Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA patients.

PubMed

van de Luijtgaarden, Koen M; Rouwet, Ellen V; Hoeks, Sanne E; Stolker, Robert J; Verhagen, Hence Jm; Majoor-Krakauer, Danielle

2017-04-01

Sex affects the presentation, treatment, and outcomes of abdominal aortic aneurysm (AAA). Although AAAs are less prevalent in women, at least in the general population, women with an AAA have a poorer prognosis in comparison to men. Sex differences in the genetic predisposition for aneurysm disease remain to be established. In this study we investigated the familial risk of AAA for women compared to men. All living AAA patients included in a 2004-2012 prospective database were invited to the multidisciplinary vascular/genetics outpatient clinic between 2009 and 2012 for assessment of family history using detailed questionnaires. AAA risk for male and female relatives was calculated separately and stratified by sex of the AAA patients. Families of 568 AAA patients were investigated and 22.5% of the patients had at least one affected relative. Female relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the estimated sex-specific population risk. Relatives of female AAA patients had a higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022), corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and male relatives, respectively. The risk for aortic aneurysm in relatives of AAA patients is higher than expected from population risk. The excess risk is highest for the female relatives of AAA patients and for the relatives of female AAA patients. These findings endorse targeted AAA family screening for female and male relatives of all AAA patients.

Wall Shear Stress, Wall Pressure and Near Wall Velocity Field Relationships in a Whirling Annular Seal

NASA Technical Reports Server (NTRS)

Morrison, Gerald L.; Winslow, Robert B.; Thames, H. Davis, III

1996-01-01

The mean and phase averaged pressure and wall shear stress distributions were measured on the stator wall of a 50% eccentric annular seal which was whirling in a circular orbit at the same speed as the shaft rotation. The shear stresses were measured using flush mounted hot-film probes. Four different operating conditions were considered consisting of Reynolds numbers of 12,000 and 24,000 and Taylor numbers of 3,300 and 6,600. At each of the operating conditions the axial distribution (from Z/L = -0.2 to 1.2) of the mean pressure, shear stress magnitude, and shear stress direction on the stator wall were measured. Also measured were the phase averaged pressure and shear stress. These data were combined to calculate the force distributions along the seal length. Integration of the force distributions result in the net forces and moments generated by the pressure and shear stresses. The flow field inside the seal operating at a Reynolds number of 24,000 and a Taylor number of 6,600 has been measured using a 3-D laser Doppler anemometer system. Phase averaged wall pressure and wall shear stress are presented along with phase averaged mean velocity and turbulence kinetic energy distributions located 0.16c from the stator wall where c is the seal clearance. The relationships between the velocity, turbulence, wall pressure and wall shear stress are very complex and do not follow simple bulk flow predictions.

Characterization of the modular design of the autolysin/adhesin Aaa from Staphylococcus aureus.

PubMed

Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

2012-01-01

Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for

Research on wall shear stress considering wall roughness when shear swirling flow vibration cementing

NASA Astrophysics Data System (ADS)

Cui, Zhihua; Ai, Chi; Feng, Fuping

2017-01-01

When shear swirling flow vibration cementing, the casing is revolving periodically and eccentrically, which leads to the annulus fluid in turbulent swirling flow state. The wall shear stress is more than that in laminar flow field when conventional cementing. The paper mainly studied the wall shear stress distribution on the borehole wall when shear swirling flow vibration cementing based on the finite volume method. At the same time, the wall roughness affected and changed the turbulent flow near the borehole wall and the wall shear stress. Based on the wall function method, the paper established boundary conditions considering the wall roughness and derived the formula of the wall shear stress. The results showed that the wall roughness significantly increases the wall shear stress. However, the larger the wall roughness, the greater the thickness of mud cake, which weakening the cementing strength. Considering the effects in a comprehensive way, it is discovered that the particle size of solid phase in drilling fluid is about 0.1 mm to get better cementing quality.

On investigating wall shear stress in two-dimensional plane turbulent wall jets

NASA Astrophysics Data System (ADS)

Mehdi, Faraz; Johansson, Gunnar; White, Christopher; Naughton, Jonathan

2012-11-01

Mehdi & White [Exp Fluids 50:43-51(2011)] presented a full momentum integral based method for determining wall shear stress in zero pressure gradient turbulent boundary layers. They utilized the boundary conditions at the wall and at the outer edge of the boundary layer. A more generalized expression is presented here that uses just one boundary condition at the wall. The method is mathematically exact and has an advantage of having no explicit streamwise gradient terms. It is successfully applied to two different experimental plane turbulent wall jet datasets for which independent estimates of wall shear stress were known. Complications owing to experimental inaccuracies in determining wall shear stress from the proposed method are also discussed.

Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis

PubMed Central

Elsholz, Alexander K. W.; Birk, Marlene S.; Charpentier, Emmanuelle; Turgay, Kürşad

2017-01-01

Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis. We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics. PMID:28748186

Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis.

PubMed

Elsholz, Alexander K W; Birk, Marlene S; Charpentier, Emmanuelle; Turgay, Kürşad

2017-01-01

Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis . We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics.

Characterization of the Modular Design of the Autolysin/Adhesin Aaa from Staphylococcus Aureus

PubMed Central

Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

2012-01-01

Background Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Methodology/Principal Findings Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. Conclusions/Significance We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus

Cell Wall Metabolism in Response to Abiotic Stress

PubMed Central

Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

2015-01-01

This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2

PubMed Central

Izumi, Natsuko; Yamashita, Akio; Ohno, Shigeo

2012-01-01

Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (AAA+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative “PIKK regulatory chaperone complex” including other PIKK regulators, Hsp90 and the Tel2 complex. PMID:22540023

AAA Foundation for Traffic Safety

MedlinePlus

... of Top Deadly Mistakes Made by Teen Drivers -- AAA AAA: Road debris causes avoidable crashes, deaths Save the ... and 500 deaths! Foundation News Stay Tuned New AAA Foundation for Traffic Safety website coming Fall 2017 ...

AAA-ATPases in Protein Degradation

PubMed Central

Yedidi, Ravikiran S.; Wendler, Petra; Enenkel, Cordula

2017-01-01

Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea. PMID:28676851

AAA-ATPases in Protein Degradation.

PubMed

Yedidi, Ravikiran S; Wendler, Petra; Enenkel, Cordula

2017-01-01

Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea.

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration.

PubMed

Qi, Y; Liu, H; Daniels, M P; Zhang, G; Xu, H

2016-02-01

Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L(del)). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L(del) flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L(del) flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency.

Histopathological analysis of cellular localization of cathepsins in abdominal aortic aneurysm wall.

PubMed

Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Zimmermann, Alexander; Ockert, Stefan; Eckstein, Hans-Henning; Pelisek, Jaroslav

2012-08-01

An important feature of abdominal aortic aneurysm (AAA) is the destruction of vessel wall, especially elastin and collagen. Besides matrix metalloproteinases, cathepsins are the most potent elastolytic enzymes. The expression of cathepsins with known elastolytic and collagenolytic activities in the individual cells within AAA has not yet been determined. The vessel wall of 32 AAA patients and 10 organ donors was analysed by immunohistochemistry for expression of cathepsins B, D, K, L and S, and cystatin C in all cells localized within AAA. Luminal endothelial cells (ECs) of AAA were positive for cathepsin D and partially for cathepsins B, K and S. Endothelial cells of the neovessels and smooth muscle cells in the media were positive for all cathepsins tested, especially for cathepsin B. In the inflammatory infiltrate all cathepsins were expressed in the following pattern: B > D = S > K = L. Macrophages showed the highest staining intensity for all cathepsins. Furthermore, weak overall expression of cystatin C was observed in all the cells localized in the AAA with the exception of the ECs. There is markedly increased expression of the various cathepsins within the AAA wall compared to healthy aorta. Our data are broadly consistent with a role for cathepsins in AAA; and demonstrate expression of cathepsins D, B and S in phagocytic cells in the inflammatory infiltrate; and also may reveal a role for cathepsin B in lymphocytes. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

LMIP/AAA: Local Authentication, Authorization and Accounting (AAA) Protocol for Mobile IP

NASA Astrophysics Data System (ADS)

Chenait, Manel

Mobile IP represents a simple and scalable global mobility solution. However, it inhibits various vulnerabilities to malicious attacks and, therefore, requires the integration of appropriate security services. In this paper, we discuss two authentication schemes suggested for Mobile IP: standard authentication and Mobile IP/AAA authentication. In order to provide Mobile IP roaming services including identity verication, we propose an improvement to Mobile/AAA authentication scheme by applying a local politic key management in each domain, hence we reduce hando latency by avoiding the involvement of AAA infrastructure during mobile node roaming.

On the effect of computed tomography resolution to distinguish between abdominal aortic aneurysm wall tissue and calcification: A proof of concept.

PubMed

Barrett, H E; Cunnane, E M; O Brien, J M; Moloney, M A; Kavanagh, E G; Walsh, M T

2017-10-01

The purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. Ruptured and non-ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross-section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5-155μm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5μm) and multi-detector CT resolution (744μm) was also made. Electron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200μm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155μm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155μm is correct within 8.8%±1.86 and 26.13%±9.40 respectively with sensitivity of 87.17% when compared to the reference. The inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Engineering Silicone Rubbers for In vitro Studies: Creating AAA Models and ILT Analogues with Physiological Properties

PubMed Central

Corbett, T.J.; Doyle, B.J.; Callanan, A.; Walsh, M.T.; McGloughlin, T.M

2010-01-01

Background In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogues are used to mimic the AAA in vivo. While the models used may be physiological, their properties are frequently either not reported or investigated. Method of Approach This study is concerned with the testing and characterisation of previously used vessel analogue materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection moulding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (β) and compliance) the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared to published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure – diameter change behaviour of the models could be predicted numerically. ILT analogues were also manufactured and characterised. Ideal models were manufactured with ILT analogue internal to the aneurysm region and the effect of the ILT analogue on the model compliance and stiffness was investigated. Results The wall materials had similar properties to aortic tissue at physiological pressures (Einit 2.22MPa and 1.57MPa (aortic tissue: 1.8MPa)). ILT analogues had similar Young’s modulus to the medial layer of ILT (0.24 and 0.33MPa (ILT: 0.28MPa)). All models had aneurysm sac compliance in the physiological range (2.62 – 8.01×10-4/mmHg (AAA in vivo: 1.8 – 9.4×10-4/mmHg)). The necks of our AAA models had similar stiffness to healthy aortas (20.44 – 29.83 (healthy aortas in vivo: 17.5±5.5)). Good agreement was seen between the diameter changes due to pressurisation in the experimental and FEA wall models with a maximum error of 7.3% at 120mmHg. It was also determined that the inclusion of ILT analogue

Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic Stress Resistance.

PubMed

Ene, Iuliana V; Walker, Louise A; Schiavone, Marion; Lee, Keunsook K; Martin-Yken, Hélène; Dague, Etienne; Gow, Neil A R; Munro, Carol A; Brown, Alistair J P

2015-07-28

The fungal cell wall confers cell morphology and protection against environmental insults. For fungal pathogens, the cell wall is a key immunological modulator and an ideal therapeutic target. Yeast cell walls possess an inner matrix of interlinked β-glucan and chitin that is thought to provide tensile strength and rigidity. Yeast cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and cell integrity (Mkc1, Cek1) signaling pathways. These mitogen-activated protein kinase (MAPK) pathways modulate cell wall gene expression, leading to the construction of a new, modified cell wall. We show that the cell wall is not rigid but elastic, displaying rapid structural realignments that impact survival following osmotic shock. Lactate-grown Candida albicans cells are more resistant to hyperosmotic shock than glucose-grown cells. We show that this elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most cell death occurs within 10 min of osmotic shock. Sudden decreases in cell volume drive rapid increases in cell wall thickness. The elevated stress resistance of lactate-grown cells correlates with reduced cell wall elasticity, reflected in slower changes in cell volume following hyperosmotic shock. The cell wall elasticity of lactate-grown cells is increased by a triple mutation that inactivates the Crh family of cell wall cross-linking enzymes, leading to increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in glucose-grown cells reduces cell wall elasticity, providing partial protection against hyperosmotic shock. These changes correlate with structural realignment of the cell wall and with the ability of cells to withstand osmotic shock. The C. albicans cell wall is the first line of defense against external insults, the site of immune recognition by the host, and an attractive target for antifungal therapy. Its tensile strength is conferred by

Wall shear stress in intracranial aneurysms and adjacent arteries☆

PubMed Central

Wang, Fuyu; Xu, Bainan; Sun, Zhenghui; Wu, Chen; Zhang, Xiaojun

2013-01-01

Hemodynamic parameters play an important role in aneurysm formation and growth. However, it is difficult to directly observe a rapidly growing de novo aneurysm in a patient. To investigate possible associations between hemodynamic parameters and the formation and growth of intracranial aneurysms, the present study constructed a computational model of a case with an internal carotid artery aneurysm and an anterior communicating artery aneurysm, based on the CT angiography findings of a patient. To simulate the formation of the anterior communicating artery aneurysm and the growth of the internal carotid artery aneurysm, we then constructed a model that virtually removed the anterior communicating artery aneurysm, and a further two models that also progressively decreased the size of the internal carotid artery aneurysm. Computational simulations of the fluid dynamics of the four models were performed under pulsatile flow conditions, and wall shear stress was compared among the different models. In the three aneurysm growth models, increasing size of the aneurysm was associated with an increased area of low wall shear stress, a significant decrease in wall shear stress at the dome of the aneurysm, and a significant change in the wall shear stress of the parent artery. The wall shear stress of the anterior communicating artery remained low, and was significantly lower than the wall shear stress at the bifurcation of the internal carotid artery or the bifurcation of the middle cerebral artery. After formation of the anterior communicating artery aneurysm, the wall shear stress at the dome of the internal carotid artery aneurysm increased significantly, and the wall shear stress in the upstream arteries also changed significantly. These findings indicate that low wall shear stress may be associated with the initiation and growth of aneurysms, and that aneurysm formation and growth may influence hemodynamic parameters in the local and adjacent arteries. PMID:25206394

A film-based wall shear stress sensor for wall-bounded turbulent flows

NASA Astrophysics Data System (ADS)

Amili, Omid; Soria, Julio

2011-07-01

In wall-bounded turbulent flows, determination of wall shear stress is an important task. The main objective of the present work is to develop a sensor which is capable of measuring surface shear stress over an extended region applicable to wall-bounded turbulent flows. This sensor, as a direct method for measuring wall shear stress, consists of mounting a thin flexible film on the solid surface. The sensor is made of a homogeneous, isotropic, and incompressible material. The geometry and mechanical properties of the film are measured, and particles with the nominal size of 11 μm in diameter are embedded on the film's surface to act as markers. An optical technique is used to measure the film deformation caused by the flow. The film has typically deflection of less than 2% of the material thickness under maximum loading. The sensor sensitivity can be adjusted by changing the thickness of the layer or the shear modulus of the film's material. The paper reports the sensor fabrication, static and dynamic calibration procedure, and its application to a fully developed turbulent channel flow at Reynolds numbers in the range of 90,000-130,000 based on the bulk velocity and channel full height. The results are compared to alternative wall shear stress measurement methods.

KRE5 Suppression Induces Cell Wall Stress and Alternative ER Stress Response Required for Maintaining Cell Wall Integrity in Candida glabrata

PubMed Central

Sasaki, Masato; Ito, Fumie; Aoyama, Toshio; Sato-Okamoto, Michiyo; Takahashi-Nakaguchi, Azusa; Chibana, Hiroji; Shibata, Nobuyuki

2016-01-01

The maintenance of cell wall integrity in fungi is required for normal cell growth, division, hyphae formation, and antifungal tolerance. We observed that endoplasmic reticulum stress regulated cell wall integrity in Candida glabrata, which possesses uniquely evolved mechanisms for unfolded protein response mechanisms. Tetracycline-mediated suppression of KRE5, which encodes a predicted UDP-glucose:glycoprotein glucosyltransferase localized in the endoplasmic reticulum, significantly increased cell wall chitin content and decreased cell wall β-1,6-glucan content. KRE5 repression induced endoplasmic reticulum stress-related gene expression and MAP kinase pathway activation, including Slt2p and Hog1p phosphorylation, through the cell wall integrity signaling pathway. Moreover, the calcineurin pathway negatively regulated cell wall integrity, but not the reduction of β-1,6-glucan content. These results indicate that KRE5 is required for maintaining both endoplasmic reticulum homeostasis and cell wall integrity, and that the calcineurin pathway acts as a regulator of chitin-glucan balance in the cell wall and as an alternative mediator of endoplasmic reticulum stress in C. glabrata. PMID:27548283

Determination of wall shear stress from mean velocity and Reynolds shear stress profiles

NASA Astrophysics Data System (ADS)

Volino, Ralph J.; Schultz, Michael P.

2018-03-01

An analytical method is presented for determining the Reynolds shear stress profile in steady, two-dimensional wall-bounded flows using the mean streamwise velocity. The method is then utilized with experimental data to determine the local wall shear stress. The procedure is applicable to flows on smooth and rough surfaces with arbitrary pressure gradients. It is based on the streamwise component of the boundary layer momentum equation, which is transformed into inner coordinates. The method requires velocity profiles from at least two streamwise locations, but the formulation of the momentum equation reduces the dependence on streamwise gradients. The method is verified through application to laminar flow solutions and turbulent DNS results from both zero and nonzero pressure gradient boundary layers. With strong favorable pressure gradients, the method is shown to be accurate for finding the wall shear stress in cases where the Clauser fit technique loses accuracy. The method is then applied to experimental data from the literature from zero pressure gradient studies on smooth and rough walls, and favorable and adverse pressure gradient cases on smooth walls. Data from very near the wall are not required for determination of the wall shear stress. Wall friction velocities obtained using the present method agree with those determined in the original studies, typically to within 2%.

NASA Airborne Astronomy Ambassadors (AAA)

NASA Astrophysics Data System (ADS)

Backman, D. E.; Harman, P. K.; Clark, C.

2016-12-01

NASA's Airborne Astronomy Ambassadors (AAA) is a three-part professional development (PD) program for high school physics and astronomy teachers. The AAA experience consists of: (1) blended-learning professional development composed of webinars, asynchronous content learning, and a series of hands-on workshops (2) a STEM immersion experience at NASA Armstrong Flight Research Center's B703 science research aircraft facility in Palmdale, California, and (3) ongoing participation in the AAA community of practice (CoP) connecting participants with astrophysics and planetary science Subject Matter Experts (SMEs). The SETI Institute (SI) is partnering with school districts in Santa Clara and Los Angeles Counties during the AAA program's "incubation" period, calendar years 2016 through 2018. AAAs will be selected by the school districts based on criteria developed during spring 2016 focus group meetings led by the program's external evaluator, WestEd.. Teachers with 3+ years teaching experience who are assigned to teach at least 2 sections in any combination of the high school courses Physics (non-AP), Physics of the Universe (California integrated model), Astronomy, or Earth & Space Sciences are eligible. Partner districts will select at least 48 eligible applicants with SI oversight. WestEd will randomly assign selected AAAs to group A or group B. Group A will complete PD in January - June of 2017 and then participate in SOFIA science flights during fall 2017 (SOFIA Cycle 5). Group B will act as a control during the 2017-18 school year. Group B will then complete PD in January - June of 2018 and participate in SOFIA science flights in fall 2018 (Cycle 6). Under the current plan, opportunities for additional districts to seek AAA partnerships with SI will be offered in 2018 or 2019. A nominal two-week AAA curriculum component will be developed by SI for classroom delivery that will be aligned with selected California Draft Science Framework Disciplinary Core Ideas

AAA+ Machines of Protein Destruction in Mycobacteria.

PubMed

Alhuwaider, Adnan Ali H; Dougan, David A

2017-01-01

The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or proteostasis) is vital for cell survival during normal and stressful conditions. The two key aspects of protein homeostasis are, (i) the correct folding and assembly of proteins (coupled with their delivery to the correct cellular location) and (ii) the timely removal of unwanted or damaged proteins from the cell, which are performed by molecular chaperones and proteases, respectively. A major class of proteins that contribute to both of these tasks are the AAA+ (ATPases associated with a variety of cellular activities) protein superfamily. Although much is known about the structure of these machines and how they function in the model Gram-negative bacterium Escherichia coli , we are only just beginning to discover the molecular details of these machines and how they function in mycobacteria. Here we review the different AAA+ machines, that contribute to proteostasis in mycobacteria. Primarily we will focus on the recent advances in the structure and function of AAA+ proteases, the substrates they recognize and the cellular pathways they control. Finally, we will discuss the recent developments related to these machines as novel drug targets.

Multifunctional Mitochondrial AAA Proteases

PubMed Central

Glynn, Steven E.

2017-01-01

Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle. PMID:28589125

Multifunctional Mitochondrial AAA Proteases.

PubMed

Glynn, Steven E

2017-01-01

Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

Triglyceride glucose index and common carotid wall shear stress.

PubMed

Tripolino, Cesare; Irace, Concetta; Scavelli, Faustina B; de Franceschi, Maria S; Esposito, Teresa; Carallo, Claudio; Gnasso, Agostino

2014-02-01

Alterations in wall shear stress contribute to both clinical and subclinical atherosclerosis. Several conditions such as hypertension, diabetes, and obesity can impair shear stress, but the role of insulin resistance has never been investigated. The present study was designed to investigate whether insulin resistance assessed by TyG Index associates with wall shear stress in the common carotid artery. One hundred six individuals were enrolled. Blood pressure, lipids, glucose, and cigarette smoking were evaluated. TyG Index was calculated as log[fasting triglycerides × fasting glucose / 2]. Subjects underwent blood viscosity measurement and echo-Doppler evaluation of carotid arteries to calculate wall shear stress. The association between TyG Index and carotid wall shear stress was assessed by simple and multiple regression analyses. TyG Index was significantly and inversely associated with carotid wall shear stress both in simple (r = -0.44, P < 0.001) and multiple regression analyses accounting for age, sex, and major cardiovascular risk factors. The association was further confirmed after exclusion of subjects with diabetes, dyslipidemia, fasting blood glucose greater than 100 mg/dL, and triglycerides greater than 150 mg/dL. The present findings suggest that increasing insulin resistance, as assessed by TyG Index, associates with atherosclerosis-prone shear stress reduction in the common carotid artery.

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine.

PubMed

Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

2015-09-01

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA-spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA-spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients.

Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

PubMed

Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

2015-08-01

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

Turbulence significantly increases pressure and fluid shear stress in an aortic aneurysm model under resting and exercise flow conditions.

PubMed

Khanafer, Khalil M; Bull, Joseph L; Upchurch, Gilbert R; Berguer, Ramon

2007-01-01

The numerical models of abdominal aortic aneurysm (AAA) in use do not take into account the non-Newtonian behavior of blood and the development of local turbulence. This study examines the influence of pulsatile, turbulent, non-Newtonian flow on fluid shear stresses and pressure changes under rest and exercise conditions. We numerically analyzed pulsatile turbulent flow, using simulated physiological rest and exercise waveforms, in axisymmetric-rigid aortic aneurysm models (AAMs). Discretization of governing equations was achieved using a finite element scheme. Maximum turbulence-induced shear stress was found at the distal end of an AAM. In large AAMs (dilated to undilated diameter ratio = 3.33) at peak systolic flow velocity, fluid shear stress during exercise is 70.4% higher than at rest. Our study provides a numerical, noninvasive method for obtaining detailed data on the forces generated by pulsatile turbulent flow in AAAs that are difficult to study in humans and in physical models. Our data suggest that increased flow turbulence results in increased shear stress in aneurysms. While pressure readings are fairly uniform along the length of an aneurysm, the kinetic energy generated by turbulence impacting on the wall of the distal half of the aneurysm increases fluid and wall shear stress at this site. If the increased fluid shear stress results in further dilation and hence further turbulence, wall stress may be a mechanism for aneurysmal growth and eventual rupture.

Log-layer mismatch and modeling of the fluctuating wall stress in wall-modeled large-eddy simulations

NASA Astrophysics Data System (ADS)

Yang, Xiang I. A.; Park, George Ilhwan; Moin, Parviz

2017-10-01

Log-layer mismatch refers to a chronic problem found in wall-modeled large-eddy simulation (WMLES) or detached-eddy simulation, where the modeled wall-shear stress deviates from the true one by approximately 15 % . Many efforts have been made to resolve this mismatch. The often-used fixes, which are generally ad hoc, include modifying subgrid-scale stress models, adding a stochastic forcing, and moving the LES-wall-model matching location away from the wall. An analysis motivated by the integral wall-model formalism suggests that log-layer mismatch is resolved by the built-in physics-based temporal filtering. In this work we investigate in detail the effects of local filtering on log-layer mismatch. We show that both local temporal filtering and local wall-parallel filtering resolve log-layer mismatch without moving the LES-wall-model matching location away from the wall. Additionally, we look into the momentum balance in the near-wall region to provide an alternative explanation of how LLM occurs, which does not necessarily rely on the numerical-error argument. While filtering resolves log-layer mismatch, the quality of the wall-shear stress fluctuations predicted by WMLES does not improve with our remedy. The wall-shear stress fluctuations are highly underpredicted due to the implied use of LES filtering. However, good agreement can be found when the WMLES data are compared to the direct numerical simulation data filtered at the corresponding WMLES resolutions.

Wall shear stress estimates in coronary artery constrictions

NASA Technical Reports Server (NTRS)

Back, L. H.; Crawford, D. W.

1992-01-01

Wall shear stress estimates from laminar boundary layer theory were found to agree fairly well with the magnitude of shear stress levels along coronary artery constrictions obtained from solutions of the Navier Stokes equations for both steady and pulsatile flow. The relatively simple method can be used for in vivo estimates of wall shear stress in constrictions by using a vessel shape function determined from a coronary angiogram, along with a knowledge of the flow rate.

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine

PubMed Central

Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

2015-01-01

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA–spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA–spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients. PMID:26158885

Pathophysiology of AAA: heredity vs environment.

PubMed

Björck, Martin; Wanhainen, Anders

2013-01-01

Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of food intake on left ventricular wall stress.

PubMed

Gårdinger, Ylva; Hlebowicz, Joanna; Björgell, Ola; Dencker, Magnus

2014-01-28

Left ventricular wall stress has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether left ventricular wall stress is affected by food intake in healthy subjects. Twenty-three healthy subjects aged 25.6 ± 4.5 years were investigated. Meridional end-systolic wall stress (ESS) and circumferential end-systolic wall stress (cESS) were measured before, 30 minutes after, and 110 minutes after a standardised meal. Both ESS and cESS decreased significantly (P < 0.001) from fasting values 30 minutes after the meal, and had not returned to baseline after 110 minutes. ESS decreased from 65 ± 16 kdynes/cm2 (fasting) to 44 ± 12 kdynes/cm2 30 minutes after, and to 58 ± 13 kdynes/cm2 110 minutes after eating. cESS decreased from 98 ± 24 kdynes/cm2 to 67 ± 18 kdynes/cm2 30 minutes after, and to 87 ± 19 kdynes/cm2 110 minutes after the meal. This study shows that left ventricular wall stress is affected by food intake in healthy subjects.

Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.

PubMed

Frisk, Michael; Ruud, Marianne; Espe, Emil K S; Aronsen, Jan Magnus; Røe, Åsmund T; Zhang, Lili; Norseng, Per Andreas; Sejersted, Ole M; Christensen, Geir A; Sjaastad, Ivar; Louch, William E

2016-10-01

Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation-contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca(2+) release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function. MRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca(2+) release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss. Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca(2+) release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Locally applied leptin induces regional aortic wall degeneration preceding aneurysm formation in apolipoprotein E-deficient mice.

PubMed

Tao, Ming; Yu, Peng; Nguyen, Binh T; Mizrahi, Boaz; Savion, Naphtali; Kolodgie, Frank D; Virmani, Renu; Hao, Shuai; Ozaki, C Keith; Schneiderman, Jacob

2013-02-01

Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aortic aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process. Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor, as well as mRNA for matrix metalloproteinases (MMP)-9 and MMP-12. Leptin and leptin receptor antigen were evident in all AAAs, and leptin, MMP-9, and MMP-12 mRNA was increased relative to age-matched nondilated controls. To simulate in vivo local leptin synthesis, ApoE(-/-) mice were subjected to a paravisceral periaortic application of low-dose leptin. Leptin-treated aortas exhibited decreased transforming growth factor-β and increased MMP-9 mRNA levels 5 days after surgery, and leptin receptor mRNA was upregulated by day 28. Serial ultrasonography demonstrated accelerated regional aortic diameter growth after 28 days, correlating with local medial degeneration, increased MMP-9, MMP-12, and periadventitial macrophage clustering. Furthermore, the combination of local periaortic leptin and systemic angiotensin II administration augmented medial MMP-9 synthesis and aortic aneurysm size. Leptin is locally synthesized in human AAA wall. Paravisceral aortic leptin in ApoE(-/-) mice induces local medial degeneration and augments angiotensin II-induced AAA, thus suggesting novel mechanistic links between leptin and AAA formation.

Locally Applied Leptin Induces Regional Aortic Wall Degeneration Preceding Aneurysm Formation in ApoE Deficient Mice

PubMed Central

Tao, Ming; Yu, Peng; Nguyen, Binh T.; Mizrahi, Boaz; Savion, Naphtali; Kolodgie, Frank D.; Virmani, Renu; Hao, Shuai; Ozaki, C. Keith; Schneiderman, Jacob

2013-01-01

Objective Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aorta aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process. Methods and Results Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor (ObR), as well as mRNA for matrix metalloproteinases (MMP)-9, and MMP-12. Leptin and ObR antigen were evident in all AAAs, and, leptin, MMP-9, and MMP-12 mRNA was increased relative to age-matched non-dilated controls. To simulate in vivo local leptin synthesis, ApoE-/- mice were subjected to a para-visceral peri-aortic application of low-dose leptin. Leptin-treated aortas exhibited decreased TGFβ and increased MMP-9 mRNA levels 5 days after surgery, and ObR mRNA was up-regulated by day 28. Serial ultrasonography demonstrated accelerated regional aortic diameter growth after 28 days, correlating with local medial degeneration, increased MMP-9, MMP-12 and peri-adventitial macrophage clustering. Furthermore, the combination of local peri-aortic leptin and systemic angiotensin II administration augmented medial MMP-9 synthesis and aortic aneurysm size. Conclusions Leptin is locally synthesized in human AAA wall. Para-visceral aortic leptin in ApoE-/- mice induces local medial degeneration, and augments angiotensin II-induced AAA, thus suggesting novel mechanistic links between leptin and AAA formation. PMID:23220275

Time-varying wall stress: an index of ventricular vascular coupling.

PubMed

Dell'Italia, L J; Blackwell, G G; Thorn, B T; Pearce, D J; Bishop, S P; Pohost, G M

1992-08-01

Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/- 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic Stress Resistance

PubMed Central

Ene, Iuliana V.; Walker, Louise A.; Schiavone, Marion; Lee, Keunsook K.; Martin-Yken, Hélène; Dague, Etienne; Gow, Neil A. R.; Munro, Carol A.

2015-01-01

ABSTRACT The fungal cell wall confers cell morphology and protection against environmental insults. For fungal pathogens, the cell wall is a key immunological modulator and an ideal therapeutic target. Yeast cell walls possess an inner matrix of interlinked β-glucan and chitin that is thought to provide tensile strength and rigidity. Yeast cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and cell integrity (Mkc1, Cek1) signaling pathways. These mitogen-activated protein kinase (MAPK) pathways modulate cell wall gene expression, leading to the construction of a new, modified cell wall. We show that the cell wall is not rigid but elastic, displaying rapid structural realignments that impact survival following osmotic shock. Lactate-grown Candida albicans cells are more resistant to hyperosmotic shock than glucose-grown cells. We show that this elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most cell death occurs within 10 min of osmotic shock. Sudden decreases in cell volume drive rapid increases in cell wall thickness. The elevated stress resistance of lactate-grown cells correlates with reduced cell wall elasticity, reflected in slower changes in cell volume following hyperosmotic shock. The cell wall elasticity of lactate-grown cells is increased by a triple mutation that inactivates the Crh family of cell wall cross-linking enzymes, leading to increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in glucose-grown cells reduces cell wall elasticity, providing partial protection against hyperosmotic shock. These changes correlate with structural realignment of the cell wall and with the ability of cells to withstand osmotic shock. PMID:26220968

Endothelial MMP-9 drives the inflammatory response in abdominal aortic aneurysm (AAA).

PubMed

Ramella, Martina; Boccafoschi, Francesca; Bellofatto, Kevin; Md, Antonia Follenzi; Fusaro, Luca; Boldorini, Renzo; Casella, Francesco; Porta, Carla; Settembrini, Piergiorgio; Cannas, Mario

2017-01-01

Progression of abdominal aortic aneurysm (AAA) is typified by chronic inflammation and extracellular matrix (ECM) degradation of the aortic wall. Vascular inflammation involves complex interactions among inflammatory cells, endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and ECM. Although vascular endothelium and medial neoangiogenesis play a key role in AAA, the molecular mechanisms underlying their involvement are only partially understood. In AAA biopsies, we found increased MMP-9, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which correlated with massive medial neo-angiogenesis (C4d positive staining). In this study, we developed an in vitro model in order to characterize the role of endothelial matrix metalloproteinase-9 (e-MMP-9) as a potential trigger of medial disruption and in the inflammatory response bridging between ECs and vSMC. Lentiviral-mediated silencing of e-MMP-9 through RNA interference inhibited TNF-alpha-mediated activation of NF-κB in EA.hy926 human endothelial cells. In addition, EA.hy926 cells void of MMP-9 failed to migrate in a 3D matrix. Moreover, silenced EA.hy926 affected vSMC behavior in terms of matrix remodeling. In fact, also MMP-9 in vSMC resulted inhibited when endothelial MMP-9 was suppressed.

Genetic analysis of abdominal aortic aneurysms (AAA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

St. Jean, P.L.; Hart, B.K.; Zhang, X.C.

1994-09-01

The association between AAA and gender, smoking (SM), hypertension (HTN) and inguinal herniation (IH) was examined in 141 AAA probands and 139 of their 1st degree relatives with aortic exam (36 affected, 103 unaffected). There was no significant difference between age at diagnosis of affecteds and age at exam of unaffecteds. Of 181 males, 142 had AAA; of 99 females, 35 had AAA. Using log-linear modeling AAA was significantly associated at the 5% level with gender, SM and HTN but not IH. The association of AAA with SM and HTN held when males and females were analyzed separately. HTN wasmore » -1.5 times more common in both affected males and females, while SM was 1.5 and 2 times more common in affected males and females, respectively. Tests of association and linkage analyses were performed with relevant candidate genes: 3 COL3A1 polymorphisms (C/T, ALA/THR, AvaII), 2 ELN polymorphisms (SER/GLY, (CA)n), FBN1(TAAA)n, 2 APOB polymorphisms (Xbal,Ins/Del), CLB4B (CA)n, PI and markers D1S243 (CA)n, HPR (CA)n and MFD23(CA)n. The loci were genotyped in > 100 AAA probands and > 95 normal controls. No statistically significant evidence of association at the 5% level was obtained for any of the loci using chi-square test of association. 28 families with 2 or more affecteds were analyzed using the affected pedigree member method (APM) and lod-score analyses. There was no evidence for linkage with any loci using APM. Lod-score analysis under an autosomal recessive model resulted in excluding linkage (lod score < -2) of all loci to AAA at {theta}=0.0. Under an autosomal dominant model, linkage was excluded at {theta}=0.0 to ELN, APOB, CLG4B, D1S243, HPR and MFD23. The various genes previously proposed in AAA pathogenesis are neither associated nor casually related in our study population.« less

Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue.

PubMed

O'Leary, Siobhan A; Mulvihill, John J; Barrett, Hilary E; Kavanagh, Eamon G; Walsh, Michael T; McGloughlin, Tim M; Doyle, Barry J

2015-02-01

Varying degrees of calcification are present in most abdominal aortic aneurysms (AAAs). However, their impact on AAA failure properties and AAA rupture risk is unclear. The aim of this work is evaluate and compare the failure properties of partially calcified and predominantly fibrous AAA tissue and investigate the potential reasons for failure. Uniaxial mechanical testing was performed on AAA samples harvested from 31 patients undergoing open surgical repair. Individual tensile samples were divided into two groups: fibrous (n=31) and partially calcified (n=38). The presence of calcification was confirmed by fourier transform infrared spectroscopy (FTIR). A total of 69 mechanical tests were performed and the failure stretch (λf), failure stress (σf) and failure tension (Tf) were recorded for each test. Following mechanical testing, the failure sites of a subset of both tissue types were examined using scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) to investigate the potential reasons for failure. It has been shown that the failure properties of partially calcified tissue are significantly reduced compared to fibrous tissue and SEM and EDS results suggest that the junction between a calcification deposit and the fibrous matrix is highly susceptible to failure. This study implicates the presence of calcification as a key player in AAA rupture risk and provides further motivation for the development of non-invasive methods of measuring calcification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural Elements Regulating AAA+ Protein Quality Control Machines.

PubMed

Chang, Chiung-Wen; Lee, Sukyeong; Tsai, Francis T F

2017-01-01

Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines.

Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm.

PubMed

Crawford, Jeffrey D; Chivukula, Venkat Keshav; Haller, Stephen; Vatankhah, Nasibeh; Bohannan, Colin J; Moneta, Gregory L; Rugonyi, Sandra; Azarbal, Amir F

2016-12-01

Current threshold recommendations for elective abdominal aortic aneurysm (AAA) repair are based solely on maximal AAA diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than AAA diameter of AAA rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict AAA rupture risk. Patients treated at our institution from 2001 to 2014 for ruptured AAA (rAAA) were retrospectively identified and grouped into patients with small rAAA (maximum diameter <6 cm) or large rAAA (>6 cm). Patients with large (>6 cm) non-rAAA were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. We identified 61 patients with rAAA, of which 15 ruptured with AAA diameter <60 mm (small rAAA group). Patients with small rAAAs were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-rAAA group. Patients with small rAAAs were also more likely to have AOO compared with non-rAAAs >60 mm (27% vs 8%; P = .047). Among all patients with rAAAs, those with AOO ruptured at smaller mean AAA diameters than in patients without AOO (62.1 ± 11.8 mm vs 72.5 ± 16.4 mm; P = .024). PWS calculations of a representative small rAAA and a large non-rAAA showed a substantial increase in PWS with AOO. We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at

Adventitial adipogenic degeneration is an unidentified contributor to aortic wall weakening in the abdominal aortic aneurysm.

PubMed

Doderer, Stefan A; Gäbel, Gabor; Kokje, Vivianne B C; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-06-01

The processes driving human abdominal aortic aneurysm (AAA) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in AAA progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and AAAs; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in AAA-related wall debilitation. A better understanding of the pathophysiologic processes driving AAA growth can contribute to pharmaceutical treatments in the future. Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture. Histologic evaluation of AAAs, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (AAA), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of AAAs (P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in AAA tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of AAA adventitial mesenchymal cells (P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured AAA (P < .0003) supports an association between the extent of fatty degeneration and rupture. This

Thinner regions of intracranial aneurysm wall correlate with regions of higher wall shear stress: a 7.0 tesla MRI

PubMed Central

Blankena, Roos; Kleinloog, Rachel; Verweij, Bon H.; van Ooij, Pim; ten Haken, Bennie; Luijten, Peter R.; Rinkel, Gabriel J.E.; Zwanenburg, Jaco J.M.

2016-01-01

Purpose To develop a method for semi-quantitative wall thickness assessment on in vivo 7.0 tesla (7T) MRI images of intracranial aneurysms for studying the relation between apparent aneurysm wall thickness and wall shear stress. Materials and Methods Wall thickness was analyzed in 11 unruptured aneurysms in 9 patients, who underwent 7T MRI with a TSE based vessel wall sequence (0.8 mm isotropic resolution). A custom analysis program determined the in vivo aneurysm wall intensities, which were normalized to signal of nearby brain tissue and were used as measure for apparent wall thickness (AWT). Spatial wall thickness variation was determined as the interquartile range in AWT (the middle 50% of the AWT range). Wall shear stress was determined using phase contrast MRI (0.5 mm isotropic resolution). We performed visual and statistical comparisons (Pearson’s correlation) to study the relation between wall thickness and wall shear stress. Results 3D colored AWT maps of the aneurysms showed spatial AWT variation, which ranged from 0.07 to 0.53, with a mean variation of 0.22 (a variation of 1.0 roughly means a wall thickness variation of one voxel (0.8mm)). In all aneurysms, AWT was inversely related to WSS (mean correlation coefficient −0.35, P<0.05). Conclusions A method was developed to measure the wall thickness semi-quantitatively, using 7T MRI. An inverse correlation between wall shear stress and AWT was determined. In future studies, this non-invasive method can be used to assess spatial wall thickness variation in relation to pathophysiologic processes such as aneurysm growth and –rupture. PMID:26892986

A Reynolds stress model for near-wall turbulence

NASA Technical Reports Server (NTRS)

Durbin, P. A.

1993-01-01

The paper formulates a tensorially consistent near-wall second-order closure model. Redistributive terms in the Reynolds stress equations are modeled by an elliptic relaxation equation in order to represent strongly nonhomogeneous effects produced by the presence of walls; this replaces the quasi-homogeneous algebraic models that are usually employed, and avoids the need for ad hoc damping functions. The model is solved for channel flow and boundary layers with zero and adverse pressure gradients. Good predictions of Reynolds stress components, mean flow, skin friction, and displacement thickness are obtained in various comparisons to experimental and direct numerical simulation data. The model is also applied to a boundary layer flowing along a wall with a 90-deg, constant-radius, convex bend.

Biomechanical Indices for Rupture Risk Estimation in Abdominal Aortic Aneurysms.

PubMed

Leemans, Eva L; Willems, Tineke P; van der Laan, Maarten J; Slump, Cornelis H; Zeebregts, Clark J

2017-04-01

To review the use of biomechanical indices for the estimation of abdominal aortic aneurysm (AAA) rupture risk, emphasizing their potential use in a clinical setting. A search of the PubMed, Embase, Scopus, and Compendex databases was made up to June 2015 to identify articles involving biomechanical analysis of AAA rupture risk. Outcome variables [aneurysm diameter, peak wall stress (PWS), peak wall shear stress (PWSS), wall strain, peak wall rupture index (PWRI), and wall stiffness] were compared for asymptomatic intact AAAs vs symptomatic or ruptured AAAs. For quantitative analysis of the pooled data, a random effects model was used to calculate the standard mean differences (SMDs) with the 95% confidence interval (CI) for the biomechanical indices. The initial database searches yielded 1894 independent articles of which 19 were included in the analysis. The PWS was significantly higher in the symptomatic/ruptured group, with a SMD of 1.11 (95% CI 0.93 to 1.26, p<0.001). Likewise, the PWRI was significantly higher in the ruptured or symptomatic group, with a SMD of 1.15 (95% CI 0.30 to 2.01, p=0.008). After adjustment for the aneurysm diameter, the PWS remained higher in the ruptured or symptomatic group, with a SMD of 0.85 (95% CI 0.46 to 1.23, p<0.001). Less is known of the wall shear stress and wall strain indices, as too few studies were available for analysis. Biomechanical indices are a promising tool in the assessment of AAA rupture risk as they incorporate several factors, including geometry, tissue properties, and patient-specific risk factors. However, clinical implementation of biomechanical AAA assessment remains a challenge owing to a lack of standardization.

Extremely high wall-shear stress events in a turbulent boundary layer

NASA Astrophysics Data System (ADS)

Pan, Chong; Kwon, Yongseok

2018-04-01

The present work studies the fluctuating characteristics of the streamwise wall-shear stress in a DNS of a turbulent boundary layer at Re τ =1500 from a structural view. The two-dimensional field of the fluctuating friction velocity u‧ τ (x,z) is decomposed into the large- and small-scale components via a recently proposed scale separation algorithm, Quasi-bivariate Variational Mode Decomposition (QB-VMD). Both components are found to be dominated by streak-like structures, which can be regarded as the wall signature of the inner-layer streaks and the outer-layer LSMs, respectively. Extreme positive/negative wall-shear stress fluctuation events are detected in the large-scale component. The former’s occurrence frequency is nearly one order of magnitude higher than the latter; therefore, they contribute a significant portion of the long tail of the wall-shear stress distribution. Both two-point correlations and conditional averages show that these extreme positive wall-shear stress events are embedded in the large-scale positive u‧ τ streaks. They seem to be formed by near-wall ‘splatting’ process, which are related to strong finger-like sweeping (Q4) events originated from the outer-layer positive LSMs.

In vivo assessment of aortic aneurysm wall integrity using elastin-specific molecular magnetic resonance imaging.

PubMed

Botnar, René M; Wiethoff, Andrea J; Ebersberger, Ullrich; Lacerda, Sara; Blume, Ulrike; Warley, Alice; Jansen, Christian H P; Onthank, David C; Cesati, Richard R; Razavi, Reza; Marber, Michael S; Hamm, Bernd; Schaeffter, Tobias; Robinson, Simon P; Makowski, Marcus R

2014-07-01

The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. To induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs. © 2014 American Heart Association, Inc.

Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA.

PubMed

Gao, Qiuqiang; Liou, Liang-Chun; Ren, Qun; Bao, Xiaoming; Zhang, Zhaojie

2014-03-03

The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ 0 ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ 0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ 0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ 0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent.

Protein quality control in organelles - AAA/FtsH story.

PubMed

Janska, Hanna; Kwasniak, Malgorzata; Szczepanowska, Joanna

2013-02-01

This review focuses on organellar AAA/FtsH proteases, whose proteolytic and chaperone-like activity is a crucial component of the protein quality control systems of mitochondrial and chloroplast membranes. We compare the AAA/FtsH proteases from yeast, mammals and plants. The nature of the complexes formed by AAA/FtsH proteases and the current view on their involvement in degradation of non-native organellar proteins or assembly of membrane complexes are discussed. Additional functions of AAA proteases not directly connected with protein quality control found in yeast and mammals but not yet in plants are also described shortly. Following an overview of the molecular functions of the AAA/FtsH proteases we discuss physiological consequences of their inactivation in yeast, mammals and plants. The molecular basis of phenotypes associated with inactivation of the AAA/FtsH proteases is not fully understood yet, with the notable exception of those observed in m-AAA protease-deficient yeast cells, which are caused by impaired maturation of mitochondrial ribosomal protein. Finally, examples of cytosolic events affecting protein quality control in mitochondria and chloroplasts are given. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

Updates on AAA screening and surveillance

PubMed

Theivendran, Mayo; Chuen, Jason

2018-05-01

Screening and diagnostic surveillance of latent conditions have a profound impact on public healthcare expenditure and clinical outcomes. Abdominal aortic aneurysm (AAA) remains one of the hallmark pathologies in vascular surgery and an area of intense research interest. This article is the second of two that will outline current areas of controversy and research in AAA disease in order to support a more detailed understanding of issues in managing patients with this condition, and inform the development of Australasian clinical guidelines and health policy. Screening and surveillance of AAA should be evidence-based and follow clinical guidelines; however, advances in treatment technology and epidemiological data have influenced results. Goals of care and cost‑effectiveness should play central parts in screening and surveillance strategies.

A Methodology for the Derivation of Unloaded Abdominal Aortic Aneurysm Geometry With Experimental Validation

PubMed Central

Chandra, Santanu; Gnanaruban, Vimalatharmaiyah; Riveros, Fabian; Rodriguez, Jose F.; Finol, Ender A.

2016-01-01

In this work, we present a novel method for the derivation of the unloaded geometry of an abdominal aortic aneurysm (AAA) from a pressurized geometry in turn obtained by 3D reconstruction of computed tomography (CT) images. The approach was experimentally validated with an aneurysm phantom loaded with gauge pressures of 80, 120, and 140 mm Hg. The unloaded phantom geometries estimated from these pressurized states were compared to the actual unloaded phantom geometry, resulting in mean nodal surface distances of up to 3.9% of the maximum aneurysm diameter. An in-silico verification was also performed using a patient-specific AAA mesh, resulting in maximum nodal surface distances of 8 μm after running the algorithm for eight iterations. The methodology was then applied to 12 patient-specific AAA for which their corresponding unloaded geometries were generated in 5–8 iterations. The wall mechanics resulting from finite element analysis of the pressurized (CT image-based) and unloaded geometries were compared to quantify the relative importance of using an unloaded geometry for AAA biomechanics. The pressurized AAA models underestimate peak wall stress (quantified by the first principal stress component) on average by 15% compared to the unloaded AAA models. The validation and application of the method, readily compatible with any finite element solver, underscores the importance of generating the unloaded AAA volume mesh prior to using wall stress as a biomechanical marker for rupture risk assessment. PMID:27538124

Impact of wall thickness and saccular geometry on the computational wall stress of descending thoracic aortic aneurysms.

