Sample records for developing mouse axial
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van den Brink, Susanne C.; Baillie-Johnson, Peter; Balayo, Tina; Hadjantonakis, Anna-Katerina; Nowotschin, Sonja; Turner, David A.; Martinez Arias, Alfonso
2014-01-01
Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call ‘gastruloids’. PMID:25371360
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van den Brink, Susanne C; Baillie-Johnson, Peter; Balayo, Tina; Hadjantonakis, Anna-Katerina; Nowotschin, Sonja; Turner, David A; Martinez Arias, Alfonso
2014-11-01
Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call 'gastruloids'. © 2014. Published by The Company of Biologists Ltd.
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Single-shot dimension measurements of the mouse eye using SD-OCT.
Jiang, Minshan; Wu, Pei-Chang; Fini, M Elizabeth; Tsai, Chia-Ling; Itakura, Tatsuo; Zhang, Xiangyang; Jiao, Shuliang
2012-01-01
The authors demonstrate the feasibility and advantage of spectral-domain optical coherence tomography (SD-OCT) for single-shot ocular biometric measurement during the development of the mouse eye. A high-resolution SD-OCT system was built for single-shot imaging of the whole mouse eye in vivo. The axial resolution and imaging depth of the system are 4.5 μm (in tissue) and 5.2 mm, respectively. The system is capable of acquiring a cross-sectional OCT image consisting of 2,048 depth scans in 85 ms. The imaging capability of the SD-OCT system was validated by imaging the normal ocular growth and experimental myopia model using C57BL/6J mice. The biometric dimensions of the mouse eye can be calculated directly from one snapshot of the SD-OCT image. The biometric parameters of the mouse eye including axial length, corneal thickness, anterior chamber depth, lens thickness, vitreous chamber depth, and retinal thickness were successfully measured by the SD-OCT. In the normal ocular growth group, the axial length increased significantly from 28 to 82 days of age (P < .001). The lens thickness increased and the vitreous chamber depth decreased significantly during this period (P < .001 and P = .001, respectively). In the experimental myopia group, there were significant increases in vitreous chamber depth and axial length in comparison to the control eyes (P = .040 and P < .001, respectively). SD-OCT is capable of providing single-shot direct, fast, and high-resolution measurements of the dimensions of young and adult mouse eyes. As a result, SD-OCT is a potentially powerful tool that can be easily applied to research in eye development and myopia using small animal models. Copyright 2012, SLACK Incorporated.
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NASA Astrophysics Data System (ADS)
Yen, WeiWei; Burdsal, Carol; Periasamy, Ammasi; Sutherland, Ann E.
2006-02-01
The cell mechanical and signaling pathways involved in gastrulation have been studied extensively in invertebrates and amphibians, such as Xenopus, and more recently in non-mammalian vertebrates such as zebrafish and chick. However, because culturing mouse embryos extra-utero is very difficult, this fundamental process has been least characterized in the mouse. As the primary mammalian model for genetics, biochemistry, and the study of human disease and birth defects, it is important to investigate how gastrulation proceeds in murine embryos. We have developed a method of using 4D multiphoton excitation microscopy and extra-utero culture to visualize and characterize the morphogenetic movements in mouse embryos dissected at 8.5 days of gestation. Cells are labeled by expression of an X chromosome-linked enhanced green fluorescent protein (EGFP) transgene. This method has provided a unique approach, where, for the first time, patterns of cell behavior in the notochord and surrounding paraxial mesoderm can be visualized and traced quantitatively. Our observations of mouse embryos reveal both distinct differences as well as striking similarities in patterned cell motility relative to other vertebrate models such as Xenopus, where axial extension is driven primarily by mediolateral oriented cell behaviors in the notochord and paraxial somitic mesoderm. Unlike Xenopus, the width of the mouse notochord remains the same between 4-somite stage and 8-somite stage embryos. This implies the mouse notochord plays a lesser role in driving axial extension compared to Xenopus, although intercalation may occur where the anterior region of the node becomes notochordal plate. In contrast, the width of mouse paraxial mesoderm narrows significantly during this period and cells within the paraxial mesoderm are both elongated and aligned perpendicular to the midline. In addition, these cells are observed to intercalate, consistent with a role for paraxial mesoderm in driving convergence and extension. These cell behaviors are similar to those characterized in the axial mesoderm of frog embryos during convergence and extension[1], and suggests that tissues may play different roles in axial elongation between the frog and the mouse.
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Huang, Yi; Guo, Xiaomei; Kassab, Ghassan S
2006-02-01
The hemodynamic conditions of aorta are relatively uniform prenatally and become more heterogeneous postnatally. Our objective was to quantify the heterogeneity of geometry and mechanical properties during growth and development. To accomplish this objective, we obtained a systematic set of data on the geometry and mechanical properties along the length of mouse aorta during postnatal development. C57BL/6 mice of ages 1-33 days were studied. The ascending aorta was cannulated in situ and preconditioned with several cyclic changes in pressure. We investigated the axial variations of geometry (diameter and length) and mechanical properties (stress-stain relation, elastic modulus and compliance) of the mouse aorta from the aortic valve to the common iliac. Our results show that the arterial blood pressure of mice increased from approximately 30 to 80 mmHg during the first 2 wk of life. The stretch ratio, diameter, wall (intima-media) thickness, and total lumen volume of mouse aorta increased with age. The aorta was transformed from a cylindrical tube at birth to a tapered structure during growth. Furthermore, we found the mechanical properties were fairly uniform along the length of the aorta at birth and become more nonuniform with age. We conclude that the rapid change of blood pressure and blood flow after birth alter the geometric and mechanical properties differentially along the length of the aorta. Hence, the axial nonuniformity of the aorta increases as the organ becomes more specialized during growth and development.
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In vivo biometry in the mouse eye with low coherence interferometry.
Schmucker, Christine; Schaeffel, Frank
2004-01-01
A major drawback of the mouse model of myopia is that the ocular dimensions cannot be measured in vivo, and that histological techniques post-mortem suffer from limited resolution. We have tested the potential of a newly developed technique, optical low coherence interferometry (OLCI), adapted for short measurement distances by Meditec, Carl Zeiss, Jena, Germany (the "ACMaster"). Using this technique, ocular biometry was performed in mice with normal vision and after deprivation of form vision. Axial eye length, corneal thickness and anterior chamber depth were measured in 23 mice, aged 25-53 days, and standard deviations from repeated measurements in the same eyes, as well as intra-individual and inter-individual variability were determined in different age groups. The data were compared to those from a preceding study in which biometrical data were obtained from frozen sections [Vision Res. 44 (2004) 1857]. Refractions were measured by automated infrared photorefraction. Mice had either normal visual exposure or were monocularly deprived of form vision for 14 days. Using OLCI, axial length could be determined with an average standard deviation of 8.0 +/- 2.9 microm, corneal thickness with 3.5 +/- 2.1 microm, and anterior chamber depth with 10.6 +/- 12.3 microm. Neither axial length, nor corneal thickness, nor anterior chamber depth were significantly different in left and right eyes of individual mice that had normal visual experience (mean absolute difference between axial lengths: 17 +/- 18 microm, between corneal thickness 5.1 +/- 4.8 microm, and between anterior chamber depths 16.7 +/- 14.8 microm). Compared to the variability that was previously found in frozen sections, the variability of axial length measurements with OLCI was 2.7 times less. After two weeks of form deprivation, OLCI revealed a significant axial elongation in the occluded eyes, compared to the contralateral fellow eyes (+38 +/- 36 microm or 1.16%, p = 0.045, n = 7, paired t-test). In this sample, no accompanying myopic shift was observed in the occluded eyes but this observation is not unexpected given the inherently variable responses of mouse eye growth to visual deprivation. OLCI had sufficient resolution in living mice to detect axial length changes in vivo that were equivalent to a dioptric change of 2 D. Using this technique, it was confirmed that mouse eyes respond to form deprivation by axial elongation, similar to the eyes of other animal models. The lack of a myopic shift in this sample, despite the axial elongation, demonstrates that biometric data are particularly important when the mouse eye is used as a model to study myopia.
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Notchless is required for axial skeleton formation in mice.
Beck-Cormier, Sarah; Escande, Marie; Souilhol, Céline; Vandormael-Pournin, Sandrine; Sourice, Sophie; Pilet, Paul; Babinet, Charles; Cohen-Tannoudji, Michel
2014-01-01
Maintenance of cell survival is essential for proper embryonic development. In the mouse, Notchless homolog 1 (Drosophila) (Nle1) is instrumental for survival of cells of the inner cell mass upon implantation. Here, we analyze the function of Nle1 after implantation using the Meox2(tm1(cre)Sor) mouse that expresses the Cre recombinase specifically in the epiblast at E5.5. First, we find that NLE1 function is required in epiblast cells, as Nle1-deficient cells are rapidly eliminated. In this report, we also show that the Meox2(Cre) transgene is active in specific tissues during organogenesis. In particular, we detect high Cre expression in the vertebral column, ribs, limbs and tailbud. We took advantage of this dynamic expression profile to analyze the effects of inducing mosaic deletion of Nle1 in the embryo. We show that Nle1 deletion in this context, results in severe developmental anomalies leading to lethality at birth. Mutant embryos display multiple developmental defects in particular during axial skeletal formation. We also provide evidence that axial defects are due to an increase in apoptotic cell death in the somite at E9.5. These data demonstrate an essential role for Nle1 during organogenesis and in particular during axial development.
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Notchless Is Required for Axial Skeleton Formation in Mice
Beck-Cormier, Sarah; Escande, Marie; Souilhol, Céline; Vandormael-Pournin, Sandrine; Sourice, Sophie; Pilet, Paul; Cohen-Tannoudji, Michel
2014-01-01
Maintenance of cell survival is essential for proper embryonic development. In the mouse, Notchless homolog 1 (Drosophila) (Nle1) is instrumental for survival of cells of the inner cell mass upon implantation. Here, we analyze the function of Nle1 after implantation using the Meox2tm1(cre)Sor mouse that expresses the Cre recombinase specifically in the epiblast at E5.5. First, we find that NLE1 function is required in epiblast cells, as Nle1-deficient cells are rapidly eliminated. In this report, we also show that the Meox2Cre transgene is active in specific tissues during organogenesis. In particular, we detect high Cre expression in the vertebral column, ribs, limbs and tailbud. We took advantage of this dynamic expression profile to analyze the effects of inducing mosaic deletion of Nle1 in the embryo. We show that Nle1 deletion in this context, results in severe developmental anomalies leading to lethality at birth. Mutant embryos display multiple developmental defects in particular during axial skeletal formation. We also provide evidence that axial defects are due to an increase in apoptotic cell death in the somite at E9.5. These data demonstrate an essential role for Nle1 during organogenesis and in particular during axial development. PMID:24875805
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Development of a small prototype for a proof-of-concept of OpenPET imaging
NASA Astrophysics Data System (ADS)
Yamaya, Taiga; Yoshida, Eiji; Inaniwa, Taku; Sato, Shinji; Nakajima, Yasunori; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Tsuji, Atsushi; Mitsuhashi, Takayuki; Kawai, Hideyuki; Tashima, Hideaki; Nishikido, Fumihiko; Inadama, Naoko; Murayama, Hideo; Haneishi, Hideaki; Suga, Mikio; Kinouchi, Shoko
2011-02-01
The OpenPET geometry is our new idea to visualize a physically opened space between two detector rings. In this paper, we developed the first small prototype to show a proof-of-concept of OpenPET imaging. Two detector rings of 110 mm diameter and 42 mm axial length were placed with a gap of 42 mm. The basic imaging performance was confirmed through phantom studies; the open imaging was realized at the cost of slight loss of axial resolution and 24% loss of sensitivity. For a proof-of-concept of PET image-guided radiation therapy, we carried out the in-beam tests with 11C radioactive beam irradiation in the heavy ion medical accelerator in Chiba to visualize in situ distribution of primary particles stopped in a phantom. We showed that PET images corresponding to dose distribution were obtained. For an initial proof-of-concept of real-time multimodal imaging, we measured a tumor-inoculated mouse with 18F-FDG, and an optical image of the mouse body surface was taken during the PET measurement by inserting a digital camera in the ring gap. We confirmed that the tumor in the gap was clearly visualized. The result also showed the extension effect of an axial field-of-view (FOV); a large axial FOV of 126 mm was obtained with the detectors that originally covered only an 84 mm axial FOV. In conclusion, our initial imaging studies showed promising performance of the OpenPET.
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In Vivo Axial Loading of the Mouse Tibia
Melville, Katherine M.; Robling, Alexander G.
2015-01-01
Summary Non-invasive methods to apply controlled, cyclic loads to the living skeleton are used as an anabolic agent to stimulate new bone formation in adults and enhance bone mass accrual in growing animals. These methods are also invaluable for understanding bone signaling pathways. Our focus here is on a particular loading model: in vivo axial compression of the mouse tibia. An advantage of loading the tibia is that changes are present in both the cancellous envelope of the proximal tibia and the cortical bone of the tibial diaphysis. To load the tibia of the mouse axially in vivo, a cyclic compressive load is applied up to five times a week to a single tibia per mouse for a duration lasting from 1 day to 6 weeks. With the contralateral limb as an internal control, the anabolic response of the skeleton to mechanical stimuli can be studied in a pairwise experimental design. Here, we describe the key parameters that must be considered before beginning an in vivo mouse tibial loading experiment, including methods for in vivo strain gauging of the tibial midshaft, and then we describe general methods for loading the mouse tibia for an experiment lasting multiple days. PMID:25331046
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The mouse bagpipe gene controls development of axial skeleton, skull, and spleen
Lettice, Laura A.; Purdie, Lorna A.; Carlson, Geoffrey J.; Kilanowski, Fiona; Dorin, Julia; Hill, Robert E.
1999-01-01
The mouse Bapx1 gene is homologous to the Drosophila homeobox containing bagpipe (bap) gene. A shared characteristic of the genes in these two organisms is expression in gut mesoderm. In Drosophila, bap functions to specify the formation of the musculature of the midgut. To determine the function of the mammalian cognate, we targeted a mutation into the Bapx1 locus. Bapx1, similar to Drosophila, does have a conspicuous role in gut mesoderm; however, this appears to be restricted to development of the spleen. In addition, Bapx1 has a major role in the development of the axial skeleton. Loss of Bapx1 affects the distribution of sclerotomal cells, markedly reducing the number that appear ventromedially around the notochord. Subsequently, the structures in the midaxial region, the intervertebral discs, and centra of the vertebral bodies, fail to form. Abnormalities are also found in those bones of the basal skull (basioccipital and basisphenoid bones) associated with the notochord. We postulate that Bapx1 confers the capacity of cells to interact with the notochord, effecting inductive interactions essential for development of the vertebral column and chondrocranium. PMID:10449756
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Müller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error.
Paylakhi, Seyyedhassan; Labelle-Dumais, Cassandre; Tolman, Nicholas G; Sellarole, Michael A; Seymens, Yusef; Saunders, Joseph; Lakosha, Hesham; deVries, Wilhelmine N; Orr, Andrew C; Topilko, Piotr; John, Simon Wm; Nair, K Saidas
2018-03-01
A mismatch between optical power and ocular axial length results in refractive errors. Uncorrected refractive errors constitute the most common cause of vision loss and second leading cause of blindness worldwide. Although the retina is known to play a critical role in regulating ocular growth and refractive development, the precise factors and mechanisms involved are poorly defined. We have previously identified a role for the secreted serine protease PRSS56 in ocular size determination and PRSS56 variants have been implicated in the etiology of both hyperopia and myopia, highlighting its importance in refractive development. Here, we use a combination of genetic mouse models to demonstrate that Prss56 mutations leading to reduced ocular size and hyperopia act via a loss of function mechanism. Using a conditional gene targeting strategy, we show that PRSS56 derived from Müller glia contributes to ocular growth, implicating a new retinal cell type in ocular size determination. Importantly, we demonstrate that persistent activity of PRSS56 is required during distinct developmental stages spanning the pre- and post-eye opening periods to ensure optimal ocular growth. Thus, our mouse data provide evidence for the existence of a molecule contributing to both the prenatal and postnatal stages of human ocular growth. Finally, we demonstrate that genetic inactivation of Prss56 rescues axial elongation in a mouse model of myopia caused by a null mutation in Egr1. Overall, our findings identify PRSS56 as a potential therapeutic target for modulating ocular growth aimed at preventing or slowing down myopia, which is reaching epidemic proportions.
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Müller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error
Tolman, Nicholas G; Sellarole, Michael A.; Saunders, Joseph; Lakosha, Hesham; Topilko, Piotr; John, Simon WM.
2018-01-01
A mismatch between optical power and ocular axial length results in refractive errors. Uncorrected refractive errors constitute the most common cause of vision loss and second leading cause of blindness worldwide. Although the retina is known to play a critical role in regulating ocular growth and refractive development, the precise factors and mechanisms involved are poorly defined. We have previously identified a role for the secreted serine protease PRSS56 in ocular size determination and PRSS56 variants have been implicated in the etiology of both hyperopia and myopia, highlighting its importance in refractive development. Here, we use a combination of genetic mouse models to demonstrate that Prss56 mutations leading to reduced ocular size and hyperopia act via a loss of function mechanism. Using a conditional gene targeting strategy, we show that PRSS56 derived from Müller glia contributes to ocular growth, implicating a new retinal cell type in ocular size determination. Importantly, we demonstrate that persistent activity of PRSS56 is required during distinct developmental stages spanning the pre- and post-eye opening periods to ensure optimal ocular growth. Thus, our mouse data provide evidence for the existence of a molecule contributing to both the prenatal and postnatal stages of human ocular growth. Finally, we demonstrate that genetic inactivation of Prss56 rescues axial elongation in a mouse model of myopia caused by a null mutation in Egr1. Overall, our findings identify PRSS56 as a potential therapeutic target for modulating ocular growth aimed at preventing or slowing down myopia, which is reaching epidemic proportions. PMID:29529029
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A paraxial schematic eye model for the growing C57BL/6 mouse.
Schmucker, Christine; Schaeffel, Frank
2004-01-01
The mouse eye has potential to become an important model for studies on the genetic control of eye growth and myopia. However, no data are published on the development of its optical properties. We developed a paraxial schematic model of the growing eye for the most common laboratory mouse strain, the C57BL/6 mouse, for the age range between 22 and 100 days. Refractive development was followed with eccentric infrared photorefraction and corneal curvature with infrared photokeratometry. To measure ocular dimensions, freshly excised eyes were immediately frozen after enucleation to minimize distortions. Eyes were cut with a cryostat down to the bisecting horizontal plane, until the optic nerve head became visible. The standard deviations were +/-10 microm for repeated measurements in highly magnified videographs, taken in several section planes close to the equator in the same eyes. To evaluate inter-eye and inter-individual variability, a total of 20 mice (34 eyes) were studied, with 3-4 eyes for each of the 9 sampling ages. Schematic eye models were developed using paraxial ray tracing software (OSLO, LT Lambda Research Corporation, and a self-written program). The measured refractive errors were initially +4.0+/-0.6 D at approximately 30 days, and levelled off with +7.0+/-2.5 D at about 70 days. Corneal radius of curvature did not change with age (1.414+/-0.019 mm). Both axial lens diameter and axial eye length grew linearly (regression equations: lens, 1619 microm +5.5 microm/day, R=0.916; axial length, 2899 microm +4.4 microm/day, R=0.936). The lens grew so fast that vitreous chamber depth declined with age (regression equation: 896 microm -3.2 microm/day, R=0.685). The radii of curvature of the anterior lens surface increased during development (from 0.982 mm at day 22 to 1.208 mm at day 100), whereas the radii of the posterior lens surface remained constant (-1.081+/-0.054 mm). The calculated homogeneous lens index increased linearly with age (from 1.568 to 1.605). The small eye artifact, calculated from the dioptric difference of the positions of the vitreo-retinal interface and the photoreceptor plane, increased from +35.2 to +39.1 D, which was much higher than the hyperopia measured with photorefraction. Retinal image magnification increased from 31 to 34 microm/deg, and the f/number remained < or =1 at all ages, suggesting a bright retinal image. A calculated axial eye elongation of 5.4-6.5 microm was sufficient to make the schematic eye 1 D more myopic. The most striking features of the mouse eye were that linear growth was slow but extended far beyond sexual maturity, that the corneal curvature did not increase, and that the prominent lens growth caused a developmental decline of the vitreous chamber depth.
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Lam, France; Cladière, Damien; Guillaume, Cyndélia; Wassmann, Katja; Bolte, Susanne
2017-02-15
In the presented work we aimed at improving confocal imaging to obtain highest possible resolution in thick biological samples, such as the mouse oocyte. We therefore developed an image processing workflow that allows improving the lateral and axial resolution of a standard confocal microscope. Our workflow comprises refractive index matching, the optimization of microscope hardware parameters and image restoration by deconvolution. We compare two different deconvolution algorithms, evaluate the necessity of denoising and establish the optimal image restoration procedure. We validate our workflow by imaging sub resolution fluorescent beads and measuring the maximum lateral and axial resolution of the confocal system. Subsequently, we apply the parameters to the imaging and data restoration of fluorescently labelled meiotic spindles of mouse oocytes. We measure a resolution increase of approximately 2-fold in the lateral and 3-fold in the axial direction throughout a depth of 60μm. This demonstrates that with our optimized workflow we reach a resolution that is comparable to 3D-SIM-imaging, but with better depth penetration for confocal images of beads and the biological sample. Copyright © 2016 Elsevier Inc. All rights reserved.
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Ozbay, Baris N.; Losacco, Justin T.; Cormack, Robert; Weir, Richard; Bright, Victor M.; Gopinath, Juliet T.; Restrepo, Diego; Gibson, Emily A.
2015-01-01
We report a miniature, lightweight fiber-coupled confocal fluorescence microscope that incorporates an electrowetting variable focus lens to provide axial scanning for full three-dimensional (3D) imaging. Lateral scanning is accomplished by coupling our device to a laser-scanning confocal microscope through a coherent imaging fiber-bundle. The optical components of the device are combined in a custom 3D-printed adapter with an assembled weight of <2 g that can be mounted onto the head of a mouse. Confocal sectioning provides an axial resolution of ~12 µm and an axial scan range of ~80 µm. The lateral field-of-view is 300 µm, and the lateral resolution is 1.8 µm. We determined these parameters by imaging fixed sections of mouse neuronal tissue labeled with green fluorescent protein (GFP) and fluorescent bead samples in agarose gel. To demonstrate viability for imaging intact tissue, we resolved multiple optical sections of ex vivo mouse olfactory nerve fibers expressing yellow fluorescent protein (YFP). PMID:26030555
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Association of Body Length with Ocular Parameters in Mice
Chakraborty, Ranjay; Park, Han na; Tan, Christopher C.; Weiss, Paul; Prunt, Megan C.; Pardue, Machelle T.
2017-01-01
Purpose To determine the association between changes in body length with ocular refraction, corneal radii, axial length, and lens thickness in two different mouse strains. Methods Body length, ocular refraction, corneal radii, axial length, and lens thickness were measured for two inbred mouse strains: 129S1/SvJ (n=7) and C57BL/6J (n=10) from 4 to 12 weeks of age. Body length, from tip of nose to base of tail was obtained using a digital camera. Biometric parameters, corneal radii and refractions were measured using spectral-domain optical coherence tomography, automated keratometry and infrared photorefraction, respectively. A mixed model ANOVA was performed to examine the changes in ocular parameters as a function of body length and strain in mice controlling for age, gender and weight over time. Results C57BL/6J mice had significantly longer body length (average body length at 10 weeks, 8.60 ± 0.06 cm) compared 129S1/SvJ mice (8.31 ± 0.05 cm) during development (p<0.001). C57BL/6J mice had significantly hyperopic refractions compared to 129S1/SvJ mice across age (mean refraction at 10 weeks, 129S1/SvJ: +0.99 ± 0.44 D versus C57BL/6J: +6.24 ± 0.38 D, p<0.001). Corneal radius of curvature, axial length and lens thickness (except 10 weeks lens thickness) were similar between the two strains throughout the measurement. In the mixed model ANOVA, changes in body length showed an independent and significant association with the changes in refraction (p=0.002) and corneal radii (p=0.016) for each mouse strain. No significant association was found between the changes in axial length (p=0.925) or lens thickness (p=0.973) as a function of body length and strain. Conclusions Changes in body length are significantly associated with the changes in ocular refraction and corneal radii in different mouse strains. Future studies are needed to determine if the association between body length and ocular refraction are related to changes in corneal curvature in mice. PMID:28005683
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Axial level-specific regulation of neuronal development: lessons from PITX2.
Waite, Mindy R; Martin, Donna M
2015-02-01
Transcriptional regulation of gene expression is vital for proper control of proliferation, migration, differentiation, and survival of developing neurons. Pitx2 encodes a homeodomain transcription factor that is highly expressed in the developing and adult mammalian brain. In humans, mutations in PITX2 result in Rieger syndrome, characterized by defects in the development of the eyes, umbilicus, and teeth and variable abnormalities in the brain, including hydrocephalus and cerebellar hypoplasia. Alternative splicing of Pitx2 in the mouse results in three isoforms, Pitx2a, Pitx2b, and Pitx2c, each of which is expressed symmetrically along the left-right axis of the brain throughout development. Here, we review recent evidence for axial and brain region-specific requirements for Pitx2 during neuronal migration and differentiation, highlighting known isoform contributions. © 2014 Wiley Periodicals, Inc.
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Disordered vertebral and rib morphology in pudgy mice. Structural relationships to human scoliosis.
Shapiro, Frederic
2016-01-01
Normal and abnormal vertebral development have been studied over the past 200 years at increasing levels of resolution as techniques for biological investigation have improved. Disordered development of the axial skeleton from the early embryonic period on leads to structurally malformed vertebrae and intervertebral discs and ribs causing the severe deformities of scoliosis, kyphosis, and kyphoscoliosis. Developmental malformation of the axial skeleton therefore has led to considerable biological and clinical interest. This work will detail our studies on the structural deformities of the vertebral column and adjacent ribs in the pudgy mouse [1] caused by mutations in the delta-like 3 (Dll3) gene of the Notch family [2]. While gene abnormalities in the pudgy mouse have been outlined, there has been no in-depth assessment of the histopathology of the pudgy vertebral and rib abnormalities that this study will provide. In addition, although congenital scoliosis has been recognized as a clinical problem since the mid-nineteenth century (1800s) [3] and accurately defined by radiography since the early twentieth century (1900s) [4-6], there have been few detailed histopathologic studies of human cases. We will also relate our histopathologic findings in the pudgy mouse to the histopathology of human vertebral and rib malformations in clinical cases of congenital scoliosis, one of which we defined in detail previously [7].
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Yue, Xin; Zhang, Rui; Kim, Brian; Ma, Aiqun; Philipson, Kenneth D; Goldhaber, Joshua I
2017-07-01
Transverse-axial tubules (TATs) are commonly assumed to be sparse or absent in atrial myocytes from small animals. Atrial myocytes from rats, cats and rabbits lack TATs, which results in a characteristic "V"-shaped Ca release pattern in confocal line-scan recordings due to the delayed rise of Ca in the center of the cell. To examine TAT expression in isolated mouse atrial myocytes, we loaded them with the membrane dye Di-4-ANEPPS to label TATs. We found that >80% of atrial myocytes had identifiable TATs. Atria from male mice had a higher TAT density than female mice, and TAT density correlated with cell width. Using the fluorescent Ca indicator Fluo-4-AM and confocal imaging, we found that wild type (WT) mouse atrial myocytes generate near-synchronous Ca transients, in contrast to the "V"-shaped pattern typically reported in other small animals such as rat. In atrial-specific Na-Ca exchanger (NCX) knockout (KO) mice, which develop sinus node dysfunction and atrial hypertrophy with dilation, we found a substantial loss of atrial TATs in isolated atrial myocytes. There was a greater loss of transverse tubules compared to axial tubules, resulting in a dominance of axial tubules. Consistent with the overall loss of TATs, NCX KO atrial myocytes displayed a "V"-shaped Ca transient with slower and reduced central (CT) Ca release and uptake in comparison to subsarcolemmal (SS) Ca release. We compared chemically detubulated (DT) WT cells to KO, and found similar slowing of CT Ca release and uptake. However, SS Ca transients in the WT DT cells had faster uptake kinetics than KO cells, consistent with the presence of NCX and normal sarcolemmal Ca efflux in the WT DT cells. We conclude that the remodeling of NCX KO atrial myocytes is accompanied by a loss of TATs leading to abnormal Ca release and uptake that could impact atrial contractility and rhythm. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Slit-Slat Collimator Equipped Gamma Camera for Whole-Mouse SPECT-CT Imaging
NASA Astrophysics Data System (ADS)
Cao, Liji; Peter, Jörg
2012-06-01
A slit-slat collimator is developed for a gamma camera intended for small-animal imaging (mice). The tungsten housing of a roof-shaped collimator forms a slit opening, and the slats are made of lead foils separated by sparse polyurethane material. Alignment of the collimator with the camera's pixelated crystal is performed by adjusting a micrometer screw while monitoring a Co-57 point source for maximum signal intensity. For SPECT, the collimator forms a cylindrical field-of-view enabling whole mouse imaging with transaxial magnification and constant on-axis sensitivity over the entire axial direction. As the gamma camera is part of a multimodal imaging system incorporating also x-ray CT, five parameters corresponding to the geometric displacements of the collimator as well as to the mechanical co-alignment between the gamma camera and the CT subsystem are estimated by means of bimodal calibration sources. To illustrate the performance of the slit-slat collimator and to compare its performance to a single pinhole collimator, a Derenzo phantom study is performed. Transaxial resolution along the entire long axis is comparable to a pinhole collimator of same pinhole diameter. Axial resolution of the slit-slat collimator is comparable to that of a parallel beam collimator. Additionally, data from an in-vivo mouse study are presented.
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Baillie-Johnson, Peter; van den Brink, Susanne Carina; Balayo, Tina; Turner, David Andrew; Martinez Arias, Alfonso
2015-11-24
We have developed a protocol improving current Embryoid Body (EB) culture which allows the study of self-organization, symmetry breaking, axial elongation and cell fate specification using aggregates of mouse embryonic stem cells (mESCs) in suspension culture. Small numbers of mESCs are aggregated in basal medium for 48 hr in non-tissue-culture-treated, U-bottomed 96-well plates, after which they are competent to respond to experimental signals. Following treatment, these aggregates begin to show signs of polarized gene expression and gradually alter their morphology from a spherical mass of cells to an elongated, well organized structure in the absence of external asymmetry cues. These structures are not only able to display markers of the three germ layers, but actively display gastrulation-like movements, evidenced by a directional dislodgement of individual cells from the aggregate, which crucially occurs at one region of the elongated structure. This protocol provides a detailed method for the reproducible formation of these aggregates, their stimulation with signals such as Wnt/β-Catenin activation and BMP inhibition and their analysis by single time-point or time-lapse fluorescent microscopy. In addition, we describe modifications to current whole-mount mouse embryo staining procedures for immunocytochemical analysis of specific markers within fixed aggregates. The changes in morphology, gene expression and length of the aggregates can be quantitatively measured, providing information on how signals can alter axial fates. It is envisaged that this system can be applied both to the study of early developmental events such as axial development and organization, and more broadly, the processes of self-organization and cellular decision-making. It may also provide a suitable niche for the generation of cell types present in the embryo that are unobtainable from conventional adherent culture such as spinal cord and motor neurones.
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Rotatin is a novel gene required for axial rotation and left-right specification in mouse embryos.
Faisst, Anja M; Alvarez-Bolado, Gonzalo; Treichel, Dieter; Gruss, Peter
2002-04-01
The genetic cascade that governs left-right (L-R) specification is starting to be elucidated. In the mouse, the lateral asymmetry of the body axis is revealed first by the asymmetric expression of nodal, lefty2 and pitx2 in the left lateral plate mesoderm of the neurulating embryo. Here we describe a novel gene, rotatin, essential for the correct expression of the key L-R specification genes nodal, lefty and Pitx2. Embryos deficient in rotatin show also randomized heart looping and delayed neural tube closure, and fail to undergo the critical morphogenetic step of axial rotation. The amino acid sequence deduced from the cDNA is predicted to contain at least three transmembrane domains. Our results show a novel key player in the genetic cascade that determines L-R specification, and suggest a causal link between this process and axial rotation.
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Optical coherence elastography for cellular-scale stiffness imaging of mouse aorta
NASA Astrophysics Data System (ADS)
Wijesinghe, Philip; Johansen, Niloufer J.; Curatolo, Andrea; Sampson, David D.; Ganss, Ruth; Kennedy, Brendan F.
2017-04-01
We have developed a high-resolution optical coherence elastography system capable of estimating Young's modulus in tissue volumes with an isotropic resolution of 15 μm over a 1 mm lateral field of view and a 100 μm axial depth of field. We demonstrate our technique on healthy and hypertensive, freshly excised and intact mouse aortas. Our technique has the capacity to delineate the individual mechanics of elastic lamellae and vascular smooth muscle. Further, we observe global and regional vascular stiffening in hypertensive aortas, and note the presence of local micro-mechanical signatures, characteristic of fibrous and lipid-rich regions.
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Video-rate functional photoacoustic microscopy at depths
NASA Astrophysics Data System (ADS)
Wang, Lidai; Maslov, Konstantin; Xing, Wenxin; Garcia-Uribe, Alejandro; Wang, Lihong V.
2012-10-01
We report the development of functional photoacoustic microscopy capable of video-rate high-resolution in vivo imaging in deep tissue. A lightweight photoacoustic probe is made of a single-element broadband ultrasound transducer, a compact photoacoustic beam combiner, and a bright-field light delivery system. Focused broadband ultrasound detection provides a 44-μm lateral resolution and a 28-μm axial resolution based on the envelope (a 15-μm axial resolution based on the raw RF signal). Due to the efficient bright-field light delivery, the system can image as deep as 4.8 mm in vivo using low excitation pulse energy (28 μJ per pulse, 0.35 mJ/cm2 on the skin surface). The photoacoustic probe is mounted on a fast-scanning voice-coil scanner to acquire 40 two-dimensional (2-D) B-scan images per second over a 9-mm range. High-resolution anatomical imaging is demonstrated in the mouse ear and brain. Via fast dual-wavelength switching, oxygen dynamics of mouse cardio-vasculature is imaged in realtime as well.
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NASA Astrophysics Data System (ADS)
Huang, Yongyang; Degenhardt, Karl R.; Astrof, Sophie; Zhou, Chao
2016-03-01
We have demonstrated the capability of spectral domain optical coherence tomography (SDOCT) system to image full development of mouse embryonic cardiovascular system. Monitoring morphological changes of mouse embryonic heart occurred in different embryonic stages helps identify structural or functional cardiac anomalies and understand how these anomalies lead to congenital heart diseases (CHD) present at birth. In this study, mouse embryo hearts ranging from E9.5 to E15.5 were prepared and imaged in vitro. A customized spectral domain OCT system was used for imaging, with a central wavelength of 1310nm, spectral bandwidth of ~100nm and imaging speed of 47kHz A-scans/s. Axial resolution of this system was 8.3µm in air, and transverse resolution was 6.2 µm with 5X objective. Key features of mouse embryonic cardiovascular development such as vasculature remodeling into circulatory system, separation of atria and ventricles and emergence of valves could be clearly seen in three-dimensional OCT images. Optical clearing was applied to overcome the penetration limit of OCT system. With high resolution, fast imaging speed, 3D imaging capability, OCT proves to be a promising biomedical imaging modality for developmental biology studies, rivaling histology and micro-CT.
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Cross-correlation photothermal optical coherence tomography with high effective resolution.
Tang, Peijun; Liu, Shaojie; Chen, Junbo; Yuan, Zhiling; Xie, Bingkai; Zhou, Jianhua; Tang, Zhilie
2017-12-01
We developed a cross-correlation photothermal optical coherence tomography (CC-PTOCT) system for photothermal imaging with high lateral and axial resolution. The CC-PTOCT system consists of a phase-sensitive OCT system, a modulated pumping laser, and a digital cross-correlator. The pumping laser was used to induce the photothermal effect in the sample, causing a slight phase modulation of the OCT signals. A spatial phase differentiation method was employed to reduce phase accumulation. The noise brought by the phase differentiation method and the strong background noise were suppressed efficiently by the cross-correlator, which was utilized to extract the photothermal signals from the modulated signals. Combining the cross-correlation technique with spatial phase differentiation can improve both lateral and axial resolution of the PTOCT imaging system. Clear photothermal images of blood capillaries of a mouse ear in vivo were successfully obtained with high lateral and axial resolution. The experimental results demonstrated that this system can enhance the effective transverse resolution, effective depth resolution, and contrast of the PTOCT image effectively, aiding the ongoing development of the accurate 3D functional imaging.
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A Prototype High-Resolution Small-Animal PET Scanner Dedicated to Mouse Brain Imaging.
Yang, Yongfeng; Bec, Julien; Zhou, Jian; Zhang, Mengxi; Judenhofer, Martin S; Bai, Xiaowei; Di, Kun; Wu, Yibao; Rodriguez, Mercedes; Dokhale, Purushottam; Shah, Kanai S; Farrell, Richard; Qi, Jinyi; Cherry, Simon R
2016-07-01
We developed a prototype small-animal PET scanner based on depth-encoding detectors using dual-ended readout of small scintillator elements to produce high and uniform spatial resolution suitable for imaging the mouse brain. The scanner consists of 16 tapered dual-ended-readout detectors arranged in a 61-mm-diameter ring. The axial field of view (FOV) is 7 mm, and the transaxial FOV is 30 mm. The scintillator arrays consist of 14 × 14 lutetium oxyorthosilicate elements, with a crystal size of 0.43 × 0.43 mm at the front end and 0.80 × 0.43 mm at the back end, and the crystal elements are 13 mm long. The arrays are read out by 8 × 8 mm and 13 × 8 mm position-sensitive avalanche photodiodes (PSAPDs) placed at opposite ends of the array. Standard nuclear-instrumentation-module electronics and a custom-designed multiplexer are used for signal processing. The detector performance was measured, and all but the crystals at the very edge could be clearly resolved. The average intrinsic spatial resolution in the axial direction was 0.61 mm. A depth-of-interaction resolution of 1.7 mm was achieved. The sensitivity of the scanner at the center of the FOV was 1.02% for a lower energy threshold of 150 keV and 0.68% for a lower energy threshold of 250 keV. The spatial resolution within a FOV that can accommodate the entire mouse brain was approximately 0.6 mm using a 3-dimensional maximum-likelihood expectation maximization reconstruction. Images of a hot-rod microphantom showed that rods with a diameter of as low as 0.5 mm could be resolved. The first in vivo studies were performed using (18)F-fluoride and confirmed that a 0.6-mm resolution can be achieved in the mouse head in vivo. Brain imaging studies with (18)F-FDG were also performed. We developed a prototype PET scanner that can achieve a spatial resolution approaching the physical limits of a small-bore PET scanner set by positron range and detector interaction. We plan to add more detector rings to extend the axial FOV of the scanner and increase sensitivity. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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A high resolution prototype small-animal PET scanner dedicated to mouse brain imaging
Yang, Yongfeng; Bec, Julien; Zhou, Jian; Zhang, Mengxi; Judenhofer, Martin S; Bai, Xiaowei; Di, Kun; Wu, Yibao; Rodriguez, Mercedes; Dokhale, Purushottam; Shah, Kanai S.; Farrell, Richard; Qi, Jinyi; Cherry, Simon R.
2017-01-01
A prototype small-animal PET scanner was developed based on depth-encoding detectors using dual-ended readout of very small scintillator elements to produce high and uniform spatial resolution suitable for imaging the mouse brain. Methods The scanner consists of 16 tapered dual-ended readout detectors arranged in a ring of diameter 61 mm. The axial field of view is 7 mm and the transaxial field of view is 30 mm. The scintillator arrays consist of 14×14 lutetium oxyorthosilicate (LSO) elements, with a crystal size of 0.43×0.43 mm2 at the front end and 0.80×0.43 mm2 at the back end, and the crystal elements are 13 mm long. The arrays are read out by 8×8 mm2 and a 13×8 mm2 position-sensitive avalanche photodiodes (PSAPDs) placed at opposite ends of the array. Standard nuclear instrumentation module (NIM) electronics and a custom designed multiplexer are used for signal processing. Results The detector performance was measured and all except the very edge crystals could be clearly resolved. The average detector intrinsic spatial resolution in the axial direction was 0.61 mm. A depth of interaction resolution of 1.7 mm was achieved. The sensitivity of the scanner at center of the field of view was 1.02% for a lower energy threshold of 150 keV and 0.68% for a lower energy threshold of 250 keV. The spatial resolution within a field of view that can accommodate the entire mouse brain was ~0.6 mm using a 3D Maximum Likelihood-Expectation Maximization (ML-EM) reconstruction algorithm. Images of a micro hot-rod phantom showed that rods with diameter down to 0.5 mm could be resolved. First in vivo studies were obtained using 18F-fluoride and confirmed that 0.6 mm resolution can be achieved in the mouse head in vivo. Brain imaging studies with 18F-fluorodeoxyglucose were also acquired. Conclusion A prototype PET scanner achieving a spatial resolution approaching the physical limits for a small-bore PET scanner set by positron range and acolinearity was developed. Future plans are to add more detector rings to extend the axial field of view of the scanner and increase sensitivity. PMID:27013696
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Jean-Xavier, Céline; Perreault, Marie-Claude
2018-01-01
The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.
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Jean-Xavier, Céline; Perreault, Marie-Claude
2018-01-01
The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor. PMID:29479302
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Critical Buckling Pressure in Mouse Carotid Arteries with Altered Elastic Fibers
Luetkemeyer, Callan M.; James, Rhys H.; Devarakonda, Siva Teja; Le, Victoria P.; Liu, Qin; Han, Hai-Chao; Wagenseil, Jessica E.
2015-01-01
Arteries can buckle axially under applied critical buckling pressure due to a mechanical instability. Buckling can cause arterial tortuosity leading to flow irregularities and stroke. Genetic mutations in elastic fiber proteins are associated with arterial tortuosity in humans and mice, and may be the result of alterations in critical buckling pressure. Hence, the objective of this study is to investigate how genetic defects in elastic fibers affect buckling pressure. We use mouse models of human disease with reduced amounts of elastin (Eln+/−) and with defects in elastic fiber assembly due to the absence of fibulin-5 (Fbln5−/−). We find that Eln+/− arteries have reduced buckling pressure compared to their wild-type controls. Fbln5−/− arteries have similar buckling pressure to wild-type at low axial stretch, but increased buckling pressure at high stretch. We fit material parameters to mechanical test data for Eln+/−, Fbln5−/− and wild-type arteries using Fung and four-fiber strain energy functions. Fitted parameters are used to predict theoretical buckling pressure based on equilibrium of an inflated, buckled, thick-walled cylinder. In general, the theoretical predictions underestimate the buckling pressure at low axial stretch and overestimate the buckling pressure at high stretch. The theoretical predictions with both models replicate the increased buckling pressure at high stretch for Fbln5−/− arteries, but the four-fiber model predictions best match the experimental trends in buckling pressure changes with axial stretch. This study provides experimental and theoretical methods for further investigating the influence of genetic mutations in elastic fibers on buckling behavior and the development of arterial tortuosity. PMID:25771258
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Relative axial myopia in Egr-1 (ZENK) knockout mice.
Schippert, Ruth; Burkhardt, Eva; Feldkaemper, Marita; Schaeffel, Frank
2007-01-01
Experiments in chickens have implicated the transcription factor ZENK (also known as Egr-1, NGFI-A, zif268, tis8, cef5, and Krox24) in the feedback mechanisms for visual control of axial eye growth and myopia development. ZENK is upregulated in retinal glucagon amacrine cells when axial eye growth is inhibited by positive spectacle lens wear and is downregulated when it is enhanced by negative spectacle lens wear, suggesting that ZENK may be linked to an inhibitory signal for axial eye growth. This study was undertaken to determine whether a Egr-1(-/-) knockout mouse mutant, lacking ZENK completely, has longer eyes and more myopic refraction, than do Egr-1(+/)(-) heterozygous and Egr-1(+/+) wild-type mice with near-identical genetic backgrounds. Eye growth and refractive development were tracked from day P28 to P98. Corneal radius of curvature was measured with infrared photokeratometry, refractive state with infrared photoretinoscopy, and ocular dimensions with low-coherence interferometry. As a functional vision test, grating acuity was determined in an automated optomotor task. The abundance of ZENK protein in the retina was quantified by immunohistochemistry. Egr-1 knockout mice had longer eyes and a relative myopic shift in refraction, with additional minor effects on anterior chamber depth and corneal radius of curvature. Paraxial schematic eye modeling suggested changes in the optics of the crystalline lens as well. With increasing age, the differences between mutant and wild-type mice declined, although the differences in refraction persisted over the observation period. Grating acuity was not affected by the lack of the Egr-1 protein during development. Although it has been shown that different mouse strains may have differently large eyes, the present study shows that a specific gene knockout can produce relative myopia, compared with the wild-type with near-identical genetic background. Further experiments are needed to determine whether the observed effects of Egr-1 deletion are due to changes in function within the retina or other ocular tissues or to changes of function in other systems that may affect ocular growth from outside the eye.
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A Flexure-Guided Piezo Drill for Penetrating the Zona Pellucida of Mammalian Oocytes.
Johnson, Wesley; Dai, Changsheng; Liu, Jun; Wang, Xian; Luu, Devin K; Zhang, Zhuoran; Ru, Changhai; Zhou, Chao; Tan, Min; Pu, Huayan; Xie, Shaorong; Peng, Yan; Luo, Jun; Sun, Yu
2018-03-01
Mammalian oocytes such as mouse oocytes have a highly elastic outer membrane, zona pellucida (ZP) that cannot be penetrated without significantly deforming the oocyte, even with a sharp micropipette. Piezo drill devices leverage lateral and axial vibration of the micropipette to accomplish ZP penetration with greatly reduced oocyte deformation. However, existing piezo drills all rely on a large lateral micropipette vibration amplitude ( 20 ) and a small axial vibration amplitude (0.1 ). The very large lateral vibration amplitude has been deemed to be necessary for ZP penetration although it also induces larger oocyte deformation and more oocyte damage. This paper reports on a new piezo drill device that uses a flexure guidance mechanism and a systematically designed pulse train with an appropriate base frequency. Both simulation and experimental results demonstrate that a small lateral vibration amplitude (e.g., 2 ) and an axial vibration amplitude as large as 1.2 were achieved. Besides achieving 100% effectiveness in the penetration of mouse oocytes (n = 45), the new piezo device during ZP penetration induced a small oocyte deformation of 3.4 versus larger than 10 using existing piezo drill devices.
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Turner, David A.; Hayward, Penelope C.; Baillie-Johnson, Peter; Rué, Pau; Broome, Rebecca; Faunes, Fernando; Martinez Arias, Alfonso
2014-01-01
The development of the central nervous system is known to result from two sequential events. First, an inductive event of the mesoderm on the overlying ectoderm that generates a neural plate that, after rolling into a neural tube, acts as the main source of neural progenitors. Second, the axial regionalization of the neural plate that will result in the specification of neurons with different anteroposterior identities. Although this description of the process applies with ease to amphibians and fish, it is more difficult to confirm in amniote embryos. Here, a specialized population of cells emerges at the end of gastrulation that, under the influence of Wnt and FGF signalling, expands and generates the spinal cord and the paraxial mesoderm. This population is known as the long-term neuromesodermal precursor (NMp). Here, we show that controlled increases of Wnt/β-catenin and FGF signalling during adherent culture differentiation of mouse embryonic stem cells (mESCs) generates a population with many of the properties of the NMp. A single-cell analysis of gene expression within this population reveals signatures that are characteristic of stem cell populations. Furthermore, when this activation is triggered in three-dimensional aggregates of mESCs, the population self-organizes macroscopically and undergoes growth and axial elongation that mimics some of the features of the embryonic spinal cord and paraxial mesoderm. We use both adherent and three-dimensional cultures of mESCs to probe the establishment and maintenance of NMps and their differentiation. PMID:25371361
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High-throughput multiple-mouse imaging with micro-PET/CT for whole-skeleton assessment.
Yagi, Masashi; Arentsen, Luke; Shanley, Ryan M; Hui, Susanta K
2014-11-01
Recent studies have proven that skeleton-wide functional assessment is essential to comprehensively understand physiological aspects of the skeletal system. Therefore, in contrast to regional imaging studies utilizing a multiple-animal holder (mouse hotel), we attempted to develop and characterize a multiple-mouse imaging system with micro-PET/CT for high-throughput whole-skeleton assessment. Using items found in a laboratory, a simple mouse hotel that houses four mice linked with gas anesthesia was constructed. A mouse-simulating phantom was used to measure uniformity in a cross sectional area and flatness (Amax/Amin*100) along the axial, radial and tangential directions, where Amax and Amin are maximum and minimum activity concentration in the profile, respectively. Fourteen mice were used for single- or multiple-micro-PET/CT scans. NaF uptake was measured at eight skeletal sites (skull to tibia). Skeletal (18)F activities measured with mice in the mouse hotel were within 1.6 ± 4% (mean ± standard deviation) of those measured with mice in the single-mouse holder. Single-holder scanning yields slightly better uniformity and flatness over the hotel. Compared to use of the single-mouse holder, scanning with the mouse hotel reduced study time (by 65%), decreased the number of scans (four-fold), reduced cost, required less computer storage space (40%), and maximized (18)F usage. The mouse hotel allows high-throughput, quantitatively equivalent scanning compared to the single-mouse holder for micro-PET/CT imaging for whole-skeleton assessment of mice. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
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Park, Jong Kang; Rowlands, Christopher J; So, Peter T C
2017-01-01
Temporal focusing multiphoton microscopy is a technique for performing highly parallelized multiphoton microscopy while still maintaining depth discrimination. While the conventional wide-field configuration for temporal focusing suffers from sub-optimal axial resolution, line scanning temporal focusing, implemented here using a digital micromirror device (DMD), can provide substantial improvement. The DMD-based line scanning temporal focusing technique dynamically trades off the degree of parallelization, and hence imaging speed, for axial resolution, allowing performance parameters to be adapted to the experimental requirements. We demonstrate this new instrument in calibration specimens and in biological specimens, including a mouse kidney slice.
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Park, Jong Kang; Rowlands, Christopher J.; So, Peter T. C.
2017-01-01
Temporal focusing multiphoton microscopy is a technique for performing highly parallelized multiphoton microscopy while still maintaining depth discrimination. While the conventional wide-field configuration for temporal focusing suffers from sub-optimal axial resolution, line scanning temporal focusing, implemented here using a digital micromirror device (DMD), can provide substantial improvement. The DMD-based line scanning temporal focusing technique dynamically trades off the degree of parallelization, and hence imaging speed, for axial resolution, allowing performance parameters to be adapted to the experimental requirements. We demonstrate this new instrument in calibration specimens and in biological specimens, including a mouse kidney slice. PMID:29387484
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Shazeeb, Mohammed Salman; Cox, Megan K; Gupta, Anurag; Tang, Wen; Singh, Kuldeep; Pryce, Cynthia T; Fogle, Robert; Mu, Ying; Weber, William D; Bangari, Dinesh S; Ying, Xiaoyou; Sabbagh, Yves
2018-01-11
Achondroplasia, the most common form of dwarfism, affects more than a quarter million people worldwide and remains an unmet medical need. Achondroplasia is caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene which results in over-activation of the receptor, interfering with normal skeletal development leading to disproportional short stature. Multiple mouse models have been generated to study achondroplasia. The characterization of these preclinical models has been primarily done with 2D measurements. In this study, we explored the transgenic model expressing mouse Fgfr3 containing the achondroplasia mutation G380R under the Col2 promoter (Ach). Survival and growth rate of the Ach mice were reduced compared to wild-type (WT) littermates. Axial skeletal defects and abnormalities of the sternebrae and vertebrae were observed in the Ach mice. Further evaluation of the Ach mouse model was performed by developing 3D parameters from micro-computed tomography (micro-CT) and magnetic resonance imaging (MRI). The 3-week-old mice showed greater differences between the Ach and WT groups compared to the 6-week-old mice for all parameters. Deeper understanding of skeletal abnormalities of this model will help guide future studies for evaluating novel and effective therapeutic approaches for the treatment of achondroplasia.
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Sonic hedgehog: restricted expression and limb dysmorphologies
Hill, Robert E; Heaney, Simon JH; Lettice, Laura A
2003-01-01
Sonic hedgehog, SHH, is required for patterning the limb. The array of skeletal elements that compose the hands and feet, and the ordered arrangement of these bones to form the pattern of fingers and toes are dependent on SHH. The mechanism of action of SHH in the limb is not fully understood; however, an aspect that appears to be important is the localized, asymmetric expression of Shh. Shh is expressed in the posterior margin of the limb bud in a region defined as the zone of polarizing activity (ZPA). Analysis of mouse mutants which have polydactyly (extra toes) shows that asymmetric expression of Shh is lost due to the appearance of an ectopic domain of expression in the anterior limb margin. One such polydactylous mouse mutant, sasquatch (Ssq), maps to the corresponding chromosomal region of the human condition pre-axial polydactyly (PPD) and thus represents a model for this condition. The mutation responsible for Ssq is located 1 Mb away from the Shh gene; however, the mutation disrupts a long-range cis-acting regulator of Shh expression. By inference, human pre-axial polydactyly results from a similar disruption of Shh expression. Other human congenital abnormalities also map near the pre-axial polydactyly locus, suggesting a major chromosomal region for limb dysmorphologies. The distinct phenotypes range from loss of all bones of the hands and feet to syndactyly of the soft tissue and fusion of the digits. We discuss the role played by Shh expression in mouse mutant phenotypes and the human limb dysmorphologies. PMID:12587915
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NEMA NU 2-2007 performance measurements of the Siemens Inveon™ preclinical small animal PET system
Kemp, Brad J; Hruska, Carrie B; McFarland, Aaron R; Lenox, Mark W; Lowe, Val J
2010-01-01
National Electrical Manufacturers Association (NEMA) NU 2-2007 performance measurements were conducted on the Inveon™ preclinical small animal PET system developed by Siemens Medical Solutions. The scanner uses 1.51 × 1.51 × 10 mm LSO crystals grouped in 20 × 20 blocks; a tapered light guide couples the LSO crystals of a block to a position-sensitive photomultiplier tube. There are 80 rings with 320 crystals per ring and the ring diameter is 161 mm. The transaxial and axial fields of view (FOVs) are 100 and 127 mm, respectively. The scanner can be docked to a CT scanner; the performance characteristics of the CT component are not included herein. Performance measurements of spatial resolution, sensitivity, scatter fraction and count rate performance were obtained for different energy windows and coincidence timing window widths. For brevity, the results described here are for an energy window of 350–650 keV and a coincidence timing window of 3.43 ns. The spatial resolution at the center of the transaxial and axial FOVs was 1.56, 1.62 and 2.12 mm in the tangential, radial and axial directions, respectively, and the system sensitivity was 36.2 cps kBq−1 for a line source (7.2% for a point source). For mouse- and rat-sized phantoms, the scatter fraction was 5.7% and 14.6%, respectively. The peak noise equivalent count rate with a noisy randoms estimate was 1475 kcps at 130 MBq for the mouse-sized phantom and 583 kcps at 74 MBq for the rat-sized phantom. The performance measurements indicate that the Inveon™ PET scanner is a high-resolution tomograph with excellent sensitivity that is capable of imaging at a high count rate. PMID:19321924
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NEMA NU 2-2007 performance measurements of the Siemens Inveon™ preclinical small animal PET system
NASA Astrophysics Data System (ADS)
Kemp, Brad J.; Hruska, Carrie B.; McFarland, Aaron R.; Lenox, Mark W.; Lowe, Val J.
2009-04-01
National Electrical Manufacturers Association (NEMA) NU 2-2007 performance measurements were conducted on the Inveon™ preclinical small animal PET system developed by Siemens Medical Solutions. The scanner uses 1.51 × 1.51 × 10 mm LSO crystals grouped in 20 × 20 blocks; a tapered light guide couples the LSO crystals of a block to a position-sensitive photomultiplier tube. There are 80 rings with 320 crystals per ring and the ring diameter is 161 mm. The transaxial and axial fields of view (FOVs) are 100 and 127 mm, respectively. The scanner can be docked to a CT scanner; the performance characteristics of the CT component are not included herein. Performance measurements of spatial resolution, sensitivity, scatter fraction and count rate performance were obtained for different energy windows and coincidence timing window widths. For brevity, the results described here are for an energy window of 350-650 keV and a coincidence timing window of 3.43 ns. The spatial resolution at the center of the transaxial and axial FOVs was 1.56, 1.62 and 2.12 mm in the tangential, radial and axial directions, respectively, and the system sensitivity was 36.2 cps kBq-1 for a line source (7.2% for a point source). For mouse- and rat-sized phantoms, the scatter fraction was 5.7% and 14.6%, respectively. The peak noise equivalent count rate with a noisy randoms estimate was 1475 kcps at 130 MBq for the mouse-sized phantom and 583 kcps at 74 MBq for the rat-sized phantom. The performance measurements indicate that the Inveon™ PET scanner is a high-resolution tomograph with excellent sensitivity that is capable of imaging at a high count rate.
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NASA Astrophysics Data System (ADS)
Zhi, Zhongwei; Yin, Xin; Dziennis, Suzan; Alpers, Charles E.; Wang, Ruikang K.
2013-03-01
Visualization and measurement of retinal blood flow (RBF) is important to the diagnosis and management of different eye diseases, including diabetic retinopathy. Optical microangiography (OMAG) is developed for generating 3D dynamic microcirculation image and later refined into ultra-high sensitive OMAG (UHS-OMAG) for true capillary vessels imaging. Here, we present the application of OMAG imaging technique for visualization of depth-resolved vascular network within retina and choroid as well as measurement of total retinal blood flow in mice. A fast speed spectral domain OCT imaging system at 820nm with a line scan rate of 140 kHz was developed to image mouse posterior eye. By applying UHS-OMAG scanning protocol and processing algorithm, we achieved true capillary level imaging of retina and choroid vasculature in mouse eye. The vascular pattern within different retinal layers and choroid was presented. An en face Doppler OCT approach [1] without knowing Doppler angle was adopted for the measurement of total retinal blood flow. The axial blood flow velocity is measured in an en face plane by raster scanning and the flow is calculated by integrating over the vessel area of the central retinal artery.
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Quantitative PET and SPECT performance characteristics of the Albira Trimodal pre-clinical tomograph
NASA Astrophysics Data System (ADS)
Spinks, T. J.; Karia, D.; Leach, M. O.; Flux, G.
2014-02-01
The Albira Trimodal pre-clinical scanner comprises PET, SPECT and CT sub-systems and thus provides a range of pre-clinical imaging options. The PET component consists of three rings of single-crystal LYSO detectors with axial/transverse fields-of-view (FOVs) of 148/80 mm. The SPECT component has two opposing CsI detectors (100 × 100 mm2) with single-pinhole (SPH) or multi(9)-pinhole (MPH) collimators; the detectors rotate in 6° increments and their spacing can be adjusted to provide different FOVs (25 to 120 mm). The CT sub-system provides ‘low’ (200 µA, 35 kVp) or ‘high’ (400 µA, 45 kVp) power x-rays onto a flat-panel CsI detector. This study examines the performance characteristics and quantitative accuracy of the PET and SPECT components. Using the NEMA NU 4-2008 specifications (22Na point source), the PET spatial resolution is 1.5 + 0.1 mm on axis and sensitivity 6.3% (axial centre) and 4.6% (central 70 mm). The usable activity range is ≤ 10 MBq (18F) over which good linearity (within 5%) is obtained for a uniform cylinder spanning the axial FOV; increasing deviation from linearity with activity is, however, observed for the NEMA (mouse) line source phantom. Image uniformity axially is within 5%. Spatial resolution (SPH/MPH) for the minimum SPECT FOV used for mouse imaging (50 mm) is 1.5/1.7 mm and point source sensitivity 69/750 cps MBq-1. Axial uniformity of SPECT images (%CV of regions-of-interest counts along the axis) is mostly within 8% although there is a range of 30-40% for the largest FOV. The variation is significantly smaller within the central 40 mm. Instances of count rate nonlinearity (PET) and axial non-uniformity (SPECT) were found to be reproducible and thus amenable to empirical correction.
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Ramcharan, M A; Faillace, M E; Guengerich, Z; Williams, V A; Jepsen, K J
2017-03-01
How cortical and trabecular bone co-develop to establish a mechanically functional structure is not well understood. Comparing early postnatal differences in morphology of lumbar vertebral bodies for three inbred mouse strains identified coordinated changes within and between cortical and trabecular traits. These early coordinate changes defined the phenotypic differences among the inbred mouse strains. Age-related changes in cortical and trabecular traits have been well studied; however, very little is known about how these bone tissues co-develop from day 1 of postnatal growth to establish functional structures by adulthood. In this study, we aimed to establish how cortical and trabecular tissues within the lumbar vertebral body change during growth for three inbred mouse strains that express wide variation in adult bone structure and function. Bone traits were quantified for lumbar vertebral bodies of female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse strains from 1 to 105 days of age (n = 6-10 mice/age/strain). Inter-strain differences in external bone size were observed as early as 1 day of age. Reciprocal and rapid changes in the trabecular bone volume fraction and alignment in the direction of axial compression were observed by 7 days of age. Importantly, the inter-strain difference in adult trabecular bone volume fraction was established by 7 days of age. Early variation in external bone size and trabecular architecture was followed by progressive increases in cortical area between 28 and 105 days of age, with the greatest increases in cortical area seen in the mouse strain with the lowest trabecular mass. Establishing the temporal changes in bone morphology for three inbred mouse strains revealed that genetic variation in adult trabecular traits were established early in postnatal development. Early variation in trabecular architecture preceded strain-specific increases in cortical area and changes in cortical thickness. This study established the sequence of how cortical and trabecular traits co-develop during growth, which is important for identifying critical early ages to further focus on intervention studies that optimize adult bone strength.
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Comparison of three methods of calculating strain in the mouse ulna in exogenous loading studies.
Norman, Stephanie C; Wagner, David W; Beaupre, Gary S; Castillo, Alesha B
2015-01-02
Axial compression of mouse limbs is commonly used to induce bone formation in a controlled, non-invasive manner. Determination of peak strains caused by loading is central to interpreting results. Load-strain calibration is typically performed using uniaxial strain gauges attached to the diaphyseal, periosteal surface of a small number of sacrificed animals. Strain is measured as the limb is loaded to a range of physiological loads known to be anabolic to bone. The load-strain relationship determined by this subgroup is then extrapolated to a larger group of experimental mice. This method of strain calculation requires the challenging process of strain gauging very small bones which is subject to variability in placement of the strain gauge. We previously developed a method to estimate animal-specific periosteal strain during axial ulnar loading using an image-based computational approach that does not require strain gauges. The purpose of this study was to compare the relationship between load-induced bone formation rates and periosteal strain at ulnar midshaft using three different methods to estimate strain: (A) Nominal strain values based solely on load-strain calibration; (B) Strains calculated from load-strain calibration, but scaled for differences in mid-shaft cross-sectional geometry among animals; and (C) An alternative image-based computational method for calculating strains based on beam theory and animal-specific bone geometry. Our results show that the alternative method (C) provides comparable correlation between strain and bone formation rates in the mouse ulna relative to the strain gauge-dependent methods (A and B), while avoiding the need to use strain gauges. Published by Elsevier Ltd.
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Straub, Adam; Durst, Michael E.; Xu, Chris
2011-01-01
Simultaneous spatial and temporal focusing is used to acquire high speed (200Hz), chemically specific axial scans of mouse skin through a single-mode fiber. The temporal focus is remotely scanned by modulating the group delay dispersion (GDD) at the proximal end of the fiber. No moving parts or electronics are required at the distal end. A novel GDD modulation technique is implemented using a piezo bimorph mirror in a folded grating pair to achieve a large GDD tuning range at high speed. PMID:21326638
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Wnt5a and Wnt11 regulate mammalian anterior-posterior axis elongation
Andre, Philipp; Song, Hai; Kim, Wantae; Kispert, Andreas; Yang, Yingzi
2015-01-01
Mesoderm formation and subsequent anterior-posterior (A-P) axis elongation are fundamental aspects of gastrulation, which is initiated by formation of the primitive streak (PS). Convergent extension (CE) movements and epithelial-mesenchymal transition (EMT) are important for A-P axis elongation in vertebrate embryos. The evolutionarily conserved planar cell polarity (PCP) pathway regulates CE, and Wnts regulate many aspects of gastrulation including CE and EMT. However, the Wnt ligands that regulate A-P axis elongation in mammalian development remain unknown. Wnt11 and Wnt5a regulate axis elongation in lower vertebrates, but only Wnt5a, not Wnt11, regulates mammalian PCP signaling and A-P axis elongation in development. Here, by generating Wnt5a; Wnt11 compound mutants, we show that Wnt11 and Wnt5a play redundant roles during mouse A-P axis elongation. Both genes regulate trunk notochord extension through PCP-controlled CE of notochord cells, establishing a role for Wnt11 in mammalian PCP. We show that Wnt5a and Wnt11 are required for proper patterning of the neural tube and somites by regulating notochord formation, and provide evidence that both genes are required for the generation and migration of axial and paraxial mesodermal precursor cells by regulating EMT. Axial and paraxial mesodermal precursors ectopically accumulate in the PS at late gastrula stages in Wnt5a−/−; Wnt11−/− embryos and these cells ectopically express epithelial cell adhesion molecules. Our data suggest that Wnt5a and Wnt11 regulate EMT by inducing p38 (Mapk14) phosphorylation. Our findings provide new insights into the role of Wnt5a and Wnt11 in mouse early development and also in cancer metastasis, during which EMT plays a crucial role. PMID:25813538
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Submicron-resolution photoacoustic microscopy of endogenous light-absorbing biomolecules
NASA Astrophysics Data System (ADS)
Zhang, Chi
Photoacoustic imaging in biomedicine has the unique advantage of probing endogenous light absorbers at various length scales with a 100% relative sensitivity. Among the several modalities of photoacoustic imaging, optical-resolution photoacoustic microscopy (OR-PAM) can achieve high spatial resolution, on the order of optical wavelength, at <1 mm depth in biological tissue (the optical ballistic regime). OR-PAM has been applied successfully to structural and functional imaging of blood vasculature and red blood cells in vivo. Any molecules which absorb sufficient light at certain wavelengths can potentially be imaged by PAM. Compared with pure optical imaging, which typically targets fluorescent markers, label-free PAM avoids the major concerns that the fluorescent labeling probes may disturb the function of biomolecules and may have an insufficient density. This dissertation aims to advance label-free OR-PAM to the subcellular scale. The first part of this dissertation describes the technological advancement of PAM yielding high spatial resolution in 3D. The lateral resolution was improved by using optical objectives with high numerical apertures for optical focusing. The axial resolution was improved by using broadband ultrasonic transducers for ultrasound detection. We achieved 220 nm lateral resolution in transmission mode, 0.43 microm lateral resolution in reflection mode, 7.6 microm axial resolution in normal tissue, and 5.8 microm axial resolution with silicone oil immersion/injection. The achieved lateral resolution and axial resolution were the finest reported at the time. With high-resolution in 3D, PAM was demonstrated to resolve cellular and subcellular structures in vivo, such as red blood cells and melanosomes in melanoma cells. Compared with previous PAM systems, our high-resolution PAM could resolve capillaries in mouse ears more clearly. As an example application, we demonstrated intracellular temperature imaging, assisted by fluorescence signal detection, with sub-degree temperature resolution and sub-micron lateral resolution. The second part of this dissertation describes the exploration of endogenous light-absorbing biomolecules for PAM. We demonstrated cytochromes and myoglobin as new absorption contrasts for PAM and identified the corresponding optimal wavelengths for imaging. Fixed fibroblasts on slides and mouse ear sections were imaged by PAM at 422 nm and 250 nm wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard hematoxylin and eosin (H&E) histology. By imaging a blood-perfused mouse heart at 532 nm down to 150 microm in depth, we derived the myocardial sheet thickness and the cleavage height from an undehydrated heart for the first time. The findings promote PAM at new wavelengths and open up new possibilities for characterizing biological tissue. Of particular interest, dual-wavelength PAM around 250 nm and 420 nm wavelengths is analogous to H&E histology. The last part of this dissertation describes the development of sectioning photoacoustic microscopy (SPAM), based on the advancement in spatial resolution and new contrasts for PAM, with applications in brain histology. Label-free SPAM, assisted by a microtome, acquires serial distortion-free images of a specimen on the surface. By exciting cell nuclei at 266 nm wavelength with high resolution, SPAM could pinpoint cell nuclei sensitively and specifically in the mouse brain section, as confirmed by H&E histology. SPAM was demonstrated to generate high-resolution 3D images, highlighting cell nuclei, of formalin-fixed paraffin-embedded mouse brains without tissue staining or clearing. SPAM can potentially serve as a high-throughput and minimal-artifact substitute for histology, probe many other biomolecules and cells, and become a universal tool for animal or human whole-organ microscopy, with diverse applications in life sciences.
