performance. The selection of proper radial gap for a given impeller-volute combination results in an appreciable reduction in vibration levels

    Crustal Contamination and Hybridization of an Embryonic Oceanic Crust during the Red Sea Rifting (Tihama Asir Igneous Complex, Saudi Arabia)

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    The Red Sea rift system represents a key case study of the transition from a continental to an oceanic rift. The Red Sea rifting initiated in Late Oligocene to Early Miocene (24-23 Ma) and was accompanied by extensive magmatism throughout the rifted basin, from Afar and Yemen to northern Egypt. Here, we present a petrological and geochemical study of two gabbro bodies and associated basalts from the Tihama Asir igneous complex, which formed at 24-20 Ma within the rifted Arabian-Nubian Shield (ANS). The Tihama Asir is therefore an ideal location to study the initial phase of syn-rift magmatism and its influence on the geodynamic evolution of the Red Sea rift system. The most primitive olivine gabbros present modal, bulk and mineral compositions consistent with formation from Mid-Ocean Ridge Basalt (MORB)-type parental melts, whereas the evolved olivine-free gabbros and oxide-bearing gabbros show saturation of phlogopite and a crystal line of descent diverging from fractional crystallization trends. In detail, whole-rock and mineral compositions in the most evolved lithologies show high Light over Middle Rare Earth Elements (LREE/MREE) ratios (La-N/Sm-N = 0.89-1.31) and selective enrichments in Sr, K and highly incompatible elements (Rb, Ba, U, Th). We relate these geochemical characteristics to a process of progressive assimilation of host continental crust during the emplacement of the gabbroic plutons. Interestingly, high LREE/MREE ratios (La-N/Sm-N = 1.45-4.58) and high Rb, Ba, Th and U contents also characterize the basaltic dike swarms associated to the gabbros. Incompatible trace element compositions of these basalts approach those of the melts that formed the most hybridized gabbros. Therefore, we propose that the dike swarms represent melts partially contaminated by assimilation of continental crust material, extracted from the underlying gabbroic crystal mush. Our results suggest that early syn-rift magmatism led to the partial replacement of the thinned continental crust by MORB-type gabbroic bodies, in turn suggesting that oceanic magmatism started prior to continental break-up. Extensive syn-rift magmatism is consistent with the interpretation of the southern Red Sea rift system as a volcanic rifted margin. One possible implication of this study is that extensive but diffuse syn-rift magmatism possibly hampered continental break-up, leading to a protracted rifting stage

    GT2004-53828 Instrumentation Selection and Uncertainty Analysis for Performance Test of Small Centrifugal Compressors

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    ABSTRACT In the design phase of centrifugal compressors, it is essential to have some experimental results on performance. The extent of usefulness of the experiments depends on quality and accuracy of the results. Part of proper experimental procedure is the correct selection of instrumentation leading to lower uncertainty in the final results. ASME PTC 10 (Performance Test Code on Compressors and Exhausters) requires fluctuation limits on the measured performance parameters. This does not guarantee limits for accuracy of performance parameters. Also, different experimental setup will affect uncertainty of the results, even with similar instrumentation accuracy. The present research deals with uncertainty analysis for performance evaluation of small-scale centrifugal compressor. The instrumentation errors are accommodated in the relation to ASME PTC 19.1 (test uncertainty). The analysis takes into consideration the correlated bias limits. Selection of proper type of instruments for measuring associated parameters is based on literature review. A case study is included as an example to illustrate the selection on instrumentation accuracy and preferred bias correlations. The analysis is a useful tool in designing experiments for testing compressor and optimizing accuracy of results