PubMed

Shang, Eric K; Nathan, Derek P; Sprinkle, Shanna R; Fairman, Ronald M; Bavaria, Joseph E; Gorman, Robert C; Gorman, Joseph H; Jackson, Benjamin M

2013-09-10

Wall stress calculated using finite element analysis has been used to predict rupture risk of aortic aneurysms. Prior models often assume uniform aortic wall thickness and fusiform geometry. We examined the effects of including local wall thickness, intraluminal thrombus, calcifications, and saccular geometry on peak wall stress (PWS) in finite element analysis of descending thoracic aortic aneurysms. Computed tomographic angiography of descending thoracic aortic aneurysms (n=10 total, 5 fusiform and 5 saccular) underwent 3-dimensional reconstruction with custom algorithms. For each aneurysm, an initial model was constructed with uniform wall thickness. Experimental models explored the addition of variable wall thickness, calcifications, and intraluminal thrombus. Each model was loaded with 120 mm Hg pressure, and von Mises PWS was computed. The mean PWS of uniform wall thickness models was 410 ± 111 kPa. The imposition of variable wall thickness increased PWS (481 ± 126 kPa, P<0.001). Although the addition of calcifications was not statistically significant (506 ± 126 kPa, P=0.07), the addition of intraluminal thrombus to variable wall thickness (359 ± 86 kPa, P ≤ 0.001) reduced PWS. A final model incorporating all features also reduced PWS (368 ± 88 kPa, P<0.001). Saccular geometry did not increase diameter-normalized stress in the final model (77 ± 7 versus 67 ± 12 kPa/cm, P=0.22). Incorporation of local wall thickness can significantly increase PWS in finite element analysis models of thoracic aortic aneurysms. Incorporating variable wall thickness, intraluminal thrombus, and calcifications significantly impacts computed PWS of thoracic aneurysms; sophisticated models may, therefore, be more accurate in assessing rupture risk. Saccular aneurysms did not demonstrate a significantly higher normalized PWS than fusiform aneurysms.

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

PubMed Central

Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

2014-01-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

Casimir stress in materials: Hard divergency at soft walls

NASA Astrophysics Data System (ADS)

Griniasty, Itay; Leonhardt, Ulf

2017-11-01

The Casimir force between macroscopic bodies is well understood, but not the Casimir stress inside bodies. Suppose empty space or a uniform medium meets a soft wall where the refractive index is continuous but its derivative jumps. For this situation we predict a characteristic power law for the stress inside the soft wall and close to its edges. Our result shows that such edges are not tolerated in the aggregation of liquids at surfaces, regardless whether the liquid is attracted or repelled.

NASA Airborne Astronomy Ambassadors (AAA) Professional Development and NASA Connections

NASA Astrophysics Data System (ADS)

Backman, D. E.; Clark, C.; Harman, P. K.

2017-12-01

NASA's Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content learning, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong's B703 science research aircraft facility in Palmdale, California, and (3) ongoing opportunities for connection with NASA astrophysics and planetary science Subject Matter Experts (SMEs). AAA implementation in 2016-18 involves partnerships between the SETI Institute and seven school districts in northern and southern California. AAAs in the current cohort were selected by the school districts based on criteria developed by AAA program staff working with WestEd evaluation consultants. The selected teachers were then randomly assigned by WestEd to a Group A or B to support controlled testing of student learning. Group A completed their PD during January - August 2017, then participated in NASA SOFIA science flights during fall 2017. Group B will act as a control during the 2017-18 school year, then will complete their professional development and SOFIA flights during 2018. A two-week AAA electromagnetic spectrum and multi-wavelength astronomy curriculum aligned with the Science Framework for California Public Schools and Next Generation Science Standards was developed by program staff for classroom delivery. The curriculum (as well as the AAA's pre-flight PD) capitalizes on NASA content by using "science snapshot" case studies regarding astronomy research conducted by SOFIA. AAAs also interact with NASA SMEs during flight weeks and will translate that interaction into classroom content. The AAA program will make controlled measurements of student gains in standards-based learning plus changes in student attitudes towards STEM, and observe & record the AAAs' implementation of curricular changes. Funded by NASA: NNX16AC51

Mating-Induced Shedding of Cell Walls, Removal of Walls from Vegetative Cells, and Osmotic Stress Induce Presumed Cell Wall Genes in Chlamydomonas1

PubMed Central

Hoffmann, Xenia-Katharina; Beck, Christoph F.

2005-01-01

The first step in sexual differentiation of the unicellular green alga Chlamydomonas reinhardtii is the formation of gametes. Three genes, GAS28, GAS30, and GAS31, encoding Hyp-rich glycoproteins that presumably are cell wall constituents, are expressed in the late phase of gametogenesis. These genes, in addition, are activated by zygote formation and cell wall removal and by the application of osmotic stress. The induction by zygote formation could be traced to cell wall shedding prior to gamete fusion since it was seen in mutants defective in cell fusion. However, it was absent in mutants defective in the initial steps of mating, i.e. in flagellar agglutination and in accumulation of adenosine 3′,5′-cyclic monophosphate in response to this agglutination. Induction of the three GAS genes was also observed when cultures were exposed to hypoosmotic or hyperosmotic stress. To address the question whether the induction seen upon cell wall removal from both gametes and vegetative cells was elicited by osmotic stress, cell wall removal was performed under isosmotic conditions. Also under such conditions an activation of the genes was observed, suggesting that the signaling pathway(s) is (are) activated by wall removal itself. PMID:16183845

A review of near-wall Reynolds-stress

NASA Technical Reports Server (NTRS)

So, R. M. C.; Lai, Y. G.; Zhang, H. S.; Hwang, B. C.

1991-01-01

The advances made in second-order near-wall turbulence closures are summarized. All closures examined are based on some form of high Reynolds number models for the Reynolds stress and the turbulent kinetic energy dissipation rate equations. Consequently, most near-wall closures proposed to data attempt to modify the high Reynolds number models for the dissipation rate equation so that the resultant models are applicable all the way to the wall. The near-wall closures are examined for their asymptotic behavior so that they can be compared with the proper near-wall behavior of the exact equations. A comparison of the closure's performance in the calculation of a low Reynolds number plane channel flow is carried out. In addition, the closures are evaluated for their ability to predict the turbulence statistics and the limiting behavior of the structure parameters compared to direct simulation data.

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

PubMed

Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

2014-06-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Application of mean wall shear stress boundary condition to complex turbulent flows using a wall-modeled large eddy simulation

NASA Astrophysics Data System (ADS)

Cho, Minjeong; Lee, Jungil; Choi, Haecheon

2012-11-01

The mean wall shear stress boundary condition was successfully applied to turbulent channel and boundary flows using large eddy simulation without resolving near-wall region (see Lee, Cho & Choi in this book of abstracts). In the present study, we apply this boundary condition to more complex flows where flow separation and redeveloping flow exist. As a test problem, we consider flow over a backward-facing step at Reh = 22860 based on the step height. Turbulent boundary layer flow at the inlet (Reθ = 1050) is obtained using inflow generation technique by Lund et al. (1998) but with wall shear stress boundary condition. First, we prescribe the mean wall shear stress distribution obtained from DNS (Kim, 2011, Ph.D. Thesis, Stanford U.) as the boundary condition of present simulation. Here we give no-slip boundary condition at flow-reversal region. The present results are in good agreements with the flow statistics by DNS. Currently, a dynamic approach of obtaining mean wall shear stress based on the log-law is being applied to the flow having flow separation and its results will be shown in the presentation. Supported by the WCU and NRF programs.

Prior Radiological Investigations in 65-Year-Old Men Screened for AAA.

PubMed

Meecham, Lewis; Summerour, Virginia; Hobbs, Simon; Newman, Jeremy; Wall, Michael L

2018-05-01

The National Health Service abdominal aortic aneurysm screening programme (NAAASP) is now fully operational. Those who have previously been formally investigated for abdominal aortic aneurysm (AAA) are excluded; however, many patients undergo radiological investigation of the abdomen for other reasons. Such practices may find incidental AAA which may be eroding the performance of the NAAASP. We investigated the rates of preinvestigation before invitation to screening in our local AAA screening programme. Electronic patient records were retrospectively reviewed for all patients called between March 2013 and February 2016 in 1 local AAA screening programme. Their records were interrogated to identify any abdominal imaging within 5 years of their invitation to screening. Two thousand six hundred thirty-eight men were invited for screening; of these, 563 (21.3%) had been "prescreened". Median time between prescreening and screening was 19 months (0-60 months). Ultrasound abdomen was the most prevalent at 248 (44.0%). Two thousand two hundred forty-three (85.0%) men attended screening, and 6 (0.27%) were excluded for known AAA. Prevalence of AAA was 1.8% (n = 41). Of these, 15 (36.6%) had prior investigation with 6 (40.0%) having AAA diagnosed. Therefore, 9 (22.0%) had potential missed AAA on "prescreening" (mean diameter 35 mm [30-45], mean time lapse between investigation and screening 21.1 months [1-49]). Incidence of missed aneurysm in the "prescreened" cohort was 1.6% (9/563). Large numbers of men invited for AAA screening have undergone preinvestigation of their abdominal aorta, with 60% of the present AAA being missed. Reliance on incidental detection of AAA would leave many patients undiagnosed in the community-at risk of future rupture. Copyright © 2018 Elsevier Inc. All rights reserved.

SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells.

PubMed

Toghill, Bradley J; Saratzis, Athanasios; Freeman, Peter J; Sylvius, Nicolas; Bown, Matthew J

2018-01-01

Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter ( P  < 0.0001, R 2  = 0.3175).We then determined CpG methylation status of regulatory regions in genes located at AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R , 2 CpGs were hyper-methylated ( P  = 0.0145); in ERG , 13 CpGs were hyper-methylated ( P  = 0.0005); in SERPINB9 , 6 CpGs were hypo-methylated ( P  = 0.0037) and 1 CpG was hyper-methylated ( P  = 0.0098); and in SMYD2 , 4 CpGs were hypo-methylated ( P  = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression ( P  = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that

Fundamental Characteristics of AAA+ Protein Family Structure and Function

PubMed Central

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins. PMID:27703410

Fundamental Characteristics of AAA+ Protein Family Structure and Function.

PubMed

Miller, Justin M; Enemark, Eric J

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

Convection of wall shear stress events in a turbulent boundary layer

NASA Astrophysics Data System (ADS)

Pabon, Rommel; Mills, David; Ukeiley, Lawrence; Sheplak, Mark

2017-11-01

The fluctuating wall shear stress is measured in a zero pressure gradient turbulent boundary layer of Reτ 1700 simultaneously with velocity measurements using either hot-wire anemometry or particle image velocimetry. These experiments elucidate the patterns of large scale structures in a single point measurement of the wall shear stress, as well as their convection velocity at the wall. The wall shear stress sensor is a CS-A05 one-dimensional capacitice floating element from Interdisciplinary Consulting Corp. It has a nominal bandwidth from DC to 5 kHz and a floating element size of 1 mm in the principal sensing direction (streamwise) and 0.2 mm in the cross direction (spanwise), allowing the large scales to be well resolved in the current experimental conditions. In addition, a two sensor array of CS-A05 aligned in the spanwise direction with streamwise separations O (δ) is utilized to capture the convection velocity of specific scales of the shear stress through a bandpass filter and peaks in the correlation. Thus, an average wall normal position for the corresponding convecting event can be inferred at least as high as the equivalent local streamwise velocity. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1315138.

AAA-DDD triple hydrogen bond complexes.

PubMed

Blight, Barry A; Camara-Campos, Amaya; Djurdjevic, Smilja; Kaller, Martin; Leigh, David A; McMillan, Fiona M; McNab, Hamish; Slawin, Alexandra M Z

2009-10-07

Experiment and theory both suggest that the AAA-DDD pattern of hydrogen bond acceptors (A) and donors (D) is the arrangement of three contiguous hydrogen bonding centers that results in the strongest association between two species. Murray and Zimmerman prepared the first example of such a system (complex 3*2) and determined the lower limit of its association constant (K(a)) in CDCl(3) to be 10(5) M(-1) by (1)H NMR spectroscopy (Murray, T. J. and Zimmerman, S. C. J. Am. Chem. Soc. 1992, 114, 4010-4011). The first cationic AAA-DDD pair (3*4(+)) was described by Bell and Anslyn (Bell, D. A. and Anslyn, E. A. Tetrahedron 1995, 51, 7161-7172), with a K(a) > 5 x 10(5) M(-1) in CH(2)Cl(2) as determined by UV-vis spectroscopy. We were recently able to quantify the strength of a neutral AAA-DDD arrangement using a more chemically stable AAA-DDD system, 6*2, which has an association constant of 2 x 10(7) M(-1) in CH(2)Cl(2) (Djurdjevic, S., Leigh, D. A., McNab, H., Parsons, S., Teobaldi, G. and Zerbetto, F. J. Am. Chem. Soc. 2007, 129, 476-477). Here we report on further AA(A) and DDD partners, together with the first precise measurement of the association constant of a cationic AAA-DDD species. Complex 6*10(+)[B(3,5-(CF(3))(2)C(6)H(3))(4)(-)] has a K(a) = 3 x 10(10) M(-1) at RT in CH(2)Cl(2), by far the most strongly bound triple hydrogen bonded system measured to date. The X-ray crystal structure of 6*10(+) with a BPh(4)(-) counteranion shows a planar array of three short (NH...N distances 1.95-2.15 A), parallel (but staggered rather than strictly linear; N-H...N angles 165.4-168.8 degrees), primary hydrogen bonds. These are apparently reinforced, as theory predicts, by close electrostatic interactions (NH-*-N distances 2.78-3.29 A) between each proton and the acceptor atoms of the adjacent primary hydrogen bonds.

Assessing heterogeneity in oligomeric AAA+ machines.

PubMed

Sysoeva, Tatyana A

2017-03-01

ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.

Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

PubMed Central

Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

2015-01-01

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

Measurements of wall shear stress in a planar turbulent Couette flow with porous walls

NASA Astrophysics Data System (ADS)

Beuther, Paul

2013-11-01

Measurements of drag on a moving web in a multi-span festoon show a stronger than expected dependency on the porosity of the web. The experiments suggest a wall shear stress 3-4 times larger than non-porous webs or historical Couette flow data for solid walls. Previous DNS studies by Jimenez et al. (JFM Vol 442) of boundary layers with passive porous surfaces predict a much smaller increase in wall shear stress for a porous wall of only 40%. Other DNS studies by Quadrio et al. (JFM Vol 576) of porous walls with periodic transpiration do show a large increase in drag under certain periodic conditions of modest amplitude. Although those results are aligned in magnitude with this study, the exact reason for the observed high drag for porous webs in this present study is not understood because there was no external disturbance applied to the web. It can be hypothesized that natural flutter of the web results in a similar mechanism shown in the periodic DNS study, but when the natural flutter was reduced by increasing web tension, there was only a small decrease of the drag. A key difference in this study is that because of the multiple parallel spans in a festoon, any transpiration in one layer must act in the opposite manner on the adjacent span.

Investigation of Wall Shear Stress Behavior for Rough Surfaces with Blowing

NASA Astrophysics Data System (ADS)

Helvey, Jacob; Borchetta, Colby; Miller, Mark; Martin, Alexandre; Bailey, Sean

2014-11-01

We present an experimental study conducted in a turbulent channel flow wind tunnel to determine the modifications made to the turbulent flow over rough surfaces with flow injection through the surfaces. Hot-wire profile results from a quasi-two-dimensional, sinusoidally-rough surface indicate that the effects of roughness are enhanced by momentum injection through the surface. In particular, the wall shear stress was found to show behavior consistent with increased roughness height when surface blowing was increased. This observed behavior contradicts previously reported results for regular three-dimensional roughness which show a decrease in wall shear stress with additional blowing. It is unclear whether this discrepancy is due to differences in the roughness geometry under consideration or the use of the Clauser fit to estimate wall shear stress. Additional PIV experiments are being conducted for a three-dimensional fibrous surface to obtain Reynolds shear stress profiles. These results provide an additional method for estimation of wall-shear stress and thus allow verification of the use of the Clauser chart approach for flows with momentum injection through the surface. This research is supported by NASA Kentucky EPSCoR Award NNX10AV39A, and NASA RA Award NNX13AN04A.

Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

PubMed

Htun, Nay Min; Peter, Karlheinz

2014-10-01

Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright �

Debonding Stress Concentrations in a Pressurized Lobed Sandwich-Walled Generic Cryogenic Tank

NASA Technical Reports Server (NTRS)

Ko, William L.

2004-01-01

A finite-element stress analysis has been conducted on a lobed composite sandwich tank subjected to internal pressure and cryogenic cooling. The lobed geometry consists of two obtuse circular walls joined together with a common flat wall. Under internal pressure and cryogenic cooling, this type of lobed tank wall will experience open-mode (a process in which the honeycomb is stretched in the depth direction) and shear stress concentrations at the junctures where curved wall changes into flat wall (known as a curve-flat juncture). Open-mode and shear stress concentrations occur in the honeycomb core at the curve-flat junctures and could cause debonding failure. The levels of contributions from internal pressure and temperature loading to the open-mode and shear debonding failure are compared. The lobed fuel tank with honeycomb sandwich walls has been found to be a structurally unsound geometry because of very low debonding failure strengths. The debonding failure problem could be eliminated if the honeycomb core at the curve-flat juncture is replaced with a solid core.

AAAS: Politics. . . and Science

ERIC Educational Resources Information Center

Science News, 1978

1978-01-01

Reviews topics discussed during the American Association for the Advancement of Science (AAAS) meeting held in Washington, D.C. Topics included: the equal rights amendment, laetrile, nuclear radiation hazards, sociobiology, and various science topics. (SL)

Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

PubMed

Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

2017-11-22

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease.

PubMed

Lee, Sukyeong; Augustin, Steffen; Tatsuta, Takashi; Gerdes, Florian; Langer, Thomas; Tsai, Francis T F

2011-02-11

FtsH-related AAA proteases are conserved membrane-anchored, ATP-dependent molecular machines, which mediate the processing and turnover of soluble and membrane-embedded proteins in eubacteria, mitochondria, and chloroplasts. Homo- and hetero-oligomeric proteolytic complexes exist, which are composed of homologous subunits harboring an ATPase domain of the AAA family and an H41 metallopeptidase domain. Mutations in subunits of mitochondrial m-AAA proteases have been associated with different neurodegenerative disorders in human, raising questions on the functional differences between homo- and hetero-oligomeric AAA proteases. Here, we have analyzed the hetero-oligomeric yeast m-AAA protease composed of homologous Yta10 and Yta12 subunits. We combined genetic and structural approaches to define the molecular determinants for oligomer assembly and to assess functional similarities between Yta10 and Yta12. We demonstrate that replacement of only two amino acid residues within the metallopeptidase domain of Yta12 allows its assembly into homo-oligomeric complexes. To provide a molecular explanation, we determined the 12 Å resolution structure of the intact yeast m-AAA protease with its transmembrane domains by electron cryomicroscopy (cryo-EM) and atomic structure fitting. The full-length m-AAA protease has a bipartite structure and is a hexamer in solution. We found that residues in Yta12, which facilitate homo-oligomerization when mutated, are located at the interface between neighboring protomers in the hexamer ring. Notably, the transmembrane and intermembrane space domains are separated from the main body, creating a passage on the matrix side, which is wide enough to accommodate unfolded but not folded polypeptides. These results suggest a mechanism regarding how proteins are recognized and degraded by m-AAA proteases.

m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration

PubMed Central

Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

2018-01-01

The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders. PMID:29451229

m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.

PubMed

Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

2018-03-01

The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders.

The impact of personalized probabilistic wall thickness models on peak wall stress in abdominal aortic aneurysms.

PubMed

Biehler, J; Wall, W A

2018-02-01

If computational models are ever to be used in high-stakes decision making in clinical practice, the use of personalized models and predictive simulation techniques is a must. This entails rigorous quantification of uncertainties as well as harnessing available patient-specific data to the greatest extent possible. Although researchers are beginning to realize that taking uncertainty in model input parameters into account is a necessity, the predominantly used probabilistic description for these uncertain parameters is based on elementary random variable models. In this work, we set out for a comparison of different probabilistic models for uncertain input parameters using the example of an uncertain wall thickness in finite element models of abdominal aortic aneurysms. We provide the first comparison between a random variable and a random field model for the aortic wall and investigate the impact on the probability distribution of the computed peak wall stress. Moreover, we show that the uncertainty about the prevailing peak wall stress can be reduced if noninvasively available, patient-specific data are harnessed for the construction of the probabilistic wall thickness model. Copyright © 2017 John Wiley & Sons, Ltd.

Mitochondrial AAA proteases--towards a molecular understanding of membrane-bound proteolytic machines.

PubMed

Gerdes, Florian; Tatsuta, Takashi; Langer, Thomas

2012-01-01

Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. Copyright © 2011 Elsevier B.V. All rights reserved.

The effects of nicotine administration on the pathophysiology of rat aortic wall.

PubMed

Kugo, H; Zaima, N; Tanaka, H; Urano, T; Unno, N; Moriyama, T

2017-01-01

Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.

Dispersive aortic cannulas reduce aortic wall shear stress affecting atherosclerotic plaque embolization.

PubMed

Assmann, Alexander; Gül, Fethi; Benim, Ali Cemal; Joos, Franz; Akhyari, Payam; Lichtenberg, Artur

2015-03-01

Neurologic complications during on-pump cardiovascular surgery are often induced by mobilization of atherosclerotic plaques, which is directly related to enhanced wall shear stress. In the present study, we numerically evaluated the impact of dispersive aortic cannulas on aortic blood flow characteristics, with special regard to the resulting wall shear stress profiles. An idealized numerical model of the human aorta and its branches was created and used to model straight as well as bent dispersive aortic cannulas with meshlike tips inserted in the distal ascending aorta. Standard cannulas with straight beveled or bent tips served as controls. Using a recently optimized computing method, simulations of pulsatile and nonpulsatile extracorporeal circulation were performed. Dispersive aortic cannulas reduced the maximum and average aortic wall shear stress values to approximately 50% of those with control cannulas, while the difference in local values was even larger. Moreover, under pulsatile circulation, dispersive cannulas shortened the time period during which wall shear stress values were increased. The turbulent kinetic energy was also diminished by utilizing dispersive cannulas, reducing the risk of hemolysis. In summary, dispersive aortic cannulas decrease aortic wall shear stress and turbulence during extracorporeal circulation and may therefore reduce the risk of endothelial and blood cell damage as well as that of neurologic complications caused by atherosclerotic plaque mobilization. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines.

PubMed

Monroe, Nicole; Hill, Christopher P

2016-05-08

Meiotic clade AAA ATPases (ATPases associated with diverse cellular activities), which were initially grouped on the basis of phylogenetic classification of their AAA ATPase cassette, include four relatively well characterized family members, Vps4, spastin, katanin and fidgetin. These enzymes all function to disassemble specific polymeric protein structures, with Vps4 disassembling the ESCRT-III polymers that are central to the many membrane-remodeling activities of the ESCRT (endosomal sorting complexes required for transport) pathway and spastin, katanin p60 and fidgetin affecting multiple aspects of cellular dynamics by severing microtubules. They share a common domain architecture that features an N-terminal MIT (microtubule interacting and trafficking) domain followed by a single AAA ATPase cassette. Meiotic clade AAA ATPases function as hexamers that can cycle between the active assembly and inactive monomers/dimers in a regulated process, and they appear to disassemble their polymeric substrates by translocating subunits through the central pore of their hexameric ring. Recent studies with Vps4 have shown that nucleotide-induced asymmetry is a requirement for substrate binding to the pore loops and that recruitment to the protein lattice via MIT domains also relieves autoinhibition and primes the AAA ATPase cassettes for substrate binding. The most striking, unifying feature of meiotic clade AAA ATPases may be their MIT domain, which is a module that is found in a wide variety of proteins that localize to ESCRT-III polymers. Spastin also displays an adjacent microtubule binding sequence, and the presence of both ESCRT-III and microtubule binding elements may underlie the recent findings that the ESCRT-III disassembly function of Vps4 and the microtubule-severing function of spastin, as well as potentially katanin and fidgetin, are highly coordinated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microbubbles and Blood Brain Barrier Opening: A Numerical Study on Acoustic Emissions and Wall Stress Predictions

PubMed Central

Goertz, David E.; Hynynen, Kullervo

2015-01-01

Focused ultrasound with microbubbles is an emerging technique for blood brain barrier (BBB) opening. Here, a comprehensive theoretical model of a bubble-fluid-vessel system has been developed which accounts for the bubble’s non-spherical oscillations inside a microvessel, and its resulting acoustic emissions. Numerical simulations of unbound and confined encapsulated bubbles were performed to evaluate the effect of the vessel wall on acoustic emissions and vessel wall stresses. Using a Marmottant shell model, the normalized second harmonic to fundamental emissions first decreased as a function of pressure (>50 kPa) until reaching a minima ("transition point") at which point they increased. The transition point of unbound compared to confined bubble populations occurred at different pressures and was associated with an accompanying increase in shear and circumferential wall stresses. As the wall stresses depend on the bubble to vessel wall distance, the stresses were evaluated for bubbles with their wall at a constant distance to a flat wall. As a result, the wall stresses were bubble size and frequency dependent and the peak stress values induced by bubbles larger than resonance remained constant versus frequency at a constant mechanical index. PMID:25546853

Development of a shear stress sensor to analyse the influence of polymers on the turbulent wall shear stress.

PubMed

Nottebrock, Bernardo; Grosse, Sebastian; Schröder, Wolfgang

2011-05-11

The drag reducing effect of polymers in a channel flow is well known and it is assumed that the polymer filaments interfere with the turbulent structures in the very near-wall flow. To analyse their precise effect, a micro-pillar shear stress sensor (MPS³) measurement system is developed which allows the detection of wall shear stress at high spatial and temporal resolutions. Different manufacturing techniques for the required micro-pillars are discussed and their influence on the flow is investigated evidencing the non-intrusive character of the pillars. Subsequently, a complete calibration is presented to relate the recorded deflection to wall shear stress values and to assure the correct detection over the whole expected frequency spectrum. A feasibility study about the ability to visualize the two-dimensional wall shear stress distribution completes the discussion about the validity of MPS³. In the last step, the drag reduction of a polymer filament grafted on a micro-pillar compared to a plain pillar and the application of MPS³ in an ocean-type polymer solution are investigated. The results confirm the expected behaviour found in the literature.

CFD modelling of abdominal aortic aneurysm on hemodynamic loads using a realistic geometry with CT.

PubMed

Soudah, Eduardo; Ng, E Y K; Loong, T H; Bordone, Maurizio; Pua, Uei; Narayanan, Sriram

2013-01-01

The objective of this study is to find a correlation between the abdominal aortic aneurysm (AAA) geometric parameters, wall stress shear (WSS), abdominal flow patterns, intraluminal thrombus (ILT), and AAA arterial wall rupture using computational fluid dynamics (CFD). Real AAA 3D models were created by three-dimensional (3D) reconstruction of in vivo acquired computed tomography (CT) images from 5 patients. Based on 3D AAA models, high quality volume meshes were created using an optimal tetrahedral aspect ratio for the whole domain. In order to quantify the WSS and the recirculation inside the AAA, a 3D CFD using finite elements analysis was used. The CFD computation was performed assuming that the arterial wall is rigid and the blood is considered a homogeneous Newtonian fluid with a density of 1050 kg/m(3) and a kinematic viscosity of 4 × 10(-3) Pa·s. Parallelization procedures were used in order to increase the performance of the CFD calculations. A relation between AAA geometric parameters (asymmetry index ( β ), saccular index ( γ ), deformation diameter ratio ( χ ), and tortuosity index ( ε )) and hemodynamic loads was observed, and it could be used as a potential predictor of AAA arterial wall rupture and potential ILT formation.

Breaking symmetry in non-planar bifurcations: distribution of flow and wall shear stress.

PubMed

Lu, Yiling; Lu, Xiyun; Zhuang, Lixian; Wang, Wen

2002-01-01

Non-planarity in blood vessels is known to influence arterial flows and wall shear stress. To gain insight, computational fluid dynamics (CFD) has been used to investigate effects of curvature and out-of-plane geometry on the distribution of fluid flows and wall shear stresses in a hypothetical non-planar bifurcation. Three-dimensional Navier-Stokes equations for a steady state Newtonian fluid were solved numerically using a finite element method. Non-planarity in one of the two daughter vessels is found to deflect flow from the inner wall of the vessel to the outer wall and to cause changes in the distribution of wall shear stresses. Results from this study agree to experimental observations and CFD simulations in the literature, and support the view that non-planarity in blood vessels is a factor with important haemodynamic significance and may play a key role in vascular biology and pathophysiology.

Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning

PubMed Central

D’Mello, Sidney; Dieterle, Ed; Duckworth, Angela

2017-01-01

It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research. PMID:29038607

Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning.

PubMed

D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

2017-01-01

It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research.

The Weekend Effect in AAA Repair.

PubMed

O'Donnell, Thomas F X; Li, Chun; Swerdlow, Nicholas J; Liang, Patric; Pothof, Alexander B; Patel, Virendra I; Giles, Kristina A; Malas, Mahmoud B; Schermerhorn, Marc L

2018-04-18

Conflicting reports exist regarding whether patients undergoing surgery on the weekend or later in the week experience worse outcomes. We identified patients undergoing abdominal aortic aneurysm (AAA) repair in the Vascular Quality Initiative between 2009 and 2017 [n = 38,498; 30,537 endovascular aneurysm repair (EVAR) and 7961 open repair]. We utilized mixed effects logistic regression to compare adjusted rates of perioperative mortality based on the day of repair. Tuesday was the most common day for elective repair (22%), Friday for symptomatic repairs (20%), and ruptured aneurysms were evenly distributed. Patients with ruptured aneurysms experienced similar adjusted mortality whether they underwent repair during the week or on weekends. Transfers of ruptured AAA were more common over the weekend. However, patients transferred on the weekend experienced higher adjusted mortality than those transferred during the week (28% vs 21%, P = 0.02), despite the fact that during the week, transferred patients actually experienced lower adjusted mortality than patients treated at the index hospital (21% vs 31%, P < 0.01). Among symptomatic patients, adjusted mortality was higher for those undergoing repair over the weekend than those whose surgeries were delayed until a weekday (7.9% vs 3.1%, P = 0.02). Adjusted mortality in elective cases did not vary across the days of the week. Results were consistent between open and EVAR patients. We found no evidence of a weekend effect for ruptured or symptomatic AAA repair. However, patients with ruptured AAA transferred on the weekend experienced higher mortality than those transferred during the week, suggesting a need for improvement in weekend transfer processes.

Runge-Kutta method for wall shear stress of blood flow in stenosed artery

NASA Astrophysics Data System (ADS)

Awaludin, Izyan Syazana; Ahmad, Rokiah@Rozita

2014-06-01

A mathematical model of blood flow through stenotic artery is considered. A stenosis is defined as the partial occlusion of the blood vessels due to the accumulation of cholesterols, fats and the abnormal growth of tissue on the artery walls. The development of stenosis in the artery is one of the factors that cause problem in blood circulation system. This study was conducted to determine the wall shear stress of blood flow in stenosed artery. Modified mathematical model is used to analyze the relationship of the wall shear stress versus the length and height of stenosis. The existing models that have been created by previous researchers are solved using fourth order Runge-Kutta method. Numerical results show that the wall shear stress is proportionate to the length and height of stenosis.

The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.

PubMed

Wang, Shuaiyu; Jacquemyn, Julie; Murru, Sara; Martinelli, Paola; Barth, Esther; Langer, Thomas; Niessen, Carien M; Rugarli, Elena I

2016-12-01

The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.

Control of Mechanical Stresses of High Pressure Container Walls by Magnetoelastic Method

NASA Astrophysics Data System (ADS)

Kulak, S. M.; Novikov, V. F.; Baranov, A. V.

2016-10-01

Deformations of the walls of pressure vessels arising in the process of testing and operation, as well as reduce their thickness due to corrosion, to create the prerequisites for the growth of mechanical stresses which accelerating the processes of strain aging, embrittlement of the material and reducing its fatigue properties. This article is devoted to researches of the magnetoelastic demagnetization in the wall of steel vessel of loading by internal pressure. It is established that the increasing pressure on the vessel wall is accompanied by a monotonic decrease in the intensity of the magnetic stray field of local magnetization of steel. It is shown that a magnetic stray field of local magnetization of the wall of steel vessel is non-uniform due to differences in structure and stresses. It is proposed to use the obtained results to control the stress state of vessels, experiencing multi-axial loads generated by internal pressure (pipelines, oil tanks, etc.) The method of magnetoelastic of the demagnetization of the steel has a high sensitivity to mechanical stress, the simplicity of implementation and expressiveness compared to the strain gauge and method of coercive force.

APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

PubMed

Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

2013-11-01

To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

Fluid-structure interaction in abdominal aortic aneurysms: Structural and geometrical considerations

NASA Astrophysics Data System (ADS)

Mesri, Yaser; Niazmand, Hamid; Deyranlou, Amin; Sadeghi, Mahmood Reza

2015-08-01

Rupture of the abdominal aortic aneurysm (AAA) is the result of the relatively complex interaction of blood hemodynamics and material behavior of arterial walls. In the present study, the cumulative effects of physiological parameters such as the directional growth, arterial wall properties (isotropy and anisotropy), iliac bifurcation and arterial wall thickness on prediction of wall stress in fully coupled fluid-structure interaction (FSI) analysis of five idealized AAA models have been investigated. In particular, the numerical model considers the heterogeneity of arterial wall and the iliac bifurcation, which allows the study of the geometric asymmetry due to the growth of the aneurysm into different directions. Results demonstrate that the blood pulsatile nature is responsible for emerging a time-dependent recirculation zone inside the aneurysm, which directly affects the stress distribution in aneurismal wall. Therefore, aneurysm deviation from the arterial axis, especially, in the lateral direction increases the wall stress in a relatively nonlinear fashion. Among the models analyzed in this investigation, the anisotropic material model that considers the wall thickness variations, greatly affects the wall stress values, while the stress distributions are less affected as compared to the uniform wall thickness models. In this regard, it is confirmed that wall stress predictions are more influenced by the appropriate structural model than the geometrical considerations such as the level of asymmetry and its curvature, growth direction and its extent.

Large scale structures in a turbulent boundary layer and their imprint on wall shear stress

NASA Astrophysics Data System (ADS)

Pabon, Rommel; Barnard, Casey; Ukeiley, Lawrence; Sheplak, Mark

2015-11-01

Experiments were performed on a turbulent boundary layer developing on a flat plate model under zero pressure gradient flow. A MEMS differential capacitive shear stress sensor with a 1 mm × 1 mm floating element was used to capture the fluctuating wall shear stress simultaneously with streamwise velocity measurements from a hot-wire anemometer traversed in the wall normal direction. Near the wall, the peak in the cross correlation corresponds to an organized motion inclined 45° from the wall. In the outer region, the peak diminishes in value, but is still significant at a distance greater than half the boundary layer thickness, and corresponds to a structure inclined 14° from the wall. High coherence between the two signals was found for the low-frequency content, reinforcing the belief that large scale structures have a vital impact on wall shear stress. Thus, estimation of the wall shear stress from the low-frequency velocity signal will be performed, and is expected to be statistically significant in the outer boundary layer. Additionally, conditionally averaged mean velocity profiles will be presented to assess the effects of high and low shear stress. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1315138.

Reciprocal Interactions between Cadmium-Induced Cell Wall Responses and Oxidative Stress in Plants

PubMed Central

Loix, Christophe; Huybrechts, Michiel; Vangronsveld, Jaco; Gielen, Marijke; Keunen, Els; Cuypers, Ann

2017-01-01

Cadmium (Cd) pollution renders many soils across the world unsuited or unsafe for food- or feed-orientated agriculture. The main mechanism of Cd phytotoxicity is the induction of oxidative stress, amongst others through the depletion of glutathione. Oxidative stress can damage lipids, proteins, and nucleic acids, leading to growth inhibition or even cell death. The plant cell has a variety of tools to defend itself against Cd stress. First and foremost, cell walls might prevent Cd from entering and damaging the protoplast. Both the primary and secondary cell wall have an array of defensive mechanisms that can be adapted to cope with Cd. Pectin, which contains most of the negative charges within the primary cell wall, can sequester Cd very effectively. In the secondary cell wall, lignification can serve to immobilize Cd and create a tougher barrier for entry. Changes in cell wall composition are, however, dependent on nutrients and conversely might affect their uptake. Additionally, the role of ascorbate (AsA) as most important apoplastic antioxidant is of considerable interest, due to the fact that oxidative stress is a major mechanism underlying Cd toxicity, and that AsA biosynthesis shares several links with cell wall construction. In this review, modifications of the plant cell wall in response to Cd exposure are discussed. Focus lies on pectin in the primary cell wall, lignification in the secondary cell wall and the importance of AsA in the apoplast. Regarding lignification, we attempt to answer the question whether increased lignification is merely a consequence of Cd toxicity, or rather an elicited defense response. We propose a model for lignification as defense response, with a central role for hydrogen peroxide as substrate and signaling molecule. PMID:29163592

AAA (2010) CAPD clinical practice guidelines: need for an update.

PubMed

DeBonis, David A

2017-09-01

Review and critique of the clinical value of the AAA CAPD guidance document in light of criteria for credible and useful guidance documents, as discussed by Field and Lohr. A qualitative review of the of the AAA CAPD guidelines using a framework by Field and Lohr to assess their relative value in supporting the assessment and management of CAPD referrals. Relevant literature available through electronic search tools and published texts were used along with the AAA CAPD guidance document and the chapter by Field and Lohr. The AAA document does not meet many of the key requirements discussed by Field and Lohr. It does not reflect the current literature, fails to help clinicians understand for whom auditory processing testing and intervention would be most useful, includes contradictory suggestions which reduce clarity and appears to avoid conclusions that might cast the CAPD construct in a negative light. It also does not include input from diverse affected groups. All of these reduce the document's credibility. The AAA CAPD guidance document will need to be updated and re-conceptualised in order to provide meaningful guidance for clinicians.

Wall shear stress fixed points in blood flow

NASA Astrophysics Data System (ADS)

Arzani, Amirhossein; Shadden, Shawn

2017-11-01

Patient-specific computational fluid dynamics produces large datasets, and wall shear stress (WSS) is one of the most important parameters due to its close connection with the biological processes at the wall. While some studies have investigated WSS vectorial features, the WSS fixed points have not received much attention. In this talk, we will discuss the importance of WSS fixed points from three viewpoints. First, we will review how WSS fixed points relate to the flow physics away from the wall. Second, we will discuss how certain types of WSS fixed points lead to high biochemical surface concentration in cardiovascular mass transport problems. Finally, we will introduce a new measure to track the exposure of endothelial cells to WSS fixed points.

Advanced, Analytic, Automated (AAA) Measurement of Engagement during Learning

ERIC Educational Resources Information Center

D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

2017-01-01

It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in…

Wall shear stress measurements using a new transducer

NASA Technical Reports Server (NTRS)

Vakili, A. D.; Wu, J. M.; Lawing, P. L.

1986-01-01

A new instrument has been developed for direct measurement of wall shear stress. This instrument is simple and symmetric in design with small moving mass and no internal friction. Features employed in the design of this instrument eliminate most of the difficulties associated with the traditional floating element balances. Vibration problems associated with the floating element skin friction balances have been found to be minimized by the design features and optional damping provided. The unique design of this instrument eliminates or reduces the errors associated with conventional floating-element devices: such as errors due to gaps, pressure gradient, acceleration, heat transfer and temperature change. The instrument is equipped with various sensing systems and the output signal is a linear function of the wall shear stress. Measurement made in three different tunnels show good agreement with theory and data obtained by the floating element devices.

Molecularly Defined Nanostructures Based on a Novel AAA-DDD Triple Hydrogen-Bonding Motif.

PubMed

Papmeyer, Marcus; Vuilleumier, Clément A; Pavan, Giovanni M; Zhurov, Konstantin O; Severin, Kay

2016-01-26

A facile and flexible method for the synthesis of a new AAA-DDD triple hydrogen-bonding motif is described. Polytopic supramolecular building blocks with precisely oriented AAA and DDD groups are thus accessible in few steps. These building blocks were used for the assembly of large macrocycles featuring four AAA-DDD interactions and a macrobicyclic complex with a total of six AAA-DDD interactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.

PubMed

König, Tim; Tröder, Simon E; Bakka, Kavya; Korwitz, Anne; Richter-Dennerlein, Ricarda; Lampe, Philipp A; Patron, Maria; Mühlmeister, Mareike; Guerrero-Castillo, Sergio; Brandt, Ulrich; Decker, Thorsten; Lauria, Ines; Paggio, Angela; Rizzuto, Rosario; Rugarli, Elena I; De Stefani, Diego; Langer, Thomas

2016-10-06

Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca 2+ uniporter MCU. While MAIP1 assists biogenesis of the MCU subunit EMRE, the m-AAA protease degrades non-assembled EMRE and ensures efficient assembly of gatekeeper subunits with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria and facilitates mitochondrial Ca 2+ overload, mitochondrial permeability transition pore opening, and neuronal death. Together, our results explain neuronal loss in m-AAA protease deficiency by deregulated mitochondrial Ca 2+ homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

An AAA-DDD triply hydrogen-bonded complex easily accessible for supramolecular polymers.

PubMed

Han, Yi-Fei; Chen, Wen-Qiang; Wang, Hong-Bo; Yuan, Ying-Xue; Wu, Na-Na; Song, Xiang-Zhi; Yang, Lan

2014-12-15

For a complementary hydrogen-bonded complex, when every hydrogen-bond acceptor is on one side and every hydrogen-bond donor is on the other, all secondary interactions are attractive and the complex is highly stable. AAA-DDD (A=acceptor, D=donor) is considered to be the most stable among triply hydrogen-bonded sequences. The easily synthesized and further derivatized AAA-DDD system is very desirable for hydrogen-bonded functional materials. In this case, AAA and DDD, starting from 4-methoxybenzaldehyde, were synthesized with the Hantzsch pyridine synthesis and Friedländer annulation reaction. The association constant determined by fluorescence titration in chloroform at room temperature is 2.09×10(7)  M(-1) . The AAA and DDD components are not coplanar, but form a V shape in the solid state. Supramolecular polymers based on AAA-DDD triply hydrogen bonded have also been developed. This work may make AAA-DDD triply hydrogen-bonded sequences easily accessible for stimuli-responsive materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Shear stress enhances microcin B17 production in a rotating wall bioreactor, but ethanol stress does not

NASA Technical Reports Server (NTRS)

Gao, Q.; Fang, A.; Pierson, D. L.; Mishra, S. K.; Demain, A. L.

2001-01-01

Stress, including that caused by ethanol, has been shown to induce or promote secondary metabolism in a number of microbial systems. Rotating-wall bioreactors provide a low stress and simulated microgravity environment which, however, supports only poor production of microcin B17 by Escherichia coli ZK650, as compared to production in agitated flasks. We wondered whether the poor production is due to the low level of stress and whether increasing stress in the bioreactors would raise the amount of microcin B17 formed. We found that applying shear stress by addition of a single Teflon bead to a rotating wall bioreactor improved microcin B17 production. By contrast, addition of various concentrations of ethanol to such bioreactors (or to shaken flasks) failed to increase microcin B17 production. Ethanol stress merely decreased production and, at higher concentrations, inhibited growth. Interestingly, cells growing in the bioreactor were much more resistant to the growth-inhibitory and production-inhibitory effects of ethanol than cells growing in shaken flasks.

Role of AAA(+)-proteins in peroxisome biogenesis and function.

PubMed

Grimm, Immanuel; Erdmann, Ralf; Girzalsky, Wolfgang

2016-05-01

Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.

Endoplasmic reticulum-derived reactive oxygen species (ROS) is involved in toxicity of cell wall stress to Candida albicans.

PubMed

Yu, Qilin; Zhang, Bing; Li, Jianrong; Zhang, Biao; Wang, Honggang; Li, Mingchun

2016-10-01

The cell wall is an important cell structure in both fungi and bacteria, and hence becomes a common antimicrobial target. The cell wall-perturbing agents disrupt synthesis and function of cell wall components, leading to cell wall stress and consequent cell death. However, little is known about the detailed mechanisms by which cell wall stress renders fungal cell death. In this study, we found that ROS scavengers drastically attenuated the antifungal effect of cell wall-perturbing agents to the model fungal pathogen Candida albicans, and these agents caused remarkable ROS accumulation and activation of oxidative stress response (OSR) in this fungus. Interestingly, cell wall stress did not cause mitochondrial dysfunction and elevation of mitochondrial superoxide levels. Furthermore, the iron chelator 2,2'-bipyridyl (BIP) and the hydroxyl radical scavengers could not attenuate cell wall stress-caused growth inhibition and ROS accumulation. However, cell wall stress up-regulated expression of unfold protein response (UPR) genes, enhanced protein secretion and promoted protein folding-related oxidation of Ero1, an important source of ROS production. These results indicated that oxidation of Ero1 in the endoplasmic reticulum (ER), rather than mitochondrial electron transport and Fenton reaction, contributed to cell wall stress-related ROS accumulation and consequent growth inhibition. Our findings uncover a novel link between cell wall integrity (CWI), ER function and ROS production in fungal cells, and shed novel light on development of strategies promoting the antifungal efficacy of cell wall-perturbing agents against fungal infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Dimensionless number is central to stress relaxation and expansive growth of the cell wall.

PubMed

Ortega, Joseph K E

2017-06-07

Experiments demonstrate that both plastic and elastic deformation of the cell wall are necessary for wall stress relaxation and expansive growth of walled cells. A biophysical equation (Augmented Growth Equation) was previously shown to accurately model the experimentally observed wall stress relaxation and expansive growth rate. Here, dimensional analysis is used to obtain a dimensionless Augmented Growth Equation with dimensionless coefficients (groups of variables, or Π parameters). It is shown that a single Π parameter controls the wall stress relaxation rate. The Π parameter represents the ratio of plastic and elastic deformation rates, and provides an explicit relationship between expansive growth rate and the wall's mechanical properties. Values for Π are calculated for plant, algal, and fungal cells from previously reported experimental results. It is found that the Π values for each cell species are large and very different from each other. Expansive growth rates are calculated using the calculated Π values and are compared to those measured for plant and fungal cells during different growth conditions, after treatment with IAA, and in different developmental stages. The comparison shows good agreement and supports the claim that the Π parameter is central to expansive growth rate of walled cells.

A methodology for developing anisotropic AAA phantoms via additive manufacturing.