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Feasibility of Whole-Body Functional Mouse Imaging Using Helical Pinhole SPECT
Metzler, Scott D.; Vemulapalli, Sreekanth; Jaszczak, Ronald J.; Akabani, Gamal; Chin, Bennett B.
2010-01-01
Purpose Detailed in vivo whole-body biodistributions of radiolabeled tracers may characterize the longitudinal progression of disease, and changes with therapeutic interventions. Small-animal imaging in mice is particularly attractive due to the wide array of well characterized genetically and surgically created models of disease. Single Photon Emission Computed Tomography (SPECT) imaging using pinhole collimation provides high resolution and sensitivity, but conventional methods using circular acquisitions result in severe image truncation and incomplete sampling of data which prevent the accurate determination of whole-body radiotracer biodistributions. This study describes the feasibility of helical acquisition paths to mitigate these effects. Procedures Helical paths of pinhole apertures were implemented using an external robotic stage aligned with the axis of rotation (AOR) of the scanner. Phantom and mouse scans were performed using helical paths and either circular or bi-circular orbits at the same radius of rotation (ROR). The bi-circular orbits consisted of two 360-degree scans separated by an axial shift to increase the axial field of view (FOV) and to improve the complete-sampling properties. Results Reconstructions of phantoms and mice acquired with helical paths show good image quality and are visually free of both truncation and axial-blurring artifacts. Circular orbits yielded reconstructions with both artifacts and a limited effective FOV. The bi-circular scans enlarged the axial FOV, but still suffered from truncation and sampling artifacts. Conclusions Helical paths can provide complete sampling data and large effective FOV, yielding 3D full-body in vivo biodistributions while still maintaining a small distance from the aperture to the object for good sensitivity and resolution. PMID:19521736
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Adaptive optics retinal imaging in the living mouse eye
Geng, Ying; Dubra, Alfredo; Yin, Lu; Merigan, William H.; Sharma, Robin; Libby, Richard T.; Williams, David R.
2012-01-01
Correction of the eye’s monochromatic aberrations using adaptive optics (AO) can improve the resolution of in vivo mouse retinal images [Biss et al., Opt. Lett. 32(6), 659 (2007) and Alt et al., Proc. SPIE 7550, 755019 (2010)], but previous attempts have been limited by poor spot quality in the Shack-Hartmann wavefront sensor (SHWS). Recent advances in mouse eye wavefront sensing using an adjustable focus beacon with an annular beam profile have improved the wavefront sensor spot quality [Geng et al., Biomed. Opt. Express 2(4), 717 (2011)], and we have incorporated them into a fluorescence adaptive optics scanning laser ophthalmoscope (AOSLO). The performance of the instrument was tested on the living mouse eye, and images of multiple retinal structures, including the photoreceptor mosaic, nerve fiber bundles, fine capillaries and fluorescently labeled ganglion cells were obtained. The in vivo transverse and axial resolutions of the fluorescence channel of the AOSLO were estimated from the full width half maximum (FWHM) of the line and point spread functions (LSF and PSF), and were found to be better than 0.79 μm ± 0.03 μm (STD)(45% wider than the diffraction limit) and 10.8 μm ± 0.7 μm (STD)(two times the diffraction limit), respectively. The axial positional accuracy was estimated to be 0.36 μm. This resolution and positional accuracy has allowed us to classify many ganglion cell types, such as bistratified ganglion cells, in vivo. PMID:22574260
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Zhang, Pengfei; Zam, Azhar; Jian, Yifan; Wang, Xinlei; Li, Yuanpei; Lam, Kit S.; Burns, Marie E.; Sarunic, Marinko V.; Pugh, Edward N.; Zawadzki, Robert J.
2015-01-01
Abstract. Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) provide complementary views of the retina, with the former collecting fluorescence data with good lateral but relatively low-axial resolution, and the latter collecting label-free backscattering data with comparable lateral but much higher axial resolution. To take maximal advantage of the information of both modalities in mouse retinal imaging, we have constructed a compact, four-channel, wide-field (∼50 deg) system that simultaneously acquires and automatically coregisters three channels of confocal SLO and Fourier domain OCT data. The scanner control system allows “zoomed” imaging of a region of interest identified in a wide-field image, providing efficient digital sampling and localization of cellular resolution features in longitudinal imaging of individual mice. The SLO is equipped with a “flip-in” spectrometer that enables spectral “fingerprinting” of fluorochromes. Segmentation of retina layers and en face display facilitate spatial comparison of OCT data with SLO fluorescence patterns. We demonstrate that the system can be used to image an individual retinal ganglion cell over many months, to simultaneously image microglia and Müller glia expressing different fluorochromes, to characterize the distinctive spatial distributions and clearance times of circulating fluorochromes with different molecular sizes, and to produce unequivocal images of the heretofore uncharacterized mouse choroidal vasculature. PMID:26677070
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Le, Victoria P.; Yamashiro, Yoshito; Yanagisawa, Hiromi; Wagenseil, Jessica E.
2014-01-01
Mice with a smooth muscle cell (SMC) specific deletion of fibulin-4 (SMKO) show decreased expression of SMC contractile genes, decreased circumferential compliance, and develop aneurysms in the ascending aorta. Neonatal administration of drugs that inhibit the angiotensin II pathway encourage expression of contractile genes and prevent aneurysm development, but do not increase compliance in SMKO aorta. We hypothesized that multidimensional mechanical changes in the aorta and/or other elastic arteries may contribute to aneurysm pathophysiology. We found that the SMKO ascending aorta and carotid artery showed mechanical changes in the axial direction. These changes were not reversed by angiotensin II inhibitors, hence reversing the axial changes is not required for aneurysm prevention. Mechanical changes in the circumferential direction were specific to the ascending aorta, therefore mechanical changes in the carotid do not contribute to aortic aneurysm development. We also hypothesized that a published model of postnatal aortic growth and remodeling could be used to investigate mechanisms behind the changes in SMKO aorta and aneurysm development over time. Dimensions and mechanical behavior of adult SMKO aorta were reproduced by the model after modifying the initial component material constants and the aortic dilation with each postnatal time step. The model links biological observations to specific mechanical responses in aneurysm development and treatment. PMID:24526456
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Le, Victoria P; Yamashiro, Yoshito; Yanagisawa, Hiromi; Wagenseil, Jessica E
2014-10-01
Mice with a smooth muscle cell (SMC)-specific deletion of Fibulin-4 (SMKO) show decreased expression of SMC contractile genes, decreased circumferential compliance, and develop aneurysms in the ascending aorta. Neonatal administration of drugs that inhibit the angiotensin II pathway encourages the expression of contractile genes and prevents aneurysm development, but does not increase compliance in SMKO aorta. We hypothesized that multidimensional mechanical changes in the aorta and/or other elastic arteries may contribute to aneurysm pathophysiology. We found that the SMKO ascending aorta and carotid artery showed mechanical changes in the axial direction. These changes were not reversed by angiotensin II inhibitors, hence reversing the axial changes is not required for aneurysm prevention. Mechanical changes in the circumferential direction were specific to the ascending aorta; therefore, mechanical changes in the carotid do not contribute to aortic aneurysm development. We also hypothesized that a published model of postnatal aortic growth and remodeling could be used to investigate mechanisms behind the changes in SMKO aorta and aneurysm development over time. Dimensions and mechanical behavior of adult SMKO aorta were reproduced by the model after modifying the initial component material constants and the aortic dilation with each postnatal time step. The model links biological observations to specific mechanical responses in aneurysm development and treatment.
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Cryo-imaging of fluorescently labeled single cells in a mouse
NASA Astrophysics Data System (ADS)
Steyer, Grant J.; Roy, Debashish; Salvado, Olivier; Stone, Meredith E.; Wilson, David L.
2009-02-01
We developed a cryo-imaging system to provide single-cell detection of fluorescently labeled cells in mouse, with particular applicability to stem cells and metastatic cancer. The Case cryoimaging system consists of a fluorescence microscope, robotic imaging positioner, customized cryostat, PC-based control system, and visualization/analysis software. The system alternates between sectioning (10-40 μm) and imaging, collecting color brightfield and fluorescent blockface image volumes >60GB. In mouse experiments, we imaged quantum-dot labeled stem cells, GFP-labeled cancer and stem cells, and cell-size fluorescent microspheres. To remove subsurface fluorescence, we used a simplified model of light-tissue interaction whereby the next image was scaled, blurred, and subtracted from the current image. We estimated scaling and blurring parameters by minimizing entropy of subtracted images. Tissue specific attenuation parameters were found [uT : heart (267 +/- 47.6 μm), liver (218 +/- 27.1 μm), brain (161 +/- 27.4 μm)] to be within the range of estimates in the literature. "Next image" processing removed subsurface fluorescence equally well across multiple tissues (brain, kidney, liver, adipose tissue, etc.), and analysis of 200 microsphere images in the brain gave 97+/-2% reduction of subsurface fluorescence. Fluorescent signals were determined to arise from single cells based upon geometric and integrated intensity measurements. Next image processing greatly improved axial resolution, enabled high quality 3D volume renderings, and improved enumeration of single cells with connected component analysis by up to 24%. Analysis of image volumes identified metastatic cancer sites, found homing of stem cells to injury sites, and showed microsphere distribution correlated with blood flow patterns. We developed and evaluated cryo-imaging to provide single-cell detection of fluorescently labeled cells in mouse. Our cryo-imaging system provides extreme (>60GB), micron-scale, fluorescence, and bright field image data. Here we describe our image preprocessing, analysis, and visualization techniques. Processing improves axial resolution, reduces subsurface fluorescence by 97%, and enables single cell detection and counting. High quality 3D volume renderings enable us to evaluate cell distribution patterns. Applications include the myriad of biomedical experiments using fluorescent reporter gene and exogenous fluorophore labeling of cells in applications such as stem cell regenerative medicine, cancer, tissue engineering, etc.
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McCann, Matthew R; Tamplin, Owen J; Rossant, Janet; Séguin, Cheryle A
2012-01-01
Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.
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McCann, Matthew R.; Tamplin, Owen J.; Rossant, Janet; Séguin, Cheryle A.
2012-01-01
SUMMARY Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration. PMID:22028328
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Ozbay, Baris N; Futia, Gregory L; Ma, Ming; Bright, Victor M; Gopinath, Juliet T; Hughes, Ethan G; Restrepo, Diego; Gibson, Emily A
2018-05-25
We present a miniature head mounted two-photon fiber-coupled microscope (2P-FCM) for neuronal imaging with active axial focusing enabled using a miniature electrowetting lens. We show three-dimensional two-photon imaging of neuronal structure and record neuronal activity from GCaMP6s fluorescence from multiple focal planes in a freely-moving mouse. Two-color simultaneous imaging of GFP and tdTomato fluorescence is also demonstrated. Additionally, dynamic control of the axial scanning of the electrowetting lens allows tilting of the focal plane enabling neurons in multiple depths to be imaged in a single plane. Two-photon imaging allows increased penetration depth in tissue yielding a working distance of 450 μm with an additional 180 μm of active axial focusing. The objective NA is 0.45 with a lateral resolution of 1.8 μm, an axial resolution of 10 μm, and a field-of-view of 240 μm diameter. The 2P-FCM has a weight of only ~2.5 g and is capable of repeatable and stable head-attachment. The 2P-FCM with dynamic axial scanning provides a new capability to record from functionally distinct neuronal layers, opening new opportunities in neuroscience research.
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No turning, a mouse mutation causing left-right and axial patterning defects.
Melloy, P G; Ewart, J L; Cohen, M F; Desmond, M E; Kuehn, M R; Lo, C W
1998-01-01
Patterning along the left/right axes helps establish the orientation of visceral organ asymmetries, a process which is of fundamental importance to the viability of an organism. A linkage between left/right and axial patterning is indicated by the finding that a number of genes involved in left/right patterning also play a role in anteroposterior and dorsoventral patterning. We have recovered a spontaneous mouse mutation causing left/right patterning defects together with defects in anteroposterior and dorsoventral patterning. This mutation is recessive lethal and was named no turning (nt) because the mutant embryos fail to undergo embryonic turning. nt embryos exhibit cranial neural tube closure defects and malformed somites and are caudally truncated. Development of the heart arrests at the looped heart tube stage, with cardiovascular defects indicated by ballooning of the pericardial sac and the pooling of blood in various regions of the embryo. Interestingly, in nt embryos, the direction of heart looping was randomized. Nodal and lefty, two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate mesoderm. Lefty, which is normally also expressed in the floorplate, is not found in the prospective floor plate of nt embryos. This suggests the possibility of notochordal defects. This was confirmed by histological analysis and the examination of sonic hedgehog, Brachyury, and HNF-3 beta gene expression. These studies showed that the notochord is present in the early nt embryo, but degenerates as development progresses. Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expression of HNF-3 beta.
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In vivo photoacoustic tomography of total blood flow and Doppler angle
NASA Astrophysics Data System (ADS)
Yao, Junjie; Maslov, Konstantin I.; Wang, Lihong V.
2012-02-01
As two hallmarks of cancer, angiogenesis and hypermetabolism are closely related to increased blood flow. Volumetric blood flow measurement is important to understanding the tumor microenvironment and developing new means to treat cancer. Current photoacoustic blood flow estimation methods focus on either the axial or transverse component of the flow vector. Here, we propose a method to compute the total flow speed and Doppler angle by combining the axial and transverse flow measurements. Both the components are measured in M-mode. Collating the A-lines side by side yields a 2D matrix. The columns are Hilbert transformed to compare the phases for the computation of the axial flow. The rows are Fourier transformed to quantify the bandwidth for the computation of the transverse flow. From the axial and transverse flow components, the total flow speed and Doppler angle can be derived. The method has been verified by flowing bovine blood in a plastic tube at various speeds from 0 to 7.5 mm/s and at Doppler angles from 30 to 330°. The measurement error for total flow speed was experimentally determined to be less than 0.3 mm/s; for the Doppler angle, it was less than 15°. In addition, the method was tested in vivo on a mouse ear. The advantage of this method is simplicity: No system modification or additional data acquisition is required to use our existing system. We believe that the proposed method has the potential to be used for cancer angiogenesis and hypermetabolism imaging.
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Bazzi, Hisham; Soroka, Ekaterina; Alcorn, Heather L; Anderson, Kathryn V
2017-12-19
Regulated mesoderm migration is necessary for the proper morphogenesis and organ formation during embryonic development. Cell migration and its dependence on the cytoskeleton and signaling machines have been studied extensively in cultured cells; in contrast, remarkably little is known about the mechanisms that regulate mesoderm cell migration in vivo. Here, we report the identification and characterization of a mouse mutation in striatin-interacting protein 1 ( Strip1 ) that disrupts migration of the mesoderm after the gastrulation epithelial-to-mesenchymal transition (EMT). STRIP1 is a core component of the biochemically defined mammalian striatin-interacting phosphatases and kinase (STRIPAK) complexes that appear to act through regulation of protein phosphatase 2A (PP2A), but their functions in mammals in vivo have not been examined. Strip1 -null mutants arrest development at midgestation with profound disruptions in the organization of the mesoderm and its derivatives, including a complete failure of the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants and mouse embryonic fibroblasts from null mutants shows that the mesoderm migration defect is correlated with decreased cell spreading, abnormal focal adhesions, changes in the organization of the actin cytoskeleton, and decreased velocity of cell migration. The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo. Copyright © 2017 the Author(s). Published by PNAS.
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An Asymmetric Birdcage Coil for Small-animal MR Imaging at 7T
Kim, Kyoung-Nam; Han, Sang-Doc; Seo, Jeung-Hoon; Heo, Phil; Yoo, Dongkyeom; Im, Geun Ho; Lee, Jung Hee
2017-01-01
The birdcage (BC) coil is currently being utilized for uniform radiofrequency (RF) transmit/receive (Tx/Rx) or Tx-only configuration in many magnetic resonance (MR) imaging applications, but insufficient magnetic flux (|B1|) density and their non-uniform distribution still exists in high-field (HF) environments. We demonstrate that the asymmetric birdcage (ABC) transmit/receive (Tx/Rx) volume coil, which is a modified standard birdcage (SBC) coil with the end ring split into two halves, is suitable for improving the |B1| sensitivity in 7T small-animal MR imaging. Cylindrical SBC and ABC coils with 35 mm diameter were constructed and bench tested for mouse body MR imaging at 300 MHz using a 7T scanner. To assess the ABC coil performance, computational electromagnetic (EM) simulation and 7T MR experiment were performed by using a cylindrical phantom and in vivo mouse body and quantitatively compared with the SBC coil in terms of |B1| distribution, RF transmit (|B1+|) field, and signal-to-noise ratio (SNR). The bench measurements of the two BC coils are similar, yielding a quality value (Q-value) of 74.42 for the SBC coil and 77.06 for the ABC coil. The computational calculation results clearly show that the proposed ABC coil offers superior |B1| field and |B1+| field sensitivity in the central axial slice compared with the SBC coil. There was also high SNR and uniformly distributed flip angle (FA) under the loaded condition of mouse body in the 7T experiment. Although ABC geometry allows a further increase in the |B1| field and |B1+| field sensitivity in only the central axial slice, the geometrical modification of the SBC coil can make a high performance RF coil feasible in the central axial slice and also make target imaging possible in the diagonal direction. PMID:27725573
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Clark, R M; Marker, P C; Kingsley, D M
2000-07-01
Polydactyly is a common malformation of vertebrate limbs. In humans a major locus for nonsyndromic pre-axial polydactyly (PPD) has been mapped previously to 7q36. The mouse Hemimelic extra-toes (Hx) mutation maps to a homologous chromosome segment and has been proposed to affect a homologous gene. To understand the molecular changes underlying PPD, we used a positional cloning approach to identify the gene or genes disrupted by the Hx mutation and a closely linked limb mutation, Hammertoe (Hm). High resolution genetic mapping identified a small candidate interval for the mouse mutations located 1.2 cM distal to the Shh locus. The nonrecombinant interval was completely cloned in bacterial artificial chromosomes and searched for genes using a combination of exon trapping, sample sequencing, and mapping of known genes. Two novel genes, Lmbr1 and Lmbr2, are entirely within the candidate interval we defined genetically. The open reading frame of both genes is intact in mutant mice, but the expression of the Lmbr1 gene is dramatically altered in developing limbs of Hx mutant mice. The correspondence between the spatial and temporal changes in Lmbr1 expression and the embryonic onset of the Hx mutant phenotype suggests that the mouse Hx mutation may be a regulatory allele of Lmbr1. The human ortholog of Lmbr1 maps within the recently described interval for human PPD, strengthening the possibility that both mouse and human limb abnormalities are due to defects in the same highly conserved gene.
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Measurement of refractive state and deprivation myopia in two strains of mice.
Schaeffel, Frank; Burkhardt, Eva; Howland, Howard C; Williams, Robert W
2004-02-01
The mouse eye has a bright retinal image (f/number <1) but low optical quality (visual acuity about 0.5 cpd) that may render emmetropization unnecessary. However, this species is potentially a powerful model to study eye growth and myopia because its genome can be readily manipulated and has been completely sequenced. We have investigated how precisely eyes of mice can be refracted and tested whether deprivation myopia can be induced by frosted diffusers. An automated eccentric infrared photorefractor was adapted to refract eyes of two mouse strains--C57BL/6 (B6) and DBA/2 (D2)--during Tropicamide cycloplegia without anesthesia. Axial lengths were measured in highly magnified video images of freshly excised eyes. Plastic hemispherical diffusers were applied between postnatal days and 29 and left attached for 7 or 14 days. (1) Trial lenses ranging from +10 to -10 D produced high correlations between the brightness slope in the pupil and applied lens power (r = 0.81 and r = 0.87), demonstrating reliable refraction. Five repeated measures in 12 eyes showed an average standard deviation of 3.0 D, equivalent to an axial length change <10 microm (derived from schematic eye modeling). (2) Deprivation produced a significant shift toward myopia, relative to untreated eyes, but only after 14 days and only in B6 mice (p = 0.02 with or p = 0.00038 without one outlier; N = 9). In contrast, DBA/2J were unaffected by occlusion, perhaps due to mutations that target eye, lens, or anterior segment. (3) Both eyes of untreated animals often had axial lengths that differed markedly. Surprisingly, we detected no significant correlation between refractive error and axial length after treatment. The infrared refraction technique is sufficiently sensitive to resolve equivalent changes in axial length of only +/- 10 microm in alert mice. Prolonged occlusion produces a significant myopic shift in B6 mice, but not in D2 mice. Even among isogenic B6 mice, the response is variable for reasons that presumably trace back to subtle developmental, environmental, and technical factors.
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SLITRK6 mutations cause myopia and deafness in humans and mice
Tekin, Mustafa; Chioza, Barry A.; Matsumoto, Yoshifumi; Diaz-Horta, Oscar; Cross, Harold E.; Duman, Duygu; Kokotas, Haris; Moore-Barton, Heather L.; Sakoori, Kazuto; Ota, Maya; Odaka, Yuri S.; Foster, Joseph; Cengiz, F. Basak; Tokgoz-Yilmaz, Suna; Tekeli, Oya; Grigoriadou, Maria; Petersen, Michael B.; Sreekantan-Nair, Ajith; Gurtz, Kay; Xia, Xia-Juan; Pandya, Arti; Patton, Michael A.; Young, Juan I.; Aruga, Jun; Crosby, Andrew H.
2013-01-01
Myopia is by far the most common human eye disorder that is known to have a clear, albeit poorly defined, heritable component. In this study, we describe an autosomal-recessive syndrome characterized by high myopia and sensorineural deafness. Our molecular investigation in 3 families led to the identification of 3 homozygous nonsense mutations (p.R181X, p.S297X, and p.Q414X) in SLIT and NTRK-like family, member 6 (SLITRK6), a leucine-rich repeat domain transmembrane protein. All 3 mutant SLITRK6 proteins displayed defective cell surface localization. High-resolution MRI of WT and Slitrk6-deficient mouse eyes revealed axial length increase in the mutant (the endophenotype of myopia). Additionally, mutant mice exhibited auditory function deficits that mirrored the human phenotype. Histological investigation of WT and Slitrk6-deficient mouse retinas in postnatal development indicated a delay in synaptogenesis in Slitrk6-deficient animals. Taken together, our results showed that SLITRK6 plays a crucial role in the development of normal hearing as well as vision in humans and in mice and that its disruption leads to a syndrome characterized by severe myopia and deafness. PMID:23543054
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Improving axial resolution in confocal microscopy with new high refractive index mounting media.
Fouquet, Coralie; Gilles, Jean-François; Heck, Nicolas; Dos Santos, Marc; Schwartzmann, Richard; Cannaya, Vidjeacoumary; Morel, Marie-Pierre; Davidson, Robert Stephen; Trembleau, Alain; Bolte, Susanne
2015-01-01
Resolution, high signal intensity and elevated signal to noise ratio (SNR) are key issues for biologists who aim at studying the localisation of biological structures at the cellular and subcellular levels using confocal microscopy. The resolution required to separate sub-cellular biological structures is often near to the resolving power of the microscope. When optimally used, confocal microscopes may reach resolutions of 180 nm laterally and 500 nm axially, however, axial resolution in depth is often impaired by spherical aberration that may occur due to refractive index mismatches. Spherical aberration results in broadening of the point-spread function (PSF), a decrease in peak signal intensity when imaging in depth and a focal shift that leads to the distortion of the image along the z-axis and thus in a scaling error. In this study, we use the novel mounting medium CFM3 (Citifluor Ltd., UK) with a refractive index of 1.518 to minimize the effects of spherical aberration. This mounting medium is compatible with most common fluorochromes and fluorescent proteins. We compare its performance with established mounting media, harbouring refractive indices below 1.500, by estimating lateral and axial resolution with sub-resolution fluorescent beads. We show furthermore that the use of the high refractive index media renders the tissue transparent and improves considerably the axial resolution and imaging depth in immuno-labelled or fluorescent protein labelled fixed mouse brain tissue. We thus propose to use those novel high refractive index mounting media, whenever optimal axial resolution is required.
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Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice
Barathi, Veluchamy A.; Kwan, Jia Lin; Tan, Queenie S. W.; Weon, Sung Rhan; Seet, Li Fong; Goh, Liang Kee; Vithana, Eranga N.; Beuerman, Roger W.
2013-01-01
SUMMARY Myopia is a huge public health problem worldwide, reaching the highest incidence in Asia. Identification of susceptible genes is crucial for understanding the biological basis of myopia. In this paper, we have identified and characterized a functional myopia-associated gene using a specific mouse-knockout model. Mice lacking the muscarinic cholinergic receptor gene (M2; also known as Chrm2) were less susceptible to lens-induced myopia compared with wild-type mice, which showed significantly increased axial length and vitreous chamber depth when undergoing experimental induction of myopia. The key findings of this present study are that the sclera of M2 mutant mice has higher expression of collagen type I and lower expression of collagen type V than do wild-type mice and mice that are mutant for other muscarinic subtypes, and, therefore, M2 mutant mice were resistant to the development of experimental myopia. Pharmacological blockade of M2 muscarinic receptor proteins retarded myopia progression in the mouse. These results suggest for the first time a role of M2 in growth-related changes in extracellular matrix genes during myopia development in a mammalian model. M2 receptor antagonists might thus provide a targeted therapeutic approach to the management of this refractive error. PMID:23649821
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Non-contact measurement of linear external dimensions of the mouse eye
Wisard, Jeffrey; Chrenek, Micah A.; Wright, Charles; Dalal, Nupur; Pardue, Machelle T.; Boatright, Jeffrey H.; Nickerson, John M.
2010-01-01
Biometric analyses of quantitative traits in eyes of mice can reveal abnormalities related to refractive or ocular development. Due to the small size of the mouse eye, highly accurate and precise measurements are needed to detect meaningful differences. We sought a non-contact measuring technique to obtain highly accurate and precise linear dimensions of the mouse eye. Laser micrometry was validated with gauge block standards. Simple procedures to measure eye dimensions on three axes were devised. Mouse eyes from C57BL/6J and rd10 on a C57BL/6J background were dissected and extraocular muscle and fat removed. External eye dimensions of axial length (anterior-posterior (A-P) axis) and equatorial diameter (superior-inferior (S-I) and nasal-temporal (N-T) axes) were obtained with a laser micrometer. Several approaches to prevent or ameliorate evaporation due to room air were employed. The resolution of the laser micrometer was less than 0.77 microns, and it provided accurate and precise non-contact measurements of eye dimensions on three axes. External dimensions of the eye strongly correlated with eye weight. The N-T and S-I dimensions of the eye correlated with each other most closely from among the 28 pair-wise combinations of the several parameters that were collected. The equatorial axis measurements correlated well from the right and left eye of each mouse. The A-P measurements did not correlate or correlated poorly in each pair of eyes. The instrument is well suited for the measurement of enucleated eyes and other structures from most commonly used species in experimental vision research and ophthalmology. PMID:20067806
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Non-contact measurement of linear external dimensions of the mouse eye.
Wisard, Jeffrey; Chrenek, Micah A; Wright, Charles; Dalal, Nupur; Pardue, Machelle T; Boatright, Jeffrey H; Nickerson, John M
2010-03-30
Biometric analyses of quantitative traits in eyes of mice can reveal abnormalities related to refractive or ocular development. Due to the small size of the mouse eye, highly accurate and precise measurements are needed to detect meaningful differences. We sought a non-contact measuring technique to obtain highly accurate and precise linear dimensions of the mouse eye. Laser micrometry was validated with gauge block standards. Simple procedures to measure eye dimensions on three axes were devised. Mouse eyes from C57BL/6J and rd10 on a C57BL/6J background were dissected and extraocular muscle and fat removed. External eye dimensions of axial length (anterior-posterior (A-P) axis) and equatorial diameter (superior-inferior (S-I) and nasal-temporal (N-T) axes) were obtained with a laser micrometer. Several approaches to prevent or ameliorate evaporation due to room air were employed. The resolution of the laser micrometer was less than 0.77 microm, and it provided accurate and precise non-contact measurements of eye dimensions on three axes. External dimensions of the eye strongly correlated with eye weight. The N-T and S-I dimensions of the eye correlated with each other most closely from among the 28 pair-wise combinations of the several parameters that were collected. The equatorial axis measurements correlated well from the right and left eye of each mouse. The A-P measurements did not correlate or correlated poorly in each pair of eyes. The instrument is well suited for the measurement of enucleated eyes and other structures from most commonly used species in experimental vision research and ophthalmology. Copyright (c) 2010 Elsevier B.V. All rights reserved.
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Yamanaka, Yojiro; Tamplin, Owen J; Beckers, Anja; Gossler, Achim; Rossant, Janet
2007-12-01
The node and notochord have been extensively studied as signaling centers in the vertebrate embryo. The morphogenesis of these tissues, particularly in mouse, is not well understood. Using time-lapse live imaging and cell lineage tracking, we show the notochord has distinct morphogenetic origins along the anterior-posterior axis. The anterior head process notochord arises independently of the node by condensation of dispersed cells. The trunk notochord is derived from the node and forms by convergent extension. The tail notochord forms by node-derived progenitors that actively migrate toward the posterior. We also reveal distinct genetic regulation within these different regions. We show that Foxa2 compensates for and genetically interacts with Noto in the trunk notochord, and that Noto has an evolutionarily conserved role in regulating axial versus paraxial cell fate. Therefore, we propose three distinct regions within the mouse notochord, each with unique morphogenetic origins.
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Improving Axial Resolution in Confocal Microscopy with New High Refractive Index Mounting Media
Fouquet, Coralie; Gilles, Jean-François; Heck, Nicolas; Dos Santos, Marc; Schwartzmann, Richard; Cannaya, Vidjeacoumary; Morel, Marie-Pierre; Davidson, Robert Stephen; Trembleau, Alain; Bolte, Susanne
2015-01-01
Resolution, high signal intensity and elevated signal to noise ratio (SNR) are key issues for biologists who aim at studying the localisation of biological structures at the cellular and subcellular levels using confocal microscopy. The resolution required to separate sub-cellular biological structures is often near to the resolving power of the microscope. When optimally used, confocal microscopes may reach resolutions of 180 nm laterally and 500 nm axially, however, axial resolution in depth is often impaired by spherical aberration that may occur due to refractive index mismatches. Spherical aberration results in broadening of the point-spread function (PSF), a decrease in peak signal intensity when imaging in depth and a focal shift that leads to the distortion of the image along the z-axis and thus in a scaling error. In this study, we use the novel mounting medium CFM3 (Citifluor Ltd., UK) with a refractive index of 1.518 to minimize the effects of spherical aberration. This mounting medium is compatible with most common fluorochromes and fluorescent proteins. We compare its performance with established mounting media, harbouring refractive indices below 1.500, by estimating lateral and axial resolution with sub-resolution fluorescent beads. We show furthermore that the use of the high refractive index media renders the tissue transparent and improves considerably the axial resolution and imaging depth in immuno-labelled or fluorescent protein labelled fixed mouse brain tissue. We thus propose to use those novel high refractive index mounting media, whenever optimal axial resolution is required. PMID:25822785
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Huang, Yong; Furtmüller, Georg J.; Tong, Dedi; Zhu, Shan; Lee, W. P. Andrew; Brandacher, Gerald; Kang, Jin U.
2014-01-01
Purpose To demonstrate the feasibility of a miniature handheld optical coherence tomography (OCT) imager for real time intraoperative vascular patency evaluation in the setting of super-microsurgical vessel anastomosis. Methods A novel handheld imager Fourier domain Doppler optical coherence tomography based on a 1.3-µm central wavelength swept source for extravascular imaging was developed. The imager was minimized through the adoption of a 2.4-mm diameter microelectromechanical systems (MEMS) scanning mirror, additionally a 12.7-mm diameter lens system was designed and combined with the MEMS mirror to achieve a small form factor that optimize functionality as a handheld extravascular OCT imager. To evaluate in-vivo applicability, super-microsurgical vessel anastomosis was performed in a mouse femoral vessel cut and repair model employing conventional interrupted suture technique as well as a novel non-suture cuff technique. Vascular anastomosis patency after clinically successful repair was evaluated using the novel handheld OCT imager. Results With an adjustable lateral image field of view up to 1.5 mm by 1.5 mm, high-resolution simultaneous structural and flow imaging of the blood vessels were successfully acquired for BALB/C mouse after orthotopic hind limb transplantation using a non-suture cuff technique and BALB/C mouse after femoral artery anastomosis using a suture technique. We experimentally quantify the axial and lateral resolution of the OCT to be 12.6 µm in air and 17.5 µm respectively. The OCT has a sensitivity of 84 dB and sensitivity roll-off of 5.7 dB/mm over an imaging range of 5 mm. Imaging with a frame rate of 36 Hz for an image size of 1000(lateral)×512(axial) pixels using a 50,000 A-lines per second swept source was achieved. Quantitative vessel lumen patency, lumen narrowing and thrombosis analysis were performed based on acquired structure and Doppler images. Conclusions A miniature handheld OCT imager that can be used for intraoperative evaluation of microvascular anastomosis was successfully demonstrated. PMID:25474742
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Cardamone, L.; Valentín, A.; Eberth, J. F.; Humphrey, J. D.
2010-01-01
Motivated by recent clinical and laboratory findings of important effects of pulsatile pressure and flow on arterial adaptations, we employ and extend an established constrained mixture framework of growth (change in mass) and remodelling (change in structure) to include such dynamical effects. New descriptors of cell and tissue behavior (constitutive relations) are postulated and refined based on new experimental data from a transverse aortic arch banding model in the mouse that increases pulsatile pressure and flow in one carotid artery. In particular, it is shown that there was a need to refine constitutive relations for the active stress generated by smooth muscle, to include both stress- and stress rate-mediated control of the turnover of cells and matrix and to account for a cyclic stress-mediated loss of elastic fibre integrity and decrease in collagen stiffness in order to capture the reported evolution, over 8 weeks, of luminal radius, wall thickness, axial force and in vivo axial stretch of the hypertensive mouse carotid artery. We submit, therefore, that complex aspects of adaptation by elastic arteries can be predicted by constrained mixture models wherein individual constituents are produced or removed at individual rates and to individual extents depending on changes in both stress and stress rate from normal values. PMID:20484365
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Lee, Kyounghwan; Harris, Samantha P.; Sadayappan, Sakthivel; Craig, Roger
2014-01-01
Myosin binding protein-C is a thick filament protein of vertebrate striated muscle. The cardiac isoform (cMyBP-C) is essential for normal cardiac function, and mutations in cMyBP-C cause cardiac muscle disease. The rod-shaped molecule is composed primarily of 11 immunoglobulin- or fibronectin-like domains, and is located at 9 sites, 43 nm apart, in each half of the A-band. To understand how cMyBP-C functions, it is important to know its structural organization in the sarcomere, as this will affect its ability to interact with other sarcomeric proteins. Several models have been proposed, in which cMyBP-C wraps around, extends radially from, or runs axially along the thick filament. Our goal was to define cMyBP-C orientation by determining the relative axial positions of different cMyBP-C domains. Immuno-electron microscopy was performed using mouse cardiac myofibrils labeled with antibodies specific to the N- and C-terminal domains and to the middle of cMyBP-C. Antibodies to all regions of the molecule, except the C-terminus, labeled at the same nine axial positions in each half A-band, consistent with a circumferential and/or radial rather than an axial orientation of the bulk of the molecule. The C-terminal antibody stripes were slightly displaced axially, demonstrating an axial orientation of the C-terminal 3 domains, with the C-terminus closer to the M-line. These results, combined with previous studies, suggest that the C-terminal domains of cMyBP-C run along the thick filament surface, while the N-terminus extends towards neighboring thin filaments. This organization provides a structural framework for understanding cMyBP-C’s modulation of cardiac muscle contraction. PMID:25451032
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Yeh, Lung-Kun; Liu, Chia-Yang; Kao, Winston W.-Y.; Huang, Chang-Jen; Hu, Fung-Rong; Chien, Chung-Liang; Wang, I-Jong
2010-01-01
The lumican gene (lum), which encodes one of the major keratan sulfate proteoglycans (KSPGs) in the vertebrate cornea and sclera, has been linked to axial myopia in humans. In this study, we chose zebrafish (Danio rerio) as an animal model to elucidate the role of lumican in the development of axial myopia. The zebrafish lumican gene (zlum) spans ∼4.6 kb of the zebrafish genome. Like human (hLUM) and mouse (mlum), zlum consists of three exons, two introns, and a TATA box-less promoter at the 5′-flanking region of the transcription initiation site. Sequence analysis of the cDNA predicts that zLum encodes 344 amino acids. zLum shares 51% amino acid sequence identity with human lumican. Similar to hLUM and mlum, zlum mRNA is expressed in the eye and many other tissues, such as brain, muscle, and liver as well. Transgenic zebrafish harboring an enhanced GFP reporter gene construct downstream of a 1.7-kb zlum 5′-flanking region displayed enhanced GFP expression in the cornea and sclera, as well as throughout the body. Down-regulation of zlum expression by antisense zlum morpholinos manifested ocular enlargement resembling axial myopia due to disruption of the collagen fibril arrangement in the sclera and resulted in scleral thinning. Administration of muscarinic receptor antagonists, e.g. atropine and pirenzepine, effectively subdued the ocular enlargement caused by morpholinos in in vivo zebrafish larvae assays. The observation suggests that zebrafish can be used as an in vivo model for screening compounds in treating myopia. PMID:20551313
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Effects of unilateral topical atropine on binocular pupil responses and eye growth in mice.
Barathi, V A; Beuerman, Roger W; Schaeffel, Frank
2009-02-01
Studies on drugs selected to target myopia development often use the vehicle-treated fellow eye as a control. However, it is not clear how much of the drug reaches the fellow eye, rendering it a potentially invalid control. Therefore, in this study, pupil responses were used to probe the effects of atropine in both eyes in mice, after unilateral topical application. In a second experiment, interocular differences in refractive development and axial eye growth were studied while atropine was applied daily to one eye. In 20 C57BL/6 (B6) wildtype mice, a single drop of 1% atropine solution was instilled into one eye. Mice were gently restrained by holding their necks while video image processing software detected the pupil and measured its diameter at a sampling rate of 30 Hz. A bright green LED, attached to the photoretinoscope of the video camera, was flashed. Pupil responses were quantified daily over a period of 2 weeks. In another group of 24 mice, one drop of 1% atropine was applied daily for 28 days. Axial length was measured pre- and post-treatment, using low coherence interferometry (the Zeiss AC-Master). Refractive development was measured by infrared photorefraction. Similar to previous findings with the same device, untreated eyes displayed a pupil constriction of 24.84+/-1.73% upon stimulation with the green LED. A single drop of 1% atropine caused complete suppression with no significant recovery over the whole observation period of two weeks. The responses in the fellow eye were temporarily reduced to about 75% and then recovered towards baseline. After daily atropine application, there was significant reduction in axial length of the eyes, relative to the saline-treated fellow eyes (3.234+/-0.186 versus 3.378+/-0.176 mm, n=24, p<0.01, paired t-test) and the refractions became more hyperopic/less myopic (+13.46+/-2.15 D versus +10.06+/-2.02 D, n=24, p<0.01). In line with previous findings, one drop of atropine solution caused a long lasting suppression of pupil responses in the mouse eye. New data show that the transfer to the fellow eye was limited, making interocular comparisons feasible. It is also new that topical atropine reduced axial eye growth even when mice had largely normal vision.
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Mohn, Deanna; Chen, Siming W; Dias, Dora Campos; Weinstein, Daniel C; Dyer, Michael A; Sahr, Kenneth; Ducker, Charles E; Zahradka, Elizabeth; Keller, Gordon; Zaret, Kenneth S; Gudas, Lorraine J; Baron, Margaret H
2003-03-01
In frog and zebrafish, the Mix/Bix family of paired type homeodomain proteins play key roles in specification and differentiation of mesendoderm. However, in mouse, only a single Mix gene (mMix) has been identified to date and its function is unknown. We have analyzed the expression of mouse Mix RNA and protein in embryos, embryoid bodies formed from embryonic stem cells and F9 teratocarcinoma cells, as well as several differentiated cell types. Expression in embryoid bodies in culture mirrors that in embryos, where Mix is transcribed transiently in primitive (visceral) endoderm (VE) and in nascent mesoderm. In F9 cells induced by retinoic acid to differentiate to VE, mMix is coordinately expressed with three other endodermal transcription factors, well before AFP, and its protein product is localized to the nucleus. In a subpopulation of nascent mesodermal cells from embryonic stem cell embryoid bodies, mMix is coexpressed with Brachyury. Intriguingly, mMix mRNA is detected in a population (T+Flk1+) of cells which may contain hemangioblasts, before the onset of hematopoiesis and activation of hematopoietic markers. In vitro and in vivo, mMix expression in nascent mesoderm is rapidly down-regulated and becomes undetectable in differentiated cell types. In the region of the developing gut, mMix expression is confined to the mesoderm of mid- and hindgut but is absent from definitive endoderm. Injection of mouse mMix RNA into early frog embryos results in axial truncation of developing tadpoles and, in animal cap assays, mMix alone is sufficient to activate expression of several endodermal (but not mesodermal) markers. Although these observations do not exclude a possible cell-autonomous function for mMix in mesendodermal progenitor cells, they do suggest an additional, non-cell autonomous role in nascent mesoderm in the formation and/or patterning of adjacent definitive endoderm. Copyright 2003 Wiley-Liss, Inc.
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Tomographic imaging of transparent biological samples using the pyramid phase microscope
Iglesias, Ignacio
2016-01-01
We show how a pyramid phase microscope can be used to obtain tomographic information of the spatial variation of refractive index in biological samples using the Radon transform. A method that uses the information provided by the phase microscope for axial and lateral repositioning of the sample when it rotates is also described. Its application to the reconstruction of mouse embryos in the blastocyst stage is demonstrated. PMID:27570696
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Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope
NASA Astrophysics Data System (ADS)
Saldua, Meagan A.; Olsovsky, Cory A.; Callaway, Evelyn S.; Chapkin, Robert S.; Maitland, Kristen C.
2012-01-01
Large area confocal microscopy may provide fast, high-resolution image acquisition for evaluation of tissue in pre-clinical studies with reduced tissue processing in comparison to histology. We present a rapid beam and stage-scanning confocal fluorescence microscope to image cellular and tissue features along the length of the entire excised mouse colon. The beam is scanned at 8,333 lines/sec by a polygon scanning mirror while the specimen is scanned in the orthogonal axis by a motorized translation stage with a maximum speed of 7 mm/sec. A single 1×60 mm2 field of view image spanning the length of the mouse colon is acquired in 10 s. Z-projection images generated from axial image stacks allow high resolution imaging of the surface of non-flat specimens. In contrast to the uniform size, shape, and distribution of colon crypts in confocal images of normal colon, confocal images of chronic bowel inflammation exhibit heterogeneous tissue structure with localized severe crypt distortion.
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Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards.
Sato, K; Shidahara, M; Watabe, H; Watanuki, S; Ishikawa, Y; Arakawa, Y; Nai, Y H; Furumoto, S; Tashiro, M; Shoji, T; Yanai, K; Gonda, K
2016-01-21
The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10 min after intravenous injection of (18)F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415 kcps at 14.6 MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.
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Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards
NASA Astrophysics Data System (ADS)
Sato, K.; Shidahara, M.; Watabe, H.; Watanuki, S.; Ishikawa, Y.; Arakawa, Y.; Nai, YH; Furumoto, S.; Tashiro, M.; Shoji, T.; Yanai, K.; Gonda, K.
2016-01-01
The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10min after intravenous injection of 18F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415kcps at 14.6MBq ml-1. The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.
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Development of a simultaneous optical/PET imaging system for awake mice
NASA Astrophysics Data System (ADS)
Takuwa, Hiroyuki; Ikoma, Yoko; Yoshida, Eiji; Tashima, Hideaki; Wakizaka, Hidekatsu; Shinaji, Tetsuya; Yamaya, Taiga
2016-09-01
Simultaneous measurements of multiple physiological parameters are essential for the study of brain disease mechanisms and the development of suitable therapies to treat them. In this study, we developed a measurement system for simultaneous optical imaging and PET for awake mice. The key elements of this system are the OpenPET, optical imaging and fixation apparatus for an awake mouse. The OpenPET is our original open-type PET geometry, which can be used in combination with another device because of the easily accessible open space of the former. A small prototype of the axial shift single-ring OpenPET was used. The objective lens for optical imaging with a mounted charge-coupled device camera was placed inside the open space of the AS-SROP. Our original fixation apparatus to hold an awake mouse was also applied. As a first application of this system, simultaneous measurements of cerebral blood flow (CBF) by laser speckle imaging (LSI) and [11C]raclopride-PET were performed under control and 5% CO2 inhalation (hypercapnia) conditions. Our system successfully obtained the CBF and [11C]raclopride radioactivity concentration simultaneously. Accumulation of [11C]raclopride was observed in the striatum where the density of dopamine D2 receptors is high. LSI measurements could be stably performed for more than 60 minutes. Increased CBF induced by hypercapnia was observed while CBF under the control condition was stable. We concluded that our imaging system should be useful for investigating the mechanisms of brain diseases in awake animal models.
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NASA Astrophysics Data System (ADS)
Hong, R.; Li, J. C.; Hajjar, R.; Chakraborty Thakur, S.; Diamond, P. H.; Tynan, G. R.
2018-05-01
Detailed measurements of intrinsic axial flow generation parallel to the magnetic field in the controlled shear decorrelation experiment linear plasma device with no axial momentum input are presented and compared to theory. The results show a causal link from the density gradient to drift-wave turbulence with broken spectral symmetry and development of the axial mean parallel flow. As the density gradient steepens, the axial and azimuthal Reynolds stresses increase and radially sheared azimuthal and axial mean flows develop. A turbulent axial momentum balance analysis shows that the axial Reynolds stress drives the radially sheared axial mean flow. The turbulent drive (Reynolds power) for the azimuthal flow is an order of magnitude greater than that for axial flow, suggesting that the turbulence fluctuation levels are set by azimuthal flow shear regulation. The direct energy exchange between axial and azimuthal mean flows is shown to be insignificant. Therefore, the axial flow is parasitic to the turbulence-zonal flow system and is driven primarily by the axial turbulent stress generated by that system. The non-diffusive, residual part of the axial Reynolds stress is found to be proportional to the density gradient and is formed due to dynamical asymmetry in the drift-wave turbulence.
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2015-01-01
Atropine, a muscarinic antagonist, is known to inhibit myopia progression in several animal models and humans. However, the mode of action is not established yet. In this study, we compared quantitative iTRAQ proteomic analysis in the retinas collected from control and lens-induced myopic (LIM) mouse eyes treated with atropine. The myopic group received a (−15D) spectacle lens over the right eye on postnatal day 10 with or without atropine eye drops starting on postnatal day 24. Axial length was measured by optical low coherence interferometry (OLCI), AC-Master, and refraction was measured by automated infrared photorefractor at postnatal 24, 38, and 52 days. Retinal tissue samples were pooled from six eyes for each group. The experiments were repeated twice, and technical replicates were also performed for liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. MetaCore was used to perform protein profiling for pathway analysis. We identified a total of 3882 unique proteins with <1% FDR by analyzing the samples in replicates for two independent experiments. This is the largest number of mouse retina proteome reported to date. Thirty proteins were found to be up-regulated (ratio for myopia/control > global mean ratio + 1 standard deviation), and 28 proteins were down-regulated (ratio for myopia/control < global mean ratio - 1 standard deviation) in myopic eyes as compared with control retinas. Pathway analysis using MetaCore revealed regulation of γ-aminobutyric acid (GABA) levels in the myopic eyes. Detailed analysis of the quantitative proteomics data showed that the levels of GABA transporter 1 (GAT-1) were elevated in myopic retina and significantly reduced after atropine treatment. These results were further validated with immunohistochemistry and Western blot analysis. In conclusion, this study provides a comprehensive quantitative proteomic analysis of atropine-treated mouse retina and suggests the involvement of GABAergic signaling in the antimyopic effects of atropine in mouse eyes. The GABAergic transmission in the neural retina plays a pivotal role in the maintenance of axial eye growth in mammals. PMID:25211393
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NASA Astrophysics Data System (ADS)
Staier, Florian; Eipel, Heinz; Matula, Petr; Evsikov, Alexei V.; Kozubek, Michal; Cremer, Christoph; Hausmann, Michael
2011-09-01
With the development of novel fluorescence techniques, high resolution light microscopy has become a challenging technique for investigations of the three-dimensional (3D) micro-cosmos in cells and sub-cellular components. So far, all fluorescence microscopes applied for 3D imaging in biosciences show a spatially anisotropic point spread function resulting in an anisotropic optical resolution or point localization precision. To overcome this shortcoming, micro axial tomography was suggested which allows object tilting on the microscopic stage and leads to an improvement in localization precision and spatial resolution. Here, we present a miniaturized device which can be implemented in a motor driven microscope stage. The footprint of this device corresponds to a standard microscope slide. A special glass fiber can manually be adjusted in the object space of the microscope lens. A stepwise fiber rotation can be controlled by a miniaturized stepping motor incorporated into the device. By means of a special mounting device, test particles were fixed onto glass fibers, optically localized with high precision, and automatically rotated to obtain views from different perspective angles under which distances of corresponding pairs of objects were determined. From these angle dependent distance values, the real 3D distance was calculated with a precision in the ten nanometer range (corresponding here to an optical resolution of 10-30 nm) using standard microscopic equipment. As a proof of concept, the spindle apparatus of a mature mouse oocyte was imaged during metaphase II meiotic arrest under different perspectives. Only very few images registered under different rotation angles are sufficient for full 3D reconstruction. The results indicate the principal advantage of the micro axial tomography approach for many microscopic setups therein and also those of improved resolutions as obtained by high precision localization determination.
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Hmx1 is required for the normal development of somatosensory neurons in the geniculate ganglion
Quina, Lely A.; Tempest, Lynne; Hsu, Yun-Wei A.; Cox, Timothy C.; Turner, Eric E.
2012-01-01
Hmx1 is a variant homeodomain transcription factor expressed in the developing sensory nervous system, retina, and craniofacial mesenchyme. Recently, mutations at the Hmx1 locus have been linked to craniofacial defects in humans, rats, and mice, but its role in nervous system development is largely unknown. Here we show that Hmx1 is expressed in a subset of sensory neurons in the cranial and dorsal root ganglia which does not correspond to any specific sensory modality. Sensory neurons in the dorsal root and trigeminal ganglia of Hmx1dm/dm mouse embryos have no detectable Hmx1 protein, yet they undergo neurogenesis and express sensory subtype markers normally, demonstrating that Hmx1 is not globally required for the specification of sensory neurons from neural crest precursors. Loss of Hmx1 expression has no obvious effect on the early development of the trigeminal (V), superior (IX/X), or dorsal root ganglia neurons in which it is expressed, but results in marked defects in the geniculate (VII) ganglion. Hmx1dm/dm mouse embryos possess only a vestigial posterior auricular nerve, and general somatosensory neurons in the geniculate ganglion are greatly reduced by mid-gestation. Although Hmx1 is expressed in geniculate neurons prior to cell cycle exit, it does not appear to be required for neurogenesis, and the loss of geniculate neurons is likely to be the result of increased cell death. Fate mapping of neural crest-derived tissues indicates that Hmx1-expressing somatosensory neurons at different axial levels may be derived from either the neural crest or the neurogenic placodes. PMID:22586713
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Pure optical photoacoustic microscopy
Xie, Zhixing; Chen, Sung-Liang; Ling, Tao; Guo, L. Jay; Carson, Paul L.; Wang, Xueding
2011-01-01
The concept of pure optical photoacoustic microscopy(POPAM) was proposed based on optical rastering of a focused excitation beam and optically sensing the photoacoustic signal using a microring resonator fabricated by a nanoimprinting technique. After the refinements of the microring’s working wavelength and in the resonator structure and mold fabrication, an ultrahigh Q factor of 3.0×105 was achieved which provided high sensitivity with a noise equivalent detectable pressure(NEDP) value of 29Pa. This NEDP is much lower than the hundreds of Pascals achieved with existing optical resonant structures such as etalons, fiber gratings and dielectric multilayer interference filters available for acoustic measurement. The featured high sensitivity allowed the microring resonator to detect the weak photoacoustic signals from micro- or submicroscale objects. The inherent superbroad bandwidth of the optical microring resonator combined with an optically focused scanning beam provided POPAM with high resolution in the axial as well as both lateral directions while the axial resolution of conventional photoacoustic microscopy (PAM) suffers from the limited bandwidth of PZT detectors. Furthermore, the broadband microring resonator showed similar sensitivity to that of our most sensitive PZT detector. The current POPAM system provides a lateral resolution of 5 μm and an axial resolution of 8 μm, comparable to that achieved by optical microscopy while presenting the unique contrast of optical absorption and functional information complementing other optical modalities. The 3D structure of microvasculature, including capillary networks, and even individual red blood cells have been discerned successfully in the proof-of-concept experiments on mouse bladders ex vivo and mouse ears in vivo. The potential of approximately GHz bandwidth of the microring resonator also might allow much higher resolution than shown here in microscopy of optical absorption and acoustic propagation properties at depths in unfrozen tissue specimens or thicker tissue sections, which is not now imageable with current optical or acoustic microscopes of comparable resolution. PMID:21643156
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Johanson, Zerina; Boisvert, Catherine; Maksimenko, Anton; Currie, Peter; Trinajstic, Kate
2015-01-01
The synarcual is a structure incorporating multiple elements of two or more anterior vertebrae of the axial skeleton, forming immediately posterior to the cranium. It has been convergently acquired in the fossil group 'Placodermi', in Chondrichthyes (Holocephali, Batoidea), within the teleost group Syngnathiformes, and to varying degrees in a range of mammalian taxa. In addition, cervical vertebral fusion presents as an abnormal pathology in a variety of human disorders. Vertebrae develop from axially arranged somites, so that fusion could result from a failure of somite segmentation early in development, or from later heterotopic development of intervertebral bone or cartilage. Examination of early developmental stages indicates that in the Batoidea and the 'Placodermi', individual vertebrae developed normally and only later become incorporated into the synarcual, implying regular somite segmentation and vertebral development. Here we show that in the holocephalan Callorhinchus milii, uniform and regular vertebral segmentation also occurs, with anterior individual vertebra developing separately with subsequent fusion into a synarcual. Vertebral elements forming directly behind the synarcual continue to be incorporated into the synarcual through growth. This appears to be a common pattern through the Vertebrata. Research into human disorders, presenting as cervical fusion at birth, focuses on gene misexpression studies in humans and other mammals such as the mouse. However, in chondrichthyans, vertebral fusion represents the normal morphology, moreover, taxa such Leucoraja (Batoidea) and Callorhinchus (Holocephali) are increasingly used as laboratory animals, and the Callorhinchus genome has been sequenced and is available for study. Our observations on synarcual development in three major groups of early jawed vertebrates indicate that fusion involves heterotopic cartilage and perichondral bone/mineralised cartilage developing outside the regular skeleton. We suggest that chondrichthyans have potential as ideal extant models for identifying the genes involved in these processes, for application to human skeletal heterotopic disorders.
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Johanson, Zerina; Boisvert, Catherine; Maksimenko, Anton; Currie, Peter; Trinajstic, Kate
2015-01-01
The synarcual is a structure incorporating multiple elements of two or more anterior vertebrae of the axial skeleton, forming immediately posterior to the cranium. It has been convergently acquired in the fossil group ‘Placodermi’, in Chondrichthyes (Holocephali, Batoidea), within the teleost group Syngnathiformes, and to varying degrees in a range of mammalian taxa. In addition, cervical vertebral fusion presents as an abnormal pathology in a variety of human disorders. Vertebrae develop from axially arranged somites, so that fusion could result from a failure of somite segmentation early in development, or from later heterotopic development of intervertebral bone or cartilage. Examination of early developmental stages indicates that in the Batoidea and the ‘Placodermi’, individual vertebrae developed normally and only later become incorporated into the synarcual, implying regular somite segmentation and vertebral development. Here we show that in the holocephalan Callorhinchus milii, uniform and regular vertebral segmentation also occurs, with anterior individual vertebra developing separately with subsequent fusion into a synarcual. Vertebral elements forming directly behind the synarcual continue to be incorporated into the synarcual through growth. This appears to be a common pattern through the Vertebrata. Research into human disorders, presenting as cervical fusion at birth, focuses on gene misexpression studies in humans and other mammals such as the mouse. However, in chondrichthyans, vertebral fusion represents the normal morphology, moreover, taxa such Leucoraja (Batoidea) and Callorhinchus (Holocephali) are increasingly used as laboratory animals, and the Callorhinchus genome has been sequenced and is available for study. Our observations on synarcual development in three major groups of early jawed vertebrates indicate that fusion involves heterotopic cartilage and perichondral bone/mineralised cartilage developing outside the regular skeleton. We suggest that chondrichthyans have potential as ideal extant models for identifying the genes involved in these processes, for application to human skeletal heterotopic disorders. PMID:26339918
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NASA Astrophysics Data System (ADS)
Li, Yinbo; Yang, Zequan; French, Brent A.; Hossack, John A.
2005-04-01
An intact mouse model of surgically-induced myocardial infarction (MI) caused by permanent occlusion of the Left Anterior Descending (LAD) coronary artery was studied. Normal mice with no occlusion were also studied as controls. For each mouse, contrast enhanced ultrasound images of the heart were acquired in parallel cross-sections perpendicular to the sternum at millimeter increments. For accurate 3D reconstruction, ECG gating and a tri-axial adjustable micromanipulator were used for temporal and spatial registration. Ultrasound images at steady-state of blood refilling were color-coded in each slice to show relative perfusion. Myocardial perfusion defects and necrosis were also examined postmortem by staining with Phthalo blue and TTC red dyes. Good correlation (R>0.93) in perfused area size was observed between in vivo measurements and histological staining. A 3D multi-slice model and a 3D rendering of perfusion distribution were created and showed a promising match with postmortem results, lending further credence to its use as a more comprehensive and more reliable tool for in vivo assessment of myocardial perfusion than 2D tomographic analysis.
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Mean-line Modeling of an Axial Turbine
NASA Astrophysics Data System (ADS)
Tkachenko, A. Yu; Ostapyuk, Ya A.; Filinov, E. P.
2018-01-01
The article describes the approach for axial turbine modeling along the mean line. It bases on the developed model of an axial turbine blade row. This model is suitable for both nozzle vanes and rotor blades simulations. Consequently, it allows the simulation of the single axial turbine stage as well as a multistage turbine. The turbine stage model can take into account the cooling air flow before and after a throat of each blade row, outlet straightener vanes existence and stagger angle controlling of nozzle vanes. The axial turbine estimation method includes the loss estimation and thermogasdynamic analysis. The single stage axial turbine was calculated with the developed model. The obtained results deviation was within 3% when comparing with the results of CFD modeling.
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Development and Testing of an Axial Halbach Magnetic Bearing
NASA Technical Reports Server (NTRS)
Eichenberg, Dennis J.; Gallo, Christopher A.; Thompson, William K.
2006-01-01
The NASA Glenn Research Center has developed and tested a revolutionary Axial Halbach Magnetic Bearing. The objective of this work is to develop a viable non-contact magnetic thrust bearing utilizing Halbach arrays for all-electric flight, and many other applications. This concept will help to reduce harmful emissions, reduce the Nation s dependence on fossil fuels and mitigate many of the concerns and limitations encountered in conventional axial bearings such as bearing wear, leaks, seals and friction loss. The Axial Halbach Magnetic Bearing is inherently stable and requires no active feedback control system or superconductivity as required in many magnetic bearing designs. The Axial Halbach Magnetic Bearing is useful for very high speed applications including turbines, instrumentation, medical systems, computer memory systems, and space power systems such as flywheels. Magnetic fields suspend and support a rotor assembly within a stator. Advanced technologies developed for particle accelerators, and currently under development for maglev trains and rocket launchers, served as the basis for this application. Experimental hardware was successfully designed and developed to validate the basic principles and analyses. The report concludes that the implementation of Axial Halbach Magnetic Bearings can provide significant improvements in rotational system performance and reliability.
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Mechanical loading, damping, and load-driven bone formation in mouse tibiae.
Dodge, Todd; Wanis, Mina; Ayoub, Ramez; Zhao, Liming; Watts, Nelson B; Bhattacharya, Amit; Akkus, Ozan; Robling, Alexander; Yokota, Hiroki
2012-10-01
Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone's compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality. Copyright © 2012 Elsevier Inc. All rights reserved.
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A small animal PET based on GAPDs and charge signal transmission approach for hybrid PET-MR imaging
NASA Astrophysics Data System (ADS)
Kang, Jihoon; Choi, Yong; Hong, Key Jo; Hu, Wei; Jung, Jin Ho; Huh, Yoonsuk; Kim, Byung-Tae
2011-08-01
Positron emission tomography (PET) employing Geiger-mode avalanche photodiodes (GAPDs) and charge signal transmission approach was developed for small animal imaging. Animal PET contained 16 LYSO and GAPD detector modules that were arranged in a 70 mm diameter ring with an axial field of view of 13 mm. The GAPDs charge output signals were transmitted to a preamplifier located remotely using 300 cm flexible flat cables. The position decoder circuits (PDCs) were used to multiplex the PET signals from 256 to 4 channels. The outputs of the PDCs were digitized and further-processed in the data acquisition unit. The cross-compatibilities of the PET detectors and MRI were assessed outside and inside the MRI. Experimental studies of the developed full ring PET were performed to examine the spatial resolution and sensitivity. Phantom and mouse images were acquired to examine the imaging performance. The mean energy and time resolution of the PET detector were 17.6% and 1.5 ns, respectively. No obvious degradation on PET and MRI was observed during simultaneous PET-MRI data acquisition. The measured spatial resolution and sensitivity at the CFOV were 2.8 mm and 0.7%, respectively. In addition, a 3 mm diameter line source was clearly resolved in the hot-sphere phantom images. The reconstructed transaxial PET images of the mouse brain and tumor displaying the glucose metabolism patterns were imaged well. These results demonstrate GAPD and the charge signal transmission approach can allow the development of high performance small animal PET with improved MR compatibility.
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Cell tracing reveals a dorsoventral lineage restriction plane in the mouse limb bud mesenchyme.
Arques, Carlos G; Doohan, Roisin; Sharpe, James; Torres, Miguel
2007-10-01
Regionalization of embryonic fields into independent units of growth and patterning is a widespread strategy during metazoan development. Compartments represent a particular instance of this regionalization, in which unit coherence is maintained by cell lineage restriction between adjacent regions. Lineage compartments have been described during insect and vertebrate development. Two common characteristics of the compartments described so far are their occurrence in epithelial structures and the presence of signaling regions at compartment borders. Whereas Drosophila compartmental organization represents a background subdivision of embryonic fields that is not necessarily related to anatomical structures, vertebrate compartment borders described thus far coincide with, or anticipate, anatomical or cell-type discontinuities. Here, we describe a general method for clonal analysis in the mouse and use it to determine the topology of clone distribution along the three limb axes. We identify a lineage restriction boundary at the limb mesenchyme dorsoventral border that is unrelated to any anatomical discontinuity, and whose lineage restriction border is not obviously associated with any signaling center. This restriction is the first example in vertebrates of a mechanism of primordium subdivision unrelated to anatomical boundaries. Furthermore, this is the first lineage compartment described within a mesenchymal structure in any organism, suggesting that lineage restrictions are fundamental not only for epithelial structures, but also for mesenchymal field patterning. No lineage compartmentalization was found along the proximodistal or anteroposterior axes, indicating that patterning along these axes does not involve restriction of cell dispersion at specific axial positions.
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Rainger, Joe; van Beusekom, Ellen; Ramsay, Jacqueline K.; McKie, Lisa; Al-Gazali, Lihadh; Pallotta, Rosanna; Saponari, Anita; Branney, Peter; Fisher, Malcolm; Morrison, Harris; Bicknell, Louise; Gautier, Philippe; Perry, Paul; Sokhi, Kishan; Sexton, David; Bardakjian, Tanya M.; Schneider, Adele S.; Elcioglu, Nursel; Ozkinay, Ferda; Koenig, Rainer; Mégarbané, Andre; Semerci, C. Nur; Khan, Ayesha; Zafar, Saemah; Hennekam, Raoul; Sousa, Sérgio B.; Ramos, Lina; Garavelli, Livia; Furga, Andrea Superti; Wischmeijer, Anita; Jackson, Ian J.; Gillessen-Kaesbach, Gabriele; Brunner, Han G.; Wieczorek, Dagmar; van Bokhoven, Hans; FitzPatrick, David R.
2011-01-01
Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice. PMID:21750680
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Rainger, Joe; van Beusekom, Ellen; Ramsay, Jacqueline K; McKie, Lisa; Al-Gazali, Lihadh; Pallotta, Rosanna; Saponari, Anita; Branney, Peter; Fisher, Malcolm; Morrison, Harris; Bicknell, Louise; Gautier, Philippe; Perry, Paul; Sokhi, Kishan; Sexton, David; Bardakjian, Tanya M; Schneider, Adele S; Elcioglu, Nursel; Ozkinay, Ferda; Koenig, Rainer; Mégarbané, Andre; Semerci, C Nur; Khan, Ayesha; Zafar, Saemah; Hennekam, Raoul; Sousa, Sérgio B; Ramos, Lina; Garavelli, Livia; Furga, Andrea Superti; Wischmeijer, Anita; Jackson, Ian J; Gillessen-Kaesbach, Gabriele; Brunner, Han G; Wieczorek, Dagmar; van Bokhoven, Hans; Fitzpatrick, David R
2011-07-01
Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1(tm1a)) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1(tm1a/tm1a)). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1(tm1a/tm1a) embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice.
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2011-07-01
and lower surfaces by two steel plates. To represent an infinite MT, a 2 nm long model is constructed with symmetric boundary conditions on each...are 2 nm wide. The AFM tip with a radius of 20 nm is loaded with a distributed loading on the top surface. The base of the bottom steel plate is...constrained rigidly in all directions, again to replicate the AFM experiments. It should be noted that the axial faces have symmetric boundary
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Design of a handheld optical coherence microscopy endoscope
NASA Astrophysics Data System (ADS)
Korde, Vrushali R.; Liebmann, Erica; Barton, Jennifer K.
2011-06-01
Optical coherence microscopy (OCM) combines coherence gating, high numerical aperture optics, and a fiber-core pinhole to provide high axial and lateral resolution with relatively large depth of imaging. We present a handheld rigid OCM endoscope designed for small animal surgical imaging, with a 6-mm diam tip, 1-mm scan width, and 1-mm imaging depth. X-Y scanning is performed distally with mirrors mounted to micro galvonometer scanners incorporated into the endoscope handle. The endoscope optical design consists of scanning doublets, an afocal Hopkins relay lens system, a 0.4 numerical aperture water immersion objective, and a cover glass. This endoscope can resolve laterally a 1.4-μm line pair feature and has an axial resolution (full width half maximum) of 5.4 μm. Images taken with this endoscope of fresh ex-vivo mouse ovaries show structural features, such as corpus luteum, primary follicles, growing follicles, and fallopian tubes. This rigid handheld OCM endoscope can be useful for a variety of minimally invasive and surgical imaging applications.