    A phased SNP-based classification of sickle cell anemia HBB haplotypes

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    Background: Sickle cell anemia causes severe complications and premature death. Five common beta-globin gene cluster haplotypes are each associated with characteristic fetal hemoglobin (HbF) levels. As HbF is the major modulator of disease severity, classifying patients according to haplotype is useful. The first method of haplotype classification used restriction fragment length polymorphisms (RFLPs) to detect single nucleotide polymorphisms (SNPs) in the beta-globin gene cluster. This is labor intensive, and error prone. Methods: We used genome-wide SNP data imputed to the 1000 Genomes reference panel to obtain phased data distinguishing parental alleles. Results: We successfully haplotyped 813 sickle cell anemia patients previously classified by RFLPs with a concordance >98%. Four SNPs (rs3834466, rs28440105, rs10128556, and rs968857) marking four different restriction enzyme sites unequivocally defined most haplotypes. We were able to assign a haplotype to 86% of samples that were either partially or misclassified using RFLPs. Conclusion: Phased data using only four SNPs allowed unequivocal assignment of a haplotype that was not always possible using a larger number of RFLPs. Given the availability of genome-wide SNP data, our method is rapid and does not require high computational resources.NIH Bethesda, MDBoston Univ, Sch Med, Dept Med, 72 E Concord St, Boston, MA 02118 USABoston Univ, Bioinformat Program, Boston, MA 02215 USAKing Saud Univ, Coll Med, Sickle Cell Dis Res Ctr, Riyadh, Saudi ArabiaKing Saud Univ, Coll Med, Dept Pediat, Riyadh, Saudi ArabiaKing Faisal Univ, Al Omran Sci Chair, Al Hasa, Saudi ArabiaImam Abdulrahman bin Faisal Univ, Inst Res & Med Consultat, Dammam, Saudi ArabiaEscola Paulista Med, Hematol & Blood Transfus Div, São Paulo, BrazilBoston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USAEscola Paulista Med, Hematol & Blood Transfus Div, São Paulo, BrazilNIH: R01 HL 068970NIH: RC2 HL 101212NIH: R01 87681NIH: T32 HL007501Web of Scienc

    Elongation, proliferation & migration differentiate endothelial cell phenotypes and determine capillary sprouting

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    <p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of capillaries from preexisting blood vessels, has been extensively studied experimentally over the past thirty years. Molecular insights from these studies have lead to therapies for cancer, macular degeneration and ischemia. In parallel, mathematical models of angiogenesis have helped characterize a broader view of capillary network formation and have suggested new directions for experimental pursuit. We developed a computational model that bridges the gap between these two perspectives, and addresses a remaining question in angiogenic sprouting: how do the processes of endothelial cell elongation, migration and proliferation contribute to vessel formation?</p> <p>Results</p> <p>We present a multiscale systems model that closely simulates the mechanisms underlying sprouting at the onset of angiogenesis. Designed by agent-based programming, the model uses logical rules to guide the behavior of individual endothelial cells and segments of cells. The activation, proliferation, and movement of these cells lead to capillary growth in three dimensions. By this means, a novel capillary network emerges out of combinatorially complex interactions of single cells. Rules and parameter ranges are based on literature data on endothelial cell behavior in vitro. The model is designed generally, and will subsequently be applied to represent species-specific, tissue-specific in vitro and in vivo conditions.</p> <p>Initial results predict tip cell activation, stalk cell development and sprout formation as a function of local vascular endothelial growth factor concentrations and the Delta-like 4 Notch ligand, as it might occur in a three-dimensional in vitro setting. Results demonstrate the differential effects of ligand concentrations, cell movement and proliferation on sprouting and directional persistence.</p> <p>Conclusion</p> <p>This systems biology model offers a paradigm closely related to biological phenomena and highlights previously unexplored interactions of cell elongation, migration and proliferation as a function of ligand concentration, giving insight into key cellular mechanisms driving angiogenesis.</p

    Module-based multiscale simulation of angiogenesis in skeletal muscle

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    <p>Abstract</p> <p>Background</p> <p>Mathematical modeling of angiogenesis has been gaining momentum as a means to shed new light on the biological complexity underlying blood vessel growth. A variety of computational models have been developed, each focusing on different aspects of the angiogenesis process and occurring at different biological scales, ranging from the molecular to the tissue levels. Integration of models at different scales is a challenging and currently unsolved problem.</p> <p>Results</p> <p>We present an object-oriented module-based computational integration strategy to build a multiscale model of angiogenesis that links currently available models. As an example case, we use this approach to integrate modules representing microvascular blood flow, oxygen transport, vascular endothelial growth factor transport and endothelial cell behavior (sensing, migration and proliferation). Modeling methodologies in these modules include algebraic equations, partial differential equations and agent-based models with complex logical rules. We apply this integrated model to simulate exercise-induced angiogenesis in skeletal muscle. The simulation results compare capillary growth patterns between different exercise conditions for a single bout of exercise. Results demonstrate how the computational infrastructure can effectively integrate multiple modules by coordinating their connectivity and data exchange. Model parameterization offers simulation flexibility and a platform for performing sensitivity analysis.</p> <p>Conclusions</p> <p>This systems biology strategy can be applied to larger scale integration of computational models of angiogenesis in skeletal muscle, or other complex processes in other tissues under physiological and pathological conditions.</p

    Effect of nocturnal hypoxemia on glycemic control among diabetic Saudi patients presenting with obstructive sleep apnea