PubMed

Ruiz de Galarreta, Sergio; Antón, Raúl; Cazón, Aitor; Finol, Ender A

2017-05-24

An Abdominal Aortic Aneurysm (AAA) is a permanent focal dilatation of the abdominal aorta at least 1.5 times its normal diameter. The criterion of maximum diameter is still used in clinical practice, although numerical studies have demonstrated the importance of biomechanical factors for rupture risk assessment. AAA phantoms could be used for experimental validation of the numerical studies and for pre-intervention testing of endovascular grafts. We have applied multi-material 3D printing technology to manufacture idealized AAA phantoms with anisotropic mechanical behavior. Different composites were fabricated and the phantom specimens were characterized by biaxial tensile tests while using a constitutive model to fit the experimental data. One composite was chosen to manufacture the phantom based on having the same mechanical properties as those reported in the literature for human AAA tissue; the strain energy and anisotropic index were compared to make this choice. The materials for the matrix and fibers of the selected composite are, respectively, the digital materials FLX9940 and FLX9960 developed by Stratasys. The fiber proportion for the composite is equal to 0.15. The differences between the composite behavior and the AAA tissue are small, with a small difference in the strain energy (0.4%) and a maximum difference of 12.4% in the peak Green strain ratio. This work represents a step forward in the application of 3D printing technology for the manufacturing of AAA phantoms with anisotropic mechanical behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Social stress in mice induces voiding dysfunction and bladder wall remodeling

PubMed Central

Chang, Andy; Butler, Stephan; Sliwoski, Joanna; Valentino, Rita; Canning, Douglas

2009-01-01

Several studies have anecdotally reported the occurrence of altered urinary voiding patterns in rodents exposed to social stress. A recent study characterized the urodynamic and central changes in a rat model of social defeat. Here, we describe a similar voiding phenotype induced in mice by social stress and in addition we describe potential molecular mechanisms underlying the resulting bladder wall remodeling. The mechanism leading to the altered voiding habits and underlying bladder phenotype may be relevant to the human syndrome of dysfunctional voiding which is thought to have a psychological component. To better characterize and investigate social stress-induced bladder wall hypertrophy, FVB mice (6 wk old) were randomized to either social stress or control manipulation. The stress involved repeated cycles of a 1-h direct exposure to a larger aggressive C57Bl6 breeder mouse followed by a 23-h period of barrier separation over 4 wk. Social stress resulted in altered urinary voiding patterns suggestive of urinary retention and increased bladder mass. In vivo cystometry revealed an increased volume at micturition with no change in the voiding pressure. Examination of these bladders revealed increased nuclear expression of the transcription factors MEF-2 and NFAT, as well as increased expression of the myosin heavy chain B isoform mRNA. BrdU uptake was increased within the urothelium and lamina propria layers in the social stress group. We conclude that social stress induces urinary retention that ultimately leads to shifts in transcription factors, alterations in myosin heavy chain isoform expression, and increases in DNA synthesis that mediate bladder wall remodeling. Social stress-induced bladder dysfunction in rodents may provide insight into the underlying mechanisms and potential treatment of dysfunctional voiding in humans. PMID:19587139

Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

PubMed

Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

2018-03-20

The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of α 2 -antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Impact of wall shear stress on initial bacterial adhesion in rotating annular reactor

PubMed Central

Saur, Thibaut; Morin, Emilie; Habouzit, Frédéric; Bernet, Nicolas

2017-01-01

The objective of this study was to investigate the bacterial adhesion under different wall shear stresses in turbulent flow and using a diverse bacterial consortium. A better understanding of the mechanisms governing microbial adhesion can be useful in diverse domains such as industrial processes, medical fields or environmental biotechnologies. The impact of wall shear stress—four values ranging from 0.09 to 7.3 Pa on polypropylene (PP) and polyvinyl chloride (PVC)—was carried out in rotating annular reactors to evaluate the adhesion in terms of morphological and microbiological structures. A diverse inoculum consisting of activated sludge was used. Epifluorescence microscopy was used to quantitatively and qualitatively characterize the adhesion. Attached bacterial communities were assessed by molecular fingerprinting profiles (CE-SSCP). It has been demonstrated that wall shear stress had a strong impact on both quantitative and qualitative aspects of the bacterial adhesion. ANOVA tests also demonstrated the significant impact of wall shear stress on all three tested morphological parameters (surface coverage, number of objects and size of objects) (p-values < 2.10−16). High wall shear stresses increased the quantity of attached bacteria but also altered their spatial distribution on the substratum surface. As the shear increased, aggregates or clusters appeared and their size grew when increasing the shears. Concerning the microbiological composition, the adhered bacterial communities changed gradually with the applied shear. PMID:28207869

Multi-Centre Study on Cardiovascular Risk Management on Patients Undergoing AAA Surveillance.

PubMed

Saratzis, A; Dattani, N; Brown, A; Shalhoub, J; Bosanquet, D; Sidloff, D; Stather, P

2017-07-01

The risk of cardiovascular events and death in patients with abdominal aortic aneurysms (AAA) is high. Screening has been introduced to reduce AAA related mortality; however, after AAA diagnosis, cardiovascular modification may be as important to patient outcomes as surveillance. The aim of this study was to assess cardiovascular risk reduction in patients with small AAA. Institutional approval was granted for The Vascular and Endovascular Research Network (VERN) to retrospectively collect data pertaining to cardiovascular risk reduction from four tertiary vascular units in England. Patients with small AAA (January 2013-December 2015) were included. Demographic details, postcode, current medications, and smoking status were recorded using a bespoke electronic database and analysed. In a secondary analysis VERN contacted all AAA screening units in England and Wales to assess their current protocols relating to CV protection. In total, 1053 patients were included (mean age 74 ± 9 years, all men). Of these, 745 patients (70.8%) had been prescribed an antiplatelet agent and 787 (74.7%) a statin. Overall, only 666 patients (63.2%) were prescribed both a statin and antiplatelet. Two hundred and sixty eight patients (32.1%) were current smokers and the proportion of patients who continued to smoke decreased with age. Overall, only 401 patients (48.1%) were prescribed a statin, antiplatelet, and had stopped smoking. In the secondary analysis 38 AAA screening units (84% national coverage) replied. Thirty-one units (82%) suggest changes to the patient's prescription; however, none monitor compliance with these recommendations or assess whether the general practitioner has been made aware of the AAA diagnosis or prescription advice. Many patients with small AAA are not prescribed an antiplatelet/statin, and still smoke cigarettes, and therefore remain at high risk of cardiovascular morbidity and mortality. National guidance to ensure this high risk group of patients is

Pressure and wall shear stress in blood hammer - Analytical theory.

PubMed

Mei, Chiang C; Jing, Haixiao

2016-10-01

We describe an analytical theory of blood hammer in a long and stiffened artery due to sudden blockage. Based on the model of a viscous fluid in laminar flow, we derive explicit expressions of oscillatory pressure and wall shear stress. To examine the effects on local plaque formation we also allow the blood vessel radius to be slightly nonuniform. Without resorting to discrete computation, the asymptotic method of multiple scales is utilized to deal with the sharp contrast of time scales. The effects of plaque and blocking time on blood pressure and wall shear stress are studied. The theory is validated by comparison with existing water hammer experiments. Copyright © 2016. Published by Elsevier Inc.

Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with tricuspid aortic valve.

PubMed

Xuan, Yue; Wang, Zhongjie; Liu, Raymond; Haraldsson, Henrik; Hope, Michael D; Saloner, David A; Guccione, Julius M; Ge, Liang; Tseng, Elaine

2018-03-08

Guidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts. Patients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress. Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid

Combination of endovascular graft exclusion and drug therapy in AAA with hypertension or hyperglycemia.

PubMed

Wang, Dile; Qu, Bihui; He, Tao

2017-08-01

The objective of the present study was to evaluate the efficacy of combination of endovascular graft exclusion and drugs for hypertension/hyperglycemia for the treatment of abdominal aortic aneurysm (AAA). We analyzed 156 patients with AAA. Eighty-four patients were hypertensive and 72 were hyperglycemic. After endovascular graft exclusion, hypertensive patients were divided into four groups and treated with cyclopenthiazide, reserpine, propranolol, and placebo respectively. Hyperglycemic patients were divided into three groups and treated with metformin, insulin, and placebo respectively. Body temperature and peripheral blood leukocytes were measured at day 1, 2, 7, and 14 after endovascular graft exclusion. Size of AAAs, blood pressure, and blood sugar were measured again after 1 year. In hypertensive patients, the size of AAAs reduced after endovascular graft exclusion, while the combined treatments with cyclopenthiazide, reserpine, or propranolol helped to reduce blood pressure (blood pressure decrease <10 mmHg (18/21), <10 mmHg (12/21), <10 mmHg (8/21), and <10 mmHg (10/21) in the control group, cyclopenthiazide group, reserpine group, and propranolol group, respectively. AAA size decreased in the control group (P<0.001) and in the other three groups (P<0.0001). Similar results were obtained in hyperglycemic patients. The size of AAAs reduced after endovascular graft exclusion. Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar >7.8 mmol/L (22/24), AAA size (P<0.001); metformin, blood sugar >7.8 mmol/L (14/24), AAA size (P<0.0001); insulin, blood sugar >7.8 mmol/L (11/24), AAA size (P<0.0001). Combination of endovascular graft exclusion with medicine is more effective than the former treatment alone for AAA therapy.

Pulsatile flows and wall-shear stresses in models simulating normal and stenosed aortic arches

NASA Astrophysics Data System (ADS)

Huang, Rong Fung; Yang, Ten-Fang; Lan, Y.-K.

2010-03-01

Pulsatile aqueous glycerol solution flows in the models simulating normal and stenosed human aortic arches are measured by means of particle image velocimetry. Three transparent models were used: normal, 25% stenosed, and 50% stenosed aortic arches. The Womersley parameter, Dean number, and time-averaged Reynolds number are 17.31, 725, and 1,081, respectively. The Reynolds numbers based on the peak velocities of the normal, 25% stenosed, and 50% stenosed aortic arches are 2,484, 3,456, and 3,931, respectively. The study presents the temporal/spatial evolution processes of the flow pattern, velocity distribution, and wall-shear stress during the systolic and diastolic phases. It is found that the flow pattern evolving in the central plane of normal and stenosed aortic arches exhibits (1) a separation bubble around the inner arch, (2) a recirculation vortex around the outer arch wall upstream of the junction of the brachiocephalic artery, (3) an accelerated main stream around the outer arch wall near the junctions of the left carotid and the left subclavian arteries, and (4) the vortices around the entrances of the three main branches. The study identifies and discusses the reasons for the flow physics’ contribution to the formation of these features. The oscillating wall-shear stress distributions are closely related to the featured flow structures. On the outer wall of normal and slightly stenosed aortas, large wall-shear stresses appear in the regions upstream of the junction of the brachiocephalic artery as well as the corner near the junctions of the left carotid artery and the left subclavian artery. On the inner wall, the largest wall-shear stress appears in the region where the boundary layer separates.

Simultaneous wall-shear-stress and wide-field PIV measurements in a turbulent boundary layer

NASA Astrophysics Data System (ADS)

Gomit, Guillaume; Fourrie, Gregoire; de Kat, Roeland; Ganapathisubramani, Bharathram

2015-11-01

Simultaneous particle image velocimetry (PIV) and hot-film shear stress sensor measurements were performed to study the large-scale structures associated with shear stress events in a flat plate turbulent boundary layer at a high Reynolds number (Reτ ~ 4000). The PIV measurement was performed in a streamwise-wall normal plane using an array of six high resolution cameras (4 ×16MP and 2 ×29MP). The resulting field of view covers 8 δ (where δ is the boundary layer thickness) in the streamwise direction and captures the entire boundary layer in the wall-normal direction. The spatial resolution of the measurement is approximately is approximately 70 wall units (1.8 mm) and sampled each 35 wall units (0.9 mm). In association with the PIV setup, a spanwise array of 10 skin-friction sensors (spanning one δ) was used to capture the footprint of the large-scale structures. This combination of measurements allowed the analysis of the three-dimensional conditional structures in the boundary layer. Particularly, from conditional averages, the 3D organisation of the wall normal and streamwise velocity components (u and v) and the Reynolds shear stress (-u'v') related to a low and high shear stress events can be extracted. European Research Council Grant No-277472-WBT.

Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases.

PubMed

Lucas, Márcio L; Carraro, Cristina C; Belló-Klein, Adriane; Kalil, Antônio N; Aerts, Newton R; Carvalho, Fabiano B; Fernandes, Marilda C; Zettler, Claudio G

2018-06-06

Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA. Copyright © 2018 Elsevier Inc. All rights reserved.

Readily functionalized AAA-DDD triply hydrogen-bonded motifs.

PubMed

Tong, Feng; Linares-Mendez, Iamnica J; Han, Yi-Fei; Wisner, James A; Wang, Hong-Bo

2018-04-25

Herein we present a new, readily functionalized AAA-DDD hydrogen bond array. A novel AAA monomeric unit (3a-b) was obtained from a two-step synthetic procedure starting with 2-aminonicotinaldehyde via microwave radiation (overall yield of 52-66%). 1H NMR and fluorescence spectroscopy confirmed the complexation event with a calculated association constant of 1.57 × 107 M-1. Likewise, the usefulness of this triple hydrogen bond motif in supramolecular polymerization was demonstrated through viscosity measurements in a crosslinked supramolecular alternating copolymer.

On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm.

PubMed

Pincemail, J; Defraigne, J O; Cheramy-Bien, J P; Dardenne, N; Donneau, A F; Albert, A; Labropoulos, N; Sakalihasan, N

2012-01-01

Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients. Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤ 50 or > 50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.

Numerical design and optimization of hydraulic resistance and wall shear stress inside pressure-driven microfluidic networks.

PubMed

Damiri, Hazem Salim; Bardaweel, Hamzeh Khalid

2015-11-07

Microfluidic networks represent the milestone of microfluidic devices. Recent advancements in microfluidic technologies mandate complex designs where both hydraulic resistance and pressure drop across the microfluidic network are minimized, while wall shear stress is precisely mapped throughout the network. In this work, a combination of theoretical and modeling techniques is used to construct a microfluidic network that operates under minimum hydraulic resistance and minimum pressure drop while constraining wall shear stress throughout the network. The results show that in order to minimize the hydraulic resistance and pressure drop throughout the network while maintaining constant wall shear stress throughout the network, geometric and shape conditions related to the compactness and aspect ratio of the parent and daughter branches must be followed. Also, results suggest that while a "local" minimum hydraulic resistance can be achieved for a geometry with an arbitrary aspect ratio, a "global" minimum hydraulic resistance occurs only when the aspect ratio of that geometry is set to unity. Thus, it is concluded that square and equilateral triangular cross-sectional area microfluidic networks have the least resistance compared to all rectangular and isosceles triangular cross-sectional microfluidic networks, respectively. Precise control over wall shear stress through the bifurcations of the microfluidic network is demonstrated in this work. Three multi-generation microfluidic network designs are considered. In these three designs, wall shear stress in the microfluidic network is successfully kept constant, increased in the daughter-branch direction, or decreased in the daughter-branch direction, respectively. For the multi-generation microfluidic network with constant wall shear stress, the design guidelines presented in this work result in identical profiles of wall shear stresses not only within a single generation but also through all the generations of the

Measurement of Wall Shear Stress in High Speed Air Flow Using Shear-Sensitive Liquid Crystal Coating.

PubMed

Zhao, Jisong

2018-05-17

Wall shear stress is an important quantity in fluid mechanics, but its measurement is a challenging task. An approach to measure wall shear stress vector distribution using shear-sensitive liquid crystal coating (SSLCC) is described. The wall shear stress distribution on the test surface beneath high speed jet flow is measured while using the proposed technique. The flow structures inside the jet flow are captured and the results agree well with the streakline pattern that was visualized using the oil-flow technique. In addition, the shock diamonds inside the supersonic jet flow are visualized clearly using SSLCC and the results are compared with the velocity contour that was measured using the particle image velocimetry (PIV) technique. The work of this paper demonstrates the application of SSLCC in the measurement/visualization of wall shear stress in high speed flow.

Measurement of Wall Shear Stress in High Speed Air Flow Using Shear-Sensitive Liquid Crystal Coating

PubMed Central

Zhao, Jisong

2018-01-01

Wall shear stress is an important quantity in fluid mechanics, but its measurement is a challenging task. An approach to measure wall shear stress vector distribution using shear-sensitive liquid crystal coating (SSLCC) is described. The wall shear stress distribution on the test surface beneath high speed jet flow is measured while using the proposed technique. The flow structures inside the jet flow are captured and the results agree well with the streakline pattern that was visualized using the oil-flow technique. In addition, the shock diamonds inside the supersonic jet flow are visualized clearly using SSLCC and the results are compared with the velocity contour that was measured using the particle image velocimetry (PIV) technique. The work of this paper demonstrates the application of SSLCC in the measurement/visualization of wall shear stress in high speed flow. PMID:29772822

The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders

PubMed Central

Law, Kelsey B.; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O.; Moser, Ann; Brumell, John H.; Braverman, Nancy

2017-01-01

ABSTRACT Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs. PMID:28521612

The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders.

PubMed

Law, Kelsey B; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O; Moser, Ann; Brumell, John H; Braverman, Nancy; Kim, Peter K

2017-05-04

Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs.

Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

PubMed

Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

2011-07-01

ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

Regionalization of Emergent Vascular Surgery for Patients With Ruptured AAA Improves Outcomes.

PubMed

Warner, Courtney J; Roddy, Sean P; Chang, Benjamin B; Kreienberg, Paul B; Sternbach, Yaron; Taggert, John B; Ozsvath, Kathleen J; Stain, Steven C; Darling, R Clement

2016-09-01

Safe and efficient endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (r-AAA) requires advanced infrastructure and surgical expertise not available at all US hospitals. The objective was to assess the impact of regionalizing r-AAA care to centers equipped for both open surgical repair (r-OSR) and EVAR (r-EVAR) by vascular surgeons. A retrospective review of all patients with r-AAA undergoing open or endovascular repair in a 12-hospital region. Patient demographics, transfer status, type of repair, and intraoperative variables were recorded. Outcomes included perioperative morbidity and mortality. Four hundred fifty-one patients with r-AAA were treated from 2002 to 2015. Three hundred twenty-one patients (71%) presented initially to community hospitals (CHs) and 130 (29%) presented to the tertiary medical center (MC). Of the 321 patients presenting to CH, 133 (41%) were treated locally (131 OSR; 2 EVAR) and 188 (59%) were transferred to the MC. In total, 318 patients were treated at the MC (122 OSR; 196 EVAR). At the MC, r-EVAR was associated with a lower mortality rate than r-OSR (20% vs 37%, P = 0.001). Transfer did not influence r-EVAR mortality (20% in r-EVAR presenting to MC vs 20% in r-EVAR transferred, P > 0.2). Overall, r-AAA mortality at the MC was 20% lower than CH (27% vs 46%, P < 0.001). Regionalization of r-AAA repair to centers equipped for both r-EVAR and r-OSR decreased mortality by approximately 20%. Transfer did not impact the mortality of r-EVAR at the tertiary center. Care of r-AAA in the US should be centralized to centers equipped with available technology and vascular surgeons.

Stent implantation influence wall shear stress evolution

NASA Astrophysics Data System (ADS)

Bernad, S. I.; Totorean, A. F.; Bosioc, A. I.; Petre, I.; Bernad, E. S.

2016-06-01

Local hemodynamic factors are known affect the natural history of the restenosis critically after coronary stenting of atherosclerosis. Stent-induced flows disturbance magnitude dependent directly on the strut design. The impact of flow alterations around struts vary as the strut geometrical parameters change. Our results provide data regarding the hemodynamic parameters for the blood flow in both stenosed and stented coronary artery under physiological conditions, namely wall shear stress and pressure drop.

Identifying patients with AAA with the highest risk following endovascular repair.

PubMed

Cadili, Ali; Turnbull, Robert; Hervas-Malo, Marilou; Ghosh, Sunita; Chyczij, Harold

2012-08-01

It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. Patients with AAA greater than 85 years of age are at a greater risk of mortality

An Experimental and Numerical Comparison of the Rupture Locations of an Abdominal Aortic Aneurysm

PubMed Central

Doyle, Barry J.; Corbett, Timothy J.; Callanan, Anthony; Walsh, Michael T.; Vorp, David A.; McGloughlin, Timothy M.

2009-01-01

Purpose: To identify the rupture locations of idealized physical models of abdominal aortic aneurysm (AAA) using an in-vitro setup and to compare the findings to those predicted numerically. Methods: Five idealized AAAs were manufactured using Sylgard 184 silicone rubber, which had been mechanically characterized from tensile tests, tear tests, and finite element analysis. The models were then inflated to the point of rupture and recorded using a high-speed camera. Numerical modeling attempted to confirm these rupture locations. Regional variations in wall thickness of the silicone models was also quantified and applied to numerical models. Results: Four of the 5 models tested ruptured at inflection points in the proximal and distal regions of the aneurysm sac and not at regions of maximum diameter. These findings agree with high stress regions computed numerically. Wall stress appears to be independent of wall thickness, with high stress occurring at regions of inflection regardless of wall thickness variations. Conclusion: According to these experimental and numerical findings, AAAs experience higher stresses at regions of inflection compared to regions of maximum diameter. Ruptures of the idealized silicone models occurred predominantly at the inflection points, as numerically predicted. Regions of inflection can be easily identified from basic 3-dimensional reconstruction; as ruptures appear to occur at inflection points, these findings may provide a useful insight into the clinical significance of inflection regions. This approach will be applied to patient-specific models in a future study. PMID:19642790

18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.

PubMed

Courtois, Audrey; Nusgens, Betty V; Hustinx, Roland; Namur, Gauthier; Gomez, Pierre; Somja, Joan; Defraigne, Jean-Olivier; Delvenne, Philippe; Michel, Jean-Baptiste; Colige, Alain C; Sakalihasan, Natzi

2013-10-01

Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of (18)F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the (18)F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no (18)F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. Biopsies of the AAA wall were obtained from patients with no (18)F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. The sites of the aneurysmal wall with a positive (18)F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. Positive (18)F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC

Correlation between vortices and wall shear stress in a curved artery model under pulsatile flow conditions

NASA Astrophysics Data System (ADS)

Cox, Christopher; Plesniak, Michael W.

2017-11-01

One of the most physiologically relevant factors within the cardiovascular system is the wall shear stress. The wall shear stress affects endothelial cells via mechanotransduction and atherosclerotic regions are strongly correlated with curvature and branching in the human vasculature, where the shear stress is both oscillatory and multidirectional. Also, the combined effect of curvature and pulsatility in cardiovascular flows produces unsteady vortices. In this work, our goal is to assess the correlation between multiple vortex pairs and wall shear stress. To accomplish this, we use an in-house high-order flux reconstruction Navier-Stokes solver to simulate pulsatile flow of a Newtonian blood-analog fluid through a rigid 180° curved artery model. We use a physiologically relevant flow rate and generate results using both fully developed and uniform entrance conditions, the latter motivated by the fact that flow upstream to a curved artery may not be fully developed. Under these two inflow conditions, we characterize the evolution of various vortex pairs and their subsequent effect on several wall shear stress metrics. Supported by GW Center for Biomimetics and Bioinspired Engineering.

A multi-component parallel-plate flow chamber system for studying the effect of exercise-induced wall shear stress on endothelial cells.

PubMed

Wang, Yan-Xia; Xiang, Cheng; Liu, Bo; Zhu, Yong; Luan, Yong; Liu, Shu-Tian; Qin, Kai-Rong

2016-12-28

In vivo studies have demonstrated that reasonable exercise training can improve endothelial function. To confirm the key role of wall shear stress induced by exercise on endothelial cells, and to understand how wall shear stress affects the structure and the function of endothelial cells, it is crucial to design and fabricate an in vitro multi-component parallel-plate flow chamber system which can closely replicate exercise-induced wall shear stress waveforms in artery. The in vivo wall shear stress waveforms from the common carotid artery of a healthy volunteer in resting and immediately after 30 min acute aerobic cycling exercise were first calculated by measuring the inner diameter and the center-line blood flow velocity with a color Doppler ultrasound. According to the above in vivo wall shear stress waveforms, we designed and fabricated a parallel-plate flow chamber system with appropriate components based on a lumped parameter hemodynamics model. To validate the feasibility of this system, human umbilical vein endothelial cells (HUVECs) line were cultured within the parallel-plate flow chamber under abovementioned two types of wall shear stress waveforms and the intracellular actin microfilaments and nitric oxide (NO) production level were evaluated using fluorescence microscope. Our results show that the trends of resting and exercise-induced wall shear stress waveforms, especially the maximal, minimal and mean wall shear stress as well as oscillatory shear index, generated by the parallel-plate flow chamber system are similar to those acquired from the common carotid artery. In addition, the cellular experiments demonstrate that the actin microfilaments and the production of NO within cells exposed to the two different wall shear stress waveforms exhibit different dynamic behaviors; there are larger numbers of actin microfilaments and higher level NO in cells exposed in exercise-induced wall shear stress condition than resting wall shear stress condition

Assessment of the accuracy of AortaScan for detection of abdominal aortic aneurysm (AAA).

PubMed

Abbas, A; Smith, A; Cecelja, M; Waltham, M

2012-02-01

AortaScan AMI 9700 is a portable 3D ultrasound device that automatically measures the maximum diameter of the abdominal aorta without the need for a trained sonographer. It is designed to rapidly diagnose or exclude an AAA and may have particular use in screening programs. Our objective was to determine its accuracy to detect AAA. Subjects from our AAA screening and surveillance programs were examined. The aorta was scanned using the AortaScan and computed tomography (CT). Ninety-one subjects underwent imaging (44 AAA on conventional ultrasound surveillance and 47 controls). The largest measurement obtained by AortaScan was compared against the CT-aortic measurement. The mean aortic diameter was 2.8 cm. The CT scan confirmed the diagnosis of AAA in 43 subjects. There was one false positive measurement on conventional ultrasound. AortaScan missed the diagnosis of AAA in eight subjects. There were thirteen false positive measurements. The sensitivity, specificity, positive and negative predictive values were 81%, 72%, 72% and 81% respectively. A device to detect AAA without the need for a trained operator would have potential in a community-based screening programme. The AortaScan, however, lacks adequate sensitivity and significant technical improvement is necessary before it could be considered a replacement for trained screening personnel. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall

PubMed Central

Hiorns, J. E.

2016-01-01

Airway hyperresponsiveness (AHR) is a key characteristic of asthma that remains poorly understood. Tidal breathing and deep inspiration ordinarily cause rapid relaxation of airway smooth muscle (ASM) (as demonstrated via application of length fluctuations to tissue strips) and are therefore implicated in modulation of AHR, but in some cases (such as application of transmural pressure oscillations to isolated intact airways) this mechanism fails. Here we use a multiscale biomechanical model for intact airways that incorporates strain stiffening due to collagen recruitment and dynamic force generation by ASM cells to show that the geometry of the airway, together with interplay between dynamic active and passive forces, gives rise to large stress and compliance heterogeneities across the airway wall that are absent in tissue strips. We show further that these stress heterogeneities result in auxotonic loading conditions that are currently not replicated in tissue-strip experiments; stresses in the strip are similar to hoop stress only at the outer airway wall and are under- or overestimates of stresses at the lumen. Taken together these results suggest that a previously underappreciated factor, stress heterogeneities within the airway wall and consequent ASM cellular response to this micromechanical environment, could contribute to AHR and should be explored further both theoretically and experimentally. PMID:27197860

PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

PubMed

Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

2015-11-01

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

A Relation Between Near-Wall Particle-Hemodynamics and Onset of Thrombus Formation in Abdominal Aortic Aneurysms

PubMed Central

Basciano, C.; Kleinstreuer, C.; Hyun, S.; Finol, E. A.

2014-01-01

A novel computational particle-hemodynamics analysis of key criteria for the onset of an intraluminal thrombus (ILT) in a patient-specific abdominal aortic aneurysm (AAA) is presented. The focus is on enhanced platelet and white blood cell residence times as well as their elevated surface-shear loads in near-wall regions of the AAA sac. The generalized results support the hypothesis that a patient's AAA geometry and associated particle-hemodynamics have the potential to entrap activated blood particles, which will play a role in the onset of ILT. Although the ILT history of only a single patient was considered, the modeling and simulation methodology provided allow for the development of an efficient computational tool to predict the onset of ILT formation in complex patient-specific cases. PMID:21373952

Effect of shape and size of lung and chest wall on stresses in the lung

NASA Technical Reports Server (NTRS)

Vawter, D. L.; Matthews, F. L.; West, J. B.

1975-01-01

To understand better the effect of shape and size of lung and chest wall on the distribution of stresses, strains, and surface pressures, we analyzed a theoretical model using the technique of finite elements. First we investigated the effects of changing the chest wall shape during expansion, and second we studied lungs of a variety of inherent shapes and sizes. We found that, in general, the distributions of alveolar size, mechanical stresses, and surface pressures in the lungs were dominated by the weight of the lung and that changing the shape of the lung or chest wall had relatively little effect. Only at high states of expansion where the lung was very stiff did changing the shape of the chest wall cause substantial changes. Altering the inherent shape of the lung generally had little effect but the topographical differences in stresses and surface pressures were approximately proportional to lung height. The results are generally consistent with those found in the dog by Hoppin et al (1969).

Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

PubMed

Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

2017-01-01

There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights

Gender, smoking, body size, and aneurysm geometry influence the biomechanical rupture risk of abdominal aortic aneurysms as estimated by finite element analysis.

PubMed

Lindquist Liljeqvist, Moritz; Hultgren, Rebecka; Siika, Antti; Gasser, T Christian; Roy, Joy

2017-04-01

Finite element analysis (FEA) has been suggested to be superior to maximal diameter measurements in predicting rupture of abdominal aortic aneurysms (AAAs). Our objective was to investigate to what extent previously described rupture risk factors were associated with FEA-estimated rupture risk. One hundred forty-six patients with an asymptomatic AAA of a 40- to 60-mm diameter were retrospectively identified and consecutively included. The patients' computed tomography angiograms were analyzed by FEA without (neutral) and with (specific) input of patient-specific mean arterial pressure (MAP), gender, family history, and age. The maximal wall stress/wall strength ratio was described as a rupture risk equivalent diameter (RRED), which translated this ratio into an average aneurysm diameter of corresponding rupture risk. In multivariate linear regression, RRED neutral increased with female gender (3.7 mm; 95% confidence interval [CI], 0.13-7.3) and correlated with patient height (0.27 mm/cm; 95% CI, 0.11-0.43) and body surface area (BSA, 16 mm/m 2 ; 95% CI, 8.3-24) and inversely with body mass index (BMI, -0.40 mm/kg m -2 ; 95% CI, -0.75 to -0.054) in a wall stress-dependent manner. Wall stress-adjusted RRED neutral was raised if the patient was currently smoking (1.1 mm; 95% CI, 0.21-1.9). Age, MAP, family history, and patient weight were unrelated to RRED neutral . In specific FEA, RRED specific increased with female gender, MAP, family history positive for AAA, height, and BSA, whereas it was inversely related to BMI. All results were independent of aneurysm diameter. Peak wall stress and RRED correlated with aneurysm diameter and lumen volume. Female gender, current smoking, increased patient height and BSA, and low BMI were found to increase the mechanical rupture risk of AAAs. Previously described rupture risk factors may in part be explained by patient characteristic-dependent variations in aneurysm biomechanics. Copyright © 2016 Society for Vascular

The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast

PubMed Central

Sanz, Ana Belén; García, Raúl; Rodríguez-Peña, José M.; Arroyo, Javier

2017-01-01

Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI) pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies. PMID:29371494

Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm

PubMed Central

Sun, Jingyuan; Deng, Hongping; Zhou, Zhen

2018-01-01

Abdominal aortic aneurysm (AAA) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for AAA. However, so far, it is unclear whether such drugs have any beneficial effect on AAA prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that AAA is highly associated with endothelial dysfunction in the aged population. Additionally, animal models of endothelial dysfunction and endothelial nitric oxide synthase (eNOS) uncoupling had a very high rate of AAA formation, indicating there is crucial involvement of the endothelium and a possible pharmacological solution targeting the endothelium in AAA treatment. Endothelial cells have been found to trigger vascular wall remodeling by releasing proteases, or recruiting macrophages along with other neutrophils, into the medial layer. Moreover, inflammation and oxidative stress of the arterial wall were induced by endothelial dysfunction. Interestingly, there is a paradoxical differential correlation between diabetes and aneurysm formation in retinal capillaries and the aorta. Deciphering the significance of such a difference may explain current unsuccessful AAA medications and offer a solution to this treatment challenge. It is now believed that AAA and atherosclerosis are two separate but related diseases, based on their different clinical patterns which have further complicated the puzzle. Therefore, a thorough investigation of the interaction between endothelium and medial/adventitial layer may provide us a better understanding and new perspective on AAA formation, especially after taking into account the importance of endothelium in the development of AAA. Moreover, a novel medication strategy replacing the currently used, but suboptimal treatments for AAA, could be

Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

PubMed

An, Young Jun; Na, Jung-Hyun; Kim, Myung-Il; Cha, Sun-Shin

2015-10-01

Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.

The AAA protein spastin possesses two levels of basal ATPase activity.

PubMed

Fan, Xiangyu; Lin, Zhijie; Fan, Guanghui; Lu, Jing; Hou, Yongfei; Habai, Gulijiazi; Sun, Linyue; Yu, Pengpeng; Shen, Yuequan; Wen, Maorong; Wang, Chunguang

2018-05-01

The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected. © 2018 Federation of European Biochemical Societies.

A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.

PubMed

Prattes, Michael; Loibl, Mathias; Zisser, Gertrude; Luschnig, Daniel; Kappel, Lisa; Rössler, Ingrid; Grassegger, Manuela; Hromic, Altijana; Krieger, Elmar; Gruber, Karl; Pertschy, Brigitte; Bergler, Helmut

2017-03-17

AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research. Here, we present the characterization of a novel mutant variant of the eukaryotic AAA-ATPase Drg1 that shows dysregulation of ATPase activity and altered interaction with Rlp24, its substrate in ribosome biogenesis. This defective regulation is the consequence of amino acid exchanges at the interface between the regulatory N-domain and the adjacent D1 AAA-domain. The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). Our results therefore suggest well conserved mechanisms of regulation between structurally, but not functionally related members of the AAA-family.

Spatio-temporal characteristics of large scale motions in a turbulent boundary layer from direct wall shear stress measurement

NASA Astrophysics Data System (ADS)

Pabon, Rommel; Barnard, Casey; Ukeiley, Lawrence; Sheplak, Mark

2016-11-01

Particle image velocimetry (PIV) and fluctuating wall shear stress experiments were performed on a flat plate turbulent boundary layer (TBL) under zero pressure gradient conditions. The fluctuating wall shear stress was measured using a microelectromechanical 1mm × 1mm floating element capacitive shear stress sensor (CSSS) developed at the University of Florida. The experiments elucidated the imprint of the organized motions in a TBL on the wall shear stress through its direct measurement. Spatial autocorrelation of the streamwise velocity from the PIV snapshots revealed large scale motions that scale on the order of boundary layer thickness. However, the captured inclination angle was lower than that determined using the classic method by means of wall shear stress and hot-wire anemometry (HWA) temporal cross-correlations and a frozen field hypothesis using a convection velocity. The current study suggests the large size of these motions begins to degrade the applicability of the frozen field hypothesis for the time resolved HWA experiments. The simultaneous PIV and CSSS measurements are also used for spatial reconstruction of the velocity field during conditionally sampled intense wall shear stress events. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1315138.

PIV Measurement of Wall Shear Stress and Flow Structures within an Intracranial Aneurysm Model

NASA Astrophysics Data System (ADS)

Chow, Ricky; Sparrow, Eph; Campbell, Gary; Divani, Afshin; Sheng, Jian

2012-11-01

The formation and rupture of an intracranial aneurysm (IA) is a debilitating and often lethal event. Geometric features of the aneurysm bulb and upstream artery, such as bulb size, bulb shape, and curvature of the artery, are two groups of factors that define the flow and stresses within an IA. Abnormal flow stresses are related to rupture. This presentation discusses the development of a quasi-3D PIV technique and its application in various glass models at Re = 275 and 550 to experimentally assess at a preliminary level the impact of geometry and flow rate. Some conclusions are to be drawn linking geometry of the flow domain to rupture risk. The extracted results also serve as the baseline case and as a precursor to a companion presentation by the authors discussing the impact of flow diverters, a new class of medical devices. The PIV experiments were performed in a fully index-matched flow facility, allowing for unobstructed observations over complex geometry. A reconstruction and analysis method was devised to obtain 3D mean wall stress distributions and flow fields. The quasi 3D measurements were reconstructed from orthogonal planes encompassing the entire glass model, spaced 0.4mm apart. Wall shear stresses were evaluated from the near-wall flow viscous stresses.

Stresses In And Near A Bend In A Thin-Walled Duct

NASA Technical Reports Server (NTRS)

Min, J. B.; Aggarwal, P. K.

1995-01-01

Report describes computational study of distributions of stresses in and near 90 degrees bend in thin-walled duct subject to various applied loads. Purpose of study to help satisfy need for more accurate knowledge of local concentrations of stresses caused by loads: such knowledge makes possible to design light-weight ducts to survive reasonably foreseeable operating conditions with some degree of reliability. Also guides selection of locations for mounting strain gauges to measure local stresses for comparison with computed values, contributing to refinement of theoretical concepts and computational techniques.

Estimation of aneurysm wall stresses created by treatment with a shape memory polymer foam device

PubMed Central

Hwang, Wonjun; Volk, Brent L.; Akberali, Farida; Singhal, Pooja; Criscione, John C.

2012-01-01

In this study, compliant latex thin-walled aneurysm models are fabricated to investigate the effects of expansion of shape memory polymer foam. A simplified cylindrical model is selected for the in-vitro aneurysm, which is a simplification of a real, saccular aneurysm. The studies are performed by crimping shape memory polymer foams, originally 6 and 8 mm in diameter, and monitoring the resulting deformation when deployed into 4-mm-diameter thin-walled latex tubes. The deformations of the latex tubes are used as inputs to physical, analytical, and computational models to estimate the circumferential stresses. Using the results of the stress analysis in the latex aneurysm model, a computational model of the human aneurysm is developed by changing the geometry and material properties. The model is then used to predict the stresses that would develop in a human aneurysm. The experimental, simulation, and analytical results suggest that shape memory polymer foams have potential of being a safe treatment for intracranial saccular aneurysms. In particular, this work suggests oversized shape memory foams may be used to better fill the entire aneurysm cavity while generating stresses below the aneurysm wall breaking stresses. PMID:21901546

The FERONIA Receptor Kinase Maintains Cell-Wall Integrity during Salt Stress through Ca2+ Signaling.

PubMed

Feng, Wei; Kita, Daniel; Peaucelle, Alexis; Cartwright, Heather N; Doan, Vinh; Duan, Qiaohong; Liu, Ming-Che; Maman, Jacob; Steinhorst, Leonie; Schmitz-Thom, Ina; Yvon, Robert; Kudla, Jörg; Wu, Hen-Ming; Cheung, Alice Y; Dinneny, José R

2018-03-05

Cells maintain integrity despite changes in their mechanical properties elicited during growth and environmental stress. How cells sense their physical state and compensate for cell-wall damage is poorly understood, particularly in plants. Here we report that FERONIA (FER), a plasma-membrane-localized receptor kinase from Arabidopsis, is necessary for the recovery of root growth after exposure to high salinity, a widespread soil stress. The extracellular domain of FER displays tandem regions of homology with malectin, an animal protein known to bind di-glucose in vitro and important for protein quality control in the endoplasmic reticulum. The presence of malectin-like domains in FER and related receptor kinases has led to widespread speculation that they interact with cell-wall polysaccharides and can potentially serve a wall-sensing function. Results reported here show that salinity causes softening of the cell wall and that FER is necessary to sense these defects. When this function is disrupted in the fer mutant, root cells explode dramatically during growth recovery. Similar defects are observed in the mur1 mutant, which disrupts pectin cross-linking. Furthermore, fer cell-wall integrity defects can be rescued by treatment with calcium and borate, which also facilitate pectin cross-linking. Sensing of these salinity-induced wall defects might therefore be a direct consequence of physical interaction between the extracellular domain of FER and pectin. FER-dependent signaling elicits cell-specific calcium transients that maintain cell-wall integrity during salt stress. These results reveal a novel extracellular toxicity of salinity, and identify FER as a sensor of damage to the pectin-associated wall. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Astragaloside IV Attenuated 3,4-Benzopyrene-Induced Abdominal Aortic Aneurysm by Ameliorating Macrophage-Mediated Inflammation.

PubMed

Wang, Jiaoni; Zhou, Yingying; Wu, Shaoze; Huang, Kaiyu; Thapa, Saroj; Tao, Luyuan; Wang, Jie; Shen, Yigen; Wang, Jinsheng; Xue, Yangjing; Ji, Kangting

2018-01-01

Abdominal aortic aneurysm (AAA), characterized by macrophage infiltration-mediated inflammation and oxidative stress, is a potentially fatal disease. Astragaloside IV (AS-IV) has been acknowledged to exhibit antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effect of AS-IV against AAA formation induced by 3,4-benzopyrene (Bap) and angiotensin II (Ang II), and to explore probable mechanisms. Results showed that AS-IV decreased AAA formation, and reduced macrophage infiltration and expression of matrix metalloproteinase. Furthermore, AS-IV abrogated Bap-/Ang II-induced NF-κB activation and oxidative stress. In vitro , AS-IV inhibition of macrophage activation and NF-κB was correlated with increased phosphorylation of phosphatidylinositol 3-kinase (PI3-K)/AKT. Together, our findings suggest that AS-IV has potential as an intervention in the formation of AAA. (1)The protective effect of Astragaloside IV (AS-IV) on abdominal aortic aneurysm (AAA) is associated with its suppressing effects on inflammation in the aortic wall.(2)AS-IV abrogated 3,4-benzopyrene (Bap)/angiotensin II (Ang II)-induced nuclear factor-κB (NF-κB) activation and oxidative stress.(3)AS-IV inhibited Bap-induced RAW264.7 macrophage cells activation by inhibiting oxidative stress and NF-κB activation through phosphatidylinositol 3-kinase (PI3-K)/AKT pathway.AS-IV is a potential preventive agent for cigarette smoking-related AAA.

Difference in hemodynamic and wall stress of ascending thoracic aortic aneurysms with bicuspid and tricuspid aortic valve

PubMed Central

Pasta, Salvatore; Rinaudo, Antonino; Luca, Angelo; Pilato, Michele; Scardulla, Cesare; Gleason, Thomas G.; Vorp, David A.

2014-01-01

The aortic dissection (AoD) of an ascending thoracic aortic aneurysm (ATAA) initiates when the hemodynamic loads exerted on the aneurysmal wall overcome the adhesive forces holding the elastic layers together. Parallel coupled, two-way fluid–structure interaction (FSI) analyses were performed on patient-specific ATAAs obtained from patients with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) to evaluate hemodynamic predictors and wall stresses imparting aneurysm enlargement and AoD. Results showed a left-handed circumferential flow with slower-moving helical pattern in the aneurysm's center for BAV ATAAs whereas a slight deviation of the blood flow toward the anterolateral region of the ascending aorta was observed for TAV ATAAs. Blood pressure and wall shear stress were found key hemodynamic predictors of aneurysm dilatation, and their dissimilarities are likely associated to the morphological anatomy of the aortic valve. We also observed discontinues, wall stresses on aneurysmal aorta, which was modeled as a composite with two elastic layers (i.e., inhomogeneity of vessel structural organization). This stress distribution was caused by differences on elastic material properties of aortic layers. Wall stress distribution suggests AoD just above sinotubular junction. Moreover, abnormal flow and lower elastic material properties that are likely intrinsic in BAV individuals render the aneurysm susceptible to the initiation of AoD. PMID:23664314

Thermal-stress analysis of IFMIF target back-wall made of reduced-activation ferritic steel and austenitic stainless steel

NASA Astrophysics Data System (ADS)

Ida, Mizuho; Chida, Teruo; Furuya, Kazuyuki; Wakai, Eiichi; Nakamura, Hiroo; Sugimoto, Masayoshi

2009-04-01

For long time operation of a liquid lithium target of the International Fusion Materials Irradiation Facility, annual replacement of a back-wall, a part of the flow channel, is planned, since the target suffers neutron damage of more than 50 dpa/fpy. Considering irradiation/activation conditions, remote weld on stainless steel 316L between a back-wall and a target assembly was employed. Furthermore, dissimilar weld between the 316L and a reduced-activation ferritic/martensitic steel F82H in the back-wall was employed. The objective of this study is to clarify structures and materials of the back-wall with acceptable thermal-stress under nuclear heating. Thermal-stress analysis was done using a code ABAQUS and data of the nuclear heating. As a result, thermal-stress in the back-wall is acceptable level, if thickness of the stress-mitigation part is more than 5 mm. With results of the analysis, necessity of material data for F82H and 316L under conditions of irradiation tests and mechanical tests are clarified.

Flow stagnation volume and abdominal aortic aneurysm growth: Insights from patient-specific computational flow dynamics of Lagrangian-coherent structures.

PubMed

Joly, Florian; Soulez, Gilles; Garcia, Damien; Lessard, Simon; Kauffmann, Claude

2018-01-01

Abdominal aortic aneurysms (AAA) are localized, commonly-occurring dilations of the aorta. When equilibrium between blood pressure (loading) and wall mechanical resistance is lost, rupture ensues, and patient death follows, if not treated immediately. Experimental and numerical analyses of flow patterns in arteries show direct correlations between wall shear stress and wall mechano-adaptation with the development of zones prone to thrombus formation. For further insights into AAA flow topology/growth interaction, a workout of patient-specific computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov exponents and extract Lagrangian-coherent structures (LCS). This computational model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI) in 5 patients. To better understand the impact of flow topology and transport on AAA growth, hyperbolic, repelling LCS were computed in 1 patient during 8-year follow-up, including 9 volumetric morphologic AAA measures by computed tomography-angiography (CTA). LCS defined barriers to Lagrangian jet cores entering AAA. Domains enclosed between LCS and the aortic wall were considered to be stagnation zones. Their evolution was studied during AAA growth. Good correlation - 2-D cross-correlation coefficients of 0.65, 0.86 and 0.082 (min, max, SD) - was obtained between numerical simulations and 4-D MRI acquisitions in 6 specific cross-sections from 4 patients. In follow-up study, LCS divided AAA lumens into 3 dynamically-isolated zones: 2 stagnation volumes lying in dilated portions of the AAA, and circulating volume connecting the inlet to the outlet. The volume of each zone was tracked over time. Although circulating volume remained unchanged during 8-year follow-up, the AAA lumen and main stagnation zones grew significantly (8 cm 3 /year and 6 cm 3 /year, respectively). This study reveals that transient transport topology can be quantified in patient-specific AAA during disease progression

Analysis of Cell Wall-Related Genes in Organs of Medicago sativa L. under Different Abiotic Stresses.

PubMed

Behr, Marc; Legay, Sylvain; Hausman, Jean-Francois; Guerriero, Gea

2015-07-16

Abiotic constraints are a source of concern in agriculture, because they can have a strong impact on plant growth and development, thereby affecting crop yield. The response of plants to abiotic constraints varies depending on the type of stress, on the species and on the organs. Although many studies have addressed different aspects of the plant response to abiotic stresses, only a handful has focused on the role of the cell wall. A targeted approach has been used here to study the expression of cell wall-related genes in different organs of alfalfa plants subjected for four days to three different abiotic stress treatments, namely salt, cold and heat stress. Genes involved in different steps of cell wall formation (cellulose biosynthesis, monolignol biosynthesis and polymerization) have been analyzed in different organs of Medicago sativa L. Prior to this analysis, an in silico classification of dirigent/dirigent-like proteins and class III peroxidases has been performed in Medicago truncatula and M. sativa. The final goal of this study is to infer and compare the expression patterns of cell wall-related genes in response to different abiotic stressors in the organs of an important legume crop.

Analysis of Cell Wall-Related Genes in Organs of Medicago sativa L. under Different Abiotic Stresses

PubMed Central

Behr, Marc; Legay, Sylvain; Hausman, Jean-Francois; Guerriero, Gea

2015-01-01

Abiotic constraints are a source of concern in agriculture, because they can have a strong impact on plant growth and development, thereby affecting crop yield. The response of plants to abiotic constraints varies depending on the type of stress, on the species and on the organs. Although many studies have addressed different aspects of the plant response to abiotic stresses, only a handful has focused on the role of the cell wall. A targeted approach has been used here to study the expression of cell wall-related genes in different organs of alfalfa plants subjected for four days to three different abiotic stress treatments, namely salt, cold and heat stress. Genes involved in different steps of cell wall formation (cellulose biosynthesis, monolignol biosynthesis and polymerization) have been analyzed in different organs of Medicago sativa L. Prior to this analysis, an in silico classification of dirigent/dirigent-like proteins and class III peroxidases has been performed in Medicago truncatula and M. sativa. The final goal of this study is to infer and compare the expression patterns of cell wall-related genes in response to different abiotic stressors in the organs of an important legume crop. PMID:26193255

Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation.

PubMed

Biasetti, Jacopo; Hussain, Fazle; Gasser, T Christian

2011-10-07

Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

Pulsatile extracorporeal circulation during on-pump cardiac surgery enhances aortic wall shear stress.

PubMed

Assmann, Alexander; Benim, Ali Cemal; Gül, Fethi; Lux, Philipp; Akhyari, Payam; Boeken, Udo; Joos, Franz; Feindt, Peter; Lichtenberg, Artur

2012-01-03

Controversy on superiority of pulsatile versus non-pulsatile extracorporeal circulation in cardiac surgery still continues. Stroke as one of the major adverse events during cardiopulmonary bypass is, in the majority of cases, caused by mobilization of aortic arteriosclerotic plaques that is inducible by pathologically elevated wall shear stress values. The present study employs computational fluid dynamics to evaluate the aortic blood flow and wall shear stress profiles under the influence of antegrade or retrograde perfusion with pulsatile versus non-pulsatile extracorporeal circulation. While, compared to physiological flow, a non-pulsatile perfusion resulted in generally decreased blood velocities and only moderately increased shear forces (48 Pa versus 20 Pa antegradely and 127 Pa versus 30 Pa retrogradely), a pulsatile perfusion extensively enhanced the occurrence of turbulences, maximum blood flow speed and maximum wall shear stress (1020 Pa versus 20 Pa antegradely and 1178 Pa versus 30 Pa retrogradely). Under these circumstances arteriosclerotic embolism has to be considered. Further simulations and experimental work are necessary to elucidate the impact of our findings on the scientific discourse of pulsatile versus non-pulsatile extracorporeal circulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Selective Intra-procedural AAA sac Embolization During EVAR Reduces the Rate of Type II Endoleak.