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Photopic visual input is necessary for emmetropization in mice
Tkatchenko, Tatiana V.; Shen, Yimin; Braun, Rod D.; Bawa, Gurinder; Kumar, Pradeep; Avrutsky, Ivan; Tkatchenko, Andrei V.
2013-01-01
It was recently demonstrated that refractive errors in mice stabilize around emmetropic values during early postnatal development, and that they develop experimental myopia in response to both visual form deprivation and imposed optical defocus similar to other vertebrate species. Animal studies also suggest that photopic vision plays critical role in emmetropization in diurnal species; however, it is unknown whether refractive eye development is guided by photopic vision in the mouse, which is a nocturnal species. We used an infrared mouse photorefractor and a high-resolution MRI to clarify the role of photopic visual input in refractive eye development in the mouse. Refractive eye development and form-deprivation myopia in P21-P89 C57BL/6J mice were analyzed under 12:12 h light-dark cycle, constant light and constant darkness regimens. Animals in all experimental groups were myopic at P21 (-13.2 ± 1.6 D, light-dark cycle; -12.5 ± 0.9 D, constant light; -12.5 ± 2.0 D, constant dark). The mean refractive error in the light-dark-cycle-reared animals was -0.5 ± 1.3 D at P32 and, and did not change significantly until P40 (+0.3 ± 0.6 D, P40). Animals in this group became progressively hyperopic between P40 and P89 (+2.2 ± 0.6, P67; +3.7 ± 2.0, P89). The mean refractive error in the constant-light-reared mice was -1.0 ± 0.7 D at P32 and remained stable until P89 (+0.1 ± 0.6, P40; +0.3 ± 0.6, P67; 0.0 ± 0.4, P89). Dark-reared animals exhibited highly hyperopic refractive errors at P32 (+5.2 ± 1.8) and became progressively more hyperopic with age (+8.7 ± 1.9, P40; +11.2 ± 1.4, P67). MRI analysis revealed that emmetropization in the P40-P89 constant-light-reared animals was associated with larger eyes, a longer axial length and a larger vitreous chamber compared to the light-dark-cycle-reared mice. Constant-light-reared mice also developed 4 times higher degrees of form-deprivation myopia on average compared to light-dark-cycle-reared animals (-12.0 ± 1.4, constant light; -2.7 ± 0.7, light-dark cycle). Dark-rearing completely prevented the development of form-deprivation myopia (-0.3 ± 0.5). Thus, photopic vision plays important role in normal refractive eye development and ocular response to visual form deprivation in the mouse. PMID:23838522
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Tetrapod axial evolution and developmental constraints; Empirical underpinning by a mouse model
Woltering, Joost M.; Duboule, Denis
2015-01-01
The tetrapod vertebral column has become increasingly complex during evolution as an adaptation to a terrestrial life. At the same time, the evolution of the vertebral formula became subject to developmental constraints acting on the size of the cervical and thoraco-lumbar regions. In the course of our studies concerning the evolution of Hox gene regulation, we produced a transgenic mouse model expressing fish Hox genes, which displayed a reduced number of thoraco-lumbar vertebrae and concurrent sacral homeotic transformations. Here, we analyze this mutant stock and conclude that the ancestral, pre-tetrapodial Hox code already possessed the capacity to induce vertebrae with sacral characteristics. This suggests that alterations in the interpretation of the Hox code may have participated to the evolution of this region in tetrapods, along with potential modifications of the HOX proteins themselves. With its reduced vertebral number, this mouse stock violates a previously described developmental constraint, which applies to the thoraco-lumbar region. The resulting offset between motor neuron morphology, vertebral patterning and the relative positioning of hind limbs illustrates that the precise orchestration of the Hox-clock in parallel with other ontogenetic pathways places constraints on the evolvability of the body plan. PMID:26238020
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Se-Hee; Schmitt, Christopher E.; Woolls, Melissa J.
Highlights: ► VEGF-A signaling regulates the segregation of axial vessels. ► VEGF-A signaling is mediated by PKC and ERK in this process. ► Ectopic activation of ERK is sufficient to rescue defects in vessel segregation. -- Abstract: Segregation of two axial vessels, the dorsal aorta and caudal vein, is one of the earliest patterning events occur during development of vasculature. Despite the importance of this process and recent advances in our understanding on vascular patterning during development, molecular mechanisms that coordinate the segregation of axial vessels remain largely elusive. In this report, we find that vascular endothelial growth factor-A (Vegf-A)more » signaling regulates the segregation of dorsal aorta and axial vein during development. Inhibition of Vegf-A pathway components including ligand Vegf-A and its cognate receptor Kdrl, caused failure in segregation of axial vessels in zebrafish embryos. Similarly, chemical inhibition of Mitogen-activated protein kinase kinase (Map2k1)/Extracellular-signal-regulated kinases (Erk) and phosphatidylinositol 3-kinases (PI3 K), which are downstream effectors of Vegf-A signaling pathway, led to the fusion of two axial vessels. Moreover, we find that restoring Erk activity by over-expression of constitutively active MEK in embryos with a reduced level of Vegf-A signaling can rescue the defects in axial vessel segregation. Taken together, our data show that segregation of axial vessels requires the function of Vegf-A signaling, and Erk may function as the major downstream effector in this process.« less
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Nalbach, Stephen V; Ropper, Alexander E; Dunn, Ian F; Gormley, William B
2012-09-01
Extra-axial fluid collections following decompressive craniectomy have been observed in a variety of patient populations. These collections have traditionally been thought to represent extra-axial signs of hydrocephalus, but they often occur even in settings where hydrocephalus has been optimally treated. This study aims to elucidate the phenomenon of extra-axial fluid collections after decompressive craniectomy in patients with treated hydrocephalus, in order to improve identification, classification, prevention and treatment. We retrospectively reviewed all patients at a single institution undergoing decompressive craniectomy for refractory intracranial pressure elevations from June 2007 through December 2009. We identified 39 patients by reviewing clinical reports and imaging. Any patient who died on or prior to the third post-operative day (POD) was excluded. The analysis focused on patients with extra-axial collections and treated hydrocephalus. Twenty-one of 34 (62%) patients developed extra-axial collections and 18 of these developed collections despite ventricular drainage. Subgroup analysis revealed that seven of seven patients (100%) with subarachnoid hemorrhage, and 11 of 14 (79%) with traumatic brain injury developed collections. Extra-axial collections may develop after decompressive craniectomy despite aggressive treatment of communicating hydrocephalus. In these patients, the term "external hydrocephalus" does not appropriately capture the relevant pathophysiology. Instead, we define a new phenomenon, "Craniectomy-associated Progressive Extra-Axial Collections with Treated Hydrocephalus" (CAPECTH), as progressive collections despite aggressive cerebral spinal fluid (CSF) drainage. Our data indicate that early cranioplasty can help prevent the formation and worsening of this condition, presumably by returning normal CSF dynamics. Copyright © 2012 Elsevier Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Phillips, Kevin G.; Wang, Yun; Levitz, David; Choudhury, Niloy; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven L.
2011-04-01
Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of inflammation in psoriasis remain unclear. We undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to noninvasively document cutaneous alterations in mouse skin treated topically with Imiquimod (IMQ), an established model of a psoriasis-like disease. Quantitative appraisal of dermal architectural changes was achieved through a two parameter fit of OCT axial scans in the dermis of the form A(x, y, z) = ρ(x, y)exp [ - μ(x, y)z]. Ensemble averaging over 2000 axial scans per mouse in each treatment arm revealed no significant changes in the average dermal attenuation rate, <μ>, however the average local dermal reflectivity <ρ>, decreased significantly following 1, 3, and 6 days of IMQ treatment (p < 0.001) in comparison to vehicle-treated control mice. In contrast, epidermal and dermal thickness changes were only significant when comparing controls and 6-day IMQ treated mice. This suggests that dermal alterations, attributed to collagen fiber bundle enlargement, occur prior to epidermal thickness changes due to hyperplasia and dermal thickness changes due to edema. Dermal reflectivity positively correlated with epidermal hyperplasia (repi2 = 0.78) and dermal edema (rderm2 = 0.86). Our results suggest that dermal reflectivity as measured by OCT can be utilized to quantify a psoriasis-like disease in mice, and thus has the potential to aid in the quantitative assessment of psoriasis in humans.
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Performance evaluation of the Trans-PET®BioCaliburn® SH system
NASA Astrophysics Data System (ADS)
Zhu, Jun; Wang, Luyao; Kao, Chien-Min; Kim, Heejong; Xie, Qingguo
2015-03-01
The Trans-PET®BioCaliburn® SH system, recently introduced by the Raycan Technology Co. Ltd. (Suzhou, China), is a commercial positron emission tomography (PET) system designed for rodent imaging. The system contains 6 basic detector modules (BDMs) arranged on a 10.8 cm diameter ring to provide a transaxial field of view (FOV) of 6.5 cm and an axial FOV of 5.3 cm. In this paper, we report on its performance properties in accordance with the National Electrical Manufacturers Association (NEMA) 2008 NU-4 standards with modifications. The measured spatial resolution at the center of the FOV was 1.05 mm, 1.12 mm and 1.13 mm in the tangential, radial and axial directions, respectively. The measured system sensitivity was 3.29% for a point source at the center of the FOV when using a 350-650 keV energy window and a 5 ns coincidence time window. When a wider 250-750 keV energy window was used, it increased to 4.21%. For mouse- and rat-sized phantoms, the scatter fraction was 10.7% and 16.1%, respectively. The peak noise equivalent count rate were 36 kcps@8.52 MBq for the mouse-sized phantom and 16 kcps@6.79 MBq for the rat-sized phantom. The Derenzo phantom image showed that the system can resolve 1.0 mm diameter rods. The measured performance properties of the system indicate that the Trans-PET®BioCaliburn® SH is a versatile imaging device that can provide high spatial resolution for rodent imaging while offering competitive sensitivity and count-rate performance.
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Inverse axial mounting stiffness design for lithographic projection lenses.
Wen-quan, Yuan; Hong-bo, Shang; Wei, Zhang
2014-09-01
In order to balance axial mounting stiffness of lithographic projection lenses and the image quality under dynamic working conditions, an easy inverse axial mounting stiffness design method is developed in this article. Imaging quality deterioration at the wafer under different axial vibration levels is analyzed. The desired image quality can be determined according to practical requirements, and axial vibrational tolerance of each lens is solved with the damped least-squares method. Based on adaptive interval adjustment, a binary search algorithm, and the finite element method, the axial mounting stiffness of each lens can be traveled in a large interval, and converges to a moderate numerical solution which makes the axial vibrational amplitude of the lens converge to its axial vibrational tolerance. Model simulation is carried out to validate the effectiveness of the method.
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NASA Astrophysics Data System (ADS)
Quagliato, Luca; Berti, Guido A.
2017-10-01
In this paper, a statically determined slip-line solution algorithm is proposed for the calculation of the axial forming force in the radial-axial ring rolling process of flat rings. The developed solution is implemented in an Excel spreadsheet for the construction of the slip-line field and the calculation of the pressure factor to be used in the force model. The comparison between analytical solution and authors' FE simulation allows stating that the developed model supersedes the previous literature ones and proves the reliability of the proposed approach.
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Wnt Signaling in Form Deprivation Myopia of the Mice Retina
Ma, Mingming; Zhang, Zhengwei; Du, Ergang; Zheng, Wenjing; Gu, Qing; Xu, Xun; Ke, Bilian
2014-01-01
Background The canonical Wnt signaling pathway plays important roles in cellular proliferation and differentiation, axonal outgrowth, cellular maintenance in retinas. Here we test the hypothesis that elements of the Wnt signaling pathway are involved in the regulation of eye growth and prevention of myopia, in the mouse form-deprivation myopia model. Methodology/Principal Findings (1) One hundred twenty-five C57BL/6 mice were randomly distributed into form-deprivation myopia and control groups. Form-deprivation myopia (FDM) was induced by suturing the right eyelid, while the control group received no treatment. After 1, 2, and 4 weeks of treatment, eyes were assessed in vivo by cycloplegic retinoscopic refraction and axial length measurement by photography or A-scan ultrasonography. Levels of retinal Wnt2b, Fzd5 and β-catenin mRNA and protein were evaluated using RT-PCR and western blotting, respectively. (2) Another 96 mice were divided into three groups: control, drugs-only, and drugs+FDM (by diffuser). Experimentally treated eyes in the last two groups received intravitreal injections of vehicle or the proteins, DKK-1 (Wnt-pathway antagonist) or Norrin (Wnt-pathway agonist), once every three days, for 4 injections total. Axial length and retinoscopic refraction were measured on the 14th day of form deprivation. Following form-deprivation for 1, 2, and 4 weeks, FDM eyes had a relatively myopic refractive error, compared with contralateral eyes. There were no significant differences in refractive error between right and left eye in control group. The amounts of Wnt2b, Fzd5 and β-catenin mRNA and protein were significantly greater in form-deprived myopia eyes than in control eyes.DKK-1 (antagonist) reduced the myopic shift in refractive error and increase in axial elongation, whereas Norrin had the opposite effect in FDM eyes. Conclusions/Significance Our studies provide the first evidence that the Wnt2b signaling pathway may play a role in the development and progression of form-deprivation myopia, in a mammalian model. PMID:24755605
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Chiang, Chia-Wen; Wang, Yong; Sun, Peng; Lin, Tsen-Hsuan; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei
2014-01-01
The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA), increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice. PMID:25017446
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Wnt signaling in form deprivation myopia of the mice retina.
Ma, Mingming; Zhang, Zhengwei; Du, Ergang; Zheng, Wenjing; Gu, Qing; Xu, Xun; Ke, Bilian
2014-01-01
The canonical Wnt signaling pathway plays important roles in cellular proliferation and differentiation, axonal outgrowth, cellular maintenance in retinas. Here we test the hypothesis that elements of the Wnt signaling pathway are involved in the regulation of eye growth and prevention of myopia, in the mouse form-deprivation myopia model. (1) One hundred twenty-five C57BL/6 mice were randomly distributed into form-deprivation myopia and control groups. Form-deprivation myopia (FDM) was induced by suturing the right eyelid, while the control group received no treatment. After 1, 2, and 4 weeks of treatment, eyes were assessed in vivo by cycloplegic retinoscopic refraction and axial length measurement by photography or A-scan ultrasonography. Levels of retinal Wnt2b, Fzd5 and β-catenin mRNA and protein were evaluated using RT-PCR and western blotting, respectively. (2) Another 96 mice were divided into three groups: control, drugs-only, and drugs+FDM (by diffuser). Experimentally treated eyes in the last two groups received intravitreal injections of vehicle or the proteins, DKK-1 (Wnt-pathway antagonist) or Norrin (Wnt-pathway agonist), once every three days, for 4 injections total. Axial length and retinoscopic refraction were measured on the 14th day of form deprivation. Following form-deprivation for 1, 2, and 4 weeks, FDM eyes had a relatively myopic refractive error, compared with contralateral eyes. There were no significant differences in refractive error between right and left eye in control group. The amounts of Wnt2b, Fzd5 and β-catenin mRNA and protein were significantly greater in form-deprived myopia eyes than in control eyes.DKK-1 (antagonist) reduced the myopic shift in refractive error and increase in axial elongation, whereas Norrin had the opposite effect in FDM eyes. Our studies provide the first evidence that the Wnt2b signaling pathway may play a role in the development and progression of form-deprivation myopia, in a mammalian model.
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High-resolution raster scan optoacoustic mesoscopy of genetically modified drosophila pupae
NASA Astrophysics Data System (ADS)
Omar, Murad; Gateau, Jérôme; Ntziachristos, Vasilis
2014-03-01
Optoacoutic mesoscopy aims to bridge the gap between optoacoustic microscopy and optoacoustic tomography. We have developed a setup for optoacoustic mesoscopy where we use a high frequency, high numerical aperture spherically focused ultrasound transducer, with a wide bandwidth of 25-125 MHz. The excitation is performed using a diode laser capable of >500 μJ/pulse, 1.8ns pulse width, 1.4 kHz pulse repetition rate, at 515 nm. The system is capable to penetrate more than 5 mm with a resolution of 7 μm axially and 30 μm transversally. Using high-speed stages and scanning the transducer in a quasi-continuous mode, a field of view of 2×2 mm2 is scanned in less than 2 minutes. The system is suitable for imaging biological samples that have a diameter of 1-5 mm; zebrafish, drosophila melanogaster, and thin biological samples such as the mouse ear and mouse extremities. We have used our mesoscopic setup to generate 3- dimensional images of genetically modified drosophila fly, and drosophila pupae expressing GFP from the wings, high resolution images were generated in both cases, in the fly we can see the wings, the legs, the eyes, and the shape of the body. In the pupae the outline of the pupae, the spiracles at both ends and a strong signal corresponding to the location of the future wings are observed.
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Arbogast, Sandrine; Lainé, Jeanne; Vassilopoulos, Stéphane; Beuvin, Maud; Dubourg, Odile; Vignaud, Alban; Ferry, Arnaud; Krol, Alain; Allamand, Valérie; Guicheney, Pascale; Ferreiro, Ana; Lescure, Alain
2011-01-01
Selenium is an essential trace element and selenoprotein N (SelN) was the first selenium-containing protein shown to be directly involved in human inherited diseases. Mutations in the SEPN1 gene, encoding SelN, cause a group of muscular disorders characterized by predominant affection of axial muscles. SelN has been shown to participate in calcium and redox homeostasis, but its pathophysiological role in skeletal muscle remains largely unknown. To address SelN function in vivo, we generated a Sepn1-null mouse model by gene targeting. The Sepn1−/− mice had normal growth and lifespan, and were macroscopically indistinguishable from wild-type littermates. Only minor defects were observed in muscle morphology and contractile properties in SelN-deficient mice in basal conditions. However, when subjected to challenging physical exercise and stress conditions (forced swimming test), Sepn1−/− mice developed an obvious phenotype, characterized by limited motility and body rigidity during the swimming session, as well as a progressive curvature of the spine and predominant alteration of paravertebral muscles. This induced phenotype recapitulates the distribution of muscle involvement in patients with SEPN1-Related Myopathy, hence positioning this new animal model as a valuable tool to dissect the role of SelN in muscle function and to characterize the pathophysiological process. PMID:21858002
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Wendt, Daniel J; Dvorak-Ewell, Melita; Bullens, Sherry; Lorget, Florence; Bell, Sean M; Peng, Jeff; Castillo, Sianna; Aoyagi-Scharber, Mika; O'Neill, Charles A; Krejci, Pavel; Wilcox, William R; Rimoin, David L; Bunting, Stuart
2015-04-01
Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. Genetic overexpression of C-type natriuretic peptide (CNP), a positive regulator of endochondral bone growth, prevents dwarfism in mouse models of ACH. However, administration of exogenous CNP is compromised by its rapid clearance in vivo through receptor-mediated and proteolytic pathways. Using in vitro approaches, we developed modified variants of human CNP, resistant to proteolytic degradation by neutral endopeptidase, that retain the ability to stimulate signaling downstream of the CNP receptor, natriuretic peptide receptor B. The variants tested in vivo demonstrated significantly longer serum half-lives than native CNP. Subcutaneous administration of one of these CNP variants (BMN 111) resulted in correction of the dwarfism phenotype in a mouse model of ACH and overgrowth of the axial and appendicular skeletons in wild-type mice without observable changes in trabecular and cortical bone architecture. Moreover, significant growth plate widening that translated into accelerated bone growth, at hemodynamically tolerable doses, was observed in juvenile cynomolgus monkeys that had received daily subcutaneous administrations of BMN 111. BMN 111 was well tolerated and represents a promising new approach for treatment of patients with ACH. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
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NASA Astrophysics Data System (ADS)
Cao, Liji; Peter, Jörg
2013-06-01
The adoption of axially oriented line illumination patterns for fluorescence excitation in small animals for fluorescence surface imaging (FSI) and fluorescence optical tomography (FOT) is being investigated. A trimodal single-photon-emission-computed-tomography/computed-tomography/optical-tomography (SPECT-CT-OT) small animal imaging system is being modified for employment of point- and line-laser excitation sources. These sources can be arbitrarily positioned around the imaged object. The line source is set to illuminate the object along its entire axial direction. Comparative evaluation of point and line illumination patterns for FSI and FOT is provided involving phantom as well as mouse data. Given the trimodal setup, CT data are used to guide the optical approaches by providing boundary information. Furthermore, FOT results are also being compared to SPECT. Results show that line-laser illumination yields a larger axial field of view (FOV) in FSI mode, hence faster data acquisition, and practically acceptable FOT reconstruction throughout the whole animal. Also, superimposed SPECT and FOT data provide additional information on similarities as well as differences in the distribution and uptake of both probe types. Fused CT data enhance further the anatomical localization of the tracer distribution in vivo. The feasibility of line-laser excitation for three-dimensional fluorescence imaging and tomography is demonstrated for initiating further research, however, not with the intention to replace one by the other.
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Fisher, C.L.; Lee, I.; Bloyer, S.; Bozza, S.; Chevalier, J.; Dahl, A; Bodner, C.; Helgason, C. D.; Hess, J.L.; Humphries, R.K.; Brock, H.W.
2009-01-01
The Additional sex combs (Asx) gene of Drosophila behaves genetically as an enhancer of trithorax and Polycomb (ETP) in displaying bidirectional homeotic phenotypes, suggesting that is required for maintenance of both activation and silencing of Hox genes. There are 3 murine homologs of Asx called Additional sex combs-like1, 2, and-3. Asxl1 is required for normal adult hematopoiesis; however its embryonic function is unknown. We used a targeted mouse mutant line Asxl1tm1Bc to determine if Asxl1 is required to silence and activate Hox genes in mice during axial patterning. The mutant embryos exhibit simultaneous anterior and posterior transformations of the axial skeleton, consistent with a role for Asxl1 in activation and silencing of Hox genes. Transformations of the axial skeleton are enhanced in compound mutant embryos for the Polycomb group gene M33/Cbx2. Hox a4, a7, and c8 are derepressed in Asxl1tm1Bc mutants in the antero-posterior axis, but Hox c8 expression is reduced in the brain of mutants, consistent with Asxl1 being required both for activation and repression of Hox genes. We discuss the genetic and molecular definition of ETPs, and suggest that the function of Asxl1 depends on its cellular context. PMID:19833123
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Chiang, Mao-Hsiung
2010-01-01
This study aims to develop a X-Y dual-axial intelligent servo pneumatic-piezoelectric hybrid actuator for position control with high response, large stroke (250 mm, 200 mm) and nanometer accuracy (20 nm). In each axis, the rodless pneumatic actuator serves to position in coarse stroke and the piezoelectric actuator compensates in fine stroke. Thus, the overall control systems of the single axis become a dual-input single-output (DISO) system. Although the rodless pneumatic actuator has relatively larger friction force, it has the advantage of mechanism for multi-axial development. Thus, the X-Y dual-axial positioning system is developed based on the servo pneumatic-piezoelectric hybrid actuator. In addition, the decoupling self-organizing fuzzy sliding mode control is developed as the intelligent control strategies. Finally, the proposed novel intelligent X-Y dual-axial servo pneumatic-piezoelectric hybrid actuators are implemented and verified experimentally.
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Chiang, Mao-Hsiung
2010-01-01
This study aims to develop a X-Y dual-axial intelligent servo pneumatic-piezoelectric hybrid actuator for position control with high response, large stroke (250 mm, 200 mm) and nanometer accuracy (20 nm). In each axis, the rodless pneumatic actuator serves to position in coarse stroke and the piezoelectric actuator compensates in fine stroke. Thus, the overall control systems of the single axis become a dual-input single-output (DISO) system. Although the rodless pneumatic actuator has relatively larger friction force, it has the advantage of mechanism for multi-axial development. Thus, the X-Y dual-axial positioning system is developed based on the servo pneumatic-piezoelectric hybrid actuator. In addition, the decoupling self-organizing fuzzy sliding mode control is developed as the intelligent control strategies. Finally, the proposed novel intelligent X-Y dual-axial servo pneumatic-piezoelectric hybrid actuators are implemented and verified experimentally. PMID:22319266
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NASA Astrophysics Data System (ADS)
Canadas, Mario; Embid, Miguel; Lage, Eduardo; Desco, Manuel; Vaquero, Juan José; Perez, José Manuel
2011-02-01
In this work, we compare two commercial positron emission tomography (PET) scanners installed at CIEMAT (Madrid, Spain): the ClearPET and the rPET-1. These systems have significant geometrical differences, such as the axial field of view (110 mm on ClearPET versus 45.6 mm on rPET-1), the configuration of the detectors (whole ring on ClearPET versus one pair of planar blocks on rPET-1) and the use of an axial shift between ClearPET detector modules. We used an assessment procedure that fulfilled the recommendations of the National Electrical Manufacturers Association (NEMA) NU 4-2008 standard. The methodology includes studies of spatial resolution, sensitivity, scatter fraction, count losses and image quality. Our experiments showed a central spatial resolution of 1.5 mm (transaxial), 3.2 mm (axial) for the ClearPET and 1.5 mm (transaxial), 1.6 mm (axial) for the rPET-1, with a small variation across the transverse axis on both scanners ( 1 mm). The absolute sensitivity at the centre of the field of view was 4.7% for the ClearPET and 1.0% for the rPET-1. The peak noise equivalent counting rate for the mouse-sized phantom was 73.4 kcps reached at 0.51 MBq/mL on the ClearPET and 29.2 kcps at 1.35 MBq/mL on the rPET-1. The recovery coefficients measured using the image quality phantom ranged from 0.11 to 0.89 on the ClearPET and from 0.14 to 0.81 on the rPET-1. The overall performance shows that both the ClearPET and the rPET-1 systems are very suitable for preclinical research and imaging of small animals.
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Resolution of extra-axial collections after decompressive craniectomy for ischemic stroke.
Ropper, Alexander E; Nalbach, Stephen V; Lin, Ning; Dunn, Ian F; Gormley, William B
2012-02-01
Extra-axial fluid collections are known consequences of decompressive hemicraniectomy. Studies have examined these collections and their management. We retrospectively reviewed 12 consecutive patients who underwent decompressive hemicraniectomy for the treatment of malignant cerebral edema after infarction and evaluated the evolution, resolution and treatment of post-operative extra-axial fluid collections. All patients underwent standard-sized frontotemporoparietal hemicraniectomy with duraplasty as treatment for medically intractable malignant cerebral edema at an average of 3 days after the stroke (median 2 days). Their 30-day mortality was 25%. Three patients developed some extra-axial fluid collections after craniectomy: two patients developed the collections early in their post-operative course, 3 days and 5 days after the craniectomy. Both experienced spontaneous resolution of the collections without corrective cranioplasty or shunt placement at 34 days and 58 days after surgery. The third patient developed a collection 55 days after the operation related to a subgaleal bacterial infection. In the final analysis, 18% of patients developed extra-axial collections and all resolved spontaneously. The incidence of extra-axial collections after decompressive hemicraniectomy following ischemic stroke was lower in our retrospective series than has been reported by others. The collections resolved spontaneously, suggesting that early anticipatory, corrective treatment with cerebrospinal fluid diversion or cranioplasty may not be warranted. Copyright © 2011 Elsevier Ltd. All rights reserved.
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1990-12-17
were measured with LVDT’s mounted on rings encircling the sample. Axial force was generated from an amplified D/A sinusoidal voltage and up to 1000...19 inch rack mount or stand-alone, 7.0 inches high 10 Mbit Ethernet With on-board Transceiver 1.5 Mb/Sec Asynchronous SCSI Bus UNIX and C right to...use license HA RD WARE 4 or 12 MByte Expansion Memory Boards Monochrome or Color Video, Monitor, Keyboard, and Mouse 19-inch Rack- Mount Removable Disk
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Phototropic growth in a reef flat acroporid branching coral species.
Kaniewska, Paulina; Campbell, Paul R; Fine, Maoz; Hoegh-Guldberg, Ove
2009-03-01
Many terrestrial plants form complex morphological structures and will alter these growth patterns in response to light direction. Similarly reef building corals have high morphological variation across coral families, with many species also displaying phenotypic plasticity across environmental gradients. In particular, the colony geometry in branching corals is altered by the frequency, location and direction of branch initiation and growth. This study demonstrates that for the branching species Acropora pulchra, light plays a key role in axial polyp differentiation and therefore axial corallite development--the basis for new branch formation. A. pulchra branches exhibited a directional growth response, with axial corallites only developing when light was available, and towards the incident light. Field experimentation revealed that there was a light intensity threshold of 45 micromol m(-2) s(-1), below which axial corallites would not develop and this response was blue light (408-508 nm) dependent. There was a twofold increase in axial corallite growth above this light intensity threshold and a fourfold increase in axial corallite growth under the blue light treatment. These features of coral branch growth are highly reminiscent of the initiation of phototropic branch growth in terrestrial plants, which is directed by the blue light component of sunlight.
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Organizer formation in Hydra is disrupted by thalidomide treatment.
Brooun, Maria; Manoukian, Armen; Shimizu, Hiroshi; Bode, Hans R; McNeill, Helen
2013-06-01
Thalidomide is a drug that is well known for its teratogenic properties in humans. Surprisingly, thalidomide does not have teratogenic effects on mouse development. We investigated the effect of thalidomide on patterning in hydra, an early metazoan with a very simple axial symmetry. Hydra develops asexually via Wnt-dependent organizer formation, leading to the budding of a new organism. We observe both induction and inhibition of organizer formation depending on cellular context. Interestingly, thalidomide treatment altered budding and the developing organizer, but had little effect on the adult. Expression of Hybra1, a marker of the organizer increased upon thalidomide treatment. However when the organizer is induced by ectopic activation of Wnt signaling via GSK3 inhibition, thalidomide suppresses induction. We show that inhibition of Wnt signaling is not mediated by induction of the BMP pathway. We show that thalidomide activity on organizer formation in hydra depends on the activity of casein kinase1 and the abundance of β-catenin. Finally, we find that interstitial cells, multipotent cells which give rise to nemoatocytes, neural, digestive and germline cells, are partially responsible for the inhibitory effect of thalidomide. Copyright © 2013 Elsevier Inc. All rights reserved.
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Validation of a Monte Carlo simulation of the Inveon PET scanner using GATE
NASA Astrophysics Data System (ADS)
Lu, Lijun; Zhang, Houjin; Bian, Zhaoying; Ma, Jianhua; Feng, Qiangjin; Chen, Wufan
2016-08-01
The purpose of this study is to validate the application of GATE (Geant4 Application for Tomographic Emission) Monte Carlo simulation toolkit in order to model the performance characteristics of Siemens Inveon small animal PET system. The simulation results were validated against experimental/published data in accordance with the NEMA NU-4 2008 protocol for standardized evaluation of spatial resolution, sensitivity, scatter fraction (SF) and noise equivalent counting rate (NECR) of a preclinical PET system. An agreement of less than 18% was obtained between the radial, tangential and axial spatial resolutions of the simulated and experimental results. The simulated peak NECR of mouse-size phantom agreed with the experimental result, while for the rat-size phantom simulated value was higher than experimental result. The simulated and experimental SFs of mouse- and rat- size phantom both reached an agreement of less than 2%. It has been shown the feasibility of our GATE model to accurately simulate, within certain limits, all major performance characteristics of Inveon PET system.
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Axial Halbach Magnetic Bearings
NASA Technical Reports Server (NTRS)
Eichenberg, Dennis J.; Gallo, Christopher A.; Thompson, William K.
2008-01-01
Axial Halbach magnetic bearings have been investigated as part of an effort to develop increasingly reliable noncontact bearings for future high-speed rotary machines that may be used in such applications as aircraft, industrial, and land-vehicle power systems and in some medical and scientific instrumentation systems. Axial Halbach magnetic bearings are passive in the sense that unlike most other magnetic bearings that have been developed in recent years, they effect stable magnetic levitation without need for complex active control.
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Axial length and proliferative diabetic retinopathy.
Yang, Ko-Jen; Sun, Chi-Chin; Ku, Wan-Chen; Chuang, Lan-Hsin; Ng, Soh Ching; Chou, Kuei-Mei; Kuo, Sheng-Fong; Yeung, Ling
2012-04-01
To determine the correlation between axial length and diabetic retinopathy (DR) in patients with diabetes mellitus for 10 years or more. This study was a prospective, observational, cross-sectional study. Patients with diabetes for 10 years or more were included. We excluded eyes with any other significant ocular disease or any prior intraocular surgery, except uncomplicated cataract surgery. Only one eye of each patient was included as the study eye. The severity of DR was graded as no DR, non-proliferative DR (NPDR), or proliferative DR (PDR). Axial length was measured by A-scan ultrasound (10 MHz Transducer, AL-2000 Biometer/Pachymeter; Tomey, Phoenix, AZ). Univariate logistic regression models were used to evaluate the relationship between the dependent variables (any DR, PDR) and all potential risk factors. Axial length and other factors with p value <0.1 were included in multivariate logistic regression models. Backward selection based on the likelihood ratio statistic was used to select the final models. We included 166 eyes from 166 patients (93 female and 73 male; mean age, 68.8 years). The mean diabetes duration was 15.4 years. Fifty-four (32.5%) eyes had no DR, 72 (43.4%) eyes had NPDR, and 40 (24.1%) eyes had PDR. In univariate analysis, hypertension (p = 0.009), renal impairment (p = 0.079), and insulin use (p = 0.009) were associated with developing any DR. Hypertension (p = 0.042), renal impairment (p = 0.014), insulin use (p = 0.040), pseudophakia (p = 0.019), and axial length (p = 0.076) were associated with developing PDR. In multivariate analysis, hypertension (p = 0.005) and insulin use (p = 0.010) were associated with developing any DR. Hypertension (p = 0.020), renal impairment (p = 0.025), pseudophakia (p = 0.006), and axial length (p = 0.024) were associated with developing PDR. This observational study suggests an inverse relationship between axial length and the development of PDR in patients with diabetes for 10 years or more. No relationship was found between axial length and the development of any DR.
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Ultrahigh resolution optical coherence elastography using a Bessel beam for extended depth of field
NASA Astrophysics Data System (ADS)
Curatolo, Andrea; Villiger, Martin; Lorenser, Dirk; Wijesinghe, Philip; Fritz, Alexander; Kennedy, Brendan F.; Sampson, David D.
2016-03-01
Visualizing stiffness within the local tissue environment at the cellular and sub-cellular level promises to provide insight into the genesis and progression of disease. In this paper, we propose ultrahigh-resolution optical coherence elastography, and demonstrate three-dimensional imaging of local axial strain of tissues undergoing compressive loading. The technique employs a dual-arm extended focus optical coherence microscope to measure tissue displacement under compression. The system uses a broad bandwidth supercontinuum source for ultrahigh axial resolution, Bessel beam illumination and Gaussian beam detection, maintaining sub-2 μm transverse resolution over nearly 100 μm depth of field, and spectral-domain detection allowing high displacement sensitivity. The system produces strain elastograms with a record resolution (x,y,z) of 2×2×15 μm. We benchmark the advances in terms of resolution and strain sensitivity by imaging a suitable inclusion phantom. We also demonstrate this performance on freshly excised mouse aorta and reveal the mechanical heterogeneity of vascular smooth muscle cells and elastin sheets, otherwise unresolved in a typical, lower resolution optical coherence elastography system.
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NASA Astrophysics Data System (ADS)
He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi
2016-07-01
Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.
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NASA Astrophysics Data System (ADS)
Qin, Wei; Qi, Weizhi; Jin, Tian; Guo, Heng; Xi, Lei
2017-12-01
Oral diseases, especially oral cancers, are becoming serious health problems in humans. To image vasculatures and structures simultaneously in the human oral cavity which are tightly associated with various oral diseases, we develop a dual-modality portable optical resolution photoacoustic microscopy (ORPAM) and optical coherence tomography (OCT) system. This system utilizes a new rotary scanning mechanism and a compact design of the imaging head, making it portable and free of translation of the imaging interface or samples. Through the phantom experiments, both modalities yield high lateral resolutions of 8.1 μm (ORPAM) and 8.56 μm (OCT), respectively. The axial resolutions are measured to be 116.5 μm for ORPAM and 6.1 μm for OCT. In vivo imaging of a mouse ear was carried out to evaluate the performance of the system in biological tissues. In addition, in vivo oral imaging of a healthy human lip and monitoring recovery progress of a lip ulcer demonstrate the clinical potential of this system.
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Canny edge-based deformable image registration
NASA Astrophysics Data System (ADS)
Kearney, Vasant; Huang, Yihui; Mao, Weihua; Yuan, Baohong; Tang, Liping
2017-02-01
This work focuses on developing a 2D Canny edge-based deformable image registration (Canny DIR) algorithm to register in vivo white light images taken at various time points. This method uses a sparse interpolation deformation algorithm to sparsely register regions of the image with strong edge information. A stability criterion is enforced which removes regions of edges that do not deform in a smooth uniform manner. Using a synthetic mouse surface ground truth model, the accuracy of the Canny DIR algorithm was evaluated under axial rotation in the presence of deformation. The accuracy was also tested using fluorescent dye injections, which were then used for gamma analysis to establish a second ground truth. The results indicate that the Canny DIR algorithm performs better than rigid registration, intensity corrected Demons, and distinctive features for all evaluation matrices and ground truth scenarios. In conclusion Canny DIR performs well in the presence of the unique lighting and shading variations associated with white-light-based image registration.
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Tetrapod axial evolution and developmental constraints; Empirical underpinning by a mouse model.
Woltering, Joost M; Duboule, Denis
2015-11-01
The tetrapod vertebral column has become increasingly complex during evolution as an adaptation to a terrestrial life. At the same time, the evolution of the vertebral formula became subject to developmental constraints acting on the size of the cervical and thoraco-lumbar regions. In the course of our studies concerning the evolution of Hox gene regulation, we produced a transgenic mouse model expressing fish Hox genes, which displayed a reduced number of thoraco-lumbar vertebrae and concurrent sacral homeotic transformations. Here, we analyze this mutant stock and conclude that the ancestral, pre-tetrapodial Hox code already possessed the capacity to induce vertebrae with sacral characteristics. This suggests that alterations in the interpretation of the Hox code may have participated to the evolution of this region in tetrapods, along with potential modifications of the HOX proteins themselves. With its reduced vertebral number, this mouse stock violates a previously described developmental constraint, which applies to the thoraco-lumbar region. The resulting offset between motor neuron morphology, vertebral patterning and the relative positioning of hind limbs illustrates that the precise orchestration of the Hox-clock in parallel with other ontogenetic pathways places constraints on the evolvability of the body plan. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
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NASA Astrophysics Data System (ADS)
Roy, Sthitadhi; Kolodrubetz, Michael; Goldman, Nathan; Grushin, Adolfo G.
2018-04-01
In this work, we describe a toolbox to realize and probe synthetic axial gauge fields in engineered Weyl semimetals. These synthetic electromagnetic fields, which are sensitive to the chirality associated with Weyl nodes, emerge due to spatially and temporally dependent shifts of the corresponding Weyl momenta. First, we introduce two realistic models, inspired by recent cold-atom developments, which are particularly suitable for the exploration of these synthetic axial gauge fields. Second, we describe how to realize and measure the effects of such axial fields through center-of-mass observables, based on semiclassical equations of motion and exact numerical simulations. In particular, we suggest realistic protocols to reveal an axial Hall response due to the axial electric field \
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Huang, Chung-Ying; Hou, Chiun-Ho; Lin, Ken-Kuo; Lee, Jiahn-Shing; Yang, Meng-Ling
2014-08-01
The development of myopia and growth of the eye, occur at a time when body stature is increasing. To investigate the relationship of lifestyle and body growth with axial elongation and myopia development among schoolchildren aged 7 to 9 years. Prospective study. Children in elementary schools without serious eye disorders were invited to participate. We measured cycloplegic refraction, corneal curvature, intraocular pressure, axial length, body height, and weight. Questionnaires about the children's daily lifestyles, family members' myopia and parents' socio-demographic status were completed. The children were followed up every 6 months in a 3-year period. Bivariate correlations, simple and multiple regression. Eighty-eight children participated in this study. Forty-eight were myopic at the beginning of the study, and their myopia correlated with longer axial length and parental myopia (P = 0.015, 0.012). Sixty-five children (74%) completed the study, and the rates of change per year were -0.43 ± 0.58 (mean + standard deviation) diopters in spherical equivalence, 0.32 ± 0.25 mm in axial length (AL), 5.73 ± 2.71 cm in body height, and 3.84 ± 2.23 kg in weight. The axial length change was positively correlated with the height change (P < 0.001). The myopia shift was correlated to axial length change (P = 0.000) but not correlated to height change. Using multiple regression test, near work was the only significant risk factor for myopia progression (P = 0.022). Our study showed that body height increment was correlated to axial length elongation but not to myopia shift in children aged 7-9 years. Genetic factors such as parental myopia and body height had a possible influence on myopia development, and the environment factor as near work intensity was related to myopia progression.
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The Relation Between Plate Spreading Rate, Crustal Thickness and Axial Relief at Mid-Ocean Ridges
NASA Astrophysics Data System (ADS)
Liu, Z.; Buck, W. R.
2017-12-01
Variations in axial valley relief and in faulting at plate spreading centers are clearly related to magma supply and axial lithospheric structure. Previous models that consider the interaction of magmatic dikes with lithospheric stretching do not successfully reproduce both of these trends. We present the first model that reproduces these trends by making simple assumptions about the partitioning of magma between dikes, gabbros and extrusives. A key concept is that dikes open not only in the brittle axial lithosphere but also into the underlying ductile crust, where they cool to form gabbro. The amount of gabbro so intruded depends on magma pressure that is related to axial relief. The deeper the valley the less magma goes into gabbros and the more magma is available for dikes to accommodate plate separation. We define the fraction of plate separation rate accommodated by dikes as M. If M<1 then part of the plate separation occurs as fault offset which deepens the axial valley. This axial deepening decreases the amount of magma go into gabbros and this increases M. If the valley reaches the depth where M =1 then the faulting ceases and the valley stays at that depth. However, even if M<1, the valley depth cannot increase without limit. Through a distributed pattern of tectonic faults, the valley depth reaches a maximum possible depth that depends on the thickness of the axial lithosphere. If M < 1, where the axial depth reaches this tectonic limit, then moderate to large offset faults can develop. If M = 1 before the depth reaches the tectonic limit, normal faults only develop in response to oscillations in magma supply and fault offset is proportional to the amount of extruded lava. We have derived analytic expressions relates axial lithospheric thickness (HL) and crustal thickness (Hc) to axial valley depth. We then used a 2D model numerical model with a fixed axial lithospheric structure to show that the analytic model predictions are reasonable. Finally, we describe themo-mechanical models that allow us to relate plate spreading rate and crustal thickness and to axial valley depth.
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On the black hole lens and its foci
NASA Technical Reports Server (NTRS)
Eshleman, Von R.; Gurrola, Eric M.; Lindal, Gunnar F.
1989-01-01
Methods developed for radio occultation studies of planetary atmospheres are used to predict the electromagnetic focusing properties of a refracting lens representation of a Schwarzschild black hole. The infinity of foci are of three distinct types: a principal forward axial focus which is by far the strongest; higher-order forward axial foci; and backward conical foci with axial nulls.
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Conjugate adaptive optics with remote focusing in multiphoton microscopy
NASA Astrophysics Data System (ADS)
Tao, Xiaodong; Lam, Tuwin; Zhu, Bingzhao; Li, Qinggele; Reinig, Marc R.; Kubby, Joel
2018-02-01
The small correction volume for conventional wavefront shaping methods limits their application in biological imaging through scattering media. In this paper, we take advantage of conjugate adaptive optics (CAO) and remote focusing (CAORF) to achieve three-dimensional (3D) scanning through a scattering layer with a single correction. Our results show that the proposed system can provide 10 times wider axial field of view compared with a conventional conjugate AO system when 16,384 segments are used on a spatial light modulator. We demonstrate two-photon imaging with CAORF through mouse skull. The fluorescent microspheres embedded under the scattering layers can be clearly observed after applying the correction.
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NASA Astrophysics Data System (ADS)
Yuan, Wu; Alemohammad, Milad; Yu, Xiaoyun; Yu, Shaoyong; Li, Xingde
2016-03-01
In this paper, we report a super-achromatic microprobe made with fiber-optic ball lens to enable ultrahigh-resolution endoscopic OCT imaging. An axial resolution of ~2.4 µm (in air) can be achieved with a 7-fs Ti:Sapphire laser. The microprobe has minimal astigmatism which affords a high transverse resolution of ~5.6 µm. The miniaturized microprobe has an outer diameter of ~520 µm including the encasing metal guard and can be used to image small luminal organs. The performance of the ultrahigh-resolution OCT microprobe was demonstrated by imaging rat esophagus, guinea pig esophagus, and mouse rectum in vivo.
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Superina, Simone; Borovina, Antonia; Ciruna, Brian
2014-03-15
Growth factors and morphogens regulate embryonic patterning, cell fate specification, cell migration, and morphogenesis. The activity and behavior of these signaling molecules are regulated in the extracellular space through interactions with proteoglycans (Bernfield et al., 1999; Perrimon and Bernfield 2000; Lander and Selleck 2000; Selleck 2000). Proteoglycans are high molecular-weight proteins consisting of a core protein with covalently linked glycosaminoglycan (GAG) side chains, which are thought to mediate ligand interaction. Drosophila mutant embryos deficient for UDP-glucose dehydrogenase activity (Ugdh, required for GAG synthesis) exhibit abnormal Fgf, Wnt and TGFß signaling and die during gastrulation, indicating a broad and critical role for proteoglycans during early embryonic development (Lin et al., 1999; Lin and Perrimon 2000) (Hacker et al., 1997). Mouse Ugdh mutants also die at gastrulation, however, only Fgf signaling appears disrupted (Garcia-Garcia and Anderson, 2003). These findings suggested a possible divergence in the requirement for proteoglycans during Drosophila and mouse embryogenesis, and that mammals may have evolved alternative means of regulating Wnt and TGFß activity. To further examine the function of proteoglycans in vertebrate development, we have characterized zebrafish mutants devoid of both maternal and zygotic Ugdh/Jekyll activity (MZjekyll). We demonstrate that MZjekyll mutant embryos display abnormal Fgf, Shh, and Wnt signaling activities, with concomitant defects in central nervous system patterning, cardiac ventricular fate specification and axial morphogenesis. Furthermore, we uncover a novel role for proteoglycans in left-right pattern formation. Our findings resolve longstanding questions into the evolutionary conservation of Ugdh function and provide new mechanistic insights into the initiation of left-right asymmetry. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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Ritter, K. Elaine; Southard-Smith, E. Michelle
2017-01-01
Sensory afferent signaling is required for normal function of the lower urinary tract (LUT). Despite the wide prevalence of bladder dysfunction and pelvic pain syndromes, few effective treatment options are available. Serotonin receptor 5-HT3A is a known mediator of visceral afferent signaling and has been implicated in bladder function. However, basic expression patterns for this gene and others among developing bladder sensory afferents that could be used to inform regenerative efforts aimed at treating deficiencies in pelvic innervation are lacking. To gain greater insight into the molecular characteristics of bladder sensory innervation, we conducted a thorough characterization of Htr3a expression in developing and adult bladder-projecting lumbosacral dorsal root ganglia (DRG) neurons. Using a transgenic Htr3a-EGFP reporter mouse line, we identified 5-HT3A expression at 10 days post coitus (dpc) in neural crest derivatives and in 12 dpc lumbosacral DRG. Using immunohistochemical co-localization we observed Htr3a-EGFP expression in developing lumbosacral DRG that partially coincides with neuropeptides CGRP and Substance P and capsaicin receptor TRPV1. A majority of Htr3a-EGFP+ DRG neurons also express a marker of myelinated Aδ neurons, NF200. There was no co-localization of 5-HT3A with the TRPV4 receptor. We employed retrograde tracing in adult Htr3a-EGFP mice to quantify the contribution of 5-HT3A+ DRG neurons to bladder afferent innervation. We found that 5-HT3A is expressed in a substantial proportion of retrograde traced DRG neurons in both rostral (L1, L2) and caudal (L6, S1) axial levels that supply bladder innervation. Most bladder-projecting Htr3a-EGFP+ neurons that co-express CGRP, Substance P, or TRPV1 are found in L1, L2 DRG, whereas Htr3a-EGFP+, NF200+ bladder-projecting neurons are from the L6, S1 axial levels. Our findings contribute much needed information regarding the development of LUT innervation and highlight the 5-HT3A serotonin receptor as a candidate for future studies of neurally mediated bladder control. PMID:28111539
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DOE Office of Scientific and Technical Information (OSTI.GOV)
McCarroll, R; Rubinstein, A; Kingsley, C
Purpose: New small-animal irradiators include extremely precise IGRT capabilities. However, mouse immobilization and localization remains a challenge. In particular, unlike week-to-week translational displacements, rotational changes in positioning are not easily corrected for in subject setup. Using two methods of setup, we aim to quantify week-to-week rotational variation in mice for the purpose of IGRT planning in small animal studies. Methods: Ten mice were imaged weekly using breath-hold CBCT (X-RAD 225 Cx), with the mouse positioned in a half-pipe support, providing 40 scans. A second group of two mice were positioned in a 3D printed immobilization device, which was created usingmore » a CT from a similarly shaped mouse, providing 10 scans. For each mouse, the first image was taken to be the reference image. Subsequent CT images were then rigidly registered, based on bony anatomy. Rotations in the axial (roll), sagittal (pitch), and coronal (yaw) planes were recorded and used to quantify variation in angular setup. Results: For the mice imaged in the half pipe, average magnitude of roll was found to be 5.4±4.6° (range: −12.9:18.86°), of pitch 1.6±1.3° (range: −1.4:4.7°), and of yaw 1.9±1.5° (range −5.4:1.1°). For the mice imaged in the printed setup; average magnitude of roll was found to be 0.64±0.6° (range: −2.1:1.0°), of pitch 0.6±0.4° (range: 0.0:1.3°), and of yaw 0.2±0.1° (range: 0.0:0.4°). The printed setup provided reduction in roll, pitch, and yaw by 88, 62, and 90 percent, respectively. Conclusion: For the typical setup routine, roll in mouse position is the dominant source of rotational variation. However, when a printed device was used, drastic improvements in mouse immobilization were seen. This work provides a promising foundation for mouse immobilization, required for full scale small animal IGRT. Currently, we are making improvements to allo±w the use of a similar system for MR, PET, and bioluminescence.« less
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NASA Astrophysics Data System (ADS)
Hong, R.; Li, J. C.; Chakraborty Thakur, S.; Hajjar, R.; Diamond, P. H.; Tynan, G. R.
2018-05-01
This study traces the emergence of sheared axial flow from collisional drift-wave turbulence with broken symmetry in a linear plasma device—the controlled shear decorrelation experiment. As the density profile steepens, the axial Reynolds stress develops and drives a radially sheared axial flow that is parallel to the magnetic field. Results show that the nondiffusive piece of the Reynolds stress is driven by the density gradient, results from spectral asymmetry of the turbulence, and, thus, is dynamical in origin. Taken together, these findings constitute the first simultaneous demonstration of the causal link between the density gradient, turbulence, and stress with broken spectral symmetry and the mean axial flow.
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Why coronal flux tubes have axially invariant cross-section
NASA Astrophysics Data System (ADS)
Bellan, Paul
2001-10-01
We present here a model that not only explains the long-standing mystery^1 of why solar coronal flux tubes tend towards having axially invariant cross-sections but also explains several other enigmatic features, namely: rotating jets emanating from the ends (surges), counter-streaming beams, ingestion of photospheric material, and elevated pressure/temperature compared to adjacent plasma. The model shows that when a steady current flows along a flux tube with a bulging middle (i.e., a flux tube that is initially produced by a potential magnetic field), non-conservative forces develop which accelerate fluid axially from both ends towards the middle. Remarkably, this axial pumping of fluid into the flux tube causes the flux tube cross-section and volume to decrease in a manner such that the flux tube develops an axial uniform cross-section as observed in coronal loops. The pumping process produces counter-rotating, counter-streaming Alfvenic bulk motion consistent with observations. Collision of the counter-streaming beams causes non-localized bulk heating. This picture also has relevance to astrophysical jets and coaxial spheromak guns and explains why these systems tend to form an axial jet along the geometric axis. Supported by USDOE. l ^1 J. A. Klimchuk, Solar Phys. 193, 53 (2000)
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Why coronal flux tubes have axially invariant cross-section
NASA Astrophysics Data System (ADS)
Bellan, P. M.
2001-12-01
We present here a model that not only explains the long-standing mystery of why solar coronal flux tubes tend towards having axially in-variant cross-sections but also explains several other enigmatic features, namely: rotating jets emanating from the ends (surges), counter-streaming beams, ingestion of photospheric material, and elevated pressure/temperature compared to adjacent plasma. The model shows that when a steady current flows along a flux tube with a bulging middle (i.e., a flux tube that is initially produced by a potential magnetic field), non-conservative forces develop which accelerate fluid axially from both ends towards the middle. Remarkably, this axial pumping of fluid into the flux tube causes the flux tube cross-section and volume to decrease in a manner such that the flux tube develops an axial uniform cross-section as observed in coronal loops. The pumping process produces counter-rotating, counter-streaming Alfvenic bulk motion consistent with observations. Collision of the counter-streaming beams causes non-localized bulk heating. This picture also has relevance to astrophysical jets and coaxial spheromak guns and explains why these systems tend to form an axial jet along the geometric axis. Supported by USDOE. [1]J. A. Klimchuk, Solar Phys. 193, 53 (2000)
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NASA Astrophysics Data System (ADS)
Hassan, Wael Mohammed
Beam-column joints in concrete buildings are key components to ensure structural integrity of building performance under seismic loading. Earthquake reconnaissance has reported the substantial damage that can result from inadequate beam-column joints. In some cases, failure of older-type corner joints appears to have led to building collapse. Since the 1960s, many advances have been made to improve seismic performance of building components, including beam-column joints. New design and detailing approaches are expected to produce new construction that will perform satisfactorily during strong earthquake shaking. Much less attention has been focused on beam-column joints of older construction that may be seismically vulnerable. Concrete buildings constructed prior to developing details for ductility in the 1970s normally lack joint transverse reinforcement. The available literature concerning the performance of such joints is relatively limited, but concerns about performance exist. The current study aimed to improve understanding and assessment of seismic performance of unconfined exterior and corner beam-column joints in existing buildings. An extensive literature survey was performed, leading to development of a database of about a hundred tests. Study of the data enabled identification of the most important parameters and the effect of each parameter on the seismic performance. The available analytical models and guidelines for strength and deformability assessment of unconfined joints were surveyed and evaluated. In particular, The ASCE 41 existing building document proved to be substantially conservative in joint shear strength estimation. Upon identifying deficiencies in these models, two new joint shear strength models, a bond capacity model, and two axial capacity models designed and tailored specifically for unconfined beam-column joints were developed. The proposed models strongly correlated with previous test results. In the laboratory testing phase of the current study, four full-scale corner beam-column joint subassemblies, with slab included, were designed, built, instrumented, tested, and analyzed. The specimens were tested under unidirectional and bidirectional displacement-controlled quasi-static loading that incorporated varying axial loads that simulated overturning seismic moment effects. The axial loads varied between tension and high compression loads reaching about 50% of the column axial capacity. The test parameters were axial load level, loading history, joint aspect ratio, and beam reinforcement ratio. The test results proved that high axial load increases joint shear strength and decreases the deformability of joints failing in pure shear failure mode without beam yielding. On the contrary, high axial load did not affect the strength of joints failing in shear after significant beam yielding; however, it substantially increased their displacement ductility. Joint aspect ratio proved to be instrumental in deciding joint shear strength; that is the deeper the joint the lower the shear strength. Bidirectional loading reduced the apparent strength of the joint in the uniaxial principal axes. However, circular shear strength interaction is an appropriate approximation to predict the biaxial strength. The developed shear strength models predicted successfully the strength of test specimens. Based on the literature database investigation, the shear and axial capacity models developed and the test results of the current study, an analytical finite element component model based on a proposed joint shear stress-rotation backbone constitutive curve was developed to represent the behavior of unconfined beam-column joints in computer numerical simulations of concrete frame buildings. The proposed finite element model included the effect of axial load, mode of joint failure, joint aspect ratio and axial capacity of joint. The proposed backbone curve along with the developed joint element exhibited high accuracy in simulating the test response of the current test specimens as well as previous test joints. Finally, a parametric study was conducted to assess the axial failure vulnerability of unconfined beam-column joints based on the developed shear and axial capacity models. This parametric study compared the axial failure potential of unconfined beam-column joint with that of shear critical columns to provide a preliminary insight into the axial collapse vulnerability of older-type buildings during intense ground shaking.
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EFFECTS OF HYPERTHERMIA AND BORIC ACID ON SKELETAL DEVELOPMENT IN RAT EMBRYOS
BACKGROUND: The individual effects of boric acid (BA) and hyperthermia on the development of the axial skeleton have previously been reported. Both cause an increased incidence of axial skeletal defects including a decrease in the total number of ribs and vertebrae. Because of th...
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Fu, Jian; Li, Chen; Liu, Zhenzhong
2015-10-01
Synchrotron radiation nanoscale computed tomography (SR nano-CT) is a powerful analysis tool and can be used to perform chemical identification, mapping, or speciation of carbon and other elements together with X-ray fluorescence and X-ray absorption near edge structure (XANES) imaging. In practical applications, there are often challenges for SR nano-CT due to the misaligned geometry caused by the sample stage axial vibration. It occurs quite frequently because of experimental constraints from the mechanical error of manufacturing and assembly and the thermal expansion during the time-consuming scanning. The axial vibration will lead to the structure overlap among neighboring layers and degrade imaging results by imposing artifacts into the nano-CT images. It becomes worse for samples with complicated axial structure. In this work, we analyze the influence of axial vibration on nano-CT image by partial derivative. Then, an axial vibration calibration method for SR nano-CT is developed and investigated. It is based on the cross correlation of plane integral curves of the sample at different view angles. This work comprises a numerical study of the method and its experimental verification using a dataset measured with the full-field transmission X-ray microscope nano-CT setup at the beamline 4W1A of the Beijing Synchrotron Radiation Facility. The results demonstrate that the presented method can handle the stage axial vibration. It can work for random axial vibration and needs neither calibration phantom nor additional calibration scanning. It will be helpful for the development and application of synchrotron radiation nano-CT systems.
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Navy High-Strength Steel Corrosion-Fatigue Modeling Program
2006-10-01
interest. In the global analysis, the axial loading and residual stress (via the temperature profile discussed in the previous section) were applied to...developed based on observa- tions from analyses of axial load components with sinusoidally varying surface geometries. These observations indicated that...profile parameters (height and wavelength in each surface direction) and the applied axial loading . Stress Varies Sinusoidally 180° Out of Phase
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Axial forces in centrifugal compressor couplings
NASA Astrophysics Data System (ADS)
Ivanov, A. N.; Ivanov, N. M.; Yun, V. K.
2017-08-01
The article presents the results of the theoretical and experimental investigation of axial forces arising in the toothed and plate couplings of centrifugal compressor shaft lines. Additional loads on the thrust bearing are considered that can develop in the toothed couplings as a result of coupled rotors misalignment. Design relationships to evaluate the level of axial forces and recommendations for their reduction in the operating conditions are given.
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NASA Astrophysics Data System (ADS)
Merkle, Conrad W.; Chong, Shau Poh; Kho, Aaron M.; Zhu, Jun; Kholiqov, Oybek; Dubra, Alfredo; Srinivasan, Vivek J.
2018-02-01
Most flying-spot Optical Coherence Tomography (OCT) and Optical Coherence Microscopy (OCM) systems use a symmetric confocal geometry, where the detection path retraces the illumination path starting from and ending with the spatial mode of a single mode optical fiber. Here, we describe a visible light OCM instrument that breaks this symmetry to improve transverse resolution without sacrificing collection efficiency in scattering tissue. This was achieved by overfilling a 0.3 numerical aperture (NA) water immersion objective on the illumination path, while maintaining a conventional Gaussian mode detection path (1/e2 intensity diameter 0.82 Airy disks), enabling 1.1 μm full-width at half-maximum (FWHM) transverse resolution. At the same time, a 0.9 μm FWHM axial resolution in tissue, achieved by a broadband visible light source, enabled femtoliter volume resolution. We characterized this instrument according to paraxial coherent microscopy theory, and then used it to image the meningeal layers, intravascular red blood cell-free layer, and myelinated axons in the mouse neocortex in vivo through the thinned skull. Finally, by introducing a 0.8 NA water immersion objective, we improved the lateral resolution to 0.44 μm FWHM, which provided a volumetric resolution of 0.2 fL, revealing cell bodies in cortical layer I of the mouse brain with OCM for the first time.
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Gong, Hui; Xu, Dongli; Yuan, Jing; Li, Xiangning; Guo, Congdi; Peng, Jie; Li, Yuxin; Schwarz, Lindsay A.; Li, Anan; Hu, Bihe; Xiong, Benyi; Sun, Qingtao; Zhang, Yalun; Liu, Jiepeng; Zhong, Qiuyuan; Xu, Tonghui; Zeng, Shaoqun; Luo, Qingming
2016-01-01
The precise annotation and accurate identification of neural structures are prerequisites for studying mammalian brain function. The orientation of neurons and neural circuits is usually determined by mapping brain images to coarse axial-sampling planar reference atlases. However, individual differences at the cellular level likely lead to position errors and an inability to orient neural projections at single-cell resolution. Here, we present a high-throughput precision imaging method that can acquire a co-localized brain-wide data set of both fluorescent-labelled neurons and counterstained cell bodies at a voxel size of 0.32 × 0.32 × 2.0 μm in 3 days for a single mouse brain. We acquire mouse whole-brain imaging data sets of multiple types of neurons and projections with anatomical annotation at single-neuron resolution. The results show that the simultaneous acquisition of labelled neural structures and cytoarchitecture reference in the same brain greatly facilitates precise tracing of long-range projections and accurate locating of nuclei. PMID:27374071
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NASA Astrophysics Data System (ADS)
Ivanova, T. M.; Serebryany, V. N.
2017-12-01
The component fit method in quantitative texture analysis assumes that the texture of the polycrystalline sample can be represented by a superposition of weighted standard distributions those are characterized by position in the orientation space, shape and sharpness of the scattering. The components of the peak and axial shapes are usually used. It is known that an axial texture develops in materials subjected to direct pressing. In this paper we considered the possibility of modelling a texture of a magnesium sample subjected to equal-channel angular pressing with axial components only. The results obtained make it possible to conclude that ECAP is also a process leading to the appearance of an axial texture in magnesium alloys.
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Wall boundary layer development near the tip region of an IGV of an axial flow compressor
NASA Technical Reports Server (NTRS)
Lakshminarayana, B.; Sitaram, N.
1983-01-01
The annulus wall boundary layer inside the blade passage of the inlet guide vane (IGV) passage of a low-speed axial compressor stage was measured with a miniature five-hole probe. The three-dimensional velocity and pressure fields were measured at various axial and tangential locations. Limiting streamline angles and static pressures were also measured on the casing of the IGV passage. Strong secondary vorticity was developed. The data were analyzed and correlated with the existing velocity profile correlations. The end wall losses were also derived from these data.
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Rotating stall simulation for axial and centrifugal compressors
NASA Astrophysics Data System (ADS)
Halawa, Taher; Gadala, Mohamed S.
2017-05-01
This study presents a numerical simulation of the rotating stall phenomenon in axial and centrifugal compressors with detailed descriptions of stall precursors and its development with time. Results showed that the vaneless region of the centrifugal compressor is the most critical location affected by stall. It was found that the tip leakage flow and the back flow impingement are the main cause of the stall development at the impeller exit area for centrifugal compressors. The results of the axial compressor simulations indicated that the early separated flow combined with the tip leakage flow can block the impeller passages during stall.
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NASA Astrophysics Data System (ADS)
Salvini, Francesco; Storti, Fabrizio
2001-01-01
In fault-related folds that form by axial surface migration, rocks undergo deformation as they pass through axial surfaces. The distribution and intensity of deformation in these structures has been impacted by the history of axial surface migration. Upon fold initiation, unique dip panels develop, each with a characteristic deformation intensity, depending on their history. During fold growth, rocks that pass through axial surfaces are transported between dip panels and accumulate additional deformation. By tracking the pattern of axial surface migration in model folds, we predict the distribution of relative deformation intensity in simple-step, parallel fault-bend and fault-propagation anticlines. In both cases the deformation is partitioned into unique domains we call deformation panels. For a given rheology of the folded multilayer, deformation intensity will be homogeneously distributed in each deformation panel. Fold limbs are always deformed. The flat crests of fault-propagation anticlines are always undeformed. Two asymmetric deformation panels develop in fault-propagation folds above ramp angles exceeding 29°. For lower ramp angles, an additional, more intensely-deformed panel develops at the transition between the crest and the forelimb. Deformation in the flat crests of fault-bend anticlines occurs when fault displacement exceeds the length of the footwall ramp, but is never found immediately hinterland of the crest to forelimb transition. In environments dominated by brittle deformation, our models may serve as a first-order approximation of the distribution of fractures in fault-related folds.