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    BackgroundObstructive sleep apnea (OSA) is a prevalent disease that is associated with an increased incidence of type II diabetes mellitus (DM) if left untreated. We aimed to determine the association between glycosylated hemoglobin (HbA1c) levels and both nocturnal hypoxemia and apnea-hypopnea index (AHI) among a Saudi patients with OSA.MethodsA cross-sectional study that enrolled 103 adult patients diagnosed with DM and confirmed to have OSA by full night attended polysomnography between 2018 and 2021. Those who presented with acute illness, chronic obstructive pulmonary disease (COPD)/restrictive lung diseases causing sleep-related hypoxemia, or no available HbA1c level within 6 months before polysomnography were excluded from the study. Univariate and multivariate linear regression analyses between HbA1c levels and parameters of interest were tested.ResultsSixty-seven (65%) of the studied population had uncontrolled DM (HbA1c ≥7%). In univariate regression analysis, there was a significant positive association between HbA1c, and sleep time spent with an oxygen saturation below 90% (T90), female gender, and body mass index (BMI) (p&lt;0.05) but not AHI, or associated comorbidities (p&gt;0.05). In the multivariate analysis, HbA1c was positively associated with increasing T90 (p&lt;0.05), and ODI (p&lt;0.05), but not with AHI (p&gt;0.05).ConclusionNocturnal hypoxemia could be an important factor affecting glycemic control in patients with OSA suffering from DM irrespective of the severity of both diseases

    Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signaling

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    Lipopolysaccharide (LPS) of Porphyromonas gingivalis exists in at least two known forms, O-LPS and A-LPS. A-LPS shows heterogeneity in which two isoforms designated LPS1435/1449 and LPS1690 appear responsible for tissue specific immune signalingpathways activation and increased virulence. The modification of lipid A to tetra-acylated1435/1449 and/or penta-acylated1690 fatty acids indicates poor growth conditions and bioavailability of hemin. Hemin protects P. gingivalis from serum resistance and the lipid A serves as a site for its binding. The LPS1435/1449 and LPS1690 isoforms can produce opposite effects on the human Toll-like receptors (TLR) TLR 2 and TLR 4 activation. This enabless P. gingivalis to select the conditions for its entry, survival and that of its co-habiting species in the host, orchestrating its virulence to control innate immune pathway activation and biofilm dysbiosis. Thismini review describes a number of effects that LPS1435/1449 and LPS1690 can exert on the host tissues such as deregulation of the innate immune system, subversion of host cell autophagy, regulation of outer membrane vesicle production and adverse effects on pregnancy outcome. The ability to change its LPS1435/1449 and/or LPS1690 composition may enables P. gingivalis to paralyze local pro-inflammatory cytokine production, thereby gaining access to its primary location in periodontal tissue

    Tipping the Balance: Robustness of Tip Cell Selection, Migration and Fusion in Angiogenesis

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    Vascular abnormalities contribute to many diseases such as cancer and diabetic retinopathy. In angiogenesis new blood vessels, headed by a migrating tip cell, sprout from pre-existing vessels in response to signals, e.g., vascular endothelial growth factor (VEGF). Tip cells meet and fuse (anastomosis) to form blood-flow supporting loops. Tip cell selection is achieved by Dll4-Notch mediated lateral inhibition resulting, under normal conditions, in an interleaved arrangement of tip and non-migrating stalk cells. Previously, we showed that the increased VEGF levels found in many diseases can cause the delayed negative feedback of lateral inhibition to produce abnormal oscillations of tip/stalk cell fates. Here we describe the development and implementation of a novel physics-based hierarchical agent model, tightly coupled to in vivo data, to explore the system dynamics as perpetual lateral inhibition combines with tip cell migration and fusion. We explore the tipping point between normal and abnormal sprouting as VEGF increases. A novel filopodia-adhesion driven migration mechanism is presented and validated against in vivo data. Due to the unique feature of ongoing lateral inhibition, ‘stabilised’ tip/stalk cell patterns show sensitivity to the formation of new cell-cell junctions during fusion: we predict cell fates can reverse. The fusing tip cells become inhibited and neighbouring stalk cells flip fate, recursively providing new tip cells. Junction size emerges as a key factor in establishing a stable tip/stalk pattern. Cell-cell junctions elongate as tip cells migrate, which is shown to provide positive feedback to lateral inhibition, causing it to be more susceptible to pathological oscillations. Importantly, down-regulation of the migratory pathway alone is shown to be sufficient to rescue the sprouting system from oscillation and restore stability. Thus we suggest the use of migration inhibitors as therapeutic agents for vascular normalisation in cancer

    Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

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    Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression
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