PubMed

Mascoli, C; Freyrie, A; Gargiulo, M; Gallitto, E; Pini, R; Faggioli, G; Serra, C; De Molo, C; Stella, A

2016-05-01

The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp. Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p < .001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p = .001, and 5/25 vs. 32/44, respectively, p < .001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p < .001). No differences in median AAA sac

The Airborne Astronomy Ambassadors (AAA) Program and NASA Astrophysics Connections

NASA Astrophysics Data System (ADS)

Backman, Dana Edward; Clark, Coral; Harman, Pamela

2018-01-01

The NASA Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content delivery, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong’s B703 science research aircraft facility in Palmdale, California, including interactions with NASA astrophysics & planetary science Subject Matter Experts (SMEs) during science flights on SOFIA, and (3) continuing post-flight opportunities for teacher & student connections with SMEs.

Orbitally shaken shallow fluid layers. II. An improved wall shear stress model

NASA Astrophysics Data System (ADS)

Alpresa, Paola; Sherwin, Spencer; Weinberg, Peter; van Reeuwijk, Maarten

2018-03-01

A new model for the analytical prediction of wall shear stress distributions at the base of orbitally shaken shallow fluid layers is developed. This model is a generalisation of the classical extended Stokes solution and will be referred to as the potential theory-Stokes model. The model is validated using a large set of numerical simulations covering a wide range of flow regimes representative of those used in laboratory experiments. It is demonstrated that the model is in much better agreement with the simulation data than the classical Stokes solution, improving the prediction in 63% of the studied cases. The central assumption of the model—which is to link the wall shear stress with the surface velocity—is shown to hold remarkably well over all regimes covered.

Structure of Lmaj006129AAA, a hypothetical protein from Leishmania major

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arakaki, Tracy; Le Trong, Isolde; Structural Genomics of Pathogenic Protozoa

2006-03-01

The crystal structure of a conserved hypothetical protein from L. major, Pfam sequence family PF04543, structural genomics target ID Lmaj006129AAA, has been determined at a resolution of 1.6 Å. The gene product of structural genomics target Lmaj006129 from Leishmania major codes for a 164-residue protein of unknown function. When SeMet expression of the full-length gene product failed, several truncation variants were created with the aid of Ginzu, a domain-prediction method. 11 truncations were selected for expression, purification and crystallization based upon secondary-structure elements and disorder. The structure of one of these variants, Lmaj006129AAH, was solved by multiple-wavelength anomalous diffraction (MAD)more » using ELVES, an automatic protein crystal structure-determination system. This model was then successfully used as a molecular-replacement probe for the parent full-length target, Lmaj006129AAA. The final structure of Lmaj006129AAA was refined to an R value of 0.185 (R{sub free} = 0.229) at 1.60 Å resolution. Structure and sequence comparisons based on Lmaj006129AAA suggest that proteins belonging to Pfam sequence families PF04543 and PF01878 may share a common ligand-binding motif.« less

Improved Resident Adherence to AAA Screening Guidelines via an Electronic Reminder.

PubMed

Sypert, David; Van Dyke, Kenneth; Dhillon, Namrata; Elliott, John O; Jordan, Kim

The 2014 United States Preventive Services Task Force systematic review found abdominal aortic aneurysm (AAA) screening decreased related mortality by close to half. Despite the simplicity of screening, research suggests poor adherence to the recommended AAA screening guidelines. Using the quality improvement plan-study-do-act cycle, we retrospectively established poor adherence to AAA screening and poor documentation of smoking history in our resident clinic. An electronic reminder was prospectively implemented into our electronic medical record (EMR) with the goal of improving screening rates. After 1 year, a retrospective chart review was conducted. Comparisons of the pre- and post-electronic reminder intervention data were made using chi-square tests and odds ratios (OR). The purposeful AAA screening rate improved 27.8% during the intervention, 40.3% (95% confidence interval [CI]: 28.6-52.0%) versus 12.5% (95% CI: 3.1-21.9%), p = .002, suggesting patients were more likely to be screened as a result of the electronic reminder, OR = 4.73 (95% CI: 1.77-12.65). This improvement translates to a large effect size, Cohen's d = 0.86 (95% CI: 0.31-1.40). Electronic reminders are a simple EMR addition that can provide evidence-based education while improving adherence rates with preventive health screening measures.

Relationships of left ventricular strain and strain rate to wall stress and their afterload dependency.

PubMed

Murai, Daisuke; Yamada, Satoshi; Hayashi, Taichi; Okada, Kazunori; Nishino, Hisao; Nakabachi, Masahiro; Yokoyama, Shinobu; Abe, Ayumu; Ichikawa, Ayako; Ono, Kota; Kaga, Sanae; Iwano, Hiroyuki; Mikami, Taisei; Tsutsui, Hiroyuki

2017-05-01

Whether and how left ventricular (LV) strain and strain rate correlate with wall stress is not known. Furthermore, it is not determined whether strain or strain rate is less dependent on the afterload. In 41 healthy young adults, LV global peak strain and systolic peak strain rate in the longitudinal direction (LS and LSR, respectively) and circumferential direction (CS and CSR, respectively) were measured layer-specifically using speckle tracking echocardiography (STE) before and during a handgrip exercise. Among all the points before and during the exercise, all the STE parameters significantly correlated linearly with wall stress (LS: r = -0.53, p < 0.01, LSR: r = -0.28, p < 0.05, CS in the inner layer: r = -0.72, p < 0.01, CSR in the inner layer: r = -0.47, p < 0.01). Strain more strongly correlated with wall stress than strain rate (r = -0.53 for LS vs. r = -0.28 for LSR, p < 0.05; r = -0.72 for CS vs. r = -0.47 for CSR in the inner layer, p < 0.05), whereas the interobserver variability was similar between strain and strain rate (longitudinal 6.2 vs. 5.2 %, inner circumferential 4.8 vs. 4.7 %, mid-circumferential 7.9 vs. 6.9 %, outer circumferential 10.4 vs. 9.7 %), indicating that the differences in correlation coefficients reflect those in afterload dependency. It was thus concluded that LV strain and strain rate linearly and inversely correlated with wall stress in the longitudinal and circumferential directions, and strain more strongly depended on afterload than did strain rate. Myocardial shortening should be evaluated based on the relationships between these parameters and wall stress.

Persistent type II endoleak after EVAR: the predictive value of the AAA thrombus volume.

PubMed

Gallitto, Enrico; Gargiulo, Mauro; Mascoli, Chiara; Freyrie, Antonio; DE Matteis, Massimo; Serra, Carla; Bianchini Massoni, Claudio; Faggioli, Gianluca; Stella, Andrea

2018-02-01

Persistent type II endoleaks (ELIIp, ≥6 months) after an endovascular aneurysm repair (EVAR) can be associated with adverse outcomes. The aims of this study are the evaluation of the incidence of ELIIp, their preoperative morphological predictive features (PMF) and the post-EVAR abdominal aortic aneurysm (AAA) evolution in the presence of ELIIp. Patients underwent EVAR between 2008 and 2010 were prospectively collected. Cases with ELIIp (group A: AG) were identified. A control group without ELIIp (group B: BG), homogeneous for clinical characteristics, follow-up timing and methods (CTA and/or CEUS at 6.12 months and yearly thereafter) was retrospectively selected. The PMF evaluated by computed-tomography-angiography (CTA) were: AAA-diameter, number and diameter of AAA efferent patent vessels (EPV), AAA-total volume (TV), AAA-thrombus volume (THV) and TV/THV rate (%VR). Volumes were calculated by the dedicated vessels analysis software. AG and BG were compared. The primary endpoint was to evaluate the incidence of ELIIp. Secondary endpoints were to analyze the relation between PMF and ELIIp and to assess the post-EVAR AAA-evolution in the presence of ELIIp. Between 2008 and 2010, 200 patients underwent EVAR to treat AAA electively. An ELIIp was detected in 35cases (17.5%) (AG). Twenty-seven patients (13.5%) were included in BG. An overall of 62 patients (GA+GB) were analyzed. The mean pre-operative AAA diameter and EPV were 58±11.6 mm and 5.5±1.8 mm, respectively. The mean TV and THV were 187±111.5 cc and 82±75 cc, respectively. The median %VR was 42.3%. ELIIp was correlated to EPV≥6 (χ2, p=.015) and %VR <40% (logistic regression, P=0.032). The mean follow-up was 22±9 months. Seven (20%) ELIIp spontaneously sealed and 6 (17%) required reinterventions (2 conversions to OR). There were not PMF associated to ELIIp evolution and AAA growth post-EVAR. ELIIp is a not rare complication and it could require re-interventions. Our data suggest that VEP≥6 or %VT<40

Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

PubMed

Dunne, Jonathan A; Bailey, Marc A; Griffin, Kathryn J; Sohrabi, Soroush; Coughlin, Patrick A; Scott, D Julian A

2014-01-01

In the era of Abdominal Aortic Aneurysm (AAA) screening, pharmacotherapies to attenuate AAA growth are sought. HMG Co-A reductase inhibitors (statins) have pleiotropic actions independent of their lipid lowering effects and have been suggested as potential treatment for small AAAs. We systematically review the clinical evidence for this effect. Medline, EMBASE and the Cochrane Central Register of Controlled Trials (1950-2011) were searched for studies reporting data on the role of statin therapy on AAA growth rate. No language restrictions were placed on the search. References of retrieved articles and pertinent journals were hand searched. Included studies were reviewed by 2 independent observers. The search retrieved 164 papers, 100 were irrelevant based on their title, 47 were reviews and 1 was a letter. 8 studies were excluded based on review of their abstract leaving 8 for inclusion in the study. Eight observational clinical studies with a total of 4,466 patients were reviewed. Four studies demonstrated reduced AAA expansion in statin users while 4 studies failed to demonstrate this effect. The method of determining AAA growth rates varied significantly between the studies and the ability of many studies to control for misclassification bias was poor. The claim that statins attenuate AAA growth remains questionable. Further prospective studies with stringent identification and verification of statin usage and a standardised method of estimating AAA growth rates are required. Statin type and dose also merit consideration.

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

PubMed Central

Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

2013-01-01

Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

Prevalence of abdominal aortic aneurysm (AAA) in a population undergoing computed tomography colonography in Canterbury, New Zealand.

PubMed

Khashram, M; Jones, G T; Roake, J A

2015-08-01

There is compelling level 1 evidence in support of screening men for abdominal aortic aneurysm (AAA) to reduce AAA mortality. However, New Zealand (NZ) lacks data on AAA prevalence, and national screening has not been implemented. The aim of this study was to determine the prevalence of AAA in a population undergoing a computed tomography colonography (CTC) for gastrointestinal symptoms. This was an observational study; all consecutive CTCs performed in three regions of the South Island of NZ over a 4 year period were reviewed. Data on abdominal and thoracic aorta diameters ≥30 mm, and iliac and femoral aneurysms ≥20 mm were recorded. Previous aortic surgical grafts or endovascular stents were also documented. Demographics, survival, and AAA related outcomes were collected and used for analysis. Included were 4,893 scans on 4,644 patients (1,933 men [41.6%], 2,711 women [58.4%]) with a median age of 69.3 years (range 17.0-97.0 years). There were 309 scans on 289 patients (75.4% men) who had either an aneurysm or a previous aortic graft with a median age of 79.6 years (range 57.0-96.0 years). Of these, 223 had a native AAA ≥30 mm. The prevalence of AAA rose with age from 1.3% in men aged 55-64 years, to 9.1% in 65-74 year olds, 16.8% in 75-84 year olds, and 22.0% in ≥85 year olds. The corresponding figures in women were 0.4%, 2%, 3.9%, and 6.2%, respectively. In this observational study, the prevalence of AAA was high and warrants further evaluation. The results acquired help to define a population that may benefit from a national AAA screening programme. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Cell wall pectic arabinans influence the mechanical properties of Arabidopsis thaliana inflorescence stems and their response to mechanical stress.

PubMed

Verhertbruggen, Yves; Marcus, Susan E; Chen, Jianshe; Knox, J Paul

2013-08-01

Little is known of the dynamics of plant cell wall matrix polysaccharides in response to the impact of mechanical stress on plant organs. The capacity of the imposition of a mechanical stress (periodic brushing) to reduce the height of the inflorescence stem of Arabidopsis thaliana seedlings has been used to study the role of pectic arabinans in the mechanical properties and stress responsiveness of a plant organ. The arabinan-deficient-1 (arad1) mutation that affects arabinan structures in epidermal cell walls of inflorescence stems is demonstrated to reduce the impact on inflorescence stem heights caused by mechanical stress. The arabinan-deficient-2 (arad2) mutation, that does not have detectable impact on arabinan structures, is also shown to reduce the impact on stem heights caused by mechanical stress. The LM13 linear arabinan epitope is specifically detected in epidermal cell walls of the younger, flexible regions of inflorescence stems and increases in abundance at the base of inflorescence stems in response to an imposed mechanical stress. The strain (percentage deformation) of stem epidermal cells in the double mutant arad1 × arad2 is lower in unbrushed plants than in wild-type plants, but rises to wild-type levels in response to brushing. The study demonstrates the complexity of arabinan structures within plant cell walls and also that their contribution to cell wall mechanical properties is a factor influencing responsiveness to mechanical stress.

Peak AAA fatty acid homolog contaminants present in the dietary supplement l-Tryptophan associated with the onset of eosinophilia-myalgia syndrome.

PubMed

Klarskov, Klaus; Gagnon, Hugo; Racine, Mathieu; Boudreault, Pierre-Luc; Normandin, Chad; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

2018-05-22

The eosinophilia-myalgia syndrome (EMS) outbreak that occurred in the USA and elsewhere in 1989 was caused by the ingestion of Showa Denko K.K. (SD) L-tryptophan (L-Trp). "Six compounds" detected in the L-Trp were reported as case-associated contaminants. Recently the final and most statistically significant contaminant, "Peak AAA" was structurally characterized. The "compound" was actually shown to be two structural isomers resulting from condensation reactions of L-Trp with fatty acids derived from the bacterial cell membrane. They were identified as the indole C-2 anteiso (AAA 1 -343) and linear (AAA 2 -343) aliphatic chain isomers. Based on those findings, we utilized a combination of on-line HPLC-electrospray ionization mass spectrometry (LC-MS), as well as both precursor and product ion tandem mass spectrometry (MS/MS) to facilitate identification of a homologous family of condensation products related to AAA 1 -343 and AAA 2 -343. We structurally characterized eight new AAA 1 -XXX/AAA 2 -XXX contaminants, where XXX represents the integer molecular ions of all the related homologs, differing by aliphatic chain length and isomer configuration. The contaminants were derived from the following fatty acids of the bacterial cell membrane, 5-methylheptanoic acid (anteiso-C8:0) for AAA 1 -315; n-octanoic acid (n-C8:0) for AAA 2 -315; 6-methyloctanoic acid (anteiso-C9:0) for AAA 1 -329; n-nonanoic acid (n-C9:0) for AAA 2 -329; 10-methyldodecanoic acid (anteiso-C13:0) for AAA 1 -385; n-tridecanoic acid (n-C13:0) for AAA 2 -385; 11-methyltridecanoic acid (anteiso-C14:0) for AAA 1 -399; and n-tetradecanoic acid (n-C14:0) for AAA 2 -399. The concentration levels for these contaminants were estimated to be 0.1-7.9 μg / 500 mg of an individual SD L-Trp tablet or capsule The structural similarity of these homologs to case-related contaminants of Spanish Toxic Oil Syndrome (TOS) is discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Multibands tunneling in AAA-stacked trilayer graphene

NASA Astrophysics Data System (ADS)

Redouani, Ilham; Jellal, Ahmed; Bahaoui, Abdelhadi; Bahlouli, Hocine

2018-04-01

We study the electronic transport through np and npn junctions for AAA-stacked trilayer graphene. Two kinds of gates are considered where the first is a single gate and the second is a double gate. After obtaining the solutions for the energy spectrum, we use the transfer matrix method to determine the three transmission probabilities for each individual cone τ = 0 , ± 1 . We show that the quasiparticles in AAA-stacked trilayer graphene are not only chiral but also labeled by an additional cone index τ. The obtained bands are composed of three Dirac cones that depend on the chirality indexes. We show that there is perfect transmission for normal or near normal incidence, which is a manifestation of the Klein tunneling effect. We analyze also the corresponding total conductance, which is defined as the sum of the conductance channels in each individual cone. Our results are numerically discussed and compared with those obtained for ABA- and ABC-stacked trilayer graphene.

SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA Algorithms.

PubMed

Yuan, Y; Duan, J; Popple, R; Brezovich, I

2012-06-01

To evaluate the accuracy of dose calculation for intensity modulated radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic Algorithm (AAA) computation algorithms. IMRT plans of twelve patients with different treatment sites, including head/neck, lung and pelvis, were investigated. For each patient, dose calculation with PB and AAA algorithms using dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite-beam ion chamber and film measurements in patient specific QA. Discrepancies between the calculation and the measurement were evaluated by percentage error for ion chamber dose and γ〉l failure rate in gamma analysis (3%/3mm) for film dosimetry. For 9 patients, ion chamber dose calculated with AAA-algorithms is closer to ion chamber measurement than that calculated with PB algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are within 3% of the measurements. For head/neck patients and other patients with large treatment volumes, γ〉l failure rate is significantly reduced (within 5%) with AAA-based treatment planning compared to generally more than 10% with PB-based treatment planning (grid size=2.5 mm). For lung and brain cancer patients with medium and small treatment volumes, γ〉l failure rates are typically within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For both PB and AAA-based treatment planning, improvements of dose calculation accuracy with finer dose grids were observed in film dosimetry of 11 patients and in ion chamber measurements for 3 patients. AAA-based treatment planning provides more accurate dose calculation for head/neck patients and other patients with large treatment volumes. Compared with film dosimetry, a γ〉l failure rate within 5% can be achieved for AAA-based treatment planning. © 2012 American Association of Physicists in Medicine.

Histology and Biaxial Mechanical Behavior of Abdominal Aortic Aneurysm Tissue Samples.

PubMed

Pancheri, Francesco Q; Peattie, Robert A; Reddy, Nithin D; Ahamed, Touhid; Lin, Wenjian; Ouellette, Timothy D; Iafrati, Mark D; Luis Dorfmann, A

2017-03-01

Abdominal aortic aneurysms (AAAs) represent permanent, localized dilations of the abdominal aorta that can be life-threatening if progressing to rupture. Evaluation of risk of rupture depends on understanding the mechanical behavior of patient AAA walls. In this project, a series of patient AAA wall tissue samples have been evaluated through a combined anamnestic, mechanical, and histopathologic approach. Mechanical properties of the samples have been characterized using a novel, strain-controlled, planar biaxial testing protocol emulating the in vivo deformation of the aorta. Histologically, the tissue ultrastructure was highly disrupted. All samples showed pronounced mechanical stiffening with stretch and were notably anisotropic, with greater stiffness in the circumferential than the axial direction. However, there were significant intrapatient variations in wall stiffness and stress. In biaxial tests in which the longitudinal stretch was held constant at 1.1 as the circumferential stretch was extended to 1.1, the maximum average circumferential stress was 330 ± 70 kPa, while the maximum average axial stress was 190 ± 30 kPa. A constitutive model considering the wall as anisotropic with two preferred directions fit the measured data well. No statistically significant differences in tissue mechanical properties were found based on patient gender, age, maximum bulge diameter, height, weight, body mass index, or smoking history. Although a larger patient cohort is merited to confirm these conclusions, the project provides new insight into the relationships between patient natural history, histopathology, and mechanical behavior that may be useful in the development of accurate methods for rupture risk evaluation.

Structural Insights into the Allosteric Operation of the Lon AAA+ Protease.

PubMed

Lin, Chien-Chu; Su, Shih-Chieh; Su, Ming-Yuan; Liang, Pi-Hui; Feng, Chia-Cheng; Wu, Shih-Hsiung; Chang, Chung-I

2016-05-03

The Lon AAA+ protease (LonA) is an evolutionarily conserved protease that couples the ATPase cycle into motion to drive substrate translocation and degradation. A hallmark feature shared by AAA+ proteases is the stimulation of ATPase activity by substrates. Here we report the structure of LonA bound to three ADPs, revealing the first AAA+ protease assembly where the six protomers are arranged alternately in nucleotide-free and bound states. Nucleotide binding induces large coordinated movements of conserved pore loops from two pairs of three non-adjacent protomers and shuttling of the proteolytic groove between the ATPase site and a previously unknown Arg paddle. Structural and biochemical evidence supports the roles of the substrate-bound proteolytic groove in allosteric stimulation of ATPase activity and the conserved Arg paddle in driving substrate degradation. Altogether, this work provides a molecular framework for understanding how ATP-dependent chemomechanical movements drive allosteric processes for substrate degradation in a major protein-destruction machine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantification of wall shear stress in large blood vessels using Lagrangian interpolation functions with cine phase-contrast magnetic resonance imaging.

PubMed

Cheng, Christopher P; Parker, David; Taylor, Charles A

2002-09-01

Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm2, respectively.

Wall shear stress characterization of a 3D bluff-body separated flow

NASA Astrophysics Data System (ADS)

Fourrié, Grégoire; Keirsbulck, Laurent; Labraga, Larbi

2013-10-01

Efficient flow control strategies aimed at reducing the aerodynamic drag of road vehicles require a detailed knowledge of the reference flow. In this work, the flow around the rear slanted window of a generic car model was experimentally studied through wall shear stress measurements using an electrochemical method. The mean and fluctuating wall shear stress within the wall impact regions of the recirculation bubble and the main longitudinal vortex structures which develop above the rear window are presented. Correlations allow a more detailed characterization of the recirculation phenomenon within the separation bubble. In the model symmetry plane the recirculation structure compares well with simpler 2D configurations; specific lengths, flapping motion and shedding of large-scale vortices are observed, these similarities diminish when leaving the middle plane due to the strong three-dimensionality of the flow. A specific attention is paid to the convection processes occurring within the recirculation: a downstream convection velocity is observed, in accordance with 2D recirculations from the literature, and an upstream convection is highlighted along the entire bubble length which has not been underlined in some previous canonical configurations.

Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair

PubMed Central

Bhat, Javaid Y.; Thieulin-Pardo, Gabriel; Hartl, F. Ulrich; Hayer-Hartl, Manajit

2017-01-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO2 molecule and binding of a Mg2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are “misfire” products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins. PMID:28443288

Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair.

PubMed

Bhat, Javaid Y; Thieulin-Pardo, Gabriel; Hartl, F Ulrich; Hayer-Hartl, Manajit

2017-01-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO 2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO 2 molecule and binding of a Mg 2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are "misfire" products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins.

Reynolds stress closure modeling in wall-bounded flows

NASA Technical Reports Server (NTRS)

Durbin, Paul A.

1993-01-01

This report describes two projects. Firstly, a Reynolds stress closure for near-wall turbulence is described. It was motivated by the simpler k-epsilon-(v-bar(exp 2)) model described in last year's annual research brief. Direct Numerical Simulation of three-dimensional channel flow shows a curious decrease of the turbulent kinetic energy. The second topic of this report is a model which reproduces this effect. That model is described and used to discuss the relevance of the three dimensional channel flow simulation to swept wing boundary layers.

National dosimetric audit network finds discrepancies in AAA lung inhomogeneity corrections.

PubMed

Dunn, Leon; Lehmann, Joerg; Lye, Jessica; Kenny, John; Kron, Tomas; Alves, Andrew; Cole, Andrew; Zifodya, Jackson; Williams, Ivan

2015-07-01

This work presents the Australian Clinical Dosimetry Service's (ACDS) findings of an investigation of systematic discrepancies between treatment planning system (TPS) calculated and measured audit doses. Specifically, a comparison between the Anisotropic Analytic Algorithm (AAA) and other common dose-calculation algorithms in regions downstream (≥2cm) from low-density material in anthropomorphic and slab phantom geometries is presented. Two measurement setups involving rectilinear slab-phantoms (ACDS Level II audit) and anthropomorphic geometries (ACDS Level III audit) were used in conjunction with ion chamber (planar 2D array and Farmer-type) measurements. Measured doses were compared to calculated doses for a variety of cases, with and without the presence of inhomogeneities and beam-modifiers in 71 audits. Results demonstrate a systematic AAA underdose with an average discrepancy of 2.9 ± 1.2% when the AAA algorithm is implemented in regions distal from lung-tissue interfaces, when lateral beams are used with anthropomorphic phantoms. This systemic discrepancy was found for all Level III audits of facilities using the AAA algorithm. This discrepancy is not seen when identical measurements are compared for other common dose-calculation algorithms (average discrepancy -0.4 ± 1.7%), including the Acuros XB algorithm also available with the Eclipse TPS. For slab phantom geometries (Level II audits), with similar measurement points downstream from inhomogeneities this discrepancy is also not seen. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Wall shear stress fixed points in cardiovascular fluid mechanics.

PubMed

Arzani, Amirhossein; Shadden, Shawn C

2018-05-17

Complex blood flow in large arteries creates rich wall shear stress (WSS) vectorial features. WSS acts as a link between blood flow dynamics and the biology of various cardiovascular diseases. WSS has been of great interest in a wide range of studies and has been the most popular measure to correlate blood flow to cardiovascular disease. Recent studies have emphasized different vectorial features of WSS. However, fixed points in the WSS vector field have not received much attention. A WSS fixed point is a point on the vessel wall where the WSS vector vanishes. In this article, WSS fixed points are classified and the aspects by which they could influence cardiovascular disease are reviewed. First, the connection between WSS fixed points and the flow topology away from the vessel wall is discussed. Second, the potential role of time-averaged WSS fixed points in biochemical mass transport is demonstrated using the recent concept of Lagrangian WSS structures. Finally, simple measures are proposed to quantify the exposure of the endothelial cells to WSS fixed points. Examples from various arterial flow applications are demonstrated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Polar nature of stress-induced twin walls in ferroelastic CaTiO3

NASA Astrophysics Data System (ADS)

Yokota, H.; Niki, S.; Haumont, R.; Hicher, P.; Uesu, Y.

2017-08-01

A compressive uniaxial mechanical stress is applied on ferroelastic CaTiO3 (CTO), and a change in the domain structure is observed under a polarization microscope and a second harmonic generation (SHG) microscope. New twin walls (TWs) appear perpendicular to the original TWs under stress. The SHG microscope observations and analyses confirm that this type of stress-induced TWs is polar, similar to the original TWs, and is crystallographically prominent with monoclinic symmetry m. A quantitative estimation of this stress-induced effect reveals that CTO is hard ferroelastic in the sense that the TW movement requires a large stress. A possible application of this phenomenon is discussed.

Impact of Wall Shear Stress and Pressure Variation on the Stability of Atherosclerotic Plaque

NASA Astrophysics Data System (ADS)

Taviani, V.; Li, Z. Y.; Sutcliffe, M.; Gillard, J.

Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady and unsteady conditions assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding one dimensional models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed linearly elastic, homogeneous isotropic. The analysis showed that wall shear stress is small (less than 3.5%) with respect to pressure drop throughout the cycle even for severe stenosis. On the contrary, the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by one dimensional models. This suggests that the primary source of mistakes in one dimensional studies comes from neglecting the three dimensional geometry of the plaque. Neglecting axial forces only involves minor errors.

Analysis of a Typical Chinese High School Biology Textbook Using the AAAS Textbook Standards

ERIC Educational Resources Information Center

Liang, Ye; Cobern, William W.

2013-01-01

The purpose of this study was to evaluate a typical Chinese high school biology textbook using the textbook standards of the American Association for the Advancement of Science (AAAS). The data were composed of three chapters selected from the textbook. Each chapter was analyzed and rated using the AAAS textbook standards. Pearson correlations…

SOFIA Technology: The NASA Airborne Astronomy Ambassador (AAA) Experience and Online Resources

NASA Astrophysics Data System (ADS)

Clark, C.; Harman, P. K.; Backman, D. E.

2016-12-01

SOFIA, an 80/20 partnership of NASA and the German Aerospace Center (DLR), consists of a modified Boeing 747SP carrying a reflecting telescope with an effective diameter of 2.5 meters. SOFIA is the largest airborne observatory in the world, capable of observations impossible for even the largest and highest ground-based telescopes. The SOFIA Program Office is at NASA ARC, Moffett Field, CA; the aircraft is based in Palmdale, CA. During its planned 20-year lifetime, SOFIA will foster development of new scientific instrumentation and inspire the education of young scientists and engineers. Astrophysicists are awarded time on SOFIA to study many kinds of astronomical objects and phenomena. Among the most interesting are: Star birth, evolution, and death Formation of new planetary systems Chemistry of complex molecules in space Planet and exoplanet atmospheres Galactic gas & dust "ecosystems" Environments around supermassive black holes SOFIA currently has eight instruments, five US-made and three German. The instruments — cameras, spectrometers, and a photometer,— operate at near-, mid- and far-infrared wavelengths, each spectral range being best suited to studying particular celestial phenomena. NASA's Airborne Astronomy Ambassadors' (AAAs) experience includes a STEM immersion component. AAAs are onboard during two overnight SOFIA flights that provide insight into the acquisition of scientific data as well as the interfaces between the telescope, instrument, & aircraft. AAAs monitor system performance and view observation targets from their dedicated workstation during flights. Future opportunities for school district partnerships leading to selection of future AAA cohorts will be offered in 2018-19. AAAs may access public archive data via the SOFIA Data Cycle System (DCS) https://dcs.sofia.usra.edu/. Additional SOFIA science and other resources are available at: www.sofia.usra.edu, including lessons that use photovoltaic circuits, and other technology for the

Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

PubMed

Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

2017-07-24

This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (p<0.05). AAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging

NASA Astrophysics Data System (ADS)

Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter

2017-06-01

Abdominal aortic aneurysms (AAA) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term AAA rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of AAA development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without AAA, and AAA patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the AAA group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and AAA patients is a promising step towards a new method for in vivo assessment of AAA wall strength or stratification of AAA rupture risk as basis for improved clinical decision making on surgical or endovascular

Clinical implementation of AXB from AAA for breast: Plan quality and subvolume analysis.

PubMed

Guebert, Alexandra; Conroy, Leigh; Weppler, Sarah; Alghamdi, Majed; Conway, Jessica; Harper, Lindsay; Phan, Tien; Olivotto, Ivo A; Smith, Wendy L; Quirk, Sarah

2018-05-01

Two dose calculation algorithms are available in Varian Eclipse software: Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB). Many Varian Eclipse-based centers have access to AXB; however, a thorough understanding of how it will affect plan characteristics and, subsequently, clinical practice is necessary prior to implementation. We characterized the difference in breast plan quality between AXB and AAA for dissemination to clinicians during implementation. Locoregional irradiation plans were created with AAA for 30 breast cancer patients with a prescription dose of 50 Gy to the breast and 45 Gy to the regional node, in 25 fractions. The internal mammary chain (IMC CTV ) nodes were covered by 80% of the breast dose. AXB, both dose-to-water and dose-to-medium reporting, was used to recalculate plans while maintaining constant monitor units. Target coverage and organ-at-risk doses were compared between the two algorithms using dose-volume parameters. An analysis to assess location-specific changes was performed by dividing the breast into nine subvolumes in the superior-inferior and left-right directions. There were minimal differences found between the AXB and AAA calculated plans. The median difference between AXB and AAA for breast CTV V 95% , was <2.5%. For IMC CTV , the median differences V 95% , and V 80% were <5% and 0%, respectively; indicating IMC CTV coverage only decreased when marginally covered. Mean superficial dose increased by a median of 3.2 Gy. In the subvolume analysis, the medial subvolumes were "hotter" when recalculated with AXB and the lateral subvolumes "cooler" with AXB; however, all differences were within 2 Gy. We observed minimal difference in magnitude and spatial distribution of dose when comparing the two algorithms. The largest observable differences occurred in superficial dose regions. Therefore, clinical implementation of AXB from AAA for breast radiotherapy is not expected to result in changes in clinical

The impact of wall shear stress and pressure drop on the stability of the atherosclerotic plaque.

PubMed

Li, Zhi-Yong; Taviani, Valentina; Gillard, Jonathan H

2008-01-01

Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady state conditions and unsteady conditions by assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding 2D cross-section structural models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed hyperelastic, homogeneous, isotropic and incompressible. The analysis showed that the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by cross-section models. Pressure drop across the stenosis was found to be much higher than shear stress. Therefore, pressure may be the more important mechanical trigger for plaque rupture other than shear stress, although shear stress is closely related to plaque formation and progression.

The major-effect quantitative trait locus CsARN6.1 encodes an AAA ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation.

PubMed

Xu, Xuewen; Ji, Jing; Xu, Qiang; Qi, Xiaohua; Weng, Yiqun; Chen, Xuehao

2018-03-01

In plants, the formation of hypocotyl-derived adventitious roots (ARs) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole-genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL, ARN6.1, that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that CsARN6.1 is the most possible candidate for ARN6.1 which encodes an AAA ATPase. The increased formation of ARs under waterlogging in Zaoer-N could be attributed to a non-synonymous SNP in the coiled-coil domain region of this gene. CsARN6.1 increases the number of ARs via its ATPase activity. Ectopic expression of CsARN6.1 in Arabidopsis resulted in better rooting ability and lateral root development in transgenic plants. Transgenic cucumber expressing the CsARN6.1 Asp allele from Zaoer-N exhibited a significant increase in number of ARs compared with the wild type expressing the allele from Pepino under waterlogging conditions. Taken together, these data support that the AAA ATPase gene CsARN6.1 has an important role in increasing cucumber AR formation and waterlogging tolerance. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Sustained expression of MCP-1 by low wall shear stress loading concomitant with turbulent flow on endothelial cells of intracranial aneurysm.

PubMed

Aoki, Tomohiro; Yamamoto, Kimiko; Fukuda, Miyuki; Shimogonya, Yuji; Fukuda, Shunichi; Narumiya, Shuh

2016-05-09

Enlargement of a pre-existing intracranial aneurysm is a well-established risk factor of rupture. Excessive low wall shear stress concomitant with turbulent flow in the dome of an aneurysm may contribute to progression and rupture. However, how stress conditions regulate enlargement of a pre-existing aneurysm remains to be elucidated. Wall shear stress was calculated with 3D-computational fluid dynamics simulation using three cases of unruptured intracranial aneurysm. The resulting value, 0.017 Pa at the dome, was much lower than that in the parent artery. We loaded wall shear stress corresponding to the value and also turbulent flow to the primary culture of endothelial cells. We then obtained gene expression profiles by RNA sequence analysis. RNA sequence analysis detected hundreds of differentially expressed genes among groups. Gene ontology and pathway analysis identified signaling related with cell division/proliferation as overrepresented in the low wall shear stress-loaded group, which was further augmented by the addition of turbulent flow. Moreover, expression of some chemoattractants for inflammatory cells, including MCP-1, was upregulated under low wall shear stress with concomitant turbulent flow. We further examined the temporal sequence of expressions of factors identified in an in vitro study using a rat model. No proliferative cells were detected, but MCP-1 expression was induced and sustained in the endothelial cell layer. Low wall shear stress concomitant with turbulent flow contributes to sustained expression of MCP-1 in endothelial cells and presumably plays a role in facilitating macrophage infiltration and exacerbating inflammation, which leads to enlargement or rupture.

Introducing AAA-MS, a rapid and sensitive method for amino acid analysis using isotope dilution and high-resolution mass spectrometry.

PubMed

Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Dupierris, Véronique; Couté, Yohann; Bruley, Christophe; Garin, Jérôme; Dupuis, Alain; Jaquinod, Michel; Brun, Virginie

2012-07-06

Accurate quantification of pure peptides and proteins is essential for biotechnology, clinical chemistry, proteomics, and systems biology. The reference method to quantify peptides and proteins is amino acid analysis (AAA). This consists of an acidic hydrolysis followed by chromatographic separation and spectrophotometric detection of amino acids. Although widely used, this method displays some limitations, in particular the need for large amounts of starting material. Driven by the need to quantify isotope-dilution standards used for absolute quantitative proteomics, particularly stable isotope-labeled (SIL) peptides and PSAQ proteins, we developed a new AAA assay (AAA-MS). This method requires neither derivatization nor chromatographic separation of amino acids. It is based on rapid microwave-assisted acidic hydrolysis followed by high-resolution mass spectrometry analysis of amino acids. Quantification is performed by comparing MS signals from labeled amino acids (SIL peptide- and PSAQ-derived) with those of unlabeled amino acids originating from co-hydrolyzed NIST standard reference materials. For both SIL peptides and PSAQ standards, AAA-MS quantification results were consistent with classical AAA measurements. Compared to AAA assay, AAA-MS was much faster and was 100-fold more sensitive for peptide and protein quantification. Finally, thanks to the development of a labeled protein standard, we also extended AAA-MS analysis to the quantification of unlabeled proteins.

Ion Transport and Precipitation Kinetics as Key Aspects of Stress Generation on Pore Walls Induced by Salt Crystallization

NASA Astrophysics Data System (ADS)

Naillon, A.; Joseph, P.; Prat, M.

2018-01-01

The stress generation on pore walls due to the growth of a sodium chloride crystal in a confined aqueous solution is studied from evaporation experiments in microfluidic channels in conjunction with numerical computations of crystal growth. The study indicates that the stress buildup on the pore walls is a highly transient process taking place over a very short period of time (in less than 1 s in our experiments). The analysis makes clear that what matters for the stress generation is not the maximum supersaturation at the onset of the crystal growth but the supersaturation at the interface between the solution and the crystal when the latter is about to be confined between the pore walls. The stress generation is summarized in a simple stress diagram involving the pore aspect ratio and the Damkhöler number characterizing the competition between the precipitation reaction kinetics and the ion transport towards the growing crystal. This opens up the route for a better understanding of the damage of porous materials induced by salt crystallization, an important issue in Earth sciences, reservoir engineering, and civil engineering.

Interaction between a normal shock wave and a turbulent boundary layer at high transonic speeds. Part 2: Wall shear stress

NASA Technical Reports Server (NTRS)

Liou, M. S.; Adamson, T. C., Jr.

1979-01-01

An analysis is presented of the flow in the two inner layers, the Reynolds stress sublayer and the wall layer. Included is the calculation of the shear stress at the wall in the interaction region. The limit processes considered are those used for an inviscid flow.

Molecular insights into the m-AAA protease-mediated dislocation of transmembrane helices in the mitochondrial inner membrane.

PubMed

Lee, Seoeun; Lee, Hunsang; Yoo, Suji; Kim, Hyun

2017-12-08

Protein complexes involved in respiration, ATP synthesis, and protein import reside in the mitochondrial inner membrane; thus, proper regulation of these proteins is essential for cell viability. The m -AAA protease, a conserved hetero-hexameric AAA (ATPase associated with diverse cellular activities) protease, composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates the dislocation of membrane-embedded substrates, including foreign transmembrane (TM) segments, but the molecular mechanism involved in these processes remains elusive. This study investigated the role of the TM domains in the m -AAA protease by systematic replacement of one TM domain at a time in yeast. Our data indicated that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs membrane dislocation for all tested substrates, suggesting different roles of the TM domains in each m -AAA protease subunit. Furthermore, m -AAA protease-mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate. This finding suggested that the m -AAA protease cannot dislocate large hydrophilic domains across the membrane, indicating that the membrane dislocation probably occurs in a lipid environment. In summary, this study highlights previously underappreciated biological roles of TM domains of the m -AAA proteases in mediating the recognition and dislocation of membrane-embedded substrates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Time-Resolved Particle Image Velocimetry Measurements with Wall Shear Stress and Uncertainty Quantification for the FDA Nozzle Model.

PubMed

Raben, Jaime S; Hariharan, Prasanna; Robinson, Ronald; Malinauskas, Richard; Vlachos, Pavlos P

2016-03-01

We present advanced particle image velocimetry (PIV) processing, post-processing, and uncertainty estimation techniques to support the validation of computational fluid dynamics analyses of medical devices. This work is an extension of a previous FDA-sponsored multi-laboratory study, which used a medical device mimicking geometry referred to as the FDA benchmark nozzle model. Experimental measurements were performed using time-resolved PIV at five overlapping regions of the model for Reynolds numbers in the nozzle throat of 500, 2000, 5000, and 8000. Images included a twofold increase in spatial resolution in comparison to the previous study. Data was processed using ensemble correlation, dynamic range enhancement, and phase correlations to increase signal-to-noise ratios and measurement accuracy, and to resolve flow regions with large velocity ranges and gradients, which is typical of many blood-contacting medical devices. Parameters relevant to device safety, including shear stress at the wall and in bulk flow, were computed using radial basis functions. In addition, in-field spatially resolved pressure distributions, Reynolds stresses, and energy dissipation rates were computed from PIV measurements. Velocity measurement uncertainty was estimated directly from the PIV correlation plane, and uncertainty analysis for wall shear stress at each measurement location was performed using a Monte Carlo model. Local velocity uncertainty varied greatly and depended largely on local conditions such as particle seeding, velocity gradients, and particle displacements. Uncertainty in low velocity regions in the sudden expansion section of the nozzle was greatly reduced by over an order of magnitude when dynamic range enhancement was applied. Wall shear stress uncertainty was dominated by uncertainty contributions from velocity estimations, which were shown to account for 90-99% of the total uncertainty. This study provides advancements in the PIV processing methodologies over

SU-F-T-609: Impact of Dosimetric Variation for Prescription Dose Using Analytical Anisotropic Algorithm (AAA) in Lung SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawai, D; Takahashi, R; Kamima, T

Purpose: Actual irradiated prescription dose to patients cannot be verified. Thus, independent dose verification and second treatment planning system are used as the secondary check. AAA dose calculation engine has contributed to lung SBRT. We conducted a multi-institutional study to assess variation of prescription dose for lung SBRT when using AAA in reference to using Acuros XB and Clarkson algorithm. Methods: Six institutes in Japan participated in this study. All SBRT treatments were planed using AAA in Eclipse and Adaptive Convolve (AC) in Pinnacle3. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU,more » Triangle Product, Ishikawa, Japan), which implemented a Clarkson-based dose calculation algorithm using CT image dataset. A retrospective analysis for lung SBRT plans (73 patients) was performed to compute the confidence limit (CL, Average±2SD) in dose between the AAA and the SMU. In one of the institutes, a additional analysis was conducted to evaluate the variations between the AAA and the Acuros XB (AXB). Results: The CL for SMU shows larger systematic and random errors of 8.7±9.9 % for AAA than the errors of 5.7±4.2 % for AC. The variations of AAA correlated with the mean CT values in the voxels of PTV (a correlation coefficient : −0.7) . The comparison of AXB vs. AAA shows smaller systematic and random errors of −0.7±1.7%. The correlation between dose variations for AXB and the mean CT values in PTV was weak (0.4). However, there were several plans with more than 2% deviation of AAPM TG114 (Maximum: −3.3 %). Conclusion: In comparison for AC, prescription dose calculated by AAA may be more variable in lung SBRT patient. Even AXB comparison shows unexpected variation. Care should be taken for the use of AAA in lung SBRT. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

PubMed

Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

2017-11-15

Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Prevalence of previously undiagnosed abdominal aortic aneurysms in the area of Como: the ComoCuore "looking for AAA" ultrasonography screening.

PubMed

Corrado, Giovanni; Durante, Alessandro; Genchi, Vincenzo; Trabattoni, Loris; Beretta, Sandro; Rovelli, Enza; Foglia-Manzillo, Giovanni; Ferrari, Giovanni

2016-08-01

The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p < 0.0001). Independent predictors of AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p < 0.0001), male gender (OR 8.23, 1.79-37.91; p = 0.007), and both current (OR 4.98, 1.57-15.79; p = 0.007) and previous smoking (OR 2.76, 1.12-8.94; p = 0.03). Our study confirms the feasibility of one time US screening for AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy.

SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamichhane, N; Studenski, M

2016-06-15

Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobendmore » block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.« less

Heat stress causes alterations in the cell-wall polymers and anatomy of coffee leaves (Coffea arabica L.).

PubMed

Lima, Rogério Barbosa; dos Santos, Tiago Benedito; Vieira, Luiz Gonzaga Esteves; Ferrarese, Maria de Lourdes Lúcio; Ferrarese-Filho, Osvaldo; Donatti, Lucélia; Boeger, Maria Regina Torres; Petkowicz, Carmen Lúcia de Oliveira

2013-03-01

Coffee plants were subjected to heat stress (37 °C) and compared with control plants (24 °C). Cell wall polysaccharides were extracted using water (W), EDTA (E) and 4M NaOH (H30 and H70). In addition, monolignols were analyzed, and the leaves were observed by microscopy. Plants under heat stress accumulated higher contents of arabinose and galactose in fraction W. Xylose contents were observed to decrease in H30 fractions after the heat stress, whereas galactose and uronic acid increased. H70 fractions from plants exposed to heat stress showed increased xylose contents, whereas the contents of arabinose and glucose decreased. Differences in the molar-mass profiles of polysaccharides were also observed. The primary monolignol contents increased after the heat stress. Structural alterations in palisade cells and ultrastructural damage in chloroplasts were also observed. Our results demonstrate that the chemical profile of coffee cell-wall polymers and structural cell anatomy change under heat stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein*

PubMed Central

Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

2013-01-01

The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function. PMID:23979136

Structural insights into the unusually strong ATPase activity of the AAA domain of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.

PubMed

Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

2013-10-11

The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function.

Crystal Structure and Biochemical Characterization of a Mycobacterium smegmatis AAA-Type Nucleoside Triphosphatase Phosphohydrolase (Msm0858).

PubMed

Unciuleac, Mihaela-Carmen; Smith, Paul C; Shuman, Stewart

2016-05-15

AAA proteins (ATPases associated with various cellular activities) use the energy of ATP hydrolysis to drive conformational changes in diverse macromolecular targets. Here, we report the biochemical characterization and 2.5-Å crystal structure of a Mycobacterium smegmatis AAA protein Msm0858, the ortholog of Mycobacterium tuberculosis Rv0435c. Msm0858 is a magnesium-dependent ATPase and is active with all nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) as substrates. The Msm0858 structure comprises (i) an N-terminal domain (amino acids [aa] 17 to 201) composed of two β-barrel modules and (ii) two AAA domains, D1 (aa 212 to 473) and D2 (aa 476 to 744), each of which has ADP in the active site. Msm0858-ADP is a monomer in solution and in crystallized form. Msm0858 domains are structurally homologous to the corresponding modules of mammalian p97. However, the position of the N-domain modules relative to the AAA domains in the Msm0858-ADP tertiary structure is different and would impede the formation of a p97-like hexameric quaternary structure. Mutational analysis of the A-box and B-box motifs indicated that the D1 and D2 AAA domains are both capable of ATP hydrolysis. Simultaneous mutations of the D1 and D2 active-site motifs were required to abolish ATPase activity. ATPase activity was effaced by mutation of the putative D2 arginine finger, suggesting that Msm0858 might oligomerize during the ATPase reaction cycle. A truncated variant Msm0858 (aa 212 to 745) that lacks the N domain was characterized as a catalytically active homodimer. Recent studies have underscored the importance of AAA proteins (ATPases associated with various cellular activities) in the physiology of mycobacteria. This study reports the ATPase activity and crystal structure of a previously uncharacterized mycobacterial AAA protein, Msm0858. Msm0858 consists of an N-terminal β-barrel domain and two AAA domains, each with ADP bound in the active site. Msm0858 is a

The two faces of hydrogen-bond strength on triple AAA-DDD arrays.