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Cheng, Ching-Yu; Schache, Maria; Ikram, M. Kamran; Young, Terri L.; Guggenheim, Jeremy A.; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J.M.; Barathi, Veluchamy A.; Liao, Jiemin; Hysi, Pirro G.; Bailey-Wilson, Joan E.; St. Pourcain, Beate; Kemp, John P.; McMahon, George; Timpson, Nicholas J.; Evans, David M.; Montgomery, Grant W.; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F.; Amin, Najaf; van Leeuwen, Elisabeth M.; Wilson, James F.; Pennell, Craig E.; van Duijn, Cornelia M.; de Jong, Paulus T.V.M.; Vingerling, Johannes R.; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Rahi, Jugnoo S.; Hysi, Pirro G.; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Delcourt, Cécile; Maubaret, Cecilia; Williams, Cathy; Guggenheim, Jeremy A.; Northstone, Kate; Ring, Susan M.; Davey-Smith, George; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Stambolian, Dwight; Wilson, Joan E. Bailey; MacGregor, Stuart; Lu, Yi; Jonas, Jost B.; Xu, Liang; Saw, Seang-Mei; Baird, Paul N.; Rochtchina, Elena; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B.; Nangia, Vinay; Hayward, Caroline; Wright, Alan F.; Vitart, Veronique; Polasek, Ozren; Campbell, Harry; Vitart, Veronique; Rudan, Igor; Vatavuk, Zoran; Vitart, Veronique; Paterson, Andrew D.; Hosseini, S. Mohsen; Iyengar, Sudha K.; Igo, Robert P.; Fondran, Jeremy R.; Young, Terri L.; Feng, Sheng; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Metspalu, Andres; Haller, Toomas; Mihailov, Evelin; Pärssinen, Olavi; Wedenoja, Juho; Wilson, Joan E. Bailey; Wojciechowski, Robert; Baird, Paul N.; Schache, Maria; Pfeiffer, Norbert; Höhn, René; Pang, Chi Pui; Chen, Peng; Meitinger, Thomas; Oexle, Konrad; Wegner, Aharon; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Pärssinen, Olavi; Yip, Shea Ping; Ho, Daniel W.H.; Pirastu, Mario; Murgia, Federico; Portas, Laura; Biino, Genevra; Wilson, James F.; Fleck, Brian; Vitart, Veronique; Stambolian, Dwight; Wilson, Joan E. Bailey; Hewitt, Alex W.; Ang, Wei; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Tai, E-Shyong; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Mackey, David A.; MacGregor, Stuart; Hammond, Christopher J.; Hysi, Pirro G.; Deangelis, Margaret M.; Morrison, Margaux; Zhou, Xiangtian; Chen, Wei; Paterson, Andrew D.; Hosseini, S. Mohsen; Mizuki, Nobuhisa; Meguro, Akira; Lehtimäki, Terho; Mäkelä, Kari-Matti; Raitakari, Olli; Kähönen, Mika; Burdon, Kathryn P.; Craig, Jamie E.; Iyengar, Sudha K.; Igo, Robert P.; Lass, Jonathan H.; Reinhart, William; Belin, Michael W.; Schultze, Robert L.; Morason, Todd; Sugar, Alan; Mian, Shahzad; Soong, Hunson Kaz; Colby, Kathryn; Jurkunas, Ula; Yee, Richard; Vital, Mark; Alfonso, Eduardo; Karp, Carol; Lee, Yunhee; Yoo, Sonia; Hammersmith, Kristin; Cohen, Elisabeth; Laibson, Peter; Rapuano, Christopher; Ayres, Brandon; Croasdale, Christopher; Caudill, James; Patel, Sanjay; Baratz, Keith; Bourne, William; Maguire, Leo; Sugar, Joel; Tu, Elmer; Djalilian, Ali; Mootha, Vinod; McCulley, James; Bowman, Wayne; Cavanaugh, H. Dwight; Verity, Steven; Verdier, David; Renucci, Ann; Oliva, Matt; Rotkis, Walter; Hardten, David R.; Fahmy, Ahmad; Brown, Marlene; Reeves, Sherman; Davis, Elizabeth A.; Lindstrom, Richard; Hauswirth, Scott; Hamilton, Stephen; Lee, W. Barry; Price, Francis; Price, Marianne; Kelly, Kathleen; Peters, Faye; Shaughnessy, Michael; Steinemann, Thomas; Dupps, B.J.; Meisler, David M.; Mifflin, Mark; Olson, Randal; Aldave, Anthony; Holland, Gary; Mondino, Bartly J.; Rosenwasser, George; Gorovoy, Mark; Dunn, Steven P.; Heidemann, David G.; Terry, Mark; Shamie, Neda; Rosenfeld, Steven I.; Suedekum, Brandon; Hwang, David; Stone, Donald; Chodosh, James; Galentine, Paul G.; Bardenstein, David; Goddard, Katrina; Chin, Hemin; Mannis, Mark; Varma, Rohit; Borecki, Ingrid; Chew, Emily Y.; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L.; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C.A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; Spencer, Chris C.A.; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M.; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E.; Hosseini, S. Mohsen; Paterson, Andrew D.; Genuth, S.; Nathan, D.M.; Zinman, B.; Crofford, O.; Crandall, J.; Reid, M.; Brown-Friday, J.; Engel, S.; Sheindlin, J.; Martinez, H.; Shamoon, H.; Engel, H.; Phillips, M.; Gubitosi-Klug, R.; Mayer, L.; Pendegast, S.; Zegarra, H.; Miller, D.; Singerman, L.; Smith-Brewer, S.; Novak, M.; Quin, J.; Dahms, W.; Genuth, Saul; Palmert, M.; Brillon, D.; Lackaye, M.E.; Kiss, S.; Chan, R.; Reppucci, V.; Lee, T.; Heinemann, M.; Whitehouse, F.; Kruger, D.; Jones, J.K.; McLellan, M.; Carey, J.D.; Angus, E.; Thomas, A.; Galprin, A.; Bergenstal, R.; Johnson, M.; Spencer, M.; Morgan, K.; Etzwiler, D.; Kendall, D.; Aiello, Lloyd Paul; Golden, E.; Jacobson, A.; Beaser, R.; Ganda, O.; Hamdy, O.; Wolpert, H.; Sharuk, G.; Arrigg, P.; Schlossman, D.; Rosenzwieg, J.; Rand, L.; Nathan, D.M.; Larkin, M.; Ong, M.; Godine, J.; Cagliero, E.; Lou, P.; Folino, K.; Fritz, S.; Crowell, S.; Hansen, K.; Gauthier-Kelly, C.; Service, J.; Ziegler, G.; Luttrell, L.; Caulder, S.; Lopes-Virella, M.; Colwell, J.; Soule, J.; Fernandes, J.; Hermayer, K.; Kwon, S.; Brabham, M.; Blevins, A.; Parker, J.; Lee, D.; Patel, N.; Pittman, C.; Lindsey, P.; Bracey, M.; Lee, K.; Nutaitis, M.; Farr, A.; Elsing, S.; Thompson, T.; Selby, J.; Lyons, T.; Yacoub-Wasef, S.; Szpiech, M.; Wood, D.; Mayfield, R.; Molitch, M.; Schaefer, B.; Jampol, L.; Lyon, A.; Gill, M.; Strugula, Z.; Kaminski, L.; Mirza, R.; Simjanoski, E.; Ryan, D.; Kolterman, O.; Lorenzi, G.; Goldbaum, M.; Sivitz, W.; Bayless, M.; Counts, D.; Johnsonbaugh, S.; Hebdon, M.; Salemi, P.; Liss, R.; Donner, T.; Gordon, J.; Hemady, R.; Kowarski, A.; Ostrowski, D.; Steidl, S.; Jones, B.; Herman, W.H.; Martin, C.L.; Pop-Busui, R.; Sarma, A.; Albers, J.; Feldman, E.; Kim, K.; Elner, S.; Comer, G.; Gardner, T.; Hackel, R.; Prusak, R.; Goings, L.; Smith, A.; Gothrup, J.; Titus, P.; Lee, J.; Brandle, M.; Prosser, L.; Greene, D.A.; Stevens, M.J.; Vine, A.K.; Bantle, J.; Wimmergren, N.; Cochrane, A.; Olsen, T.; Steuer, E.; Rath, P.; Rogness, B.; Hainsworth, D.; Goldstein, D.; Hitt, S.; Giangiacomo, J.; Schade, D.S.; Canady, J.L.; Chapin, J.E.; Ketai, L.H.; Braunstein, C.S.; Bourne, P.A.; Schwartz, S.; Brucker, A.; Maschak-Carey, B.J.; Baker, L.; Orchard, T.; Silvers, N.; Ryan, C.; Songer, T.; Doft, B.; Olson, S.; Bergren, R.L.; Lobes, L.; Rath, P. Paczan; Becker, D.; Rubinstein, D.; Conrad, P.W.; Yalamanchi, S.; Drash, A.; Morrison, A.; Bernal, M.L.; Vaccaro-Kish, J.; Malone, J.; Pavan, P.R.; Grove, N.; Iyer, M.N.; Burrows, A.F.; Tanaka, E.A.; Gstalder, R.; Dagogo-Jack, S.; Wigley, C.; Ricks, H.; Kitabchi, A.; Murphy, M.B.; Moser, S.; Meyer, D.; Iannacone, A.; Chaum, E.; Yoser, S.; Bryer-Ash, M.; Schussler, S.; Lambeth, H.; Raskin, P.; Strowig, S.; Zinman, B.; Barnie, A.; Devenyi, R.; Mandelcorn, M.; Brent, M.; Rogers, S.; Gordon, A.; Palmer, J.; Catton, S.; Brunzell, J.; Wessells, H.; de Boer, I.H.; Hokanson, J.; Purnell, J.; Ginsberg, J.; Kinyoun, J.; Deeb, S.; Weiss, M.; Meekins, G.; Distad, J.; Van Ottingham, L.; Dupre, J.; Harth, J.; Nicolle, D.; Driscoll, M.; Mahon, J.; Canny, C.; May, M.; Lipps, J.; Agarwal, A.; Adkins, T.; Survant, L.; Pate, R.L.; Munn, G.E.; Lorenz, R.; Feman, S.; White, N.; Levandoski, L.; Boniuk, I.; Grand, G.; Thomas, M.; Joseph, D.D.; Blinder, K.; Shah, G.; Boniuk; Burgess; Santiago, J.; Tamborlane, W.; Gatcomb, P.; Stoessel, K.; Taylor, K.; Goldstein, J.; Novella, S.; Mojibian, H.; Cornfeld, D.; Lima, J.; Bluemke, D.; Turkbey, E.; van der Geest, R.J.; Liu, C.; Malayeri, A.; Jain, A.; Miao, C.; Chahal, H.; Jarboe, R.; Maynard, J.; Gubitosi-Klug, R.; Quin, J.; Gaston, P.; Palmert, M.; Trail, R.; Dahms, W.; Lachin, J.; Cleary, P.; Backlund, J.; Sun, W.; Braffett, B.; Klumpp, K.; Chan, K.; Diminick, L.; Rosenberg, D.; Petty, B.; Determan, A.; Kenny, D.; Rutledge, B.; Younes, Naji; Dews, L.; Hawkins, M.; Cowie, C.; Fradkin, J.; Siebert, C.; Eastman, R.; Danis, R.; Gangaputra, S.; Neill, S.; Davis, M.; Hubbard, L.; Wabers, H.; Burger, M.; Dingledine, J.; Gama, V.; Sussman, R.; Steffes, M.; Bucksa, J.; Nowicki, M.; Chavers, B.; O’Leary, D.; Polak, J.; Harrington, A.; Funk, L.; Crow, R.; Gloeb, B.; Thomas, S.; O’Donnell, C.; Soliman, E.; Zhang, Z.M.; Prineas, R.; Campbell, C.; Ryan, C.; Sandstrom, D.; Williams, T.; Geckle, M.; Cupelli, E.; Thoma, F.; Burzuk, B.; Woodfill, T.; Low, P.; Sommer, C.; Nickander, K.; Budoff, M.; Detrano, R.; Wong, N.; Fox, M.; Kim, L.; Oudiz, R.; Weir, G.; Espeland, M.; Manolio, T.; Rand, L.; Singer, D.; Stern, M.; Boulton, A.E.; Clark, C.; D’Agostino, R.; Lopes-Virella, M.; Garvey, W.T.; Lyons, T.J.; Jenkins, A.; Virella, G.; Jaffa, A.; Carter, Rickey; Lackland, D.; Brabham, M.; McGee, D.; Zheng, D.; Mayfield, R.K.; Boright, A.; Bull, S.; Sun, L.; Scherer, S.; Zinman, B.; Natarajan, R.; Miao, F.; Zhang, L.; Chen;, Z.; Nathan, D.M.; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K.H.; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J.; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G.; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W.; Williams, Cathy; Oostra, Ben A.; Teo, Yik-Ying; Hammond, Christopher J.; Stambolian, Dwight; Mackey, David A.; Klaver, Caroline C.W.; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N.
2013-01-01
Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. PMID:24144296
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Freeform inkjet printing of cellular structures with bifurcations.
Christensen, Kyle; Xu, Changxue; Chai, Wenxuan; Zhang, Zhengyi; Fu, Jianzhong; Huang, Yong
2015-05-01
Organ printing offers a great potential for the freeform layer-by-layer fabrication of three-dimensional (3D) living organs using cellular spheroids or bioinks as building blocks. Vascularization is often identified as a main technological barrier for building 3D organs. As such, the fabrication of 3D biological vascular trees is of great importance for the overall feasibility of the envisioned organ printing approach. In this study, vascular-like cellular structures are fabricated using a liquid support-based inkjet printing approach, which utilizes a calcium chloride solution as both a cross-linking agent and support material. This solution enables the freeform printing of spanning and overhang features by providing a buoyant force. A heuristic approach is implemented to compensate for the axially-varying deformation of horizontal tubular structures to achieve a uniform diameter along their axial directions. Vascular-like structures with both horizontal and vertical bifurcations have been successfully printed from sodium alginate only as well as mouse fibroblast-based alginate bioinks. The post-printing fibroblast cell viability of printed cellular tubes was found to be above 90% even after a 24 h incubation, considering the control effect. © 2014 Wiley Periodicals, Inc.
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Notochord Morphogenesis in Mice: Current Understanding & Open Questions
Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina
2016-01-01
The notochord is the structure which defines chordates. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Interestingly, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. PMID:26845388
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A data acquisition and control program for axial-torsional fatigue testing
NASA Technical Reports Server (NTRS)
Kalluri, Sreeramesh; Bonacuse, Peter J.
1989-01-01
A computer program was developed for data acquisition and control of axial-torsional fatigue experiments. The multitasked, interrupt-driven program was written in Pascal and Assembly. This program is capable of dual-channel control and six-channel data acquisition. It can be utilized to perform inphase and out-of-phase axial-torsional isothermal fatigue or deformation experiments. The program was successfully used to conduct inphase axial-torsional fatigue experiments on 304 stainless steel at room temperature and on Hastelloy X at 800 C. The details of the software and some of the results generated to date are presented.
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Performance evaluation of an Inveon PET preclinical scanner
NASA Astrophysics Data System (ADS)
Constantinescu, Cristian C.; Mukherjee, Jogeshwar
2009-05-01
We evaluated the performance of an Inveon preclinical PET scanner (Siemens Medical Solutions), the latest MicroPET system. Spatial resolution was measured with a glass capillary tube (0.26 mm inside diameter, 0.29 mm wall thickness) filled with 18F solution. Transaxial and axial resolutions were measured with the source placed parallel and perpendicular to the axis of the scanner. The sensitivity of the scanner was measured with a 22Na point source, placed on the animal bed and positioned at different offsets from the center of the field of view (FOV), as well as at different energy and coincidence windows. The noise equivalent count rates (NECR) and the system scatter fraction were measured using rat-like (Φ = 60, L = 150 mm) and mouse-like (Φ = 25 mm, L = 70 mm) cylindrical phantoms. Line sources filled with high activity 18F (>250 MBq) were inserted parallel to the axes of the phantoms (13.5 and 10 mm offset). For each phantom, list-mode data were collected over 24 h at 350-650 keV and 250-750 keV energy windows and 3.4 ns coincidence window. System scatter fraction was measured when the random event rates were below 1%. Performance phantoms consisting of cylinders with hot rod inserts filled with 18F were imaged. In addition, we performed imaging studies that show the suitability of the Inveon scanner for imaging small structures such as those in mice with a variety of tracers. The radial, tangential and axial resolutions at the center of FOV were 1.46 mm, 1.49 and 1.15 mm, respectively. At a radial offset of 2 cm, the FWHM values were 1.73, 2.20 and 1.47 mm, respectively. At a coincidence window of 3.4 ns, the sensitivity was 5.75% for EW = 350-650 keV and 7.4% for EW = 250-750 keV. For an energy window of 350-650 keV, the peak NECR was 538 kcps at 131.4 MBq for the rat-like phantom, and 1734 kcps at 147.4 MBq for the mouse-like phantom. The system scatter fraction values were 0.22 for the rat phantom and 0.06 for the mouse phantom. The Inveon system presents high image resolution, low scatter fraction values and improved sensitivity and count rate performance.
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Szanda, Istvan; Mackewn, Jane; Patay, Gergely; Major, Peter; Sunassee, Kavitha; Mullen, Gregory E; Nemeth, Gabor; Haemisch, York; Blower, Philip J; Marsden, Paul K
2011-11-01
The NanoPET/CT represents the latest generation of commercial preclinical PET/CT systems. This article presents a performance evaluation of the PET component of the system according to the National Electrical Manufacturers Association (NEMA) NU-4 2008 standard. The NanoPET/CT consists of 12 lutetium yttrium orthosilicate:cerium modular detectors forming 1 ring, with 9.5-cm axial coverage and a 16-cm animal port. Each detector crystal is 1.12 × 1.12 × 13 mm, and 1 module contains 81 × 39 of these crystals. An optical light guide transmits the scintillation light to the flat-panel multianode position-sensitive photomultiplier tubes. Analog-to-digital converter cards and a field-programmable gate array-based data-collecting card provide the readout. Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated in accordance with the NEMA NU-4 standard. Energy and temporal resolution measurements and a mouse imaging study were performed in addition to the standard. Energy resolution was 19% at 511 keV. The spatial resolution, measured as full width at half maximum on single-slice rebinning/filtered backprojection-reconstructed images, approached 1 mm on the axis and remained below 2.5 mm in the central 5-cm transaxial region both in the axial center and at one-quarter field of view. The maximum absolute sensitivity for a point source at the center of the field of view was 7.7%. The maximum noise equivalent counting rates were 430 kcps at 36 MBq and 130 kcps at 27 MBq for the mouse- and rat-sized phantoms, respectively. The uniformity and recovery coefficients were measured with the image-quality phantom, giving good-quality images. In a mouse study with an (18)F-labeled thyroid-specific tracer, the 2 lobes of the thyroid were clearly distinguishable, despite the small size of this organ. The flexible readout system allowed experiments to be performed in an efficient manner, and the system remained stable throughout. The large number of detector crystals, arranged with a fine pitch, results in excellent spatial resolution, which is the best reported for currently available commercial systems. The absolute sensitivity is high over the field of view. Combined with the excellent image quality, these features make the NanoPET/CT a powerful tool for preclinical research.
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Shin, Jeong-Oh; Ankamreddy, Harinarayana; Jakka, Naga Mahesh; Lee, Seokwon; Kim, Un-Kyung; Bok, Jinwoong
2017-01-01
The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc). However, little is known about the role of these Hh co-receptors in inner ear development. In this study, we examined the expression patterns of Gas1, Cdon, and Boc, as well as that of Ptch1, in the developing mouse inner ear from otocyst (embryonic day (E) 9.5) until birth and in the developing middle ear at E15.5. Ptch1, a readout of Hh signaling, was expressed in a graded pattern in response to Shh signaling throughout development. Expression patterns of Gas1, Cdon, and Boc differed from that of Ptch1, and each Hh co-receptor was expressed in specific cells and domains in the developing inner and middle ear. These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development.
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Design and Test of a Transonic Axial Splittered Rotor
2015-06-15
AXIAL SPLITTERED ROTOR A new design procedure was developed that uses commercial-off-the-shelf software (MATLAB, SolidWorks, and ANSYS-CFX) for the...geometric rendering and analysis of a transonic axial compressor rotor with splitter blades. Predictive numerical simulations were conducted and...Compressor, Splittered Rotor REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 10. SPONSOR/MONITOR’S ACRONYM(S) ARO 8. PERFORMING
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Sahmani, S; Fattahi, A M
2017-08-01
New ceramic materials containing nanoscaled crystalline phases create a main object of scientific interest due to their attractive advantages such as biocompatibility. Zirconia as a transparent glass ceramic is one of the most useful binary oxides in a wide range of applications. In the present study, a new size-dependent plate model is constructed to predict the nonlinear axial instability characteristics of zirconia nanosheets under axial compressive load. To accomplish this end, the nonlocal continuum elasticity of Eringen is incorporated to a refined exponential shear deformation plate theory. A perturbation-based solving process is put to use to derive explicit expressions for nonlocal equilibrium paths of axial-loaded nanosheets. After that, some molecular dynamics (MD) simulations are performed for axial instability response of square zirconia nanosheets with different side lengths, the results of which are matched with those of the developed nonlocal plate model to capture the proper value of nonlocal parameter. It is demonstrated that the calibrated nonlocal plate model with nonlocal parameter equal to 0.37nm has a very good capability to predict the axial instability characteristics of zirconia nanosheets, the accuracy of which is comparable with that of MD simulation. Copyright © 2017 Elsevier Inc. All rights reserved.
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Classical and numerical approaches to determining V-section band clamp axial stiffness
NASA Astrophysics Data System (ADS)
Barrans, Simon M.; Khodabakhshi, Goodarz; Muller, Matthias
2015-01-01
V-band clamp joints are used in a wide range of applications to connect circular flanges, for ducts, pipes and the turbocharger housing. Previous studies and research on V-bands are either purely empirical or analytical with limited applicability on the variety of V-band design and working conditions. In this paper models of the V-band are developed based on the classical theory of solid mechanics and the finite element method to study the behaviour of theV-bands under axial loading conditions. The good agreement between results from the developed FEA and the classical model support the suitability of the latter to modelV-band joints with diameters greater than 110mm under axial loading. The results from both models suggest that the axial stiffness for thisV-band cross section reaches a peak value for V-bands with radius of approximately 150 mmacross a wide range of coefficients of friction. Also, it is shown that the coefficient of friction and the wedge angle have a significant effect on the axial stiffness of V-bands.
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Predicting the Performance of an Axial-Flow Compressor
NASA Technical Reports Server (NTRS)
Steinke, R. J.
1986-01-01
Stage-stacking computer code (STGSTK) developed for predicting off-design performance of multi-stage axial-flow compressors. Code uses meanline stagestacking method. Stage and cumulative compressor performance calculated from representative meanline velocity diagrams located at rotor inlet and outlet meanline radii. Numerous options available within code. Code developed so user modify correlations to suit their needs.
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Development of a three-dimensional Navier-Stokes code on CDC star-100 computer
NASA Technical Reports Server (NTRS)
Vatsa, V. N.; Goglia, G. L.
1978-01-01
A three-dimensional code in body-fitted coordinates was developed using MacCormack's algorithm. The code is structured to be compatible with any general configuration, provided that the metric coefficients for the transformation are available. The governing equations are developed in primitive variables in order to facilitate the incorporation of physical boundary conditions and turbulence-closure models. MacCormack's two-step, unsplit, time-marching algorithm is used to solve the unsteady Navier-Stokes equations until steady-state solution is achieved. Cases discussed include (1) flat plate in supersonic free stream; (2) supersonic flow along an axial corner; (3) subsonic flow in an axial corner at M infinity = 0.95; and (4) supersonic flow in an axial corner at M infinity 1.5.
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Selović, Alen; Juresa, Vesna; Ivankovic, Davor; Malcic, Davor; Selović Bobonj, Gordana
2005-01-01
This report assesses the relationship of axial length of emmetropic (without refractive error) eyes to age, height, and weight in 1,600 Croatian schoolchildren. Axial eye lengths were determined by an ultrasonic eye biometry (A scan). Axial length of both eyes increases with age, height, and weight but shows a closer correlation to height and weight than to age. Boys have a significantly longer axial eye length than girls (P < 0.01). Boys or girls of similar or nearing body height and body weight and with emmetropic eyes have close linear measures of anatomic eye structures within their sex, regardless their age. Body height demonstrates the closest correlation to the growth and development of the emmetropic eye. Copyright 2005 Wiley-Liss, Inc.
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Clinical applications of in vivo fluorescence confocal laser scanning microscopy
NASA Astrophysics Data System (ADS)
Oh, Chilhwan; Park, Sangyong; Kim, Junhyung; Ha, Seunghan; Park, Gyuman; Lee, Gunwoo; Lee, Onseok; Chun, Byungseon; Gweon, Daegab
2008-02-01
Living skin for basic and clinical research can be evaluated by Confocal Laser Scanning Microscope (CLSM) non-invasively. CLSM imaging system can achieve skin image its native state either "in vivo" or "fresh biopsy (ex vivo)" without fixation, sectioning and staining that is necessary for routine histology. This study examines the potential fluorescent CLSM with a various exogenous fluorescent contrast agent, to provide with more resolution images in skin. In addition, in vivo fluorescent CLSM researchers will be extended a range of potential clinical application. The prototype of our CLSM system has been developed by Prof. Gweon's group. The operating parameters are composed of some units, such as illuminated wavelength 488 nm, argon illumination power up to 20mW on the skin, objective lens, 0.9NA oil immersion, axial resolution 1.0μm, field of view 200μm x 100μm (lateral resolution , 0.3μm). In human volunteer, fluorescein sodium was administrated topically and intradermally. Animal studies were done in GFP transgenic mouse, IRC mouse and pig skin. For imaging of animal skin, fluorescein sodium, acridine orange, and curcumine were used for fluorescein contrast agent. We also used the GFP transgenic mouse for fluorescein CLSM imaging. In intact skin, absorption of fluorescein sodium by individual corneocyte and hair. Intradermal administrated the fluorescein sodium, distinct outline of keratinocyte cell border could be seen. Curcumin is a yellow food dye that has similar fluorescent properties to fluorescein sodium. Acridin Orange can be highlight nuclei in viable keratinocyte. In vivo CLSM of transgenic GFP mouse enable on in vivo, high resolution view of GFP expressing skin tissue. GFP signals are brightest in corneocyte, kertinocyte, hair and eccrine gland. In intact skin, absorption of fluorescein sodium by individual corneocyte and hair. Intradermal administrated the fluorescein sodium, distinct outline of keratinocyte cell border could be seen. In papillary dermis, fluorescein distribution is more homogeneous. Curcumin is a yellow food dye that has similar fluorescent properties to fluorescein sodium. In vivo CLSM of transgenic GFP mouse enable on in vivo, high resolution view of GFP expressing skin tissue. GFP signals are brightest in corneocyte, kertinocyte, skin appendage and blood vessels. In conclusion, this study demonstrates the usefulness of CLSM as technique for imaging skin in vivo. In addition, CLSM is non-invasive, the same tissue site may be imaged over a period of time to monitor the various change such as wound healing, severity of skin diseases and effect of therapeutic management.
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CONFOCAL MICROSCOPY SYSTEM PERFORMANCE: AXIAL RESOLUTION
Abstract
Confocal Microscopy System Performance: Axial resolution.
Robert M. Zucker, PhD
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Re... -
Li, Song-Tao; Liu, Yong; Zhou, Qiang; Lue, Ren-Fa; Song, Lei; Dong, Shi-Wu; Guo, Ping; Kopjar, Branko
2014-03-01
This study introduced a prototype of an axial-stress bioreactor system that supports long-term growth and development of engineered tissues. The main features of this bioreactor are an integrated substance exchanger and feedback control of pH and PO₂. A 21-day study was conducted to validate the system's ability to maintain a stable environment, while remaining sterile. Our results showed that the pH, PO₂, and nutrient (glucose) remained balanced at appropriate levels, while metabolic waste (lactic acid) was removed. No bacteria or fungi were detected in the system or tissue; thus, demonstrating that it was sterile. These data indicate the bioreactor's strong potential for long-term tissue culture. To explore this idea, the effect of dynamic culture, including cyclic compression and automatic substance exchange, on mouse bone-marrow mesenchymal stem cells (BMSCs) seeded in decalcified bone matrix was studied using the bioreactor prototype. Histological sections of the engineered tissues showed higher cell densities in scaffolds in dynamic culture compared to those in static culture, while cell cycle analysis showed that dynamic culture promoted BMSC proliferation (proliferation index, PI=34.02±1.77) more effectively than static culture (PI=26.66±1.81). The results from a methyl thiazolyl tetrazolium assay were consistent with the loading experimental data. Furthermore, elevated alkaline phosphatase activity and calcium content were observed in dynamic condition compared to static culture. In conclusion, this bioreactor system supplies a method of modulating the pH and PO₂ in defined ranges with only small fluctuations; it can be used as a physiological or pathological analog. Automatic control of the environment is a practical solution for long-term, steady-state culture for future commercialization.
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Main, Russell P.; Lynch, Maureen E.; van der Meulen, Marjolein C.H.
2010-01-01
Whole bone morphology, cortical geometry, and tissue material properties modulate skeletal stresses and strains that in turn influence skeletal physiology and remodeling. Understanding how bone stiffness, the relationship between applied load and tissue strain, is regulated by developmental changes in bone structure and tissue material properties is important in implementing biophysical strategies for promoting healthy bone growth and preventing bone loss. The goal of this study was to relate developmental patterns of in vivo whole bone stiffness to whole bone morphology, cross-sectional geometry, and tissue properties using a mouse axial loading model. We measured in vivo tibial stiffness in three age groups (6wks, 10wks, 16wks old) of female C57Bl/6 mice during cyclic tibial compression. Tibial stiffness was then related to cortical geometry, longitudinal bone curvature, and tissue mineral density using microcomputed tomography (microCT). Tibial stiffness and the stresses induced by axial compression were generally maintained from 6 to 16wks of age. Growth-related increases in cortical cross-sectional geometry and longitudinal bone curvature had counteracting effects on induced bone stresses and, therefore, maintained tibial stiffness similarly with growth. Tissue mineral density increased slightly from 6 to 16wks of age, and although the effects of this increase on tibial stiffness were not directly measured, its role in the modulation of whole bone stiffness was likely minor over the age range examined. Thus, whole bone morphology, as characterized by longitudinal curvature, along with cortical geometry, plays an important role in modulating bone stiffness during development and should be considered when evaluating and designing in vivo loading studies and biophysical skeletal therapies. PMID:20673665
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Real-time chirp-coded imaging with a programmable ultrasound biomicroscope.
Bosisio, Mattéo R; Hasquenoph, Jean-Michel; Sandrin, Laurent; Laugier, Pascal; Bridal, S Lori; Yon, Sylvain
2010-03-01
Ultrasound biomicroscopy (UBM) of mice can provide a testing ground for new imaging strategies. The UBM system presented in this paper facilitates the development of imaging and measurement methods with programmable design, arbitrary waveform coding, broad bandwidth (2-80 MHz), digital filtering, programmable processing, RF data acquisition, multithread/multicore real-time display, and rapid mechanical scanning (
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Chang, Chia-Yuan; Lin, Cheng-Han; Lin, Chun-Yu; Sie, Yong-Da; Hu, Yvonne Yuling; Tsai, Sheng-Feng; Chen, Shean-Jen
2018-01-01
A developed temporal focusing-based multiphoton excitation microscope (TFMPEM) has a digital micromirror device (DMD) which is adopted not only as a blazed grating for light spatial dispersion but also for patterned illumination simultaneously. Herein, the TFMPEM has been extended to implement spatially modulated illumination at structured frequency and orientation to increase the beam coverage at the back-focal aperture of the objective lens. The axial excitation confinement (AEC) of TFMPEM can be condensed from 3.0 μm to 1.5 μm for a 50 % improvement. By using the TFMPEM with HiLo technique as two structured illuminations at the same spatial frequency but different orientation, reconstructed biotissue images according to the condensed AEC structured illumination are shown obviously superior in contrast and better scattering suppression. Picture: TPEF images of the eosin-stained mouse cerebellar cortex by conventional TFMPEM (left), and the TFMPEM with HiLo technique as 1.09 μm -1 spatially modulated illumination at 90° (center) and 0° (right) orientations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Feldkaemper, Marita P; Burkhardt, Eva; Schaeffel, Frank
2004-09-01
Myopia is a condition in which the eye is too long for the focal length of cornea and lens. Analysis of the messengers that are released by the retina to control axial eye growth in the animal model of the chicken revealed that glucagon-immunoreactive amacrine cells are involved in the retinal image processing that controls the growth of the sclera. It was found that the amount of retinal glucagon mRNA increased during treatment with positive lenses and pharmacological studies supported the idea that glucagon may act as a stop signal for eye growth. Glucagon exerts its regulatory effects by binding to a single type of glucagon receptor. In this study, we have sequenced the chicken glucagon receptor and compared its DNA and amino acid sequence with the human and mouse homologues. After sequencing about 80% of the receptor, we found a homology between 79.4 and 75.6% on cDNA level. At the protein level, about 73% of the amino acids were identical. Moreover, the cellular localization and regulation of the glucagon receptor in the chick retina was studied. In situ hybridization studies showed that many cells in the ganglion cell layer and inner nuclear layer, and some cells in the outer nuclear layer, express the receptor mRNA. Injection of the glucagon agonist Lys17,18,Glu21-glucagon induced a down-regulation of glucagon receptor mRNA content. Since the mouse would be an attractive mammalian model to study the biochemical and genetic basis of myopia, and because recent studies have demonstrated that form deprivation myopia can be induced, the expression of preproglucagon and glucagon receptor genes were also studied in the mouse retina and were found to be expressed.
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An Axial-Torsional, Thermomechanical Fatigue Testing Technique
NASA Technical Reports Server (NTRS)
Kalluri, Sreeramesh; Bonacuse, Peter J.
1995-01-01
A technique for conducting strain-controlled, thermomechanical, axial-torsional fatigue tests on thin-walled tubular specimens was developed. Three waveforms of loading, namely, the axial strain waveform, the engineering shear strain waveform, and the temperature waveform were required in these tests. The phasing relationships between the mechanical strain waveforms and the temperature and axial strain waveforms were used to define a set of four axial-torsional, thermomechanical fatigue (AT-TMF) tests. Real-time test control (3 channels) and data acquisition (a minimum of 7 channels) were performed with a software program written in C language and executed on a personal computer. The AT-TMF testing technique was used to investigate the axial-torsional thermomechanical fatigue behavior of a cobalt-base superalloy, Haynes 188. The maximum and minimum temperatures selected for the AT-TMF tests were 760 and 316 C, respectively. Details of the testing system, calibration of the dynamic temperature profile of the thin-walled tubular specimen, thermal strain compensation technique, and test control and data acquisition schemes, are reported. The isothermal, axial, torsional, and in- and out-of-phase axial-torsional fatigue behaviors of Haynes 188 at 316 and 760 C were characterized in previous investigations. The cyclic deformation and fatigue behaviors of Haynes 188 in AT-TMF tests are compared to the previously reported isothermal axial-torsional behavior of this superalloy at the maximum and minimum temperatures.
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ANSYS UIDL-Based CAE Development of Axial Support System for Optical Mirror
NASA Astrophysics Data System (ADS)
Yang, De-Hua; Shao, Liang
2008-09-01
The Whiffle-tree type axial support mechanism is widely adopted by most relatively large optical mirrors. Based on the secondary developing tools offered by the commonly used Finite Element Anylysis (FEA) software ANSYS, ANSYS Parametric Design Language (APDL) is used for creating the mirror FEA model driven by parameters, and ANSYS User Interface Design Language (UIDL) for generating custom menu of interactive manner, whereby, the relatively independent dedicated Computer Aided Engineering (CAE) module is embedded in ANSYS for calculation and optimization of axial Whiffle-tree support of optical mirrors. An example is also described to illustrate the intuitive and effective usage of the dedicated module by boosting work efficiency and releasing related engineering knowledge of user. The philosophy of secondary-developed special module with commonly used software also suggests itself for product development in other industries.
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Altered Axial Skeletal Development
The axial skeleton is routinely examined in standard developmental toxicity bioassays and has proven to be sensitive to a wide variety of chemical agents. Dysmorphogenesis in the skull, vertebral column and ribs has been described in both human populations and in laboratory anima...
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Method of characteristics for three-dimensional axially symmetrical supersonic flows.
NASA Technical Reports Server (NTRS)
Sauer, R
1947-01-01
An approximation method for three-dimensional axially symmetrical supersonic flows is developed; it is based on the characteristics theory (represented partly graphically, partly analytically). Thereafter this method is applied to the construction of rotationally symmetrical nozzles. (author)
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Axially symmetrical stresses measurement in the cylindrical tube using DIC with hole-drilling
NASA Astrophysics Data System (ADS)
Ma, Yinji; Yao, Xuefeng; Zhang, Danwen
2015-03-01
In this paper, a new method combining the digital image correlation (DIC) with the hole-drilling technology to characterize the axially symmetrical stresses of the cylindrical tube is developed. First, the theoretical expressions of the axially symmetrical stresses in the cylindrical tube are derived based on the displacement or strain fields before and after hole-drilling. Second, the release of the axially symmetrical stresses for the cylindrical tube caused by hole-drilling is simulated by the finite element method (FEM), which indicates that the axially symmetrical stresses of the cylindrical tube calculated by the cylindrical solution is more accuracy than that for traditionally planar solution. Finally, both the speckle image information and the displacement field of the cylindrical tube before and after hole-drilling are extracted by combining the DIC with the hole-drilling technology, then the axially symmetrical loading induced stresses of the cylindrical tube are obtained, which agree well with the results from the strain gauge method.
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D-D neutron generator development at LBNL.
Reijonen, J; Gicquel, F; Hahto, S K; King, M; Lou, T-P; Leung, K-N
2005-01-01
The plasma and ion source technology group in Lawrence Berkeley National Laboratory is developing advanced, next generation D-D neutron generators. There are three distinctive developments, which are discussed in this presentation, namely, multi-stage, accelerator-based axial neutron generator, high-output co-axial neutron generator and point source neutron generator. These generators employ RF-induction discharge to produce deuterium ions. The distinctive feature of RF-discharge is its capability to generate high atomic hydrogen species, high current densities and stable and long-life operation. The axial neutron generator is designed for applications that require fast pulsing together with medium to high D-D neutron output. The co-axial neutron generator is aimed for high neutron output with cw or pulsed operation, using either the D-D or D-T fusion reaction. The point source neutron generator is a new concept, utilizing a toroidal-shaped plasma generator. The beam is extracted from multiple apertures and focus to the target tube, which is located at the middle of the generator. This will generate a point source of D-D, T-T or D-T neutrons with high output flux. The latest development together with measured data will be discussed in this article.
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Nguyen, Cathy; Cone, Frances E.; Nguyen, Thao D.; Coudrillier, Baptiste; Pease, Mary E.; Steinhart, Matthew R.; Oglesby, Ericka N.; Jefferys, Joan L.; Quigley, Harry A.
2013-01-01
Purpose. To study anatomical changes and mechanical behavior of the sclera in mice with experimental glaucoma by comparing CD1 to B6 mice. Methods. Chronic experimental glaucoma for 6 weeks was produced in 2- to 4-month-old CD1 (43 eyes) and B6 mice (42 eyes) using polystyrene bead injection into the anterior chamber with 126 control CD1 and 128 control B6 eyes. Intraocular pressure (IOP) measurements were made with the TonoLab at baseline and after bead injection. Axial length and scleral thickness were measured after sacrifice in the CD1 and B6 animals and compared to length data from 78 eyes of DBA/2J mice. Inflation testing of posterior sclera was conducted, and circumferential and meridional strain components were determined from the displacement response. Results. Experimental glaucoma led to increases in axial length and width by comparison to fellow eyes (6% in CD1 and 10% in B6; all P < 0.03). While the peripapillary sclera became thinner in both mouse types with glaucoma, the remainder of the sclera uniformly thinned in CD1, but thickened in B6. Peripapillary sclera in CD1 controls had significantly greater temporal meridional strain than B6 and had differences in the ratios of meridional to effective circumferential strain from B6 mice. In both CD1 and B6 mice, exposure to chronic IOP elevation resulted in stiffer pressure–strain responses for both the effective circumferential and meridional strains (multivariable regression model, P = 0.01–0.03). Conclusions. Longer eyes, greater scleral strain in some directions at baseline, and generalized scleral thinning after glaucoma were characteristic of CD1 mice that have greater tendency to retinal ganglion cell damage than B6 mice. Increased scleral stiffness after glaucoma exposure in mice mimics findings in monkey and human glaucoma eyes. PMID:23404116
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He, Xingchi; Handa, James; Gehlbach, Peter; Taylor, Russell; Iordachita, Iulian
2013-01-01
Vitreoretinal surgery requires very fine motor control to perform precise manipulation of the delicate tissue in the interior of the eye. Besides physiological hand tremor, fatigue, poor kinesthetic feedback, and patient movement, the absence of force sensing is one of the main technical challenges. Previous two degrees of freedom (DOF) force sensing instruments have demonstrated robust force measuring performance. The main design challenge is to incorporate high sensitivity axial force sensing. This paper reports the development of a sub-millimetric 3-DOF force sensing pick instrument based on fiber Bragg grating (FBG) sensors. The configuration of the four FBG sensors is arranged to maximize the decoupling between axial and transverse force sensing. A super-elastic nitinol flexure is designed to achieve high axial force sensitivity. An automated calibration system was developed for repeatability testing, calibration, and validation. Experimental results demonstrate a FBG sensor repeatability of 1.3 pm. The linear model for calculating the transverse forces provides an accurate global estimate. While the linear model for axial force is only locally accurate within a conical region with a 30° vertex angle, a second-order polynomial model can provide a useful global estimate for axial force. Combining the linear model for transverse forces and nonlinear model for axial force, the 3-DOF force sensing instrument can provide sub-millinewton resolution for axial force and a quarter millinewton for transverse forces. Validation with random samples show the force sensor can provide consistent and accurate measurement of three dimensional forces. PMID:24108455
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Effect of Control Blade History, and Axial Coolant Density and Burnup Profiles on BWR Burnup Credit
DOE Office of Scientific and Technical Information (OSTI.GOV)
Marshall, William BJ J
2016-01-01
A technical basis for peak reactivity boiling water reactor (BWR) burnup credit (BUC) methods was recently generated, and the technical basis for extended BWR BUC is now being developed. In this paper, a number of effects related to extended BWR BUC are analyzed, including three major operational effects in BWRs: the coolant density axial distribution, the use of control blades during operation, and the axial burnup profile. Specifically, uniform axial moderator density profiles are analyzed and compared to previous results and an additional temporal fidelity study combing moderator density profiles for three different fuel assemblies is presented. Realistic control blademore » histories and cask criticality results are compared to previously generated constructed control blade histories. Finally, a preliminary study of the axial burnup profile is provided.« less
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The Slotted Blade Axial-Flow Blower
1955-09-01
YORK 18, NEW YORK w is|’ .THE SLOTTED BLADE AXIAL-FLOW BLOVER AUG 0 1 13941J F Dr. H. E. Sheets, Member ASME Chief Research and Development Engineer ... blades of an axial flow blower. The subject of boundary-layer control has attracted considerable attention in respect to the isolated airfoil (1)1 but... blades . Flow through airfoils displays a region of laminar flow beginning at the leading edge. Further downstream, at approximately the location of the
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Development of Axial Continuous Metal Expeller for melt conditioning of alloys
NASA Astrophysics Data System (ADS)
Cassinath, Z.; Prasada Rao, A. K.
2016-02-01
ACME (Axial, centrifugal metal expeller) is a novel processing technology developed independently for conditioning liquid metal prior to solidification processing. The ACME process is based on an axial compressor and uses a rotor stator mechanism to impose a high shear rate and a high intensity of turbulence to the liquid metal, so that the conditioned liquid metal has uniform temperature and uniform chemical composition as it is expelled. The microstructural refinement is achieved through the process of dendrite fragmentation while taking advantage of the thixotropic property of semisolid metal slurry so that it can be conveyed for further downstream operations. This paper introduces the concept and its advantages over current technologies.
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NASA Astrophysics Data System (ADS)
Oliveriusová, Ludmila; Němec, Pavel; Pavelková, Zuzana; Sedláček, František
2014-07-01
Magnetoreception has been convincingly demonstrated in only a few mammalian species. Among rodents, magnetic compass orientation has been documented in four species of subterranean mole rats and two epigeic (i.e. active above ground) species—the Siberian hamster and the C57BL/6J mouse. The mole rats use the magnetic field azimuth to determine compass heading; their directional preference is spontaneous and unimodal, and their magnetic compass is magnetite-mediated. By contrast, the primary component of orientation response is learned in the hamster and the mouse, but both species also exhibit a weak spontaneous bimodal preference in the natural magnetic field. To determine whether the magnetic compass of wild epigeic rodents features the same functional properties as that of laboratory rodents, we investigated magnetic compass orientation in the bank vole Clethrionomys glareolus (Cricetidae, Rodentia). The voles exhibited a robust spontaneous bimodal directional preference, i.e. built nests and slept preferentially along the north-south axis, and deflected their directional preference according to a shift in the direction of magnetic north, clearly indicating that they were deriving directional information from the magnetic field. Thus, bimodal, axially symmetrical directional choice seems to be a common feature shared by epigeic rodents. However, spontaneous directional preference in the bank vole appeared to be more pronounced than that reported in the hamster and the mouse. These findings suggest that bank voles are well suited for future studies investigating the adaptive significance and mechanisms of magnetic orientation in epigeic rodents.
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Oliveriusová, Ludmila; Němec, Pavel; Pavelková, Zuzana; Sedláček, František
2014-07-01
Magnetoreception has been convincingly demonstrated in only a few mammalian species. Among rodents, magnetic compass orientation has been documented in four species of subterranean mole rats and two epigeic (i.e. active above ground) species-the Siberian hamster and the C57BL/6J mouse. The mole rats use the magnetic field azimuth to determine compass heading; their directional preference is spontaneous and unimodal, and their magnetic compass is magnetite-mediated. By contrast, the primary component of orientation response is learned in the hamster and the mouse, but both species also exhibit a weak spontaneous bimodal preference in the natural magnetic field. To determine whether the magnetic compass of wild epigeic rodents features the same functional properties as that of laboratory rodents, we investigated magnetic compass orientation in the bank vole Clethrionomys glareolus (Cricetidae, Rodentia). The voles exhibited a robust spontaneous bimodal directional preference, i.e. built nests and slept preferentially along the north-south axis, and deflected their directional preference according to a shift in the direction of magnetic north, clearly indicating that they were deriving directional information from the magnetic field. Thus, bimodal, axially symmetrical directional choice seems to be a common feature shared by epigeic rodents. However, spontaneous directional preference in the bank vole appeared to be more pronounced than that reported in the hamster and the mouse. These findings suggest that bank voles are well suited for future studies investigating the adaptive significance and mechanisms of magnetic orientation in epigeic rodents.
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Vrigneaud, Jean-Marc; McGrath, John; Courteau, Alan; Pegg, Rosie; Sanchez-Pastor Gomis, Alberto; Camacho, Angela; Martin, Gary; Schramm, Nils; Brunotte, François
2018-05-15
We evaluated the performance characteristics of a prototype preclinical PET scanner available as an easy clippable assembly that can dock to an MRI system. The single ring version of the PET system consists of 8 detectors, each of which comprises a 12 × 12 silicon photomultipliers (SiPMs) array coupled with a dual layer of offset scintillation crystals to measure depth of interaction. The crystal arrays have 29 × 29 (30 × 30 for the outer layer) 4 mm long LYSO crystals (6 mm for the outer layer). The ring diameter is 119.2 mm and the axial field of view is 50.4 mm. The NEMA NU-4-2008 protocol was followed for studying the PET performance. Temperature stability of SiPMs was also investigated. The peak system absolute sensitivity was 4.70% with an energy window of 250-750 keV. The spatial resolution was 1.28/1.88/1.85 mm FWHM (radial/tangential/axial) at a distance of 5 mm from the center. Peak noise equivalent counting rate (NECR) and scatter fraction for mouse phantom were 61.9 kcps at 14.9 MBq and 21.0%, respectively. The uniformity was 6.3% and the spill-over ratios in the images of the water- and air-filled chambers were 0.07 and 0.17, respectively. Recovery coefficients ranged from 0.13 to 0.96. Change in sensitivity as a function of ambient temperature was 0.3%/°C. These first results indicate excellent spatial resolution performance for use with animal studies. Moreover, the clippable assembly can be upgraded to accept a second ring of SiPMs modules, leading to improved sensitivity and axial coverage. © 2018 Institute of Physics and Engineering in Medicine.
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Effects of fried potato chip supplementation on mouse pregnancy and fetal development.
El-Sayyad, Hassan I; Abou-Egla, Mohamed H; El-Sayyad, Fawkia I; El-Ghawet, Heba A; Gaur, Rajiv L; Fernando, Augusta; Raj, Madhwa H G; Ouhtit, Allal
2011-03-01
Acrylamide (ACR), a proven rodent carcinogen, is present at significantly high quantities in commonly consumed foods such as potato chips, raising a health concern worldwide. The effects of ACR and fried potato chips (FPC) on pregnant mice and their offspring before and after birth were investigated and compared. In the pregnant mice, similar histologic abnormalities were found in various tissues for ACR intoxication and FPC supplementation. Drastic alterations were mainly seen in the liver, kidney, heart muscle, and epiphyseal cartilage of experimental dams. ACR and FPC increased the rate of abortion and neonatal mortality and decreased the total number, body weight, size, and crown-rump length of the offspring before and after birth. Interestingly, however, higher rates of congenital malformations were observed in the FPC-treated group. Although ossification of axial and appendicular bones was markedly retarded during fetal development, some ossified bones were missing in newly born offspring of treated groups. Furthermore, the incidence of missing ossification centers was higher in the FPC-treated than in the ACR-treated neonates. These results suggest that FPC can cause hazardous health effects and warrant a systematic study on the health effects of consumption of FPC and French fries in the general population. Copyright © 2011 Elsevier Inc. All rights reserved.
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Chaffey, Nigel; Barlow, Peter; Sundberg, Björn
2002-03-01
The involvement of microfilaments and microtubules in the development of the radial and axial components of secondary xylem (wood) in hybrid aspen (Populus tremula L. x P. tremuloides Michx.) was studied by indirect immunofluorescent localization techniques. In addition to cambial cells, the differentiated cell types considered were early- and late-wood vessel elements, axial parenchyma, normal-wood fibers and gelatinous fibers, and contact and isolation ray cells. Microfilaments were rare in ray cambial cells, but were abundant and axially arranged in their derivatives once cell elongation had begun, and persisted in that orientation in mature ray cells. Microfilaments were axially arranged in fusiform cambial cells and persisted in that orientation in all xylem derivatives of those cells. Microtubules were randomly oriented in ray and fusiform cells of the cambial zone. Dense arrays of parallel-aligned microtubules were oriented near axially in the developing gelatinous fibers, but at a wide range of angles in normal-wood fibers. Ellipses of microfilaments were associated with pit development in fiber cells and isolation ray cells. Rings of co-localized microtubules and microfilaments were associated with developing inter-vessel bordered pits and vessel-contact ray cell contact pits, and, in the case of bordered pits, these rings decreased in diameter as the over-arching pit border increased in size. Although only microtubules were seen at the periphery of the perforation plate of vessel elements, a prominent meshwork of microfilaments overlaid the perforation plate itself. A consensus view of the roles of the cytoskeleton during wood formation in angiosperm trees is presented.
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Axial force measurement for esophageal function testing
Gravesen, Flemming H; Funch-Jensen, Peter; Gregersen, Hans; Drewes, Asbjørn Mohr
2009-01-01
The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the “golden standard” for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method. PMID:19132762
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A Unified Development of Basis Reduction Methods for Rotor Blade Analysis
NASA Technical Reports Server (NTRS)
Ruzicka, Gene C.; Hodges, Dewey H.; Rutkowski, Michael (Technical Monitor)
2001-01-01
The axial foreshortening effect plays a key role in rotor blade dynamics, but approximating it accurately in reduced basis models has long posed a difficult problem for analysts. Recently, though, several methods have been shown to be effective in obtaining accurate,reduced basis models for rotor blades. These methods are the axial elongation method,the mixed finite element method, and the nonlinear normal mode method. The main objective of this paper is to demonstrate the close relationships among these methods, which are seemingly disparate at first glance. First, the difficulties inherent in obtaining reduced basis models of rotor blades are illustrated by examining the modal reduction accuracy of several blade analysis formulations. It is shown that classical, displacement-based finite elements are ill-suited for rotor blade analysis because they can't accurately represent the axial strain in modal space, and that this problem may be solved by employing the axial force as a variable in the analysis. It is shown that the mixed finite element method is a convenient means for accomplishing this, and the derivation of a mixed finite element for rotor blade analysis is outlined. A shortcoming of the mixed finite element method is that is that it increases the number of variables in the analysis. It is demonstrated that this problem may be rectified by solving for the axial displacements in terms of the axial forces and the bending displacements. Effectively, this procedure constitutes a generalization of the widely used axial elongation method to blades of arbitrary topology. The procedure is developed first for a single element, and then extended to an arbitrary assemblage of elements of arbitrary type. Finally, it is shown that the generalized axial elongation method is essentially an approximate solution for an invariant manifold that can be used as the basis for a nonlinear normal mode.
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Interference techniques in fluorescence microscopy
NASA Astrophysics Data System (ADS)
Dogan, Mehmet
We developed a set of interference-based optical microscopy techniques to study biological structures through nanometer-scale axial localization of fluorescent biomarkers. Spectral self-interference fluorescence microscopy (SSFM) utilizes interference of direct and reflected waves emitted from fluorescent molecules in the vicinity of planar reflectors to reveal the axial position of the molecules. A comprehensive calculation algorithm based on Green's function formalism is presented to verify the validity of approximations used in a far-field approach that describes the emission of fluorescent markers near interfaces. Using the validated model, theoretical limits of axial localization were determined with emphasis given to numerical aperture (NA) dependence of localization uncertainty. SSFM was experimentally demonstrated in conformational analysis of nucleoproteins. In particular, interaction between surface-tethered 75-mer double strand DNA and integration host factor (IHF) protein was probed on Si-SiO2 substrates by determining the axial position of fluorescent labels attached to the free ends of DNA molecules. Despite its sub-nanometer precision axial localization capability, SSFM lacks high lateral resolution due to the low-NA requirement for planar reflectors. We developed a second technique, 4Pi-SSFM, which improves the lateral resolution of a conventional SSFM system by an order of magnitude while achieving nanometer-scale axial localization precision. Using two opposing high-NA objectives, fluorescence signal is interferometrically collected and spectral interference pattern is recorded. Axial position of emitters is found from analysis of the spectra. The 4Pi-SSFM technique was experimentally demonstrated by determining the surface profiles of fabricated glass surfaces and outer membranes of Shigella, a type of Gram-negative bacteria. A further discussion is presented to localize surface O antigen, which is an important oligosaccharide structure in the virulence mechanism of the Gram-negative bacteria, including E. coli and Shigella.
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NASA Astrophysics Data System (ADS)
Kernicky, Timothy; Whelan, Matthew; Al-Shaer, Ehab
2018-06-01
A methodology is developed for the estimation of internal axial force and boundary restraints within in-service, prismatic axial force members of structural systems using interval arithmetic and contractor programming. The determination of the internal axial force and end restraints in tie rods and cables using vibration-based methods has been a long standing problem in the area of structural health monitoring and performance assessment. However, for structural members with low slenderness where the dynamics are significantly affected by the boundary conditions, few existing approaches allow for simultaneous identification of internal axial force and end restraints and none permit for quantifying the uncertainties in the parameter estimates due to measurement uncertainties. This paper proposes a new technique for approaching this challenging inverse problem that leverages the Set Inversion Via Interval Analysis algorithm to solve for the unknown axial forces and end restraints using natural frequency measurements. The framework developed offers the ability to completely enclose the feasible solutions to the parameter identification problem, given specified measurement uncertainties for the natural frequencies. This ability to propagate measurement uncertainty into the parameter space is critical towards quantifying the confidence in the individual parameter estimates to inform decision-making within structural health diagnosis and prognostication applications. The methodology is first verified with simulated data for a case with unknown rotational end restraints and then extended to a case with unknown translational and rotational end restraints. A laboratory experiment is then presented to demonstrate the application of the methodology to an axially loaded rod with progressively increased end restraint at one end.
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Ion trajectory simulations of axial ac dipolar excitation in the Orbitrap
NASA Astrophysics Data System (ADS)
Wu, Guangxiang; Noll, Robert J.; Plass, Wolfgang R.; Hu, Qizhi; Perry, Richard H.; Cooks, R. Graham
2006-07-01
The newly developed version of the multi-particle ion trajectory simulation program, ITSIM 6.0, was applied to simulate ac dipolar excitation of ion axial motion in the Orbitrap. The Orbitrap inner and outer electrodes were generated in AutoCAD, a 3D drawing program. The electrode geometry was imported into the 3D field solver COMSOL; the field array was then imported into ITSIM 6.0. Ion trajectories were calculated by solving Newton's equations using Runge-Kutta integration methods. Compared to the analytical solution, calculated radial components of the field at the device's "equator" (z = 0) were within 0.5% and calculated axial components midway between the inner and outer electrodes were within 0.2%. The experiments simulated here involved the control of axial motion of ions in the Orbitrap by the application of dipolar ac signals to the split outer electrodes, as described in a recently published paper from this laboratory [Hu et al., J. Phys. Chem. A 110 (2006) 2682]. In these experiments, ac signal was applied at the axial resonant frequency of a selected ion. Axial excitation and eventual ion ejection resulted when the ac was in phase with, i.e., had 0° phase relative to ion axial motion. De-excitation of ion axial motion until the ions were at z = 0 and at rest with respect to the z-axis resulted if the applied ac was out of phase with ion motion, with re-excitation of ion axial motion occurring if the dipolar ac was continued beyond this point. Both de-excitation and re-excitation could be achieved mass-selectively and depended on the amplitude and duration (number of cycles) of the applied ac. The effects of ac amplitude, frequency, phase relative to ion motion, and bandwidth of applied waveform were simulated. All simulation results were compared directly with the experimental data and good agreement was observed. Such ion motion control experiments and their simulation provide the possibility to improve Orbitrap performance and to develop tandem mass spectrometry (MS/MS) capabilities inside the Orbitrap.
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Foerst-Potts, L; Sadler, T W
1997-05-01
In mouse embryos, the muscle segment homeobox genes, Msx-1 and Msx-2 are expressed during critical stages of neural tube, neural crest, and craniofacial development, suggesting that these genes play important roles in organogenesis and cell differentiation. Although the patterns of expression are intriguing, little is known about the function of these genes in vertebrate embryonic development. Therefore, the expression of both genes, separately and together, was disrupted using antisense oligodeoxynucleotides and whole embryo culture techniques. Antisense attenuation of Msx-1 during early stages of neurulation produced hypoplasia of the maxillary, mandibular, and frontonasal prominences, eye anomalies, and somite and neural tube abnormalities. Eye defects consisted of enlarged optic vesicles, which may ultimately result in micropthalmia similar to that observed in Small eye mice homozygous for mutations in the Pax-6 gene. Histological sections and SEM analysis revealed a thinning of the neuroepithelium in the diencephalon and optic vesicle and mesenchymal deficiencies in the craniofacial region. Injections of Msx-2 antisense oligodeoxynucleotides produced similar malformations as those targeting Msx-1, with the exception that there was an increase in number and severity of neural tube and somite defects. Embryos injected with the combination of Msx-1 + Msx-2 antisense oligodeoxynucleotides showed no novel abnormalities, suggesting that the genes do not operate in a redundant manner.
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Eye size and shape in newborn children and their relation to axial length and refraction at 3 years.
Lim, Laurence Shen; Chua, Sharon; Tan, Pei Ting; Cai, Shirong; Chong, Yap-Seng; Kwek, Kenneth; Gluckman, Peter D; Fortier, Marielle V; Ngo, Cheryl; Qiu, Anqi; Saw, Seang-Mei
2015-07-01
To determine if eye size and shape at birth are associated with eye size and refractive error 3 years later. A subset of 173 full-term newborn infants from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort underwent magnetic resonance imaging (MRI) to measure the dimensions of the internal eye. Eye shape was assessed by an oblateness index, calculated as 1 - (axial length/width) or 1 - (axial length/height). Cycloplegic autorefraction (Canon Autorefractor RK-F1) and optical biometry (IOLMaster) were performed 3 years later. Both eyes of 173 children were analysed. Eyes with longer axial length at birth had smaller increases in axial length at 3 years (p < 0.001). Eyes with larger baseline volumes and surface areas had smaller increases in axial length at 3 years (p < 0.001 for both). Eyes which were more oblate at birth had greater increases in axial length at 3 years (p < 0.001). Using width to calculate oblateness, prolate eyes had smaller increases in axial length at 3 years compared to oblate eyes (p < 0.001), and, using height, prolate and spherical eyes had smaller increases in axial length at 3 years compared to oblate eyes (p < 0.001 for both). There were no associations between eye size and shape at birth and refraction, corneal curvature or myopia at 3 years. Eyes that are larger and have prolate or spherical shapes at birth exhibit smaller increases in axial length over the first 3 years of life. Eye size and shape at birth influence subsequent eye growth but not refractive error development. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.
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Cheng, Ching-Yu; Schache, Maria; Ikram, M Kamran; Young, Terri L; Guggenheim, Jeremy A; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J M; Barathi, Veluchamy A; Liao, Jiemin; Hysi, Pirro G; Bailey-Wilson, Joan E; St Pourcain, Beate; Kemp, John P; McMahon, George; Timpson, Nicholas J; Evans, David M; Montgomery, Grant W; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F; Amin, Najaf; van Leeuwen, Elisabeth M; Wilson, James F; Pennell, Craig E; van Duijn, Cornelia M; de Jong, Paulus T V M; Vingerling, Johannes R; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Burdon, Kathryn P; Craig, Jamie E; Iyengar, Sudha K; Igo, Robert P; Lass, Jonathan H; Chew, Emily Y; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E; Hosseini, S Mohsen; Paterson, Andrew D; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K H; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W; Williams, Cathy; Oostra, Ben A; Teo, Yik-Ying; Hammond, Christopher J; Stambolian, Dwight; Mackey, David A; Klaver, Caroline C W; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N
2013-08-08
Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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Gaertner, Maria; Cimalla, Peter; Meissner, Sven; Kuebler, Wolfgang M; Koch, Edmund
2012-07-01
Although several strategies exist for a minimal-invasive treatment of patients with lung failure, the mortality rate of acute respiratory distress syndrome still reaches 30% at minimum. This striking number indicates the necessity of understanding lung dynamics on an alveolar level. To investigate the dynamical behavior on a microscale, we used three-dimensional geometrical and functional imaging to observe tissue parameters including alveolar size and length of embedded elastic fibers during ventilation. We established a combined optical coherence tomography (OCT) and confocal fluorescence microscopy system that is able to monitor the distension of alveolar tissue and elastin fibers simultaneously within three dimensions. The OCT system can laterally resolve a 4.9 μm line pair feature and has an approximately 11 μm full-width-half-maximum axial resolution in air. confocal fluorescence microscopy visualizes molecular properties of the tissue with a resolution of 0.75 μm (laterally), and 5.9 μm (axially) via fluorescence detection of the dye sulforhodamine B specifically binding to elastin. For system evaluation, we used a mouse model in situ to perform lung distension by application of different constant pressure values within the physiological regime. Our method enables the investigation of alveolar dynamics by helping to reveal basic processes emerging during artificial ventilation and breathing.
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Notochord morphogenesis in mice: Current understanding & open questions.
Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina
2016-05-01
The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Two-color temporal focusing multiphoton excitation imaging with tunable-wavelength excitation
NASA Astrophysics Data System (ADS)
Lien, Chi-Hsiang; Abrigo, Gerald; Chen, Pei-Hsuan; Chien, Fan-Ching
2017-02-01
Wavelength tunable temporal focusing multiphoton excitation microscopy (TFMPEM) is conducted to visualize optical sectioning images of multiple fluorophore-labeled specimens through the optimal two-photon excitation (TPE) of each type of fluorophore. The tunable range of excitation wavelength was determined by the groove density of the grating, the diffraction angle, the focal length of lenses, and the shifting distance of the first lens in the beam expander. Based on a consideration of the trade-off between the tunable-wavelength range and axial resolution of temporal focusing multiphoton excitation imaging, the presented system demonstrated a tunable-wavelength range from 770 to 920 nm using a diffraction grating with groove density of 830 lines/mm. TPE fluorescence imaging examination of a fluorescent thin film indicated that the width of the axial confined excitation was 3.0±0.7 μm and the shifting distance of the temporal focal plane was less than 0.95 μm within the presented wavelength tunable range. Fast different wavelength excitation and three-dimensionally rendered imaging of Hela cell mitochondria and cytoskeletons and mouse muscle fibers were demonstrated. Significantly, the proposed system can improve the quality of two-color TFMPEM images through different excitation wavelengths to obtain higher-quality fluorescent signals in multiple-fluorophore measurements.
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Constitutive relations describing creep deformation for multi-axial time-dependent stress states
NASA Astrophysics Data System (ADS)
McCartney, L. N.
1981-02-01
A THEORY of primary and secondary creep deformation in metals is presented, which is based upon the concept of tensor internal state variables and the principles of continuum mechanics and thermodynamics. The theory is able to account for both multi-axial and time-dependent stress and strain states. The wellknown concepts of elastic, anelastic and plastic strains follow naturally from the theory. Homogeneous stress states are considered in detail and a simplified theory is derived by linearizing with respect to the internal state variables. It is demonstrated that the model can be developed in such a way that multi-axial constant-stress creep data can be presented as a single relationship between an equivalent stress and an equivalent strain. It is shown how the theory may be used to describe the multi-axial deformation of metals which are subjected to constant stress states. The multi-axial strain response to a general cyclic stress state is calculated. For uni-axial stress states, square-wave loading and a thermal fatigue stress cycle are analysed.
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Integrated controls and health monitoring fiberoptic shaft monitor
NASA Technical Reports Server (NTRS)
Coleman, P.; Darejeh, H.; Collins, J. J.
1989-01-01
Recent work was performed on development optical technology to provide real time monitoring of shaft speed, shaft axial displacement, and shaft orbit of the OTVE hydrostatic bearing tester. Results show shaft axial displacement can be optically measured (at the same time as shaft orbital motion and speed) to within 0.3 mills by two fiber optic deflectometers. The final results of this condition monitoring development effort are presented.
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Evaluation of a Multi-Axial, Temperature, and Time Dependent (MATT) Failure Model
NASA Technical Reports Server (NTRS)
Richardson, D. E.; Anderson, G. L.; Macon, D. J.; Rudolphi, Michael (Technical Monitor)
2002-01-01
To obtain a better understanding the response of the structural adhesives used in the Space Shuttle's Reusable Solid Rocket Motor (RSRM) nozzle, an extensive effort has been conducted to characterize in detail the failure properties of these adhesives. This effort involved the development of a failure model that includes the effects of multi-axial loading, temperature, and time. An understanding of the effects of these parameters on the failure of the adhesive is crucial to the understanding and prediction of the safety of the RSRM nozzle. This paper documents the use of this newly developed multi-axial, temperature, and time (MATT) dependent failure model for modeling failure for the adhesives TIGA 321, EA913NA, and EA946. The development of the mathematical failure model using constant load rate normal and shear test data is presented. Verification of the accuracy of the failure model is shown through comparisons between predictions and measured creep and multi-axial failure data. The verification indicates that the failure model performs well for a wide range of conditions (loading, temperature, and time) for the three adhesives. The failure criterion is shown to be accurate through the glass transition for the adhesive EA946. Though this failure model has been developed and evaluated with adhesives, the concepts are applicable for other isotropic materials.
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Lee, Sang-Mok; Choi, Hyuk Jin; Choi, Heejin; Kim, Mee Kum; Wee, Won Ryang
2016-10-07
BACKGROUND: Though the development and fitting of scleral contact lenses are expanding steadily, there is no simple method to provide scleral metrics for scleral contact lens fitting yet. The aim of this study was to establish formulae for estimation of the axial radius of curvature (ARC) of the anterior sclera using ocular biometric parameters that can be easily obtained with conventional devices. A semi-automated stitching method and a computational analysis tool for calculating ARC were developed by using the ImageJ and MATLAB software. The ARC of all the ocular surface points were analyzed from the composite horizontal cross-sectional images of the right eyes of 24 volunteers; these measurements were obtained using anterior segment optical coherence tomography for a previous study (AS-OCT; Visante). Ocular biometric parameters were obtained from the same volunteers with slit-scanning topography and partial coherence interferometry. Correlation analysis was performed between the ARC at 8 mm to the axis line (ARC[8]) and other ocular parameters (including age). With ARC obtained on several nasal and temporal points (7.0, 7.5, 8.0, 8.5, and 9.0 mm from the axis line), univariate and multivariate linear regression analyses were performed to develop a model for estimating ARC with the help of ocular biometric parameters. Axial length, spherical equivalent, and angle kappa showed correlations with temporal ARC[8] (tARC[8]; Pearson's r = 0.653, -0.579, and -0.341; P = 0.001, 0.015, and 0.015, respectively). White-to-white corneal diameter (WTW) and anterior chamber depth (ACD) showed correlation with nasal ARC[8] (nARC[8]; Pearson's r = -0.492 and -0.461; P = 0.015 and 0.023, respectively). The formulae for estimating scleral curvatures (tARC, nARC, and average ARC) were developed as a function of axial length, ACD, WTW, and distance from the axis line, with good determinant power (72 - 80 %; SPSS ver. 22.0). Angle kappa showed strong correlation with axial length (Pearson's r = -0.813, P <0.001), and the different correlation patterns of nasal and temporal ARC with axial length can be explained by the ocular surface deviation represented by angle kappa. Axial length, ACD, and WTW are useful parameters for estimating the ARC of the anterior sclera, which is important for the haptic design of scleral contact lenses. Angle kappa affects the discrepancies between the nasal and temporal scleral curvature.
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Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine
NASA Technical Reports Server (NTRS)
Kopasakis, George; Connolly, Joseph W.; Cheng, Larry
2015-01-01
This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design.
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Kumar, Narender; Rodrigues, G; Lakshmy, P S; Baskaran, R; Mathur, Y; Ahuja, R; Kanjilal, D
2014-02-01
A compact microwave ion source has been designed and developed for operation at a frequency of 2.45 GHz. The axial magnetic field is based on two permanent magnet rings, operating in the "off-resonance" mode and is tunable by moving the permanent magnets. In order to understand the electron energy distribution function, x-ray bremsstrahlung has been measured in the axial direction. Simulation studies on the x-ray bremsstrahlung have been carried out to compare with the experimental results. The effect of the axial magnetic field with respect to the microwave launching position and the position of the extraction electrode on the x-ray bremsstrahlung have been studied.
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Analysis of shear buckling of cylindrical shells. II - Effects of combined loadings
NASA Astrophysics Data System (ADS)
Kokubo, Kunio; Nagashima, Hideaki; Takayanagi, Masaaki; Madokoro, Manabu; Mochizuki, Akira; Ikeuchi, Hisaaki
1992-03-01
Cylindrical shells subjected to lateral loads buckle in shear or bending buckling modes. The effects of combined loadings are investigated by developing a special-purpose FEM program using the 8-node isoparametric shell element. Three types of loading, lateral and axial loads, and pure bending moments are considered. For short cylindrical shells, shear buckling modes are dominant, but elephant-foot bulges take place with an increase in bending moments. Effects of axial loads on shear buckling and the elephant-foot bulge are investigated. In the case of shear buckling the axial load affects the buckling mode as well as the buckling load. For bending bucklings, the axial loads have a great effect on the buckling load.
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J-PET: A New Technology for the Whole-body PET Imaging
NASA Astrophysics Data System (ADS)
Niedźwiecki, S.; Białas, P.; Curceanu, C.; Czerwiński, E.; Dulski, K.; Gajos, A.; Głowacz, B.; Gorgol, M.; Hiesmayr, B. C.; Jasińska, B.; Kapłon, Ł.; Kisielewska-Kamińska, D.; Korcyl, G.; Kowalski, P.; Kozik, T.; Krawczyk, N.; Krzemień, W.; Kubicz, E.; Mohammed, M.; Pawlik-Niedźwiecka, M.; Pałka, M.; Raczyński, L.; Rudy, Z.; Sharma, N. G.; Sharma, S.; Shopa, R. Y.; Silarski, M.; Skurzok, M.; Wieczorek, A.; Wiślicki, W.; Zgardzińska, B.; Zieliński, M.; Moskal, P.
The Jagiellonian Positron Emission Tomograph (J-PET) is the first PET built from plastic scintillators. J-PET prototype consists of 192 detection modules arranged axially in three layers forming a cylindrical diagnostic chamber with the inner diameter of 85 cm and the axial field-of-view of 50 cm. An axial arrangement of long strips of plastic scintillators, their small light attenuation, superior timing properties, and relative ease of the increase of the axial field-of-view opens promising perspectives for the cost effective construction of the whole-body PET scanner, as well as construction of MR and CT compatible PET inserts. Present status of the development of the J-PET tomograph will be presented and discussed.
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Finite element analysis of the axial stiffness of a ball screw
NASA Astrophysics Data System (ADS)
Zhou, L.-X.; Li, P.-Y.
2018-06-01
The ball screw was developed for high speed and high precision operation; therefore, increasingly greater demands have been placed on the stiffness of the ball screw. Firstly, ANSYS software was used to compare the axial stiffness of a single-nut and single-arc ball screw and a single-nut and double-arc ball screw when the spiral angle is not considered. On this basis, the model of a single-nut ball screw was established taking into consideration the spiral lead angle, and then the variations in displacement and stiffness when the ball screw pair was subjected to an axial force were determined. The axial contact stiffness of the double-nut ball screw pair, subject to a pre-tightening force, was analyzed, according to the above-mentioned steps. The simulation results demonstrated that under the same working conditions, the stiffness of the double-arc ball screw was larger by between 5∼100 N/um than that of the single-arc ball screw. The spiral lead angle increased the axial stiffness of the ball screw pair, and the axial stiffness of the double-nut ball screw pair subject to a pre-tightening force was larger by between 790∼1360 N/um than that of the axial stiffness of the single-nut ball screw pair.
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Effect of Culture Conditions on Viability of Mouse and Rat Embryos Developed in Vitro
Popova, Elena; Bader, Michael; Krivokharchenko, Alexander
2011-01-01
Currently in vitro culture of mouse preimplantation embryos has become a very important technique to investigate different mechanisms of early embryogenesis. However, there is a big difference in the preimplantation development between mammalian species. Despite close relatedness to mice, in vitro cultivation of rat preimplantation embryos is still delicate and needs further investigation and optimizations. In this study we have compared the in vitro developmental potential of mouse and rat embryos cultured at different culture conditions in parallel experiments. Interestingly, mouse zygotes developed in vitro until blastocyst stage even in inadequate medium without any phosphates and with low osmolarity which was formulated especially for cultivation of rat embryos. Rat parthenotes and zygotes developed in M16 medium formulated for mouse embryos only till 2-cell stage and further development is blocked completely at this stage. Moreover, developmental ability of rat embryos in vitro was significantly lower in comparison with mouse even in special rat mR1ECM medium. Mouse and rat embryos at 2-cell stage obtained in vivo developed until blastocyst stages significantly more efficiently compared to zygotes. Culture of mouse zygotes in glass capillaries resulted in a significantly higher rate of morula and blastocyst development compared with dishes. The Well-of-the-Well system resulted in a significant improvement when compared with dishes for the culture of rat zygotes only until morula stage. Reduced oxygen tension increased the developmental rate of rat but not mouse zygotes until blastocyst stage. This study demonstrates that development of early preimplantation embryos is altered by different culture conditions and show strong differences even between two related species such as mice and rats. Therefore, for understanding the fundamental mechanisms of early mammalian development it is very important to use embryos of various species. PMID:24710194
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NASA Astrophysics Data System (ADS)
Maizir, H.; Suryanita, R.
2018-01-01
A few decades, many methods have been developed to predict and evaluate the bearing capacity of driven piles. The problem of the predicting and assessing the bearing capacity of the pile is very complicated and not yet established, different soil testing and evaluation produce a widely different solution. However, the most important thing is to determine methods used to predict and evaluate the bearing capacity of the pile to the required degree of accuracy and consistency value. Accurate prediction and evaluation of axial bearing capacity depend on some variables, such as the type of soil, diameter, and length of pile, etc. The aims of the study of Artificial Neural Networks (ANNs) are utilized to obtain more accurate and consistent axial bearing capacity of a driven pile. ANNs can be described as mapping an input to the target output data. The method using the ANN model developed to predict and evaluate the axial bearing capacity of the pile based on the pile driving analyzer (PDA) test data for more than 200 selected data. The results of the predictions obtained by the ANN model and the PDA test were then compared. This research as the neural network models give a right prediction and evaluation of the axial bearing capacity of piles using neural networks.
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Biaxial Response of Passive Human Cerebral Arteries
Monson, Kenneth L.; Barbaro, Nicholas M.; Manley, Geoffrey T.
2008-01-01
The cerebral circulation is fundamental to the health and maintenance of brain tissue, but injury and disease may result in dysfunction of the vessels. Characterization of cerebral vessel mechanical response is an important step toward a more complete understanding of injury mechanisms and disease development in these vessels, paving the way for improved prevention and treatment. We recently reported a large series of uniaxial tests on fresh human cerebral vessels, but the multi-axial behavior of these vessels has not been previously described. Twelve arteries were obtained from the surface of the temporal lobe of patients undergoing surgery and were subjected to various combinations of axial stretch and pressure around typical physiological conditions before being stretched to failure. Axial and circumferential responses were compared, and measured data were fit to a four parameter, Fung-type hyperelastic constitutive model. Artery behavior was nonlinear and anisotropic, with considerably greater resistance to deformation in the axial direction than around the circumference. Results from axial failure tests of pressurized vessels resulted in a small shift in stress-stretch response compared to previously reported data from unpressurized specimens. These results further define the biaxial response of the cerebral arteries and provide data required for more rigorous study of head injury mechanisms and development of cerebrovascular disease. PMID:18855141
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NASA Astrophysics Data System (ADS)
Hérisson, Benjamin; Challamel, Noël; Picandet, Vincent; Perrot, Arnaud
2016-09-01
The static behavior of the Fermi-Pasta-Ulam (FPU) axial chain under distributed loading is examined. The FPU system examined in the paper is a nonlinear elastic lattice with linear and quadratic spring interaction. A dimensionless parameter controls the possible loss of convexity of the associated quadratic and cubic energy. Exact analytical solutions based on Hurwitz zeta functions are developed in presence of linear static loading. It is shown that this nonlinear lattice possesses scale effects and possible localization properties in the absence of energy convexity. A continuous approach is then developed to capture the main phenomena observed regarding the discrete axial problem. The associated continuum is built from a continualization procedure that is mainly based on the asymptotic expansion of the difference operators involved in the lattice problem. This associated continuum is an enriched gradient-based or nonlocal axial medium. A Taylor-based and a rational differential method are both considered in the continualization procedures to approximate the FPU lattice response. The Padé approximant used in the continualization procedure fits the response of the discrete system efficiently, even in the vicinity of the limit load when the non-convex FPU energy is examined. It is concluded that the FPU lattice system behaves as a nonlocal axial system in dynamic but also static loading.
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NASA Astrophysics Data System (ADS)
Nyilas, A.; Weiss, K. P.
2008-03-01
A new extensometer capable of measuring diametral strains during axial loading of structural materials and superconducting composite wires has been developed. Using this new transducer it is possible to determine both the averaged axial strain and the transverse strain. The diametral extensometer with a mass of around 1 g is foreseen to be clamped onto the wire inside the averaging double extensometer sensing device system. The sensitivity of this new diametral extensometer is very high, nearly a factor of ten higher than the axial extensometer system. In addition, for structural materials and for composite materials an adjustable diametral extensometer enabling to test specimens between 5 mm and 15 mm diameter has been also developed and tested successfully at 4 K. For materials 304 L, Inconel 718, and modified Type 316LN stainless steel cast alloy the Poisson's coefficient could be determined at 295 K. Type 310 S stainless steel has been investigated at 7 K and at 4 K using the adjustable extensometer to determine the Poisson's coefficient, too. Furthermore, different types of superconducting A15 phase composite wires with diameters between 0.8 and 1.3 mm's were characterized in axial and diametral orientation.
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A Digital Preclinical PET/MRI Insert and Initial Results.
Weissler, Bjoern; Gebhardt, Pierre; Dueppenbecker, Peter M; Wehner, Jakob; Schug, David; Lerche, Christoph W; Goldschmidt, Benjamin; Salomon, Andre; Verel, Iris; Heijman, Edwin; Perkuhn, Michael; Heberling, Dirk; Botnar, Rene M; Kiessling, Fabian; Schulz, Volkmar
2015-11-01
Combining Positron Emission Tomography (PET) with Magnetic Resonance Imaging (MRI) results in a promising hybrid molecular imaging modality as it unifies the high sensitivity of PET for molecular and cellular processes with the functional and anatomical information from MRI. Digital Silicon Photomultipliers (dSiPMs) are the digital evolution in scintillation light detector technology and promise high PET SNR. DSiPMs from Philips Digital Photon Counting (PDPC) were used to develop a preclinical PET/RF gantry with 1-mm scintillation crystal pitch as an insert for clinical MRI scanners. With three exchangeable RF coils, the hybrid field of view has a maximum size of 160 mm × 96.6 mm (transaxial × axial). 0.1 ppm volume-root-mean-square B 0-homogeneity is kept within a spherical diameter of 96 mm (automatic volume shimming). Depending on the coil, MRI SNR is decreased by 13% or 5% by the PET system. PET count rates, energy resolution of 12.6% FWHM, and spatial resolution of 0.73 mm (3) (isometric volume resolution at isocenter) are not affected by applied MRI sequences. PET time resolution of 565 ps (FWHM) degraded by 6 ps during an EPI sequence. Timing-optimized settings yielded 260 ps time resolution. PET and MR images of a hot-rod phantom show no visible differences when the other modality was in operation and both resolve 0.8-mm rods. Versatility of the insert is shown by successfully combining multi-nuclei MRI ((1)H/(19)F) with simultaneously measured PET ((18)F-FDG). A longitudinal study of a tumor-bearing mouse verifies the operability, stability, and in vivo capabilities of the system. Cardiac- and respiratory-gated PET/MRI motion-capturing (CINE) images of the mouse heart demonstrate the advantage of simultaneous acquisition for temporal and spatial image registration.
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Development Of A Magnetic Directional-Solidification Furnace
NASA Technical Reports Server (NTRS)
Aldrich, Bill R.; Lehoczky, Sandor L.
1996-01-01
Report describes development of directional-solidification furnace in which axial magnetic field is imposed by surrounding ring permanent magnets and/or electromagnets and pole pieces. Furnace provides controlled axial temperature gradients in multiple zones, through which ampoule containing sample of material to be solidified is translated at controlled speed by low-vibration, lead-screw, stepping-motor-driven mechanism. Intended for use in low-gravity (spaceflight) experiments on melt growth of high-purity semiconductor crystals.
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Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging
NASA Astrophysics Data System (ADS)
Yang, Yongfeng; Tai, Yuan-Chuan; Siegel, Stefan; Newport, Danny F.; Bai, Bing; Li, Quanzheng; Leahy, Richard M.; Cherry, Simon R.
2004-06-01
MicroPET II is a newly developed PET (positron emission tomography) scanner designed for high-resolution imaging of small animals. It consists of 17 640 LSO crystals each measuring 0.975 × 0.975 × 12.5 mm3, which are arranged in 42 contiguous rings, with 420 crystals per ring. The scanner has an axial field of view (FOV) of 4.9 cm and a transaxial FOV of 8.5 cm. The purpose of this study was to carefully evaluate the performance of the system and to optimize settings for in vivo mouse and rat imaging studies. The volumetric image resolution was found to depend strongly on the reconstruction algorithm employed and averaged 1.1 mm (1.4 µl) across the central 3 cm of the transaxial FOV when using a statistical reconstruction algorithm with accurate system modelling. The sensitivity, scatter fraction and noise-equivalent count (NEC) rate for mouse- and rat-sized phantoms were measured for different energy and timing windows. Mouse imaging was optimized with a wide open energy window (150-750 keV) and a 10 ns timing window, leading to a sensitivity of 3.3% at the centre of the FOV and a peak NEC rate of 235 000 cps for a total activity of 80 MBq (2.2 mCi) in the phantom. Rat imaging, due to the higher scatter fraction, and the activity that lies outside of the field of view, achieved a maximum NEC rate of 24 600 cps for a total activity of 80 MBq (2.2 mCi) in the phantom, with an energy window of 250-750 keV and a 6 ns timing window. The sensitivity at the centre of the FOV for these settings is 2.1%. This work demonstrates that different scanner settings are necessary to optimize the NEC count rate for different-sized animals and different injected doses. Finally, phantom and in vivo animal studies are presented to demonstrate the capabilities of microPET II for small-animal imaging studies.
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NASA Astrophysics Data System (ADS)
Wang, Jing; Shen, Huoming; Zhang, Bo; Liu, Juan; Zhang, Yingrong
2018-07-01
We investigate the transverse free vibration behaviour of axially moving nanobeams based on the nonlocal strain gradient theory. Considering the geometrical nonlinearity, which takes the form of von Kármán strains, the coupled plane motion equations and related boundary conditions of a new size-dependent beam model of Euler-Bernoulli type are developed using the generalized Hamilton principle. Using the simply supported axially moving nanobeams as an example, the complex modal analysis method is adopted to solve the governing equation; then, the effect of the order of modal truncation on the natural frequencies is discussed. Subsequently, the roles of the nonlocal parameter, material characteristic parameter, axial speed, stiffness and axial support rigidity parameter on the free vibration are comprehensively addressed. The material characteristic parameter induces the stiffness hardening of nanobeams, while the nonlocal parameter induces stiffness softening. In addition, the roles of small-scale parameters on the flutter critical velocity and stability are explained.
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Principal Effects of Axial Load on Moment-Distribution Analysis of Rigid Structures
NASA Technical Reports Server (NTRS)
James, Benjamin Wylie
1935-01-01
This thesis presents the method of moment distribution modified to include the effect of axial load upon the bending moments. This modification makes it possible to analyze accurately complex structures, such as rigid fuselage trusses, that heretofore had to be analyzed by approximate formulas and empirical rules. The method is simple enough to be practicable even for complex structures, and it gives a means of analysis for continuous beams that is simpler than the extended three-moment equation now in common use. When the effect of axial load is included, it is found that the basic principles of moment distribution remain unchanged, the only difference being that the factors used, instead of being constants for a given member, become functions of the axial load. Formulas have been developed for these factors, and curves plotted so that their applications requires no more work than moment distribution without axial load. Simple problems have been included to illustrate the use of the curves.
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Organocatalytic atroposelective synthesis of axially chiral styrenes
NASA Astrophysics Data System (ADS)
Zheng, Sheng-Cai; Wu, San; Zhou, Qinghai; Chung, Lung Wa; Ye, Liu; Tan, Bin
2017-05-01
Axially chiral compounds are widespread in biologically active compounds and are useful chiral ligands or organocatalysts in asymmetric catalysis. It is well-known that styrenes are one of the most abundant and principal feedstocks and thus represent excellent prospective building blocks for chemical synthesis. Driven by the development of atroposelective synthesis of axially chiral styrene derivatives, we discovered herein the asymmetric organocatalytic approach via direct Michael addition reaction of substituted diones/ketone esters/malononitrile to alkynals. The axially chiral styrene compounds were produced with good chemical yields, enantioselectivities and almost complete E/Z-selectivities through a secondary amine-catalysed iminium activation strategy under mild conditions. Such structural motifs are important precursors for further transformations into biologically active compounds and synthetic useful intermediates and may have potential applications in asymmetric synthesis as olefin ligands or organocatalysts.
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Development of Software to Model AXAF-I Image Quality
NASA Technical Reports Server (NTRS)
Geary, Joseph; Hawkins, Lamar; Ahmad, Anees; Gong, Qian
1997-01-01
This report describes work conducted on Delivery Order 181 between October 1996 through June 1997. During this period software was written to: compute axial PSD's from RDOS AXAF-I mirror surface maps; plot axial surface errors and compute PSD's from HDOS "Big 8" axial scans; plot PSD's from FITS format PSD files; plot band-limited RMS vs axial and azimuthal position for multiple PSD files; combine and organize PSD's from multiple mirror surface measurements formatted as input to GRAZTRACE; modify GRAZTRACE to read FITS formatted PSD files; evaluate AXAF-I test results; improve and expand the capabilities of the GT x-ray mirror analysis package. During this period work began on a more user-friendly manual for the GT program, and improvements were made to the on-line help manual.
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Dynamic gene expression of Lin-28 during embryonic development in mouse and chicken.
Yokoyama, Shigetoshi; Hashimoto, Megumi; Shimizu, Hirohito; Ueno-Kudoh, Hiroe; Uchibe, Kenta; Kimura, Ichiro; Asahara, Hiroshi
2008-02-01
The Caenorhabditis elegans heterochronic gene lin-28 regulates developmental timing in the nematode trunk. We report the dynamic expression patterns of Lin-28 homologues in mouse and chick embryos. Whole mount in situ hybridization revealed specific and intriguing expression patterns of Lin-28 in the developing mouse and chick limb bud. Mouse Lin-28 expression was detected in both the forelimb and hindlimb at E9.5, but disappeared from the forelimb at E10.5, and finally from the forelimb and hindlimb at E11.5. Chicken Lin-28, which was first detected in the limb primordium at stage 15/16, was also downregulated as the stage proceeded. The amino acid sequences of mouse and chicken Lin-28 genes are highly conserved and the similar expression patterns of Lin-28 during limb development in mouse and chicken suggest that this heterochronic gene is also conserved during vertebrate limb development.
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NASA Technical Reports Server (NTRS)
Martin, E. Dale
1961-01-01
A study is made of the steady laminar flow of a compressible viscous fluid in a circular pipe when the fluid is accelerated by an axial body force. The application of the theory to the magnetofluidmechanics of an electrically conducting gas accelerated by electric and magnetic fields is discussed. Constant viscosity, thermal conductivity, and electrical conductivity are assumed. Fully developed flow velocity and temperature profiles are shown, and detailed results of the accelerating flow development, including velocity and pressure as functions of distance, are given for the case where the axial body force is constant and for the case where it is a linear function of velocity. From these results are determined the pipe entry length and the pressure difference required.
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Dynamics of intrinsic axial flows in unsheared, uniform magnetic fields
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, J. C.; Diamond, P. H.; Xu, X. Q.
2016-05-15
A simple model for the generation and amplification of intrinsic axial flow in a linear device, controlled shear decorrelation experiment, is proposed. This model proposes and builds upon a novel dynamical symmetry breaking mechanism, using a simple theory of drift wave turbulence in the presence of axial flow shear. This mechanism does not require complex magnetic field structure, such as shear, and thus is also applicable to intrinsic rotation generation in tokamaks at weak or zero magnetic shear, as well as to linear devices. This mechanism is essentially the self-amplification of the mean axial flow profile, i.e., a modulational instability.more » Hence, the flow development is a form of negative viscosity phenomenon. Unlike conventional mechanisms where the residual stress produces an intrinsic torque, in this dynamical symmetry breaking scheme, the residual stress induces a negative increment to the ambient turbulent viscosity. The axial flow shear is then amplified by this negative viscosity increment. The resulting mean axial flow profile is calculated and discussed by analogy with the problem of turbulent pipe flow. For tokamaks, the negative viscosity is not needed to generate intrinsic rotation. However, toroidal rotation profile gradient is enhanced by the negative increment in turbulent viscosity.« less
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Aerodynamic Analysis of Multistage Turbomachinery Flows in Support of Aerodynamic Design
NASA Technical Reports Server (NTRS)
Adamczyk, John J.
1999-01-01
This paper summarizes the state of 3D CFD based models of the time average flow field within axial flow multistage turbomachines. Emphasis is placed on models which are compatible with the industrial design environment and those models which offer the potential of providing credible results at both design and off-design operating conditions. The need to develop models which are free of aerodynamic input from semi-empirical design systems is stressed. The accuracy of such models is shown to be dependent upon their ability to account for the unsteady flow environment in multistage turbomachinery. The relevant flow physics associated with some of the unsteady flow processes present in axial flow multistage machinery are presented along with procedures which can be used to account for them in 3D CFD simulations. Sample results are presented for both axial flow compressors and axial flow turbines which help to illustrate the enhanced predictive capabilities afforded by including these procedures in 3D CFD simulations. Finally, suggestions are given for future work on the development of time average flow models.
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Development of optimized, graded-permeability axial groove heat pipes
NASA Technical Reports Server (NTRS)
Kapolnek, Michael R.; Holmes, H. Rolland
1988-01-01
Heat pipe performance can usually be improved by uniformly varying or grading wick permeability from end to end. A unique and cost effective method for grading the permeability of an axial groove heat pipe is described - selective chemical etching of the pipe casing. This method was developed and demonstrated on a proof-of-concept test article. The process improved the test article's performance by 50 percent. Further improvement is possible through the use of optimally etched grooves.
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A mini axial and a permanent maglev radial heart pump.
Qian, Kun-Xi; Ru, Wei-Min; Wang, Hao; Jing, Teng
2007-05-31
The implantability and durability have been for decades the focus of artificial heart R&D. A mini axial and a maglev radial pump have been developed to meet with such requirements.The mini axial pump weighing 27g (incl.5g rotor) has an outer diameter of 21mm and a length of 10mm in its largest point, but can produce a maximal blood flow of 6l/min with 50mmHg pressure increase. Therefore, it is suitable for the patients of 40-60kg body weight. For other patients of 60-80kg or 80-100kg body weight, the mini axial pumps of 23mm and 25mm outer diameter had been developed before, these devices were acknowledged to be the world smallest LVADs by Guinness World Record Center in 2004.The permanent maglev radial pump weighing 150g is a shaft-less centrifugal pump with permanent magnetic bearings developed by the author. It needs no second coil for suspension of the rotor except the motor coil, different from all other maglev pumps developed in USA, Japan, European, etc. Thus no detecting and controlling systems as well as no additional power supply for maglev are necessary. The pump can produce a blood flow up to as large as 10l/min against 100mmHg pressure.An implantable and durable blood pump will be a viable alternative to natural donor heart for transplantation.
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Association of Axial Length With Risk of Uncorrectable Visual Impairment for Europeans With Myopia.
Tideman, J Willem L; Snabel, Margaretha C C; Tedja, Milly S; van Rijn, Gwyneth A; Wong, King T; Kuijpers, Robert W A M; Vingerling, Johannes R; Hofman, Albert; Buitendijk, Gabriëlle H S; Keunen, Jan E E; Boon, Camiel J F; Geerards, Annette J M; Luyten, Gregorius P M; Verhoeven, Virginie J M; Klaver, Caroline C W
2016-12-01
Myopia (ie, nearsightedness) is becoming the most common eye disorder to cause blindness in younger persons in many parts of the world. Visual impairment due to myopia is associated with structural changes of the retina and the globe because of elongation of the eye axis. How axial length-a sum of the anterior chamber depth, lens thickness, and vitreous chamber depth-and myopia relate to the development of visual impairment over time is unknown. To evaluate the association between axial length, spherical equivalent, and the risk of visual impairment and to make projections of visual impairment for regions with high prevalence rates. This cross-sectional study uses population-based data from the Rotterdam Study I (1990 to 1993), II (2000 to 2002), and III (2006 to 2008) and the Erasmus Rucphen Family Study (2002 to 2005) as well as case-control data from the Myopia Study (2010 to 2012) from the Netherlands. In total, 15 404 individuals with data on spherical equivalent and 9074 individuals with data on axial length were included in the study; right eyes were used for analyses. Data were analyzed from September 2014 to May 2016. Visual impairment and blindness (defined according to the World Health Organization criteria as a visual acuity less than 0.3) and predicted rates of visual impairment specifically for persons with myopia. Of the 15 693 individuals included in this study, the mean (SD) age was 61.3 (11.4) years, and 8961 (57.1%) were female. Axial length ranged from 15.3 to 37.8 mm; 819 individuals had an axial length of 26 mm or greater. Spherical equivalent ranged from -25 to +14 diopters; 796 persons had high myopia (ie, a spherical equivalent of -6 diopters or less). The prevalence of visual impairment varied from 1.0% to 4.1% in the population-based studies, was 5.4% in the Myopia Study, and was 0.3% in controls. The prevalence of visual impairment rose with increasing axial length and spherical equivalent, with a cumulative incidence (SE) of visual impairment of 3.8% (1.3) for participants aged 75 years with an axial length of 24 to less than 26 mm and greater than 90% (8.1) with an axial length of 30 mm or greater. The cumulative risk (SE) of visual impairment was 5.7% (1.3) for participants aged 60 years and 39% (4.9) for those aged 75 years with a spherical equivalent of -6 diopters or less. Projections of these data suggest that visual impairment will increase 7- to 13-fold by 2055 in high-risk areas. This study demonstrated that visual impairment is associated with axial length and spherical equivalent and may be unavoidable at the most extreme values in this population. Developing strategies to prevent the development of myopia and its complications could help to avoid an increase of visual impairment in the working-age population.
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NASA Astrophysics Data System (ADS)
Choi, Sam B.; Zamarbide, Marta; Manzini, M. Chiara; Nemes, Peter
2017-04-01
Ultrasensitive characterization of the proteome raises the potential to understand how differential gene expression orchestrates cell heterogeneity in the brain. Here, we report a microanalytical capillary electrophoresis nano-flow electrospray ionization (CE-nanoESI) interface for mass spectrometry to enable the measurement of limited amounts of proteins in the mouse cortex. Our design integrates a custom-built CE system to a tapered-tip metal emitter in a co-axial sheath-flow configuration. This interface can be constructed in <15 min using readily available components, facilitating broad adaptation. Tapered-tip CE-nanoESI generates stable electrospray by reproducibly anchoring the Taylor cone, minimizes sample dilution in the ion source, and ensures efficient ion generation by sustaining the cone-jet spraying regime. Parallel reaction monitoring provided a 260-zmol lower limit of detection for angiotensin II (156,000 copies). CE was able to resolve a complex mixture of peptides in 330,000 theoretical plates and identify 15 amol ( 1 pg) of BSA or cytochrome c. Over 30 min of separation, 1 ng protein digest from the mouse cortex yielded 217 nonredundant proteins encompassing a 3-log-order concentration range using a quadrupole time-of-flight mass spectrometer. Identified proteins included many products from genes that are traditionally used to mark oligodendrocytes, astrocytes, and microglia. Finally, key proteins involved in neurodegenerative disorders were detected (e.g., parkinsonism and spastic paraplegia). CE-nanoESI-HRMS delivers sufficient sensitivity to detect proteins in limited amounts of tissues and cell populations to help understand how gene expression differences maintain cell heterogeneity in the brain.
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A Magneto-Inductive Sensor Based Wireless Tongue-Computer Interface
Huo, Xueliang; Wang, Jia; Ghovanloo, Maysam
2015-01-01
We have developed a noninvasive, unobtrusive magnetic wireless tongue-computer interface, called “Tongue Drive,” to provide people with severe disabilities with flexible and effective computer access and environment control. A small permanent magnet secured on the tongue by implantation, piercing, or tissue adhesives, is utilized as a tracer to track the tongue movements. The magnetic field variations inside and around the mouth due to the tongue movements are detected by a pair of three-axial linear magneto-inductive sensor modules mounted bilaterally on a headset near the user’s cheeks. After being wirelessly transmitted to a portable computer, the sensor output signals are processed by a differential field cancellation algorithm to eliminate the external magnetic field interference, and translated into user control commands, which could then be used to access a desktop computer, maneuver a powered wheelchair, or control other devices in the user’s environment. The system has been successfully tested on six able-bodied subjects for computer access by defining six individual commands to resemble mouse functions. Results show that the Tongue Drive system response time for 87% correctly completed commands is 0.8 s, which yields to an information transfer rate of ~130 b/min. PMID:18990653
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NASA Technical Reports Server (NTRS)
Dorney, D. J.; Marci, Bogdan; Tran, Ken; Sargent, Scott
2003-01-01
Each single reusable Space Launch Initiative (SLI) booster rocket is an engine operating at a record vacuum thrust level of over 730,000 Ibf using LOX and LH2. This thrust is more than 10% greater than that of the Delta IV rocket, resulting in relatively large LOX and LH2 turbopumps. Since the SLI rocket employs a staged combustion cycle the level of pressure is very high (thousands of psia). This high pressure creates many engineering challenges, including the balancing of axial-forces on the turbopumps. One of the main parameters in the calculation of the axial force is the cavity pressure upstream of the turbine disk. The flow in this cavity is very complex. The lack of understanding of this flow environment hinders the accurate prediction of axial thrust. In order to narrow down the uncertainty band around the actual turbine axial force, a coupled, unsteady computational methodology has been developed to simulate the interaction between the turbine main flow path and the cavity flow. The CORSAIR solver, an unsteady three- dimensional Navier-Stokes code for turbomachinery applications, was used to solve for both the main and the secondary flow fields. Turbine axial thrust values are presented in conjunction with the CFD simulation, together with several considerations regarding the turbine instrumentation for axial thrust estimations during test.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Jun; Tang, Zhilie; Wu, Yongbo
2015-04-15
We designed, fabricated, and tested a rapid and noncontact photoacoustic tomography (PAT) imaging system using a low-coherence interferometer with high-speed phase modulation technique. Such a rapid and noncontact probing system can greatly decrease the time of imaging. The proposed PAT imaging system is experimentally verified by capturing images of a simulated tissue sample and the blood vessels within the ear flap of a mouse (pinna) in vivo. The axial and lateral resolutions of the system are evaluated at 45 and ∼15 μm, respectively. The imaging depth of the system is 1 mm in a special phantom. Our results show thatmore » the proposed system opens a promising way to realize noncontact, real-time PAT.« less
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2012-12-01
a case hardened steel bushing with interference of 0.127 mm (0.005 in), 2,600 N (590 lbs) of static holding force in the axial direction is...radial force, along with the materials’ coefficient of friction, produces the axial and torsional holding strength. The pressure between the two parts...2 4 dT pL (1.7) nF = Normal force (relative to the press-fit surface) nF p dL (1.8) F= Frictional axial “holding” force of the
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Quadriplegia in a child following adenotonsillectomy.
Agarwal, J; Tandon, M S; Singh, D; Ganjoo, P
2013-05-01
Neurological deterioration in a child following routine surgery, although rare, has potentially life threatening consequences. We report the case of a child who, following adentonsillectomy, developed quadriplegia and acute respiratory distress due to previously undetected atlanto-axial instability. Patients with atlanto-axial instability often have mild or non-specific symptoms, despite severe cervical cord compression. Subtle manifestations may be ignored or attributed to other disease processes, which render patients with undiagnosed atlanto-axial instability at risk of serious neurological injury during general anaesthesia, particularly at the time of laryngoscopy and tracheal intubation. Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.
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Wang, K W; Chueh, L L; Wang, M H; Huang, Y T; Fang, B H; Chang, C Y; Fang, M C; Chou, J Y; Hsieh, S C; Wan, C H
2013-04-01
Mouse parvoviruses are among the most prevalent infectious pathogens in contemporary mouse colonies. To improve the efficiency of routine screening for mouse parvovirus infections, a multiplex polymerase chain reaction (PCR) assay targeting the VP gene was developed. The assay detected minute virus of mice (MVM), mouse parvovirus (MPV) and a mouse housekeeping gene (α-actin) and was able to specifically detect MVM and MPV at levels as low as 50 copies. Co-infection with the two viruses with up to 200-fold differences in viral concentrations can easily be detected. The multiplex PCR assay developed here could be a useful tool for monitoring mouse health and the viral contamination of biological materials.
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Sieper, Joachim; Braun, Jürgen; Dougados, Maxime; Baeten, Dominique
2015-07-09
The term axial spondyloarthritis covers both non-radiographic disease and radiographic disease (also known as ankylosing spondylitis). Some studies have been performed to investigate the prevalence of axial spondyloarthritis, although most are limited to patients with radiographic disease. A strong genetic association has been shown between axial spondyloarthritis and human leukocyte antigen-B27 (HLA-B27), but the pathogenetic role of HLA-B27 has not yet been clarified. Tumour necrosis factor (TNF), IL-17, IL-23 and downstream pathways also seem to be important - based on the good results of therapies directed against these molecules - but their exact role in the inflammatory process is also not yet clear. Elucidating the interaction between osteoproliferation and inflammation will be crucial for the prevention of long-term structural damage of the bone. The development of new criteria for classification, diagnosis and screening of patients with axial spondyloarthritis will enable earlier intervention for this chronic inflammatory disease. MRI has become an important tool for the early detection of axial spondyloarthritis. NSAIDs and TNF blockers are effective therapies, including in the early non-radiographic stage. Therapeutic blockade of IL-17 or IL-23 seems to be a promising new treatment option. Tools for measuring quality of life in axial spondyloarthritis have become relevant to assess the impact that the disease has on patients. These diagnostic and therapeutic advances will continue to change the management of axial spondyloarthritis, and new insights into the disease pathogenesis will hopefully accelerate this process. For an illustrated summary of this Primer, visit: http://go.nature.com/51b1af.
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Conjunct rotation: Codman's paradox revisited.
Wolf, Sebastian I; Fradet, Laetitia; Rettig, Oliver
2009-05-01
This contribution mathematically formalizes Codman's idea of conjunct rotation, a term he used in 1934 to describe a paradoxical phenomenon arising from a closed-loop arm movement. Real (axial) rotation is distinguished from conjunct rotation. For characterizing the latter, the idea of reference vector fields is developed to define the neutral axial position of the humerus for any given orientation of its long axis. This concept largely avoids typical coordinate singularities arising from decomposition of 3D joint motion and therefore can be used for postural (axial) assessment of the shoulder joint both clinically and in sports science in almost the complete accessible range of motion. The concept, even though algebraic rather complex, might help to get an easier and more intuitive understanding of axial rotation of the shoulder in complex movements present in daily life and in sports.
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The numerical simulation of a high-speed axial flow compressor
NASA Technical Reports Server (NTRS)
Mulac, Richard A.; Adamczyk, John J.
1991-01-01
The advancement of high-speed axial-flow multistage compressors is impeded by a lack of detailed flow-field information. Recent development in compressor flow modeling and numerical simulation have the potential to provide needed information in a timely manner. The development of a computer program is described to solve the viscous form of the average-passage equation system for multistage turbomachinery. Programming issues such as in-core versus out-of-core data storage and CPU utilization (parallelization, vectorization, and chaining) are addressed. Code performance is evaluated through the simulation of the first four stages of a five-stage, high-speed, axial-flow compressor. The second part addresses the flow physics which can be obtained from the numerical simulation. In particular, an examination of the endwall flow structure is made, and its impact on blockage distribution assessed.
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Genetically Engineered Mouse Models for Studying Inflammatory Bowel Disease
Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko
2015-01-01
Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. PMID:26387641
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Dehydration Preparation of Mouse Sperm for Vitrification and Rapid Laser Warming.
Paredes, E; Mazur, P
Mice are fundamental models of study due to their ease of breeding, manipulation, and the well-studied genome. There has been extensive research focused on the cryopreservation of mouse germaplasm, as a way to help maintain the different transgenic mouse breeds. The first protocols for mouse sperm were developed in the 90's using slow cooling and a mixture of raffinose and glycerol. Since then, the rate of success reported remains highly variable. The Aim of this work is to study factors that are key for developing vitrification protocols for ultra-rapid laser warming of mouse sperm. Our results show that due to the exquisite sensitivity of sperm cells to osmotic excursions, our target levels of dehydration (~85% water content) cannot be achieved without causing a significant decrease in sperm motility and membrane fusion. It seems likely that mouse sperm vitrification is going to be difficult to develop due to the exquisite sensitivity of mouse sperm cells to handling and dehydration.
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Cervical spine injuries and flexibilities following axial impact with lateral eccentricity.
Van Toen, C; Street, J; Oxland, T R; Cripton, Peter A
2015-01-01
Determine the effects of dynamic injurious axial compression applied at various lateral eccentricities (lateral distance to the centre of the spine) on mechanical flexibilities and structural injury patterns of the cervical spine. 13 three-vertebra human cadaver cervical spine specimens (6 C3-5, 3 C4-6, 2 C5-7, 2 C6-T1) were subjected to pure moment flexibility tests (±1.5 Nm) before and after impact trauma was applied in two groups: low and high lateral eccentricity (1 and 150 % of the lateral diameter of the vertebral body, respectively). Relative range of motion (ROM) and relative neutral zone (NZ) were calculated as the ratio of post and pre-trauma values. Injuries were diagnosed by a spine surgeon and scored. Classification functions were developed using discriminant analysis. Low and high eccentric loading resulted in primarily bony fractures and soft tissue injuries, respectively. Axial impacts with high lateral eccentricities resulted in greater spinal motion in lateral bending [median relative ROM 3.5 (interquartile range, IQR 2.3) vs. 1.4 (IQR 0.5) and median relative NZ 4.7 (IQR 3.7) vs. 2.3 (IQR 1.1)] and in axial rotation [median relative ROM 5.3 (IQR 13.7) vs. 1.3 (IQR 0.5), p < 0.05 for all comparisons] than those that resulted from low eccentricity impacts. The developed classification functions had 92 % classification accuracy. Dynamic axial compression loading of the cervical spine with high lateral eccentricities produced primarily soft tissue injuries resulting in more post-injury spinal flexibility in lateral bending and axial rotation than that associated with the bony fractures resulting from low eccentricity impacts.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Webb, Carol F., E-mail: carol-webb@omrf.org; Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights:more » • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.« less
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The roles of ERAS during cell lineage specification of mouse early embryonic development.
Zhao, Zhen-Ao; Yu, Yang; Ma, Huai-Xiao; Wang, Xiao-Xiao; Lu, Xukun; Zhai, Yanhua; Zhang, Xiaoxin; Wang, Haibin; Li, Lei
2015-08-01
Eras encodes a Ras-like GTPase protein that was originally identified as an embryonic stem cell-specific Ras. ERAS has been known to be required for the growth of embryonic stem cells and stimulates somatic cell reprogramming, suggesting its roles on mouse early embryonic development. We now report a dynamic expression pattern of Eras during mouse peri-implantation development: its expression increases at the blastocyst stage, and specifically decreases in E7.5 mesoderm. In accordance with its expression pattern, the increased expression of Eras promotes cell proliferation through controlling AKT activation and the commitment from ground to primed state through ERK activation in mouse embryonic stem cells; and the reduced expression of Eras facilitates primitive streak and mesoderm formation through AKT inhibition during gastrulation. The expression of Eras is finely regulated to match its roles in mouse early embryonic development during which Eras expression is negatively regulated by the β-catenin pathway. Thus, beyond its well-known role on cell proliferation, ERAS may also play important roles in cell lineage specification during mouse early embryonic development. © 2015 The Authors.
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Common-path digital holographic microscopy based on a beam displacer unit
NASA Astrophysics Data System (ADS)
Di, Jianglei; Zhang, Jiwei; Song, Yu; Wang, Kaiqiang; Wei, Kun; Zhao, Jianlin
2018-02-01
Digital holographic microscopy (DHM) has become a novel tool with advantages of full field, non-destructive, high-resolution and 3D imaging, which captures the quantitative amplitude and phase information of microscopic specimens. It's a well-established method for digital recording and numerical reconstructing the full complex field of wavefront of the samples with a diffraction-limited lateral resolution down to 0.3 μm depending on the numerical aperture of microscope objective. Meanwhile, its axial resolution through axial direction is less than 10 nm due to the interferometric nature in phase imaging. Compared with the typical optical configurations such as Mach-Zehnder interferometer and Michelson interferometer, the common-path DHM has the advantages of simple and compact configuration, high stability, and so on. Here, a simple, compact, and low-cost common-path DHM based on a beam displacer unit is proposed for quantitative phase imaging of biological cells. The beam displacer unit is completely compatible with commercial microscope and can be easily set up in the output port of the microscope as a compact independent device. This technique can be used to achieve the quantitative phase measurement of biological cells with an excellent temporal stability of 0.51 nm, which makes it having a good prospect in the fields of biological and medical science. Living mouse osteoblastic cells are quantitatively measured with the system to demonstrate its capability and applicability.
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Gas Flux and Density Surrounding a Cylindrical Aperture in the Free Molecular Flow Regime
NASA Technical Reports Server (NTRS)
Soulas, George C.
2011-01-01
The equations for rigorously calculating the particle flux and density surrounding a cylindrical aperture in the free molecular flow regime are developed and presented. The fundamental equations for particle flux and density from a reservoir and a diffusely reflecting surface will initially be developed. Assumptions will include a Maxwell-Boltzmann speed distribution, equal particle and wall temperatures, and a linear flux distribution along the cylindrical aperture walls. With this information, the equations for axial flux and density surrounding a cylindrical aperture will be developed. The cylindrical aperture will be divided into multiple volumes and regions to rigorously determine the surrounding axial flux and density, and appropriate limits of integration will be determined. The results of these equations will then be evaluated. The linear wall flux distribution assumption will be assessed. The axial flux and density surrounding a cylindrical aperture with a thickness-to-radius ratio of 1.25 will be presented. Finally, the equations determined in this study will be verified using multiple methods.
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Sivertsen, Magne S.; Glover, Joel C.
2014-01-01
Using optical recording of synaptically mediated calcium transients and selective spinal lesions, we investigated the pattern of activation of spinal motoneurons (MNs) by the pontine reticulospinal projection in isolated brain stem-spinal cord preparations from the neonatal mouse. Stimulation sites throughout the region where the pontine reticulospinal neurons reside reliably activated MNs at cervical, thoracic, and lumbar levels. Activation was similar in MNs ipsi- and contralateral to the stimulation site, similar in medial and lateral motor columns that contain trunk and limb MNs, respectively, and similar in the L2 and L5 segments that predominantly contain flexor and extensor MNs, respectively. In nonlesioned preparations, responses in both ipsi- and contralateral MNs followed individual stimuli in stimulus trains nearly one-to-one (with few failures). After unilateral hemisection at C1 on the same side as the stimulation, responses had substantially smaller magnitudes and longer latencies and no longer followed individual stimuli. After unilateral hemisection at C1 on the side opposite to the stimulation, the responses were also smaller, but their latencies were not affected. Thus we distinguish two pontine reticulospinal pathways to spinal MNs, one uncrossed and the other crossed, of which the uncrossed pathway transmits more faithfully and appears to be more direct. PMID:24944221
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ERIC Educational Resources Information Center
Shih, Ching-Hsiang; Chiu, Sheng-Kai; Chu, Chiung-Ling; Shih, Ching-Tien; Liao, Yung-Kun; Lin, Chia-Chen
2010-01-01
This study evaluated whether two people with multiple disabilities would be able to improve their pointing performance using hand swing with a standard mouse through an Extended Dynamic Pointing Assistive Program (EDPAP) and a newly developed mouse driver (i.e., a new mouse driver replaces standard mouse driver, and changes a mouse into a precise…
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ERIC Educational Resources Information Center
Shih, Ching-Hsiang; Shih, Ching-Tien; Lin, Kun-Tsan; Chiang, Ming-Shan
2009-01-01
This study assessed whether two people with profound multiple disabilities and minimal motor behavior would be able to control environmental stimulation using thumb poke ability with a mouse wheel and a newly developed mouse driver (i.e., a new mouse driver replacing standard mouse driver, and turning a mouse into a precise thumb poke detector).…
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Vibration localization in dual-span, axially moving beams. Part I: Formulation and results
NASA Astrophysics Data System (ADS)
Al-Jawi, A. A. N.; Pierre, C.; Ulsoy, A. G.
1995-01-01
An investigation of the vibration localization phenomenon in dual-span, axially moving beams is presented. The effects of a tension difference among the spans, also referred to as disorder, on the natural modes of free vibration are studied in terms of inter-span coupling and transport speed. The equations governing the transverse vibration of the two-span, axially moving beam are derived through Hamilton's principle and solution methods are developed. Results demonstrate that normal mode localizationindeed occurs for both stationary and translating disordered two-span beams, especially for small inter-span coupling. The occurrence of localization is characterized by a peak deflection much greater in one span than in the other. In the stationary disordered case, localization becomes more pronounced as inter-span coupling decreases, i.e., as the span axial tension increases. In the axially moving disordered case, the transport speed has a significant influence on localization and, generally speaking, localization becomes stronger with increasing speed. For a moving beam with identical spans, the two loci of each pair of natural frequencies may exhibit one or more crossing(s) (depending on the value of tension) when plotted against the axial transport speed. These crossings become veerings when the beam is disordered, and localization is strongest at those speeds at which the eigenvalue veerings occur.
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Theoretical analysis to investigate thermal performance of co-axial heat pipe solar collector
NASA Astrophysics Data System (ADS)
Azad, E.
2011-12-01
The thermal performance of co-axial heat pipe solar collector which consist of a collector 15 co-axial heat pipes surrounded by a transparent envelope and which heat a fluid flowing through the condenser tubes have been predicted using heat transfer analytical methods. The analysis considers conductive and convective losses and energy transferred to a fluid flowing through the collector condenser tubes. The thermal performances of co-axial heat pipe solar collector is developed and are used to determine the collector efficiency, which is defined as the ratio of heat taken from the water flowing in the condenser tube and the solar radiation striking the collector absorber. The theoretical water outlet temperature and efficiency are compared with experimental results and it shows good agreement between them. The main advantage of this collector is that inclination of collector does not have influence on performance of co-axial heat pipe solar collector therefore it can be positioned at any angle from horizontal to vertical. In high building where the roof area is not enough the co-axial heat pipe solar collectors can be installed on the roof as well as wall of the building. The other advantage is each heat pipe can be topologically disconnected from the manifold.
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Label-free, multi-contrast optical coherence tomography for study of skin melanoma mice in vivo
NASA Astrophysics Data System (ADS)
Lai, Pei-Yu; Lin, Tim-Han; Chou, Ya-Shuan; Chang, Chung-Hsing; Kuo, Wen-Chuan
2018-02-01
The lymphatic system plays an important role in inflammation and cancer such as melanoma. Due to the limitations of current developed imaging techniques, visualization of lymphatic vessels within the tissue in vivo has been challenging. Optical imaging of lymphatic vessel is gaining increased interests because it does not involve any radiation and can achieve very high resolution. Here, we developed a multi-contrast, label-free optical coherence tomography (OCT) imaging technology with an axial resolution of 5 μm and lateral resolution of 7 μm, which is capable of providing microstructural information and microcirculatory system including blood and lymphatic vessels simultaneously. Using this technique, we observed the melanoma mice in vivo. Mice were treated topically on the ear with (Z)-4- Hydroxytamoxifen(4-OHT) to elicit BRAFV600E and to silence Pten expression. Also, to observing the structural information, angiogenesis and lymphangiogenesis in the ear of the induced melanoma mouse can be done. The advantage of using OCT over other imaging modalities is its ability to assess label-free blood flow along with lymphatic vessels simultaneously for imaging the microcirculatory system within tissue beds without any exogenous agents. Because the metastasis of melanoma is highly related to the lymphatic vessels, our findings can be a powerful tool to help the diagnosis of the metastasis melanoma. In the future, this may become a helpful tool for better understanding pathologic mechanisms and treatment technique development in some diseases.
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Tang, Jiqiang; Xiang, Biao; Zhang, Yongbin
2014-07-01
For a magnetically suspended control moment gyroscope, stiffness and damping of magnetic bearing will influence modal frequency of a rotor. In this paper the relationship between modal frequency and stiffness and damping has been investigated. The mathematic calculation model of axial passive magnetic bearing (PMB) stiffness is developed. And PID control based on internal model control is introduced into control of radial active magnetic bearing (AMB), considering the radial coupling of axial PMB, a mathematic calculation model of stiffness and damping of radial AMB is established. According to modal analysis, the relationship between modal frequency and modal shapes is achieved. Radial vibration frequency is mainly influenced by stiffness of radial AMB; however, when stiffness increases, radial vibration will disappear and a high frequency bending modal will appear. Stiffness of axial PMB mainly affects the axial vibration mode, which will turn into high-order bending modal. Axial PMB causes bigger influence on torsion modal of the rotor. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Wang, Qibin; Zhao, Bo; Fu, Yang; Kong, Xianguang; Ma, Hui
2018-06-01
An improved time-varying mesh stiffness (TVMS) model of a helical gear pair is proposed, in which the total mesh stiffness contains not only the common transverse tooth bending stiffness, transverse tooth shear stiffness, transverse tooth radial compressive stiffness, transverse gear foundation stiffness and Hertzian contact stiffness, but also the axial tooth bending stiffness, axial tooth torsional stiffness and axial gear foundation stiffness proposed in this paper. In addition, a rapid TVMS calculation method is proposed. Considering each stiffness component, the TVMS can be calculated by the integration along the tooth width direction. Then, three cases are applied to validate the developed model. The results demonstrate that the proposed analytical method is accurate, effective and efficient for helical gear pairs and the axial mesh stiffness should be taken into consideration in the TVMS of a helical gear pair. Finally, influences of the helix angle on TVMS are studied. The results show that the improved TVMS model is effective for any helix angle and the traditional TVMS model is only effective under a small helix angle.
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A new axial smoothing method based on elastic mapping
NASA Astrophysics Data System (ADS)
Yang, J.; Huang, S. C.; Lin, K. P.; Czernin, J.; Wolfenden, P.; Dahlbom, M.; Hoh, C. K.; Phelps, M. E.
1996-12-01
New positron emission tomography (PET) scanners have higher axial and in-plane spatial resolutions but at the expense of reduced per plane sensitivity, which prevents the higher resolution from being fully realized. Normally, Gaussian-weighted interplane axial smoothing is used to reduce noise. In this study, the authors developed a new algorithm that first elastically maps adjacent planes, and then the mapped images are smoothed axially to reduce the image noise level. Compared to those obtained by the conventional axial-directional smoothing method, the images by the new method have improved signal-to-noise ratio. To quantify the signal-to-noise improvement, both simulated and real cardiac PET images were studied. Various Hanning reconstruction filters with cutoff frequency=0.5, 0.7, 1.0/spl times/Nyquist frequency and Ramp filter were tested on simulated images. Effective in-plane resolution was measured by the effective global Gaussian resolution (EGGR) and noise reduction was evaluated by the cross-correlation coefficient. Results showed that the new method was robust to various noise levels and indicated larger noise reduction or better image feature preservation (i.e., smaller EGGR) than by the conventional method.
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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.
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Nonlinear Deformation Behavior of New Braided Composites with Six-axis Yarn Orientations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahn, H.-C.; Yu, W.-R.; Guo, Z.
The braiding technology is one of fabrication methods that can produce three-dimensional fiber preforms. Braided composites have many advantages over other two-dimensional composites such as no delamination, high impact and fatigue properties, near-net shape preform, etc. Due to the undulated yarns in the braided preforms, however, their axial stiffness is lower than that of uni-directional or woven composites. To improve the axial stiffness, the longitudinal axial yarns were already introduced along with the braiding axis (five-axis braiding technology). In this study, we developed a new braided structure using six-axis braiding technology. In addition to braiding and longitudinal axial yarns, transversemore » axial yarn was introduced. New braided composites, so called six-axis braiding composites, were manufactured using ultra high molecular weight polyethylene and epoxy resin and their mechanical properties were characterized. To investigate the mechanical performance of these braided composites according to their manufacturing conditions, a numerical analysis was performed using their unit-cell modeling and finite element analysis. In the analysis the nonlinear deformation behavior will be included.« less
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Maleckis, Kaspars; Deegan, Paul; Poulson, William; Sievers, Cole; Desyatova, Anastasia; MacTaggart, Jason; Kamenskiy, Alexey
2017-11-01
High failure rates of Peripheral Arterial Disease (PAD) stenting appear to be associated with the inability of certain stent designs to accommodate severe biomechanical environment of the femoropopliteal artery (FPA) that bends, twists, and axially compresses during limb flexion. Twelve Nitinol stents (Absolute Pro, Supera, Lifestent, Innova, Zilver, Smart Control, Smart Flex, EverFlex, Viabahn, Tigris, Misago, and Complete SE) were quasi-statically tested under bench-top axial and radial compression, axial tension, bending, and torsional deformations. Stents were compared in terms of force-strain behavior, stiffness, and geometrical shape under each deformation mode. Tigris was the least stiff stent under axial compression (6.6N/m axial stiffness) and bending (0.1N/m) deformations, while Smart Control was the stiffest (575.3N/m and 105.4N/m, respectively). Under radial compression Complete SE was the stiffest (892.8N/m), while Smart Control had the lowest radial stiffness (211.0N/m). Viabahn and Supera had the lowest and highest torsional stiffness (2.2μNm/° and 959.2μNm/°), respectively. None of the 12 PAD stents demonstrated superior characteristics under all deformation modes and many experienced global buckling and diameter pinching. Though it is yet to be determined which of these deformation modes might have greater clinical impact, results of the current analysis may help guide development of new stents with improved mechanical characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.
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NASA Technical Reports Server (NTRS)
Knox, James Clinton
2016-01-01
The 1-D axially dispersed plug flow model is a mathematical model widely used for the simulation of adsorption processes. Lumped mass transfer coefficients such as the Glueckauf linear driving force (LDF) term and the axial dispersion coefficient are generally obtained by fitting simulation results to the experimental breakthrough test data. An approach is introduced where these parameters, along with the only free parameter in the energy balance equations, are individually fit to specific test data that isolates the appropriate physics. It is shown that with this approach this model provides excellent simulation results for the C02 on zeolite SA sorbent/sorbate system; however, for the H20 on zeolite SA system, non-physical deviations from constant pattern behavior occur when fitting dispersive experimental results with a large axial dispersion coefficient. A method has also been developed that determines a priori what values of the LDF and axial dispersion terms will result in non-physical simulation results for a specific sorbent/sorbate system when using the one-dimensional axially dispersed plug flow model. A relationship between the steepness of the adsorption equilibrium isotherm as indicated by the distribution factor, the magnitude of the axial dispersion and mass transfer coefficient, and the resulting non-physical behavior is derived. This relationship is intended to provide a guide for avoiding non-physical behavior by limiting the magnitude of the axial dispersion term on the basis of the mass transfer coefficient and distribution factor.
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A Study of the Zero-Lift Drag-Rise Characteristics of Wing-Body Combinations Near the Speed of Sound
NASA Technical Reports Server (NTRS)
Whitcomb, Richard T
1956-01-01
Comparisons have been made of the shock phenomena and drag-rise increments for representative wing and central-body combinations with those for bodies of revolution having the same axial developments of cross-sectional areas normal to the airstream. On the basis of these comparisons, it is concluded that near the speed of sound the zero-lift drag rise of a low-aspect-ratio thin-wing and body combination is primarily dependent on the axial development of the cross-sectional areas normal to the airstream. It follows that the drag rise for any such configuration is approximately the same as that for any other with the same development of cross-sectional areas. Investigations have also been made of representative wing-body combinations with the body so indented that the axial developments of cross-sectional areas for the combinations were the same as that for the original body alone. Such indentations greatly reduced or eliminated the zero-lift drag-rise increments associated with the wings near the speed of sound.
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Simulation of in vivo dynamics during robot assisted joint movement.
Bobrowitsch, Evgenij; Lorenz, Andrea; Wülker, Nikolaus; Walter, Christian
2014-12-16
Robots are very useful tools in orthopedic research. They can provide force/torque controlled specimen motion with high repeatability and precision. A method to analyze dissipative energy outcome in an entire joint was developed in our group. In a previous study, a sheep knee was flexed while axial load remained constant during the measurement of dissipated energy. We intend to apply this method for the investigation of osteoarthritis. Additionally, the method should be improved by simulation of in vivo knee dynamics. Thus, a new biomechanical testing tool will be developed for analyzing in vitro joint properties after different treatments. Discretization of passive knee flexion was used to construct a complex flexion movement by a robot and simulate altering axial load similar to in vivo sheep knee dynamics described in a previous experimental study. The robot applied an in vivo like axial force profile with high reproducibility during the corresponding knee flexion (total standard deviation of 0.025 body weight (BW)). A total residual error between the in vivo and simulated axial force was 0.16 BW. Posterior-anterior and medio-lateral forces were detected by the robot as a backlash of joint structures. Their curve forms were similar to curve forms of corresponding in vivo measured forces, but in contrast to the axial force, they showed higher total standard deviation of 0.118 and 0.203 BW and higher total residual error of 0.79 and 0.21 BW for posterior-anterior and medio-lateral forces respectively. We developed and evaluated an algorithm for the robotic simulation of complex in vivo joint dynamics using a joint specimen. This should be a new biomechanical testing tool for analyzing joint properties after different treatments.
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A Mini Axial and a Permanent Maglev Radial Heart Pump§
Qian, Kun-Xi; Ru, Wei-Min; Wang, Hao; Jing, Teng
2007-01-01
The implantability and durability have been for decades the focus of artificial heart R&D. A mini axial and a maglev radial pump have been developed to meet with such requirements. The mini axial pump weighing 27g (incl.5g rotor) has an outer diameter of 21mm and a length of 10mm in its largest point, but can produce a maximal blood flow of 6l/min with 50mmHg pressure increase. Therefore, it is suitable for the patients of 40-60kg body weight. For other patients of 60-80kg or 80-100kg body weight, the mini axial pumps of 23mm and 25mm outer diameter had been developed before, these devices were acknowledged to be the world smallest LVADs by Guinness World Record Center in 2004. The permanent maglev radial pump weighing 150g is a shaft-less centrifugal pump with permanent magnetic bearings developed by the author. It needs no second coil for suspension of the rotor except the motor coil, different from all other maglev pumps developed in USA, Japan, European, etc. Thus no detecting and controlling systems as well as no additional power supply for maglev are necessary. The pump can produce a blood flow up to as large as 10l/min against 100mmHg pressure. An implantable and durable blood pump will be a viable alternative to natural donor heart for transplantation. PMID:19662120
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Boedtkjer, Ebbe; Bentzon, Jacob F; Dam, Vibeke S; Aalkjaer, Christian
2016-08-01
Arterial remodelling can cause luminal narrowing and obstruct blood flow. We tested the hypothesis that cellular acid-base transport facilitates proliferation and migration of vascular smooth muscle cells (VSMCs) and enhances remodelling of conduit arteries. [Formula: see text]-cotransport via NBCn1 (Slc4a7) mediates net acid extrusion and controls steady-state intracellular pH (pHi) in VSMCs of mouse carotid arteries and primary aortic explants. Carotid arteries undergo hypertrophic inward remodelling in response to partial or complete ligation in vivo, but the increase in media area and thickness and reduction in lumen diameter are attenuated in arteries from NBCn1 knock-out compared with wild-type mice. With [Formula: see text] present, gradients for pHi (∼0.2 units magnitude) exist along the axis of VSMC migration in primary explants from wild-type but not NBCn1 knock-out mice. Knock-out or pharmacological inhibition of NBCn1 also reduces filopodia and lowers initial rates of VSMC migration after scratch-wound infliction. Interventions to reduce H(+)-buffer mobility (omission of [Formula: see text] or inhibition of carbonic anhydrases) re-establish axial pHi gradients, filopodia, and migration rates in explants from NBCn1 knock-out mice. The omission of [Formula: see text] also lowers global pHi and inhibits proliferation in primary explants. Under physiological conditions (i.e. with [Formula: see text] present), NBCn1-mediated [Formula: see text] uptake raises VSMC pHi and promotes filopodia, VSMC migration, and hypertrophic inward remodelling. We propose that axial pHi gradients enhance VSMC migration whereas global acidification inhibits VSMC proliferation and media hypertrophy after carotid artery ligation. These findings support a key role of acid-base transport, particularly via NBCn1, for development of occlusive artery disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
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Thermal characterization of phacoemulsification probes operated in axial and torsional modes.
Zacharias, Jaime
2015-01-01
To analyze temperature increases and identify potential sources of heat generated when sleeved and sleeveless phacoemulsification probes were operated in axial and torsional modes using the Infiniti Vision System with the Ozil torsional handpiece. Phacodynamics Laboratory, Pasteur Ophthalmic Clinic, Santiago, Chile. Experimental study. Two computer-controlled thermal transfer systems were developed to evaluate the contribution of internal metal stress and tip-to-sleeve friction on heat generation during phacoemulsification using axial and torsional ultrasound modalities. Both systems incorporated infrared thermal imaging and used a black-body film to accurately capture temperature measurements. Axial mode was consistently associated with greater temperature increases than torsional mode whether tips were operated with or without sleeves. In tests involving bare tips, axial mode and torsional mode peaked at 51.7°C and 34.2°C, respectively. In an example using sleeved tips in which a 30.0 g load was applied for 1 second, temperatures for axial mode reached 45°C and for torsional mode, 38°C. Friction between the sleeved probe and the incisional wall contributed more significantly to the temperature increase than internal metal stress regardless of the mode used. In all experiments, the temperature increase observed with axial mode was greater than that observed with torsional mode, even when conditions such as power or amplitude and flow rate were varied. Tip-to-sleeve friction was a more dominant source of phaco probe heating than internal metal stress. The temperature increase due to internal metal stress was greater with axial mode than with torsional mode. Dr. Zacharias received research funding from Alcon Laboratories, Inc., to conduct this study. He has no financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
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Fast-axial turbulent flow CO2 laser output characteristics and scaling parameters
NASA Astrophysics Data System (ADS)
Dembovetsky, V. V.; Zavalova, Valentina Y.; Zavalov, Yuri N.
1996-04-01
The paper presents the experimental results of evaluating the output characteristics of TLA- 600 carbon-dioxide laser with axial turbulent gas flow, as well as the results of numerical modeling. The output characteristic and spatial distribution of laser beam were measured with regard to specific energy input, working mixture pressure, active media length and output mirror reflection. The paper presents the results of experimental and theoretical study and design decisions on a succession of similar type industrial carbon-dioxide lasers with fast-axial gas-flow and dc discharge excitation of active medium developed at NICTL RAN. As an illustration, characteristics of the TLA-600 laser are cited.
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Model of an axially strained weakly guiding optical fiber modal pattern
NASA Technical Reports Server (NTRS)
Egalon, Claudio O.; Rogowski, Robert S.
1992-01-01
Axial strain can be determined by monitoring the modal pattern variation of an optical fiber. The results of a numerical model developed to calculate the modal pattern variation at the end of a weakly guiding optical fiber under axial strain is presented. Whenever an optical fiber is under stress, the optical path length, the index of refraction, and the propagation constants of each fiber mode change. In consequence, the modal phase term for the fields and the fiber output pattern are also modified. For multimode fibers, very complicated patterns result. The predicted patterns are presented, and an expression for the phase variation with strain is derived.
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Jinghao Li; John F. Hunt; Shaoqin Gong; Zhiyong Cai
2014-01-01
As the demand for sustainable materials increases, there are unique challenges and opportunities to develop light-weight green composites materials for a wide range of applications. Thus wood-based composite materials from renewable forests may provide options for some niche applications while helping to protect our environment. In this paper, the wood-based tri-axial...
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Axial tomography in 3D live cell microscopy
NASA Astrophysics Data System (ADS)
Richter, Verena; Bruns, Sarah; Bruns, Thomas; Piper, Mathis; Weber, Petra; Wagner, Michael; Cremer, Christoph; Schneckenburger, Herbert
2017-07-01
A miniaturized setup for sample rotation on a microscope stage has been developed, combined with light sheet, confocal or structured illumination microscopy and applied to living cells as well as to small organisms. This setup permits axial tomography with improved visualization of single cells or small cell clusters as well as an enhanced effective 3D resolution upon sample rotation.
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NASA Astrophysics Data System (ADS)
Liu, Qing; Li, Hejun; Zhang, Yulei; Zhao, Zhigang
2018-06-01
A series of theoretical analysis is carried out for the axial vapor-liquid-solid (VLS) growth of nanowires starting with a binary eutectic droplet. The growth model considering the entire process of axial VLS growth is a development of the approaches already developed by previous studies. In this model, the steady and unsteady state growth are considered both. The amount of solute species in a variable liquid droplet, the nanowire length, radius, growth rate and all other parameters during the entire axial growth process are treated as functions of growth time. The model provides theoretical predictions for the formation of nanowire shape, the length-radius and growth rate-radius dependences. It is also suggested by the model that the initial growth of single nanowire is significantly affected by Gibbs-Thompson effect due to the shape change. The model was applied on predictions of available experimental data of Si and Ge nanowires grown from Au-Si and Au-Ge systems respectively reported by other works. The calculations with the proposed model are in satisfactory agreement with the experimental results of the previous works.
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NASA Astrophysics Data System (ADS)
Alessandri, S.; Monti, G.
2008-05-01
A simple procedure is proposed for the assessment of reinforced rectangular concrete columns under combined biaxial bending and axial loads and for the design of a correct amount of FRP-strengthening for underdesigned concrete sections. Approximate closed-form equations are developed based on the load contour method originally proposed by Bresler for reinforced concrete sections. The 3D failure surface is approximated along its contours, at a constant axial load, by means of equations given as the sum of the acting/resisting moment ratio in the directions of principal axes of the sections, raised to a power depending on the axial load, the steel reinforcement ratio, and the section shape. The method is extended to FRP-strengthened sections. Moreover, to make it possible to apply the load contour method in a more practical way, simple closed-form equations are developed for rectangular reinforced concrete sections with a two-way steel reinforcement and FRP strengthenings on each side. A comparison between the approach proposed and the fiber method (which is considered exact) shows that the simplified equations correctly represent the section interaction diagram.
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Towards Large Eddy Simulation of gas turbine compressors
NASA Astrophysics Data System (ADS)
McMullan, W. A.; Page, G. J.