PubMed

Lopez, Alfredo Henrique Duarte; Caramori, Giovanni Finoto; Coimbra, Daniel Fernando; Parreira, Renato Luis Tame; da Silva, Éder Henrique

2013-12-02

Systems that are connected through multiple hydrogen bonds are the cornerstone of molecular recognition processes in biology, and they are increasingly being employed in supramolecular chemistry, specifically in molecular self-assembly processes. For this reason, the effects of different substituents (NO2, CN, F, Cl, Br, OCH3 and NH2) on the electronic structure, and consequently on the magnitude of hydrogen bonds in triple AAA-DDD arrays (A=acceptor, D=donor) were evaluated in the light of topological [electron localization function (ELF) and quantum theory of atoms in molecules (QTAIM)], energetic [Su-Li energy-decomposition analysis (EDA) and natural bond orbital analysis (NBO)], and geometrical analysis. The results based on local H-bond descriptors (geometries, QTAIM, ELF, and NBO) indicate that substitutions with electron-withdrawing groups on the AAA module tend to strengthen, whereas electron-donating substituents tend to weaken the covalent character of the AAA-DDD intermolecular H-bonds, and also indicate that the magnitude of the effect is dependent on the position of substitution. In contrast, Su-Li EDA results show an opposite behavior when compared to local H-bond descriptors, indicating that electron-donating substituents tend to increase the magnitude of H-bonds in AAA-DDD arrays, and thus suggesting that the use of local H-bond descriptors describes the nature of H bonds only partially, not providing enough insight about the strength of such H bonds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of doping and bias voltage on the screening in AAA-stacked trilayer graphene

NASA Astrophysics Data System (ADS)

Mohammadi, Yawar; Moradian, Rostam; Shirzadi Tabar, Farzad

2014-09-01

We calculate the static polarization of AAA-stacked trilayer graphene (TLG) and study its screening properties within the random phase approximation (RPA) in all undoped, doped and biased regimes. We find that the static polarization of undoped AAA-stacked TLG is a combination of the doped and undoped single-layer graphene static polarization. This leads to an enhancement of the dielectric background constant along a Thomas-Fermi screening with the Thomas-Fermi wave vector which is independent of carrier concentrations and a 1/r3 power law decay for the long-distance behavior of the screened Coulomb potential. We show that effects of a bias voltage can be taken into account by a renormalization of the interlayer hopping energy to a new bias-voltage-dependent value, indicating screening properties of AAA-stacked TLG can be tuned electrically. We also find that screening properties of doped AAA-stacked TLG, when μ exceeds √{2}γ, are similar to that of doped SLG only depending on doping. While for μ<√{2}γ, its screening properties are combination of SLG and AA-stacked bilayer graphene screening properties and they are determined by doping and the interlayer hopping energy.

Evaluation of Aortic Blood Flow and Wall Shear Stress in Aortic Stenosis and Its Association With Left Ventricular Remodeling.

PubMed

von Knobelsdorff-Brenkenhoff, Florian; Karunaharamoorthy, Achudhan; Trauzeddel, Ralf Felix; Barker, Alex J; Blaszczyk, Edyta; Markl, Michael; Schulz-Menger, Jeanette

2016-03-01

Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. The aim of this study was to describe blood flow patterns in the ascending aorta of patients with AS and determine their association with remodeling. Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age, 63±13 years) and 37 healthy controls (age, 60±10 years) underwent 4-dimensional-flow magnetic resonance imaging. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index and the ratio of LV mass:end-diastolic volume (relative wall mass). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and patients with AS exhibited an asymmetrical and elevated distribution of peak systolic wall shear stress. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (P=0.0274), eccentricity (P=0.0070), and flow displacement (P=0.0021). Bicuspid aortic valve was associated with more intense helical (P=0.0098) and vortical flow formation (P=0.0536), higher flow displacement (P=0.11), and higher peak systolic wall shear stress (P=0.0926). LV mass index and relative wall mass were significantly associated with aortic orifice area (P=0.0611, P=0.0058) and flow displacement (P=0.0058, P=0.0283). In this pilot study, AS leads to abnormal blood flow pattern and peak systolic wall shear stress in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling. © 2016 American Heart Association, Inc.

Asymmetric processing of a substrate protein in sequential allosteric cycles of AAA+ nanomachines

NASA Astrophysics Data System (ADS)

Kravats, Andrea N.; Tonddast-Navaei, Sam; Bucher, Ryan J.; Stan, George

2013-09-01

Essential protein quality control includes mechanisms of substrate protein (SP) unfolding and translocation performed by powerful ring-shaped AAA+ (ATPases associated with various cellular activities) nanomachines. These SP remodeling actions are effected by mechanical forces imparted by AAA+ loops that protrude into the central channel. Sequential intra-ring allosteric motions, which underlie repetitive SP-loop interactions, have been proposed to comprise clockwise (CW), counterclockwise (CCW), or random (R) conformational transitions of individual AAA+ subunits. To probe the effect of these allosteric mechanisms on unfoldase and translocase functions, we perform Langevin dynamics simulations of a coarse-grained model of an all-alpha SP processed by the single-ring ClpY ATPase or by the double-ring p97 ATPase. We find that, in all three allosteric mechanisms, the SP undergoes conformational transitions along a common set of pathways, which reveals that the active work provided by the ClpY machine involves single loop-SP interactions. Nevertheless, the rates and yields of SP unfolding and translocation are controlled by mechanism-dependent loop-SP binding events, as illustrated by faster timescales of SP processing in CW allostery compared with CCW and R allostery. The distinct efficacy of allosteric mechanisms is due to the asymmetric collaboration of adjacent subunits, which involves CW-biased structural motions of AAA+ loops and results in CW-compatible torque applied onto the SP. Additional simulations of mutant ClpY rings, which render a subset of subunits catalytically-defective or reduce their SP binding affinity, reveal that subunit-based conformational transitions play the major role in SP remodeling. Based on these results we predict that the minimally functional AAA+ ring includes three active subunits, only two of which are adjacent.

Mechanical analysis of the strains generated by water tension in plant stems. Part I: stress transmission from the water to the cell walls.

PubMed

Alméras, Tancrède; Gril, Joseph

2007-11-01

Plant tissues shrink and swell in response to changes in water pressure. These strains can be easily measured, e.g., at the surface of tree stems, to obtain indirect information about plant water status and other physiological parameters. We developed a mechanical model to clarify how water pressure is transmitted to cell walls and causes shrinkage of plant tissues, particularly in the case of thick-walled cells such as wood fibers. Our analysis shows that the stress inside the fiber cell walls is lower than the water tension. The difference is accounted for by a stress transmission factor that depends on two main effects. The first effect is the dilution of the stress through the cell wall, because water acts at the lumen border and is transmitted to the outer border of the cell, which has a larger circumference. The second effect is the partial conversion of radial stress into tangential stress. Both effects are quantified as functions of parameters of the cell wall structure and its mechanical properties.

Development of a wall-shear-stress sensor and measurements in mini-channels with partial blockages

NASA Astrophysics Data System (ADS)

Afara, Samer; Medvescek, James; Mydlarski, Laurent; Baliga, Bantwal R.; MacDonald, Mark

2014-05-01

The design, construction, operation and validation of a wall-shear-stress sensor, and measurements obtained using this sensor in air flows downstream of partial blockages in a mini-channel are presented. The sensor consisted of a hot wire mounted over a small rectangular slot and operated using a constant-temperature anemometer. It was used to investigate flows similar to those within the mini-channels inside notebook computers. The overall goal of the present work was to develop a sensor suitable for measurements of the wall-shear stress in such flows, which can be used to validate corresponding numerical simulations, as the latter are known to be often surprisingly inaccurate. To this end, measurements of the wall-shear stress, and the corresponding statistical moments and power spectral densities, were obtained at different distances downstream of the partial blockage, with blockage ratios of 39.7, 59.2, and 76.3 %. The Reynolds number (based on average velocity and hydraulic diameter) ranged from 100 to 900. The results confirmed the presence of unsteadiness, separation, reattachment, and laminar-turbulent transition in the ostensibly laminar flow of air in mini-channels with partial blockages. The present results demonstrate why accurate numerical predictions of cooling air flows in laptop and notebook computers remain a challenging task.

Wall shear stress estimation in the aorta: Impact of wall motion, spatiotemporal resolution, and phase noise.

PubMed

Zimmermann, Judith; Demedts, Daniel; Mirzaee, Hanieh; Ewert, Peter; Stern, Heiko; Meierhofer, Christian; Menze, Bjoern; Hennemuth, Anja

2018-04-01

Wall shear stress (WSS) presents an important parameter for assessing blood flow characteristics and evaluating flow-mediated lesions in the aorta. To investigate the robustness of WSS and oscillatory shear index (OSI) estimation based on 4D flow MRI against vessel wall motion, spatiotemporal resolution, and velocity encoding (VENC). Simulated and prospective. Synthetic 4D flow MRI data of the aorta, simulated using the Lattice-Boltzmann method; in vivo 4D flow MRI data of the aorta from healthy volunteers (n = 11) and patients with congenital heart defects (n = 17). 1.5T; 4D flow MRI with PEAK-GRAPPA acceleration and prospective electrocardiogram triggering. Predicated upon 3D cubic B-splines interpolation of the image velocity field, WSS was estimated in mid-systole, early-diastole, and late-diastole and OSI was derived. We assessed the impact of spatiotemporal resolution and phase noise, and compared results based on tracked-using deformable registration-and static vessel wall location. Bland-Altman analysis to assess WSS/OSI differences; Hausdorff distance (HD) to assess wall motion; and Pearson's correlation coefficient (PCC) to assess correlation of HD with WSS. Synthetic data results show systematic over-/underestimation of WSS when different spatial resolution (mean ± 1.96 SD up to -0.24 ± 0.40 N/m 2 and 0.5 ± 1.38 N/m 2 for 8-fold and 27-fold voxel size, respectively) and VENC-depending phase noise (mean ± 1.96 SD up to 0.31 ± 0.12 N/m 2 and 0.94 ± 0.28 N/m 2 for 2-fold and 4-fold VENC increase, respectively) are given. Neglecting wall motion when defining the vessel wall perturbs WSS estimates to a considerable extent (1.96 SD up to 1.21 N/m 2 ) without systematic over-/underestimation (Bland-Altman mean range -0.06 to 0.05). In addition to sufficient spatial resolution and velocity to noise ratio, accurate tracking of the vessel wall is essential for reliable image-based WSS estimation and should not be

The lantibiotic mersacidin is a strong inducer of the cell wall stress response of Staphylococcus aureus

PubMed Central

Sass, Peter; Jansen, Andrea; Szekat, Christiane; Sass, Vera; Sahl, Hans-Georg; Bierbaum, Gabriele

2008-01-01

Background The lantibiotic mersacidin is an antimicrobial peptide of 20 amino acids that is ribosomally produced by Bacillus sp. strain HIL Y-85,54728. Mersacidin acts by complexing the sugar phosphate head group of the peptidoglycan precursor lipid II, thereby inhibiting the transglycosylation reaction of peptidoglycan biosynthesis. Results Here, we studied the growth of Staphylococcus aureus in the presence of subinhibitory concentrations of mersacidin. Transcriptional data revealed an extensive induction of the cell wall stress response, which is partly controlled by the two-component regulatory system VraSR. In contrast to other cell wall-active antibiotics such as vancomycin, very low concentrations of mersacidin (0.15 × MIC) were sufficient for induction. Interestingly, the cell wall stress response was equally induced in vancomycin intermediately resistant S. aureus (VISA) and in a highly susceptible strain. Since the transcription of the VraDE ABC transporter genes was induced up to 1700-fold in our experiments, we analyzed the role of VraDE in the response to mersacidin. However, the deletion of the vraE gene did not result in an increased susceptibility to mersacidin compared to the wild type strain. Moreover, the efficacy of mersacidin was not affected by an increased cell wall thickness, which is part of the VISA-type resistance mechanism and functions by trapping the vancomycin molecules in the cell wall before they reach lipid II. Therefore, the relatively higher concentration of mersacidin at the membrane might explain why mersacidin is such a strong inducer of VraSR compared to vancomycin. Conclusion In conclusion, mersacidin appears to be a strong inducer of the cell wall stress response of S. aureus at very low concentrations, which reflects its general mode of action as a cell wall-active peptide as well as its use of a unique target site on lipid II. Additionally, mersacidin does not seem to be a substrate for the resistance transporter Vra

Dosimetric comparison of Acuros XB, AAA, and XVMC in stereotactic body radiotherapy for lung cancer.

PubMed

Tsuruta, Yusuke; Nakata, Manabu; Nakamura, Mitsuhiro; Matsuo, Yukinori; Higashimura, Kyoji; Monzen, Hajime; Mizowaki, Takashi; Hiraoka, Masahiro

2014-08-01

To compare the dosimetric performance of Acuros XB (AXB), anisotropic analytical algorithm (AAA), and x-ray voxel Monte Carlo (XVMC) in heterogeneous phantoms and lung stereotactic body radiotherapy (SBRT) plans. Water- and lung-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. The radiation treatment machine Novalis (BrainLab AG, Feldkirchen, Germany) with an x-ray beam energy of 6 MV was used to calculate the doses in the composite phantom at a source-to-surface distance of 100 cm with a gantry angle of 0°. Subsequently, the clinical lung SBRT plans for the 26 consecutive patients were transferred from the iPlan (ver. 4.1; BrainLab AG) to the Eclipse treatment planning systems (ver. 11.0.3; Varian Medical Systems, Palo Alto, CA). The doses were then recalculated with AXB and AAA while maintaining the XVMC-calculated monitor units and beam arrangement. Then the dose-volumetric data obtained using the three different radiation dose calculation algorithms were compared. The results from AXB and XVMC agreed with measurements within ± 3.0% for the lung-equivalent phantom with a 6 × 6 cm(2) field size, whereas AAA values were higher than measurements in the heterogeneous zone and near the boundary, with the greatest difference being 4.1%. AXB and XVMC agreed well with measurements in terms of the profile shape at the boundary of the heterogeneous zone. For the lung SBRT plans, AXB yielded lower values than XVMC in terms of the maximum doses of ITV and PTV; however, the differences were within ± 3.0%. In addition to the dose-volumetric data, the dose distribution analysis showed that AXB yielded dose distribution calculations that were closer to those with XVMC than did AAA. Means ± standard deviation of the computation time was 221.6 ± 53.1 s (range, 124-358 s), 66.1 ± 16.0 s (range, 42-94 s), and 6.7 ± 1.1 s (range, 5-9 s) for XVMC, AXB, and AAA, respectively. In the phantom evaluations, AXB and XVMC agreed better with

Structure determination of disease associated peak AAA from l-Tryptophan implicated in the eosinophilia-myalgia syndrome.

PubMed

Klarskov, Klaus; Gagnon, Hugo; Boudreault, Pierre-Luc; Normandin, Chad; Plancq, Baptiste; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

2018-01-05

The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA and elsewhere was caused by the ingestion of l-Tryptophan (L-Trp) solely manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present in the SD L-Trp were reported to be case-associated contaminants. However, "one" of these compounds, Peak AAA has remained structurally uncharacterized, despite the fact that it was described as "the only statistically significant (p=0.0014) contaminant". Here, we employ on-line microcapillary-high performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS), and tandem mass spectrometry (MS/MS) to determine that Peak AAA is in fact two structurally related isomers. Peak AAA 1 and Peak AAA 2 differed in LC retention times, and were determined by accurate mass-LC-MS to both have a protonated molecular ion (MH +) of mass 343.239Da (Da), corresponding to a molecular formula of C 21 H 30 N 2 O 2, and possessing eight degrees of unsaturation (DoU) for the non-protonated molecule. By comparing the LC-MS and LC-MS-MS retention times and spectra with authentic synthetic standards, Peak AAA 1 was identified as the intermolecular condensation product of L-Trp with anteiso 7-methylnonanoic acid, to afford (S)-2-amino-3-(2-((S,E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Peak AAA 2 was determined to be a condensation product of L-Trp with decanoic acid, which produced (S)-2-amino-3-(2-((E)-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine.

PubMed

Liu, Jing; Mei, Ziqing; Li, Ningning; Qi, Yutao; Xu, Yanji; Shi, Yigong; Wang, Feng; Lei, Jianlin; Gao, Ning

2013-06-14

The MecA-ClpC complex is a bacterial type II AAA(+) molecular machine responsible for regulated unfolding of substrates, such as transcription factors ComK and ComS, and targeting them to ClpP for degradation. The six subunits of the MecA-ClpC complex form a closed barrel-like structure, featured with three stacked rings and a hollow passage, where substrates are threaded and translocated through successive pores. Although the general concepts of how polypeptides are unfolded and translocated by internal pore loops of AAA(+) proteins have long been conceived, the detailed mechanistic model remains elusive. With cryoelectron microscopy, we captured four different structures of the MecA-ClpC complexes. These complexes differ in the nucleotide binding states of the two AAA(+) rings and therefore might presumably reflect distinctive, representative snapshots from a dynamic unfolding cycle of this hexameric complex. Structural analysis reveals that nucleotide binding and hydrolysis modulate the hexameric complex in a number of ways, including the opening of the N-terminal ring, the axial and radial positions of pore loops, the compactness of the C-terminal ring, as well as the relative rotation between the two nucleotide-binding domain rings. More importantly, our structural and biochemical data indicate there is an active allosteric communication between the two AAA(+) rings and suggest that concerted actions of the two AAA(+) rings are required for the efficiency of the substrate unfolding and translocation. These findings provide important mechanistic insights into the dynamic cycle of the MecA-ClpC unfoldase and especially lay a foundation toward the complete understanding of the structural dynamics of the general type II AAA(+) hexamers.

Structure and evolution of N-domains in AAA metalloproteases.

PubMed

Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D; Habeck, Michael; Martin, Jörg; Lupas, Andrei N; Alva, Vikram

2015-02-27

Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn(2+)-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichia coli FtsH-N, exhibiting an unusual α+β fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors. Copyright © 2015. Published by Elsevier Ltd.

Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes.

PubMed

Saffert, Paul; Enenkel, Cordula; Wendler, Petra

2017-01-01

Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria. Tremendous efforts have been undertaken to understand the conformational dynamics of protein remodeling type II AAA+ complexes. A uniform mode of action has not been derived from these works. This review focuses on p97/VCP and the Pex1/6 complex, which both structurally remodel ubiquitinated substrate proteins. P97/VCP plays a role in many processes, including ER- associated protein degradation, and the Pex1/Pex6 complex dislocates and recycles the transport receptor Pex5 from the peroxisomal membrane during peroxisomal protein import. We give an introduction into existing knowledge about the biochemical and cellular activities of the complexes before discussing structural information. We particularly emphasize recent electron microscopy structures of the two AAA+ complexes and summarize their structural differences.

Role of Wall Shear Stress in Cryptosporidium parvum Oocyst Attachment to Environmental Biofilms.

PubMed

Luo, Xia; Jedlicka, Sabrina S; Jellison, Kristen L

2017-12-15

This study investigated Cryptosporidium parvum oocyst deposition onto biofilms as a function of shear stress under laminar or turbulent flow. Annular rotating bioreactors were used to grow stabilized stream biofilms at shear stresses ranging from 0.038 to 0.46 Pa. These steady-state biofilms were then used to assess the impact of hydrodynamic conditions on C. parvum oocyst attachment. C. parvum deposition onto biofilms followed a pseudo-second-order model under both laminar (after a lag phase) and turbulent flows. The total number of oocysts attached to the biofilm at steady state decreased as the hydrodynamic wall shear stress increased. The oocyst deposition rate constant increased with shear stress but decreased at high shear, suggesting that increasing wall shear stress results in faster attachment of Cryptosporidium due to higher mass transport until the shear forces exceed a critical limit that prevents oocyst attachment. These data show that oocyst attachment in the short and long term are impacted differently by shear: higher shear (to a certain limit) may be associated with faster initial oocyst attachment, but lower shear is associated with greater numbers of oocysts attached at equilibrium. IMPORTANCE This research provides experimental evidence to demonstrate that shear stress plays a critical role in protozoan-pathogen transport and deposition in environmental waters. The data presented in this work expand scientific understanding of Cryptosporidium attachment and fate, which will further influence the development of timely and accurate sampling strategies, as well as advanced water treatment technologies, to target protozoan pathogens in surface waters that serve as municipal drinking water sources. Copyright © 2017 American Society for Microbiology.

Roles of the Skn7 response regulator in stress resistance, cell wall integrity and GA biosynthesis in Ganoderma lucidum.

PubMed

Wang, Shengli; Shi, Liang; Hu, Yanru; Liu, Rui; Ren, Ang; Zhu, Jing; Zhao, Mingwen

2018-05-01

The transcription factor Skn7 is a highly conserved fungal protein that participates in a variety of processes, including oxidative stress adaptation, fungicide sensitivity, cell wall biosynthesis, cell cycle, and sporulation. In this study, a homologous gene of Saccharomyces cerevisiae Skn7 was cloned from Ganoderma lucidum. RNA interference (RNAi) was used to study the functions of Skn7, and the two knockdown strains Skn7i-5 and Skn7i-7 were obtained in G. lucidum. The knockdown of GlSkn7 resulted in hypersensitivity to oxidative and cell wall stresses. The concentrations of chitin and β-1,3-glucan distinctly decreased in the GlSkn7 knockdown strains compared with those of the wild type (WT). In addition, the expression of cell wall biosynthesis related genes was also significantly down-regulated and the thickness of the cell wall also significantly reduced in the GlSkn7 knockdown strains. The intracellular reactive oxygen species (ROS) content and ganoderic acids biosynthesis increased significantly in the GlSkn7 knockdown strains. Interestingly, the level of intracellular ROS and the content of ganoderic acids decreased after N-acetyl-L-cysteine (NAC), an ROS scavenger, was added, indicating that GlSkn7 might regulate ganoderic acids biosynthesis via the intracellular ROS level. The transcript level of GlSkn7 were up-regulated in osmotic stress, heat stress and fungicide condition. At the same time, the content of ganoderic acids in the GlSkn7 knockdown strains also changed distinctly in these conditions. Overall, GlSkn7 is involved in stress resistance, cell wall integrity and ganoderic acid biosynthesis in G. lucidum. Copyright © 2018 Elsevier Inc. All rights reserved.

Stress-intensity factors for a thick-walled cylinder containing an annular imbedded or external or internal surface crack

NASA Technical Reports Server (NTRS)

Erdol, R.; Erdogan, F.

1976-01-01

The elastostatic axisymmetric problem for a long thick-walled cylinder containing a ring-shaped internal or edge crack is considered. Using the standard transform technique the problem is formulated in terms of an integral equation which has a simple Cauchy kernel for the internal crack and a generalized Cauchy kernel for the edge crack as the dominant part. As examples the uniform axial load and the steady-state thermal stress problems have been solved and the related stress intensity factors have been calculated. Among other findings the results show that in the cylinder under uniform axial stress containing an internal crack the stress intensity factor at the inner tip is always greater than that at the outer tip for equal net ligament thicknesses and in the cylinder with an edge crack which is under a state of thermal stress the stress intensity factor is a decreasing function of the crack depth, tending to zero as the crack depth approaches the wall thickness.

Understanding the fluid mechanics behind transverse wall shear stress.

PubMed

Mohamied, Yumnah; Sherwin, Spencer J; Weinberg, Peter D

2017-01-04

The patchy distribution of atherosclerosis within arteries is widely attributed to local variation in haemodynamic wall shear stress (WSS). A recently-introduced metric, the transverse wall shear stress (transWSS), which is the average over the cardiac cycle of WSS components perpendicular to the temporal mean WSS vector, correlates particularly well with the pattern of lesions around aortic branch ostia. Here we use numerical methods to investigate the nature of the arterial flows captured by transWSS and the sensitivity of transWSS to inflow waveform and aortic geometry. TransWSS developed chiefly in the acceleration, peak systolic and deceleration phases of the cardiac cycle; the reverse flow phase was too short, and WSS in diastole was too low, for these periods to have a significant influence. Most of the spatial variation in transWSS arose from variation in the angle by which instantaneous WSS vectors deviated from the mean WSS vector rather than from variation in the magnitude of the vectors. The pattern of transWSS was insensitive to inflow waveform; only unphysiologically high Womersley numbers produced substantial changes. However, transWSS was sensitive to changes in geometry. The curvature of the arch and proximal descending aorta were responsible for the principal features, the non-planar nature of the aorta produced asymmetries in the location and position of streaks of high transWSS, and taper determined the persistence of the streaks down the aorta. These results reflect the importance of the fluctuating strength of Dean vortices in generating transWSS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rôle of contrast media viscosity in altering vessel wall shear stress and relation to the risk of contrast extravasations.

PubMed

Sakellariou, Sophia; Li, Wenguang; Paul, Manosh C; Roditi, Giles

2016-12-01

Iodinated contrast media (CM) are the most commonly used injectables in radiology today. A range of different media are commercially available, combining various physical and chemical characteristics (ionic state, osmolality, viscosity) and thus exhibiting distinct in vivo behaviour and safety profiles. In this paper, numerical simulations of blood flow with contrast media were conducted to investigate the effects of contrast viscosity on generated vessel wall shear stress and vessel wall pressure to elucidate any possible relation to extravasations. Five different types of contrast for Iodine fluxes ranging at 1.5-2.2gI/s were modelled through 18G and 20G cannulae placed in an ideal vein at two different orientation angles. Results demonstrate that the least viscous contrast media generate the least maximum wall shear stress as well as the lowest total pressure for the same flow rate. This supports the empirical clinical observations and hypothesis that more viscous contrast media are responsible for a higher percentage of contrast extravasations. In addition, results support the clinical hypothesis that a catheter tip directed obliquely to the vein wall always produces the highest maximum wall shear stress and total pressure due to impingement of the contrast jet on the vessel wall. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

The Adult Asperger Assessment (AAA): A Diagnostic Method

ERIC Educational Resources Information Center

Baron-Cohen, Simon; Wheelwright, Sally; Robinson, Janine; Woodbury-Smith, Marc

2005-01-01

At the present time there are a large number of adults who have "suspected" Asperger syndrome (AS). In this paper we describe a new instrument, the Adult Asperger Assessment (AAA), developed in our clinic for adults with AS. The need for a new instrument relevant to the diagnosis of AS in adulthood arises because existing instruments are designed…

Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA) in comparison to Ulex europaeus agglutinin I (UEA-I).

PubMed

Baldus, S E; Thiele, J; Park, Y O; Hanisch, F G; Bara, J; Fischer, R

1996-08-01

Using immunochemical and immunohistochemical methods, the binding site of Anguilla anguilla agglutinin (AAA) was characterized and compared with the related fucose-specific lectin from Ulex europaeus (UEA-I). In solid-phase enzyme-linked immunoassays, the two lectins recognized Fuc alpha 1-2Gal beta-HSA. AAA additionally cross-reacted with neoglycolipids bearing lacto-N-fucopentaose (LNFP) I [H type 1] and II [Le(a)] and lactodifucotetraose (LDFT) as glycan moieties. UEA-I, on the other hand, bound to a LDFT-derived neoglycolipid but not to the other neoglycolipids tested. Binding of AAA to gastric mucin was competitively neutralized by Le(a)-specific monoclonal antibodies. UEA-I binding, on the other hand, was reduced after co-incubation with H type 2- and Le(y)-specific monoclonal antibodies. According to our results, AAA reacts with fucosylated type 1 chain antigens, whereas UEA-I binds only to the alpha 1-2-fucosylated LDFT-derived neoglycolipid. In immunohistochemical studies, the reactivity of AAA and UEA-I in normal pyloric mucosa from individuals with known Lewis and secretor status was analysed. AAA showed a broad reaction in the superficial pyloric mucosa from secretors and non-secretors, but AAA reactivity was more pronounced in Le(a+b-) individuals. On the other hand, UEA-I stained the superficial pyloric mucosa only from secretor individuals. A staining of deep mucous glands by the lectins was found in all specimens. Both reacted with most human carcinomas of different origin. Slight differences in their binding pattern were observed and may be explained by the different fine-specificities of the lectins.

Family Members of Patients with Abdominal Aortic Aneurysms are at Increased Risk for Aneurysms: Analysis of 618 Probands and their Families from the Liège AAA Family Study

PubMed Central

Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T.; Tromp, Gerard; Kuivaniemi, Helena

2014-01-01

Background The objectives were to answer the following questions using a well-characterized population in Liège, Belgium: 1) what percentage of abdominal aortic aneurysm (AAA) patients have a positive family history for AAA, 2) what is the prevalence of AAAs among relatives of AAA patients; and 3) do familial and sporadic AAA cases differ in clinical characteristics. Methods and Results Unrelated AAA patients diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. In the initial interview 62 (10%) of the 618 AAA patients reported a positive family history for AAA. We divided the 618 patients into two study groups: Group I: 296 AAA patients (268; 91% males) were followed up with computerized tomography combined with positron emission tomography, and Group II: 322 AAA patients (295; 92% males) whose families were invited to ultrasonography screening. Ultrasonography screening identified 24 new AAAs among 186 relatives (≥ 50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonography screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P<0.0001). Conclusions The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis and provide rationale for targeted screening of relatives of AAA patients. PMID:24365082

Advanced Oxidation Protein Products and Carbonylated Proteins as Biomarkers of Oxidative Stress in Selected Atherosclerosis-Mediated Diseases.

PubMed

Gryszczyńska, Bogna; Formanowicz, Dorota; Budzyń, Magdalena; Wanic-Kossowska, Maria; Pawliczak, Elżbieta; Formanowicz, Piotr; Majewski, Wacław; Strzyżewski, Krzysztof Wojciech; Kasprzak, Magdalena P; Iskra, Maria

2017-01-01

The main question of this study was to evaluate the intensity of oxidative protein modification shown as advanced oxidation protein products (AOPP) and carbonylated proteins, expressed as protein carbonyl content (C=O) in abdominal aortic aneurysms (AAA), aortoiliac occlusive disease (AIOD), and chronic kidney disease (CKD). The study was carried out in a group of 35 AAA patients and 13 AIOD patients. However, CKD patients were divided into two groups: predialysis (PRE) included 50 patients or hemodialysis (HD) consisted of 34 patients. AOPP and C=O were measured using colorimetric assay kit, while C-reactive protein concentration was measured by high-sensitivity assay (hsCRP). The concentration of AOPP in both AAA and AIOD groups was higher than in PRE and HD groups according to descending order: AAA~AIOD > HD > PRE. The content of C=O was higher in the PRE group in comparison to AIOD and AAA according to the descending order: PRE~HD > AAA~AIOD. AAA, AIOD, and CKD-related atherosclerosis (PRE and HD) contribute to the changes in the formation of AOPP and C=O. They may promote modification of proteins in a different way, probably due to the various factors that influence oxidative stress here.

Family members of patients with abdominal aortic aneurysms are at increased risk for aneurysms: analysis of 618 probands and their families from the Liège AAA Family Study.

PubMed

Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T; Tromp, Gerard; Kuivaniemi, Helena

2014-05-01

The objectives were to answer the following questions with the help of a well-characterized population in Liège, Belgium: 1) what percentage of patients with abdominal aortic aneurysm (AAA) have a positive family history for AAA? 2) what is the prevalence of AAAs among relatives of patients with AAA? and 3) do familial and sporadic AAA cases differ in clinical characteristics? Patients with unrelated AAA diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. We divided the 618 patients into 2 study groups: group I, 296 patients with AAA (268; 91% men) were followed up with computerized tomography combined with positron emission tomography; and group II, 322 patients with AAA (295; 92% men) whose families were invited to ultrasonographic screening. In the initial interview, 62 (10%) of the 618 patients with AAA reported a positive family history for AAA. Ultrasonographic screening identified 24 new AAAs among 186 relatives (≥50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonographic screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P < 0.0001). The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis, and provide rationale for targeted screening of relatives of patients with AAA. Copyright © 2014 Elsevier Inc. All rights reserved.

3D-Printed Tissue-Mimicking Phantoms for Medical Imaging and Computational Validation Applications

PubMed Central

Shahmirzadi, Danial; Li, Ronny X.; Doyle, Barry J.; Konofagou, Elisa E.; McGloughlin, Tim M.

2014-01-01

Abstract Abdominal aortic aneurysm (AAA) is a permanent, irreversible dilation of the distal region of the aorta. Recent efforts have focused on improved AAA screening and biomechanics-based failure prediction. Idealized and patient-specific AAA phantoms are often employed to validate numerical models and imaging modalities. To produce such phantoms, the investment casting process is frequently used, reconstructing the 3D vessel geometry from computed tomography patient scans. In this study the alternative use of 3D printing to produce phantoms is investigated. The mechanical properties of flexible 3D-printed materials are benchmarked against proven elastomers. We demonstrate the utility of this process with particular application to the emerging imaging modality of ultrasound-based pulse wave imaging, a noninvasive diagnostic methodology being developed to obtain regional vascular wall stiffness properties, differentiating normal and pathologic tissue in vivo. Phantom wall displacements under pulsatile loading conditions were observed, showing good correlation to fluid–structure interaction simulations and regions of peak wall stress predicted by finite element analysis. 3D-printed phantoms show a strong potential to improve medical imaging and computational analysis, potentially helping bridge the gap between experimental and clinical diagnostic tools. PMID:28804733

Substituent effects in double-helical hydrogen-bonded AAA-DDD complexes.

PubMed

Wang, Hong-Bo; Mudraboyina, Bhanu P; Wisner, James A

2012-01-27

Two series of DDD and AAA hydrogen-bond arrays were synthesized that form triply-hydrogen-bonded double-helical complexes when combined in CDCl(3) solution. Derivatization of the DDD arrays with electron-withdrawing groups increases the complex association constants by up to a factor of 30 in those arrays examined. Derivatization of the AAA arrays with electron donating substituents reveals a similar magnitude effect on the complex stabilities. The effect of substitution on both types of arrays are modeled quite satisfactorily (R(2) > 0.96 in all cases) as free energy relationships with respect to the sums of their Hammett substituent constants. In all, the complex stabilities can be manipulated over more than three orders of magnitude (>20 kJ mol(-1)) using this type of modification. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wall shear stress distributions on stented patent ductus arteriosus

NASA Astrophysics Data System (ADS)

Kori, Mohamad Ikhwan; Jamalruhanordin, Fara Lyana; Taib, Ishkrizat; Mohammed, Akmal Nizam; Abdullah, Mohammad Kamil; Ariffin, Ahmad Mubarak Tajul; Osman, Kahar

2017-04-01

A formation of thrombosis due to hemodynamic conditions after the implantation of stent in patent ductus arteriosus (PDA) will derived the development of re-stenosis. The phenomenon of thrombosis formation is significantly related to the distribution of wall shear stress (WSS) on the arterial wall. Thus, the aims of this study is to investigate the distribution of WSS on the arterial wall after the insertion of stent. Three dimensional model of patent ductus arteriosus inserted with different types of commercial stent are modelled. Computational modelling is used to calculate the distributions of WSS on the arterial stented PDA. The hemodynamic parameters such as high WSS and WSSlow are considered in this study. The result shows that the stented PDA with Type III stent has better hemodynamic performance as compared to others stent. This model has the lowest distributions of WSSlow and also the WSS value more than 20 dyne/cm2. From the observed, the stented PDA with stent Type II showed the highest distributions area of WSS more than 20 dyne/cm2. This situation revealed that the high possibility of atherosclerosis to be developed. However, the highest distribution of WSSlow for stented PDA with stent Type II indicated that high possibility of thrombosis to be formed. In conclusion, the stented PDA model calculated with the lowest distributions of WSSlow and WSS value more than 20dyne/cm2 are considered to be performed well in stent hemodynamic performance as compared to other stents.

Mathematical Modeling of Intravascular Blood Coagulation under Wall Shear Stress

PubMed Central

Rukhlenko, Oleksii S.; Dudchenko, Olga A.; Zlobina, Ksenia E.; Guria, Georgy Th.

2015-01-01

Increased shear stress such as observed at local stenosis may cause drastic changes in the permeability of the vessel wall to procoagulants and thus initiate intravascular blood coagulation. In this paper we suggest a mathematical model to investigate how shear stress-induced permeability influences the thrombogenic potential of atherosclerotic plaques. Numerical analysis of the model reveals the existence of two hydrodynamic thresholds for activation of blood coagulation in the system and unveils typical scenarios of thrombus formation. The dependence of blood coagulation development on the intensity of blood flow, as well as on geometrical parameters of atherosclerotic plaque is described. Relevant parametric diagrams are drawn. The results suggest a previously unrecognized role of relatively small plaques (resulting in less than 50% of the lumen area reduction) in atherothrombosis and have important implications for the existing stenting guidelines. PMID:26222505

The AAA+ ATPase p97, a cellular multitool

PubMed Central

Stach, Lasse

2017-01-01

The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy. PMID:28819009

26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

Code of Federal Regulations, 2011 CFR

2011-04-01

... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

Code of Federal Regulations, 2014 CFR

2014-04-01

... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

Code of Federal Regulations, 2012 CFR

2012-04-01

... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

Code of Federal Regulations, 2010 CFR

2010-04-01

... TAX (CONTINUED) INCOME TAXES Small Business Corporations and Their Shareholders § 1.1368-2 Accumulated... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

Code of Federal Regulations, 2013 CFR

2013-04-01

... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

Algisyl-LVR™ with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart☆,☆☆

PubMed Central

Lee, Lik Chuan; Wall, Samuel T.; Klepach, Doron; Ge, Liang; Zhang, Zhihong; Lee, Randall J.; Hinson, Andy; Gorman, Joseph H.; Gorman, Robert C.; Guccione, Julius M.

2013-01-01

Background Left ventricular (LV) wall stress reduction is a cornerstone in treating heart failure. Large animal models and computer simulations indicate that adding non-contractile material to the damaged LV wall can potentially reduce myofiber stress. We sought to quantify the effects of a novel implantable hydrogel (Algisyl-LVR™) treatment in combination with coronary artery bypass grafting (i.e. Algisyl-LVR™+CABG) on both LV function and wall stress in heart failure patients. Methods and results Magnetic resonance images obtained before treatment (n=3), and at 3 months (n=3) and 6 months (n=2) afterwards were used to reconstruct the LV geometry. Cardiac function was quantified using end-diastolic volume (EDV), end-systolic volume (ESV), regional wall thickness, sphericity index and regional myofiber stress computed using validated mathematical modeling. The LV became more ellipsoidal after treatment, and both EDV and ESV decreased substantially 3 months after treatment in all patients; EDV decreased from 264±91 ml to 146±86 ml and ESV decreased from 184±85 ml to 86±76 ml. Ejection fraction increased from 32±8% to 47±18% during that period. Volumetric-averaged wall thickness increased in all patients, from 1.06±0.21 cm (baseline) to 1.3±0.26 cm (3 months). These changes were accompanied by about a 35% decrease in myofiber stress at end-of-diastole and at end-of-systole. Post-treatment myofiber stress became more uniform in the LV. Conclusions These results support the novel concept that Algisyl-LVR™+CABG treatment leads to decreased myofiber stress, restored LV geometry and improved function. PMID:23394895

Analysis of wall shear stress around a competitive swimmer using 3D Navier-Stokes equations in CFD.

PubMed

Popa, C V; Zaidi, H; Arfaoui, A; Polidori, G; Taiar, R; Fohanno, S

2011-01-01

This paper deals with the flow dynamics around a competitive swimmer during underwater glide phases occurring at the start and at every turn. The influence of the head position, namely lifted up, aligned and lowered, on the wall shear stress and the static pressure distributions is analyzed. The problem is considered as 3D and in steady hydrodynamic state. Three velocities (1.4 m/s, 2.2 m/s and 3.1 m/s) that correspond to inter-regional, national and international swimming levels are studied. The flow around the swimmer is assumed turbulent. The Reynolds-averaged Navier-Stokes (RANS) equations are solved with the standard k-ω turbulent model by using the CFD (computational fluid dynamics) numerical method based on a volume control approach. Numerical simulations are carried out with the ANSYS FLUENT® CFD code. The results show that the wall shear stress increases with the velocity and consequently the drag force opposing the movement of the swimmer increases as well. Also, high wall shear stresses are observed in the areas where the body shape, globally rigid in form, presents complex surface geometries such as the head, shoulders, buttocks, heel and chest.

Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion.

PubMed

Hopke, Alex; Brown, Alistair J P; Hall, Rebecca A; Wheeler, Robert T

2018-04-01

Deadly infections from opportunistic fungi have risen in frequency, largely because of the at-risk immunocompromised population created by advances in modern medicine and the HIV/AIDS pandemic. This review focuses on dynamics of the fungal polysaccharide cell wall, which plays an outsized role in fungal pathogenesis and therapy because it acts as both an environmental barrier and as the major interface with the host immune system. Human fungal pathogens use architectural strategies to mask epitopes from the host and prevent immune surveillance, and recent work elucidates how biotic and abiotic stresses present during infection can either block or enhance masking. The signaling components implicated in regulating fungal immune recognition can teach us how cell wall dynamics are controlled, and represent potential targets for interventions designed to boost or dampen immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assessing outcome after a modified vaginal wall sling for stress incontinence with intrinsic sphincter deficiency.

PubMed

Costantini, Elisabetta; Mearini, Luigi; Mearini, Ettore; Pajoncini, Cinzia; Guercini, Federico; Bini, Vittorio; Porena, Massimo

2005-01-01

Forty women with stress incontinence, intrinsic sphincter deficiency (ISD), associated or not with urethral hypermobility, a Valsalva leak point pressure (VLLP)<60 cmH(2)0 and a maximum urethral closure pressure<30 cmH(2)0 underwent in situ vaginal wall sling. The main modification to the technique was the use of two small Marlex meshes placed at the lateral edges of the sling. Outcome was assessed by pad use, surgical results and patients' satisfaction. Data of 39/40 patients were analyzed after a minimum follow-up of 1 year. After surgery 30/39 patients were completely dry (no pads), stress incontinence disappeared in 22/39, and 30/39 patients were satisfied with outcome. Reasons for dissatisfaction included recurrence of stress incontinence in three, infections in one and urge incontinence in five. Overall results are good given this category of patients. The vaginal wall sling can be recommended for patients with ISD because the results are promising, it corrects urethral hypermobility and, in our experience, it does not cause obstruction if correctly performed.

AAAS: Automated Affirmative Action System. General Description, Phase 1.

ERIC Educational Resources Information Center

Institute for Services to Education, Inc., Washington, DC. TACTICS Management Information Systems Directorate.

This document describes phase 1 of the Automated Affirmative Action System (AAAS) of the Tuskegee Institute, which was designed to organize an inventory of any patterns of job classification and assignment identifiable by sex or minority group; any job classification or organizational unit where women and minorities are not employed or are…

Stress adapted embroidered meshes with a graded pattern design for abdominal wall hernia repair

NASA Astrophysics Data System (ADS)

Hahn, J.; Bittrich, L.; Breier, A.; Spickenheuer, A.

2017-10-01

Abdominal wall hernias are one of the most relevant injuries of the digestive system with 25 million patients in 2013. Surgery is recommended primarily using allogenic non-absorbable wrap-knitted meshes. These meshes have in common that their stress-strain behaviour is not adapted to the anisotropic behaviour of native abdominal wall tissue. The ideal mesh should possess an adequate mechanical behaviour and a suitable porosity at the same time. An alternative fabrication method to wrap-knitting is the embroidery technology with a high flexibility in pattern design and adaption of mechanical properties. In this study, a pattern generator was created for pattern designs consisting of a base and a reinforcement pattern. The embroidered mesh structures demonstrated different structural and mechanical characteristics. Additionally, the investigation of the mechanical properties exhibited an anisotropic mechanical behaviour for the embroidered meshes. As a result, the investigated pattern generator and the embroidery technology allow the production of stress adapted mesh structures that are a promising approach for hernia reconstruction.

Propose a Wall Shear Stress Divergence to Estimate the Risks of Intracranial Aneurysm Rupture

PubMed Central

Zhang, Y.; Takao, H.; Murayama, Y.; Qian, Y.

2013-01-01

Although wall shear stress (WSS) has long been considered a critical indicator of intracranial aneurysm rupture, there is still no definite conclusion as to whether a high or a low WSS results in aneurysm rupture. The reason may be that the effect of WSS direction has not been fully considered. The objectives of this study are to investigate the magnitude of WSS (|WSS|) and its divergence on the aneurysm surface and to test the significance of both in relation to the aneurysm rupture. Patient-specific computational fluid dynamics (CFD) was used to compute WSS and wall shear stress divergence (WSSD) on the aneurysm surface for nineteen patients. Our results revealed that if high |WSS| is stretching aneurysm luminal surface, and the stretching region is concentrated, the aneurysm is under a high risk of rupture. It seems that, by considering both direction and magnitude of WSS, WSSD may be a better indicator for the risk estimation of aneurysm rupture (154). PMID:24191140

Vacuolar H+-ATPase Protects Saccharomyces cerevisiae Cells against Ethanol-Induced Oxidative and Cell Wall Stresses

PubMed Central

Charoenbhakdi, Sirikarn; Dokpikul, Thanittra; Burphan, Thanawat; Techo, Todsapol

2016-01-01

ABSTRACT During fermentation, increased ethanol concentration is a major stress for yeast cells. Vacuolar H+-ATPase (V-ATPase), which plays an important role in the maintenance of intracellular pH homeostasis through vacuolar acidification, has been shown to be required for tolerance to straight-chain alcohols, including ethanol. Since ethanol is known to increase membrane permeability to protons, which then promotes intracellular acidification, it is possible that the V-ATPase is required for recovery from alcohol-induced intracellular acidification. In this study, we show that the effects of straight-chain alcohols on membrane permeabilization and acidification of the cytosol and vacuole are strongly dependent on their lipophilicity. These findings suggest that the membrane-permeabilizing effect of straight-chain alcohols induces cytosolic and vacuolar acidification in a lipophilicity-dependent manner. Surprisingly, after ethanol challenge, the cytosolic pH in Δvma2 and Δvma3 mutants lacking V-ATPase activity was similar to that of the wild-type strain. It is therefore unlikely that the ethanol-sensitive phenotype of vma mutants resulted from severe cytosolic acidification. Interestingly, the vma mutants exposed to ethanol exhibited a delay in cell wall remodeling and a significant increase in intracellular reactive oxygen species (ROS). These findings suggest a role for V-ATPase in the regulation of the cell wall stress response and the prevention of endogenous oxidative stress in response to ethanol. IMPORTANCE The yeast Saccharomyces cerevisiae has been widely used in the alcoholic fermentation industry. Among the environmental stresses that yeast cells encounter during the process of alcoholic fermentation, ethanol is a major stress factor that inhibits yeast growth and viability, eventually leading to fermentation arrest. This study provides evidence for the molecular mechanisms of ethanol tolerance, which is a desirable characteristic for yeast strains

Vacuolar H+-ATPase Protects Saccharomyces cerevisiae Cells against Ethanol-Induced Oxidative and Cell Wall Stresses.

PubMed

Charoenbhakdi, Sirikarn; Dokpikul, Thanittra; Burphan, Thanawat; Techo, Todsapol; Auesukaree, Choowong

2016-05-15

During fermentation, increased ethanol concentration is a major stress for yeast cells. Vacuolar H(+)-ATPase (V-ATPase), which plays an important role in the maintenance of intracellular pH homeostasis through vacuolar acidification, has been shown to be required for tolerance to straight-chain alcohols, including ethanol. Since ethanol is known to increase membrane permeability to protons, which then promotes intracellular acidification, it is possible that the V-ATPase is required for recovery from alcohol-induced intracellular acidification. In this study, we show that the effects of straight-chain alcohols on membrane permeabilization and acidification of the cytosol and vacuole are strongly dependent on their lipophilicity. These findings suggest that the membrane-permeabilizing effect of straight-chain alcohols induces cytosolic and vacuolar acidification in a lipophilicity-dependent manner. Surprisingly, after ethanol challenge, the cytosolic pH in Δvma2 and Δvma3 mutants lacking V-ATPase activity was similar to that of the wild-type strain. It is therefore unlikely that the ethanol-sensitive phenotype of vma mutants resulted from severe cytosolic acidification. Interestingly, the vma mutants exposed to ethanol exhibited a delay in cell wall remodeling and a significant increase in intracellular reactive oxygen species (ROS). These findings suggest a role for V-ATPase in the regulation of the cell wall stress response and the prevention of endogenous oxidative stress in response to ethanol. The yeast Saccharomyces cerevisiae has been widely used in the alcoholic fermentation industry. Among the environmental stresses that yeast cells encounter during the process of alcoholic fermentation, ethanol is a major stress factor that inhibits yeast growth and viability, eventually leading to fermentation arrest. This study provides evidence for the molecular mechanisms of ethanol tolerance, which is a desirable characteristic for yeast strains used in alcoholic

Hepatorenal revascularization enables EVAR repair on a patient with AAA and an ectopic right renal artery.

PubMed

Lazaris, A M; Moulakakis, K; Mantas, G; Poulou, K; Alexiou, E; Vasdekis, S; Geroulakos, G

2018-06-07

The last thirty years the endovascular repair (EVAR) has become the standard method of treatment of abdominal aortic aneurysms (AAA). Nevertheless, the method has limitations based mainly on the anatomic characteristics of the specific aneurysm. In these cases a combination of endovascular and open techniques can be used. We describe a case of a patient with an infrarenal AAA and an ectopic right renal artery emerging from within the aneurysm sac. The patient was treated with a combination of endovascular and open techniques. In particular, he underwent a hepatorenal revascularization followed by a standard EVAR procedure, with a successful final outcome. For the treatment of AAA disease, the combination of open and endovascular procedures can overcome difficulties where a standard EVAR cannot be an option. Copyright © 2018 Elsevier Inc. All rights reserved.

Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

PubMed

Park, Brian; Dargon, Phong; Binette, Christopher; Babic, Bruna; Thomas, Tina; Divinagracia, Thomas; Dahn, Michael S; Menzoian, James O

2011-10-01

Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

Oscillatory motion based measurement method and sensor for measuring wall shear stress due to fluid flow

DOEpatents

Armstrong, William D [Laramie, WY; Naughton, Jonathan [Laramie, WY; Lindberg, William R [Laramie, WY

2008-09-02

A shear stress sensor for measuring fluid wall shear stress on a test surface is provided. The wall shear stress sensor is comprised of an active sensing surface and a sensor body. An elastic mechanism mounted between the active sensing surface and the sensor body allows movement between the active sensing surface and the sensor body. A driving mechanism forces the shear stress sensor to oscillate. A measuring mechanism measures displacement of the active sensing surface relative to the sensor body. The sensor may be operated under periodic excitation where changes in the nature of the fluid properties or the fluid flow over the sensor measurably changes the amplitude or phase of the motion of the active sensing surface, or changes the force and power required from a control system in order to maintain constant motion. The device may be operated under non-periodic excitation where changes in the nature of the fluid properties or the fluid flow over the sensor change the transient motion of the active sensor surface or change the force and power required from a control system to maintain a specified transient motion of the active sensor surface.

Distance-from-the-wall scaling of turbulent motions in wall-bounded flows

NASA Astrophysics Data System (ADS)

Baidya, R.; Philip, J.; Hutchins, N.; Monty, J. P.; Marusic, I.

2017-02-01

An assessment of self-similarity in the inertial sublayer is presented by considering the wall-normal velocity, in addition to the streamwise velocity component. The novelty of the current work lies in the inclusion of the second velocity component, made possible by carefully conducted subminiature ×-probe experiments to minimise the errors in measuring the wall-normal velocity. We show that not all turbulent stress quantities approach the self-similar asymptotic state at an equal rate as the Reynolds number is increased, with the Reynolds shear stress approaching faster than the streamwise normal stress. These trends are explained by the contributions from attached eddies. Furthermore, the Reynolds shear stress cospectra, through its scaling with the distance from the wall, are used to assess the wall-normal limits where self-similarity applies within the wall-bounded flow. The results are found to be consistent with the recent prediction from the work of Wei et al. ["Properties of the mean momentum balance in turbulent boundary layer, pipe and channel flows," J. Fluid Mech. 522, 303-327 (2005)], Klewicki ["Reynolds number dependence, scaling, and dynamics of turbulent boundary layers," J. Fluids Eng. 132, 094001 (2010)], and others that the self-similar region starts and ends at z+˜O (√{δ+}) and O (δ+) , respectively. Below the self-similar region, empirical evidence suggests that eddies responsible for turbulent stresses begin to exhibit distance-from-the-wall scaling at a fixed z+ location; however, they are distorted by viscous forces, which remain a leading order contribution in the mean momentum balance in the region z+≲O (√{δ+}) , and thus result in a departure from self-similarity.

Influence of left ventricular hypertrophy and geometry on diagnostic accuracy of wall motion and perfusion magnetic resonance during dobutamine stress.

PubMed

Gebker, Rolf; Mirelis, Jesus G; Jahnke, Cosima; Hucko, Thomas; Manka, Robert; Hamdan, Ashraf; Schnackenburg, Bernhard; Fleck, Eckart; Paetsch, Ingo

2010-09-01

The purpose of this study was to determine the influence of left ventricular (LV) hypertrophy and geometry on the diagnostic accuracy of wall motion and additional perfusion imaging during high-dose dobutamine/atropine stress magnetic resonance for the detection of coronary artery disease. Combined dobutamine stress magnetic resonance (DSMR)-wall motion and DSMR-perfusion imaging was performed in a single session in 187 patients scheduled for invasive coronary angiography. Patients were classified into 4 categories on the basis of LV mass (normal, ≤ 81 g/m(2) in men and ≤ 62 g/m(2) in women) and relative wall thickness (RWT) (normal, <0.45) as follows: normal geometry (normal mass, normal RWT), concentric remodeling (normal mass, increased RWT), concentric hypertrophy (increased mass, increased RWT), and eccentric hypertrophy (increased mass, normal RWT). Wall motion and perfusion images were interpreted sequentially, with observers blinded to other data. Significant coronary artery disease was defined as ≥ 70% stenosis. In patients with increased LV concentricity (defined by an RWT ≥ 0.45), sensitivity and accuracy of DSMR-wall motion were significantly reduced (63% and 73%, respectively; P<0.05) compared with patients without increased LV concentricity (90% and 88%, respectively; P<0.05). Although accuracy of DSMR-perfusion was higher than that of DSMR-wall motion in patients with concentric hypertrophy (82% versus 71%; P < 0.05), accuracy of DSMR-wall motion was superior to DSMR-perfusion (90% versus 85%; P < 0.05) in patients with eccentric hypertrophy. The accuracy of DSMR-wall motion is influenced by LV geometry. In patients with concentric remodeling and concentric hypertrophy, additional first-pass perfusion imaging during high-dose dobutamine stress improves the diagnostic accuracy for the detection of coronary artery disease.

Mechanism of Enzyme Repair by the AAA+ Chaperone Rubisco Activase.

PubMed

Bhat, Javaid Y; Miličić, Goran; Thieulin-Pardo, Gabriel; Bracher, Andreas; Maxwell, Andrew; Ciniawsky, Susanne; Mueller-Cajar, Oliver; Engen, John R; Hartl, F Ulrich; Wendler, Petra; Hayer-Hartl, Manajit

2017-09-07

How AAA+ chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA+ protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress intensity factors in a reinforced thick-walled cylinder

NASA Technical Reports Server (NTRS)

Tang, R.; Erdogan, F.

1984-01-01

An elastic thick-walled cylinder containing a radial crack is considered. It is assumed that the cylinder is reinforced by an elastic membrane on its inner surface. The model is intended to simulate pressure vessels with cladding. The formulation of the problem is reduced to a singular integral equation. Various special cases including that of a crack terminating at the cylinder-reinforcement interface are investigated and numerical examples are given. Results indicate that in the case of the crack touching the interface the crack surface displacement derivative is finite and consequently the stress state around the corresponding crack tip is bounded; and generally, for realistic values of the stiffness parameter, the effect of the reinforcement is not very significant.

Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR

PubMed Central

Lee, Lik Chuan; Zhihong, Zhang; Hinson, Andrew; Guccione, Julius M.

2013-01-01

Injection of Algisyl-LVR, a treatment under clinical development, is intended to treat patients with dilated cardiomyopathy. This treatment was recently used for the first time in patients who had symptomatic heart failure. In all patients, cardiac function of the left ventricle (LV) improved significantly, as manifested by consistent reduction of the LV volume and wall stress. Here we describe this novel treatment procedure and the methods used to quantify its effects on LV wall stress and function. Algisyl-LVR is a biopolymer gel consisting of Na+-Alginate and Ca2+-Alginate. The treatment procedure was carried out by mixing these two components and then combining them into one syringe for intramyocardial injections. This mixture was injected at 10 to 19 locations mid-way between the base and apex of the LV free wall in patients. Magnetic resonance imaging (MRI), together with mathematical modeling, was used to quantify the effects of this treatment in patients before treatment and at various time points during recovery. The epicardial and endocardial surfaces were first digitized from the MR images to reconstruct the LV geometry at end-systole and at end-diastole. Left ventricular cavity volumes were then measured from these reconstructed surfaces. Mathematical models of the LV were created from these MRI-reconstructed surfaces to calculate regional myofiber stress. Each LV model was constructed so that 1) it deforms according to a previously validated stress-strain relationship of the myocardium, and 2) the predicted LV cavity volume from these models matches the corresponding MRI-measured volume at end-diastole and end-systole. Diastolic filling was simulated by loading the LV endocardial surface with a prescribed end-diastolic pressure. Systolic contraction was simulated by concurrently loading the endocardial surface with a prescribed end-systolic pressure and adding active contraction in the myofiber direction. Regional myofiber stress at end-diastole and

Polymer-surfactant complex formation and its effect on turbulent wall shear stress.

PubMed

Suksamranchit, Siriluck; Sirivat, Anuvat; Jamieson, Alexander M

2006-02-01

Turbulent drag reduction in Couette flow was investigated in terms of a decrease in wall shear stress for aqueous solutions of a nonionic polymer, poly(ethylene oxide) (PEO), a cationic surfactant, hexadecyltrimethylammonium chloride (HTAC), and their mixtures. Consistent with literature data, drag reduction was observed for PEO solutions above a critical molecular weight, 0.91 x 10(5) < Mc < 3.04 x 10(5) g/mol. Maximum drag reduction occurred at an optimum concentration, c(PEO)*, which scales inversely with molecular weight, and the % maximum drag reduction increases with molecular weight. For aqueous HTAC solutions, wall shear stress decreased with increasing HTAC concentration and leveled off at an optimum concentration, c(HTAC)*, comparable to the critical micelle concentration. For HTAC/PEO mixtures, the critical PEO molecular weight for drag reduction decreases, interpreted as due to an increase in hydrodynamic volume because of binding of HTAC micelles to PEO. Consistent with this interpretation, at fixed PEO concentration, maximum drag reduction was observed at an optimum HTAC concentration, c(HTAC/PEO)*, comparable to the maximum binding concentration, MBC. Also, with HTAC concentration fixed at the MBC, the optimum PEO concentration for drag reduction, c(PEO/HTAC)*, decreases relative to that, c(PEO)*, in the absence of HTAC.

Identification of a Degradation Signal Sequence within Substrates of the Mitochondrial i-AAA Protease.

PubMed

Rampello, Anthony J; Glynn, Steven E

2017-03-24

The i-AAA protease is a component of the mitochondrial quality control machinery that regulates respiration, mitochondrial dynamics, and protein import. The protease is required to select specific substrates for degradation from among the diverse complement of proteins present in mitochondria, yet the rules that govern this selection are unclear. Here, we reconstruct the yeast i-AAA protease, Yme1p, to examine the in vitro degradation of two intermembrane space chaperone subunits, Tim9 and Tim10. Yme1p degrades Tim10 more rapidly than Tim9 despite high sequence and structural similarity, and loss of Tim10 is accelerated by the disruption of conserved disulfide bonds within the substrate. An unstructured N-terminal region of Tim10 is necessary and sufficient to target the substrate to the protease through recognition of a short phenylalanine-rich motif, and the presence of similar motifs in other small Tim proteins predicts robust degradation by the protease. Together, these results identify the first specific degron sequence within a native i-AAA protease substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic variation within the Y chromosome is not associated with histological characteristics of the atherosclerotic carotid artery or aneurysmal wall.

PubMed

Haitjema, Saskia; van Setten, Jessica; Eales, James; van der Laan, Sander W; Gandin, Ilaria; de Vries, Jean-Paul P M; de Borst, Gert J; Pasterkamp, Gerard; Asselbergs, Folkert W; Charchar, Fadi J; Wilson, James F; de Jager, Saskia C A; Tomaszewski, Maciej; den Ruijter, Hester M

2017-04-01

Haplogroup I, a common European paternal lineage of the Y chromosome, is associated with increased risk of coronary artery disease in British men. It is unclear whether this haplogroup or any other haplogroup on the Y chromosome is associated with histological characteristics of the diseased vessel wall in other vascular manifestations of cardiovascular diseases showing a male preponderance. We examined Dutch men undergoing either carotid endarterectomy from the Athero-Express biobank (AE, n = 1217) or open aneurysm repair from the Aneurysm-Express biobank (AAA, n = 393). Upon resolving the Y chromosome phylogeny, each man was assigned to one of the paternal lineages based on combinations of single nucleotide polymorphisms of the male-specific region of the Y chromosome. We examined the associations between the Y chromosome and the histological characteristics of the carotid plaque and aneurysm wall, including lipid content, leukocyte infiltration and intraplaque haemorrhage, in all men. A majority of men were carriers of either haplogroup I (AE: 28% AAA: 24%) or haplogroup R (AE: 59% AAA: 61%). We found no association between Y chromosomal haplogroups and histological characteristics of plaque collected from carotid arteries or tissue specimens of aneurysms. Moreover, the distribution of frequency for all Y chromosomal haplogroups in both cohorts was similar to that of a general population of Dutch men. Our data show that genetic variation on the Y chromosome is not associated with histological characteristics of the plaques from carotid arteries or specimens of aneurysms in men of Dutch origin. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of mitochondrial processing peptidase and AAA proteases in processing of the yeast acetohydroxyacid synthase precursor.

PubMed

Dasari, Suvarna; Kölling, Ralf

2016-07-01

We studied presequence processing of the mitochondrial-matrix targeted acetohydroxyacid synthase (Ilv2). C-terminal 3HA-tagging altered the cleavage pattern from a single step to sequential two-step cleavage, giving rise to two Ilv2-3HA forms (A and B). Both cleavage events were dependent on the mitochondrial processing peptidase (MPP). We present evidence for the involvement of three AAA ATPases, m- and i-AAA proteases, and Mcx1, in Ilv2-3HA processing. Both, precursor to A-form and A-form to B-form cleavage were strongly affected in a ∆yme1 mutant. These defects could be suppressed by overexpression of MPP, suggesting that MPP activity is limiting in the ∆yme1 mutant. Our data suggest that for some substrates AAA ATPases could play an active role in the translocation of matrix-targeted proteins.

Direct measurements of wall shear stress by buried wire gages in a shock-wave boundary-layer interaction region

NASA Technical Reports Server (NTRS)

Murthy, V. S.; Rose, W. C.

1977-01-01

Detailed measurements of wall shear stress (skin friction) were made with specially developed buried wire gages in the interaction regions of a Mach 2.9 turbulent boundary layer with externally generated shocks. Separation and reattachment points inferred by these measurements support the findings of earlier experiments which used a surface oil flow technique and pitot profile measurements. The measurements further indicate that the boundary layer tends to attain significantly higher skin-friction values downstream of the interaction region as compared to upstream. Comparisons between measured wall shear stress and published results of some theoretical calculation schemes show that the general, but not detailed, behavior is predicted well by such schemes.

Discovery of Novel Cell Wall-Active Compounds Using PywaC, a Sensitive Reporter of Cell Wall Stress, in the Model Gram-Positive Bacterium Bacillus subtilis

PubMed Central

Czarny, T. L.; Perri, A. L.; French, S.

2014-01-01

The emergence of antibiotic resistance in recent years has radically reduced the clinical efficacy of many antibacterial treatments and now poses a significant threat to public health. One of the earliest studied well-validated targets for antimicrobial discovery is the bacterial cell wall. The essential nature of this pathway, its conservation among bacterial pathogens, and its absence in human biology have made cell wall synthesis an attractive pathway for new antibiotic drug discovery. Herein, we describe a highly sensitive screening methodology for identifying chemical agents that perturb cell wall synthesis, using the model of the Gram-positive bacterium Bacillus subtilis. We report on a cell-based pilot screen of 26,000 small molecules to look for cell wall-active chemicals in real time using an autonomous luminescence gene cluster driven by the promoter of ywaC, which encodes a guanosine tetra(penta)phosphate synthetase that is expressed under cell wall stress. The promoter-reporter system was generally much more sensitive than growth inhibition testing and responded almost exclusively to cell wall-active antibiotics. Follow-up testing of the compounds from the pilot screen with secondary assays to verify the mechanism of action led to the discovery of 9 novel cell wall-active compounds. PMID:24687489

The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus Deposition in Abdominal Aortic Aneurysms.

PubMed

Lozowy, Richard J; Kuhn, David C S; Ducas, Annie A; Boyd, April J

2017-03-01

Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.

A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPases.

PubMed

Pöhler, Robert; Krahn, Jan H; van den Boom, Johannes; Dobrynin, Grzegorz; Kaschani, Farnusch; Eggenweiler, Hans-Michael; Zenke, Frank T; Kaiser, Markus; Meyer, Hemmo

2018-02-05

AAA ATPases have pivotal functions in diverse cellular processes essential for survival and proliferation. Revealing strategies for chemical inhibition of this class of enzymes is therefore of great interest for the development of novel chemotherapies or chemical tools. Here, we characterize the compound MSC1094308 as a reversible, allosteric inhibitor of the type II AAA ATPase human ubiquitin-directed unfoldase (VCP)/p97 and the type I AAA ATPase VPS4B. Subsequent proteomic, genetic and biochemical studies indicate that MSC1094308 binds to a previously characterized drugable hotspot of p97, thereby inhibiting the D2 ATPase activity. Our results furthermore indicate that a similar allosteric site exists in VPS4B, suggesting conserved allosteric circuits and drugable sites in both type I and II AAA ATPases. Our results may thus guide future chemical tool and drug discovery efforts for the biomedically relevant AAA ATPases. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Incidence and risk factors of ischemic colitis after AAA repair in our cohort of patients from 2005 through 2009].

PubMed

Biros, E; Staffa, R

2011-12-01

Using retrospective analysis, we sought to investigate the incidence, risk factors and therapeutic outcomes of ischemic colitis in patients after surgical and endovascular repair of abdominal aortic aneurysms (AAA). The complete inpatient and outpatient medical records of all patients undergoing surgical or endovascular AAA repair in our Department from January 2005 to December 2009 were retrospectively reviewed. We selected all patients who had developed an acute or chronic form of postoperative large or small bowel ischemia. We carried out data analysis and focused on determining the incidence and risk factors of this complication and the outcomes of its treatment. Two hundred and seven AAA repairs were performed in the 2nd Department of Surgery of St. Anne's University Hospital in Brno and the Faculty of Medicine of Masaryk University in Brno during the studied period. This number includes endovascular AAA repairs (13 patients; 6.3%) as well as one robot-assisted operation, and also the whole clinical spectrum of AAA manifestations, from non-symptomatic forms to ruptured aneurysm forms. The rest of the patients underwent open operation. Bowel ischemia developed in a total of 11 patients (5.3 %), who all underwent open AAA repair. Six of these patients presented with non-ruptured AAA and the remaining 5 with ruptured AAA. In 3 patients, bowel ischemia was diagnosed with a delay of several months from the original revascularization operation in the clinical form of postischemic stricture of the large bowel (2 patients) or postischemic colitis (1 patient). 8 patients were diagnosed with acute ischemic colitis affecting an isolated segment of the small bowel in one patient, extended segments of the large bowel (descending colon + sigmoid colon + rectum) in 2 patients, and typically the descending and sigmoid colon in 5 patients. None of the three patients with late manifestation of ischemic colitis died. Of the 8 patients with acute presentation, resection of the

Regulation of Cell Wall Biogenesis in Saccharomyces cerevisiae: The Cell Wall Integrity Signaling Pathway

PubMed Central

Levin, David E.

2011-01-01

The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to the Rho1 GTPase, which mobilizes a physiologic response through a variety of effectors. Activation of CWI signaling regulates the production of various carbohydrate polymers of the cell wall, as well as their polarized delivery to the site of cell wall remodeling. This review article centers on CWI signaling in Saccharomyces cerevisiae through the cell cycle and in response to cell wall stress. The interface of this signaling pathway with other pathways that contribute to the maintenance of cell wall integrity is also discussed. PMID:22174182

SU-E-T-122: Anisotropic Analytical Algorithm (AAA) Vs. Acuros XB (AXB) in Stereotactic Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mynampati, D; Scripes, P Godoy; Kuo, H

2015-06-15

Purpose: To evaluate dosimetric differences between superposition beam model (AAA) and determinant photon transport solver (AXB) in lung SBRT and Cranial SRS dose computations. Methods: Ten Cranial SRS and ten Lung SBRT plans using Varian, AAA -11.0 were re-planned using Acuros -XB-11.0 with fixed MU. 6MV photon Beam model with HD120-MLC used for dose calculations. Four non-coplanar conformal arcs used to deliver 21Gy or 18Gy to SRS targets (0.4 to 6.2cc). 54Gy (3Fractions) or 50Gy (5Fractions) was planned for SBRT targets (7.3 to 13.9cc) using two VAMT non-coplanar arcs. Plan comparison parameters were dose to 1% PTV volume (D1), dosemore » to 99% PTV volume( D99), Target mean (Dmean), Conformity index (ratio of prescription isodose volume to PTV), Homogeneity Index [ (D2%-D98%)/Dmean] and R50 (ratio of 50% of prescription isodose volume to PTV). OAR parameters were Brain volume receiving 12Gy dose (V12Gy) and maximum dose (D0.03) to Brainstem for SRS. For lung SBRT, maximum dose to Heart and Cord, Mean lung dose (MLD) and volume of lung receiving 20Gy (V20Gy) were computed. PTV parameters compared by percentage difference between AXB and AAA parameters. OAR parameters and HI compared by absolute difference between two calculations. For analysis, paired t-test performed over the parameters. Results: Compared to AAA, AXB SRS plans have on average 3.2% lower D99, 6.5% lower CI and 3cc less Brain-V12. However, AXB SBRT plans have higher D1, R50 and Dmean by 3.15%, 1.63% and 2.5%. For SRS and SBRT, AXB plans have average HI 2 % and 4.4% higher than AAA plans. In both techniques, all other parameters vary within 1% or 1Gy. In both sets only two parameters have P>0.05. Conclusion: Even though t-test results signify difference between AXB and AAA plans, dose differences in dose estimations by both algorithms are clinically insignificant.« less

CXCL8 hyper-signaling in the aortic abdominal aneurysm.

PubMed

Kokje, Vivianne B C; Gäbel, Gabor; Dalman, Ron L; Koole, Dave; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-08-01

There are indications for elevated CXCL8 levels in abdominal aortic aneurysm disease (AAA). CXCL8 is concurrently involved in neutrophil-mediated inflammation and angiogenesis, two prominent and distinctive characteristics of AAA. As such we considered an evaluation of a role for CXCL8 in AAA progression relevant. ELISA's, real time PCR and array analysis were used to explore CXCL8 signaling in AAA wall samples. A role for CXCL8 in AAA disease was tested through the oral CXCR1/2 antagonist DF2156A in the elastase model of AAA disease. There is an extreme disparity in aortic wall CXCL8 content between AAA and aortic atherosclerotic disease (median [IQR] aortic wall CXCL8 content: 425 [141-1261] (AAA) vs. 23 [2.8-89] (atherosclerotic aorta) µg/g protein (P < 1 · 10 -14 )), and abundant expression of the CXCR1 and 2 receptors in AAA. Array analysis followed by pathway analysis showed that CXCL8 hyper-expression in AAA is followed increased by IL-8 signaling (Z-score for AAA vs. atherosclerotic control: 2.97, p < 0.0001). Interference with CXCL8 signaling through DF2156A fully abrogated AAA formation and prevented matrix degradation in the murine elastase model of AAA disease (p < 0.001). CXCL8-signaling is a prominent and distinctive feature of AAA, interference with the pathway constitutes a promising target for medical stabilization of AAA. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Strain-encoded cardiac MRI as an adjunct for dobutamine stress testing: incremental value to conventional wall motion analysis.

PubMed

Korosoglou, Grigorios; Lossnitzer, Dirk; Schellberg, Dieter; Lewien, Antje; Wochele, Angela; Schaeufele, Tim; Neizel, Mirja; Steen, Henning; Giannitsis, Evangelos; Katus, Hugo A; Osman, Nael F

2009-03-01

High-dose dobutamine stress MRI is safe and feasible for the diagnosis of coronary artery disease (CAD) in humans. However, the assessment of cine scans relies on the visual interpretation of regional wall motion, which is subjective. Recently, strain-encoded MRI (SENC) has been proposed for the direct color-coded visualization of myocardial strain. The purpose of our study was to compare the diagnostic value of SENC with that provided by conventional wall motion analysis for the detection of inducible ischemia during dobutamine stress MRI. Stress-induced ischemia was assessed by wall motion analysis and by SENC in 101 patients with suspected or known CAD and in 17 healthy volunteers who underwent dobutamine stress MRI in a clinical 1.5-T scanner. Quantitative coronary angiography deemed as the standard reference for the presence or absence of significant CAD (> or =50% diameter stenosis). On a coronary vessel level, SENC detected inducible ischemia in 86 of 101 versus 71 of 101 diseased coronary vessels (P<0.01 versus cine) and showed normal strain response in 189 of 202 versus 194 of 202 vessels with <50% stenosis (P=NS versus cine). On a patient level, SENC detected inducible ischemia in 63 of 64 versus 55 of 64 patients with CAD (P<0.05 versus cine) and showed normal strain response in 32 of 37 versus 34 of 37 patients without CAD (P=NS versus cine). Quantification analysis demonstrated a significant correlation between strain rate reserve and coronary artery stenosis severity (r(2)=0.56, P<0.001), and a cutoff value of strain rate reserve of 1.64 was deemed as a highly accurate marker for the detection of > or =50% stenosis (area under the curve, 0.96; SE, 0.01; 95% CI, 0.94 to 0.98; P<0.001). The direct color-coded visualization of strain on MR images is a useful adjunct for dobutamine stress MRI, which provides incremental value for the detection of CAD compared with conventional wall motion readings on cine images.

Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine

PubMed Central

Iosefson, Ohad; Nager, Andrew R.; Baker, Tania A.; Sauer, Robert T.

2014-01-01

Hexameric AAA+ unfoldases of ATP-dependent proteases and protein-remodeling machines use conserved loops that line the axial pore to apply force to substrates during the mechanical processes of protein unfolding and translocation. Whether loops from multiple subunits act independently or coordinately in these processes is a critical aspect of mechanism but is currently unknown for any AAA+ machine. By studying covalently linked hexamers of the E. coli ClpX unfoldase bearing different numbers and configurations of wild-type and mutant pore loops, we show that loops function synergistically, with the number of wild-type loops required for efficient degradation depending upon the stability of the protein substrate. Our results support a mechanism in which a power stroke initiated in one subunit of the ClpX hexamer results in the concurrent movement of all six pore loops, which coordinately grip and apply force to the substrate. PMID:25599533

From AAA to Acuros XB-clinical implications of selecting either Acuros XB dose-to-water or dose-to-medium.

PubMed

Zifodya, Jackson M; Challens, Cameron H C; Hsieh, Wen-Long

2016-06-01

When implementing Acuros XB (AXB) as a substitute for anisotropic analytic algorithm (AAA) in the Eclipse Treatment Planning System, one is faced with a dilemma of reporting either dose to medium, AXB-Dm or dose to water, AXB-Dw. To assist with decision making on selecting either AXB-Dm or AXB-Dw for dose reporting, a retrospective study of treated patients for head & neck (H&N), prostate, breast and lung is presented. Ten patients, previously treated using AAA plans, were selected for each site and re-planned with AXB-Dm and AXB-Dw. Re-planning was done with fixed monitor units (MU) as well as non-fixed MUs. Dose volume histograms (DVH) of targets and organs at risk (OAR), were analyzed in conjunction with ICRU-83 recommended dose reporting metrics. Additionally, comparisons of plan homogeneity indices (HI) and MUs were done to further highlight the differences between the algorithms. Results showed that, on average AAA overestimated dose to the target volume and OARs by less than 2.0 %. Comparisons between AXB-Dw and AXB-Dm, for all sites, also showed overall dose differences to be small (<1.5 %). However, in non-water biological media, dose differences between AXB-Dw and AXB-Dm, as large as 4.6 % were observed. AXB-Dw also tended to have unexpectedly high 3D maximum dose values (>135 % of prescription dose) for target volumes with high density materials. Homogeneity indices showed that AAA planning and optimization templates would need to be adjusted only for the H&N and Lung sites. MU comparison showed insignificant differences between AXB-Dw relative to AAA and between AXB-Dw relative to AXB-Dm. However AXB-Dm MUs relative to AAA, showed an average difference of about 1.3 % signifying an underdosage by AAA. In conclusion, when dose is reported as AXB-Dw, the effect that high density structures in the PTV has on the dose distribution should be carefully considered. As the results show overall small dose differences between the algorithms, when

SU-E-T-516: Dosimetric Validation of AcurosXB Algorithm in Comparison with AAA & CCC Algorithms for VMAT Technique.

PubMed

Kathirvel, M; Subramanian, V Sai; Arun, G; Thirumalaiswamy, S; Ramalingam, K; Kumar, S Ashok; Jagadeesh, K

2012-06-01

To dosimetrically validate AcurosXB algorithm for Volumetric Modulated Arc Therapy (VMAT) in comparison with standard clinical Anisotropic Analytic Algorithm(AAA) and Collapsed Cone Convolution(CCC) dose calculation algorithms. AcurosXB dose calculation algorithm is available with Varian Eclipse treatment planning system (V10). It uses grid-based Boltzmann equation solver to predict dose precisely in lesser time. This study was made to realize algorithms ability to predict dose accurately as its delivery for which five clinical cases each of Brain, Head&Neck, Thoracic, Pelvic and SBRT were taken. Verification plans were created on multicube phantom with iMatrixx-2D detector array and then dose prediction was done with AcurosXB, AAA & CCC (COMPASS System) algorithm and the same were delivered onto CLINAC-iX treatment machine. Delivered dose was captured in iMatrixx plane for all 25 plans. Measured dose was taken as reference to quantify the agreement between AcurosXB calculation algorithm against previously validated AAA and CCC algorithm. Gamma evaluation was performed with clinical criteria distance-to-agreement 3&2mm and dose difference 3&2% in omnipro-I'MRT software. Plans were evaluated in terms of correlation coefficient, quantitative area gamma and average gamma. Study shows good agreement between mean correlation 0.9979±0.0012, 0.9984±0.0009 & 0.9979±0.0011 for AAA, CCC & Acuros respectively. Mean area gamma for criteria 3mm/3% was found to be 98.80±1.04, 98.14±2.31, 98.08±2.01 and 2mm/2% was found to be 93.94±3.83, 87.17±10.54 & 92.36±5.46 for AAA, CCC & Acuros respectively. Mean average gamma for 3mm/3% was 0.26±0.07, 0.42±0.08, 0.28±0.09 and 2mm/2% was found to be 0.39±0.10, 0.64±0.11, 0.42±0.13 for AAA, CCC & Acuros respectively. This study demonstrated that the AcurosXB algorithm had a good agreement with the AAA & CCC in terms of dose prediction. In conclusion AcurosXB algorithm provides a valid, accurate and speedy alternative to AAA

Comparative transcriptomics indicate changes in cell wall organization and stress response in seedlings during spaceflight.

PubMed

Johnson, Christina M; Subramanian, Aswati; Pattathil, Sivakumar; Correll, Melanie J; Kiss, John Z

2017-08-21

Plants will play an important role in the future of space exploration as part of bioregenerative life support. Thus, it is important to understand the effects of microgravity and spaceflight on gene expression in plant development. We analyzed the transcriptome of Arabidopsis thaliana using the Biological Research in Canisters (BRIC) hardware during Space Shuttle mission STS-131. The bioinformatics methods used included RMA (robust multi-array average), MAS5 (Microarray Suite 5.0), and PLIER (probe logarithmic intensity error estimation). Glycome profiling was used to analyze cell wall composition in the samples. In addition, our results were compared to those of two other groups using the same hardware on the same mission (BRIC-16). In our BRIC-16 experiments, we noted expression changes in genes involved in hypoxia and heat shock responses, DNA repair, and cell wall structure between spaceflight samples compared to the ground controls. In addition, glycome profiling supported our expression analyses in that there was a difference in cell wall components between ground control and spaceflight-grown plants. Comparing our studies to those of the other BRIC-16 experiments demonstrated that, even with the same hardware and similar biological materials, differences in results in gene expression were found among these spaceflight experiments. A common theme from our BRIC-16 space experiments and those of the other two groups was the downregulation of water stress response genes in spaceflight. In addition, all three studies found differential regulation of genes associated with cell wall remodeling and stress responses between spaceflight-grown and ground control plants. © 2017 Botanical Society of America.

Developmental Localization and Methylesterification of Pectin Epitopes during Somatic Embryogenesis of Banana (Musa spp. AAA)

PubMed Central

Xu, Chunxiang; Zhao, Lu; Pan, Xiao; Šamaj, Jozef

2011-01-01

Background The plant cell walls play an important role in somatic embryogenesis and plant development. Pectins are major chemical components of primary cell walls while homogalacturonan (HG) is the most abundant pectin polysaccharide. Developmental regulation of HG methyl-esterification degree is important for cell adhesion, division and expansion, and in general for proper organ and plant development. Methodology/Principal Findings Developmental localization of pectic homogalacturonan (HG) epitopes and the (1→4)-β-D-galactan epitope of rhamnogalacturonan I (RG-I) and degree of pectin methyl-esterification (DM) were studied during somatic embryogenesis of banana (Musa spp. AAA). Histological analysis documented all major developmental stages including embryogenic cells (ECs), pre-globular, globular, pear-shaped and cotyledonary somatic embryos. Histochemical staining of extracellularly secreted pectins with ruthenium red showed the most intense staining at the surface of pre-globular, globular and pear-shaped somatic embryos. Biochemical analysis revealed developmental regulation of galacturonic acid content and DM in diverse embryogenic stages. Immunodots and immunolabeling on tissue sections revealed developmental regulation of highly methyl-esterified HG epitopes recognized by JIM7 and LM20 antibodies during somatic embryogenesis. Cell walls of pre-globular/globular and late-stage embryos contained both low methyl-esterified HG epitopes as well as partially and highly methyl-esterified ones. Extracellular matrix which covered surface of early developing embryos contained pectin epitopes recognized by 2F4, LM18, JIM5, JIM7 and LM5 antibodies. De-esterification of cell wall pectins by NaOH caused a decrease or an elimination of immunolabeling in the case of highly methyl-esterified HG epitopes. However, immunolabeling of some low methyl-esterified epitopes appeared stronger after this base treatment. Conclusions/Significance These data suggest that both low

Understanding the pathogenesis of abdominal aortic aneurysms

PubMed Central

Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Tromp, Gerard

2016-01-01

Summary An aortic aneurysm is a dilatation in which the aortic diameter is ≥ 3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50 – 80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA. PMID:26308600

Analysis of the cooperative ATPase cycle of the AAA+ chaperone ClpB from Thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.

PubMed

Yamasaki, Takashi; Oohata, Yukiko; Nakamura, Toshiki; Watanabe, Yo-hei

2015-04-10

The ClpB/Hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with DnaK/Hsp70 and its cofactors. The ClpB/Hsp104 protomer has two AAA+ modules, AAA-1 and AAA-2, and forms a homohexamer. In the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic AAA+ modules. By ATP binding and its hydrolysis at these AAA+ modules, ClpB/Hsp104 exerts the mechanical power required for protein disaggregation. Although ATPase cycle of this chaperone has been studied by several groups, an integrated understanding of this cycle has not been obtained because of the complexity of the mechanism and differences between species. To improve our understanding of the ATPase cycle, we prepared many ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately and measured their nucleotide binding, ATP hydrolysis, and disaggregation abilities. The results indicated that the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring was sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. We also found that cooperative ATP hydrolysis in at least one ring was needed for the disaggregation activity of ClpB. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A numerical framework for studying the biomechanical behavior of abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Jalalahmadi, Golnaz; Linte, Cristian; Helguera, María.

2017-03-01

Abdominal aortic aneurysm (AAA) is known as a leading cause of death in the United States. AAA is an abnormal dilation of the aorta, which usually occurs below the renal arteries and causes an expansion at least 1.5 times its normal diameter. It has been shown that biomechanical parameters of the aortic tissue coupled with a set of specific geometric parameters characterizing the vessel expansion, affect the risk of aneurysm rupture. Here, we developed a numerical framework that incorporates both biomechanical and geometrical factors to study the behavior of abdominal aortic aneurysm. Our workflow enables the extraction of the aneurysm geometry from both clinical quality, as well as low-resolution MR images. We used a two-parameter, hyper-elastic, isotropic, incompressible material to model the vessel tissue. Our numerical model was tested using both synthetic and mouse data and we evaluated the effects of the geometrical and biomechanical properties on the developed peak wall stress. In addition, we performed several parameter sensitivity studies to investigate the effect of different factors affecting the AAA and its behavior and rupture. Lastly, relationships between different geometrical and biomechanical parameters and peak wall stress were determined. These studies help us better understand vessel tissue response to various loading, geometry and biomechanics conditions, and we plan to further correlate these findings with the pathophysiological conditions from a patient population diagnosed with abdominal aortic aneurysms.

A two-system, single-analysis, fluid-structure interaction technique for modelling abdominal aortic aneurysms.

PubMed

Kelly, S C; O'Rourke, M J

2010-01-01

This work reports on the implementation and validation of a two-system, single-analysis, fluid-structure interaction (FSI) technique that uses the finite volume (FV) method for performing simulations on abdominal aortic aneurysm (AAA) geometries. This FSI technique, which was implemented in OpenFOAM, included fluid and solid mesh motion and incorporated a non-linear material model to represent AAA tissue. Fully implicit coupling was implemented, ensuring that both the fluid and solid domains reached convergence within each time step. The fluid and solid parts of the FSI code were validated independently through comparison with experimental data, before performing a complete FSI simulation on an idealized AAA geometry. Results from the FSI simulation showed that a vortex formed at the proximal end of the aneurysm during systolic acceleration, and moved towards the distal end of the aneurysm during diastole. Wall shear stress (WSS) values were found to peak at both the proximal and distal ends of the aneurysm and remain low along the centre of the aneurysm. The maximum von Mises stress in the aneurysm wall was found to be 408kPa, and this occurred at the proximal end of the aneurysm, while the maximum displacement of 2.31 mm occurred in the centre of the aneurysm. These results were found to be consistent with results from other FSI studies in the literature.

Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48.

PubMed

Esaki, Masatoshi; Islam, Md Tanvir; Tani, Naoki; Ogura, Teru

2017-07-14

Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism.

Discovery of novel cell wall-active compounds using P ywaC, a sensitive reporter of cell wall stress, in the model gram-positive bacterium Bacillus subtilis.

PubMed

Czarny, T L; Perri, A L; French, S; Brown, E D

2014-06-01

The emergence of antibiotic resistance in recent years has radically reduced the clinical efficacy of many antibacterial treatments and now poses a significant threat to public health. One of the earliest studied well-validated targets for antimicrobial discovery is the bacterial cell wall. The essential nature of this pathway, its conservation among bacterial pathogens, and its absence in human biology have made cell wall synthesis an attractive pathway for new antibiotic drug discovery. Herein, we describe a highly sensitive screening methodology for identifying chemical agents that perturb cell wall synthesis, using the model of the Gram-positive bacterium Bacillus subtilis. We report on a cell-based pilot screen of 26,000 small molecules to look for cell wall-active chemicals in real time using an autonomous luminescence gene cluster driven by the promoter of ywaC, which encodes a guanosine tetra(penta)phosphate synthetase that is expressed under cell wall stress. The promoter-reporter system was generally much more sensitive than growth inhibition testing and responded almost exclusively to cell wall-active antibiotics. Follow-up testing of the compounds from the pilot screen with secondary assays to verify the mechanism of action led to the discovery of 9 novel cell wall-active compounds. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

An experimental study of near wall flow parameters in the blade end-wall corner region

NASA Technical Reports Server (NTRS)

Bhargava, Rakesh K.; Raj, Rishi S.

1989-01-01

The near wall flow parameters in the blade end-wall corner region is investigated. The blade end-wall corner region was simulated by mounting an airfoil section (NACA 65-015 base profile) symmetric blades on both sides of the flat plate with semi-circular leading edge. The initial 7 cm from the leading edge of the flat plate was roughened by gluing No. 4 floor sanding paper to artificially increase the boundary layer thickness on the flat plate. The initial flow conditions of the boundary layer upstream of the corner region are expected to dictate the behavior of flow inside the corner region. Therefore, an experimental investigation was extended to study the combined effect of initial roughness and increased level of free stream turbulence on the development of a 2-D turbulent boundary layer in the absence of the blade. The measurement techniques employed in the present investigation included, the conventional pitot and pitot-static probes, wall taps, the Preston tube, piezoresistive transducer and the normal sensor hot-wire probe. The pitot and pitot-static probes were used to obtain mean velocity profile measurements within the boundary layer. The measurements of mean surface static pressure were obtained with the surface static tube and the conventional wall tap method. The wall shear vector measurements were made with a specially constructed Preston tube. The flush mounted piezoresistive type pressure transducer were employed to measure the wall pressure fluctuation field. The velocity fluctuation measurements, used in obtaining the wall pressure-velocity correlation data, were made with normal single sensor hot-wire probe. At different streamwise stations, in the blade end-wall corner region, the mean values of surface static pressure varied more on the end-wall surface in the corner region were mainly caused by the changes in the curvature of the streamlines. The magnitude of the wall shear stress in the blade end-wall corner region increased significantly

m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal Growth Conditions Despite Their Importance for Mitochondrial Translation.

PubMed

Kolodziejczak, Marta; Skibior-Blaszczyk, Renata; Janska, Hanna

2018-05-01

For optimal mitochondrial activity, the mitochondrial proteome must be properly maintained or altered in response to developmental and environmental stimuli. Based on studies of yeast and humans, one of the key players in this control are m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes. This study focuses on the importance of m-AAA proteases in plant mitochondria, providing their first experimentally proven physiological substrate. We found that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial translation and functionality of OXPHOS (oxidative phosphorylation) complexes are impaired. However, in contrast to their mammalian or yeast counterparts, plant m-AAA complexes are not critical for the survival of Arabidopsis under optimal conditions; ftsh3/10 plants are only slightly smaller in size at the early developmental stage compared with plants containing m-AAA complexes. Our data suggest that a lack of significant visible morphological alterations under optimal growth conditions involves mechanisms which rely on existing functional redundancy and induced functional compensation in Arabidopsis mitochondria.

The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

PubMed

Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

2018-01-29

Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

Assessment of resistomycin, as an anticancer compound isolated and characterized from Streptomyces aurantiacus AAA5.

PubMed

Vijayabharathi, Rajendran; Bruheim, Per; Andreassen, Trygve; Raja, Duraisamy Senthil; Devi, Palanisamy Bruntha; Sathyabama, Sathyaseelan; Priyadarisini, Venkatesan Brindha

2011-12-01

A new actinomycete strain, isolated from humus soils in the Western Ghats, was found to be an efficient pigment producer. The strain, designated AAA5, was identified as a putative Streptomyces aurantiacus strain based on cultural properties, morphology, carbon source utilization, and analysis of the 16S rRNA gene. The strain produced a reddish-brown pigmented compound during the secondary metabolites phase. A yellow compound was derived from the extracted pigment and was identified as the quinone-related antibiotic resistomycin based on ultraviolet-visible spectrophotometry, fourier transform infrared spectroscopy, liquid chromatography and mass spectroscopy, and nuclear magnetic resonance analyses. The AAA5 strain was found to produce large quantities of resistomycin (52.5 mg/L). It showed potent cytotoxic activity against cell lines viz. HepG2 (hepatic carcinoma) and HeLa (cervical carcinoma) in vitro, with growth inhibition (GI(50)) of 0.006 and 0.005 μg/ml, respectively. The strain also exhibited broad antimicrobial activities against both Gram-positive and Gram-negative bacteria. Therefore, AAA5 may have great potential as an industrial resistomycin-producing strain.

The Abdominal Aortic Aneurysm Statistically Corrected Operative Risk Evaluation (AAA SCORE) for predicting mortality after open and endovascular interventions.

PubMed

Ambler, Graeme K; Gohel, Manjit S; Mitchell, David C; Loftus, Ian M; Boyle, Jonathan R

2015-01-01

Accurate adjustment of surgical outcome data for risk is vital in an era of surgeon-level reporting. Current risk prediction models for abdominal aortic aneurysm (AAA) repair are suboptimal. We aimed to develop a reliable risk model for in-hospital mortality after intervention for AAA, using rigorous contemporary statistical techniques to handle missing data. Using data collected during a 15-month period in the United Kingdom National Vascular Database, we applied multiple imputation methodology together with stepwise model selection to generate preoperative and perioperative models of in-hospital mortality after AAA repair, using two thirds of the available data. Model performance was then assessed on the remaining third of the data by receiver operating characteristic curve analysis and compared with existing risk prediction models. Model calibration was assessed by Hosmer-Lemeshow analysis. A total of 8088 AAA repair operations were recorded in the National Vascular Database during the study period, of which 5870 (72.6%) were elective procedures. Both preoperative and perioperative models showed excellent discrimination, with areas under the receiver operating characteristic curve of .89 and .92, respectively. This was significantly better than any of the existing models (area under the receiver operating characteristic curve for best comparator model, .84 and .88; P < .001 and P = .001, respectively). Discrimination remained excellent when only elective procedures were considered. There was no evidence of miscalibration by Hosmer-Lemeshow analysis. We have developed accurate models to assess risk of in-hospital mortality after AAA repair. These models were carefully developed with rigorous statistical methodology and significantly outperform existing methods for both elective cases and overall AAA mortality. These models will be invaluable for both preoperative patient counseling and accurate risk adjustment of published outcome data. Copyright © 2015 Society

Estimation of the supplementary axial wall stress generated at peak flow by an arterial stenosis

NASA Astrophysics Data System (ADS)

Doriot, Pierre-André

2003-01-01

Mechanical stresses in arterial walls are known to be implicated in the development of atherosclerosis. While shear stress and circumferential stress have received a lot of attention, axial stress has not. Yet, stenoses can be intuitively expected to produce a supplementary axial stress during flow systole in the region immediately proximal to the constriction cone. In this paper, a model for the estimation of this effect is presented, and ten numerical examples are computed. These examples show that the cyclic increase in axial stress can be quite considerable in severe stenoses (typically 120% or more of the normal stress value). This result is in best agreement with the known mechanical or morphological risk factors of stenosis progression and restenosis (hypertension, elevated pulse pressure, degree of stenosis, stenosis geometry, residual stenosis, etc). The supplementary axial stress generated by a stenosis might create the damages in the endothelium and in the elastic membranes which potentiate the action of the other risk factors (hyperlipidaemia, diabetes, etc). It could thus be an important cause of stenosis progression and of restenosis.

Interaction between a normal shock wave and a turbulent boundary layer at high transonic speeds. II - Wall shear stress

NASA Technical Reports Server (NTRS)

Liou, M. S.; Adamson, T. C., Jr.

1980-01-01

Asymptotic methods are used to calculate the shear stress at the wall for the interaction between a normal shock wave and a turbulent boundary layer on a flat plate. A mixing length model is used for the eddy viscosity. The shock wave is taken to be strong enough that the sonic line is deep in the boundary layer and the upstream influence is thus very small. It is shown that unlike the result found for laminar flow an asymptotic criterion for separation is not found; however, conditions for incipient separation are computed numerically using the derived solution for the shear stress at the wall. Results are compared with available experimental measurements.

Graphical determination of wall temperatures for heat transfers through walls of arbitrary shape

NASA Technical Reports Server (NTRS)

Lutz, Otto

1950-01-01

A graphical method is given which permits determining of the temperature distribution during heat transfer in arbitrarily shaped walls. Three examples show the application of the method. The further development of heat engines depends to a great extent on the control of the thermal stresses in the walls. The thermal stresses stem from the nonuniform temperature distribution in heat transfer through walls which are, for structural reasons, of various thicknesses and sometimes complicated shape. Thus, it is important to know the temperature distribution in these structural parts. Following, a method is given which permits solution of this problem.

Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome.

PubMed

Gavali, H; Mani, K; Tegler, G; Kawati, R; Covaciu, L; Wanhainen, A

2017-08-01

The aim of the study was to investigate the frequency and outcome of prolonged intensive care unit (ICU) length of stay (LOS) after abdominal aortic aneurysm (AAA) repair in the endovascular era. All patients operated on for AAA between 1999 and 2013 at Uppsala University hospital were identified. Data were retrieved from the Swedish Vascular registry, the Swedish Intensive Care registry, the National Population registry, and case records. Prolonged ICU LOS was defined as ≥ 48 h during the primary hospital stay. Patients surviving ≥ 48 h after AAA surgery were included in the analysis. A total of 725 patients were identified, of whom 707 (97.5%) survived ≥ 48 h; 563 (79.6%) underwent intact AAA repair and 144 (20.4%) ruptured AAA repair. A total of 548 patients (77.5%) required < 48 h of intensive care, 115 (16.3%) 2-6 days and 44 (6.2%) ≥ 7 days. The rate of prolonged ICU LOS declined considerably over time, from 41.4% of all AAA repairs in 1999 to 7.3% in 2013 (p < .001) whereas the use of endovascular aortic repair (EVAR) increased from 6.9% in 1999 to 78.0% in 2013 (p < .001). The 30 day survival rate was 98.2% for those with < 48 h ICU stay versus 93.0% for 2-6 days versus 81.8% for ≥ 7 days (p < .001); the corresponding 90 day survival was 97.1% versus 86.1% versus 63.6% (p < .001) respectively. For patients surviving 90 days after repair, there was no difference in long-term survival between the groups. During the period of progressively increasing use of EVAR, a simultaneous significant reduction in frequency of prolonged ICU LOS occurred. Although prolonged ICU LOS was associated with a high short-term mortality, long-term outcome among those surviving the initial 90 days was less affected. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Effect of aorto-iliac bifurcation and iliac stenosis on flow dynamics in an abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Patel, Shivam; Usmani, Abdullah Y.; Muralidhar, K.