2012-07-01
With increasing computing power, Large Eddy Simulation could be a useful simulation tool for gas turbine axial compressor design. This paper outlines a series of simulations performed on compressor geometries, ranging from a Controlled Diffusion Cascade stator blade to the periodic sector of a stage in a 3.5 stage axial compressor. The simulation results show that LES may offer advantages over traditional RANS methods when off-design conditions are considered - flow regimes where RANS models often fail to converge. The time-dependent nature of LES permits the resolution of transient flow structures, and can elucidate new mechanisms of vorticity generation on blade surfaces. It is shown that accurate LES is heavily reliant on both the near-wall mesh fidelity and the ability of the imposed inflow condition to recreate the conditions found in the reference experiment. For components embedded in a compressor this requires the generation of turbulence fluctuations at the inlet plane. A recycling method is developed that improves the quality of the flow in a single stage calculation of an axial compressor, and indicates that future developments in both the recycling technique and computing power will bring simulations of axial compressors within reach of industry in the coming years.
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[Eye development in children. Part I. Eyeball dimensions].
Lachowicz, Ewelina; Czepita, Damian
2010-01-01
The aim of an article is to introduce and elaborate on the available literature concerning eyeball development. The information content in the article comes from studies performed on groups of children of different ages. In some analysis study groups were chosen depending on sex. Axial length of the eye, depth of anterior chamber, lens's thickness and vitreous's dimension was defined. Intensive changes of eyeball dimensions progress with age. A period of fast and slow growth of the eye can be discerned. Axial length of the eye, depth of anterior chamber, lens's thickness and vitreous's dimension increase over time. Growth of the axial length is mainly caused by increasing axial length of vitreous cavity. The increase in depth of the anterior chamber plays a lesser role. Girls tend to have shorter eyes compared with boys. Both age and male gender are associated with deeper anterior chambers and larger vitreous cavity. Lens thickness decreases with the growth of the eyeball. However gender does not play a role. Based on current literature, it is difficult exactly indicate what are the standards of eyeball growth in children and youths. To establish these parameters, further studies on the another examination in representative group of children and teenagers are necessary.
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Inverted light-sheet microscope for imaging mouse pre-implantation development.
Strnad, Petr; Gunther, Stefan; Reichmann, Judith; Krzic, Uros; Balazs, Balint; de Medeiros, Gustavo; Norlin, Nils; Hiiragi, Takashi; Hufnagel, Lars; Ellenberg, Jan
2016-02-01
Despite its importance for understanding human infertility and congenital diseases, early mammalian development has remained inaccessible to in toto imaging. We developed an inverted light-sheet microscope that enabled us to image mouse embryos from zygote to blastocyst, computationally track all cells and reconstruct a complete lineage tree of mouse pre-implantation development. We used this unique data set to show that the first cell fate specification occurs at the 16-cell stage.
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A high performance cocurrent-flow heat pipe for heat recovery applications
NASA Technical Reports Server (NTRS)
Saaski, E. W.; Hartl, J. C.
1980-01-01
By the introduction of a plate-and-tube separator assembly into a heat pipe vapor core, it has been demonstrated that axial transport capacity in reflux mode can be improved by up to a factor of 10. This improvement is largely the result of eliminating the countercurrent shear that commonly limits reflux heat pipe axial capacity. With benzene, axial heat fluxes up to 1800 W/sq cm were obtained in the temperature range 40 to 80 C, while heat flux densities up to 3000 W/sq cm were obtained with R-11 over the temperature range 40 to 80 C. These very high axial capacities compare favorably with liquid metal limits; the sonic limit for liquid sodium, for example, is 3000 W/sq cm at 657 C. Computational models developed for these cocurrent flow heat pipes agreed with experimental data within + or - 25%.
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A generalized quasi-geostrophic core flow formalism
NASA Astrophysics Data System (ADS)
Amit, H.; Coutelier, M.
2016-12-01
The quasi-geostrophic formalism provides a theoretical coupling between toroidal and poloidal core flows. By enforcing impermeable core-mantle boundary, conservation of mass and a linear variation of the axial flow along an axial column, this coupling can be written as div_h · u_h = c tan θ/R u_θ where u_h is the tangential velocity at the top of the core, θ is co-latitude, R is the core radius and c=2 (Amit and Olson, 2004; Amit and Pais, 2013). We extend this theory and develop this expression for different profiles of the axial flow. Our results show that the same expression holds but the value of c may vary depending on the profile of the axial flow, including c=1 as in the tangential geostrophy formalism. These results may therefore provide new constraints on quasi-geostrophic core flow inversions from geomagnetic SV.
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ERIC Educational Resources Information Center
Shih, Ching-Hsiang; Shih, Ching-Tien
2009-01-01
This study assessed whether two persons with profound multiple disabilities would be able to control environmental stimulation using hand swing and a standard mouse with a newly developed mouse driver (i.e. a new mouse driver replaces standard mouse driver, and turns a mouse into a precise two-dimensional motion detector). The study was performed…
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Ultrasound biomicroscopy in mouse cardiovascular development
NASA Astrophysics Data System (ADS)
Turnbull, Daniel H.
2004-05-01
The mouse is the preferred animal model for studying mammalian cardiovascular development and many human congenital heart diseases. Ultrasound biomicroscopy (UBM), utilizing high-frequency (40-50-MHz) ultrasound, is uniquely capable of providing in vivo, real-time microimaging and Doppler blood velocity measurements in mouse embryos and neonates. UBM analyses of normal and abnormal mouse cardiovascular function will be described to illustrate the power of this microimaging approach. In particular, real-time UBM images have been used to analyze dimensional changes in the mouse heart from embryonic to neonatal stages. UBM-Doppler has been used recently to examine the precise timing of onset of a functional circulation in early-stage mouse embryos, from the first detectable cardiac contractions. In other experiments, blood velocity waveforms have been analyzed to characterize the functional phenotype of mutant mouse embryos having defects in cardiac valve formation. Finally, UBM has been developed for real-time, in utero image-guided injection of mouse embryos, enabling cell transplantation and genetic gain-of-function experiments with transfected cells and retroviruses. In summary, UBM provides a unique and powerful approach for in vivo analysis and image-guided manipulation in normal and genetically engineered mice, over a wide range of embryonic to neonatal developmental stages.
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Submerged jet mixing in nuclear waste tanks: a correlation for jet velocity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Daas, M.; Srivastava, R.; Roelant, D.
2007-07-01
Experimental studies were carried out in jet-stirred slurry tanks to correlate the influence of nozzle diameter, initial jet flow velocity, submerged depth of jet, tank diameter and slurry properties on the jet axial velocity. The tanks used in the experimental work had diameters of 0.3 m (1-ft) and 2.13 m (7-ft). The fluids emerged from nozzles of 0.003 m and 0.01 m in diameter, 1/8-inch and 3/8-inch respectively. The examined slurries were non-Newtonian and contained 5 weight percent total insoluble solids. The axial velocities along the centerline of a submerged jet stream were measured at different jet flow rates andmore » at various distances from the nozzle orifice (16 to 200 nozzle diameters) utilizing electromagnetic velocity meter. A new simplified correlation was developed to describe the jet axial velocity in submerged jet stirred tanks utilizing more than 350 data points. The Buckingham Pi theorem and non-linear regression method of multivariate approximation, in conjunction with the Gauss-Jordan elimination method, were used to develop the new correlation. The new correlation agreed well with the experimental data obtained from the current study. Good agreement was also possible with literature data except at large distances from the nozzle as the model slightly overestimated the jet axial velocity. The proposed correlation incorporates the contributions of system geometry, fluid properties, and external forces. Furthermore, it provides reasonable estimates of jet axial velocity. (authors)« less
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Mouse Models in Bone Marrow Transplantation and Adoptive Cellular Therapy
Arber, Caroline; Brenner, Malcolm K.; Reddy, Pavan
2014-01-01
Mouse models of transplantation have been indispensable to the development of bone marrow transplantation (BMT). Their role in the generation of basic science knowledge is invaluable and is subject to discussion below. However, this article focuses on the direct role and relevance of mouse models towards the clinical development and advances in BMT and adoptive T-cell therapy for human diseases. The authors aim to present a thoughtful perspective on the pros and cons of mouse models while noting that despite imperfections these models are obligatory for the development of science-based medicine. PMID:24216170
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Development of a magnetic fluid shaft seal for an axial-flow blood pump.
Sekine, Kazumitsu; Mitamura, Yoshinori; Murabayashi, Shun; Nishimura, Ikuya; Yozu, Ryouhei; Kim, Dong-Wook
2003-10-01
A rotating impeller in a rotary blood pump requires a supporting system in blood, such as a pivot bearing or magnetic suspension. To solve potential problems such as abrasive wear and complexity of a supporting system, a magnetic fluid seal was developed for use in an axial-flow blood pump. Sealing pressures at motor speeds of up to 8,000 rpm were measured with the seal immersed in water or bovine blood. The sealing pressure was about 200 mm Hg in water and blood. The calculated theoretical sealing pressure was about 230 mm Hg. The seal remained perfect for 743 days in a static condition and for 180+ days (ongoing test) at a motor speed of 7,000 rpm. Results of measurement of cell growth activity indicated that the magnetic fluid has no negative cytological effects. The specially designed magnetic fluid shaft seal is useful for an axial-flow blood pump.
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NASA Technical Reports Server (NTRS)
Lakshminarayana, B.; Davino, R.
1979-01-01
Pure tone noise, blade row vibrations, and aerodynamic losses are phenomena which are influenced by stator and IGV (inlet guide vane) blade wake production, decay, and interaction in an axial-flow compressor. The objective of this investigation is to develop a better understanding of the nature of stator and IGV blade wakes that are influenced by the presence of centrifugal forces due to flow curvature. A single sensor hot wire probe was employed to determine the three mean velocity components of stator and IGV wakes of a single stage compressor. These wake profiles indicated a varying decay rate of the tangential and axial wake velocity components and a wake profile similarity. An analysis, which predicts this trend, has been developed. The radial velocities are found to be appreciable in both IGV and the stator wakes.
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Axial protocadherin (AXPC) regulates cell fate during notochordal morphogenesis.
Yoder, Michael D; Gumbiner, Barry M
2011-11-01
The separation and specification of mesoderm into the notochord and somites involves members of the non-clustered δ-protocadherins. Axial (AXPC) and paraxial (PAPC) protocadherins are expressed in the early dorsal mesoderm and later become refined to the developing notochordal and somitic mesoderm, respectively. The role of PAPC in this process has been studied extensively, but the role of AXPC is poorly understood. Partial knockdown of AXPC causes a specific bent-axis phenotype, while more severe knockdown results in the loss of notochord formation. The inability of these embryos to develop a notochord is not due to a cell-sorting event via changes in cell adhesion during gastrulation, but rather this defect is manifested through the loss of axial mesoderm specification, but not general mesoderm induction. The results presented here show that AXPC functions in notochord morphogenesis by directing cell-fate decisions rather than cell-cell adhesion. Copyright © 2011 Wiley Periodicals, Inc.
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Genetically engineered mouse models for studying inflammatory bowel disease.
Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko
2016-01-01
Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Manipulation of the mouse genome: a multiple impact resource for drug discovery and development.
Prosser, Haydn; Rastan, Sohaila
2003-05-01
Few would deny that the pharmaceutical industry's investment in genomics throughout the 1990s has yet to deliver in terms of drugs on the market. The reasons are complex and beyond the scope of this review. The unique ability to manipulate the mouse genome, however, has already had a positive impact on all stages of the drug discovery process and, increasingly, on the drug development process too. We give an overview of some recent applications of so-called 'transgenic' mouse technology in pharmaceutical research and development. We show how genetic manipulation in the mouse can be employed at multiple points in the drug discovery and development process, providing new solutions to old problems.
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Zic3 is required in the migrating primitive streak for node morphogenesis and left–right patterning
Sutherland, Mardi J.; Wang, Shuyun; Quinn, Malgorzata E.; Haaning, Allison; Ware, Stephanie M.
2013-01-01
In humans, loss-of-function mutations in ZIC3 cause isolated cardiovascular malformations and X-linked heterotaxy, a disorder with abnormal left–right asymmetry of organs. Zic3 null mice recapitulate the human heterotaxy phenotype but also have early gastrulation defects, axial patterning defects and neural tube defects complicating an assessment of the role of Zic3 in cardiac development. Zic3 is expressed ubiquitously during critical stages of left–right patterning but its later expression in the developing heart remains controversial and the molecular mechanism(s) by which it causes heterotaxy are unknown. To define the temporal and spatial requirements, for Zic3 in left–right patterning, we generated conditional Zic3 mice and Zic3-LacZ-BAC reporter mice. The latter provide compelling evidence that Zic3 is expressed in the mouse node and absent in the heart. Conditional deletion using T-Cre identifies a requirement for Zic3 in the primitive streak and migrating mesoderm for proper left–right patterning and cardiac development. In contrast, Zic3 is not required in heart progenitors or the cardiac compartment. In addition, the data demonstrate abnormal node morphogenesis in Zic3 null mice and identify similar node dysplasia when Zic3 was specifically deleted from the migrating mesoderm and primitive streak. These results define the temporal and spatial requirements for Zic3 in node morphogenesis, left–right patterning and cardiac development and suggest the possibility that a requirement for Zic3 in node ultrastructure underlies its role in heterotaxy and laterality disorders. PMID:23303524
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NASA Astrophysics Data System (ADS)
Vrigneaud, J. M.; McGrath, J.; Courteau, A.; Pegg, R.; Sanchez-Pastor Gomis, A.; Camacho, A.; Martin, G.; Schramm, N.; Brunotte, F.
2018-06-01
We evaluated the performance characteristics of a prototype preclinical PET scanner available as an easy clippable assembly that can dock to an MRI system. The single ring version of the PET system consists of eight detectors, each of which comprises a 12 × 12 silicon photomultipliers (SiPMs) array coupled with a dual layer of offset scintillation crystals to measure depth of interaction. The crystal arrays have 29 × 29 (30 × 30 for the outer layer) 4 mm long LYSO crystals (6 mm for the outer layer). The ring diameter is 119.2 mm and the axial field of view is 50.4 mm. The NEMA NU 4-2008 protocol was followed for studying the PET performance. Temperature stability of SiPMs was also investigated. The peak system absolute sensitivity was 4.70% with an energy window of 250–750 keV. The spatial resolution was 1.28/1.88/1.85 mm FWHM (radial/tangential/axial) at a distance of 5 mm from the center. Peak noise equivalent counting rate and scatter fraction for mouse phantom were 61.9 kcps at 14.9 MBq and 21.0%, respectively. The uniformity was 6.3% and the spill-over ratios in the images of the water-and air-filled chambers were 0.07 and 0.17, respectively. Recovery coefficients ranged from 0.13 to 0.96. Change in sensitivity as a function of ambient temperature was 0.3%/°C. These first results indicate excellent spatial resolution performance for use with animal studies. Moreover, the clippable assembly can be upgraded to accept a second ring of SiPMs modules, leading to improved sensitivity and axial coverage.
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Duan, Xin; Sandell, Linda J.; Chinzei, Nobuaki; Holguin, Nilsson; Silva, Matthew J.; Schiavinato, Antonella
2017-01-01
Objective To investigate the therapeutic potential of intra-articular hyaluronan-derivative HYADD® 4-G and/or platelet-rich plasma (PRP) in a mouse model of non-invasive joint injury. Methods Non-invasive axial tibial loading was used to induce joint injury in 10-week-old C57BL/6J mice (n = 86). Mice underwent a single loading of either 6 Newton (N) or 9N axial tibial compression. HYADD® 4-G was injected intra-articularly at 8 mg/mL or 15 mg/mL either before or after loading with or without PRP. Phosphate-buffered-saline was injected as control. Knee joints were harvested at 5 or 56 days post-loading and prepared for micro-computed tomography scanning and subsequently processed for histology. Immunostaining was performed for aggrecan to monitor its distribution, for CD44 to monitor chondrocyte reactive changes and for COMP (cartilage oligomeric matrix protein) as an index for cartilage matrix changes related to loading and cartilage injury. TUNEL assay was performed to identify chondrocyte apoptosis. Results Loading initiated cartilage proteoglycan loss and chondrocyte apoptosis within 5 days with slowly progressive post-traumatic osteoarthritis (no cartilage degeneration, but increased synovitis and ectopic calcification after 9N loading) at 56 days. Mice treated with repeated HYADD® 4-G (15 mg/mL) or HYADD® 4-G (8 mg/mL) ± PRP or PRP alone exhibited no significant improvement in the short-term (5 days) and long-term (56 days) consequences of joint loading except for a trend for improved bone changes compared to non-loaded joints. Conclusion While we failed to show an overall effect of intra-articular delivery of hyaluronan-derivative and/or PRP in reversing/protecting the pathological events in cartilage and synovium following joint injury, some bone alterations were relatively less severe with hyaluronan-derivative at higher concentration or in association with PRP. PMID:28406954
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Genetic Regulatory Networks in Embryogenesis and Evolution
NASA Technical Reports Server (NTRS)
1998-01-01
The article introduces a series of papers that were originally presented at a workshop titled Genetic Regulatory Network in Embryogenesis and Evaluation. Contents include the following: evolution of cleavage programs in relationship to axial specification and body plan evolution, changes in cell lineage specification elucidate evolutionary relations in spiralia, axial patterning in the leech: developmental mechanisms and evolutionary implications, hox genes in arthropod development and evolution, heterochronic genes in development and evolution, a common theme for LIM homeobox gene function across phylogeny, and mechanisms of specification in ascidian embryos.
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spadetail-dependent cell compaction of the dorsal zebrafish blastula.
Warga, R M; Nüsslein-volhard, C
1998-11-01
The dorsal marginal zone of the zebrafish blastula, equivalent to the amphibian Spemann organizer, is destined to become the tissues of the notochord and prechordal plate. Preceding gastrulation in the zebrafish, we find that these future mesendodermal cells acquire a cohesive cell behavior characterized by flattening and maximization of intercellular contacts, somewhat resembling cell compaction in mouse blastocysts. This behavior may suppress cell intermingling. Surprisingly, this blastula cell compaction requires normal function of spadetail, a gene known to be necessary for the dorsal convergent cell movement of paraxial mesoderm later in the gastrula. We propose that spadetail-dependent cell compaction subtly controls the early mixing and dispersal of dorsal cells that coalesce into the prospective organizer region. This early process may be necessary for the correct location of the boundary separating axial and paraxial cells. Copyright 1998 Academic Press.
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NASA Astrophysics Data System (ADS)
Alqasemi, Umar; Li, Hai; Yuan, Guangqian; Kumavor, Patrick; Zanganeh, Saeid; Zhu, Quing
2014-07-01
Coregistered ultrasound (US) and photoacoustic imaging are emerging techniques for mapping the echogenic anatomical structure of tissue and its corresponding optical absorption. We report a 128-channel imaging system with real-time coregistration of the two modalities, which provides up to 15 coregistered frames per second limited by the laser pulse repetition rate. In addition, the system integrates a compact transvaginal imaging probe with a custom-designed fiber optic assembly for in vivo detection and characterization of human ovarian tissue. We present the coregistered US and photoacoustic imaging system structure, the optimal design of the PC interfacing software, and the reconfigurable field programmable gate array operation and optimization. Phantom experiments of system lateral resolution and axial sensitivity evaluation, examples of the real-time scanning of a tumor-bearing mouse, and ex vivo human ovaries studies are demonstrated.
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Miller, David R.; Hassan, Ahmed M.; Jarrett, Jeremy W.; Medina, Flor A.; Perillo, Evan P.; Hagan, Kristen; Shams Kazmi, S. M.; Clark, Taylor A.; Sullender, Colin T.; Jones, Theresa A.; Zemelman, Boris V.; Dunn, Andrew K.
2017-01-01
We perform high-resolution, non-invasive, in vivo deep-tissue imaging of the mouse neocortex using multiphoton microscopy with a high repetition rate optical parametric amplifier laser source tunable between λ=1,100 and 1,400 nm. By combining the high repetition rate (511 kHz) and high pulse energy (400 nJ) of our amplifier laser system, we demonstrate imaging of vasculature labeled with Texas Red and Indocyanine Green, and neurons expressing tdTomato and yellow fluorescent protein. We measure the blood flow speed of a single capillary at a depth of 1.2 mm, and image vasculature to a depth of 1.53 mm with fine axial steps (5 μm) and reasonable acquisition times. The high image quality enabled analysis of vascular morphology at depths to 1.45 mm. PMID:28717582
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EMG1 is essential for mouse pre-implantation embryo development.
Wu, Xiaoli; Sandhu, Sumit; Patel, Nehal; Triggs-Raine, Barbara; Ding, Hao
2010-09-21
Essential for mitotic growth 1 (EMG1) is a highly conserved nucleolar protein identified in yeast to have a critical function in ribosome biogenesis. A mutation in the human EMG1 homolog causes Bowen-Conradi syndrome (BCS), a developmental disorder characterized by severe growth failure and psychomotor retardation leading to death in early childhood. To begin to understand the role of EMG1 in mammalian development, and how its deficiency could lead to Bowen-Conradi syndrome, we have used mouse as a model. The expression of Emg1 during mouse development was examined and mice carrying a null mutation for Emg1 were generated and characterized. Our studies indicated that Emg1 is broadly expressed during early mouse embryonic development. However, in late embryonic stages and during postnatal development, Emg1 exhibited specific expression patterns. To assess a developmental role for EMG1 in vivo, we exploited a mouse gene-targeting approach. Loss of EMG1 function in mice arrested embryonic development prior to the blastocyst stage. The arrested Emg1-/- embryos exhibited defects in early cell lineage-specification as well as in nucleologenesis. Further, loss of p53, which has been shown to rescue some phenotypes resulting from defects in ribosome biogenesis, failed to rescue the Emg1-/- pre-implantation lethality. Our data demonstrate that Emg1 is highly expressed during mouse embryonic development, and essential for mouse pre-implantation development. The absolute requirement for EMG1 in early embryonic development is consistent with its essential role in yeast. Further, our findings also lend support to the previous study that showed Bowen-Conradi syndrome results from a partial EMG1 deficiency. A complete deficiency would not be expected to be compatible with a live birth.
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NASA Astrophysics Data System (ADS)
Lopez, Andrew L.; Wang, Shang; Garcia, Monica; Valladolid, Christian; Larin, Kirill V.; Larina, Irina V.
2015-03-01
Understanding mouse embryonic development is an invaluable resource for our interpretation of normal human embryology and congenital defects. Our research focuses on developing methods for live imaging and dynamic characterization of early embryonic development in mouse models of human diseases. Using multidisciplinary methods: optical coherence tomography (OCT), live mouse embryo manipulations and static embryo culture, molecular biology, advanced image processing and computational modeling we aim to understand developmental processes. We have developed an OCT based approach to image live early mouse embryos (E8.5 - E9.5) cultured on an imaging stage and visualize developmental events with a spatial resolution of a few micrometers (less than the size of an individual cell) and a frame rate of up to hundreds of frames per second and reconstruct cardiodynamics in 4D (3D+time). We are now using these methods to study how specific embryonic lethal mutations affect cardiac morphology and function during early development.
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NASA Astrophysics Data System (ADS)
Lloyd, William R.; Sinder, Benjamin P.; Salemi, Joseph; Ominsky, Michael S.; Marini, Joan C.; Caird, Michelle S.; Morris, Michael D.; Kozloff, Kenneth M.
2015-02-01
Osteogenesis imperfecta (OI) is a genetic disorder resulting in defective collagen or collagen-associated proteins and fragile, brittle bones. To date, therapies to improve OI bone mass, such as bisphosphonates, have increased bone mass in the axial skeleton of OI patients, but have shown limited effects at reducing long bone fragility. Sclerostin antibody (Scl- Ab), currently in clinical trials for osteoporosis, stimulates bone formation and may have the potential to reduce long bone fracture rates in OI patients. Scl-Ab has been investigated as an anabolic therapy for OI in the Brtl/+ mouse model of moderately severe Type IV OI. While Scl-Ab increases long bone mass in the Brtl/+ mouse, it is not known whether material properties and composition changes also occur. Here, we report on the effects of Scl-Ab on wild type and Brtl/+ young (3 week) and adult (6 month) male mice. Scl-Ab was administered over 5 weeks (25mg/kg, 2x/week). Raman microspectroscopy and nanoindentation are used for bone composition and biomechanical bone property measurements in excised bone. Fluorescent labels (calcein and alizarin) at 4 time points over the entire treatment period are used to enable measurements at specific tissue age. Differences between wild type and Brtl/+ groups included variations in the mineral and matrix lattices, particularly the phosphate v1, carbonate v1, and the v(CC) proline and hydroxyproline stretch vibrations. Results of Raman spectroscopy corresponded to nanoindentation findings which indicated that old bone (near midcortex) is stiffer (higher elastic modulus) than new bone. We compare and contrast mineral to matrix and carbonate to phosphate ratios in young and adult mice with and without treatment.
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Cadmium Alternatives for High-Strength Steel
2011-09-22
coating small parts, a barrel coater was developed which originally coated 75 pounds of steel fasteners during a coating run. By the early 1980s...technique to define design allowables. Other design authorities rely more heavily on axial tension-tension or tension- compression data. Some axial ...FINAL REPORT Cadmium Alternatives for High-Strength Steel WP-200022 Steven A. Brown Naval Air Warfare Center Aircraft Division Patuxent
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Preliminary Assessment of a Rotary Detonation Engine Concept.
1983-09-01
As advances were made in compressors (both axial and centrifugal), it was possible to develop gas turbine engines based on the Brayton cycle rather...induced cycle pressure ratio. In the case of the axial flow compressor, as stages are added to increase the pressure, the blades become progressively...DESIGN OF THE TORQUE TUBE --------- 96 APPENDIX E. EQUIPMENT LISTING- - --------- -- 104 APPENDIX F. DESIGN DRAWINGS FOR ROTARY DETONATION TURBINE
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Damage Arresting Composites for Shaped Vehicles - Phase II Final Report
NASA Technical Reports Server (NTRS)
Velicki, Alex; Yovanof, Nicolette; Baraja, Jaime; Linton, Kim; Li, Victor; Hawley, Arthur; Thrash, Patrick; DeCoux, Steve; Pickell, Robert
2011-01-01
This report describes the development of a novel structural concept, Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS), that addresses the demanding fuselage loading requirements for the Hybrid Wing or Blended Wing Body (BWB) airplane configuration. In addition to the analytical studies, a three specimen test program was also completed to assess the concept under axial tension loading, axial compression loading, and internal pressure loading.
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Wu, Feng-Rui; Ding, Biao; Qi, Bin; Shang, Ming-Bao; Yang, Xun-Xun; Liu, Yong; Li, Wen-Yong
2012-10-10
Ifrg15 is a newly identified interferon alpha responsive gene and is implicated in a wide variety of physiological roles in mammals. In the present study, multiple alignments of the deduced amino acids of 10 eutherian mammalian IFRG15/Ifrg15s isolated from open genomic database revealed that they were highly conserved. Real-time PCR showed that mouse Ifrg15 mRNA was expressed in MII stage oocytes and preimplantation embryos, and its highest value peaked at the stage of mouse blastocysts. To understand the effect of three development-related genes on the promoter activity of mouse Ifrg15, promoter analysis using luciferase assays in COS-7 cells were performed. The results showed that the transcription of mouse Ifrg15 was suppressed by Oct4 and Nanog when transfected with the longest Ifrg15 promoter reporter gene. After the relatively shorter promoters were co-transfected with Oct4, c-Myc and Nanog, the relative luciferase activities of Ifrg15 were gradually increased. These in vitro results data and expression profiles of Ifrg15 as revealed by real-time PCR partly indicated that Ifrg15 transcription might be either potentially regulated or dependent on the post-transcriptional effects of IFN-α mediated by the three genes indirectly. Our data suggested that the mouse Ifrg15 might interact with these key development-related genes and play significant roles on the mouse preimplantation embryos development, especially for the development of mouse blastocysts. Copyright © 2012 Elsevier B.V. All rights reserved.
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Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain
Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich
2014-01-01
The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior–posterior, dorsal–ventral and medial– lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson’s disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. Database URL: http://mouseidgenes.helmholtz-muenchen.de. PMID:25145340
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Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.
Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich
2014-01-01
The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.
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Disrupting the male germ line to find infertility and contraception targets.
Archambeault, Denise R; Matzuk, Martin M
2014-05-01
Genetically-manipulated mouse models have become indispensible for broadening our understanding of genes and pathways related to male germ cell development. Until suitable in vitro systems for studying spermatogenesis are perfected, in vivo models will remain the gold standard for inquiry into testicular function. Here, we discuss exciting advances that are allowing researchers faster, easier, and more customizable access to their mouse models of interest. Specifically, the trans-NIH Knockout Mouse Project (KOMP) is working to generate knockout mouse models of every gene in the mouse genome. The related Knockout Mouse Phenotyping Program (KOMP2) is performing systematic phenotypic analysis of this genome-wide collection of knockout mice, including fertility screening. Together, these programs will not only uncover new genes involved in male germ cell development but also provide the research community with the mouse models necessary for further investigations. In addition to KOMP/KOMP2, another promising development in the field of mouse models is the advent of CRISPR (clustered regularly interspaced short palindromic repeat)-Cas technology. Utilizing 20 nucleotide guide sequences, CRISPR/Cas has the potential to introduce sequence-specific insertions, deletions, and point mutations to produce null, conditional, activated, or reporter-tagged alleles. CRISPR/Cas can also successfully target multiple genes in a single experimental step, forgoing the multiple generations of breeding traditionally required to produce mouse models with deletions, insertions, or mutations in multiple genes. In addition, CRISPR/Cas can be used to create mouse models carrying variants identical to those identified in infertile human patients, providing the opportunity to explore the effects of such mutations in an in vivo system. Both the KOMP/KOMP2 projects and the CRISPR/Cas system provide powerful, accessible genetic approaches to the study of male germ cell development in the mouse. A more complete understanding of male germ cell biology is critical for the identification of novel targets for potential non-hormonal contraceptive intervention. Copyright © 2014. Published by Elsevier Masson SAS.
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Effect of Axial Force on the Performance of Micromachined Vibratory Rate Gyroscopes
Hou, Zhanqiang; Xiao, Dingbang; Wu, Xuezhong; Dong, Peitao; Chen, Zhihua; Niu, Zhengyi; Zhang, Xu
2011-01-01
It is reported in the published literature that the resonant frequency of a silicon micromachined gyroscope decreases linearly with increasing temperature. However, when the axial force is considerable, the resonant frequency might increase as the temperature increases. The axial force is mainly induced by thermal stress due to the mismatch between the thermal expansion coefficients of the structure and substrate. In this paper, two types of micromachined suspended vibratory gyroscopes with slanted beams were proposed to evaluate the effect of the axial force. One type was suspended with a clamped-free (C-F) beam and the other one was suspended with a clamped-clamped (C-C) beam. Their drive modes are the bending of the slanted beam, and their sense modes are the torsion of the slanted beam. The relationships between the resonant frequencies of the two types were developed. The prototypes were packaged by vacuum under 0.1 mbar and an analytical solution for the axial force effect on the resonant frequency was obtained. The temperature dependent performances of the operated mode responses of the micromachined gyroscopes were measured. The experimental values of the temperature coefficients of resonant frequencies (TCF) due to axial force were 101.5 ppm/°C for the drive mode and 21.6 ppm/°C for the sense mode. The axial force has a great influence on the modal frequency of the micromachined gyroscopes suspended with a C-C beam, especially for the flexure mode. The quality factors of the operated modes decreased with increasing temperature, and changed drastically when the micromachined gyroscopes worked at higher temperatures. PMID:22346578
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End wall flow characteristics and overall performance of an axial flow compressor stage
NASA Technical Reports Server (NTRS)
Sitaram, N.; Lakshminarayana, B.
1983-01-01
This review indicates the possible future directions for research on endwall flows in axial flow compressors. Theoretical investigations on the rotor blade endwall flows in axial flow compressors reported here include the secondary flow calculation and the development of the momentum integral equations for the prediction of the annulus wall boundary layer. The equations for secondary vorticity at the rotor exit are solved analytically. The solution includes the effects of rotation and the viscosity. The momentum integral equations derived include the effect of the blade boundary layers. The axial flow compressor facility of the Department of Aerospace Engineering at The Pennsylvania State University, which is used for the experimental investigations of the endwall flows, is described in some detail. The overall performance and other preliminary experimental results are presented. Extensive radial flow surveys are carried out at the design and various off design conditions. These are presented and interpreted in this report. The following experimental investigations of the blade endwall flows are carried out. (1) Rotor blade endwall flows: The following measurements are carried out at four flow coefficients. (a) The rotor blade static pressures at various axial and radial stations (with special emphasis near the blade tips). (b) The hub wall static pressures inside the rotor blade passage at various axial and tangential stations. (2) IGV endwall flows: The following measurements are carried out at the design flow coefficient. (a) The boundary layer profiles at various axial and tangential stations inside the blade passage and at the blade exit. (b) Casing static pressures and limiting streamline angles inside the blade passage.
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The Role of Xist in X-Chromosome Dosage Compensation.
Sahakyan, Anna; Yang, Yihao; Plath, Kathrin
2018-06-14
In each somatic cell of a female mammal one X chromosome is transcriptionally silenced via X-chromosome inactivation (XCI), initiating early in development. Although XCI events are conserved in mouse and human postimplantation development, regulation of X-chromosome dosage in preimplantation development occurs differently. In preimplantation development, mouse embryos undergo imprinted form of XCI, yet humans lack imprinted XCI and instead regulate gene expression of both X chromosomes by dampening transcription. The long non-coding RNA Xist/XIST is expressed in mouse and human preimplantation and postimplantation development to orchestrate XCI, but its role in dampening is unclear. In this review, we discuss recent advances in our understanding of the role of Xist in X chromosome dosage compensation in mouse and human. Copyright © 2018 Elsevier Ltd. All rights reserved.
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The latest animal models of ovarian cancer for novel drug discovery.
Magnotti, Elizabeth; Marasco, Wayne A
2018-03-01
Epithelial ovarian cancer is a heterogeneous disease classified into five subtypes, each with a different molecular profile. Most cases of ovarian cancer are diagnosed after metastasis of the primary tumor and are resistant to traditional platinum-based chemotherapeutics. Mouse models of ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the tumor's response to therapeutics. Areas covered: The authors provide a review of mouse models currently employed to understand ovarian cancer. This article focuses on advances in the development of orthotopic and patient-derived tumor xenograft (PDX) mouse models of ovarian cancer and discusses current humanized mouse models of ovarian cancer. Expert opinion: The authors suggest that humanized mouse models of ovarian cancer will provide new insight into the role of the human immune system in combating and augmenting ovarian cancer and aid in the development of novel therapeutics. Development of humanized mouse models will take advantage of the NSG and NSG-SGM3 strains of mice as well as new strains that are actively being derived.
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NASA Technical Reports Server (NTRS)
Ku, C.-P. Roger; Walton, James F., Jr.; Lund, Jorgen W.
1994-01-01
This paper provided an opportunity to quantify the angular stiffness and equivalent viscous damping coefficients of an axial spline coupling used in high-speed turbomachinery. A unique test methodology and data reduction procedures were developed. The bending moments and angular deflections transmitted across an axial spline coupling were measured while a nonrotating shaft was excited by an external shaker. A rotor dynamics computer program was used to simulate the test conditions and to correlate the angular stiffness and damping coefficients. In addition, sensitivity analyses were performed to show that the accuracy of the dynamic coefficients do not rely on the accuracy of the data reduction procedures.
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Performance of NACA Eight-stage Axial-flow Compressor Designed on the Basis of Airfoil Theory
NASA Technical Reports Server (NTRS)
Sinnette, John T; Schey, Oscar W; King, J Austin
1943-01-01
The NACA has conducted an investigation to determine the performance that can be obtained from a multistage axial-flow compressor based on airfoil research. A theory was developed; an eight-stage axial-flow compressor was designed, constructed, and tested. The performance of the compressor was determined for speeds from 5000 to 14,000 r.p.m with varying air flow at each speed. Most of the tests were made with air at room temperature. The performance was determined in accordance with the Committee's recommended procedure for testing superchargers. The expected performance was obtained, showing that a multistage compressor of high efficiency can be designed by the application of airfoil theory.
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Model of an axially strained weakly guiding optical fiber modal pattern
NASA Technical Reports Server (NTRS)
Egalon, Claudio O.; Rogowski, Robert S.
1991-01-01
Axial strain may be determined by monitoring the modal pattern variation of an optical fiber. In this paper we present the results of a numerical model that has been developed to calculate the modal pattern variation at the end of a weakly guiding optical fiber under axial strain. Whenever an optical fiber is under stress, the optical path length, the index of refraction and the propagation constants of each fiber mode change. In consequence, the modal phase term of the fields and the fiber output pattern are also modified. For multimode fibers, very complicated patterns result. The predicted patterns are presented, and an expression for the phase variation with strain is derived.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Schulz, Douglas A.
2007-10-08
A biometric system suitable for validating user identity using only mouse movements and no specialized equipment is presented. Mouse curves (mouse movements with little or no pause between them) are individually classied and used to develop classication histograms, which are representative of an individual's typical mouse use. These classication histograms can then be compared to validate identity. This classication approach is suitable for providing continuous identity validation during an entire user session.
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ERIC Educational Resources Information Center
Shih, Ching-Hsiang; Chang, Man-Ling; Shih, Ching-Tien
2009-01-01
This study evaluated whether two people with multiple disabilities and minimal motor behavior would be able to improve their pointing performance using finger poke ability with a mouse wheel through a Dynamic Pointing Assistive Program (DPAP) and a newly developed mouse driver (i.e., a new mouse driver replaces standard mouse driver, changes a…
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-28
...] Final Environmental Impact Statement and Record of Decision for Alabama Beach Mouse General Conservation... mouse (Peromyscus polionotus ammobates). For record of decision (ROD) availability, see DATES. DATES... beach mouse incidental to construction of up to 500 single-family developments potentially affecting an...
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Development of a methodology to evaluate material accountability in pyroprocess
NASA Astrophysics Data System (ADS)
Woo, Seungmin
This study investigates the effect of the non-uniform nuclide composition in spent fuel on material accountancy in the pyroprocess. High-fidelity depletion simulations are performed using the Monte Carlo code SERPENT in order to determine nuclide composition as a function of axial and radial position within fuel rods and assemblies, and burnup. For improved accuracy, the simulations use short burnups step (25 days or less), Xe-equilibrium treatment (to avoid oscillations over burnup steps), axial moderator temperature distribution, and 30 axial meshes. Analytical solutions of the simplified depletion equations are built to understand the axial non-uniformity of nuclide composition in spent fuel. The cosine shape of axial neutron flux distribution dominates the axial non-uniformity of the nuclide composition. Combined cross sections and time also generate axial non-uniformity, as the exponential term in the analytical solution consists of the neutron flux, cross section and time. The axial concentration distribution for a nuclide having the small cross section gets steeper than that for another nuclide having the great cross section because the axial flux is weighted by the cross section in the exponential term in the analytical solution. Similarly, the non-uniformity becomes flatter as increasing burnup, because the time term in the exponential increases. Based on the developed numerical recipes and decoupling of the results between the axial distributions and the predetermined representative radial distributions by matching the axial height, the axial and radial composition distributions for representative spent nuclear fuel assemblies, the Type-0, -1, and -2 assemblies after 1, 2, and 3 depletion cycles, is obtained. These data are appropriately modified to depict processing for materials in the head-end process of pyroprocess that is chopping, voloxidation and granulation. The expectation and standard deviation of the Pu-to-244Cm-ratio by the single granule sampling calculated by the central limit theorem and the Geary-Hinkley transformation. Then, the uncertainty propagation through the key-pyroprocess is conducted to analyze the Material Unaccounted For (MUF), which is a random variable defined as a receipt minus a shipment of a process, in the system. The random variable, LOPu, is defined for evaluating the non-detection probability at each Key Measurement Point (KMP) as the original Pu mass minus the Pu mass after a missing scenario. A number of assemblies for the LOPu to be 8 kg is considered in this calculation. The probability of detection for the 8 kg LOPu is evaluated with respect the size of granule and powder using the event tree analysis and the hypothesis testing method. We can observe there are possible cases showing the probability of detection for the 8 kg LOPu less than 95%. In order to enhance the detection rate, a new Material Balance Area (MBA) model is defined for the key-pyroprocess. The probabilities of detection for all spent fuel types based on the new MBA model are greater than 99%. Furthermore, it is observed that the probability of detection significantly increases by increasing granule sample sizes to evaluate the Pu-to-244Cm-ratio before the key-pyroprocess. Based on these observations, even though the Pu material accountability in pyroprocess is affected by the non-uniformity of nuclide composition when the Pu-to-244Cm-ratio method is being applied, that is surmounted by decreasing the uncertainty of measured ratio by increasing sample sizes and modifying the MBAs and KMPs. (Abstract shortened by ProQuest.).
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Advanced axial field D.C. motor development for electric passenger vehicle
NASA Technical Reports Server (NTRS)
Jones, W. J.
1982-01-01
A wound-field axial-flux dc motor was developed for an electric vehicle drive system. The motor is essentially an axial-flux version of the classical Gramme-ring winding motor, but the active conductors are recessed into slots cut into the two opposite faces of the laminated tape-wound core ring. Three motors were built and tested in the program. The second (functional) model was a six-pole machine which weighed 88.5 kg. It developed 16.9 km (33.0 hp), and a max speed of 4800 rpm. Full load efficiency was 92% and predicted SAE D-cycle efficiency was 88%. The last engineering) model was a 4-pole machine with compoles, allowing a weight reduction to 45 kg (100 lbs.) while addressing some manufacturability problems. The engineering model was rated at 13.2 kw (17.6 hp) at 3000 rpm, with a peak power of 19.8 km (26.4 hp) and a max speed of 7200 rpm. Initial test results on this motor showed poor commutation and efficiency; the program was terminated without resolution of these problems.
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Xu, Zheng; Xu, Li-Wen
2015-10-01
Recently, academic chemists have renewed their interest in the development of 1,1'-binaphthalene-2,2'-diol (BINOL)-derived chiral ligands. Six years ago, a working hypothesis, that the chirality matching of hybrid chirality on a ligand could probably lead to high levels of stereoselective induction, prompted us to use the axial chirality of BINOL derivatives to generate new stereogenic centers within the same molecule with high stereoselectivity, obtaining as a result sterically favorable ligands for applications in asymmetric catalysis. This Personal Account describes our laboratory's efforts toward the development of a novel class of BINOL-derived atropisomers bearing both axial and sp(3) central chirality, the so-called Ar-BINMOLs, for asymmetric synthesis. Furthermore, on the basis of the successful application of Ar-BINMOLs and their derivatives in asymmetric catalysis, the search for highly efficient and enantioselective processes also compelled us to give special attention to the BINOL-derived multifunctional ligands with multiple stereogenic centers for use in catalytic asymmetric reactions. Copyright © 2015 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Dong, Biqin; Li, Hao; Zhang, Zhen; Zhang, Kevin; Chen, Siyu; Sun, Cheng; Zhang, Hao F
2015-01-01
Photoacoustic microscopy (PAM) is an attractive imaging tool complementary to established optical microscopic modalities by providing additional molecular specificities through imaging optical absorption contrast. While the development of optical resolution photoacoustic microscopy (ORPAM) offers high lateral resolution, the acoustically-determined axial resolution is limited due to the constraint in ultrasonic detection bandwidth. ORPAM with isometric spatial resolution along both axial and lateral direction is yet to be developed. Although recently developed sophisticated optical illumination and reconstruction methods offer improved axial resolution in ORPAM, the image acquisition procedures are rather complicated, limiting their capabilities for high-speed imaging and being easily integrated with established optical microscopic modalities. Here we report an isometric ORPAM based on an optically transparent micro-ring resonator ultrasonic detector and a commercial inverted microscope platform. Owing to the superior spatial resolution and the ease of integrating our ORPAM with established microscopic modalities, single cell imaging with extrinsic fluorescence staining, intrinsic autofluorescence, and optical absorption can be achieved simultaneously. This technique holds promise to greatly improve the accessibility of PAM to the broader biomedical researchers.
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Kerrigan, Shannon M; Kapatkin, Amy S; Garcia, Tanya C; Robinson, Duane A; Guzman, David Sanchez-Migallon; Stover, Susan M
2018-04-01
OBJECTIVE To describe the torsional and axial compressive properties of tibiotarsal bones of red-tailed hawks (Buteo jamaicensis). SAMPLE 16 cadaveric tibiotarsal bones from 8 red-tailed hawks. PROCEDURES 1 tibiotarsal bone from each bird was randomly assigned to be tested in torsion, and the contralateral bone was tested in axial compression. Intact bones were monotonically loaded in either torsion (n = 8) or axial compression (8) to failure. Mechanical variables were derived from load-deformation curves. Fracture configurations were described. Effects of sex, limb side, and bone dimensions on mechanical properties were assessed with a mixed-model ANOVA. Correlations between equivalent torsional and compressive properties were determined. RESULTS Limb side and bone dimensions were not associated with any mechanical property. During compression tests, mean ultimate cumulative energy and postyield energy for female bones were significantly greater than those for male bones. All 8 bones developed a spiral diaphyseal fracture and a metaphyseal fissure or fracture during torsional tests. During compression tests, all bones developed a crushed metaphysis and a fissure or comminuted fracture of the diaphysis. Positive correlations were apparent between most yield and ultimate torsional and compressive properties. CONCLUSIONS AND CLINICAL RELEVANCE The torsional and axial compressive properties of tibiotarsal bones described in this study can be used as a reference for investigations into fixation methods for tibiotarsal fractures in red-tailed hawks. Although the comminuted and spiral diaphyseal fractures induced in this study were consistent with those observed in clinical practice, the metaphyseal disruption observed was not and warrants further research.
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4D atlas of the mouse embryo for precise morphological staging.
Wong, Michael D; van Eede, Matthijs C; Spring, Shoshana; Jevtic, Stefan; Boughner, Julia C; Lerch, Jason P; Henkelman, R Mark
2015-10-15
After more than a century of research, the mouse remains the gold-standard model system, for it recapitulates human development and disease and is quickly and highly tractable to genetic manipulations. Fundamental to the power and success of using a mouse model is the ability to stage embryonic mouse development accurately. Past staging systems were limited by the technologies of the day, such that only surface features, visible with a light microscope, could be recognized and used to define stages. With the advent of high-throughput 3D imaging tools that capture embryo morphology in microscopic detail, we now present the first 4D atlas staging system for mouse embryonic development using optical projection tomography and image registration methods. By tracking 3D trajectories of every anatomical point in the mouse embryo from E11.5 to E14.0, we established the first 4D atlas compiled from ex vivo 3D mouse embryo reference images. The resulting 4D atlas comprises 51 interpolated 3D images in this gestational range, resulting in a temporal resolution of 72 min. From this 4D atlas, any mouse embryo image can be subsequently compared and staged at the global, voxel and/or structural level. Assigning an embryonic stage to each point in anatomy allows for unprecedented quantitative analysis of developmental asynchrony among different anatomical structures in the same mouse embryo. This comprehensive developmental data set offers developmental biologists a new, powerful staging system that can identify and compare differences in developmental timing in wild-type embryos and shows promise for localizing deviations in mutant development. © 2015. Published by The Company of Biologists Ltd.
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Validation and Design of Sheet Retrofits
2010-10-31
enough to allow for rotation of the top of the wall without development of an axial force. Obviously, these walls are not load bearing . This type...structures are commonly constructed using CMU blocks to infill non- load bearing walls (Hammons, 1999). Many of these structures were built in a... axial loads within the sheet. 3 Figure 1. Infill Masonry Wall Retrofit Concept 2.1. Objective The objective of the research documented in
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Khosla, Nidhi; Marsteller, Jill A; Holtgrave, David R
2013-11-01
We examined whether mandated collaboration reflected in memoranda of understanding (MOUs) developed by health agencies to meet funder expectations is effective in fostering inter-agency collaboration. We conducted 22 semi-structured interviews from late 2010 to early 2012 in Baltimore, USA, with representatives of 17 HIV service agencies, three local health department units, and one agency that closed in 2008 (two interviews). While there was no consensus, most respondents perceived MOUs negatively, mainly because the process of obtaining signed MOUs was time consuming; frontline staff was mostly unaware of MOUs, agencies did not necessarily work with agencies they signed MOUs with and MOUs were rarely evaluated after being signed. A few agencies reported that MOUs could keep agencies focused and set mutual expectations. The local health department acknowledged shortcomings in MOUs but emphasized that MOUs could help agencies plan for referring clients when their own capacity was full. Although many agencies acknowledged the importance of collaboration, most respondents found that MOUs lacked practical utility. Grant-makers should consult sub-grantees to develop alternative means of fostering collaboration that would be perceived as relevant by both parties. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
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Choi, Kai Yip; Yu, Wing Yan; Lam, Christie Hang I; Li, Zhe Chuang; Chin, Man Pan; Lakshmanan, Yamunadevi; Wong, Francisca Siu Yin; Do, Chi Wai; Lee, Paul Hong; Chan, Henry Ho Lung
2017-09-01
People in Hong Kong generally live in a densely populated area and their homes are smaller compared with most other cities worldwide. Interestingly, East Asian cities with high population densities seem to have higher myopia prevalence, but the association between them has not been established. This study investigated whether the crowded habitat in Hong Kong is associated with refractive error among children. In total, 1075 subjects [Mean age (S.D.): 9.95 years (0.97), 586 boys] were recruited. Information such as demographics, living environment, parental education and ocular status were collected using parental questionnaires. The ocular axial length and refractive status of all subjects were measured by qualified personnel. Ocular axial length was found to be significantly longer among those living in districts with a higher population density (F 2,1072 = 6.15, p = 0.002) and those living in a smaller home (F 2,1072 = 3.16, p = 0.04). Axial lengths were the same among different types of housing (F 3,1071 = 1.24, p = 0.29). Non-cycloplegic autorefraction suggested a more negative refractive error in those living in districts with a higher population density (F 2,1072 = 7.88, p < 0.001) and those living in a smaller home (F 2,1072 = 4.25, p = 0.02). After adjustment for other confounding covariates, the population density and home size also significantly predicted axial length and non-cycloplegic refractive error in the multiple linear regression model, while axial length and refractive error had no relationship with types of housing. Axial length in children and childhood refractive error were associated with high population density and small home size. A constricted living space may be an environmental threat for myopia development in children. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.
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Blangy, A; Léopold, P; Vidal, F; Rassoulzadegan, M; Cuzin, F
1991-01-01
We have reported previously (1) two unexpected consequences of the microinjection into fertilized mouse eggs of a recombinant plasmid designated p12B1, carrying a 343 bp insert of non-repetitive mouse DNA. Injected at very low concentrations, this plasmid could be established as an extrachromosomal genetic element. When injected in greater concentration, an early arrest of embryonic development resulted. In the present work, we have studied this toxic effect in more detail by microinjecting short synthetic oligonucleotides with sequences from the mouse insert. Lethality was associated with the nucleotide sequence GTCACATG, identical with the CDEl element of yeast centromeres. Development of injected embryos was arrested between the one-cell and the early morula stages, with abnormal structures and DNA contents. Electrophoretic mobility shift and DNAse foot-printing assays demonstrated the binding of mouse nuclear protein(s) to the CDEl-like box. Base changes within the CDEl sequence prevented both the toxic effects in embryos and the formation of protein complex in vitro, suggesting that protein binding at such sites in chromosomal DNA plays an important role in early development. Images PMID:1766880
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Development and function of human innate immune cells in a humanized mouse model.
Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A
2014-04-01
Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.
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Development and function of human innate immune cells in a humanized mouse model
Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V.; Teichmann, Lino L.; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A. Karolina; Manz, Markus G.; Flavell, Richard A.
2014-01-01
Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models are unable to support development of human innate immune cells, including myeloid cells and NK cells. Here we describe a mouse strain, called MI(S)TRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked in to their respective mouse loci. The human cytokines support the development and function of monocytes/macrophages and natural killer cells derived from human fetal liver or adult CD34+ progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MI(S)TRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology. PMID:24633240
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2013-01-01
Background The axial skeleton is one of the defining evolutionary landmarks of vertebrates. How this structure develops and how it has evolved in the different vertebrate lineages is, however, a matter of debate. Vertebrae and vertebral structures are derived from the embryonic somites, although the mechanisms of development are different between lineages. Discussion Using the anecdotal description of a teratological newt (Triturus dobrogicus) with an unusual malformation in its axial skeleton, we review, compare, and discuss the development of vertebral structures and, in particular, the development of centra from somitic cellular domains in different vertebrate groups. Vertebrae development through re-segmentation of the somitic sclerotomal cells is considered the general mechanism among vertebrates, which has been generalized from studies in amniotic model organisms. The prevalence of this mechanism among anamniotes is, however, controversial. We propose alternative developmental mechanisms for vertebrae formation that should be experimentally tested. Summary Research in model organisms, especially amniotes, is laying the foundations for a thorough understanding of the mechanisms of development of the axial skeleton in vertebrates, foundations that should expand the extent of future comparative studies. Although immersed in the ‘-omics’ era, we emphasize the need for an integrative and organismal approach in evolutionary developmental biology for a better understanding of the causal role of development in the evolution of morphological diversity in nature. PMID:23577917
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Development of a miniature fan motor
NASA Astrophysics Data System (ADS)
Wang, Chien-Chang; Yao, Yeong-Der; Liang, Kun-Yi; Huang, Chung-Chun; Chang, Yu-Choung
2012-04-01
A novel compact axial flux fan motor was developed. Such a micromotor could be a potential candidate for using as the cooling solution for the next generation mobile devices, for example, smart phones and pico-projectors. The key parameters of the motor, such as back electromotive force, cogging torque, and axial preload are predicted using finite element method. In addition, new approaches are proposed to measure these items, and the corresponding experimental results are in good agreement with the simulated one. Moreover, the undesired vibration harmonic is successfully suppressed, and the fan motor represents a high static pressure and air flow rate.
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Experimental analysis of the flow in a two stage axial compressor at off-design conditions
NASA Astrophysics Data System (ADS)
Massardo, Aristide; Satta, Antonio
1987-05-01
The experimental analysis of the flow that develops in a two-stage axial flow compressor at off-design conditions is presented. The measurements are performed upstream, between, and downstream of the four blade rows of the compressor. The analysis shows the off-design effects on the local conditions of the flow field. Low-energy flow zones are identified, and the development of annulus-boundary-layer, secondary, and tip-clearance flows is shown. The tip-clearance flows are also present in the stator rows with various outlying conditions (stationary or rotating hub).
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NASA Technical Reports Server (NTRS)
Mcdonald, Gary H.
1987-01-01
The MSFC bearing seal material tester (BSMT) can be used to evaluate the SSME high pressure oxygen turbopump (HPOTP) bearing performance. The four HPOTP bearings have both an imposed radial and axial load. These radial and axial loads are caused by the HPOTP's shaft, main impeller, preburner impeller, turbine and by the LOX coolant flow through the bearings, respectively. These loads coupled with bearing geometry and operating speed can define bearing contact angle, contact Hertz stress, and heat generation rates. The BSMT has the capability of operating at HPOTP shaft speeds, provide proper coolant flowrates but can only apply an axial load. Due to the inability to operate the bearings in the BSMT with an applied radial load, it is important to develop an equivalency between the applied axial loads and the actual HPOTP loadings. A shaft-bearing-thermal computer code (SHABERTH/SINDA) is used to simulate the BSMT bearing-shaft geometry and thermal-fluid operating conditions.
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GaAs nanowire array solar cells with axial p-i-n junctions.
Yao, Maoqing; Huang, Ningfeng; Cong, Sen; Chi, Chun-Yung; Seyedi, M Ashkan; Lin, Yen-Ting; Cao, Yu; Povinelli, Michelle L; Dapkus, P Daniel; Zhou, Chongwu
2014-06-11
Because of unique structural, optical, and electrical properties, solar cells based on semiconductor nanowires are a rapidly evolving scientific enterprise. Various approaches employing III-V nanowires have emerged, among which GaAs, especially, is under intense research and development. Most reported GaAs nanowire solar cells form p-n junctions in the radial direction; however, nanowires using axial junction may enable the attainment of high open circuit voltage (Voc) and integration into multijunction solar cells. Here, we report GaAs nanowire solar cells with axial p-i-n junctions that achieve 7.58% efficiency. Simulations show that axial junctions are more tolerant to doping variation than radial junctions and lead to higher Voc under certain conditions. We further study the effect of wire diameter and junction depth using electrical characterization and cathodoluminescence. The results show that large diameter and shallow junctions are essential for a high extraction efficiency. Our approach opens up great opportunity for future low-cost, high-efficiency photovoltaics.
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Axial Crushing Behaviors of Thin-Walled Corrugated and Circular Tubes - A Comparative Study
NASA Astrophysics Data System (ADS)
Reyaz-Ur-Rahim, Mohd.; Bharti, P. K.; Umer, Afaque
2017-10-01
With the help of finite element analysis, this research paper deals with the energy absorption and collapse behavior with different corrugated section geometries of hollow tubes made of aluminum alloy 6060-T4. Literature available experimental data were used to validate the numerical models of the structures investigated. Based on the results available for symmetric crushing of circular tubes, models were developed to investigate corrugated thin-walled structures behavior. To study the collapse mechanism and energy absorbing ability in axial compression, the simulation was carried in ABAQUS /EXPLICIT code. In the simulation part, specimens were prepared and axially crushed to one-fourth length of the tube and the energy diagram of crushing force versus axial displacement is shown. The effect of various parameters such as pitch, mean diameter, corrugation, amplitude, the thickness is demonstrated with the help of diagrams. The overall result shows that the corrugated section geometry could be a good alternative to the conventional tubes.
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Li, Qiaoli; LaRusso, Jennifer; Grand‐Pierre, Alix E.; Uitto, Jouni
2009-01-01
Abstract Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6 −/−). This “knock‐out” (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate‐enriched diet (magnesium concentration being 5‐fold higher than in the control diet) completely prevented mineralization of the vibrissae up to 6 months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate‐enriched diet also prevented the progression of mineralization when the mice were placed on that experimental diet at 3 months of age and followed up to 6 months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over 10‐fold while the concentration of phosphorus was markedly decreased, being essentially undetectable after long‐term (>4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate‐enriched diet showed no differences in the bone density compared to mice on the control diet, and chemical assays showed a small increase in the calcium and phosphate content of the femurs by chemical assay, in comparison to mice on control diet. Similar experiments with another experimental diet supplemented with lanthanum carbonate did not interfere with the mineralization process in Abcc6 −/− mice. These results suggest that magnesium carbonate may offer a potential treatment modality for PXE, a currently intractable disease, as well as for other conditions characterized by ectopic mineralization of connective tissues. PMID:20443931
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Li, Qiaoli; Larusso, Jennifer; Grand-Pierre, Alix E; Uitto, Jouni
2009-12-01
Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6(-/-)). This "knock-out" (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate-enriched diet (magnesium concentration being 5-fold higher than in the control diet) completely prevented mineralization of the vibrissae up to 6 months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate-enriched diet also prevented the progression of mineralization when the mice were placed on that experimental diet at 3 months of age and followed up to 6 months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over 10-fold while the concentration of phosphorus was markedly decreased, being essentially undetectable after long-term (> 4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate-enriched diet showed no differences in the bone density compared to mice on the control diet, and chemical assays showed a small increase in the calcium and phosphate content of the femurs by chemical assay, in comparison to mice on control diet. Similar experiments with another experimental diet supplemented with lanthanum carbonate did not interfere with the mineralization process in Abcc6(-/-) mice. These results suggest that magnesium carbonate may offer a potential treatment modality for PXE, a currently intractable disease, as well as for other conditions characterized by ectopic mineralization of connective tissues.
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Wang, Zhijie; Chen, Dongdong; Zheng, Liqiong; Huo, Linsheng; Song, Gangbing
2018-06-01
With the advantages of high tensile, bending, and shear strength, steel fiber concrete structures have been widely used in civil engineering. The health monitoring of concrete structures, including steel fiber concrete structures, receives increasing attention, and the Electromechanical Impedance (EMI)-based method is commonly used. Structures are often subject to changing axial load and ignoring the effect of axial forces may introduce error to Structural Health Monitoring (SHM), including the EMI-based method. However, many of the concrete structure monitoring algorithms do not consider the effects of axial loading. To investigate the influence of axial load on the EMI of a steel fiber concrete structure, concrete specimens with different steel fiber content (0, 30, 60, 90, 120) (kg/m³) were casted and the Lead Zirconate Titanate (PZT)-based Smart Aggregate (SA) was used as the EMI sensor. During tests, the step-by-step loading procedure was applied on different steel fiber content specimens, and the electromechanical impedance values were measured. The Normalized root-mean-square deviation Index (NI) was developed to analyze the EMI information and evaluate the test results. The results show that the normalized root-mean-square deviation index increases with the increase of the axial load, which clearly demonstrates the influence of axial load on the EMI values for steel fiber concrete and this influence should be considered during a monitoring or damage detection procedure if the axial load changes. In addition, testing results clearly reveal that the steel fiber content, often at low mass and volume percentage, has no obvious influence on the PZT's EMI values. Furthermore, experiments to test the repeatability of the proposed method were conducted. The repeating test results show that the EMI-based indices are repeatable and there is a great linearity between the NI and the applied loading.
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Schelhorn, Juliane; Neudorf, Ulrich; Schemuth, Haemi; Nensa, Felix; Nassenstein, Kai; Schlosser, Thomas W
2015-11-01
Patients with corrected tetralogy of Fallot (cToF) are prone to develop pulmonary regurgitation and right ventricular enlargement resulting in long-term complications, thus correct right ventricular volumetric monitoring is crucial. However, it remains controversial which cardiovascular magnetic resonance imaging (CMRI) slice orientation is most appropriate in cToF for the analysis of the right ventricular volume. To investigate which slice orientation is most suited for right ventricular volumetry in cToF we compared short-axis and axial slices, and furthermore we compared right ventricular data between CMRI and echocardiography. Thirty CMRI examinations of 27 patients with cToF were included retrospectively. Right ventricular end-diastolic (EDV) and end-systolic volume (ESV) were derived from short-axis and axial cine CMRI planes. Furthermore, pulmonary trunk forward flow in phase-contrast CMRI and right ventricular inner diastolic diameter in echocardiography (R VIDdiast) were measured. By Bland-Altman and variance analysis intra- and inter-observer agreement were assessed for cine CMRI data. By Pearson correlation CMRI cine and phase-contrast data and CMRI cine and echocardiographic data were compared. Intra- and inter-observer variability for right ventricular EDV were significantly lower in axial slices (P = 0.016, P = 0.010). For right ventricular ESV a trend towards a lower intra- and inter-observer variability in axial slices was found (P = 0.063, P = 0.138). Right ventricular stroke volume in short-axis (r = 0.872, P < 0.001) and in axial (r = 0.914, P < 0.001) planes correlated highly, respectively very highly with pulmonary trunk forward flow in phase-contrast CMRI. R VIDdiast correlated highly with right ventricular EDV assessed by short-axis and axial CMRI (P < 0.001, P < 0.001). Due to lower intra- and inter-observer variability, axial slices are recommended for right ventricular volumetry in cToF. © The Foundation Acta Radiologica 2014.
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Transgenic and gene knockout mice in gastric cancer research
Jiang, Yannan; Yu, Yingyan
2017-01-01
Mouse models are useful tool for carcinogenic study. They will greatly enrich the understanding of pathogenesis and molecular mechanisms for gastric cancer. However, only few of mice could develop gastric cancer spontaneously. With the development and improvement of gene transfer technology, investigators created a variety of transgenic and knockout/knockin mouse models of gastric cancer, such as INS-GAS mice and gastrin knockout mice. Combined with helicobacter infection and carcinogens treatment, these transgenic/knockout/knockin mice developed precancerous or cancerous lesions, which are proper for gene function study or experimental therapy. Here we review the progression of genetically engineered mouse models on gastric cancer research, and emphasize the effects of chemical carcinogens or infectious factors on carcinogenesis of genetically modified mouse. We also emphasize the histological examination on mouse stomach. We expect to provide researchers with some inspirations on this field. PMID:27713138
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NASA Astrophysics Data System (ADS)
Cowperthwaite, M.
1994-03-01
Methods of differential geometry and Bernoulli's equation, written as B=0, are used to develop a new approach for constructing an exact solution for axial flow in a classical, two-dimensional, ZND detonation wave in a polytropic explosive with an arbitrary rate of decomposition. This geometric approach is fundamentally different from the traditional approaches to this axial flow problem formulated by Wood and Kirkwood (WK) and Fickett and Davis (FD), and gives equations for the axial particle velocity (u), the sound speed (c), the pressure (p), and the density (ρ), that are expressed in terms of the detonation velocity (D), the extent of decomposition (λ), the polytropic index (K), and two nonideal parameters ɛ3 and ɛ1, and reduce to the equations for steady-state, one-dimensional detonation as ɛ3 and ɛ1 approach zero. In contrast to the FD approach, the equations for u and c are obtained from first integrals of a tangent vector à on (u,c,λ) space, and the invariant condition, ÃB=aB=0, bypasses the FD eigenvalue problem by defining ɛ3 in terms of the detonation velocity deficit D/D∞ and K. In contrast to the WK approach, the equations for p and ρ are obtained from equations expressing the conservation of axial momentum and energy. Because the equations for these flow variables are derived without using the conservation of mass, the axial radial particle velocity gradient (war) associated with the flow can be obtained from the continuity equation without making approximations. The relationship between ɛ1 and ɛ3 that closes the solution is obtained from equations expressing constraints imposed on the axial flow at the shock front by the axial and radial momentum equations, the curved shock and the decomposition rate law, and a particular solution is constructed from the ɛ1-ɛ3 relationship determined by a prescribed rate law and value of K. Properties of particular solutions are presented to provide a better understanding of two-dimensional detonation, and a new axial condition for detonation failure is used to show that detonation failure can occur before the curve relating D/D∞ to the axial radius of curvature of the shock (Sa) becomes infinite.
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NASA Astrophysics Data System (ADS)
Phillips, Kevin G.; Wang, Yun; Choudhury, Niloy; Levitz, David; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven
2012-02-01
Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses responsible for skin homeostasis. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of psoriasis remains under investigated. To elucidate the spatial-temporal morphological evolution of psoriasis we undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to non-invasively document dermal alterations due to immune cell infiltration and epidermal hyperplasia in an Imiquimod (IMQ) induced model of psoriasis-like inflammation in DBA2/C57Bl6 hybrid mice. Quantitative appraisal of dermal architectural changes was achieved through a three parameter fit of OCT axial scans in the dermis of the form A(z) = ρ exp(-mu;z +ɛ(z)). Ensemble averaging of the fit parameters over 2000 axial scans per mouse in each treatment arm revealed that the local dermal reflectivity ρ, decreased significantly in response to 6 day IMQ treatment (p = 0.0001), as did the standard deviation of the attenuation fluctuation std(ɛ(z)), (p = 0.04), in comparison to cream controls and day 1 treatments. No significant changes were observed in the average dermal attenuation rate, μ. Our results suggest these label-free OCT-based metrics can be deployed to investigate new therapeutic targets in animal models as well as aid in clinical staging of psoriasis in conjunction with the psoriasis area and severity index.
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NASA Astrophysics Data System (ADS)
Li, Gaoming; Li, Haijun; Duan, Xiyu; Zhou, Quan; Zhou, Juan; Oldham, Kenn R.; Wang, Thomas D.
2017-02-01
We demonstrate a dual axes confocal architecture, which can be used to collect horizontal(XY-plane) or vertical cross-sectional(XZ-plane) images for tissue. This scanner head is 5.5mm in outer diameter(OD), and integrates a 3D MEMS scanner with a compact chip size of 3.2×2.9mm2. To realize the miniaturization, there are some obstacles of the small size of 3D MEMS scanner, MEMS wire bundle, the air pressure effect for MEMS motion, the processing of parabolic mirror, and optical alignment to come over. In our probe, separation mechanical structure for optical alignment was adopted and a step shape MEMS holder was designed to deal with the difficult of MEMS wire bundle. Peptides have been demonstrated tremendous potential for in vivo use to detect colonic dysplasia. This class of in vivo molecular probe can be labeled with near-infrared (NIR) dyes for visualizing the full depth of the epithelium in small animals. To confirm our probe performance, we take use of USAF 1951 resolution target to test its lateral and axial resolution. It has lateral and axial resolution of 2.49um and 4.98um, respectively. When we collect the fluorescence imaging of colon, it shows that the field of view are 1000um×1000um (horizontal) and 1000um×430um (vertical). The horizontal and vertical cross-sectional images of fresh mouse colonic mucosa demonstrate imaging performance with this miniature instrument.
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A head movement image (HMI)-controlled computer mouse for people with disabilities.
Chen, Yu-Luen; Chen, Weoi-Luen; Kuo, Te-Son; Lai, Jin-Shin
2003-02-04
This study proposes image processing and microprocessor technology for use in developing a head movement image (HMI)-controlled computer mouse system for the spinal cord injured (SCI). The system controls the movement and direction of the mouse cursor by capturing head movement images using a marker installed on the user's headset. In the clinical trial, this new mouse system was compared with an infrared-controlled mouse system on various tasks with nine subjects with SCI. The results were favourable to the new mouse system. The differences between the new mouse system and the infrared-controlled mouse were reaching statistical significance in each of the test situations (p<0.05). The HMI-controlled computer mouse improves the input speed. People with disabilities need only wear the headset and move their heads to freely control the movement of the mouse cursor.
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Development of the mouse vestibular system in the absence of gravity perception
NASA Technical Reports Server (NTRS)
Smith, Michael; Yuan Wang, Xiang; Wolgemuth, Debra J.; Murashov, Alexander K.
2003-01-01
The tilted mutant mouse, which lacks otoconia in the inner ear, was used to study development of the mouse vestibular system in the absence of gravity perception. Otoconia are dense particles composed of proteins and calcium carbonate crystals suspended in the gelatinous macular membrane. They enhance, and are largely responsible for, sensitivity to gravity. Morphometric analysis of the vestibular ganglion showed that the mutant developed more slowly than the normal controls, both in rate of development and cell number, particularly during the first week of post-natal development. The mutant ganglia also exhibited a reduction of cells during the first 6 days of post-natal development.
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Method to Measure Tone of Axial and Proximal Muscle
Gurfinkel, Victor S.; Cacciatore, Timothy W.; Cordo, Paul J.; Horak, Fay B.
2011-01-01
The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs1, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention. PMID:22214974
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High-Temperature (1000 F) Magnetic Thrust Bearing Test Rig Completed and Operational
NASA Technical Reports Server (NTRS)
Montague, Gerald T.
2005-01-01
Large axial loads are induced on the rolling element bearings of a gas turbine. To extend bearing life, designers use pneumatic balance pistons to reduce the axial load on the bearings. A magnetic thrust bearing could replace the balance pistons to further reduce the axial load. To investigate this option, the U.S. Army Research Laboratory, the NASA Glenn Research Center, and Texas A&M University designed and fabricated a 7-in.- diameter magnetic thrust bearing to operate at 1000 F and 30,000 rpm, with a 1000-lb load capacity. This research was funded through a NASA Space Technology Transfer Act with Allison Advance Development Company under the Ultra-Efficient Engine Technology (UEET) Intelligent Propulsion Systems Foundation Technology project.
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Both the central and peripheral retina contribute to myopia development in chicks.
Wang, Jian Chao; Chun, Rachel K M; Zhou, Yun Y; Zuo, Bing; Li, King Kit; Liu, Quan; To, Chi Ho
2015-11-01
This study examined the contribution of the central and peripheral retina to the development of form deprivation myopia in chicks. Chicks were treated for 7 days either with centrally form-deprived (CFD) lenses of 2/4/6/8 mm diameter central diffuse zone, or a full size diffuser lens on their right eyes. The left eyes wore a full field plano lens. Axial dimensions and refractions were measured before and after 4 and 7 days of lens wear. All eyes that had worn CFD lenses of 2/4/6/8 mm had significant changes in refractive errors (from -2.69 ± 0.40 D to -6.13 ± 0.76 D, p < 0.05), vitreous chamber depth (from 0.19 ± 0.04 mm to 0.56 ± 0.04 mm, p < 0.05) and axial length (from 0.42 ± 0.03 mm to 0.96 ± 0.04 mm, p < 0.05) during the experiment, except for the changes in refractive error (-2.81 ± 0.33 D, p = 0.053) and axial length (0.77 ± 0.04 mm, p = 0.050) in the 2 mm lens group after 7 days of lens wear. The myopic shift in the CFD lens wearing eyes was due primarily to an increase in vitreous chamber depth. Linear regression analysis showed that the changes of refractive error, vitreous chamber depth and axial length were positively correlated with the size of central form-deprived retina. Form depriving the central retina produced axial myopia even in the presence of clear peripheral vision. The current study showed that both the central and peripheral retina contributes to myopia development in chicks. The amount of myopia induced increased linearly with the area of retina being form-deprived. It suggests that in terms of decoding optical input for growth, the area of retina being exposed to optical signals may be critical in determining eye growth. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.
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Light Sheet Fluorescence Microscopy (LSFM)
Adams, Michael W.; Loftus, Andrew F.; Dunn, Sarah E.; Joens, Matthew S.; Fitzpatrick, James A.J.
2015-01-01
The development of confocal microscopy techniques introduced the ability to optically section fluorescent samples in the axial dimension, perpendicular to the image plane. These approaches, via the placement of a pinhole in the conjugate image plane, provided superior resolution in the axial (z) dimension resulting in nearly isotropic optical sections. However, increased axial resolution, via pinhole optics, comes at the cost of both speed and excitation efficiency. Light Sheet Fluorescent Microscopy (LSFM), a century old idea (Siedentopf and Zsigmondy, 1902) made possible with modern developments in both excitation and detection optics, provides sub-cellular resolution and optical sectioning capabilities without compromising speed or excitation efficiency. Over the past decade, several variations of LSFM have been implemented each with its own benefits and deficiencies. Here we discuss LSFM fundamentals and outline the basic principles of several major light sheet based imaging modalities (SPIM, inverted SPIM, multi-view SPIM, Bessel beam SPIM, and stimulated emission depletion SPIM while considering their biological relevance in terms of intrusiveness, temporal resolution, and sample requirements. PMID:25559221
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Imaging mouse cerebellum with serial optical coherence scanner (Conference Presentation)
NASA Astrophysics Data System (ADS)
Liu, Chao J.; Williams, Kristen; Orr, Harry; Taner, Akkin
2017-02-01
We present the serial optical coherence scanner (SOCS), which consists of a polarization sensitive optical coherence tomography and a vibratome with associated controls for serial imaging, to visualize the cerebellum and adjacent brainstem of mouse. The cerebellar cortical layers and white matter are distinguished by using intrinsic optical contrasts. Images from serial scans reveal the large-scale anatomy in detail and map the nerve fiber pathways in the cerebellum and adjacent brainstem. The optical system, which has 5.5 μm axial resolution, utilizes a scan lens or a water-immersion microscope objective resulting in 10 μm or 4 μm lateral resolution, respectively. The large-scale brain imaging at high resolution requires an efficient way to collect large datasets. It is important to improve the SOCS system to deal with large-scale and large number of samples in a reasonable time. The imaging and slicing procedure for a section took about 4 minutes due to a low speed of the vibratome blade to maintain slicing quality. SOCS has potential to investigate pathological changes and monitor the effects of therapeutic drugs in cerebellar diseases such as spinocerebellar ataxia 1 (SCA1). The SCA1 is a neurodegenerative disease characterized by atrophy and eventual loss of Purkinje cells from the cerebellar cortex, and the optical contrasts provided by SOCS is being evaluated for biomarkers of the disease.
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Ling, Karen K. Y.; Gibbs, Rebecca M.; Feng, Zhihua; Ko, Chien-Ping
2012-01-01
Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the survival of motor neuron (SMN) protein, is characterized by motoneuron loss and muscle weakness. It remains unclear whether widespread loss of neuromuscular junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic examination of NMJ innervation patterns in >20 muscles in the SMNΔ7 SMA mouse model. We found that severe denervation (<50% fully innervated endplates) occurs selectively in many vulnerable axial muscles and several appendicular muscles at the disease end stage. Since these vulnerable muscles were located throughout the body and were comprised of varying muscle fiber types, it is unlikely that muscle location or fiber type determines susceptibility to denervation. Furthermore, we found a similar extent of neurofilament accumulation at NMJs in both vulnerable and resistant muscles before the onset of denervation, suggesting that neurofilament accumulation does not predict subsequent NMJ denervation. Since vulnerable muscles were initially innervated, but later denervated, loss of innervation in SMA may be attributed to defects in synapse maintenance. Finally, we found that denervation was amendable by trichostatin A (TSA) treatment, which increased innervation in clinically relevant muscles in TSA-treated SMNΔ7 mice. Our findings suggest that neuromuscular denervation in vulnerable muscles is a widespread pathology in SMA, and can serve as a preparation for elucidating the biological basis of synapse loss, and for evaluating therapeutic efficacy. PMID:21968514
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Lorget, Florence; Kaci, Nabil; Peng, Jeff; Benoist-Lasselin, Catherine; Mugniery, Emilie; Oppeneer, Todd; Wendt, Dan J.; Bell, Sean M.; Bullens, Sherry; Bunting, Stuart; Tsuruda, Laurie S.; O'Neill, Charles A.; Di Rocco, Federico; Munnich, Arnold; Legeai-Mallet, Laurence
2012-01-01
Achondroplasia (ACH), the most common form of dwarfism, is an inherited autosomal-dominant chondrodysplasia caused by a gain-of-function mutation in fibroblast-growth-factor-receptor 3 (FGFR3). C-type natriuretic peptide (CNP) antagonizes FGFR3 downstream signaling by inhibiting the pathway of mitogen-activated protein kinase (MAPK). Here, we report the pharmacological activity of a 39 amino acid CNP analog (BMN 111) with an extended plasma half-life due to its resistance to neutral-endopeptidase (NEP) digestion. In ACH human growth-plate chondrocytes, we demonstrated a decrease in the phosphorylation of extracellular-signal-regulated kinases 1 and 2, confirming that this CNP analog inhibits fibroblast-growth-factor-mediated MAPK activation. Concomitantly, we analyzed the phenotype of Fgfr3Y367C/+ mice and showed the presence of ACH-related clinical features in this mouse model. We found that in Fgfr3Y367C/+ mice, treatment with this CNP analog led to a significant recovery of bone growth. We observed an increase in the axial and appendicular skeleton lengths, and improvements in dwarfism-related clinical features included flattening of the skull, reduced crossbite, straightening of the tibias and femurs, and correction of the growth-plate defect. Thus, our results provide the proof of concept that BMN 111, a NEP-resistant CNP analog, might benefit individuals with ACH and hypochondroplasia. PMID:23200862
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ERIC Educational Resources Information Center
Shih, Ching-Hsiang; Hsu, Nai-Yun; Shih, Ching-Tien
2009-01-01
This study evaluated whether two children with developmental disabilities would be able to improve their pointing performance through an Automatic Pointing Assistive Program (APAP) and a newly developed mouse driver (i.e. a new mouse driver replaces standard mouse driver, and is able to intercept mouse click action). Initially, both participants…
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ZINC INFLUENCES THE IN VITRO DEVELOPMENT OF PERI-IMPLANTATION MOUSE EMBRYOS
Background: For humans, it is estimated that over 70% of concepti are lost during early development. In culture, mouse peri-implantation embryos can mimic development from the blastocyst to the egg cylinder stage of development, a period during which implantation occurs in viv...
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Bronson, N R
1984-05-01
A new A-mode biometry system for determining axial length measurements of the eye has been developed that incorporates a soft-membrane transducer. The soft transducer decreases the risk of indenting the cornea with the probe resulting in inaccurate measurements. A microprocessor evaluates echo patterns and determines whether or not axial alignment has been obtained, eliminating possible user error. The new A-scan requires minimal user skill and can be used successfully by both physician and technician.
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Centralized mouse repositories.
Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T
2012-10-01
Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.
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Centralized Mouse Repositories
Donahue, Leah Rae; de Angelis, Martin Hrabe; Hagn, Michael; Franklin, Craig; Lloyd, K. C. Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T.
2013-01-01
Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world. PMID:22945696
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Using speech recognition to enhance the Tongue Drive System functionality in computer access.
Huo, Xueliang; Ghovanloo, Maysam
2011-01-01
Tongue Drive System (TDS) is a wireless tongue operated assistive technology (AT), which can enable people with severe physical disabilities to access computers and drive powered wheelchairs using their volitional tongue movements. TDS offers six discrete commands, simultaneously available to the users, for pointing and typing as a substitute for mouse and keyboard in computer access, respectively. To enhance the TDS performance in typing, we have added a microphone, an audio codec, and a wireless audio link to its readily available 3-axial magnetic sensor array, and combined it with a commercially available speech recognition software, the Dragon Naturally Speaking, which is regarded as one of the most efficient ways for text entry. Our preliminary evaluations indicate that the combined TDS and speech recognition technologies can provide end users with significantly higher performance than using each technology alone, particularly in completing tasks that require both pointing and text entry, such as web surfing.
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NASA Astrophysics Data System (ADS)
Ullah, H.; Ahmed, E.; Ikram, M.
2013-08-01
We report a pilot method, i.e., speckle variance (SV) and structured optical coherence tomography to visualize normal and malignant blood microvasculature in three and two dimensions and to monitor the glucose levels in blood by analyzing the Brownian motion of the red blood cells. The technique was applied on nude live mouse's skin and the obtained images depict the enhanced intravasculature network forum up to the depth of ˜2 mm with axial resolution of ˜8 μm. Microscopic images have also been obtained for both types of blood vessels to observe the tumor spatially. Our SV-OCT methodologies and results give satisfactory techniques in real time imaging and can potentially be applied during therapeutic techniques such as photodynamic therapy as well as to quantify the higher glucose levels injected intravenously to animal by determining the translation diffusion coefficient.
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Wide-field depth-sectioning fluorescence microscopy using projector-generated patterned illumination
NASA Astrophysics Data System (ADS)
Delica, Serafin; Mar Blanca, Carlo
2007-10-01
We present a simple and cost-effective wide-field, depth-sectioning, fluorescence microscope utilizing a commercial multimedia projector to generate excitation patterns on the sample. Highly resolved optical sections of fluorescent pollen grains at 1.9 μm axial resolution are constructed using the structured illumination technique. This requires grid excitation patterns to be scanned across the sample, which is straightforwardly implemented by creating slideshows of gratings at different phases, projecting them onto the sample, and synchronizing camera acquisition with slide transition. In addition to rapid dynamic pattern generation, the projector provides high illumination power and spectral excitation selectivity. We exploit these properties by imaging mouse neural cells in cultures multistained with Alexa 488 and Cy3. The spectral and structural neural information is effectively resolved in three dimensions. The flexibility and commercial availability of this light source is envisioned to open multidimensional imaging to a broader user base.
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Radrich, Karin; Ale, Angelique; Ermolayev, Vladimir; Ntziachristos, Vasilis
2012-12-01
We examine the improvement in imaging performance, such as axial resolution and signal localization, when employing limited-projection-angle fluorescence molecular tomography (FMT) together with x-ray computed tomography (XCT) measurements versus stand-alone FMT. For this purpose, we employed living mice, bearing a spontaneous lung tumor model, and imaged them with FMT and XCT under identical geometrical conditions using fluorescent probes for cancer targeting. The XCT data was employed, herein, as structural prior information to guide the FMT reconstruction. Gold standard images were provided by fluorescence images of mouse cryoslices, providing the ground truth in fluorescence bio-distribution. Upon comparison of FMT images versus images reconstructed using hybrid FMT and XCT data, we demonstrate marked improvements in image accuracy. This work relates to currently disseminated FMT systems, using limited projection scans, and can be employed to enhance their performance.
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Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.
2011-01-01
SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257
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Evaluation of a silicon photomultiplier PET insert for simultaneous PET and MR imaging
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ko, Guen Bae; Kim, Kyeong Yun; Yoon, Hyun Suk
2016-01-15
Purpose: In this study, the authors present a silicon photomultiplier (SiPM)-based positron emission tomography (PET) insert dedicated to small animal imaging with high system performance and robustness to temperature change. Methods: The insert consists of 64 LYSO-SiPM detector blocks arranged in 4 rings of 16 detector blocks to yield a ring diameter of 64 mm and axial field of view of 55 mm. Each detector block consists of a 9 × 9 array of LYSO crystals (1.2 × 1.2 × 10 mm{sup 3}) and a monolithic 4 × 4 SiPM array. The temperature of each monolithic SiPM is monitored, andmore » the proper bias voltage is applied according to the temperature reading in real time to maintain uniform performance. The performance of this PET insert was characterized using National Electrical Manufacturers Association NU 4-2008 standards, and its feasibility was evaluated through in vivo mouse imaging studies. Results: The PET insert had a peak sensitivity of 3.4% and volumetric spatial resolutions of 1.92 (filtered back projection) and 0.53 (ordered subset expectation maximization) mm{sup 3} at center. The peak noise equivalent count rate and scatter fraction were 42.4 kcps at 15.08 MBq and 16.5%, respectively. By applying the real-time bias voltage adjustment, an energy resolution of 14.2% ± 0.3% was maintained and the count rate varied ≤1.2%, despite severe temperature changes (10–30 °C). The mouse imaging studies demonstrate that this PET insert can produce high-quality images useful for imaging studies on the small animals. Conclusions: The developed MR-compatible PET insert is designed for insertion into a narrow-bore magnetic resonance imaging scanner, and it provides excellent imaging performance for PET/MR preclinical studies.« less
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Gsell, Kelsey Y; Zwambag, Derek P; Fournier, Dale E; Séguin, Cheryle A; Brown, Stephen H M
2017-10-01
Basic science study of the relationship between the structural properties of the spine and its surrounding musculature. To determine whether an increase in spine stiffness causes an inverse compensatory change in the passive stiffness of the adjacent paraspinal muscles. Intervertebral disc degeneration causes an increase in multifidus passive stiffness; this was hypothesized to compensate for a decrease in spine stiffness associated with disc degeneration. Mice lacking equilibrative nucleoside transporter 1 (ENT1) develop progressive ectopic calcification of the fibrous connective tissues of the spine, which affects the lumbar spine by 6 months of age and likely creates a mechanically stiffer spine. Experiments were conducted on four groups of mice (n = 8 mice/group): wild-type (WT) and ENT1 knockout (KO) at 2 or 8 months of age. Lumbar spines were removed and tested in cyclic axial compression to determine neutral zone length and stiffness. Single muscle fibers and bundles of fibers were isolated from lumbar multifidus and erector spinae, as well as tibialis anterior (a non-spine-related control) and tested to determine elastic modulus (passive stiffness). At 2 months of age, neither spine nor muscle stiffness was different between KO and WT. At 8 months of age, compared with WT the lumbar spines of ENT1 KO mice had a stiffer and shorter neutral zone, and the paraspinal muscle fibers were less stiff; however, fiber bundles were not different. In addition, tibialis anterior was not different between KO and WT. This work has confirmed that calcification of spinal connective tissues in the ENT1 KO mouse results in a stiffened spine, whereas the concurrent decrease in muscle fiber elastic modulus in the adjacent paraspinal muscles suggests a direct compensatory relationship between the stiffness of the spine and the muscles that are attached to it. N/A.
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Dai, Mengyao; Wang, Yao; Fang, Lu; Irwin, David M; Zhu, Tengteng; Zhang, Junpeng; Zhang, Shuyi; Wang, Zhe
2014-01-01
Bats are the only mammals capable of self-powered flight using wings. Differing from mouse or human limbs, four elongated digits within a broad wing membrane support the bat wing, and the foot of the bat has evolved a long calcar that spread the interfemoral membrane. Our recent mRNA sequencing (mRNA-Seq) study found unique expression patterns for genes at the 5' end of the Hoxd gene cluster and for Tbx3 that are associated with digit elongation and wing membrane growth in bats. In this study, we focused on two additional genes, Meis2 and Mab21l2, identified from the mRNA-Seq data. Using whole-mount in situ hybridization (WISH) we validated the mRNA-Seq results for differences in the expression patterns of Meis2 and Mab21l2 between bat and mouse limbs, and further characterize the timing and location of the expression of these two genes. These analyses suggest that Meis2 may function in wing membrane growth and Mab21l2 may have a role in AP and DV axial patterning. In addition, we found that Tbx3 is uniquely expressed in the unique calcar structure found in the bat hindlimb, suggesting a role for this gene in calcar growth and elongation. Moreover, analysis of the coding sequences for Meis2, Mab21l2 and Tbx3 showed that Meis2 and Mab21l2 have high sequence identity, consistent with the functions of genes being conserved, but that Tbx3 showed accelerated evolution in bats. However, evidence for positive selection in Tbx3 was not found, which would suggest that the function of this gene has not been changed. Together, our findings support the hypothesis that the modulation of the spatiotemporal expression patterns of multiple functional conserved genes control limb morphology and drive morphological change in the diversification of mammalian limbs.
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Fang, Lu; Irwin, David M.; Zhu, Tengteng; Zhang, Junpeng; Zhang, Shuyi; Wang, Zhe
2014-01-01
Bats are the only mammals capable of self-powered flight using wings. Differing from mouse or human limbs, four elongated digits within a broad wing membrane support the bat wing, and the foot of the bat has evolved a long calcar that spread the interfemoral membrane. Our recent mRNA sequencing (mRNA-Seq) study found unique expression patterns for genes at the 5′ end of the Hoxd gene cluster and for Tbx3 that are associated with digit elongation and wing membrane growth in bats. In this study, we focused on two additional genes, Meis2 and Mab21l2, identified from the mRNA-Seq data. Using whole-mount in situ hybridization (WISH) we validated the mRNA-Seq results for differences in the expression patterns of Meis2 and Mab21l2 between bat and mouse limbs, and further characterize the timing and location of the expression of these two genes. These analyses suggest that Meis2 may function in wing membrane growth and Mab21l2 may have a role in AP and DV axial patterning. In addition, we found that Tbx3 is uniquely expressed in the unique calcar structure found in the bat hindlimb, suggesting a role for this gene in calcar growth and elongation. Moreover, analysis of the coding sequences for Meis2, Mab21l2 and Tbx3 showed that Meis2 and Mab21l2 have high sequence identity, consistent with the functions of genes being conserved, but that Tbx3 showed accelerated evolution in bats. However, evidence for positive selection in Tbx3 was not found, which would suggest that the function of this gene has not been changed. Together, our findings support the hypothesis that the modulation of the spatiotemporal expression patterns of multiple functional conserved genes control limb morphology and drive morphological change in the diversification of mammalian limbs. PMID:25166052
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Sgariglia, Federica; Ibrahim, Mazen M.; Koyama, Eiki; Jones, Kevin B.
2017-01-01
Hereditary Multiple Exostoses (HME) is a rare pediatric disorder caused by loss-of-function mutations in the genes encoding the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. HME is characterized by formation of cartilaginous outgrowths—called osteochondromas- next to the growth plates of many axial and appendicular skeletal elements. Surprisingly, it is not known whether such tumors also form in endochondral elements of the craniofacial skeleton. Here, we carried out a retrospective analysis of cervical spine MRI and CT scans from 50 consecutive HME patients that included cranial skeletal images. Interestingly, nearly half of the patients displayed moderate defects or osteochondroma-like outgrowths in the cranial base and specifically in the clivus. In good correlation, osteochondromas developed in the cranial base of mutant Ext1f/f;Col2-CreER or Ext1f/f;Aggrecan-CreER mouse models of HME along the synchondrosis growth plates. Osteochondroma formation was preceded by phenotypic alteration of cells at the chondro-perichondrial boundary and was accompanied by ectopic expression of major cartilage matrix genes -collagen 2 and collagen X- within the growing ectopic masses. Because chondrogenesis requires bone morphogenetic protein (BMP) signaling, we asked whether osteochondroma formation could be blocked by a BMP signaling antagonist. Systemic administration with LDN-193189 effectively inhibited osteochondroma growth in conditional Ext1-mutant mice. In vitro studies with mouse embryo chondrogenic cells clarified the mechanisms of LDN-193189 action that turned out to include decreases in canonical BMP signaling pSMAD1/5/8 effectors but interestingly, concurrent increases in such anti-chondrogenic mechanisms as pERK1/2 and Chordin, Fgf9 and Fgf18 expression. Our study is the first to reveal that the cranial base can be affected in patients with HME and that osteochondroma formation is amenable to therapeutic drug intervention. PMID:28445472
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Vocal development and auditory perception in CBA/CaJ mice
NASA Astrophysics Data System (ADS)
Radziwon, Kelly E.
Mice are useful laboratory subjects because of their small size, their modest cost, and the fact that researchers have created many different strains to study a variety of disorders. In particular, researchers have found nearly 100 naturally occurring mouse mutations with hearing impairments. For these reasons, mice have become an important model for studies of human deafness. Although much is known about the genetic makeup and physiology of the laboratory mouse, far less is known about mouse auditory behavior. To fully understand the effects of genetic mutations on hearing, it is necessary to determine the hearing abilities of these mice. Two experiments here examined various aspects of mouse auditory perception using CBA/CaJ mice, a commonly used mouse strain. The frequency difference limens experiment tested the mouse's ability to discriminate one tone from another based solely on the frequency of the tone. The mice had similar thresholds as wild mice and gerbils but needed a larger change in frequency than humans and cats. The second psychoacoustic experiment sought to determine which cue, frequency or duration, was more salient when the mice had to identify various tones. In this identification task, the mice overwhelmingly classified the tones based on frequency instead of duration, suggesting that mice are using frequency when differentiating one mouse vocalization from another. The other two experiments were more naturalistic and involved both auditory perception and mouse vocal production. Interest in mouse vocalizations is growing because of the potential for mice to become a model of human speech disorders. These experiments traced mouse vocal development from infant to adult, and they tested the mouse's preference for various vocalizations. This was the first known study to analyze the vocalizations of individual mice across development. Results showed large variation in calling rates among the three cages of adult mice but results were highly consistent across all infant vocalizations. Although the preference experiment did not reveal significant differences between various mouse vocalizations, suggestions are given for future attempts to identify mouse preferences for auditory stimuli.
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Furniss, Dominic; Lettice, Laura A.; Taylor, Indira B.; Critchley, Paul S.; Giele, Henk; Hill, Robert E.; Wilkie, Andrew O.M.
2008-01-01
A locus for triphalangeal thumb, variably associated with pre-axial polydactyly, was previously identified in the zone of polarizing activity regulatory sequence (ZRS), a long range limb-specific enhancer of the Sonic Hedgehog (SHH) gene at human chromosome 7q36.3. Here, we demonstrate that a 295T>C variant in the human ZRS, previously thought to represent a neutral polymorphism, acts as a dominant allele with reduced penetrance. We found this variant in three independently ascertained probands from southern England with triphalangeal thumb, demonstrated significant linkage of the phenotype to the variant (LOD = 4.1), and identified a shared microsatellite haplotype around the ZRS, suggesting that the probands share a common ancestor. An individual homozygous for the 295C allele presented with isolated bilateral triphalangeal thumb resembling the heterozygous phenotype, suggesting that the variant is largely dominant to the wild-type allele. As a functional test of the pathogenicity of the 295C allele, we utilized a mutated ZRS construct to demonstrate that it can drive ectopic anterior expression of a reporter gene in the developing mouse forelimb. We conclude that the 295T>C variant is in fact pathogenic and, in southern England, appears to be the most common cause of triphalangeal thumb. Depending on the dispersal of the founding mutation, it may play a wider role in the aetiology of this disorder. PMID:18463159
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Role of Growth Hormone in Prostate Cancer
2007-02-01
syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci USA 94:13215... Laron mouse, in which the gene coding for both GHR and GH binding protein has been disrupted or knocked out, with the C3(1)/Tag mouse, which develops...the Laron mouse). Nevertheless, the new model presented here demonstrates that the loss of GHR produced a significant reduction in the level of PIN in
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Magnetostatic simulation on a novel design of axially multi-coiled magnetorheological brakes
NASA Astrophysics Data System (ADS)
Ubaidillah, Permata, A. N. S.; Wibowo, A.; Budiana, E. P.; Yahya, I.; Mazlan, S. A.
2016-03-01
This paper describes the 3D magnetostatic simulation of a novel design axially multi-coiled magnetorheological (MRB). The proposed model is expected to produce a concentrated magnetic flux on the surface of the rotor disk brake. Thus, the braking torque enhancement is expected to be higher than that of conventional big size single-coil-equipped disk-type MRB. The axially multi-coiled MRB design features multiple electromagnetic poles from by several coils placed in the axial direction outside the MRB body. The magnetostatic analysis was developed utilizing finite element software namely ANSOFT-MAXWELL in 3D environment. The distribution of magnetic flux was investigated in a pair of the coil that represents the other pairs of electromagnetic parts. The simulation was done in 0.5 mm gap filled by magnetorheological fluids (MRFs) (MRF-132DG). The simulation was performed in various applied currents i.e. 0.25, 0.5, 0.75, 1, 1.5, and 2 Amperes. The results showed that the axially multi-coiled MRB provides a considerable magnetic flux (maximum of 337 mT/area). The active energizing areas of the MRB are proven to be more intensive than the conventional MRB. The proposed MRB exhibited a compact and robust design for achieving high torque MRB.
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Tetrapod-like axial regionalization in an early ray-finned fish
Sallan, Lauren Cole
2012-01-01
Tetrapods possess up to five morphologically distinct vertebral series: cervical, thoracic, lumbar, sacral and caudal. The evolution of axial regionalization has been linked to derived Hox expression patterns during development and the demands of weight-bearing and walking on land. These evolutionary and functional explanations are supported by an absence of similar traits in fishes, living and extinct. Here, I show that, Tarrasius problematicus, a marine ray-finned fish from the Mississippian (Early Carboniferous; 359–318 Ma) of Scotland, is the first non-tetrapod known to possess tetrapod-like axial regionalization. Tarrasius exhibits five vertebral regions, including a seven-vertebrae ‘cervical’ series and a reinforced ‘sacrum’ over the pelvic area. Most vertebrae possess processes for intervertebral contact similar to tetrapod zygapophyses. The fully aquatic Tarrasius evolved these morphologies alongside other traits convergent with early tetrapods, including a naked trunk, and a single median continuous fin. Regional modifications in Tarrasius probably facilitated pelagic swimming, rather than a terrestrial lifestyle or walking gait, presenting an alternative scenario for the evolution of such traits in tetrapods. Axial regionalization in Tarrasius could indicate tetrapod-like Hox expression patterns, possibly representing the primitive state for jawed vertebrates. Alternately, it could signal a weaker relationship, or even a complete disconnect, between Hox expression domains and vertebrate axial plans. PMID:22628471
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NASA Astrophysics Data System (ADS)
Liu, Xinyu; Chen, Si; Luo, Yuemei; Bo, En; Wang, Nanshuo; Yu, Xiaojun; Liu, Linbo
2016-02-01
The evaluation of the endothelium coverage on the vessel wall is most wanted by cardiologists. Arterial endothelial cells play a crucial role in keeping low-density lipoprotein and leukocytes from entering into the intima. The damage of endothelial cells is considered as the first step of atherosclerosis development and the presence of endothelial cells is an indicator of arterial healing after stent implantation. Intravascular OCT (IVOCT) is the highest-resolution coronary imaging modality, but it is still limited by an axial resolution of 10-15 µm. This limitation in axial resolution hinders our ability to visualize cellular level details associated with coronary atherosclerosis. Spectral estimation optical coherence tomography (SE-OCT) uses modern spectral estimation techniques and may help reveal the microstructures underlying the resolution limit. In this presentation, we conduct an ex vivo study using SE-OCT to image the endothelium cells on the fresh swine aorta. We find that in OCT images with an axial resolution of 10 µm, we may gain the visibility of individual endothelium cells by applying the autoregressive spectral estimation techniques to enhance the axial resolution. We believe the SE-OCT can provide a potential to evaluate the coverage of endothelium cells using current IVOCT with a 10-µm axial resolution.
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Ward, Michael M.; Deodhar, Atul; Akl, Elie A.; Lui, Andrew; Ermann, Joerg; Gensler, Lianne S.; Smith, Judith A.; Borenstein, David; Hiratzka, Jayme; Weiss, Pamela F.; Inman, Robert D.; Majithia, Vikas; Haroon, Nigil; Maksymowych, Walter P.; Joyce, Janet; Clark, Bruce M.; Colbert, Robert A.; Figgie, Mark P.; Hallegua, David S.; Prete, Pamela E.; Rosenbaum, James T.; Stebulis, Judith A.; van den Bosch, Filip; Yu, David T. Y.; Miller, Amy S.; Reveille, John D.; Caplan, Liron
2016-01-01
Objective To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). Methods A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946–2014), PubMed (1966–2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. Results In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. Conclusion These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas. PMID:26401991
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WARD, MICHAEL M.; DEODHAR, ATUL; AKL, ELIE A.; LUI, ANDREW; ERMANN, JOERG; GENSLER, LIANNE S.; SMITH, JUDITH A.; BORENSTEIN, DAVID; HIRATZKA, JAYME; WEISS, PAMELA F.; INMAN, ROBERT D.; MAJITHIA, VIKAS; HAROON, NIGIL; MAKSYMOWYCH, WALTER P.; JOYCE, JANET; CLARK, BRUCE M.; COLBERT, ROBERT A.; FIGGIE, MARK P.; HALLEGUA, DAVID S.; PRETE, PAMELA E.; ROSENBAUM, JAMES T.; STEBULIS, JUDITH A.; VAN DEN BOSCH, FILIP; YU, DAVID T. Y.; MILLER, AMY S.; REVEILLE, JOHN D.; CAPLAN, LIRON
2016-01-01
Objective To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). Methods A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946–2014), PubMed (1966–2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. Results In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. Conclusion These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas. PMID:26401907
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Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever
2009-07-01
Microbiology. All Rights Reserved. Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever Kelly L. Warfield,* Steven B...mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV...cause severe hemorrhagic fevers in humans and non- human primates (27). The incubation time is estimated to be 3 to 21 days, with human case fatality
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ERIC Educational Resources Information Center
Shih, Ching-Hsiang; Shih, Ching-Tien; Peng, Chin-Ling
2011-01-01
This study evaluated whether two people with multiple disabilities would be able to improve their pointing performance through an Automatic Target Acquisition Program (ATAP) and a newly developed mouse driver (i.e. a new mouse driver replaces standard mouse driver, and is able to monitor mouse movement and intercept click action). Initially, both…
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ERIC Educational Resources Information Center
Shih, Ching-Hsiang; Chung, Chiao-Chen; Chiang, Ming-Shan; Shih, Ching-Tien
2010-01-01
This study evaluated whether two persons with developmental disabilities would be able to improve their pointing performance through a Dual Cursor Automatic Pointing Assistive Program (DCAPAP) with a newly developed mouse driver (i.e., a new mouse driver replaces standard mouse driver, and is able to intercept/detect mouse movement action). First,…
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Limb flexion-induced axial compression and bending in human femoropopliteal artery segments.
Poulson, William; Kamenskiy, Alexey; Seas, Andreas; Deegan, Paul; Lomneth, Carol; MacTaggart, Jason
2018-02-01
High failure rates of femoropopliteal artery (FPA) interventions are often attributed in part to severe mechanical deformations that occur with limb movement. Axial compression and bending of the FPA likely play significant roles in FPA disease development and reconstruction failure, but these deformations are poorly characterized. The goal of this study was to quantify axial compression and bending of human FPAs that are placed in positions commonly assumed during the normal course of daily activities. Retrievable nitinol markers were deployed using a custom-made catheter system into 28 in situ FPAs of 14 human cadavers. Contrast-enhanced, thin-section computed tomography images were acquired with each limb in the standing (180 degrees), walking (110 degrees), sitting (90 degrees), and gardening (60 degrees) postures. Image segmentation and analysis allowed relative comparison of spatial locations of each intra-arterial marker to determine axial compression and bending using the arterial centerlines. Axial compression in the popliteal artery (PA) was greater than in the proximal superficial femoral artery (SFA) or the adductor hiatus (AH) segments in all postures (P = .02). Average compression in the SFA, AH, and PA ranged from 9% to 15%, 11% to 19%, and 13% to 25%, respectively. The FPA experienced significantly more acute bending in the AH and PA segments compared with the proximal SFA (P < .05) in all postures. In the walking, sitting, and gardening postures, average sphere radii in the SFA, AH, and PA ranged from 21 to 27 mm, 10 to 18 mm, and 8 to 19 mm, whereas bending angles ranged from 150 to 157 degrees, 136 to 147 degrees, and 137 to 148 degrees, respectively. The FPA experiences significant axial compression and bending during limb flexion that occur at even modest limb angles. Moreover, different segments of the FPA appear to undergo significantly different degrees of deformation. Understanding the effects of limb flexion on axial compression and bending might assist with reconstructive device selection for patients requiring peripheral arterial disease intervention and may also help guide the development of devices with improved characteristics that can better adapt to the dynamic environment of the lower extremity vasculature. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
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Heart valve cardiomyocytes of mouse embryos express the serotonin transporter SERT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pavone, Luigi Michele; Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Naples; Spina, Anna
2008-12-12
Multiple evidence demonstrate a role for serotonin and its transporter SERT in heart valve development and disease. By utilizing a Cre/loxP system driven by SERT gene expression, we recently demonstrated a regionally restricted distribution of SERT-expressing cells in developing mouse heart. In order to characterize the cell types exhibiting SERT expression within the mouse heart valves at early developmental stages, in this study we performed immunohistochemistry for Islet1 (Isl1) and connexin-43 (Cx-43) on heart sections from SERT{sup Cre/+};ROSA26R embryos previously stained with X-gal. We observed the co-localization of LacZ staining with Isl1 labelling in the outflow tract, the right ventriclemore » and the conal region of E11.5 mouse heart. Cx-43 labelled cells co-localized with LacZ stained cells in the forming atrioventricular valves. These results demonstrate the cardiomyocyte phenotype of SERT-expressing cells in heart valves of the developing mouse heart, thus suggesting an active role of SERT in early heart valve development.« less
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Swindell, William R; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P; Voorhees, John J; Elder, James T; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P; DiGiovanni, John; Pittelkow, Mark R; Ward, Nicole L; Gudjonsson, Johann E
2011-04-04
Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.
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Optimizing mouse models of neurodegenerative disorders: are therapeutics in sight?
Lutz, Cathleen M; Osborne, Melissa A
2013-01-01
The genomic and biologic conservation between mice and humans, along with our increasing ability to manipulate the mouse genome, places the mouse as a premier model for deciphering disease mechanisms and testing potential new therapies. Despite these advantages, mouse models of neurodegenerative disease are sometimes difficult to generate and can present challenges that must be carefully addressed when used for preclinical studies. For those models that do exist, the standardization and optimization of the models is a critical step in ensuring success in both basic research and preclinical use. This review looks back on the history of model development for neurodegenerative diseases and highlights the key strategies that have been learned in order to improve the design, development and use of mouse models in the study of neurodegenerative disease.
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Advanced AC permanent magnet axial flux disc motor for electric passenger vehicle
NASA Technical Reports Server (NTRS)
Kliman, G. B.
1982-01-01
An ac permanent magnet axial flux disc motor was developed to operate with a thyristor load commutated inverter as part of an electric vehicle drive system. The motor was required to deliver 29.8 kW (40 hp) peak and 10.4 kW (14 hp) average with a maximum speed of 11,000 rpm. It was also required to run at leading power factor to commutate the inverter. Three motors were built.
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Varifocal MOEMS fiber scanner for confocal endomicroscopy.
Meinert, Tobias; Weber, Niklas; Zappe, Hans; Seifert, Andreas
2014-12-15
Based on an advanced silicon optical bench technology with integrated MOEMS (Micro-Opto-Electro-Mechanical-System) components, a piezo-driven fiber scanner for confocal microscopy has been developed. This highly-miniaturized technology allows integration into an endoscope with a total outer probe diameter of 2.5 mm. The system features a hydraulically-driven varifocal lens providing axial confocal scanning without any translational movement of components. The demonstrated resolutions are 1.7 μm laterally and 19 μm axially.
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Prediction of an Apparent Flame Length in a Co-Axial Jet Diffusion Flame Combustor.
1983-04-01
This report is comprised of two parts. In Part I a predictive model for an apparent flame length in a co-axial jet diffusion flame combustor is...Overall mass transfer coefficient, evaluated from an empirically developed correlation, is employed to predict total flame length . Comparison of the...experimental and predicted data on total flame length shows a reasonable agreement within sixteen percent over the investigated air and fuel flow rate
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2013-07-16
Twaron, etc., which are characterized by high specific strength and high specific stiffness. Fibers of this type are often referred to as ‘‘ballistic... high level of penetration resistance against large kinetic energy projectiles, such as bullets, detonated-mine-induced soil ejecta, improvised...increasingly being designed and developed through an extensive use of computer-aided engineering ( CAE ) methods and tools. The utility of these
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Further Development of an Optimal Design Approach Applied to Axial Magnetic Bearings
NASA Technical Reports Server (NTRS)
Bloodgood, V. Dale, Jr.; Groom, Nelson J.; Britcher, Colin P.
2000-01-01
Classical design methods involved in magnetic bearings and magnetic suspension systems have always had their limitations. Because of this, the overall effectiveness of a design has always relied heavily on the skill and experience of the individual designer. This paper combines two approaches that have been developed to aid the accuracy and efficiency of magnetostatic design. The first approach integrates classical magnetic circuit theory with modern optimization theory to increase design efficiency. The second approach uses loss factors to increase the accuracy of classical magnetic circuit theory. As an example, an axial magnetic thrust bearing is designed for minimum power.
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NASA Technical Reports Server (NTRS)
Feinberg, L.; Wilson, M.
1993-01-01
To correct for the spherical aberration in the Hubble Space Telescope primary mirror, five anamorphic aspheric mirrors representing correction for three scientific instruments have been fabricated as part of the development of the corrective-optics space telescope axial-replacement instrument (COSTAR). During the acceptance tests of these mirrors at the vendor, a quick and simple method for verifying the asphere surface figure was developed. The technique has been used on three of the aspheres relating to the three instrument prescriptions. Results indicate that the three aspheres are correct to the limited accuracy expected of this test.
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NASA Technical Reports Server (NTRS)
Kopasakis, George; Connolly, Joseph W.; Cheng, Larry
2015-01-01
This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.
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Rocket Engine Nozzle Side Load Transient Analysis Methodology: A Practical Approach
NASA Technical Reports Server (NTRS)
Shi, John J.
2005-01-01
At the sea level, a phenomenon common with all rocket engines, especially for a highly over-expanded nozzle, during ignition and shutdown is that of flow separation as the plume fills and empties the nozzle, Since the flow will be separated randomly. it will generate side loads, i.e. non-axial forces. Since rocket engines are designed to produce axial thrust to power the vehicles, it is not desirable to be excited by non-axial input forcing functions, In the past, several engine failures were attributed to side loads. During the development stage, in order to design/size the rocket engine components and to reduce the risks, the local dynamic environments as well as dynamic interface loads have to be defined. The methodology developed here is the way to determine the peak loads and shock environments for new engine components. In the past it is not feasible to predict the shock environments, e.g. shock response spectra, from one engine to the other, because it is not scaleable. Therefore, the problem has been resolved and the shock environments can be defined in the early stage of new engine development. Additional information is included in the original extended abstract.
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A family of hyperelastic models for human brain tissue
NASA Astrophysics Data System (ADS)
Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain
2017-09-01
Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.
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NASA Astrophysics Data System (ADS)
Morrev, P. G.; Gordon, V. A.
2018-03-01
Surface hardening by deep rolling can be considered as the axial symmetric problem in some special events (namely, when large R and small r radii of the deforming roller meet the requirement R>> r). An axisymmetric nodal averaged stabilized finite element is formulated. The formulation is based on a variational principle with a penalty (stabilizing) item in order to involve large elastic-plastic strain and near to incompressible materials. The deep rolling process for a steel rod is analyzed. Axial residual stress, yield stress, and Odkvist’s parameter are calculated. The residual stress is compared with the data obtained by other authors using a three-dimensional statement of the problem. The results obtained demonstrate essential advantages of the newly developed finite element.
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Buckling Imperfection Sensitivity of Axially Compressed Orthotropic Cylinders
NASA Technical Reports Server (NTRS)
Schultz, Marc R.; Nemeth, Michael P.
2010-01-01
Structural stability is a major consideration in the design of lightweight shell structures. However, the theoretical predictions of geometrically perfect structures often considerably over predict the buckling loads of inherently imperfect real structures. It is reasonably well understood how the shell geometry affects the imperfection sensitivity of axially compressed cylindrical shells; however, the effects of shell anisotropy on the imperfection sensitivity is less well understood. In the present paper, the development of an analytical model for assessing the imperfection sensitivity of axially compressed orthotropic cylinders is discussed. Results from the analytical model for four shell designs are compared with those from a general-purpose finite-element code, and good qualitative agreement is found. Reasons for discrepancies are discussed, and potential design implications of this line of research are discussed.
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Surface acoustic wave oxygen sensor
NASA Technical Reports Server (NTRS)
Collman, James P.; Oglesby, Donald M.; Upchurch, Billy T.; Leighty, Bradley D.; Zhang, Xumu; Herrmann, Paul C.
1994-01-01
A surface acoustic wave (SAW) device that responds to oxygen pressure was developed by coating a 158 MHz quartz surface acoustic wave (SAW) device with an oxygen binding agent. Two types of coatings were used. One type was prepared by dissolving an oxygen binding agent in a toluene solution of a copolymer containing the axial ligand. A second type was prepared with an oxygen binding porphyrin solution containing excess axial ligand without a polymer matrix. In the polymer based coatings, the copolymer served to provide the axial ligand to the oxygen binding agent and as a coating matrix on the surface of the SAW device. The oxygen sensing SAW device has been shown to bind oxygen following a Langmuir isotherm and may be used to measure the equilibrium constant of the oxygen binding compound in the coating matrix.
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Rega, Giuseppe
2016-01-01
The nonlinear free oscillations of a straight planar Timoshenko beam are investigated analytically by means of the asymptotic development method. Attention is focused for the first time, to the best of our knowledge, on the nonlinear coupling between the axial and the transversal oscillations of the beam, which are decoupled in the linear regime. The existence of coupled and uncoupled motion is discussed. Furthermore, the softening versus hardening nature of the backbone curves is investigated in depth. The results are summarized by means of behaviour charts that illustrate the different possible classes of motion in the parameter space. New, and partially unexpected, phenomena, such as the changing of the nonlinear behaviour from softening to hardening by adding/removing the axial vibrations, are highlighted. PMID:27436974
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Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock
Deschamps, Jacqueline; Duboule, Denis
2017-01-01
Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work of Ed Lewis in 1978. Here we discuss recent advances in our understanding of this phenomenon in relation to novel concepts associated with large-scale regulation and chromatin structure during the development of both axial and limb patterns. We further discuss how this sequential transcriptional activation marks embryonic stem cell-like axial progenitors in mammals and, consequently, how a temporal genetic system is further translated into spatial coordinates via the fate of these progenitors. In this context, we argue the benefit and necessity of implementing this unique mechanism as well as the difficulty in evolving an alternative strategy to deliver this critical positional information. PMID:28860158
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Improved Multi-Axial, Temperature and Time Dependent (MATT) Failure Model
NASA Technical Reports Server (NTRS)
Richardson, D. E.; Anderson, G. L.; Macon, D. J.
2002-01-01
An extensive effort has recently been completed by the Space Shuttle's Reusable Solid Rocket Motor (RSRM) nozzle program to completely characterize the effects of multi-axial loading, temperature and time on the failure characteristics of three filled epoxy adhesives (TIGA 321, EA913NA, EA946). As part of this effort, a single general failure criterion was developed that accounted for these effects simultaneously. This model was named the Multi- Axial, Temperature, and Time Dependent or MATT failure criterion. Due to the intricate nature of the failure criterion, some parameters were required to be calculated using complex equations or numerical methods. This paper documents some simple but accurate modifications to the failure criterion to allow for calculations of failure conditions without complex equations or numerical techniques.
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Axial strain insensitivity of weakly guiding optical fibers
NASA Technical Reports Server (NTRS)
Egalon, Claudio O.; Rogowski, Robert S.
1993-01-01
A numerical model has been developed to calculate the modal phase shift of circular step index profile weakly guiding fibers under axial strain. Whenever an optical fiber is under stress, the optical path length, the index of refraction, and the propagation constants of each mode change. In consequence, the phase of each mode is also modified. A relationship for the modal phase shift is presented. This relation is applied to both single mode and two-mode fibers in order to determine the sensitivity characteristics of strained fibers. It was found that the phase shift is strongly dependent on the core refractive index, n(co). It was also found that it is possible to design fibers which are insensitive to axial strain. Practical applications of strain insensitive fibers are discussed.
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Role of nucleation-promoting factors in mouse early embryo development.
Wang, Qiao-Chu; Liu, Jun; Wang, Fei; Duan, Xing; Dai, Xiao-Xin; Wang, Teng; Liu, Hong-Lin; Cui, Xiang-Shun; Sun, Shao-Chen; Kim, Nam-Hyung
2013-06-01
During mitosis nucleation-promoting factors (NPFs) bind to the Arp2/3 complex and activate actin assembly. JMY and WAVE2 are two critical members of the NPFs. Previous studies have demonstrated that NPFs promote multiple processes such as cell migration and cytokinesis. However, the role of NPFs in development of mammalian embryos is still unknown. Results of the present study show that the NPFs JMY and WAVE2 are critical for cytokinesis during development of mouse embryos. Both JMY and WAVE2 are expressed in mouse embryos. After injection of JMY or WAVE2 siRNA, all embryos failed to develop to the morula or blastocyst stages. Moreover, using fluorescence intensity analysis, we found that the expression of actin decreased, and multiple nuclei were observed within a single cell indicating that NPFs-induced actin reduction caused the failure of cell division. In addition, injection of JMY and WAVE2 siRNA also caused ARP2 degradation, indicating that involvement of NPFs in development of mouse embryos is mainly through regulation of ARP2/3-induced actin assembly. Taken together, these data suggested that WAVE2 and JMY are involved in development of mouse embryos, and their regulation may be through a NPFs-Arp2/3-actin pathway.
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Generation and characterization of Lhx9 – GFPCreERT2 knock-in mouse line
Xie, Xiaoling; Deng, Min; Gan, Lin
2014-01-01
Summary LHX9 is a LIM-homeodomain transcription factor essential for the development of gonads, spinal cord interneurons, and thalamic neurons to name a few. We recently reported the expression of LHX9 in retinal amacrine cells during development. In this study, we generated an Lhx9 - GFPCreERT2 (GCE) knock-in mouse line by knocking-in a GCE cassette at the Lhx9 locus, thus inactivating endogenous Lhx9. Lhx9GCE/+ mice were viable, fertile, and displayed no overt phenotypical characteristics. Lhx9GCE/GCE mice were all phenotypically female, smaller in size, viable, but infertile. The specificity and efficacy of the Lhx9-GCE mouse line was verified by crossing it to a Rosa26 - tdTomato reporter mouse line, which reveals the Cre recombinase activities in retinal amacrine cells, developing limbs, testis, hippocampal neurons, thalamic neurons, and cerebellar neurons. Taken together, the Lhx9-GCE mouse line could serve as a beneficial tool for lineage tracing and gene manipulation experiments. PMID:25112520
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Gordeeva, O F; Nikonova, T M
2013-01-01
Pluripotent stem cells represent an attractive cell source for regenerative medicine. However, the risk of teratoma formation after transplantation restricts their clinical application. Therefore, to adequately evaluate the potential risk of tumorigenicity after cell transplantation into human tissues, effective animal transplantation assays need to be developed. We performed a multiparameter (cell number, transplantation site, cell type, host) comparative analysis of the efficiency of tumor development after transplantation of mouse and human embryonic stem (ES) cells and their malignant counterparts, teratocarcinoma (EC) cells, into animal recipients and revealed several key correlations. We found that the efficiency of tumor growth was higher after intraperitoneal than after subcutaneous transplantations of all cell lines studied. The minimal cell numbers sufficient for tumor growth in immunodeficient nude mice were 100-fold lower for intraperitoneal than for subcutaneous transplantations of mouse and human ES cells (10(3) vs. 10(5) and 10(4) vs. 10(6), respectively). Moreover, mouse ES and EC cells formed tumors in immunodeficient and immunocompetent mice more effectively than human ES and EC cells. After intraperitoneal transplantation of 10(3), 10(4), and 10(5) mouse ES cells, teratomas developed in 83%, 100%, and 100% of nude mice, whereas after human ES cell transplantation, teratomas developed in 0%, 17%, and 60%, respectively. In addition, malignant mouse and human EC cells initiated tumor growth after intraperitoneal transplantation significantly faster and more effectively than ES cells. Mouse and human ES cells formed different types of teratomas containing derivatives of three germ layers but different numbers of undifferentiated cells. ES cell-like sublines with differentiation potential similar to the parental cell line were recloned only from mouse, but not from human, ES cell teratomas. These findings provide new information about the possibility and efficiency of tumor growth after transplantation of pluripotent stem cells. This information allows one to predict and possibly prevent the possible risks of tumorigenicity that could arise from stem cell therapeutics.
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Amarnath, Dasari; Wakayama, Sayaka; Zhu, Jie; Moawad, Adel R; Wakayama, Teruhiko; Campbell, Keith H S
2011-12-01
A high potassium concentration in culture media is considered detrimental to in vitro culture of mouse embryos. Here we show that pig zygotic medium (PZM) containing a higher concentration of potassium, and modified to contain 0.2 mM glucose and 0.01 mM EDTA, supported efficient pre- and post-implantation development of mouse zygotes to blastocysts and live pups, respectively. At first, modified PZM (mPZM) was compared with other culture media such as M16, CZB and KSOM-AA for its ability to support development of in vivo mouse zygotes to the blastocyst stage. The proportions of zygotes reaching 2-cell (94-99%) and blastocyst (90-96%) stages in mPZM and other media were not different. However, hatching rates of blastocysts were different (P < 0.05); whereas more than 90% of the blastocysts were hatching in mPZM or KSOM-AA, only 60% of the blastocysts did in M16 or CZB media (P < 0.05). Next we compared post-implantation development of in vitro fertilized zygotes developed to blastocysts in mPZM and KSOM-AA. The proportion of blastocysts developing into live pups was not different between mPZM (49%) and KSOM-AA (44%). Finally, we evaluated whether mPZM could be also used as a fertilization medium. Modified PZM containing 5.56 mM of glucose and 0.4% BSA efficiently supported IVF of mouse gametes. The percent of zygotes cleaving to 2-cell (94-98%) and blastocysts (91-93%) stage was not different from zygotes fertilized in human tubal fluid medium. We concluded that modified pig zygotic medium containing a higher potassium concentration than any other commonly used mouse media supported not only culture of mouse embryos, but also efficient IVF of mouse gametes. Copyright © 2011 Elsevier Inc. All rights reserved.
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2014-10-01
AD_________________ Award Number: W81XWH-13-1-0325 TITLE: Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using ...Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING ORGANIZATION ...Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER W81XWH-13-1-0325 Carcinoma Using Genetically Engineered Mouse Models and 5b
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Targeting Trypsin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model
2016-10-01
PRSS1 gene) causing hereditary pancreatitis is now well established. We developed a transgenic mouse using a Bacterial Artificial Chromosome harboring...trypsinogen gene (PRSS1 gene) causing hereditary pancreatitis is now well established. We developed a transgenic mouse using a Bacterial Artificial... Breeding and expansion of the R122H mouse colony: Period: February 2016-present. After rederivation, the colony of R122H has been expanded at the
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An interview with Patrick Tam by Kathryn Senior.
Tam, Patrick
2010-12-01
Patrick Tam's research is focused on the cellular and molecular mechanisms of body patterning during mouse development. He agreed to be interviewed by Development to talk about his interest in mouse development, new concepts in gastrulation, X-linked diseases and his dream of an African safari.
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4D MEMRI atlas of neonatal FVB/N mouse brain development.
Szulc, Kamila U; Lerch, Jason P; Nieman, Brian J; Bartelle, Benjamin B; Friedel, Miriam; Suero-Abreu, Giselle A; Watson, Charles; Joyner, Alexandra L; Turnbull, Daniel H
2015-09-01
The widespread use of the mouse as a model system to study brain development has created the need for noninvasive neuroimaging methods that can be applied to early postnatal mice. The goal of this study was to optimize in vivo three- (3D) and four-dimensional (4D) manganese (Mn)-enhanced MRI (MEMRI) approaches for acquiring and analyzing data from the developing mouse brain. The combination of custom, stage-dependent holders and self-gated (motion-correcting) 3D MRI sequences enabled the acquisition of high-resolution (100-μm isotropic), motion artifact-free brain images with a high level of contrast due to Mn-enhancement of numerous brain regions and nuclei. We acquired high-quality longitudinal brain images from two groups of FVB/N strain mice, six mice per group, each mouse imaged on alternate odd or even days (6 3D MEMRI images at each day) covering the developmental stages between postnatal days 1 to 11. The effects of Mn-exposure, anesthesia and MRI were assessed, showing small but significant transient effects on body weight and brain volume, which recovered with time and did not result in significant morphological differences when compared to controls. Metrics derived from deformation-based morphometry (DBM) were used for quantitative analysis of changes in volume and position of a number of brain regions. The cerebellum, a brain region undergoing significant changes in size and patterning at early postnatal stages, was analyzed in detail to demonstrate the spatiotemporal characterization made possible by this new atlas of mouse brain development. These results show that MEMRI is a powerful tool for quantitative analysis of mouse brain development, with great potential for in vivo phenotype analysis in mouse models of neurodevelopmental diseases. Copyright © 2015 Elsevier Inc. All rights reserved.
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In utero mouse embryonic imaging with OCT for ophthalmologic research
NASA Astrophysics Data System (ADS)
Syed, Saba H.; Larina, Irina V.; Dickinson, Mary E.; Larin, Kirill V.
2011-03-01
Live imaging of an eye during embryonic development in mammalian model is important for understanding dynamic aspects of normal and abnormal eye morphogenesis. In this study, we used Swept Source Optical Coherence Tomography (SS-OCT) for live structural imaging of mouse embryonic eye through the uterine wall. The eye structure was reconstructed in mouse embryos at 13.5 to 17.5 days post coitus (dpc). Despite the limited imaging depth of OCT in turbid tissues, we were able to visualize the whole eye globe at these stages. These results suggest that live in utero OCT imaging is a useful tool to study embryonic eye development in the mouse model.
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A Comprehensive Atlas of the Adult Mouse Penis
Phillips, Tiffany R.; Wright, David K.; Gradie, Paul E.; Johnston, Leigh A.; Pask, Andrew J.
2016-01-01
Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures. PMID:26112156
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Novel model of stator design to reduce the mass of superconducting generators
NASA Astrophysics Data System (ADS)
Kails, Kevin; Li, Quan; Mueller, Markus
2018-05-01
High temperature superconductors (HTS), with much higher current density than conventional copper wires, make it feasible to develop very powerful and compact power generators. Thus, they are considered as one promising solution for large (10 + MW) direct-drive offshore wind turbines due to their low tower head mass. However, most HTS generator designs are based on a radial topology, which requires an excessive amount of HTS material and suffers from cooling and reliability issues. Axial flux machines on the other hand offer higher torque/volume ratios than the radial machines, which makes them an attractive option where space and transportation becomes an issue. However, their disadvantage is heavy structural mass. In this paper a novel stator design is introduced for HTS axial flux machines which enables a reduction in their structural mass. The stator is for the first time designed with a 45° angle that deviates the air gap closing forces into the vertical direction reducing the axial forces. The reduced axial forces improve the structural stability and consequently simplify their structural design. The novel methodology was then validated through an existing design of the HTS axial flux machine achieving a ∼10% mass reduction from 126 tonnes down to 115 tonnes. In addition, the air gap flux density increases due to the new claw pole shapes improving its power density from 53.19 to 61.90 W kg‑1. It is expected that the HTS axial flux machines designed with the new methodology offer a competitive advantage over other proposed superconducting generator designs in terms of cost, reliability and power density.
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Nano-level instrumentation for analyzing the dynamic accuracy of a rolling element bearing
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Z.; Hong, J.; Zhang, J.
2013-12-15
The rotational performance of high-precision rolling bearings is fundamental to the overall accuracy of complex mechanical systems. A nano-level instrument to analyze rotational accuracy of high-precision bearings of machine tools under working conditions was developed. In this instrument, a high-precision (error motion < 0.15 μm) and high-stiffness (2600 N axial loading capacity) aerostatic spindle was applied to spin the test bearing. Operating conditions could be simulated effectively because of the large axial loading capacity. An air-cylinder, controlled by a proportional pressure regulator, was applied to drive an air-bearing subjected to non-contact and precise loaded axial forces. The measurement results onmore » axial loading and rotation constraint with five remaining degrees of freedom were completely unconstrained and uninfluenced by the instrument's structure. Dual capacity displacement sensors with 10 nm resolution were applied to measure the error motion of the spindle using a double-probe error separation method. This enabled the separation of the spindle's error motion from the measurement results of the test bearing which were measured using two orthogonal laser displacement sensors with 5 nm resolution. Finally, a Lissajous figure was used to evaluate the non-repetitive run-out (NRRO) of the bearing at different axial forces and speeds. The measurement results at various axial loadings and speeds showed the standard deviations of the measurements’ repeatability and accuracy were less than 1% and 2%. Future studies will analyze the relationship between geometrical errors and NRRO, such as the ball diameter differences of and the geometrical errors in the grooves of rings.« less
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Aalaei, Shima; Rajabi Naraki, Zahra; Nematollahi, Fatemeh; Beyabanaki, Elaheh; Shahrokhi Rad, Afsaneh
2017-01-01
Background. Screw-retained restorations are favored in some clinical situations such as limited inter-occlusal spaces. This study was designed to compare stresses developed in the peri-implant bone in two different types of screw-retained restorations (segmented vs. non-segmented abutment) using a finite element model. Methods. An implant, 4.1 mm in diameter and 10 mm in length, was placed in the first molar site of a mandibular model with 1 mm of cortical bone on the buccal and lingual sides. Segmented and non-segmented screw abutments with their crowns were placed on the simulated implant in each model. After loading (100 N, axial and 45° non-axial), von Mises stress was recorded using ANSYS software, version 12.0.1. Results. The maximum stresses in the non-segmented abutment screw were less than those of segmented abutment (87 vs. 100, and 375 vs. 430 MPa under axial and non-axial loading, respectively). The maximum stresses in the peri-implant bone for the model with segmented abutment were less than those of non-segmented ones (21 vs. 24 MPa, and 31 vs. 126 MPa under vertical and angular loading, respectively). In addition, the micro-strain of peri-implant bone for the segmented abutment restoration was less than that of non-segmented abutment. Conclusion. Under axial and non-axial loadings, non-segmented abutment showed less stress concentration in the screw, while there was less stress and strain in the peri-implant bone in the segmented abutment. PMID:29184629
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Nano-level instrumentation for analyzing the dynamic accuracy of a rolling element bearing.
Yang, Z; Hong, J; Zhang, J; Wang, M Y; Zhu, Y
2013-12-01
The rotational performance of high-precision rolling bearings is fundamental to the overall accuracy of complex mechanical systems. A nano-level instrument to analyze rotational accuracy of high-precision bearings of machine tools under working conditions was developed. In this instrument, a high-precision (error motion < 0.15 μm) and high-stiffness (2600 N axial loading capacity) aerostatic spindle was applied to spin the test bearing. Operating conditions could be simulated effectively because of the large axial loading capacity. An air-cylinder, controlled by a proportional pressure regulator, was applied to drive an air-bearing subjected to non-contact and precise loaded axial forces. The measurement results on axial loading and rotation constraint with five remaining degrees of freedom were completely unconstrained and uninfluenced by the instrument's structure. Dual capacity displacement sensors with 10 nm resolution were applied to measure the error motion of the spindle using a double-probe error separation method. This enabled the separation of the spindle's error motion from the measurement results of the test bearing which were measured using two orthogonal laser displacement sensors with 5 nm resolution. Finally, a Lissajous figure was used to evaluate the non-repetitive run-out (NRRO) of the bearing at different axial forces and speeds. The measurement results at various axial loadings and speeds showed the standard deviations of the measurements' repeatability and accuracy were less than 1% and 2%. Future studies will analyze the relationship between geometrical errors and NRRO, such as the ball diameter differences of and the geometrical errors in the grooves of rings.
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NASA Astrophysics Data System (ADS)
Chatzaras, Vasileios; Kruckenberg, Seth C.; Cohen, Shaina M.; Medaris, L. Gordon; Withers, Anthony C.; Bagley, Brian
2016-07-01
The effect of finite strain geometry on crystallographic preferred orientation (CPO) is poorly constrained in the upper mantle. Specifically, the relationship between shape preferred orientation (SPO) and CPO in mantle rocks remains unclear. We analyzed a suite of 40 spinel peridotite xenoliths from Marie Byrd Land, West Antarctica. X-ray computed tomography allows for quantification of spinel SPO, which ranges from prolate to oblate shape. Electron backscatter diffraction analysis reveals a range of olivine CPO patterns, including A-type, axial-[010], axial-[100], and B-type patterns. Until now, these CPO types were associated with different deformation conditions, deformation mechanisms, or strain magnitudes. Microstructures and deformation mechanism maps suggest that deformation in all studied xenoliths is dominated by dislocation-accommodated grain boundary sliding. For the range of temperatures (780-1200°C), extraction depths (39-72 km), differential stresses (2-60 MPa), and water content (up to 500 H/106Si) of the xenolith suite, variations in olivine CPO do not correlate with changes in deformation conditions. Here we establish for the first time in naturally deformed mantle rocks that finite strain geometry controls the development of axial-type olivine CPOs; axial-[010] and axial-[100] CPOs form in relation to oblate and prolate fabric ellipsoids, respectively. Girdling of olivine crystal axes results from intracrystalline slip with activation of multiple slip systems and grain boundary sliding. Our results demonstrate that mantle deformation may deviate from simple shear. Olivine texture in field studies and seismic anisotropy in geophysical investigations can provide critical constraints for the 3-D strain in the upper mantle.
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Takeda, Kazuhisa; Hozumi, Hiroki; Ohba, Koji; Yamamoto, Hiroaki; Shibahara, Shigeki
2016-01-01
Microphthalmia-associated transcription factor (Mitf) is a key regulator for differentiation of melanoblasts, precursors to melanocytes. The mouse homozygous for the black-eyed white (Mitfmi-bw) allele is characterized by the white-coat color and deafness with black eyes due to the lack of melanocytes. The Mitfmi-bw allele carries LINE-1, a retrotransposable element, which results in the Mitf deficiency. Here, we have established the black spotting mouse that was spontaneously arisen from the homozygous Mitfmi-bw mouse lacking melanocytes. The black spotting mouse shows multiple black patches on the white coat, with age-related graying. Importantly, each black patch also contains hair follicles lacking melanocytes, whereas the white-coat area completely lacks melanocytes. RT-PCR analyses of the pigmented patches confirmed that the LINE-1 insertion is retained in the Mitf gene of the black spotting mouse, thereby excluding the possibility of the somatic reversion of the Mitfmi-bw allele. The immunohistochemical analysis revealed that the staining intensity for beta-catenin was noticeably lower in hair follicles lacking melanocytes of the homozygous Mitfmi-bw mouse and the black spotting mouse, compared to the control mouse. In contrast, the staining intensity for beta-catenin and cyclin D1 was higher in keratinocytes of the black spotting mouse, compared to keratinocytes of the control mouse and the Mitfmi-bw mouse. Moreover, the keratinocyte layer appears thicker in the Mitfmi-bw mouse, with the overexpression of Ki-67, a marker for cell proliferation. We also show that the presumptive black spots are formed by embryonic day 15.5. Thus, the black spotting mouse provides the unique model to explore the molecular basis for the survival and death of developing melanoblasts and melanocyte stem cells in the epidermis. These results indicate that follicular melanocytes are responsible for maintaining the epidermal homeostasis; namely, the present study has provided evidence for the link between melanocyte development and the epidermal microenvironment.