2017-06-01

Physiological flows in rigid diseased arterial flow phantoms emulating an abdominal aortic aneurysm (AAA) under rest conditions with aorto-iliac bifurcation and iliac stenosis are examined in vitro through 2D PIV measurements. Flow characteristics are first established in the model resembling a symmetric AAA with a straight outlet tube. The influence of aorto-iliac bifurcation and iliac stenosis on AAA flow dynamics is then explored through a comparison of the nature of flow patterns, vorticity evolution, vortex core trajectory and hemodynamic factors against the reference configuration. Specifically, wall shear stress and oscillatory shear index in the bulge portion of the models are of interest. The results of this investigation indicate overall phenomenological similarity in AAA flow patterns across the models. The pattern is characterized by a central jet and wall-bounded vortices whose strength increases during the deceleration phase as it moves forward. The central jet impacts the wall of AAA at its distal end. In the presence of an aorto-iliac bifurcation as well as iliac stenosis, the flow patterns show diminished strength, expanse and speed of propagation of the primary vortices. The positions of the instantaneous vortex cores, determined using the Q-function, correlate with flow separation in the bulge, flow resistance due to a bifurcation, and the break in symmetry introduced by a stenosis in one of the legs of the model. Time-averaged WSS in a healthy aorta is around 0.70 N m-2 and is lowered to the range ±0.2 N m-2 in the presence of the downstream bifurcation with a stenosed common iliac artery. The consequence of changes in the flow pattern within the aneurysm on disease progression is discussed.

Stan Bull, Long-Time NREL Leader, Named AAAS Fellow | News | NREL

Science.gov Websites

, Named AAAS Fellow January 11, 2011 Stanley R. Bull, former associate director for Science and Technology emeritus researcher. He was cited for "distinguished leadership in creating new programs, development partner with existing energy companies, including the fossil-fuel industry, and to "provide our

Stress analysis for wall structure in mobile hot cell design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bahrin, Muhammad Hannan, E-mail: hannan@nuclearmalaysia.gov.my; Rahman, Anwar Abdul, E-mail: anwar@nuclearmalaysia.gov.my; Hamzah, Mohd Arif, E-mail: arif@nuclearmalaysia.gov.my

Malaysian Nuclear Agency is developing a Mobile Hot Cell (MHC) in order to handle and manage Spent High Activity Radioactive Sources (SHARS) such as teletherapy heads and irradiators. At present, there are only two units of MHC in the world, in South Africa and China. Malaysian Mobile Hot cell is developed by Malaysian Nuclear Agency with the assistance of IAEA expert, based on the design of South Africa and China, but with improved features. Stress analysis has been performed on the design in order to fulfil the safety requirement in operation of MHC. This paper discusses the loading analysis effectmore » from the sand to the MHC wall structure.« less

Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.

PubMed

Ni, Xian-Qiang; Lu, Wei-Wei; Zhang, Jin-Sheng; Zhu, Qing; Ren, Jin-Ling; Yu, Yan-Rong; Liu, Xiu-Ying; Wang, Xiu-Jie; Han, Mei; Jing, Qing; Du, Jie; Tang, Chao-Shu; Qi, Yong-Fen

2018-06-26

Endoplasmic reticulum stress (ERS) is involved in the development of abdominal aortic aneurysm (AAA). Since bioactive peptide intermedin (IMD)1-53 protects against AAA formation, here we investigated whether IMD1-53 attenuates AAA by inhibiting ERS. AAA model was induced by angiotensin II (AngII) in ApoE KO mouse background. AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4).The protein level of ERS marker glucose regulated protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up-regulated by AngII. Increased ERS levels were accompanied by severe VSMC apoptosis in human AAA aorta. In vivo administration of IMD1-53 greatly reduced AngII-induced AAA and abrogated the activation of ERS. To determine whether IMD inhibited AAA by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly reduced the incidence of AAA and AAA-related pathological disorders. In vitro, AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis. IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect against AAA formation by inhibiting ERS via activating AMPK phosphorylation.

Wall relaxation and the driving forces for cell expansive growth

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

1987-01-01

When water uptake by growing cells is prevented, the turgor pressure and the tensile stress in the cell wall are reduced by continued wall loosening. This process, termed in vivo stress relaxation, provides a new way to study the dynamics of wall loosening and to measure the wall yield threshold and the physiological wall extensibility. Stress relaxation experiments indicate that wall stress supplies the mechanical driving force for wall yielding. Cell expansion also requires water absorption. The driving force for water uptake during growth is created by wall relaxation, which lowers the water potential of the expanding cells. New techniques for measuring this driving force show that it is smaller than believed previously; in elongating stems it is only 0.3 to 0.5 bar. This means that the hydraulic resistance of the water transport pathway is small and that rate of cell expansion is controlled primarily by wall loosening and yielding.

Hydromagnetic couple-stress nanofluid flow over a moving convective wall: OHAM analysis

NASA Astrophysics Data System (ADS)

Awais, M.; Saleem, S.; Hayat, T.; Irum, S.

2016-12-01

This communication presents the magnetohydrodynamics (MHD) flow of a couple-stress nanofluid over a convective moving wall. The flow dynamics are analyzed in the boundary layer region. Convective cooling phenomenon combined with thermophoresis and Brownian motion effects has been discussed. Similarity transforms are utilized to convert the system of partial differential equations into coupled non-linear ordinary differential equation. Optimal homotopy analysis method (OHAM) is utilized and the concept of minimization is employed by defining the average squared residual errors. Effects of couple-stress parameter, convective cooling process parameter and energy enhancement parameters are displayed via graphs and discussed in detail. Various tables are also constructed to present the error analysis and a comparison of obtained results with the already published data. Stream lines are plotted showing a difference of Newtonian fluid model and couplestress fluid model.

AAAS Communicating Science Program: Reflections on Evaluation

NASA Astrophysics Data System (ADS)

Braha, J.

2015-12-01

The AAAS Center for Public Engagement (Center) with science builds capacity for scientists to engage public audiences by fostering collaboration among natural or physical scientists, communication researchers, and public engagement practitioners. The recently launched Leshner Leadership Institute empowers cohorts of mid-career scientists to lead public engagement by supporting their networks of scientists, researchers, and practitioners. The Center works closely with social scientists whose research addresses science communication and public engagement with science to ensure that the Communicating Science training program builds on empirical evidence to inform best practices. Researchers ( Besley, Dudo, & Storkdieck 2015) have helped Center staff and an external evaluator develop pan instrument that measures progress towards goals that are suggested by the researcher, including internal efficacy (increasing scientists' communication skills and confidence in their ability to engage with the public) and external efficacy (scientists' confidence in engagement methods). Evaluation results from one year of the Communicating Science program suggest that the model of training yields positive results that support scientists in the area that should lead to greater engagement. This talk will explore the model for training, which provides a context for strategic communication, as well as the practical factors, such as time, access to public engagement practitioners, and technical skill, that seems to contribute to increased willingness to engage with public audiences. The evaluation program results suggest willingness by training participants to engage directly or to take preliminary steps towards engagement. In the evaluation results, 38% of trained scientists reported time as a barrier to engagement; 35% reported concern that engagement would distract from their work as a barrier. AAAS works to improve practitioner-researcher-scientist networks to overcome such barriers.

Optimum Material Composition for Minimizing the Stress Intensity Factor of Edge Crack in Thick-Walled FGM Circular Pipes Under Thermomechanical Loading

NASA Astrophysics Data System (ADS)

Sekine, Hideki; Yoshida, Kimiaki

This paper deals with the optimization problem of material composition for minimizing the stress intensity factor of radial edge crack in thick-walled functionally graded material (FGM) circular pipes under steady-state thermomechanical loading. Homogenizing the FGM circular pipes by simulating the inhomogeneity of thermal conductivity by a distribution of equivalent eigentemperature gradient and the inhomogeneity of Young's modulus and Poisson's ratio by a distribution of equivalent eigenstrain, we present an approximation method to obtain the stress intensity factor of radial edge crack in the FGM circular pipes. The optimum material composition for minimizing the stress intensity factor of radial edge crack is determined using a nonlinear mathematical programming method. Numerical results obtained for a thick-walled TiC/Al2O3 FGM circular pipe reveal that it is possible to decrease remarkably the stress intensity factor of radial edge crack by setting the optimum material composition profile.

Fan filter cleaning on the CHeCS AAA in the US Lab

NASA Image and Video Library

2009-05-05

ISS019-E-013710 (5 May 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, cleans a fan filter on the Crew Health Care System Avionics Air Assembly (CHeCS AAA) in the Destiny laboratory of the International Space Station.

The capacity of Aspergillus niger to sense and respond to cell wall stress requires at least three transcription factors: RlmA, MsnA and CrzA.

PubMed

Fiedler, Markus Rm; Lorenz, Annett; Nitsche, Benjamin M; van den Hondel, Cees Amjj; Ram, Arthur Fj; Meyer, Vera

2014-01-01

Cell wall integrity, vesicle transport and protein secretion are key factors contributing to the vitality and productivity of filamentous fungal cell factories such as Aspergillus niger . In order to pioneer rational strain improvement programs, fundamental knowledge on the genetic basis of these processes is required. The aim of the present study was thus to unravel survival strategies of A. niger when challenged with compounds interfering directly or indirectly with its cell wall integrity: calcofluor white, caspofungin, aureobasidin A, FK506 and fenpropimorph. Transcriptomics signatures of A. niger and phenotypic analyses of selected null mutant strains were used to predict regulator proteins mediating the survival responses against these stressors. This integrated approach allowed us to reconstruct a model for the cell wall salvage gene network of A. niger that ensures survival of the fungus upon cell surface stress. The model predicts that (i) caspofungin and aureobasidin A induce the cell wall integrity pathway as a main compensatory response via induction of RhoB and RhoD, respectively, eventually activating the mitogen-activated protein kinase kinase MkkA and the transcription factor RlmA. (ii) RlmA is the main transcription factor required for the protection against calcofluor white but it cooperates with MsnA and CrzA to ensure survival of A. niger when challenged with caspofungin and aureobasidin A. (iii) Membrane stress provoked by aureobasidin A via disturbance of sphingolipid synthesis induces cell wall stress, whereas fenpropimorph-induced disturbance of ergosterol synthesis does not. The present work uncovered a sophisticated defence system of A. niger which employs at least three transcription factors - RlmA, MsnA and CrzA - to protect itself against cell wall stress. The transcriptomic data furthermore predicts a fourth transfactor, SrbA, which seems to be specifically important to survive fenpropimorph-induced cell membrane stress. Future studies

A novel strategy to translate the biomechanical rupture risk of abdominal aortic aneurysms to their equivalent diameter risk: method and retrospective validation.

PubMed

Gasser, T C; Nchimi, A; Swedenborg, J; Roy, J; Sakalihasan, N; Böckler, D; Hyhlik-Dürr, A

2014-03-01

To translate the individual abdominal aortic aneurysm (AAA) patient's biomechanical rupture risk profile to risk-equivalent diameters, and to retrospectively test their predictability in ruptured and non-ruptured aneurysms. Biomechanical parameters of ruptured and non-ruptured AAAs were retrospectively evaluated in a multicenter study. General patient data and high resolution computer tomography angiography (CTA) images from 203 non-ruptured and 40 ruptured aneurysmal infrarenal aortas. Three-dimensional AAA geometries were semi-automatically derived from CTA images. Finite element (FE) models were used to predict peak wall stress (PWS) and peak wall rupture index (PWRI) according to the individual anatomy, gender, blood pressure, intra-luminal thrombus (ILT) morphology, and relative aneurysm expansion. Average PWS diameter and PWRI diameter responses were evaluated, which allowed for the PWS equivalent and PWRI equivalent diameters for any individual aneurysm to be defined. PWS increased linearly and PWRI exponentially with respect to maximum AAA diameter. A size-adjusted analysis showed that PWS equivalent and PWRI equivalent diameters were increased by 7.5 mm (p = .013) and 14.0 mm (p < .001) in ruptured cases when compared to non-ruptured controls, respectively. In non-ruptured cases the PWRI equivalent diameters were increased by 13.2 mm (p < .001) in females when compared with males. Biomechanical parameters like PWS and PWRI allow for a highly individualized analysis by integrating factors that influence the risk of AAA rupture like geometry (degree of asymmetry, ILT morphology, etc.) and patient characteristics (gender, family history, blood pressure, etc.). PWRI and the reported annual risk of rupture increase similarly with the diameter. PWRI equivalent diameter expresses the PWRI through the diameter of the average AAA that has the same PWRI, i.e. is at the same biomechanical risk of rupture. Consequently, PWRI equivalent diameter facilitates a

Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery.

PubMed

Singh, S D; Xu, X Y; Pepper, J R; Izgi, C; Treasure, T; Mohiaddin, R H

2016-07-05

Aortic root motion was previously identified as a risk factor for aortic dissection due to increased longitudinal stresses in the ascending aorta. The aim of this study was to investigate the effects of aortic root motion on wall stress and strain in the ascending aorta and evaluate changes before and after implantation of personalised external aortic root support (PEARS). Finite element (FE) models of the aortic root and thoracic aorta were developed using patient-specific geometries reconstructed from pre- and post-PEARS cardiovascular magnetic resonance (CMR) images in three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Cardiovascular MR cine images were used to quantify aortic root motion, which was imposed at the aortic root boundary of the FE model, with zero-displacement constraints at the distal ends of the aortic branches and descending aorta. Measurements of the systolic downward motion of the aortic root revealed a significant reduction in the axial displacement in all three patients post-PEARS compared with its pre-PEARS counterparts. Higher longitudinal stresses were observed in the ascending aorta when compared with models without the root motion. Implantation of PEARS reduced the longitudinal stresses in the ascending aorta by up to 52%. In contrast, the circumferential stresses at the interface between the supported and unsupported aorta were increase by up to 82%. However, all peak stresses were less than half the known yield stress for the dilated thoracic aorta. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of wall couple stress in MHD flow of a micropolar fluid in a porous medium with energy and concentration transfer

NASA Astrophysics Data System (ADS)

Khalid, Asma; Khan, Ilyas; Khan, Arshad; Shafie, Sharidan

2018-06-01

The intention here is to investigate the effects of wall couple stress with energy and concentration transfer in magnetohydrodynamic (MHD) flow of a micropolar fluid embedded in a porous medium. The mathematical model contains the set of linear conservation forms of partial differential equations. Laplace transforms and convolution technique are used for computation of exact solutions of velocity, microrotations, temperature and concentration equations. Numerical values of skin friction, couple wall stress, Nusselt and Sherwood numbers are also computed. Characteristics for the significant variables on the physical quantities are graphically discussed. Comparison with previously published work in limiting sense shows an excellent agreement.

NASA Astrophysics E/PO Impact: NASA SOFIA AAA Program Evaluation Results

NASA Astrophysics Data System (ADS)

Harman, Pamela; Backman, Dana E.; Clark, Coral; Inverness Research Sofia Aaa Evaluation Team, Wested Sofia Aaa Evaluation Team

2015-01-01

SOFIA is an airborne observatory, studying the universe at infrared wavelengths, capable of making observations that are impossible for even the largest and highest ground-based telescopes. SOFIA also inspires the development of new scientific instrumentation and fosters the education of young scientists and engineers.SOFIA is an 80% - 20% partnership of NASA and the German Aerospace Center (DLR), consisting of an extensively modified Boeing 747SP aircraft carrying a reflecting telescope with an effective diameter of 2.5 meters (100 inches). The SOFIA aircraft is based at NASA Armstrong Flight Research Center, Building 703, in Palmdale, California. The Science Program and Outreach Offices are located at NASA Ames Research center. SOFIA is a program in NASA's Science Mission Directorate, Astrophysics Division.Data will be collected to study many different kinds of astronomical objects and phenomena, including star cycles, solar system formation, identification of complex molecules in space, our solar system, galactic dust, nebulae and ecosystems.Airborne Astronomy Ambassador (AAA) Program:The SOFIA Education and Communications program exploits the unique attributes of airborne astronomy to contribute to national goals for the reform of science, technology, engineering, and math (STEM) education, and to elevate public scientific and technical literacy.The AAA effort is a professional development program aspiring to improve teaching, inspire students, and inform the community. To date, 55 educators from 21 states; Cycles 0, 1 and 2; have completed their astronomy professional development and their SOFIA science flight experience. Evaluation has confirmed the program's positive impact on the teacher participants, on their students, and in their communities. The inspirational experience has positively impacted their practice and career trajectory. AAAs have incorporated content knowledge and specific components of their experience into their curricula, and have given

Mutants in the Candida glabrata Glycerol Channels Are Sensitized to Cell Wall Stress

PubMed Central

Beese-Sims, Sara E.; Pan, Shih-Jung; Lee, Jongmin; Hwang-Wong, Elizabeth; Cormack, Brendan P.

2012-01-01

Many fungal species use glycerol as a compatible solute with which to maintain osmotic homeostasis in response to changes in external osmolarity. In Saccharomyces cerevisiae, intracellular glycerol concentrations are regulated largely by the high osmolarity glycerol (HOG) response pathway, both through induction of glycerol biosynthesis and control of its flux through the plasma membrane Fps1 glycerol channel. The channel activity of Fps1 is also controlled by a pair of positive regulators, Rgc1 and Rgc2. In this study, we demonstrate that Candida glabrata, a fungal pathogen that possesses two Fps1 orthologs and two Rgc1/-2 orthologs, accumulates glycerol in response to hyperosmotic stress. We present an initial characterization of mutants with deletions in the C. glabrata FPS1 (CAGL0C03267 [www.candidagenome.org]) and FPS2 (CAGL0E03894) genes and find that a double mutant accumulates glycerol, experiences constitutive cell wall stress, and is hypersensitive to treatment by caspofungin, an antifungal agent that targets the cell wall. This mutant is cleared more efficiently in mouse infections than is wild-type C. glabrata by caspofungin treatment. Finally, we demonstrate that one of the C. glabrata RGC orthologs complements an S. cerevisiae rgc1 rgc2 null mutant, supporting the conclusion that this regulatory assembly is conserved between these species. PMID:23087370

Analysis of reactive oxygen metabolites (ROMs) after cardiovascular surgery as a marker of oxidative stress.

PubMed

Kanaoka, Yuji; Inagaki, Ei-ichirou; Hamanaka, Souhei; Masaki, Hisao; Tanemoto, Kazuo

2010-10-01

The transient systemic low perfusion that occurs during cardiovascular surgery leads to oxidative stress and the production of free radicals. A systemic increase of various markers of oxidative stress has been shown to occur during cardiopulmonary bypass (CPB). However, these markers have not been adequately evaluated because they seem to be reactive and short-lived. Here, oxidative stress was measured using the free radical analytical system (FRAS 4) assessing the derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Blood samples were taken from 21 patients undergoing elective cardiovascular surgery. CPB was used in 15 patients, and abdominal aortic aneurysm (AAA) surgery without CPB was performed in 6. Measurements of d-ROMs and BAP were taken before surgery, 1 day, 1 week, and 2 weeks after surgery, and oxidative stress was evaluated. The d-ROM level increased gradually after cardiovascular surgery up to 2 weeks. Over time, the d-ROM level after surgery involving CPB became higher than that after AAA surgery. This difference reached statistical significance at 1 week and lasted to 2 weeks. The prolongation of CPB was prone to elevate the d-ROM level whereas the duration of the aortic clamp in AAA surgery had no relation to the d-ROM level. The BAP was also elevated after surgery, and was positively correlated with the level of d-ROMs. In this study, patients who underwent cardiovascular surgery involving CPB had significant oxidative damage. The production of ROMs was shown to depend on the duration of CPB. Damage can be reduced if CPB is avoided. When CPB must be used, shortening the CPB time may be effective in reducing oxidative stress.

SFM-FDTD analysis of triangular-lattice AAA structure: Parametric study of the TEM mode

NASA Astrophysics Data System (ADS)

Hamidi, M.; Chemrouk, C.; Belkhir, A.; Kebci, Z.; Ndao, A.; Lamrous, O.; Baida, F. I.

2014-05-01

This theoretical work reports a parametric study of enhanced transmission through annular aperture array (AAA) structure arranged in a triangular lattice. The effect of the incidence angle in addition to the inner and outer radii values on the evolution of the transmission spectra is carried out. To this end, a 3D Finite-Difference Time-Domain code based on the Split Field Method (SFM) is used to calculate the spectral response of the structure for any angle of incidence. In order to work through an orthogonal unit cell which presents the advantage to reduce time and space of computation, special periodic boundary conditions are implemented. This study provides a new modeling of AAA structures useful for producing tunable ultra-compact devices.

Near-wall modelling of compressible turbulent flows

NASA Technical Reports Server (NTRS)

So, Ronald M. C.

1990-01-01

Work was carried out to formulate near-wall models for the equations governing the transport of the temperature-variance and its dissipation rate. With these equations properly modeled, a foundation is laid for their extension together with the heat-flux equations to compressible flows. This extension is carried out in a manner similar to that used to extend the incompressible near-wall Reynolds-stress models to compressible flows. The methodology used to accomplish the extension of the near-wall Reynolds-stress models is examined and the actual extension of the models for the Reynolds-stress equations and the near-wall dissipation-rate equation to compressible flows is given. Then the formulation of the near-wall models for the equations governing the transport of the temperature variance and its dissipation rate is discussed. Finally, a sample calculation of a flat plate compressible turbulent boundary-layer flow with adiabatic wall boundary condition and a free-stream Mach number of 2.5 using a two-equation near-wall closure is presented. The results show that the near-wall two-equation closure formulated for compressible flows is quite valid and the calculated properties are in good agreement with measurements. Furthermore, the near-wall behavior of the turbulence statistics and structure parameters is consistent with that found in incompressible flows.

The practicality of defensive ice walls: How would the great ice wall in Game of Thrones hold up?

NASA Astrophysics Data System (ADS)

Truffer, M.

2017-12-01

The Game of Thrones great ice wall is a colossal feature stretching several hundred miles and over 200 m high. Its purpose is to defend the realm from the wildlings. It is generally pictured as a near vertical wall. An ice wall of these proportions poses interesting challenges, mainly because ice acts as a non-linear shear-thinning fluid. A 200 m high vertical wall would create a large effective stress near its base of almost 1.8 MPa. Typical stresses responsible for ice flow in glaciers and ice sheets are more than a magnitude lower (0.1 MPa). Extrapolating a commonly used flow law for temperate ice to such high stresses would lead to strain rates at the bottom of the wall in excess of 1/day, meaning the wall would rapidly collapse and spread laterally under its own weight. To keep the wall stable, it would help to cool it significantly, as the flow of ice is also very temperature dependent. Cooling to a chilly -40 C would reduce strain rates by two orders of magnitude, but this still leads to significant slumping of the wall within just a few weeks. A time-dependent similarity solution for simplified ice flow equations that describe the evolving shape of the ice wall was provided by Halfar (1981), and demonstrates the rapid decay of the wall. A simple estimate can be derived by assuming that ice is a perfectly plastic fluid, able to maintain a basal shear stress of about 0.1 MPa. A stable ice wall would then spread laterally to about 4 km width. The resulting slope would only be steep at the very margin and the ice wall would loose much of its defensive capabilities. I conclude that the ice wall as proposed would not be a practicable defense under typical Earth conditions, and special magical powers would be necessary to maintain its shape, even for just a few days.

Second-order near-wall turbulence closures - A review

NASA Technical Reports Server (NTRS)

So, R. M. C.; Lai, Y. G.; Zhang, H. S.; Hwang, B. C.

1991-01-01

Advances in second-order near-wall turbulence closures are summarized. All closures under consideration are based on high-Reynolds-number models. Most near-wall closures proposed to date attempt to modify the high-Reynolds-number models for the dissipation function and the pressure redistribution term so that the resultant models are applicable all the way to the wall. The asymptotic behavior of the near-wall closures is examined and compared with the proper near-wall behavior of the exact Reynolds-stress equations. It is found that three second-order near-wall closures give the best correlations with simulated turbulence statistics. However, their predictions of near-wall Reynolds-stress budgets are considered to be incorrect. A proposed modification to the dissipitation-rate equation remedies part of those predictions. It is concluded that further improvements are required if a complete replication of all the turbulence properties and Reynolds-stress budgets by a statistical model of turbulence is desirable.

Method to Determine the Stress-Strain Response of As-Formed Thin-Walled Tubular Structures Using a Flaring Apparatus

NASA Astrophysics Data System (ADS)

Jurendic, S.; Anderson, D.

2017-09-01

Finite element simulations are used extensively to refine the forming steps of draw and wall iron (DWI) aluminum bottles; therefore, accurate material data is required Unfortunately, the material properties of the base sheet cannot presently be used for simulation of the later forming stages due to preceding significant deformation (ironing) and thermal treatments. Measuring the stress-strain response using traditional methods (e.g. tensile test) becomes increasingly difficult at later stages of the bottle forming process due to a significant diameter reduction of the bottle neck from successive die-necking stages. Moreover, failure during forming tends to occur in the final deformation stages when the bottle opening is rolled over, creating a brim roll, at which point brim roll splits may occur. Knowledge of the stress-strain response prior to the roll over may lead to improved product design, reduced waste, and an optimized product. Therefore, this work details a flaring apparatus and data analysis method to determine the stress-strain response in the die-necked region of thin-walled aluminum bottles fabricated from AA3104 sheet metal.

Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

NASA Astrophysics Data System (ADS)

Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

2014-03-01

Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell.

Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

PubMed Central

Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

2014-01-01

Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. PMID:24658080

The Role of Law-of-the-Wall and Roughness Scale in the Surface Stress Model for LES of the Rough-wall Boundary Layer

NASA Astrophysics Data System (ADS)

Brasseur, James; Paes, Paulo; Chamecki, Marcelo

2017-11-01

Large-eddy simulation (LES) of the high Reynolds number rough-wall boundary layer requires both a subfilter-scale model for the unresolved inertial term and a ``surface stress model'' (SSM) for space-time local surface momentum flux. Standard SSMs assume proportionality between the local surface shear stress vector and the local resolved-scale velocity vector at the first grid level. Because the proportionality coefficient incorporates a surface roughness scale z0 within a functional form taken from law-of-the-wall (LOTW), it is commonly stated that LOTW is ``assumed,'' and therefore ``forced'' on the LES. We show that this is not the case; the LOTW form is the ``drag law'' used to relate friction velocity to mean resolved velocity at the first grid level consistent with z0 as the height where mean velocity vanishes. Whereas standard SSMs do not force LOTW on the prediction, we show that parameterized roughness does not match ``true'' z0 when LOTW is not predicted, or does not exist. By extrapolating mean velocity, we show a serious mismatch between true z0 and parameterized z0 in the presence of a spurious ``overshoot'' in normalized mean velocity gradient. We shall discuss the source of the problem and its potential resolution.

TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

PubMed

Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

2017-11-01

Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

Two C-C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm.

PubMed

Jones, Gregory T; Phillips, L Victoria; Williams, Michael J A; van Rij, Andre M; Kabir, Tasnuva D

2016-04-28

Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (AAA). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA. Tissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T-cell expressed and secreted (RANTES), eotaxin, and macrophage inflammatory protein 1 beta (MIP-1b), had increased expression in AAA, particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor (bFGF) had reduced expression in all layers of the AAA wall. Examination of the circulating plasma profiles of AAA (n=442) and AAA-free controls (n=970) suggested a (risk factor adjusted) AAA-association with eotaxin, RANTES, and high sensitivity C-reactive protein (hsCRP). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with AAA (odds ratio, 4.8; 95% CI, 3.5-6.7; P<0.0001), independent of age, sex, history of ischemic heart disease, and smoking. Contrary to reports suggesting a distinct T helper 2-associated inflammatory profile in AAA, this current study suggests a more-generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES. In combination with hsCRP, these markers may have potential utility as AAA biomarkers. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Plant cell wall extensibility: connecting plant cell growth with cell wall structure, mechanics, and the action of wall-modifying enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cosgrove, Daniel J.

The advent of user-friendly instruments for measuring force/deflection curves of plant surfaces at high spatial resolution has resulted in a recent outpouring of reports of the ‘Young's modulus’ of plant cell walls. The stimulus for these mechanical measurements comes from biomechanical models of morphogenesis of meristems and other tissues, as well as single cells, in which cell wall stress feeds back to regulate microtubule organization, auxin transport, cellulose deposition, and future growth directionality. In this article I review the differences between elastic modulus and wall extensibility in the context of cell growth. Some of the inherent complexities, assumptions, and potentialmore » pitfalls in the interpretation of indentation force/deflection curves are discussed. Reported values of elastic moduli from surface indentation measurements appear to be 10- to >1000-fold smaller than realistic tensile elastic moduli in the plane of plant cell walls. Potential reasons for this disparity are discussed, but further work is needed to make sense of the huge range in reported values. The significance of wall stress relaxation for growth is reviewed and connected to recent advances and remaining enigmas in our concepts of how cellulose, hemicellulose, and pectins are assembled to make an extensible cell wall. A comparison of the loosening action of α-expansin and Cel12A endoglucanase is used to illustrate two different ways in which cell walls may be made more extensible and the divergent effects on wall mechanics.« less

Numerical study of wall shear stress-based descriptors in the human left coronary artery.

PubMed

Pinto, S I S; Campos, J B L M

2016-10-01

The present work is about the application of wall shear stress descriptors - time averaged wall shear stress (TAWSS), oscillating shear index (OSI) and relative residence time (RRT) - to the study of blood flow in the left coronary artery (LCA). These descriptors aid the prediction of disturbed flow conditions in the vessels and play a significant role in the detection of potential zones of atherosclerosis development. Hemodynamic descriptors data were obtained, numerically, through ANSYS® software, for the LCA of a patient-specific geometry and for a 3D idealized model. Comparing both cases, the results are coherent, in terms of location and magnitude. Low TAWSS, high OSI and high RRT values are observed in the bifurcation - potential zone of atherosclerosis appearance. The dissimilarities observed in the TAWSS values, considering blood as a Newtonian or non-Newtonian fluid, releases the importance of the correct blood rheologic caracterization. Moreover, for a higher Reynolds number, the TAWSS values decrease in the bifurcation and along the LAD branch, increasing the probability of plaques deposition. Furthermore, for a stenotic LCA model, very low TAWSS and high RRT values in front and behind the stenosis are observed, indicating the probable extension, in the flow direction, of the lesion.

[Cellular composition of lymphoid nodules in the trachea wall in rats with different resistance to emotional stress in a model of hemorrhagic stroke].

PubMed

Klyueva, L A

2017-01-01

To reveal regularities of changes in cellular composition of lymphoid nodules in the tracheal wall in male Wistar rats resistant and not resistant to emotional stress in a model of hemorrhagic stroke. Lymphoid formations of the tracheal wall (an area near the bifurcation of the organ) were investigated in 98 male Wistar rats using histological methods. Significant changes in the cellular composition of lymphoid nodules were found. The pattern of changes depends on the stress resistance of rats and the period of the experiment. The active cell destruction in lymphoid nodules was noted both in stress resistant and stress susceptible animals. The changes in the structure of lymphoid nodules found in the experimental hemorrhagic stroke suggest a decrease in the local immune resistance, which is most pronounced in rats not resistant to stress, that may contribute to the development of severe inflammatory complications of stroke such as pneumonia.

The Arabidopsis leucine-rich repeat receptor kinase MIK2/LRR-KISS connects cell wall integrity sensing, root growth and response to abiotic and biotic stresses

PubMed Central

Van der Does, Dieuwertje; Boutrot, Freddy; Vernhettes, Samantha; Tintor, Nico; Veerabagu, Manikandan; Miedes, Eva; Segonzac, Cécile; Hardtke, Christian S.; Molina, Antonio; Höfte, Herman; Hamann, Thorsten

2017-01-01

Plants actively perceive and respond to perturbations in their cell walls which arise during growth, biotic and abiotic stresses. However, few components involved in plant cell wall integrity sensing have been described to date. Using a reverse-genetic approach, we identified the Arabidopsis thaliana leucine-rich repeat receptor kinase MIK2 as an important regulator of cell wall damage responses triggered upon cellulose biosynthesis inhibition. Indeed, loss-of-function mik2 alleles are strongly affected in immune marker gene expression, jasmonic acid production and lignin deposition. MIK2 has both overlapping and distinct functions with THE1, a malectin-like receptor kinase previously proposed as cell wall integrity sensor. In addition, mik2 mutant plants exhibit enhanced leftward root skewing when grown on vertical plates. Notably, natural variation in MIK2 (also named LRR-KISS) has been correlated recently to mild salt stress tolerance, which we could confirm using our insertional alleles. Strikingly, both the increased root skewing and salt stress sensitivity phenotypes observed in the mik2 mutant are dependent on THE1. Finally, we found that MIK2 is required for resistance to the fungal root pathogen Fusarium oxysporum. Together, our data identify MIK2 as a novel component in cell wall integrity sensing and suggest that MIK2 is a nexus linking cell wall integrity sensing to growth and environmental cues. PMID:28604776

Intraoperative CT in the assessment of posterior wall acetabular fracture stability.

PubMed

Cunningham, Brian; Jackson, Kelly; Ortega, Gil

2014-04-01

Posterior wall acetabular fractures that involve 10% to 40% of the posterior wall may or may not require an open reduction and internal fixation. Dynamic stress examination of the acetabular fracture under fluoroscopy has been used as an intraoperative method to assess joint stability. The aim of this study was to demonstrate the value of intraoperative ISO computed tomography (CT) examination using the Siemens ISO-C imaging system (Siemens Corp, Malvern, Pennsylvania) in the assessment of posterior wall acetabular fracture stability during stress examination under anesthesia. In 5 posterior wall acetabular fractures, standard fluoroscopic images (including anteroposterior pelvis and Judet radiographs) with dynamic stress examinations were compared with the ISO-C CT imaging system to assess posterior wall fracture stability during stress examination. After review of standard intraoperative fluoroscopic images under dynamic stress examination, all 5 cases appeared to demonstrate posterior wall stability; however, when the intraoperative images from the ISO-C CT imaging system demonstrated that 1 case showed fracture instability of the posterior wall segment during stress examination, open reduction and internal fixation was performed. The use of intraoperative ISO CT imaging has shown an initial improvement in the surgeon's ability to assess the intraoperative stability of posterior wall acetabular fractures during stress examination when compared with standard fluoroscopic images. Copyright 2014, SLACK Incorporated.

Wall shear stress effects of different endodontic irrigation techniques and systems.

PubMed

Goode, Narisa; Khan, Sara; Eid, Ashraf A; Niu, Li-na; Gosier, Johnny; Susin, Lisiane F; Pashley, David H; Tay, Franklin R

2013-07-01

This study examined débridement efficacy as a result of wall shear stresses created by different irrigant delivery/agitation techniques in an inaccessible recess of a curved root canal model. A reusable, curved canal cavity containing a simulated canal fin was milled into mirrored titanium blocks. Calcium hydroxide (Ca(OH)2) paste was used as debris and loaded into the canal fin. The titanium blocks were bolted together to provide a fluid-tight seal. Sodium hypochlorite was delivered at a previously-determined flow rate of 1 mL/min that produced either negligible or no irrigant extrusion pressure into the periapex for all the techniques examined. Nine irrigation delivery/agitation techniques were examined: NaviTip passive irrigation control, Max-i-Probe(®) side-vented needle passive irrigation, manual dynamic agitation (MDA) using non-fitting and well-fitting gutta-percha points, EndoActivator™ sonic agitation with medium and large points, VPro™ EndoSafe™ irrigation system, VPro™ StreamClean™ continuous ultrasonic irrigation and EndoVac apical negative pressure irrigation. Débridement efficacies were analysed with Kruskal-Wallis ANOVA and Dunn's multiple comparisons tests (α=0.05). EndoVac was the only technique that removed more than 99% calcium hydroxide debris from the canal fin at the predefined flow rate. This group was significantly different (p<0.05) from the other groups that exhibited incomplete Ca(OH)2 removal. The ability of the EndoVac system to significantly clean more debris from a mechanically inaccessible recess of the model curved root canal may be caused by robust bubble formation during irrigant delivery, creating higher wall shear stresses by a two-phase air-liquid flow phenomenon that is well known in other industrial débridement systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Measurement of wall shear stress in chick embryonic heart using optical coherence tomography

NASA Astrophysics Data System (ADS)

Ma, Zhenhe; Dou, Shidan; Zhao, Yuqian; Wang, Yi; Suo, Yanyan; Wang, Fengwen

2015-03-01

The cardiac development is a complicated process affected by genetic and environmental factors. Wall shear stress (WSS) is one of the components which have been proved to influence the morphogenesis during early stages of cardiac development. To study the mechanism, WSS measurement is a step with significant importance. WSS is caused by blood flow imposed on the inner surface of the heart wall and it can be determined by calculating velocity gradients of blood flow in a direction perpendicular to the wall. However, the WSS of the early stage embryonic heart is difficult to measure since the embryonic heart is tiny and beating fast. Optical coherence tomography (OCT) is a non-invasive imaging modality with high spatial and temporal resolution, which is uniquely suitable for the study of early stage embryonic heart development. In this paper, we introduce a method to measure the WSS of early stage chick embryonic heart based on high speed spectral domain optical coherence tomography (SDOCT). 4D (x,y,z,t) scan was performed on the outflow tract (OFT) of HH18 (~3 days of incubation) chick embryonic heart. After phase synchronization, OFT boundary segmentation, and OFT center line calculation, Doppler angle of the blood flow in the OFT can be achieved (This method has been described in previous publications). Combining with the Doppler OCT results, we calculate absolute blood flow velocity distribution in the OFT. The boundary of the OFT was segmented at each cross-sectional structural image, then geometrical center of the OFT can be calculated. Thus, the gradients of blood flow in radial direction can be calculated. This velocity gradient near the wall is termed wall shear rate and the WSS value is proportional to the wall shear rate. Based on this method, the WSS at different heart beating phase are compare. The result demonstrates that OCT is capable of early stage chicken embryonic heart WSS study.

Flow Instability and Wall Shear Stress Ocillation in Intracranial Aneurysms

NASA Astrophysics Data System (ADS)

Baek, Hyoungsu; Jayamaran, Mahesh; Richardson, Peter; Karniadakis, George

2009-11-01

We investigate the flow dynamics and oscillatory behavior of wall shear stress (WSS) vectors in intracranial aneurysms using high-order spectral/hp simulations. We analyze four patient- specific internal carotid arteries laden with aneurysms of different characteristics : a wide-necked saccular aneurysm, a hemisphere-shaped aneurysm, a narrower-necked saccular aneurysm, and a case with two adjacent saccular aneurysms. Simulations show that the pulsatile flow in aneurysms may be subject to a hydrodynamic instability during the decelerating systolic phase resulting in a high-frequency oscillation in the range of 30-50 Hz. When the aneurysmal flow becomes unstable, both the magnitude and the directions of WSS vectors fluctuate. In particular, the WSS vectors around the flow impingement region exhibit significant spatial and temporal changes in direction as well as in magnitude.

Relation between wall shear stress and carotid artery wall thickening MRI versus CFD.

PubMed

Cibis, Merih; Potters, Wouter V; Selwaness, Mariana; Gijsen, Frank J; Franco, Oscar H; Arias Lorza, Andres M; de Bruijne, Marleen; Hofman, Albert; van der Lugt, Aad; Nederveen, Aart J; Wentzel, Jolanda J

2016-03-21

Wall shear stress (WSS), a parameter associated with endothelial function, is calculated by computational fluid dynamics (CFD) or phase-contrast (PC) MRI measurements. Although CFD is common in WSS (WSSCFD) calculations, PC-MRI-based WSS (WSSMRI) is more favorable in population studies; since it is straightforward and less time consuming. However, it is not clear if WSSMRI and WSSCFD show similar associations with vascular pathology. Our aim was to test the associations between wall thickness (WT) of the carotid arteries and WSSMRI and WSSCFD. The subjects (n=14) with an asymptomatic carotid plaque who underwent MRI scans two times within 4 years of time were selected from the Rotterdam Study. We compared WSSCFD and WSSMRI at baseline and follow-up. Baseline WSSMRI and WSSCFD values were divided into 3 categories representing low, medium and high WSS tertiles. WT of each tertile was compared by a one-way ANOVA test. The WSSMRI and WSSCFD were 0.50±0.13Pa and 0.73±0.25Pa at baseline. Although WSSMRI was underestimated, a significant regression was found between WSSMRI and WSSCFD (r(2)=0.71). No significant difference was found between baseline and follow-up WSS by CFD and MRI-based calculations. The WT at baseline was 1.36±0.16mm and did not change over time. The WT was 1.55±0.21mm in low, 1.33±0.20mm in medium and 1.21±0.21mm in the high WSSMRI tertiles. Similarly, the WT was 1.49±0.21mm in low, 1.33±0.20mm in medium and 1.26±0.21mm in high WSSCFD tertiles. We found that WSSMRI and WSSCFD were inversely related with WT. WSSMRI and WSSCFD patterns were similar although MRI-based calculations underestimated WSS. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-intensity interval exercise training before abdominal aortic aneurysm repair (HIT-AAA): protocol for a randomised controlled feasibility trial.

PubMed

Tew, Garry A; Weston, Matthew; Kothmann, Elke; Batterham, Alan M; Gray, Joanne; Kerr, Karen; Martin, Denis; Nawaz, Shah; Yates, David; Danjoux, Gerard

2014-01-10

In patients with large abdominal aortic aneurysm (AAA), open surgical or endovascular aneurysm repair procedures are often used to minimise the risk of aneurysm-related rupture and death; however, aneurysm repair itself carries a high risk. Low cardiopulmonary fitness is associated with an increased risk of early post-operative complications and death following elective AAA repair. Therefore, fitness should be enhanced before aneurysm repair. High-intensity interval exercise training (HIT) is a potent, time-efficient strategy for enhancing cardiopulmonary fitness. Here, we describe a feasibility study for a definitive trial of a pre-operative HIT intervention to improve post-operative outcomes in patients undergoing elective AAA repair. A minimum of 50 patients awaiting elective repair of a 5.5-7.0 cm infrarenal AAA will be allocated by minimisation to HIT or usual care control in a 1:1 ratio. The patients allocated to HIT will complete three hospital-based exercise sessions per week, for 4 weeks. Each session will include 2 or 4 min of high-intensity stationary cycling followed by the same duration of easy cycling or passive recovery, repeated until a total of 16 min of high-intensity exercise is accumulated. Outcomes to be assessed before randomisation and 24-48 h before aneurysm repair include cardiopulmonary fitness, maximum AAA diameter and health-related quality of life. In the post-operative period, we will record destination (ward or critical care unit), organ-specific morbidity, mortality and the durations of critical care and hospital stay. Twelve weeks after the discharge, participants will be interviewed to reassess quality of life and determine post-discharge healthcare utilisation. The costs associated with the exercise intervention and healthcare utilisation will be calculated. Ethics approval was secured through Sunderland Research Ethics Committee. The findings of the trial will be disseminated through peer-reviewed journals, and national and

OGLE16aaa - a signature of a hungry supermassive black hole

NASA Astrophysics Data System (ADS)

Wyrzykowski, Łukasz; Zieliński, M.; Kostrzewa-Rutkowska, Z.; Hamanowicz, A.; Jonker, P. G.; Arcavi, I.; Guillochon, J.; Brown, P. J.; Kozłowski, S.; Udalski, A.; Szymański, M. K.; Soszyński, I.; Poleski, R.; Pietrukowicz, P.; Skowron, J.; Mróz, P.; Ulaczyk, K.; Pawlak, M.; Rybicki, K. A.; Greiner, J.; Krühler, T.; Bolmer, J.; Smartt, S. J.; Maguire, K.; Smith, K.

2017-02-01

We present the discovery and first three months of follow-up observations of a currently on-going unusual transient detected by the Optical Gravitational Lensing Experiment (OGLE-IV) survey, located in the centre of a galaxy at redshift z = 0.1655. The long rise to absolute magnitude of -20.5 mag, slow decline, very broad He and H spectral features make OGLE16aaa similar to other optical/UV tidal disruption events (TDEs). Weak narrow emission lines in the spectrum and archival photometric observations suggest the host galaxy is a weak-line active galactic nucleus, which has been accreting at higher rate in the past. OGLE16aaa, along with SDSS J0748, seems to form a sub-class of TDEs by weakly or recently active supermassive black holes (SMBHs). This class might bridge the TDEs by quiescent SMBHs and flares observed as `changing-look quasars', if we interpret the latter as TDEs. If this picture is true, the previously applied requirement for identifying a flare as a TDE that it had to come from an inactive nucleus, could be leading to observational bias in TDE selection, thus affecting TDE-rate estimations.

Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves.

PubMed

Saikrishnan, Neelakantan; Mirabella, Lucia; Yoganathan, Ajit P

2015-06-01

Congenital bicuspid aortic valves (BAVs) are associated with accelerated disease progression, such as leaflet calcification and ascending aorta dilatation. Although common underlying genetic factors have been implicated in accelerated disease in BAV patients, several studies have suggested that altered hemodynamics also play a role in this disease process. The present study compares turbulence and wall shear stress (WSS) measurements between various BAV and trileaflet aortic valve (TAV) models to provide information for mechanobiological models of BAV disease. BAV and TAV models were constructed from excised porcine aortic valves to simulate parametric variations in BAV stenosis, hemodynamics and geometry. Particle image velocimetry experiments were conducted at physiological pressure conditions to characterize velocity fields in the ascending aorta. The velocity fields were post-processed to calculate turbulence, viscous and wall shear stresses in the ascending aorta. Stenosed BAV models showed the presence of eccentric systolic jets, causing increased WSS. Lower cardiac output resulted in a narrower jet, lower turbulence and lower viscous shear stress (VSS). The specific severe stenosis BAV model studied here showed reduced WSS due to reduction in non-fused leaflet mobility. Dilation of the aorta did not affect any turbulence or VSS, but reduced the WSS. In comparison with BAVs, TAVs have similar VSS values, but much smaller WSS and turbulence levels. These increased turbulence  and WSS levels in BAVs may play a key role in amplifying the biological responses of the ascending aorta wall and valvular leaflets, and support the hemodynamic underpinnings of BAV disease processes.

Structural insights into the Escherichia coli lysine decarboxylases and molecular determinants of interaction with the AAA+ ATPase RavA

PubMed Central

Kandiah, Eaazhisai; Carriel, Diego; Perard, Julien; Malet, Hélène; Bacia, Maria; Liu, Kaiyin; Chan, Sze W. S.; Houry, Walid A.; Ollagnier de Choudens, Sandrine; Elsen, Sylvie; Gutsche, Irina

2016-01-01

The inducible lysine decarboxylase LdcI is an important enterobacterial acid stress response enzyme whereas LdcC is its close paralogue thought to play mainly a metabolic role. A unique macromolecular cage formed by two decamers of the Escherichia coli LdcI and five hexamers of the AAA+ ATPase RavA was shown to counteract acid stress under starvation. Previously, we proposed a pseudoatomic model of the LdcI-RavA cage based on its cryo-electron microscopy map and crystal structures of an inactive LdcI decamer and a RavA monomer. We now present cryo-electron microscopy 3D reconstructions of the E. coli LdcI and LdcC, and an improved map of the LdcI bound to the LARA domain of RavA, at pH optimal for their enzymatic activity. Comparison with each other and with available structures uncovers differences between LdcI and LdcC explaining why only the acid stress response enzyme is capable of binding RavA. We identify interdomain movements associated with the pH-dependent enzyme activation and with the RavA binding. Multiple sequence alignment coupled to a phylogenetic analysis reveals that certain enterobacteria exert evolutionary pressure on the lysine decarboxylase towards the cage-like assembly with RavA, implying that this complex may have an important function under particular stress conditions. PMID:27080013

Exposure to chronic alcohol accelerates development of wall stress and eccentric remodeling in rats with volume overload.

PubMed

Mouton, Alan J; Ninh, Van K; El Hajj, Elia C; El Hajj, Milad C; Gilpin, Nicholas W; Gardner, Jason D

2016-08-01

Chronic alcohol abuse is one of the leading causes of dilated cardiomyopathy (DCM) in the United States. Volume overload (VO) also produces DCM characterized by left ventricular (LV) dilatation and reduced systolic and diastolic function, eventually progressing to congestive heart failure. For this study, we hypothesized that chronic alcohol exposure would exacerbate cardiac dysfunction and remodeling due to VO. Aortocaval fistula surgery was used to induce VO, and compensatory cardiac remodeling was allowed to progress for either 3days (acute) or 8weeks (chronic). Alcohol was administered via chronic intermittent ethanol vapor (EtOH) for 2weeks before the acute study and for the duration of the 8week chronic study. Temporal alterations in LV function were assessed by echocardiography. At the 8week end point, pressure-volume loop analysis was performed by LV catheterization and cardiac tissue collected. EtOH did not exacerbate LV dilatation (end-systolic and diastolic diameter) or systolic dysfunction (fractional shortening, ejection fraction) due to VO. The combined stress of EtOH and VO decreased the eccentric index (posterior wall thickness to end-diastolic diameter ratio), increased end-diastolic pressure (EDP), and elevated diastolic wall stress. VO also led to increases in posterior wall thickness, which was not observed in the VO+EtOH group, and wall thickness significantly correlated with LV BNP expression. VO alone led to increases in interstitial collagen staining (picrosirius red), which while not statistically significant, tended to be decreased by EtOH. VO increased LV collagen I protein expression, whereas in rats with VO+EtOH, LV collagen I was not elevated relative to Sham. The combination of VO and EtOH also led to increases in LV collagen III expression relative to Sham. Rats with VO+EtOH had significantly lower collagen I/III ratio than rats with VO alone. During the acute remodeling phase of VO (3days), VO significantly increased collagen III

Antibacterial and cytotoxic activity of isoprenylated coumarin mammea A/AA isolated from Mammea africana.

PubMed

Canning, Corene; Sun, Shi; Ji, Xiangming; Gupta, Smiti; Zhou, Kequan

2013-05-02

The stem bark of Mammea africana is widely distributed in tropical Africa and commonly used in traditional medicine. This study aims to identify the active compound in Mammea africana and to evaluate its antimicrobial and antiproliferative activity. Methanol extract from the bark of the Mammea africana was separated by liquid-liquid extraction, followed by open column chromatography. A principal antimicrobial compound was purified by high performance liquid chromatography (HPLC) and its structure was elucidated by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The antibacterial activity of the purified compound was determined using the broth microdilution method against 7 common pathogenic bacteria. The compound was also evaluated for cytotoxicity by cell proliferation assay (MTS) using the mouse embryonic fibroblast cell line NIH 3T3 and the non-small cell lung cancer cell line A549. The purified active compound was determined to be mammea A/AA and was found to be highly active against Campylobacter jejuni (MIC=0.5 μg/ml), Streptococcus pneumoniae (MIC=0.25 μg/ml), and Clostridium difficile (MIC=0.25 μg/ml). The compound exhibited significant antiproliferative activities against both NIH 3T3 and A549 cell lines. Mammea A/AA isolated from Mammea africana exerts specific inhibitory activity against Campylobacter jejuni, Streptococcus pneumoniae, and Campylobacter difficile. Mammea A/AA was also found to exhibit significant cytotoxicity against both cancer and normal cell lines. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Near-wall similarity in a pressure-driven three-dimensional turbulent boundary layer

NASA Technical Reports Server (NTRS)

Pierce, F. J.; Mcallister, J. E.

1980-01-01

Mean velocity, measured wall pressure and wall shear stress fields were made in a three dimensional pressure-driven turbulent boundary layer created by a cylinder with trailing edge placed normal to a flat plate floor. The direct force wall shear stress measurements were made with floating element direct force sensing shear meter that responded to both the magnitude and direction of the local wall shear stress. The ability of 10 near wall similarity models to describe the near wall velocity field for the measured flow under a wide range of skewing conditions and a variety of pressure gradient and wall shear vector orientations was used.

Wall shear measurement in sand-water mixture flows

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yucel, O.; Grad, W.H.

1975-07-01

The wall shear stress was measured in clear-water and sand-water mixture flows with the use of a flush-mounting hot-film shear-sensor. Data were obtained with 2 shear-sensors and 2 different sands (d50 = 0.45 mm and d50 = 0.88 mm) with solids concentrations of up to Cmax = 1.6% by vol, and for flow Reynolds number of 10/sup 5/ < RD < 6 x 10/sup 5/. The measured sensor wall shear stresses were compared with the true wall shear stresses obtained with the energy head loss measurements conducted in a pipeline system. The results of the tests in the clear-water flowsmore » confirmed the relationship between the sensor power output, Ps, and the wall shear stress, tauo, given by tauo1/3 = APs + B, in which A and B are calibration coefficients. The tests with the low-concentration sand-water mixtures in a vertical pipe indicated that for the present range of experiments, sensor power outputs with the mixtures exceeded those for clear-water by an average of 5%. It is shown that the shear sensors are delicate but accurate instruments that can be used for the measurement of the wall shear stress. (13 refs.)« less

Patient and Aneurysm Characteristics Predicting Prolonged Length of Stay After Elective Open AAA Repair in the Endovascular Era.

PubMed

Casillas-Berumen, Sergio; Rojas-Miguez, Florencia A; Farber, Alik; Komshian, Sevan; Kalish, Jeffrey A; Rybin, Denis; Doros, Gheorghe; Siracuse, Jeffrey J

2018-01-01

Open aortic aneurysm repair (AAA) repair can be resource intensive and associated with a prolonged length of stay (LOS). We sought to examine patient and aneurysm predictors of prolonged LOS to better identify those at risk in the preoperative setting. Patient data were obtained from the targeted AAA American College of Surgery National Surgical Quality Improvement Program database from 2012 to 2014 of patients undergoing open AAA repair. Multivariable logistic regression was used to determine predictors of prolonged postoperative LOS defined as greater than 10 days (75th percentile). There were 1172 open AAA repairs identified. The majority (54%) of patients were older than 70 years and male (74%). Surgical approach was transperitoneal (70.9%) and retroperitoneal (29.1%). Aneurysms were 51.4% infrarenal, 33% juxtarenal, 5.7% pararenal, 7.4% suprarenal, and 2.5% type IV thoracoabdominal. Mean and median LOS were 9.1 ± 7.4 and 7 (0-72) days, respectively. Independently associated with extended LOS factors were visceral revascularization (odds ratio [OR]: 5.32, 95% confidence interval [CI]: 2.77-10.22, P < .001), type IV thoracoabdominal extent (OR: 3.09, 95% CI: 1.01-9.46, P = .048), suprarenal extent (OR: 1.89, 95% CI: 1.07-3.34, P = .029) and juxtarenal (OR: 1.43, 95% CI: 1.01-2.02, P = .004), non-Caucasian race (OR: 2.80, 95% CI: 1.77-4.41, P < .001), chronic obstructive pulmonary disease (OR: 1.76, 95% CI: 1.20-2.59, P = .004), not-from-home admission (OR: 1.91, 95% CI: 1.13-3.24), and age greater than 70 (OR: 1.49, 95% CI: 1.08-2.05, P = .014). We identified patient and aneurysm characteristics independently associated with protracted LOS following open AAA repair. Prospective identification of high-risk patients may allow physicians and hospitals to engage in multidisciplinary collaborations preoperatively to try to improve LOS in this resource-intensive population.

Plant cell wall extensibility: connecting plant cell growth with cell wall structure, mechanics, and the action of wall-modifying enzymes.

PubMed

Cosgrove, Daniel J

2016-01-01

The advent of user-friendly instruments for measuring force/deflection curves of plant surfaces at high spatial resolution has resulted in a recent outpouring of reports of the 'Young's modulus' of plant cell walls. The stimulus for these mechanical measurements comes from biomechanical models of morphogenesis of meristems and other tissues, as well as single cells, in which cell wall stress feeds back to regulate microtubule organization, auxin transport, cellulose deposition, and future growth directionality. In this article I review the differences between elastic modulus and wall extensibility in the context of cell growth. Some of the inherent complexities, assumptions, and potential pitfalls in the interpretation of indentation force/deflection curves are discussed. Reported values of elastic moduli from surface indentation measurements appear to be 10- to >1000-fold smaller than realistic tensile elastic moduli in the plane of plant cell walls. Potential reasons for this disparity are discussed, but further work is needed to make sense of the huge range in reported values. The significance of wall stress relaxation for growth is reviewed and connected to recent advances and remaining enigmas in our concepts of how cellulose, hemicellulose, and pectins are assembled to make an extensible cell wall. A comparison of the loosening action of α-expansin and Cel12A endoglucanase is used to illustrate two different ways in which cell walls may be made more extensible and the divergent effects on wall mechanics. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Stress distribution in and equivalent width of flanges of wide, thin-wall steel beams

NASA Technical Reports Server (NTRS)

Winter, George

1940-01-01

The use of different forms of wide-flange, thin-wall steel beams is becoming increasingly widespread. Part of the information necessary for a national design of such members is the knowledge of the stress distribution in and the equivalent width of the flanges of such beams. This problem is analyzed in this paper on the basis of the theory of plane stress. As a result, tables and curves are given from which the equivalent width of any given beam can be read directly for use in practical design. An investigation is given of the limitations of this analysis due to the fact that extremely wide and thin flanges tend to curve out of their plane toward the neutral axis. A summary of test data confirms very satisfactorily the analytical results.

Prognostic value of high-dose dobutamine stress magnetic resonance imaging in 1,493 consecutive patients: assessment of myocardial wall motion and perfusion.

PubMed

Korosoglou, Grigorios; Elhmidi, Yacine; Steen, Henning; Schellberg, Dieter; Riedle, Nina; Ahrens, Johannes; Lehrke, Stephanie; Merten, Constanze; Lossnitzer, Dirk; Radeleff, Jannis; Zugck, Christian; Giannitsis, Evangelos; Katus, Hugo A

2010-10-05

This study sought to determine the prognostic value of wall motion and perfusion assessment during high-dose dobutamine stress (DS) cardiac magnetic resonance imaging (MRI) in a large patient cohort. DS-MRI offers the possibility to integrate myocardial perfusion and wall motion analysis in a single examination for the detection of coronary artery disease (CAD). A total of 1,493 consecutive patients with suspected or known CAD underwent DS-MRI, using a standard protocol in a 1.5-T magnetic resonance scanner. Wall motion and perfusion were assessed at baseline and during stress, and outcome data including cardiac death, nonfatal myocardial infarction ("hard events"), and "late" revascularization performed >90 days after the MR scans were collected during a 2 ± 1 year follow-up period. Fifty-three hard events, including 14 cardiac deaths and 39 nonfatal infarctions, occurred during the follow-up period, whereas 85 patients underwent "late" revascularization. Using multivariable regression analysis, an abnormal result for wall motion or perfusion during stress yielded the strongest independent prognostic value for both hard events and late revascularization, clearly surpassing that of clinical and baseline magnetic resonance parameters (for wall motion: adjusted hazard ratio [HR] of 5.9 [95% confidence interval (CI): 2.5 to 13.6] for hard events and of 3.1 [95% CI: 1.7 to 5.6] for late revascularization, and for perfusion: adjusted HR of 5.4 [95% CI: 2.3 to 12.9] for hard events and of 6.2 [95% CI: 3.3 to 11.3] for late revascularization, p < 0.001 for all). DS-MRI can accurately identify patients who are at increased risk for cardiac death and myocardial infarction, separating them from those with normal findings, who have very low risk for future cardiac events. (Prognostic Value of High Dose Dobutamine Stress Magnetic Resonance Imaging; NCT00837005). Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cell envelope stress response in cell wall-deficient L-forms of Bacillus subtilis.

PubMed

Wolf, Diana; Domínguez-Cuevas, Patricia; Daniel, Richard A; Mascher, Thorsten

2012-11-01

L-forms are cell wall-deficient bacteria that can grow and proliferate in osmotically stabilizing media. Recently, a strain of the Gram-positive model bacterium Bacillus subtilis was constructed that allowed controlled switching between rod-shaped wild-type cells and corresponding L-forms. Both states can be stably maintained under suitable culture conditions. Because of the absence of a cell wall, L-forms are known to be insensitive to β-lactam antibiotics, but reports on the susceptibility of L-forms to other antibiotics that interfere with membrane-anchored steps of cell wall biosynthesis are sparse, conflicting, and strongly influenced by strain background and method of L-form generation. Here we investigated the response of B. subtilis to the presence of cell envelope antibiotics, with regard to both antibiotic resistance and the induction of the known LiaRS- and BceRS-dependent cell envelope stress biosensors. Our results show that B. subtilis L-forms are resistant to antibiotics that interfere with the bactoprenol cycle, such as bacitracin, vancomycin, and mersacidin, but are hypersensitive to nisin and daptomycin, which both affect membrane integrity. Moreover, we established a lacZ-based reporter gene assay for L-forms and provide evidence that LiaRS senses its inducers indirectly (damage sensing), while the Bce module detects its inducers directly (drug sensing).

Cell Envelope Stress Response in Cell Wall-Deficient L-Forms of Bacillus subtilis

PubMed Central

Wolf, Diana; Domínguez-Cuevas, Patricia; Daniel, Richard A.

2012-01-01

L-forms are cell wall-deficient bacteria that can grow and proliferate in osmotically stabilizing media. Recently, a strain of the Gram-positive model bacterium Bacillus subtilis was constructed that allowed controlled switching between rod-shaped wild-type cells and corresponding L-forms. Both states can be stably maintained under suitable culture conditions. Because of the absence of a cell wall, L-forms are known to be insensitive to β-lactam antibiotics, but reports on the susceptibility of L-forms to other antibiotics that interfere with membrane-anchored steps of cell wall biosynthesis are sparse, conflicting, and strongly influenced by strain background and method of L-form generation. Here we investigated the response of B. subtilis to the presence of cell envelope antibiotics, with regard to both antibiotic resistance and the induction of the known LiaRS- and BceRS-dependent cell envelope stress biosensors. Our results show that B. subtilis L-forms are resistant to antibiotics that interfere with the bactoprenol cycle, such as bacitracin, vancomycin, and mersacidin, but are hypersensitive to nisin and daptomycin, which both affect membrane integrity. Moreover, we established a lacZ-based reporter gene assay for L-forms and provide evidence that LiaRS senses its inducers indirectly (damage sensing), while the Bce module detects its inducers directly (drug sensing). PMID:22964256

AAA and AXB algorithms for the treatment of nasopharyngeal carcinoma using IMRT and RapidArc techniques.

PubMed

Kamaleldin, Maha; Elsherbini, Nader A; Elshemey, Wael M

2017-09-27

The aim of this study is to evaluate the impact of anisotropic analytical algorithm (AAA) and 2 reporting systems (AXB-D m and AXB-D w ) of Acuros XB algorithm (AXB) on clinical plans of nasopharyngeal patients using intensity-modulated radiotherapy (IMRT) and RapidArc (RA) techniques. Six plans of different algorithm-technique combinations are performed for 10 patients to calculate dose-volume histogram (DVH) physical parameters for planning target volumes (PTVs) and organs at risk (OARs). The number of monitor units (MUs) and calculation time are also determined. Good coverage is reported for all algorithm-technique combination plans without exceeding the tolerance for OARs. Regardless of the algorithm, RA plans persistently reported higher D 2% values for PTV-70. All IMRT plans reported higher number of MUs (especially with AXB) than did RA plans. AAA-IMRT produced the minimum calculation time of all plans. Major differences between the investigated algorithm-technique combinations are reported only for the number of MUs and calculation time parameters. In terms of these 2 parameters, it is recommended to employ AXB in calculating RA plans and AAA in calculating IMRT plans to achieve minimum calculation times at reduced number of MUs. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Plaque components affect wall stress in stented human carotid artery: A numerical study

NASA Astrophysics Data System (ADS)

Fan, Zhen-Min; Liu, Xiao; Du, Cheng-Fei; Sun, An-Qiang; Zhang, Nan; Fan, Zhan-Ming; Fan, Yu-Bo; Deng, Xiao-Yan

2016-12-01

Carotid artery stenting presents challenges of in-stent restenosis and late thrombosis, which are caused primarily by alterations in the mechanical environment of the artery after stent implantation. The present study constructed patient-specific carotid arterial bifurcation models with lipid pools and calcified components based on magnetic resonance imaging. We numerically analyzed the effects of multicomponent plaques on the distributions of von Mises stresses (VMSs) in the patient-specific models after stenting. The results showed that when a stent was deployed, the large soft lipid pool in atherosclerotic plaques cushioned the host artery and reduced the stress within the arterial wall; however, this resulted in a sharp increase of VMS in the fibrous cap. When compared with the lipid pool, the presence of the calcified components led to slightly increased stresses on the luminal surface. However, when a calcification was located close to the luminal surface of the host artery and the stenosis, the local VMS was elevated. Overall, compared with calcified components, large lipid pools severely damaged the host artery after stenting. Furthermore, damage due to the calcified component may depend on location.

Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters

PubMed Central

2013-01-01

Purpose Retrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA. Methods The 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms. Results In the prostate plans, the AAA predicted lower NTCP value (NTCPAAA) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCPAAA, that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCPPBC’s ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCPAAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCPPBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCPAAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCPAAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0

Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters.

PubMed

Bufacchi, Antonella; Nardiello, Barbara; Capparella, Roberto; Begnozzi, Luisa

2013-07-04

Retrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA. The 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms. In the prostate plans, the AAA predicted lower NTCP value (NTCPAAA) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCPAAA, that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCPPBC's ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCPAAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCPPBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCPAAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCPAAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0.3%), while the mean NTCPPBC

How do plant cell walls extend?

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

1993-01-01

This article briefly summarizes recent work that identifies the biophysical and biochemical processes that give rise to the extension of plant cell walls. I begin with the biophysical notion of stress relaxation of the wall and follow with recent studies of wall enzymes thought to catalyze wall extension and relaxation. Readers should refer to detailed reviews for more comprehensive discussion of earlier literature (Taiz, 1984; Carpita and Gibeaut, 1993; Cosgrove, 1993).

Comparison of treadmill exercise stress cardiac MRI to stress echocardiography in healthy volunteers for adequacy of left ventricular endocardial wall visualization: A pilot study

PubMed Central

Thavendiranathan, Paaladinesh; Dickerson, Jennifer A.; Scandling, Debbie; Balasubramanian, Vijay; Pennell, Michael L.; Hinton, Alice; Raman, Subha V.; Simonetti, Orlando P.

2013-01-01

Purpose To compare exercise stress cardiac magnetic resonance (cardiac MR) to echocardiography in healthy volunteers with respect to adequacy of endocardial visualization and confidence of stress study interpretation. Materials and Methods 28 healthy volunteers (aged 28 ± 11 years, 15 males) underwent exercise stress echo and cardiac MR one week apart assigned randomly to one test first. Stress cardiac MR was performed using an MRI-compatible treadmill; stress echo was performed as per routine protocol. Cardiac MR and echo images were independently reviewed and scored for adequacy of endocardial visualization and confidence in interpretation of the stress study. Results Heart rate at the time of imaging was similar between the studies. Average time from cessation of exercise to start of imaging (21 vs. 31 seconds, p<0.001) and time to acquire stress images (20 vs. 51 seconds, p<0.001) was shorter for cardiac MR. The number of myocardial segments adequately visualized was significantly higher by cardiac MR at rest (99.8% versus 96.4%, p=0.002) and stress (99.8% versus 94.1%, p=0.001). The proportion of subjects in whom there was high confidence in the interpretation was higher for cardiac MR than echo (96% vs 60%, p=0.005). Conclusion Exercise stress cardiac MR to assess peak exercise wall motion is feasible and can be performed at least as rapidly as stress echo. PMID:24123562

Inverse measurement of wall pressure field in flexible-wall wind tunnels using global wall deformation data

NASA Astrophysics Data System (ADS)

Brown, Kenneth; Brown, Julian; Patil, Mayuresh; Devenport, William

2018-02-01

The Kevlar-wall anechoic wind tunnel offers great value to the aeroacoustics research community, affording the capability to make simultaneous aeroacoustic and aerodynamic measurements. While the aeroacoustic potential of the Kevlar-wall test section is already being leveraged, the aerodynamic capability of these test sections is still to be fully realized. The flexibility of the Kevlar walls suggests the possibility that the internal test section flow may be characterized by precisely measuring small deflections of the flexible walls. Treating the Kevlar fabric walls as tensioned membranes with known pre-tension and material properties, an inverse stress problem arises where the pressure distribution over the wall is sought as a function of the measured wall deflection. Experimental wall deformations produced by the wind loading of an airfoil model are measured using digital image correlation and subsequently projected onto polynomial basis functions which have been formulated to mitigate the impact of measurement noise based on a finite-element study. Inserting analytic derivatives of the basis functions into the equilibrium relations for a membrane, full-field pressure distributions across the Kevlar walls are computed. These inversely calculated pressures, after being validated against an independent measurement technique, can then be integrated along the length of the test section to give the sectional lift of the airfoil. Notably, these first-time results are achieved with a non-contact technique and in an anechoic environment.

Acetylation of cell wall is required for structural integrity of the leaf surface and exerts a global impact on plant stress responses

DOE PAGES

Nafisi, Majse; Stranne, Maria; Fimognari, Lorenzo; ...

2015-07-22

Here we report that the epidermis on leaves protects plants from pathogen invasion and provides a waterproof barrier. It consists of a layer of cells that is surrounded by thick cell walls, which are partially impregnated by highly hydrophobic cuticular components. We show that the Arabidopsis T-DNA insertion mutants of REDUCED WALL ACETYLATION 2 (rwa2), previously identified as having reduced O-acetylation of both pectins and hemicelluloses, exhibit pleiotrophic phenotype on the leaf surface. The cuticle layer appeared diffused and was significantly thicker and underneath cell wall layer was interspersed with electron-dense deposits. A large number of trichomes were collapsed andmore » surface permeability of the leaves was enhanced in rwa2 as compared to the wild type. A massive reprogramming of the transcriptome was observed in rwa2 as compared to the wild type, including a coordinated up-regulation of genes involved in responses to abiotic stress, particularly detoxification of reactive oxygen species and defense against microbial pathogens (e.g., lipid transfer proteins, peroxidases). In accordance, peroxidase activities were found to be elevated in rwa2 as compared to the wild type. These results indicate that cell wall acetylation is essential for maintaining the structural integrity of leaf epidermis, and that reduction of cell wall acetylation leads to global stress responses in Arabidopsis.« less

γ-Aminobutyric acid transaminase deficiency impairs central carbon metabolism and leads to cell wall defects during salt stress in Arabidopsis roots.

PubMed

Renault, Hugues; El Amrani, Abdelhak; Berger, Adeline; Mouille, Grégory; Soubigou-Taconnat, Ludivine; Bouchereau, Alain; Deleu, Carole

2013-05-01

Environmental constraints challenge cell homeostasis and thus require a tight regulation of metabolic activity. We have previously reported that the γ-aminobutyric acid (GABA) metabolism is crucial for Arabidopsis salt tolerance as revealed by the NaCl hypersensitivity of the GABA transaminase (GABA-T, At3g22200) gaba-t/pop2-1 mutant. In this study, we demonstrate that GABA-T deficiency during salt stress causes root and hypocotyl developmental defects and alterations of cell wall composition. A comparative genome-wide transcriptional analysis revealed that expression levels of genes involved in carbon metabolism, particularly sucrose and starch catabolism, were found to increase upon the loss of GABA-T function under salt stress conditions. Consistent with the altered mutant cell wall composition, a number of cell wall-related genes were also found differentially expressed. A targeted quantitative analysis of primary metabolites revealed that glutamate (GABA precursor) accumulated while succinate (the final product of GABA metabolism) significantly decreased in mutant roots after 1 d of NaCl treatment. Furthermore, sugar concentration was twofold reduced in gaba-t/pop2-1 mutant roots compared with wild type. Together, our results provide strong evidence that GABA metabolism is a major route for succinate production in roots and identify GABA as a major player of central carbon adjustment during salt stress. © 2012 Blackwell Publishing Ltd.

Wall shear stress in portal vein of cirrhotic patients with portal hypertension.

PubMed

Wei, Wei; Pu, Yan-Song; Wang, Xin-Kai; Jiang, An; Zhou, Rui; Li, Yu; Zhang, Qiu-Juan; Wei, Ya-Juan; Chen, Bin; Li, Zong-Fang

2017-05-14

To investigate wall shear stress (WSS) magnitude and distribution in cirrhotic patients with portal hypertension using computational fluid dynamics. Idealized portal vein (PV) system models were reconstructed with different angles of the PV-splenic vein (SV) and superior mesenteric vein (SMV)-SV. Patient-specific models were created according to enhanced computed tomography images. WSS was simulated by using a finite-element analyzer, regarding the blood as a Newtonian fluid and the vessel as a rigid wall. Analysis was carried out to compare the WSS in the portal hypertension group with that in healthy controls. For the idealized models, WSS in the portal hypertension group (0-10 dyn/cm 2 ) was significantly lower than that in the healthy controls (10-20 dyn/cm 2 ), and low WSS area (0-1 dyn/cm 2 ) only occurred in the left wall of the PV in the portal hypertension group. Different angles of PV-SV and SMV-SV had different effects on the magnitude and distribution of WSS, and low WSS area often occurred in smaller PV-SV angle and larger SMV-SV angle. In the patient-specific models, WSS in the cirrhotic patients with portal hypertension (10.13 ± 1.34 dyn/cm 2 ) was also significantly lower than that in the healthy controls ( P < 0.05). Low WSS area often occurred in the junction area of SV and SMV into the PV, in the area of the division of PV into left and right PV, and in the outer wall of the curving SV in the control group. In the cirrhotic patients with portal hypertension, the low WSS area extended to wider levels and the magnitude of WSS reached lower levels, thereby being more prone to disturbed flow occurrence. Cirrhotic patients with portal hypertension show dramatic hemodynamic changes with lower WSS and greater potential for disturbed flow, representing a possible causative factor of PV thrombosis.

Wall shear stress in portal vein of cirrhotic patients with portal hypertension

PubMed Central

Wei, Wei; Pu, Yan-Song; Wang, Xin-Kai; Jiang, An; Zhou, Rui; Li, Yu; Zhang, Qiu-Juan; Wei, Ya-Juan; Chen, Bin; Li, Zong-Fang

2017-01-01

AIM To investigate wall shear stress (WSS) magnitude and distribution in cirrhotic patients with portal hypertension using computational fluid dynamics. METHODS Idealized portal vein (PV) system models were reconstructed with different angles of the PV-splenic vein (SV) and superior mesenteric vein (SMV)-SV. Patient-specific models were created according to enhanced computed tomography images. WSS was simulated by using a finite-element analyzer, regarding the blood as a Newtonian fluid and the vessel as a rigid wall. Analysis was carried out to compare the WSS in the portal hypertension group with that in healthy controls. RESULTS For the idealized models, WSS in the portal hypertension group (0-10 dyn/cm2) was significantly lower than that in the healthy controls (10-20 dyn/cm2), and low WSS area (0-1 dyn/cm2) only occurred in the left wall of the PV in the portal hypertension group. Different angles of PV-SV and SMV-SV had different effects on the magnitude and distribution of WSS, and low WSS area often occurred in smaller PV-SV angle and larger SMV-SV angle. In the patient-specific models, WSS in the cirrhotic patients with portal hypertension (10.13 ± 1.34 dyn/cm2) was also significantly lower than that in the healthy controls (P < 0.05). Low WSS area often occurred in the junction area of SV and SMV into the PV, in the area of the division of PV into left and right PV, and in the outer wall of the curving SV in the control group. In the cirrhotic patients with portal hypertension, the low WSS area extended to wider levels and the magnitude of WSS reached lower levels, thereby being more prone to disturbed flow occurrence. CONCLUSION Cirrhotic patients with portal hypertension show dramatic hemodynamic changes with lower WSS and greater potential for disturbed flow, representing a possible causative factor of PV thrombosis. PMID:28566887

Growth promoting effects of prebiotic yeast cell wall products in starter broilers under an immune stress and Clostridium perfringens challenge

USDA-ARS?s Scientific Manuscript database

This study was designed to investigate the growth promoting effects of supplementing different sources and concentrations of prebiotic yeast cell wall (YCW) products containing mannanoligosaccharides in starter broilers under an immune stress and Clostridium perfringens challenge. Through a series ...

Morphological State as a Predictor for Reintervention and Mortality After EVAR for AAA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohrlander, Tomas; Dencker, Magnus; Acosta, Stefan, E-mail: stefan.acosta@telia.com

2012-10-15

Purpose: This study was designed to assess aorto-iliac morphological characteristics in relation to reintervention and all-cause long-term mortality in patients undergoing standard EVAR for infrarenal AAA. Methods: Patients treated with EVAR (Zenith{sup Registered-Sign} Stentgrafts, Cook) between May 1998 and February 2006 were prospectively enrolled in a computerized database where comorbidities and preoperative aneurysm morphology were entered. Reinterventions and mortality were checked until December 1, 2010. Median follow-up time was 68 months. Results: A total of 304 patients were included, of which 86% were men. Median age was 74 years. The reintervention rate was 23.4% (71/304). A greater diameter of themore » common iliac artery (p = 0.037; hazard ratio (HR) 1.037 [1.002-1.073]) was an independent factor for an increased number of reinterventions. The 30-day mortality rate was 3.0% (9/304). Aneurysm-related deaths due to AAA occurred in 4.9% (15/304). Five patients died due to a concomitant ruptured thoracic aortic aneurysm. The mortality until end of follow-up was 54.3% (165/304). The proportion of deaths caused by vascular diseases was 61.6%. The severity of angulation of the iliac arteries (p = 0.014; HR 1.018 [95% confidence interval (CI) 1.004-1.033]) and anemia (p = 0.044; HR 2.79 [95% CI 1.029-7.556]) remained as independent factors associated with all-cause long-term mortality. The crude reintervention-free survival rate at 1, 3, and 5 years was 84.5%, 64.8%, and 51.6%, respectively. Conclusions: The initial aorto-iliac morphological state in patients scheduled for standard EVAR for AAA seems to be strongly related to the need for reinterventions and long-term mortality.« less

Structural Basis of ATP Hydrolysis and Intersubunit Signaling in the AAA+ ATPase p97.

PubMed

Hänzelmann, Petra; Schindelin, Hermann

2016-01-05

p97 belongs to the superfamily of AAA+ ATPases and is characterized by a tandem AAA module, an N-terminal domain involved in substrate and cofactor interactions, and a functionally important unstructured C-terminal tail. The ATPase activity is controlled by an intradomain communication within the same protomer and an interdomain communication between neighboring protomers. Here, we present for the first time crystal structures in which the physiologically relevant p97 hexamer constitutes the content of the asymmetric unit, namely in the apo state without nucleotide in either the D1 or D2 module and in the pre-activated state with ATPγS bound to both modules. The structures provide new mechanistic insights into the interdomain communication mediated by conformational changes of the C terminus as well as an intersubunit signaling network, which couples the nucleotide state to the conformation of the central putative substrate binding pore. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structural basis of protein translocation by the Vps4-Vta1 AAA ATPase

PubMed Central

Monroe, Nicole; Han, Han; Shen, Peter S; Sundquist, Wesley I; Hill, Christopher P

2017-01-01

Many important cellular membrane fission reactions are driven by ESCRT pathways, which culminate in disassembly of ESCRT-III polymers by the AAA ATPase Vps4. We report a 4.3 Å resolution cryo-EM structure of the active Vps4 hexamer with its cofactor Vta1, ADP·BeFx, and an ESCRT-III substrate peptide. Four Vps4 subunits form a helix whose interfaces are consistent with ATP binding, is stabilized by Vta1, and binds the substrate peptide. The fifth subunit approximately continues this helix but appears to be dissociating. The final Vps4 subunit completes a notched-washer configuration as if transitioning between the ends of the helix. We propose that ATP binding propagates growth at one end of the helix while hydrolysis promotes disassembly at the other end, so that Vps4 ‘walks’ along ESCRT-III until it encounters the ordered N-terminal domain to destabilize the ESCRT-III lattice. This model may be generally applicable to other protein-translocating AAA ATPases. DOI: http://dx.doi.org/10.7554/eLife.24487.001 PMID:28379137

Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

PubMed Central

Zhuang, Lei; Zhang, Jun; Xiang, Xin

2007-01-01

Cytoplasmic dynein performs multiple cellular tasks but its regulation remains unclear. The dynein heavy chain has a N-terminal stem that binds to other subunits and a C-terminal motor unit that contains six AAA (ATPase associated with cellular activities) domains and a microtubule-binding site located between AAA4 and AAA5. In Aspergillus nidulans, NUDF (a LIS1 homolog) functions in the dynein pathway, and two nudF6 partial suppressors were mapped to the nudA dynein heavy chain locus. Here we identified these two mutations. The nudAL1098F mutation resides in the stem region, and nudAR3086C is in the end of AAA4. These mutations partially suppress the phenotype of nudF deletion but do not suppress the phenotype exhibited by mutants of dynein intermediate chain and Arp1. Surprisingly, the stronger ΔnudF suppressor, nudAR3086C, causes an obvious decrease in the basal level of dynein's ATPase activity and an increase in dynein's distribution along microtubules. Thus, suppression of the ΔnudF phenotype may result from mechanisms other than simply the enhancement of dynein's ATPase activity. The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo. PMID:17237507

Impact of stent mis-sizing and mis-positioning on coronary fluid wall shear and intramural stress

PubMed Central

Chen, Henry Y.; Koo, Bon-Kwon; Bhatt, Deepak L.

2013-01-01

Stent deployments with geographical miss (GM) are associated with increased risk of target-vessel revascularization and periprocedural myocardial infarction. The aim of the current study was to investigate the underlying biomechanical mechanisms for adverse events with GM. The hypothesis is that stent deployment with GM [longitudinal GM, or LGM (i.e., stent not centered on the lesion); or radial GM, RGM (i.e., stent oversizing)] results in unfavorable fluid wall shear stress (WSS), WSS gradient (WSSG), oscillatory shear index (OSI), and intramural circumferential wall stress (CWS). Three-dimensional computational models of stents and plaque were created using a computer-assisted design package. The models were then solved with validated finite element and computational fluid dynamic packages. The dynamic process of large deformation stent deployment was modeled to expand the stent to the desired vessel size. Stent deployed with GM resulted in a 45% increase in vessel CWS compared with stents that were centered and fully covered the lesion. A 20% oversized stent resulted in 72% higher CWS than a correct sized stent. The linkages between the struts had much higher stress than the main struts (i.e., 180 MPa vs. 80 MPa). Additionally, LGM and RGM reduced endothelial WSS and increased WSSG and OSI. The simulations suggest that both LGM and RGM adversely reduce WSS but increase WSSG, OSI, and CWS. These findings highlight the potential mechanical mechanism of the higher adverse events and underscore the importance of stent positioning and sizing for improved clinical outcome. PMID:23722708

The plant cell wall integrity maintenance mechanism--a case study of a cell wall plasma membrane signaling network.

PubMed

Hamann, Thorsten

2015-04-01

Some of the most important functions of plant cell walls are protection against biotic/abiotic stress and structural support during growth and development. A prerequisite for plant cell walls to perform these functions is the ability to perceive different types of stimuli in both qualitative and quantitative manners and initiate appropriate responses. The responses in turn involve adaptive changes in cellular and cell wall metabolism leading to modifications in the structures originally required for perception. While our knowledge about the underlying plant mechanisms is limited, results from Saccharomyces cerevisiae suggest the cell wall integrity maintenance mechanism represents an excellent example to illustrate how the molecular mechanisms responsible for stimulus perception, signal transduction and integration can function. Here I will review the available knowledge about the yeast cell wall integrity maintenance system for illustration purposes, summarize the limited knowledge available about the corresponding plant mechanism and discuss the relevance of the plant cell wall integrity maintenance mechanism in biotic stress responses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential proteome analysis during early somatic embryogenesis in Musa spp. AAA cv. Grand Naine.

PubMed

Kumaravel, Marimuthu; Uma, Subbaraya; Backiyarani, Suthanthiram; Saraswathi, Marimuthu Somasundaram; Vaganan, Muthu Mayil; Muthusamy, Muthusamy; Sajith, Kallu Purayil

2017-01-01

Endogenous hormone secretion proteins along with stress and defense proteins play predominant role in banana embryogenesis. This study reveals the underlying molecular mechanism during transition from vegetative to embryogenic state. Banana (Musa spp.) is well known globally as a food fruit crop for millions. The requirement of quality planting material of banana is enormous. Although mass multiplication through tissue culture is in vogue, high-throughput techniques like somatic embryogenesis (SE) as a mass multiplication tool needs to be improved. Apart from clonal propagation, SE has extensive applications in genetic improvement and mutation. SE in banana is completely genome-dependent and most of the commercial cultivars exhibit recalcitrance. Thus, understanding the molecular basis of embryogenesis in Musa will help to develop strategies for mass production of quality planting material. In this study, differentially expressed proteins between embryogenic calli (EC) and non-embryogenic calli (NEC) with respect to the explant, immature male flower buds (IMFB), of cv. Grand Naine (AAA) were determined using two-dimensional gel electrophoresis (2DE). The 2DE results were validated through qRT-PCR. In total, 65 proteins were identified: 42 were highly expressed and 23 were less expressed in EC compared to NEC and IMFB. qRT-PCR analysis of five candidate proteins, upregulated in EC, were well correlated with expression at transcript level. Further analysis of proteins showed that embryogenesis in banana is associated with the control of oxidative stress. The regulation of ROS scavenging system and protection of protein structure occurred in the presence of heat shock proteins. Alongside, high accumulation of stress-related cationic peroxidase and plant growth hormone-related proteins like indole-3-pyruvate monooxygenase and adenylate isopentenyltransferase in EC revealed the association with the induction of SE.

Comparison of Acuros (AXB) and Anisotropic Analytical Algorithm (AAA) for dose calculation in treatment of oesophageal cancer: effects on modelling tumour control probability.

PubMed

Padmanaban, Sriram; Warren, Samantha; Walsh, Anthony; Partridge, Mike; Hawkins, Maria A

2014-12-23

To investigate systematic changes in dose arising when treatment plans optimised using the Anisotropic Analytical Algorithm (AAA) are recalculated using Acuros XB (AXB) in patients treated with definitive chemoradiotherapy (dCRT) for locally advanced oesophageal cancers. We have compared treatment plans created using AAA with those recalculated using AXB. Although the Anisotropic Analytical Algorithm (AAA) is currently more widely used in clinical routine, Acuros XB (AXB) has been shown to more accurately calculate the dose distribution, particularly in heterogeneous regions. Studies to predict clinical outcome should be based on modelling the dose delivered to the patient as accurately as possible. CT datasets from ten patients were selected for this retrospective study. VMAT (Volumetric modulated arc therapy) plans with 2 arcs, collimator rotation ± 5-10° and dose prescription 50 Gy / 25 fractions were created using Varian Eclipse (v10.0). The initial dose calculation was performed with AAA, and AXB plans were created by re-calculating the dose distribution using the same number of monitor units (MU) and multileaf collimator (MLC) files as the original plan. The difference in calculated dose to organs at risk (OAR) was compared using dose-volume histogram (DVH) statistics and p values were calculated using the Wilcoxon signed rank test. The potential clinical effect of dosimetric differences in the gross tumour volume (GTV) was evaluated using three different TCP models from the literature. PTV Median dose was apparently 0.9 Gy lower (range: 0.5 Gy - 1.3 Gy; p < 0.05) for VMAT AAA plans re-calculated with AXB and GTV mean dose was reduced by on average 1.0 Gy (0.3 Gy -1.5 Gy; p < 0.05). An apparent difference in TCP of between 1.2% and 3.1% was found depending on the choice of TCP model. OAR mean dose was lower in the AXB recalculated plan than the AAA plan (on average, dose reduction: lung 1.7%, heart 2.4%). Similar trends were seen for CRT plans

Large-eddy simulations with wall models

NASA Technical Reports Server (NTRS)

Cabot, W.

1995-01-01

The near-wall viscous and buffer regions of wall-bounded flows generally require a large expenditure of computational resources to be resolved adequately, even in large-eddy simulation (LES). Often as much as 50% of the grid points in a computational domain are devoted to these regions. The dense grids that this implies also generally require small time steps for numerical stability and/or accuracy. It is commonly assumed that the inner wall layers are near equilibrium, so that the standard logarithmic law can be applied as the boundary condition for the wall stress well away from the wall, for example, in the logarithmic region, obviating the need to expend large amounts of grid points and computational time in this region. This approach is commonly employed in LES of planetary boundary layers, and it has also been used for some simple engineering flows. In order to calculate accurately a wall-bounded flow with coarse wall resolution, one requires the wall stress as a boundary condition. The goal of this work is to determine the extent to which equilibrium and boundary layer assumptions are valid in the near-wall regions, to develop models for the inner layer based on such assumptions, and to test these modeling ideas in some relatively simple flows with different pressure gradients, such as channel flow and flow over a backward-facing step. Ultimately, models that perform adequately in these situations will be applied to more complex flow configurations, such as an airfoil.

The Fluid Mechanics of a Wavy-Wall Bioreactor

NASA Astrophysics Data System (ADS)

Sucosky, Philippe; Bilgen, Bahar; Aleem, Alexander; Neitzel, Paul; Barabino, Gilda

2004-11-01

Bioreactors are devices used for the production of mammalian tissue in vitro. Although mixing has been shown to stimulate the growth of cartilage constructs, high shear-stress levels can damage the cells. In order to enhance mixing while minimizing shear, a wavy-wall bioreactor (WWB) featuring a sinusoidal internal profile has been designed. The turbulent hydrodynamic environment produced in this device is investigated experimentally using particle-image velocimetry. A model bioreactor made of acrylic and filled with an index-matching solution of zinc iodide is used to compensate for the refraction of light at the walls. The flow observed in different planes is shown to be periodic, spatially dependent, and dominated by mean-shear rather than Reynolds stresses in the vicinity of constructs. Finally, a comparison between the mean-shear stresses obtained in the WWB and in a standard spinner flask reveals similar stress levels near the construct walls.

Analysis of a dusty wall jet

NASA Technical Reports Server (NTRS)

Lim, Hock-Bin; Roberts, Leonard

1991-01-01

An analysis is given for the entrainment of dust into a turbulent radial wall jet. Equations are solved based on incompressible flow of a radial wall jet into which dust is entrained from the wall and transported by turbulent diffusion and convection throughout the flow. It is shown that the resulting concentration of dust particles in the flow depends on the difference between the applied shear stress at the surface and the maximum level of shear stress that the surface can withstand (varies as rho(sub d)a(sub g)D) i.e., the pressure due to the weight of a single layer of dust. The analysis is expected to have application to the downflow that results from helicopter and VTOL aircraft.

The MAP kinase-activated protein kinase Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen Candida albicans.

PubMed

Li, Xichuan; Du, Wei; Zhao, Jingwen; Zhang, Lilin; Zhu, Zhiyan; Jiang, Linghuo

2010-06-01

Rck2p is the Hog1p-MAP kinase-activated protein kinase required for the attenuation of protein synthesis in response to an osmotic challenge in Saccharomyces cerevisiae. Rck2p also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. In this study, we demonstrate that the deletion of CaRCK2 renders C. albicans cells sensitive to, and CaRck2p translocates from the cytosol to the nucleus in response to, cell wall stresses caused by Congo red, Calcoflor White, elevated heat and zymolyase. However, the kinase activity of CaRck2p is not required for the cellular response to these cell wall stresses. Furthermore, transcripts of cell wall protein-encoding genes CaBGL2, CaHWP1 and CaXOG1 are reduced in C. albicans cells lacking CaRCK2. The deletion of CaRCK2 also reduces the in vitro filamentation of C. albicans and its virulence in a mouse model of systemic candidasis. The kinase activity of CaRck2p is required for the virulence, but not for the in vitro filamentation, in C. albicans. Therefore, Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen C. albicans.

Preferences of AAA/AAG codon recognition by modified nucleosides, τm5s2U34 and t6A37 present in tRNALys.

PubMed

Sonawane, Kailas D; Kamble, Asmita S; Fandilolu, Prayagraj M

2017-12-27

Deficiency of 5-taurinomethyl-2-thiouridine, τm 5 s 2 U at the 34th 'wobble' position in tRNA Lys causes MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a neuromuscular disease. This modified nucleoside of mt tRNA Lys , recognizes AAA/AAG codons during protein biosynthesis process. Its preference to identify cognate codons has not been studied at the atomic level. Hence, multiple MD simulations of various molecular models of anticodon stem loop (ASL) of mt tRNA Lys in presence and absence of τm 5 s 2 U 34 and N 6 -threonylcarbamoyl adenosine (t 6 A 37 ) along with AAA and AAG codons have been accomplished. Additional four MD simulations of multiple ASL mt tRNA Lys models in the context of ribosomal A-site residues have also been performed to investigate the role of A-site in recognition of AAA/AAG codons. MD simulation results show that, ASL models in presence of τm 5 s 2 U 34 and t 6 A 37 with codons AAA/AAG are more stable than the ASL lacking these modified bases. MD trajectories suggest that τm 5 s 2 U recognizes the codons initially by 'wobble' hydrogen bonding interactions, and then tRNA Lys might leave the explicit codon by a novel 'single' hydrogen bonding interaction in order to run the protein biosynthesis process smoothly. We propose this model as the 'Foot-Step Model' for codon recognition, in which the single hydrogen bond plays a crucial role. MD simulation results suggest that, tRNA Lys with τm 5 s 2 U and t 6 A recognizes AAA codon more preferably than AAG. Thus, these results reveal the consequences of τm 5 s 2 U and t 6 A in recognition of AAA/AAG codons in mitochondrial disease, MERRF.

Comparison of the Young-Laplace law and finite element based calculation of ventricular wall stress: implications for postinfarct and surgical ventricular remodeling.

PubMed

Zhang, Zhihong; Tendulkar, Amod; Sun, Kay; Saloner, David A; Wallace, Arthur W; Ge, Liang; Guccione, Julius M; Ratcliffe, Mark B

2011-01-01

Both the Young-Laplace law and finite element (FE) based methods have been used to calculate left ventricular wall stress. We tested the hypothesis that the Young-Laplace law is able to reproduce results obtained with the FE method. Magnetic resonance imaging scans with noninvasive tags were used to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after anteroapical myocardial infarction, and in 1 of those sheep 6 weeks after a Dor procedure. Animal-specific FE models were created from the remaining 5 animals using magnetic resonance images obtained at early diastolic filling. The FE-based stress in the fiber, cross-fiber, and circumferential directions was calculated and compared to stress calculated with the assumption that wall thickness is very much less than the radius of curvature (Young-Laplace law), and without that assumption (modified Laplace). First, circumferential stress calculated with the modified Laplace law is closer to results obtained with the FE method than stress calculated with the Young-Laplace law. However, there are pronounced regional differences, with the largest difference between modified Laplace and FE occurring in the inner and outer layers of the infarct borderzone. Also, stress calculated with the modified Laplace is very different than stress in the fiber and cross-fiber direction calculated with FE. As a consequence, the modified Laplace law is inaccurate when used to calculate the effect of the Dor procedure on regional ventricular stress. The FE method is necessary to determine stress in the left ventricle with postinfarct and surgical ventricular remodeling. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

An investigation on near wall transport characteristics in an adiabatic upward gas-liquid two-phase slug flow

NASA Astrophysics Data System (ADS)

Zheng, Donghong; Che, Defu

2007-08-01

The near-wall transport characteristics, inclusive of mass transfer coefficient and wall shear stress, which have a great effect on gas-liquid two-phase flow induced internal corrosion of low alloy pipelines in vertical upward oil and gas mixing transport, have been both mechanistically and experimentally investigated in this paper. Based on the analyses on the hydrodynamic characteristics of an upward slug unit, the mass transfer in the near wall can be divided into four zones, Taylor bubble nose zone, falling liquid film zone, Taylor bubble wake zone and the remaining liquid slug zone; the wall shear stress can be divided into two zones, the positive wall shear stress zone associated with the falling liquid film and the negative wall shear stress zone associated with the liquid slug. Based on the conventional mass transfer and wall shear stress characteristics formulas of single phase liquid full-pipe turbulent flow, corrected normalized mass transfer coefficient formula and wall shear stress formula are proposed. The calculated results are in good agreement with the experimental data. The shear stress and the mass transfer coefficient in the near wall zone are increased with the increase of superficial gas velocity and decreased with the increase of superficial liquid velocity. The mass transfer coefficients in the falling liquid film zone and the wake zone of leading Taylor bubble are lager than those in the Taylor bubble nose zone and the remaining liquid slug zone, and the wall shear stress associated falling liquid film is larger than that associated the liquid slug. The mass transfer coefficient is within 10-3 m/s, and the wall shear stress below 103 Pa. It can be concluded that the alternate wall shear stress due to upward gas-liquid slug flow is considered to be the major cause of the corrosion production film fatigue cracking.

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yaparpalvi, R; Mynampati, D; Kuo, H

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performedmore » using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose

Comparison of Quantitative Wall Motion Analysis and Strain For Detection Of Coronary Stenosis With Three-Dimensional Dobutamine Stress Echocardiography

PubMed Central

Parker, Katherine M.; Clark, Alexander P.; Goodman, Norman C.; Glover, David K.; Holmes, Jeffrey W.