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Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui
2015-02-01
During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.
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SSME Seal Test Program: Test results for sawtooth pattern damper seal
NASA Technical Reports Server (NTRS)
Childs, D. W.
1986-01-01
Direct and transverse force coefficients for 11, sawtooth-pattern, and damper-seal configurations were examined. The designation damper seal uses a deliberately roughened stator and smooth rotor to increase the net damping force developed by a seal. The designation sawtooth-pattern refers to a stator roughness pattern. The sawtooth pattern yields axial grooves in the stator which are interrupted by spacer elements which act as flow constrictions or dams. All seals use the same smooth rotor and have the same, constant, minimum clearance. The stators examined the consequences of changes in the following design parameters: (1) axial-groove depth; (2) number of teeth: (3) number of sawtooth sections; (4) number of spacer elements; (5) dam width; (6) axially aligned sawtooth sections versus axially-staggered sawtooth sections; and (7) groove geometry. It is found that none of the sawtooth-pattern seal performs as well as the best round-hole-pattern seal. Maximum damping configurations for the sawtooth and round-hole-pattern stators have comparable stiffness performance. Several of the sawtooth pattern stators outperformed the best round-hole pattern seal.
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A 2-D/1-D transverse leakage approximation based on azimuthal, Fourier moments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stimpson, Shane G.; Collins, Benjamin S.; Downar, Thomas
Here, the MPACT code being developed collaboratively by Oak Ridge National Laboratory and the University of Michigan is the primary deterministic neutron transport solver within the Virtual Environment for Reactor Applications Core Simulator (VERA-CS). In MPACT, the two-dimensional (2-D)/one-dimensional (1-D) scheme is the most commonly used method for solving neutron transport-based three-dimensional nuclear reactor core physics problems. Several axial solvers in this scheme assume isotropic transverse leakages, but work with the axial S N solver has extended these leakages to include both polar and azimuthal dependence. However, explicit angular representation can be burdensome for run-time and memory requirements. The workmore » here alleviates this burden by assuming that the azimuthal dependence of the angular flux and transverse leakages are represented by a Fourier series expansion. At the heart of this is a new axial SN solver that takes in a Fourier expanded radial transverse leakage and generates the angular fluxes used to construct the axial transverse leakages used in the 2-D-Method of Characteristics calculations.« less
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A 2-D/1-D transverse leakage approximation based on azimuthal, Fourier moments
Stimpson, Shane G.; Collins, Benjamin S.; Downar, Thomas
2017-01-12
Here, the MPACT code being developed collaboratively by Oak Ridge National Laboratory and the University of Michigan is the primary deterministic neutron transport solver within the Virtual Environment for Reactor Applications Core Simulator (VERA-CS). In MPACT, the two-dimensional (2-D)/one-dimensional (1-D) scheme is the most commonly used method for solving neutron transport-based three-dimensional nuclear reactor core physics problems. Several axial solvers in this scheme assume isotropic transverse leakages, but work with the axial S N solver has extended these leakages to include both polar and azimuthal dependence. However, explicit angular representation can be burdensome for run-time and memory requirements. The workmore » here alleviates this burden by assuming that the azimuthal dependence of the angular flux and transverse leakages are represented by a Fourier series expansion. At the heart of this is a new axial SN solver that takes in a Fourier expanded radial transverse leakage and generates the angular fluxes used to construct the axial transverse leakages used in the 2-D-Method of Characteristics calculations.« less
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Characteristics of tip-leakage flow in an axial fan
NASA Astrophysics Data System (ADS)
Park, Keuntae; Choi, Haecheon; Choi, Seokho; Sa, Yongcheol
2014-11-01
An axial fan with a shroud generates complicated vortical structures by the interaction of the axial flow with the fan blades and shroud near the blade tips. Large eddy simulation (LES) is performed for flow through a forward-swept axial fan, operating at the design condition of Re = 547,000 based on the radius of blade tip and the tip velocity. A dynamic global model (Lee et al. 2010) is used for a subgrid-scale model, and an immersed boundary method in a non-inertial reference frame (Kim & Choi 2006) is adopted for the present simulation. It is found that two vortical structures are formed near the blade tip: the main tip leakage vortex (TLV) and the auxiliary TLV. The main TLV is initiated near the leading edge, develops downstream, and impinges on the pressure surface of the next blade, where the pressure fluctuations and turbulence intensity become high. On the other hand, the auxiliary TLV is initiated at the aft part of the blade but is relatively weak such that it merges with the main TLV. Supported by the KISTI Supercomputing Center (KSC-2014-C2-014).
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Principles and application of LIMS in mouse clinics.
Maier, Holger; Schütt, Christine; Steinkamp, Ralph; Hurt, Anja; Schneltzer, Elida; Gormanns, Philipp; Lengger, Christoph; Griffiths, Mark; Melvin, David; Agrawal, Neha; Alcantara, Rafael; Evans, Arthur; Gannon, David; Holroyd, Simon; Kipp, Christian; Raj, Navis Pretheeba; Richardson, David; LeBlanc, Sophie; Vasseur, Laurent; Masuya, Hiroshi; Kobayashi, Kimio; Suzuki, Tomohiro; Tanaka, Nobuhiko; Wakana, Shigeharu; Walling, Alison; Clary, David; Gallegos, Juan; Fuchs, Helmut; de Angelis, Martin Hrabě; Gailus-Durner, Valerie
2015-10-01
Large-scale systemic mouse phenotyping, as performed by mouse clinics for more than a decade, requires thousands of mice from a multitude of different mutant lines to be bred, individually tracked and subjected to phenotyping procedures according to a standardised schedule. All these efforts are typically organised in overlapping projects, running in parallel. In terms of logistics, data capture, data analysis, result visualisation and reporting, new challenges have emerged from such projects. These challenges could hardly be met with traditional methods such as pen & paper colony management, spreadsheet-based data management and manual data analysis. Hence, different Laboratory Information Management Systems (LIMS) have been developed in mouse clinics to facilitate or even enable mouse and data management in the described order of magnitude. This review shows that general principles of LIMS can be empirically deduced from LIMS used by different mouse clinics, although these have evolved differently. Supported by LIMS descriptions and lessons learned from seven mouse clinics, this review also shows that the unique LIMS environment in a particular facility strongly influences strategic LIMS decisions and LIMS development. As a major conclusion, this review states that there is no universal LIMS for the mouse research domain that fits all requirements. Still, empirically deduced general LIMS principles can serve as a master decision support template, which is provided as a hands-on tool for mouse research facilities looking for a LIMS.
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Chang, Bo
2016-01-01
Leber's congenital amaurosis (LCA) is an inherited retinal degenerative disease characterized by severe loss of vision in the first year of life. In addition to early vision loss, a variety of other eye-related abnormalities including roving eye movements, deep-set eyes, and sensitivity to bright light also occur with this disease. Many animal models of LCA are available and the study them has led to a better understanding of the pathology of the disease, and has led to the development of therapeutic strategies aimed at curing or slowing down LCA. Mouse models, with their well-developed genetics and similarity to human physiology and anatomy, serve as powerful tools with which to investigate the etiology of human LCA. Such mice provide reproducible, experimental systems for elucidating pathways of normal development, function, designing strategies and testing compounds for translational research and gene-based therapies aimed at delaying the diseases progression. In this chapter, I describe tools used in the discovery and evaluation of mouse models of LCA including a Phoenix Image-Guided Optical Coherence Tomography (OCT) and a Diagnosys Espion Visual Electrophysiology System. Three mouse models are described, the rd3 mouse model for LCA12 and LCA1, the rd12 mouse model for LCA2, and the rd16 mouse model for LCA10.
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Patterning by heritage in mouse molar row development.
Prochazka, Jan; Pantalacci, Sophie; Churava, Svatava; Rothova, Michaela; Lambert, Anne; Lesot, Hervé; Klein, Ophir; Peterka, Miroslav; Laudet, Vincent; Peterkova, Renata
2010-08-31
It is known from paleontology studies that two premolars have been lost during mouse evolution. During mouse mandible development, two bud-like structures transiently form that may represent rudimentary precursors of the lost premolars. However, the interpretation of these structures and their significance for mouse molar development are highly controversial because of a lack of molecular data. Here, we searched for typical tooth signaling centers in these two bud-like structures, and followed their fate using molecular markers, 3D reconstructions, and lineage tracing in vitro. Transient signaling centers were indeed found to be located at the tips of both the anterior and posterior rudimentary buds. These centers expressed a similar set of molecular markers as the "primary enamel knot" (pEK), the signaling center of the first molar (M1). These two transient signaling centers were sequentially patterned before and anterior to the M1 pEK. We also determined the dynamics of the M1 pEK, which, slightly later during development, spread up to the field formerly occupied by the posterior transient signaling center. It can be concluded that two rudimentary tooth buds initiate the sequential development of the mouse molars and these have previously been mistaken for early stages of M1 development. Although neither rudiment progresses to form an adult tooth, the posterior one merges with the adjacent M1, which may explain the anterior enlargement of the M1 during mouse family evolution. This study highlights how rudiments of lost structures can stay integrated and participate in morphogenesis of functional organs and help in understanding their evolution, as Darwin suspected long ago.
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Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear.
Bank, Lisa M; Bianchi, Lynne M; Ebisu, Fumi; Lerman-Sinkoff, Dov; Smiley, Elizabeth C; Shen, Yu-chi; Ramamurthy, Poornapriya; Thompson, Deborah L; Roth, Therese M; Beck, Christine R; Flynn, Matthew; Teller, Ryan S; Feng, Luming; Llewellyn, G Nicholas; Holmes, Brandon; Sharples, Cyrrene; Coutinho-Budd, Jaeda; Linn, Stephanie A; Chervenak, Andrew P; Dolan, David F; Benson, Jennifer; Kanicki, Ariane; Martin, Catherine A; Altschuler, Richard; Koch, Alisa E; Koch, Alicia E; Jewett, Ethan M; Germiller, John A; Barald, Kate F
2012-12-01
This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system 'inflammatory' cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.
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Horný, Lukáš; Adámek, Tomáš; Kulvajtová, Markéta
2017-02-01
It is known that large arteries in situ are subjected to significant axial prestretch. This prestretch plays an important physiological role in optimizing the biomechanical response of an artery. It is also known that the prestretch declines with age. However, a detailed description of age-related changes in prestretch is available only for the abdominal aorta and for the femoropliteal artery. Our study presents results of measurements of axial prestretch in 229 left common carotid arteries excised in autopsies. It was found that the prestretch of the carotid artery correlates significantly with age ([Formula: see text], p value < 0.001). A linear regression model was used to fit the observations. Simultaneously with the measurement of the prestretch in the carotid artery, the axial prestretch was also measured in abdominal aorta. By comparing data obtained from these locations, it was concluded that the axial prestretch in the carotid artery is greater than in the abdominal aorta, and that atherosclerosis develops more rapidly in the abdominal aorta than in the carotid artery. Histological sections obtained from 8 carotid arteries and aortas suggest that the medial layer of the left common carotid artery is significantly thinner than aortic media (median/IQR: 0.343/0.086 vs. 0.482/0.172 mm, [Formula: see text] in Wilcoxon signed-rank test) and simultaneously that carotid media contains a lower number of elastic membranes (median/IQR: 26.5/11.8 vs. 31.5/11.8, [Formula: see text] in the Wilcoxon signed-rank test). This could be a reason for the different extent of the prestretch observed in aorta and in carotid artery. Our data sample also contains 5 measurements of the axial prestretch in abdominal aortas suffering from an aneurysm. It was found that aneurysmatic aortas also exhibit axial retraction when excised from in situ position. To the best of our knowledge, this is the first time that detailed data characterizing axial prestretch of the human left common carotid artery have been presented.
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NASA Astrophysics Data System (ADS)
Fidolini, Francesco; Ghinassi, Massimiliano; Aldinucci, Mauro; Billi, Paolo; Boaga, Jacopo; Deiana, Rita; Brivio, Lara
2013-05-01
The present study deals with the fault-sourced, alluvial-fan deposits of the Plio-Pleistocene Upper Valdarno Basin (Northern Apennines, Italy). Different phases of alluvial fan aggradation, progradation and backstep are discussed as possible effects of the interaction among fault-generated accommodation space, sediment supply and discharge variations affecting the axial fluvial drainage. The Upper Valdarno Basin, located about 35 km SE of Florence, is filled with 550 m palustrine, lacustrine and alluvial deposits forming four main unconformity-bounded units (i.e. synthems). The study alluvial-fan deposits belong to the two uppermost synthems (Montevarchi and Torrente Ciuffenna synthems) and are Early to Middle Pleistocene in age. These deposits are sourced from the fault-bounded, NE margin of the basin and interfinger with axial fluvial deposits. Alluvial fan deposits of the Montevarchi Synthem consist of three main intervals: i) a lower interval, which lacks any evidence of a depositional trend and testify balance between the subsidence rate (i.e. fault activity) and the amount of sediment provided from the margin; ii) a coarsening-upward middle interval, pointing to a decrease in subsidence rate associated with an augment in sediment supply; iii) a fining-upward, upper interval (locally preserved), documenting a phase of tectonic quiescence associated with a progressive re-equilibration of the tectonically-induced morphological profile. The basin-scale unconformity, which separates the Montevarchi and Torrente Ciuffenna synthems was due to the entrance of the Arno River into the basin as consequence of a piracy. This event caused a dramatic increase in water discharge of the axial fluvial system, and its consequent embanking. Such an erosional surface started to develop in the axial areas, and propagated along the main tributaries, triggering erosion of the alluvial fan deposits. Alluvial-fan deposits of the Torrente Ciuffenna Synthem accumulated above the unconformity during a phase of tectonic quiescence, and show a fining-upward depositional trend. This trend was generated by a progressive decrease in sediment supply stemming out from upstream migration of the knickpoints developed during the embanking of the axial system.
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Active identification and control of aerodynamic instabilities in axial and centrifugal compressors
NASA Astrophysics Data System (ADS)
Krichene, Assad
In this thesis, it is experimentally shown that dynamic cursors to stall and surge exist in both axial and centrifugal compressors using the experimental axial and centrifugal compressor rigs located in the School of Aerospace Engineering at the Georgia Institute of Technology. Further, it is shown that the dynamic cursors to stall and surge can be identified in real-time and they can be used in a simple control scheme to avoid the occurrence of stall and surge instabilities altogether. For the centrifugal compressor, a previously developed real-time observer is used in order to detect dynamic cursors to surge in real-time. An off-line analysis using the Fast Fourier Transform (FFT) of the open loop experimental data from the centrifugal compressor rig is carried out to establish the influence of compressor speed on the dynamic cursor frequency. The variation of the amplitude of dynamic cursors with compressor operating condition from experimental data is qualitatively compared with simulation results obtained using a generic compression system model subjected to white noise excitation. Using off-line analysis results, a simple control scheme based on fuzzy logic is synthesized for surge avoidance and recovery. The control scheme is implemented in the centrifugal compressor rig using compressor bleed as well as fuel flow to the combustor. Closed loop experimental results are obtained to demonstrate the effectiveness of the controller for both surge avoidance and surge recovery. The existence of stall cursors in an axial compression system is established using the observer scheme from off-line analysis of an existing database of a commercial gas turbine engine. However, the observer scheme is found to be ineffective in detecting stall cursors in the experimental axial compressor rig in the School of Aerospace Engineering at the Georgia Institute of Technology. An alternate scheme based on the amplitude of pressure data content at the blade passage frequency obtained using a pressure sensor located (in the casing) over the blade row is developed and used in the axial compressor rig for stall and surge avoidance and recovery. (Abstract shortened by UMI.)
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Retinal degeneration increases susceptibility to myopia in mice
Park, Hanna; Tan, Christopher C.; Faulkner, Amanda; Jabbar, Seema B.; Schmid, Gregor; Abey, Jane; Iuvone, P. Michael
2013-01-01
Purpose Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associated with myopia; however, the underlying link between these conditions is not known. This study examines the influence of photoreceptor degeneration on refractive development by testing two mouse models of retinitis pigmentosa under normal and form deprivation visual conditions. Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism. Methods Refractive eye growth in mice that were homozygous for a mutation in Pde6b, Pde6brd1/rd1 (rd1), or Pde6brd10/rd10 (rd10) was measured weekly from 4 to 12 weeks of age and compared to age-matched wild-type (WT) mice. Refractive error was measured using an eccentric infrared photorefractor, and axial length was measured with partial coherence interferometry or spectral domain ocular coherence tomography. A cohort of mice received head-mounted diffuser goggles to induce form deprivation from 4 to 6 weeks of age. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured with high-performance liquid chromatography in each strain after exposure to normal or form deprivation conditions. Results The rd1 and rd10 mice had significantly greater hyperopia relative to the WT controls throughout normal development; however, axial length became significantly longer only in WT mice starting at 7 weeks of age. After 2 weeks of form deprivation, the rd1 and rd10 mice demonstrated a faster and larger myopic shift (−6.14±0.62 and −7.38±1.46 diopter, respectively) compared to the WT mice (−2.41±0.47 diopter). Under normal visual conditions, the DOPAC levels and DOPAC/dopamine ratios, a measure of dopamine turnover, were significantly lower in the rd1 and rd10 mice compared to the WT mice, while the dopamine levels were similar or higher than WT in the rd10 mice. Lower basal levels of DOPAC were highly correlated with increasing myopic shifts. Conclusions Refractive development under normal visual conditions was disrupted toward greater hyperopia from 4 to 12 weeks of age in these photoreceptor degeneration models, despite significantly lower DOPAC levels. However, the retinal degeneration models with low basal levels of DOPAC had increased susceptibility to form deprivation myopia. These results indicate that photoreceptor degeneration may alter dopamine metabolism, leading to increased susceptibility to myopia with an environmental visual challenge. PMID:24146540
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Positron emission tomography with additional γ-ray detectors for multiple-tracer imaging.
Fukuchi, Tomonori; Okauchi, Takashi; Shigeta, Mika; Yamamoto, Seiichi; Watanabe, Yasuyoshi; Enomoto, Shuichi
2017-06-01
Positron emission tomography (PET) is a useful imaging modality that quantifies the physiological distributions of radiolabeled tracers in vivo in humans and animals. However, this technique is unsuitable for multiple-tracer imaging because the annihilation photons used for PET imaging have a fixed energy regardless of the selection of the radionuclide tracer. This study developed a multi-isotope PET (MI-PET) system and evaluated its imaging performance. Our MI-PET system is composed of a PET system and additional γ-ray detectors. The PET system consists of pixelized gadolinium orthosilicate (GSO) scintillation detectors and has a ring geometry that is 95 mm in diameter with an axial field of view of 37.5 mm. The additional detectors are eight bismuth germanium oxide (BGO) scintillation detectors, each of which is 50 × 50 × 30 mm 3 , arranged into two rings mounted on each side of the PET ring with a 92-mm-inner diameter. This system can distinguish between different tracers using the additional γ-ray detectors to observe prompt γ-rays, which are emitted after positron emission and have an energy intrinsic to each radionuclide. Our system can simultaneously acquire double- (two annihilation photons) and triple- (two annihilation photons and a prompt γ-ray) coincidence events. The system's efficiency for detecting prompt de-excitation γ-rays was measured using a positron-γ emitter, 22 Na. Dual-radionuclide ( 18 F and 22 Na) imaging of a rod phantom and a mouse was performed to demonstrate the performance of the developed system. Our system's basic performance was evaluated by reconstructing two images, one containing both tracers and the other containing just the second tracer, from list-mode data sets that were categorized by the presence or absence of the prompt γ-ray. The maximum detection efficiency for 1275 keV γ-rays emitted from 22 Na was approximately 7% at the scanner's center, and the minimum detection efficiency was 5.1% at the edge of the field of view. Dual-radionuclide imaging of the point sources and rod phantom revealed that our system maintained PET's intrinsic spatial resolution and quantitative nature for the second tracer. We also successfully acquired simultaneous double- and triple-coincidence events from a mouse containing 18 F-fluoro-deoxyglucose and 22 Na dissolved in water. The dual-tracer distributions in the mouse obtained by our MI-PET were reasonable from the viewpoints of physiology and pharmacokinetics. This study demonstrates the feasibility of multiple-tracer imaging using PET with additional γ-ray detectors. This method holds promise for enabling the reconstruction of quantitative multiple-tracer images and could be very useful for analyzing multiple-molecular dynamics. © 2017 American Association of Physicists in Medicine.
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Halbach Magnetic Rotor Development
NASA Technical Reports Server (NTRS)
Gallo, Christopher A.
2008-01-01
The NASA John H. Glenn Research Center has a wealth of experience in Halbach array technology through the Fundamental Aeronautics Program. The goals of the program include improving aircraft efficiency, reliability, and safety. The concept of a Halbach magnetically levitated electric aircraft motor will help reduce harmful emissions, reduce the Nation s dependence on fossil fuels, increase efficiency and reliability, reduce maintenance and decrease operating noise levels. Experimental hardware systems were developed in the GRC Engineering Development Division to validate the basic principles described herein and the theoretical work that was performed. A number of Halbach Magnetic rotors have been developed and tested under this program. A separate test hardware setup was developed to characterize each of the rotors. A second hardware setup was developed to test the levitation characteristics of the rotors. Each system focused around a unique Halbach array rotor. Each rotor required original design and fabrication techniques. A 4 in. diameter rotor was developed to test the radial levitation effects for use as a magnetic bearing. To show scalability from the 4 in. rotor, a 1 in. rotor was developed to also test radial levitation effects. The next rotor to be developed was 20 in. in diameter again to show scalability from the 4 in. rotor. An axial rotor was developed to determine the force that could be generated to position the rotor axially while it is rotating. With both radial and axial magnetic bearings, the rotor would be completely suspended magnetically. The purpose of this report is to document the development of a series of Halbach magnetic rotors to be used in testing. The design, fabrication and assembly of the rotors will be discussed as well as the hardware developed to test the rotors.
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Multiscale Imaging of the Mouse Cortex Using Two-Photon Microscopy and Wide-Field Illumination
NASA Astrophysics Data System (ADS)
Bumstead, Jonathan R.
The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing the difference in spatial scales imaged with two-photon microscopy (TPM) and optical intrinsic signal imaging (OISI). Central to this work has been the formulation of a principled design strategy for extending the FOV of the two-photon microscope. Using this design approach, we constructed a TPM system with subcellular resolution and a FOV area 100 times greater than a conventional two-photon microscope. To image the ellipsoidal shape of the mouse cortex, we also developed the microscope to image arbitrary surfaces within a single frame using an electrically tunable lens. Finally, to address the speed limitations of the TPM systems developed during my dissertation, I also conducted research in large-scale neural phenomena occurring in the mouse brain imaged with high-speed OISI. The work conducted during my dissertation addresses some of the fundamental principles in designing and applying optical systems for multiscale imaging of the mouse brain.
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Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.
2011-01-01
Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750
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Cyclic Axial-Torsional Deformation Behavior of a Cobalt-Base Superalloy
NASA Technical Reports Server (NTRS)
Bonacuse, Peter J.; Kalluri, Sreeramesh
1995-01-01
The cyclic, high-temperature deformation behavior of a wrought cobalt-base super-alloy, Haynes 188, is investigated under combined axial and torsional loads. This is accomplished through the examination of hysteresis loops generated from a biaxial fatigue test program. A high-temperature axial, torsional, and combined axial-torsional fatigue database has been generated on Haynes 188 at 760 C. Cyclic loading tests have been conducted on uniform gage section tubular specimens in a servohydraulic axial-torsional test rig. Test control and data acquisition were accomplished with a minicomputer. The fatigue behavior of Haynes 188 at 760 C under axial, torsional, and combined axial-torsional loads and the monotonic and cyclic deformation behaviors under axial and torsional loads have been previously reported. In this paper, the cyclic hardening characteristics and typical hysteresis loops in the axial stress versus axial strain, shear stress ,versus engineering shear strain, axial strain versus engineering shear strain. and axial stress versus shear stress spaces are presented for cyclic in-phase and out-of-phase axial-torsional tests. For in-phase tests, three different values of the proportionality constant lambda (the ratio of engineering shear strain amplitude to axial strain amplitude, are examined, viz. 0.86, 1.73, and 3.46. In the out-of-phase tests, three different values of the phase angle, phi (between the axial and engineering shear strain waveforms), are studied, viz., 30, 60, and 90 degrees with lambda equals 1.73. The cyclic hardening behaviors of all the tests conducted on Haynes 188 at 760 C are evaluated using the von Mises equivalent stress-strain and the maximum shear stress-maximum engineering shear strain (Tresca) curves. Comparisons are also made between the hardening behaviors of cyclic axial, torsional, and combined in-phase (lambda = 1.73 and phi = 0) and out-of-phase (lambda = 1.73 and phi = 90') axial-torsional fatigue tests. These comparisons are accomplished through simple Ramberg-Osgood type stress-strain functions for cyclic, axial stress-strain and shear stress-engineering shear strain curves.
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In-phase and out-of-phase axial-torsional fatigue behavior of Haynes 188 at 760 C
NASA Technical Reports Server (NTRS)
Kalluri, Sreeramesh; Bonacuse, Peter J.
1991-01-01
Isothermal, in-phase and out-of-phase axial-torsional fatigue experiments have been conducted at 760 C on uniform gage section, thin-walled tubular specimens of a wrought cobalt-base superalloy, Haynes 188. Test-control and data acquisition were accomplished with a minicomputer. Fatigue lives of the in- and out-of-phase axial-torsional fatigue tests have been estimated with four different multiaxial fatigue life prediction models that were developed primarly for predicting axial-torsional fatigue lives at room temperature. The models investigated were: (1) the von Mises equivalent strain range; (2) the Modified Multiaxiality Factor Approach; (3) the Modified Smith-Watson-Topper Parameter; and (4) the critical shear plane method of Fatemi, Socie, and Kurath. In general, life predictions by the von Mises equivalent strain range model were within a factor of 2 for a majority of the tests and the predictions by the Modified Multiaxiality Factor Approach were within a factor of 2, while predictions of the Modified Smith-Watson-Topper Parameter and of the critical shear plane method of Fatemi, Socie, and Kurath were unconservative and conservative, respectively, by up to factors of 4. In some of the specimens tested under combined axial-torsional loading conditions, fatigue cracks initiated near extensometer indentations. Two design modifications have been proposed to the thin-walled tubular specimen to overcome this problem.
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Elevated temperature axial and torsional fatigue behavior of Haynes 188
NASA Technical Reports Server (NTRS)
Bonacuse, Peter J.; Kalluri, Sreeramesh
1995-01-01
The results are reported for high-temperature axial and torsional low-cycle fatigue experiments performed at 760 C in air on thin-walled tubular specimens of Haynes 188, a wrought cobalt-based superalloy. Data are also presented for mean coefficient of thermal expansion, elastic modulus, and shear modulus at various temperatures from room to 1000 C, and monotonic and cyclic stress-strain curves in tension and in shear at 760 C. This data set is used to evaluate several multiaxial fatigue life models (most were originally developed for room temperature multiaxial life prediction) including von Mises equivalent strain range (ASME Boiler and Pressure Code), Manson-Halford, modified multiaxiality factor (proposed in this paper), modified Smith-Watson-Topper, and Fatemi-Socie-Kurath. At von Mises equivalent strain ranges (the torsional strain range divided by the square root of 3, taking the Poisson's ratio to be 0.5), torsionally strained specimens lasted, on average, factors of 2 to 3 times longer than axially strained specimens. The modified multiaxiality factor approach shows promise as a useful method of estimating torsional fatigue life from axial fatigue data at high temperatures. Several difficulties arose with the specimen geometry and extensometry used in these experiments. Cracking at extensometer probe indentations was a problem at smaller strain ranges. Also, as the largest axial and torsional strain range fatigue tests neared completion, a small amount of specimen buckling was observed.
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NASA Technical Reports Server (NTRS)
Boyd, Ronald D., Sr.; Turknett, Jerry C.
1989-01-01
The effect of enhancement devices on flow boiling heat transfer in coolant channels, which are heated either from the top side or uniformly was studied. Studies are completed of the variations in the local (axial and circumferential) and mean heat transfer coefficients in horizontal, top-heated coolant channels with smooth walls and internal heat transfer enhancement devices. The working fluid is freon-11. The objectives are to: (1) examine the variations in both the mean and local (axial and circumferential) heat transfer coefficients for a circular coolant channel with either smooth walls or with both a twisted tape and spiral finned walls; (2) examine the effect of channel diameter (and the length-to-diameter aspect ratio) variations for the smooth wall channel; and (3) develop and improved data reduction analysis. The case of the top-heated, horizontal flow channel with smooth wall (1.37 cm inside diameter, and 122 cm heated length) was completed. The data were reduced using a preliminary analysis based on the heated hydraulic diameter. Preliminary examination of the local heat transfer coefficient variations indicated that there are significant axial and circumferential variations. However, it appears that the circumferential variation is more significant than the axial ones. In some cases, the circumferential variations were as much as a factor of ten. The axial variations rarely exceeded a factor of three.
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The structure and mechanics of Moso bamboo material
Dixon, P. G.; Gibson, L. J.
2014-01-01
Although bamboo has been used structurally for millennia, there is currently increasing interest in the development of renewable and sustainable structural bamboo products (SBPs). These SBPs are analogous to wood products such as plywood, oriented strand board and glue-laminated wood. In this study, the properties of natural Moso bamboo (Phyllostachys pubescens) are investigated to further enable the processing and design of SBPs. The radial and longitudinal density gradients in bamboo give rise to variations in the mechanical properties. Here, we measure the flexural properties of Moso bamboo in the axial direction, along with the compressive strengths in the axial and transverse directions. Based on the microstructural variations (observed with scanning electron microscopy) and extrapolated solid cell wall properties of bamboo, we develop models, which describe the experimental results well. Compared to common North American construction woods loaded along the axial direction, Moso bamboo is approximately as stiff and substantially stronger, in both flexure and compression but denser. This work contributes to critical knowledge surrounding the microstructure and mechanical properties of bamboo, which are vital to the engineering and design of sustainable SBPs. PMID:25056211
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Prospect for a 60 GHz multicharged ECR ion source
NASA Astrophysics Data System (ADS)
Thuillier, T.; Bondoux, D.; Angot, J.; Baylac, M.; Froidefond, E.; Jacob, J.; Lamy, T.; Leduc, A.; Sole, P.; Debray, F.; Trophime, C.; Skalyga, V.; Izotov, I.
2018-05-01
The conceptual design of a fourth generation hybrid electron cyclotron resonance (ECR) ion source operated at 60 GHz is proposed. The axial magnetic mirror is generated with a set of three Nb3Sn coils, while the hexapole is made with room temperature (RT) copper coils. The motivations for such a hybrid development are to study further the ECR plasma physics and the intense multicharged ion beams' production and transport at a time when a superconducting (SC) hexapole appears unrealistic at 60 GHz. The RT hexapole coil designed is an evolution of the polyhelix technology developed at the French High Magnetic Field Facility. The axial magnetic field is generated by means of 3 Nb3Sn SC coils operated with a maximum current density of 350 A/mm2 and a maximum coil load line factor of 81%. The ECR plasma chamber resulting from the design features an inner radius of 94 mm and a length of 500 mm. The radial magnetic intensity is 4.1 T at the wall. Characteristic axial mirror peaks are 8 and 4.5 T, with 1.45 T minimum in between.
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Metrological analysis of the human foot: 3D multisensor exploration
NASA Astrophysics Data System (ADS)
Muñoz Potosi, A.; Meneses Fonseca, J.; León Téllez, J.
2011-08-01
In the podiatry field, many of the foot dysfunctions are mainly generated due to: Congenital malformations, accidents or misuse of footwear. For the treatment or prevention of foot disorders, the podiatrist diagnoses prosthesis or specific adapted footwear, according to the real dimension of foot. Therefore, it is necessary to acquire 3D information of foot with 360 degrees of observation. As alternative solution, it was developed and implemented an optical system of threedimensional reconstruction based in the principle of laser triangulation. The system is constituted by an illumination unit that project a laser plane into the foot surface, an acquisition unit with 4 CCD cameras placed around of axial foot axis, an axial moving unit that displaces the illumination and acquisition units in the axial axis direction and a processing and exploration unit. The exploration software allows the extraction of distances on three-dimensional image, taking into account the topography of foot. The optical system was tested and their metrological performances were evaluated in experimental conditions. The optical system was developed to acquire 3D information in order to design and make more appropriate footwear.
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NASA Technical Reports Server (NTRS)
Pindera, Marek-Jerzy; Aboudi, Jacob
1998-01-01
The objective of this three-year project was to develop and deliver to NASA Lewis one-dimensional and two-dimensional higher-order theories, and related computer codes, for the analysis, optimization and design of cylindrical functionally graded materials/structural components for use in advanced aircraft engines (e.g., combustor linings, rotor disks, heat shields, blisk blades). To satisfy this objective, a quasi one-dimensional version of the higher-order theory, HOTCFGM-1D, and four computer codes based on this theory, for the analysis, design and optimization of cylindrical structural components functionally graded in the radial direction were developed. The theory is applicable to thin multi-phased composite shell/cylinders subjected to macroscopically axisymmetric thermomechanical and inertial loading applied uniformly along the axial direction such that the overall deformation is characterized by a constant average axial strain. The reinforcement phases are uniformly distributed in the axial and circumferential directions, and arbitrarily distributed in the radial direction, thereby allowing functional grading of the internal reinforcement in this direction.
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Qiu, Jia-jun; Ren, Zhao-rui; Yan, Jing-bin
2016-01-01
Epigenetics regulations have an important role in fertilization and proper embryonic development, and several human diseases are associated with epigenetic modification disorders, such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome. However, the dynamics and functions of long non-coding RNAs (lncRNAs), one type of epigenetic regulators, in human pre-implantation development have not yet been demonstrated. In this study, a comprehensive analysis of human and mouse early-stage embryonic lncRNAs was performed based on public single-cell RNA sequencing data. Expression profile analysis revealed that lncRNAs are expressed in a developmental stage–specific manner during human early-stage embryonic development, whereas a more temporal-specific expression pattern was identified in mouse embryos. Weighted gene co-expression network analysis suggested that lncRNAs involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic genome activation and mitochondrial functions. We also found that the network of lncRNAs involved in zygotic genome activation was highly preservative between human and mouse embryos, whereas in other stages no strong correlation between human and mouse embryo was observed. This study provides insight into the molecular mechanism underlying lncRNA involvement in human pre-implantation embryonic development. PMID:27542205
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MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice.
Ka, Minhan; Moffat, Jeffrey J; Kim, Woo-Yang
2017-12-01
GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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NASA Astrophysics Data System (ADS)
Burton, Jason C.; Wang, Shang; Behringer, Richard R.; Larina, Irina V.
2016-03-01
Infertility is a known major health concern and is estimated to impact ~15% of couples in the U.S. The majority of failed pregnancies occur before or during implantation of the fertilized embryo into the uterus. Understanding the mechanisms regulating development by studying mouse reproductive organs could significantly contribute to an improved understanding of normal development of reproductive organs and developmental causes of infertility in humans. Towards this goal, we report a three-dimensional (3D) imaging study of the developing mouse reproductive organs (ovary, oviduct, and uterus) using optical coherence tomography (OCT). In our study, OCT was used for 3D imaging of reproductive organs without exogenous contrast agents and provides micro-scale spatial resolution. Experiments were conducted in vitro on mouse reproductive organs ranging from the embryonic day 14.5 to adult stages. Structural features of the ovary, oviduct, and uterus are presented. Additionally, a comparison with traditional histological analysis is illustrated. These results provide a basis for a wide range of infertility studies in mouse models. Through integration with traditional genetic and molecular biology approaches, this imaging method can improve understanding of ovary, oviduct, and uterus development and function, serving to further contribute to our understanding of fertility and infertility.
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Mullen, Yoko
2017-04-01
In 1974, the discovery of a mouse and a rat that spontaneously developed hyperglycemia led to the development of 2 autoimmune diabetes models: nonobese diabetic (NOD) mouse and Bio-Breeding rat. These models have contributed to our understanding of autoimmune diabetes, provided tools to dissect autoimmune islet damage, and facilitated development of early detection, prevention, and treatment of type 1 diabetes. The genetic characterization, monoclonal antibodies, and congenic strains have made NOD mice especially useful.Although the establishment of the inbred NOD mouse strain was documented by Makino et al (Jikken Dobutsu. 1980;29:1-13), this review will focus on the not-as-well-known history leading to the discovery of a glycosuric female mouse by Yoshihiro Tochino. This discovery was spearheaded by years of effort by Japanese scientists from different disciplines and dedicated animal care personnel and by the support of the Shionogi Pharmaceutical Company, Osaka, Japan. The history is based on the early literature, mostly written in Japanese, and personal communications especially with Dr Tochino, who was involved in diabetes animal model development and who contributed to the release of NOD mice to the international scientific community. This article also reviews the scientific contributions made by the Bio-Breeding rat to autoimmune diabetes.
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Martinez‐Barbera, Juan Pedro
2017-01-01
Abstract Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ‐specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. PMID:28414891
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NASA Astrophysics Data System (ADS)
Marchukov, E.; Egorov, I.; Popov, G.; Baturin, O.; Goriachkin, E.; Novikova, Y.; Kolmakova, D.
2017-08-01
The article presents one optimization method for improving of the working process of an axial compressor of gas turbine engine. Developed method allows to perform search for the best geometry of compressor blades automatically by using optimization software IOSO and CFD software NUMECA Fine/Turbo. Optimization was performed by changing the form of the middle line in the three sections of each blade and shifts of three sections of the guide vanes in the circumferential and axial directions. The calculation of the compressor parameters was performed for work and stall point of its performance map on each optimization step. Study was carried out for seven-stage high-pressure compressor and three-stage low-pressure compressors. As a result of optimization, improvement of efficiency was achieved for all investigated compressors.
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Failure Criterion For Isotropic Time Dependent Materials Which Accounts for Multi-Axial Loading
NASA Technical Reports Server (NTRS)
Richardson, D. E.; Anderson, G. L.; Macon, D. J.
2003-01-01
The Space Shuttle's Reusable Solid Rocket Motor (RSRM) nozzle program has recently conducted testing to characterize the effects of multi-axial loading, temperature and time on the failure characteristics of TIGA321, EA913NA, EA946 (three filled epoxy adhesives). From the test data a "Multi-Axial, Temperature, and Time Dependent" or MATT failure criterion was developed. It is shown that this criterion simplifies, for constant load and constant load rate conditions, into a form that can be easily used for stress analysis. Failure for TIGA321 and EA913NA are characterized below their glass transition temperature. Failure for EA946 is characterized for conditions that pass through its glass transition. The MATT failure criterion is shown to be accurate for a wide range of conditions for these adhesives.
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A Gas Lubricant Combined Support-sealing Node
NASA Astrophysics Data System (ADS)
Falaleev, S. V.; Nadjari, H.; Vinogradov, A. S.
2018-01-01
The purpose of the research provided in this article is to develop a gas-dynamic device capable of performing the functions of support sealing, unloading devices for axial thrust bearings and damping of axial vibrations of the rotor. Some kinds of seals applied in supports of aircraft engines are known. A face gas-dynamic seal is one of the most effective and standard technology solution for compressors. As the basic element of the developed device, a face gas-dynamic seal with spiral grooves is considered. It also includes the fundamental mathematical calculation of such devices and the experimental research outcomes that form the basis of which such devices can be produced and adapted for use.
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Khan, Rabia; Oakes, Peter; Tubbs, R Shane; Oakes, W Jerry
2017-01-01
Chiari I malformation can be due to a multitude of etiologies such as craniosynostosis or hydrocephalus. A posterior fossa extra-axial cyst (PFEAC) appears to be an extremely rare cause of this form of hindbrain herniation. Herein, we report a case of PFEAC that presented with no Chiari I malformation and then presented months later with a significant Chiari I malformation. Following shunt placement of a PFEAC, striking reversal of the Chiari malformation as well as reconstitution of the cerebellum was noted. Patients with PFEAC might develop a Chiari I malformation and this might be treated with shunting of the PFEAC alone.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Woodman, B.W.; Begley, J.A.; Brown, S.D.
1995-12-01
The analysis of the issue of upper bundle axial ODSCC as it apples to steam generator tube structural integrity in Unit 1 at the Palo Verde Nuclear generating Station is presented in this study. Based on past inspection results for Units 2 and 3 at Palo Verde, the detection of secondary side stress corrosion cracks in the upper bundle region of Unit 1 may occur at some future date. The following discussion provides a description and analysis of the probability of axial ODSCC in Unit 1 leading to the exceedance of Regulatory Guide 1.121 structural limits. The probabilities of structuralmore » limit exceedance are estimated as function of run time using a conservative approach. The chosen approach models the historical development of cracks, crack growth, detection of cracks and subsequent removal from service and the initiation and growth of new cracks during a given cycle of operation. Past performance of all Palo Verde Units as well as the historical performance of other steam generators was considered in the development of cracking statistics for application to Unit 1. Data in the literature and Unit 2 pulled tube examination results were used to construct probability of detection curves for the detection of axial IGSCC/IGA using an MRPC (multi-frequency rotating panake coil) eddy current probe. Crack growth rates were estimated from Unit 2 eddy current inspection data combined with pulled tube examination results and data in the literature. A Monte-Carlo probabilistic model is developed to provide an overall assessment of the risk of Regulatory Guide exceedance during plant operation.« less
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Chen, Jianfeng; Liu, Guangli; Ma, Chengfu; Zhao, Gang; Du, Wenqiang; Zhu, Wulin; Chu, Jiaru
2017-06-01
Recently, interactions between one-dimensional structural stiffness of physical micro environments and cell biological process have been widely studied. However in previous studies, the influence of structural stiffness on biological process was coupled with the influence of micro fiber curvature. Therefore decoupling the influences of fiber curvature and structural stiffness on cell biological process is of prime importance. In this study, we proposed a novel cell culture substrate comprised of silicon nitride bridges whose structure stiffness can be regulated by altering the axial residual stress without changing material and geometry properties. Both theoretical calculations and finite element simulations were performed to study the influence of residual stress on structure stiffness of bridges. Then multi-positions AFM bending tests were implemented to measure local stiffness of a single micro bridge so as to verify our predictions. NIH/3T3 mouse fibroblast cells were cultured on our substrates to examine the feasibility of the substrate application for investigating cellular response to microenvironment with variable stiffness. The results showed that cells on the edge region near bridge ends were more spread, elongated and better aligned along the bridge axial direction than those on the bridge center region. The results suggest that cells can sense and respond to the differences of stiffness and stiffness gradient between the edge and the center region of the bridges, which makes this kind of substrates can be applied in some biomedical fields, such as cell migration and wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.
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Song, Hyun Beom; Jung, Bong-Kwang; Kim, Jin Hyoung; Lee, Young-Ha; Choi, Min-Ho; Kim, Jeong Hun
2018-06-02
The conversion of tachyzoites into bradyzoites is a way for Toxoplasma gondii to establish a chronic and asymptomatic infection and achieve lifelong persistence in the host. The bradyzoites form tissue cysts in the retina, but not much is known about the horizontal distribution of the cysts or their interactions with glial cells in the retina. A chronic ocular toxoplasmosis model was induced by per oral administration of T. gondii Me49 strain cysts to BALB/c mice. Two months after the infection, retinas were flat-mounted and immunostained to detect cysts, ganglion cells, Müller cells, astrocytes, and microglial cells, followed by observation under fluorescence and confocal microscope. The horizontal distribution showed a rather clustered pattern, but the clusters were not restricted to certain location of the retina. Axial distribution was confined to the inner retina, mostly in ganglion cell layer or the inner plexiform layer. Both ganglion cells, a type of retinal neurons, and Müller cells, predominant retinal glial cells, could harbor cysts. The cysts were spatially separated from astrocytes, the most abundant glial cells in the ganglion cell layer, while close spatial distribution of microglial cells was observed in two thirds of retinal cysts. In this study, we demonstrated that the retinal cysts were not evenly distributed horizontally and were confined to the inner retina axially. Both neurons and one type of glial cells could harbor cysts, and topographic analysis of other glial cells suggests role of microglial cells in chronic ocular toxoplasmosis.
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Schwarzer, Caroline; Esteves, Telma Cristina; Araúzo-Bravo, Marcos J; Le Gac, Séverine; Nordhoff, Verena; Schlatt, Stefan; Boiani, Michele
2012-09-01
Do different human ART culture protocols prepare embryos differently for post-implantation development? The type of ART culture protocol results in distinct cellular and molecular phenotypes in vitro at the blastocyst stage as well as subsequently during in vivo development. It has been reported that ART culture medium affects human development as measured by gestation rates and birthweights. However, due to individual variation across ART patients, it is not possible as yet to pinpoint a cause-effect relationship between choice of culture medium and developmental outcome. In a prospective study, 13 human ART culture protocols were compared two at a time against in vivo and in vitro controls. Superovulated mouse oocytes were fertilized in vivo using outbred and inbred mating schemes. Zygotes were cultured in medium or in the oviduct and scored for developmental parameters 96 h later. Blastocysts were either analyzed or transferred into fosters to measure implantation rates and fetal development. In total, 5735 fertilized mouse oocytes, 1732 blastocysts, 605 fetuses and 178 newborns were examined during the course of the study (December 2010-December 2011). Mice of the B6C3F1, C57Bl/6 and CD1 strains were used as oocyte donors, sperm donors and recipients for embryo transfer, respectively. In vivo fertilized B6C3F1 oocytes were allowed to cleave in 13 human ART culture protocols compared with mouse oviduct and optimized mouse medium (KSOM(aa)). Cell lineage composition of resultant blastocysts was analyzed by immunostaining and confocal microscopy (trophectoderm, Cdx2; primitive ectoderm, Nanog; primitive endoderm, Sox17), global gene expression by microarray analysis, and rates of development to midgestation and to term. Mouse zygotes show profound variation in blastocyst (49.9-91.9%) and fetal (15.7-62.0%) development rates across the 13 ART culture protocols tested (R(2)= 0.337). Two opposite protocols, human tubal fluid/multiblast (high fetal rate) and ISM1/ISM2 (low fetal rate), were analyzed in depth using outbred and inbred fertilization schemes. Resultant blastocysts show imbalances of cell lineage composition; culture medium-specific deviation of gene expression (38 genes, ≥ 4-fold) compared with the in vivo pattern; and produce different litter sizes (P ≤ 0.0076) after transfer into fosters. Confounding effects of subfertility, life style and genetic heterogeneity are reduced to a minimum in the mouse model compared with ART patients. This is an animal model study. Mouse embryo responses to human ART media are not transferable 1-to-1 to human development due to structural and physiologic differences between oocytes of the two species. Our data promote awareness that human ART culture media affect embryo development. Effects reported here in the mouse may apply also in human, because no ART medium presently available on the market has been optimized for human embryo development. The mouse embryo assay (MEA), which requires ART media to support at least 80% blastocyst formation, is in need of reform and should be extended to include post-implantation development.
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NASA Astrophysics Data System (ADS)
McBeck, J.; Kobchenko, M.; Hall, S.; Tudisco, E.; Cordonnier, B.; Renard, F.
2017-12-01
Previous studies have identified compaction bands primarily within sandstones, and in fewer instances, within other porous rocks and sediments. Using Digital Volume Correlation (DVC) of X-ray microtomography scans, we find evidence of localized zones of high axial contraction that form tabular structures sub-perpendicular to maximum compression, σ1, in Green River shale. To capture in situ strain localization throughout loading, two shale cores were deformed in the HADES triaxial deformation apparatus installed on the X-ray microtomography beamline ID19 at the European Synchrotron Radiation Facility. In these experiments, we increase σ1 in increments of two MPa, with constant confining pressure (20 MPa), until the sample fails in macroscopic shear. After each stress step, a 3D image of the sample inside the rig is acquired at a voxel resolution of 6.5 μm. The evolution of lower density regions within 3D reconstructions of linear attenuation coefficients reveal the development of fractures that fail with some opening. If a fracture produces negligible dilation, it may remain undetected in image segmentation of the reconstructions. We use the DVC software TomoWarp2 to identify undetected fractures and capture the 3D incremental displacement field between each successive pair of microtomography scans acquired in each experiment. The corresponding strain fields reveal localized bands of high axial contraction that host minimal shear strain, and thus match the kinematic definition of compaction bands. The bands develop sub-perpendicular to σ1 in the two samples in which pre-existing bedding laminations were oriented parallel and perpendicular to σ1. As the shales deform plastically toward macroscopic shear failure, the number of bands and axial contraction within the bands increase, while the spacing between the bands decreases. Compaction band development accelerates the rate of overall axial contraction, increasing the mean axial contraction throughout the sample, and strengthens the shale sufficiently to localize shear faults. These results are critical to robust assessment of deformation patterns in shale rocks in contexts such as nuclear waste storage, hydrocarbon recovery and groundwater access.
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Immunologic applications of conditional gene modification technology in the mouse.
Sharma, Suveena; Zhu, Jinfang
2014-04-02
Since the success of homologous recombination in altering mouse genome and the discovery of Cre-loxP system, the combination of these two breakthroughs has created important applications for studying the immune system in the mouse. Here, we briefly summarize the general principles of this technology and its applications in studying immune cell development and responses; such implications include conditional gene knockout and inducible and/or tissue-specific gene over-expression, as well as lineage fate mapping. We then discuss the pros and cons of a few commonly used Cre-expressing mouse lines for studying lymphocyte development and functions. We also raise several general issues, such as efficiency of gene deletion, leaky activity of Cre, and Cre toxicity, all of which may have profound impacts on data interpretation. Finally, we selectively list some useful links to the Web sites as valuable mouse resources. Copyright © 2014 John Wiley & Sons, Inc.
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Analysis of Mouse Growth Plate Development
Mangiavini, Laura; Merceron, Christophe; Schipani, Ernestina
2016-01-01
To investigate skeletal development, pathophysiological mechanisms of cartilage and bone disease, and eventually assess innovative treatments, the mouse is a very important resource. During embryonic development, mesenchymal condensations are formed, and cells within these mesenchymal condensations either directly differentiate into osteoblasts and give origin to intramembranous bone, or differentiate into chondrocytes and form a cartilaginous anlage. The cartilaginous anlage or fetal growth plate is then replaced with bone. This process is also called endochondral bone development, and it is responsible for the generation of most of our skeleton. In this Review, we will discuss in detail the most common in vivo and in vitro techniques our laboratory is currently using for the analysis of the mouse fetal growth plate during development. PMID:26928664
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Δ(1232) axial charge and form factors from lattice QCD.
Alexandrou, Constantia; Gregory, Eric B; Korzec, Tomasz; Koutsou, Giannis; Negele, John W; Sato, Toru; Tsapalis, Antonios
2011-09-30
We present the first calculation on the Δ axial vector and pseudoscalar form factors using lattice QCD. Two Goldberger-Treiman relations are derived and examined. A combined chiral fit is performed to the nucleon axial charge, N to Δ axial transition coupling constant and Δ axial charge.
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Generation of a mouse model for studying the role of upregulated RTEL1 activity in tumorigenesis.
Wu, Xiaoli; Sandhu, Sumit; Nabi, Zinnatun; Ding, Hao
2012-10-01
Regulator of telomere length 1 (RTEL1) is a DNA helicase protein that has been demonstrated to be required for the maintenance of telomere length and genomic stability. It has also been found to be essential for DNA homologous recombination during DNA repairing. Human RTEL1 genomic locus (20q13.3) is frequently amplified in multiple types of human cancers, including hepatocellular carcinoma and gastrointestinal tract tumors, indicating that upregulated RTEL1 activity could be important for tumorigenesis. In this study, we have developed a conditional transgenic mouse model that overexpress mouse Rtel1 in a Cre-excision manner. By crossing with a ubiquitous Cre mouse line, we further demonstrated that these established Rtel1 conditional transgenic mice allow to efficiently and highly express a functional Rtel1 that is able to rescue the embryonic defects of Rtel1 null mouse allele. Furthermore, we demonstrated that more than 70% transgenic mice that widely overexpress Rtel1 developed liver tumors that recapitulate many malignant features of human hepatocellular carcinoma (HCC). Our work not only generated a valuable mouse model for determining the role of RTEL1 in the development of cancers, but also provided the first genetic evidence to support that amplification of RTEL1, as observed in several types of human cancers, is tumorigenic.
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Axial pain after posterior cervical spine surgery: a systematic review.
Wang, Shan-Jin; Jiang, Sheng-Dan; Jiang, Lei-Sheng; Dai, Li-Yang
2011-02-01
Posterior operative approach has been the standard treatment for cervical compressive myelopathy, and axial pain after laminoplasty or laminectomy as a postoperative complication is now gradually receiving more and more attention. The objective of this study was to provide a systematic review of the current understanding of axial pain after cervical laminoplasty and laminectomy, and summarize clinical features, influence factors and preventive measures of axial pain after posterior decompressive surgery based on a review of literature published in the English language. Axial pain distributes over nuchal, periscapular and shoulder regions. Posterior surgery is not the major cause of axial pain, but axial pain can be worsened by the procedure. There are many clinical factors that influence postoperative axial pain such as age, preoperative axial pain, different surgical technique and postoperative management, but most of them are still controversial. Several surgical modifications have been innovated to reduce axial pain. Less invasive surgery, reconstruction of the extensor musculature, avoiding detachment of the semispinalis cervicis muscle and early removal of external immobilization have proved to be effective. Axial pain is under the influence of multiple factors, so comprehensive methods are required to reduce and avoid the postoperative axial pain. Because of methodological shortcomings in publications included in this systematic review, different results from different studies may be produced due to differences in study design, evaluation criteria, sample size, and incidence or severity of axial pain. More high-quality studies are necessary for drawing more reliable and convincing conclusions.
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Diagnostic developments for velocity and temperature measurements in uni-element rocket environments
NASA Astrophysics Data System (ADS)
Philippart, Kenneth D.
1995-08-01
Velocity and temperature measurements were taken within a uni-element rocket combustion chamber for hydrogen-oxygen propellants using laser Doppler velocimetry, thermocouples, and a thermocouple-based temperature rake developed for this effort. Velocity and turbulence profiles were obtained for firings with a gaseous oxygen (GO2)/gaseous hydrogen (GH2) coaxial shear injector at axial locations of 1.6 mm (0.063 in.), 6.4 mm (0.25 in.), 12.7 mm (0.5 in.), 25.4 mm (1 in.) and 50.8 mm (2 in.). Aluminum oxide particles of various sizes seeded the flow in an attempt to explain the discrepancies. While cold-flow simulations were promising, hot-fire results for the various particles were virtually identical and still lower than earlier data. The hot-firings were self-consistent and question the reproducibility of the previous data. Velocity measurements were made closer to the injector than the preceding work. Asymmetries were noted in all profiles. The shear layer displayed high turbulence levels. The central flow near the injector resembled turbulent pipe flow. Recirculation zones existed at the chamber walls and became smaller as the flow evolved downstream. The combusting flow region expanded with increasing axial distance. A thermocouple-instrumented coaxial injector was fired with GO2/GH2 propellants. The injector exit plane boundary conditions were determined. The feasibility of a thermocouple-based temperature rake was established. Tests at three axial positions for air/GM2 firings revealed asymmetric profiles. Temperatures increased with increasing axial distance.
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White Matter Microstructure in Transsexuals and Controls Investigated by Diffusion Tensor Imaging
Kranz, Georg S.; Hahn, Andreas; Kaufmann, Ulrike; Küblböck, Martin; Hummer, Allan; Ganger, Sebastian; Seiger, Rene; Winkler, Dietmar; Swaab, Dick F.; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert
2015-01-01
Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects’ sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development. PMID:25392513
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Design and Performance Checks of the NPL Axial Heat Flow Apparatus
NASA Astrophysics Data System (ADS)
Wu, J.; Clark, J.; Stacey, C.; Salmon, D.
2015-03-01
This paper describes the design and performance checks of the NPL axial heat flow apparatus developed at the National Physical Laboratory for measurement of thermal conductivity. This apparatus is based on an absolute steady-state technique and is suitable for measuring specimens with thermal conductivities in the range from to and at temperatures between and . A uniform heat flow is induced in a cylindrical bar-shaped specimen that is firmly clamped between a guarded heater unit at the top and a water-cooled base. Heat is supplied at a known rate at the top end of the specimen by the heater unit and constrained to flow axially through the specimen by a surrounding edge-guard system, which is closely matched to the temperature gradient within the test specimen. The performance of this apparatus has been checked against existing NPL thermal-conductivity reference materials NPL 2S89 (based on Stainless Steel 310) and BSC Pure Iron (pure iron supplied by the British Steel Corporation with 99.96 % purity). The measured data produced by the newly designed NPL axial heat flow apparatus agree with the reference data for NPL 2S89 within 2 % and with that of BSC Pure Iron to within 3 % at temperatures from to . This apparatus is being used to provide accurate measurements to industrial and academic organizations and has also been used to develop a new range of NPL reference materials for checking other experimental techniques and procedures for thermal-conductivity measurements.
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Neuronal Representation of Ultraviolet Visual Stimuli in Mouse Primary Visual Cortex
Tan, Zhongchao; Sun, Wenzhi; Chen, Tsai-Wen; Kim, Douglas; Ji, Na
2015-01-01
The mouse has become an important model for understanding the neural basis of visual perception. Although it has long been known that mouse lens transmits ultraviolet (UV) light and mouse opsins have absorption in the UV band, little is known about how UV visual information is processed in the mouse brain. Using a custom UV stimulation system and in vivo calcium imaging, we characterized the feature selectivity of layer 2/3 neurons in mouse primary visual cortex (V1). In adult mice, a comparable percentage of the neuronal population responds to UV and visible stimuli, with similar pattern selectivity and receptive field properties. In young mice, the orientation selectivity for UV stimuli increased steadily during development, but not direction selectivity. Our results suggest that, by expanding the spectral window through which the mouse can acquire visual information, UV sensitivity provides an important component for mouse vision. PMID:26219604
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Motion analysis study on sensitivity of finite element model of the cervical spine to geometry.
Zafarparandeh, Iman; Erbulut, Deniz U; Ozer, Ali F
2016-07-01
Numerous finite element models of the cervical spine have been proposed, with exact geometry or with symmetric approximation in the geometry. However, few researches have investigated the sensitivity of predicted motion responses to the geometry of the cervical spine. The goal of this study was to evaluate the effect of symmetric assumption on the predicted motion by finite element model of the cervical spine. We developed two finite element models of the cervical spine C2-C7. One model was based on the exact geometry of the cervical spine (asymmetric model), whereas the other was symmetric (symmetric model) about the mid-sagittal plane. The predicted range of motion of both models-main and coupled motions-was compared with published experimental data for all motion planes under a full range of loads. The maximum differences between the asymmetric model and symmetric model predictions for the principal motion were 31%, 78%, and 126% for flexion-extension, right-left lateral bending, and right-left axial rotation, respectively. For flexion-extension and lateral bending, the minimum difference was 0%, whereas it was 2% for axial rotation. The maximum coupled motions predicted by the symmetric model were 1.5° axial rotation and 3.6° lateral bending, under applied lateral bending and axial rotation, respectively. Those coupled motions predicted by the asymmetric model were 1.6° axial rotation and 4° lateral bending, under applied lateral bending and axial rotation, respectively. In general, the predicted motion response of the cervical spine by the symmetric model was in the acceptable range and nonlinearity of the moment-rotation curve for the cervical spine was properly predicted. © IMechE 2016.
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On the Limitations of Breakthrough Curve Analysis in Fixed-Bed Adsorption
NASA Technical Reports Server (NTRS)
Knox, James C.; Ebner, Armin D.; LeVan, M. Douglas; Coker, Robert F.; Ritter, James A.
2016-01-01
This work examined in detail the a priori prediction of the axial dispersion coefficient from available correlations versus obtaining it and also mass transfer information from experimental breakthrough data and the consequences that may arise when doing so based on using a 1-D axially dispersed plug flow model and its associated Danckwerts outlet boundary condition. These consequences mainly included determining the potential for erroneous extraction of the axial dispersion coefficient and/or the LDF mass transfer coefficient from experimental data, especially when non-plug flow conditions prevailed in the bed. Two adsorbent/adsorbate cases were considered, i.e., carbon dioxide and water vapor in zeolite 5A, because they both experimentally exhibited significant non-plug flow behavior, and the water-zeolite 5A system exhibited unusual concentration front sharpening that destroyed the expected constant pattern behavior (CPB) when modeled with the 1-D axially dispersed plug flow model. Overall, this work showed that it was possible to extract accurate mass transfer and dispersion information from experimental breakthrough curves using a 1-D axial dispersed plug flow model when they were measured both inside and outside the bed. To ensure the extracted information was accurate, the inside the bed breakthrough curves and their derivatives from the model were plotted to confirm whether or not the adsorbate/adsorbent system was exhibiting CPB or any concentration front sharpening near the bed exit. Even when concentration front sharpening was occurring with the water-zeolite 5A system, it was still possible to use the experimental inside and outside the bed breakthrough curves to extract fundamental mass transfer and dispersion information from the 1-D axial dispersed plug flow model based on the systematic methodology developed in this work.
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Liao, Donghua; Lottrup, Christian; Fynne, Lotte; McMahon, Barry P; Krogh, Klaus; Drewes, Asbjørn M; Zhao, Jingbo; Gregersen, Hans
2018-01-01
Background/Aims Efficient transport through the esophago-gastric junction (EGJ) requires synchronized circular and longitudinal muscle contraction of the esophagus including relaxation of the lower esophageal sphincter (LES). However, there is a scarcity of technology for measuring esophagus movements in the longitudinal (axial) direction. The aim of this study is to develop new analytical tools for dynamic evaluation of the length change and axial movement of the human LES based on the functional luminal imaging probe (FLIP) technology and to present normal signatures for the selected parameters. Methods Six healthy volunteers without hiatal hernia were included. Data were analyzed from stepwise LES distensions at 20, 30, and 40 mL bag volumes. The bag pressure and the diameter change were used for motion analysis in the LES. The cyclic bag pressure frequency was used to distinguish dynamic changes of the LES induced by respiration and secondary peristalsis. Results Cyclic fluctuations of the LES were evoked by respiration and isovolumetric distension, with phasic changes of bag pressure, diameter, length, and axial movement of the LES narrow zone. Compared to the respiration-induced LES fluctuations, peristaltic contractions increased the contraction pressure amplitude (P < 0.001), shortening (P < 0.001), axial movement (P < 0.001), and diameter change (P < 0.01) of the narrow zone. The length of the narrow zone shortened as function of the pressure increase. Conclusions FLIP can be used for evaluation of dynamic length changes and axial movement of the human LES. The method may shed light on abnormal longitudinal muscle activity in esophageal disorders. PMID:29605981
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STUDIES ON THE DEVELOPMENT OF MOUSE EMBRYOS IN VITRO
BRINSTER, RALPH L.
2016-01-01
Summary The interactions of a number of possible energy sources for in-vitro development of 2-cell mouse ova were examined using statistical experimental designs. These experiments indicated that glucose has no beneficial effect on development when employed with the optimum concentration of pyruvate. Optimum concentrations of pyruvate and oxaloacetate when employed together resulted in a significantly lower response than when either compound was employed alone. It was found that the best medium for the development of 2-cell mouse ova into blastocysts contained 2·5 to 5·0 × 10−4 M-pyruvate + 2·5 to 5·0 × 10−2 M-lactate. PMID:5836270
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Weiss, S; Schaeffel, F
1993-04-01
1. If the eyes of young chickens are deprived of clear vision by translucent occluders, they develop considerable amounts of axial myopia within days. At the same time, the day time retinal dopamine levels drop by about 30%. Because the retinal dopamine levels of normally sighted chicks also differ diurnally and are low at night, we expected that the rate of axial eye growth might also differ during this time. 2. Unexpectedly, eyes grew in length only during the day (about 0.13 mm/day) and even shrank during the night (about -0.04 mm/night, average net growth +0.09 mm in 24 h). 3. If the eyes were occluded, they grew both during the day and also at night (average net growth: +0.16 mm in 24 h). Therefore, development of deprivation myopia was a result of the lack of growth inhibition at night rather than of excessive growth during the day when the actual deprivation occurred. 4. Suppression of dopaminergic retinal pathways by intravitreal injections of the neurotoxin 6-hydroxy-dopamine (6-OHDA) also suppressed development of deprivation myopia and it restored the growth inhibition at night. With normal visual experience, the drug had no effect on axial eye growth and refractive state. 5. Diurnal growth rhythms of the eyes disappeared under continuous light.(ABSTRACT TRUNCATED AT 250 WORDS)
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Multi-frequency Axial Transmission Bone Ultrasonometer
Tatarinov, Alexey; Egorov, Vladimir; Sarvazyan, Noune; Sarvazyan, Armen
2014-01-01
The last decade has seen a surge in the development of axial transmission QUS (Quantitative UltraSound) technologies for the assessment of long bones using various modes of acoustic waves. The condition of cortical bones and the development of osteoporosis are determined by numerous mechanical, micro-structural, and geometrical or macro-structural bone properties like hardness, porosity and cortical thickness. Such complex manifestations of osteoporosis require the evaluation of multiple parameters with different sensitivities to the various properties of bone that are affected by the disease. This objective may be achieved by using a multi-frequency ultrasonic examination The ratio of the acoustic wavelength to the cortical thickness can be changed by varying the frequency of the ultrasonic pulse propagating through the long bone that results in the change in composition of the induced wave comprised of a set of numerous modes of guided, longitudinal, and surface acoustic waves. The multi-frequency axial transmission QUS method developed at Artann Laboratories (Trenton, NJ) is implemented in the Bone Ultrasonic Scanner (BUSS). In the current version of the BUSS, a train of ultrasonic pulses with 60, 100, 400, 800, and 1200 kHz frequencies is used. The developed technology was tested on a variety of bone phantoms simulating normal, osteopenic, and osteoporotic bones. The results of this study confirm the feasibility of the multi-frequency approach for the assessment of the processes leading to osteoporosis. PMID:24206675
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Khairnar, Amit; Latta, Peter; Drazanova, Eva; Ruda-Kucerova, Jana; Szabó, Nikoletta; Arab, Anas; Hutter-Paier, Birgit; Havas, Daniel; Windisch, Manfred; Sulcova, Alexandra; Starcuk, Zenon; Rektorova, Irena
2015-11-01
Evidence suggests that accumulation and aggregation of α-synuclein contribute to the pathogenesis of Parkinson's disease (PD). The aim of this study was to evaluate whether diffusion kurtosis imaging (DKI) will provide a sensitive tool for differentiating between α-synuclein-overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. This experiment was designed as a proof-of-concept study and forms a part of a complex protocol and ongoing translational research. Nine-month-old TNWT-61 mice and age-matched WT littermates underwent behavioral tests to monitor motor impairment and MRI scanning using 9.4 Tesla system in vivo. Tract-based spatial statistics (TBSS) and the DKI protocol were used to compare the whole brain white matter of TNWT-61 and WT mice. In addition, region of interest (ROI) analysis was performed in gray matter regions such as substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus known to show higher accumulation of α-synuclein. For the ROI analysis, both DKI (6 b-values) protocol and conventional (2 b-values) diffusion tensor imaging (cDTI) protocol were used. TNWT-61 mice showed significant impairment of motor coordination. With the DKI protocol, mean, axial, and radial kurtosis were found to be significantly elevated, whereas mean and radial diffusivity were decreased in the TNWT-61 group compared to that in the WT controls with both TBSS and ROI analysis. With the cDTI protocol, the ROI analysis showed decrease in all diffusivity parameters in TNWT-61 mice. The current study provides evidence that DKI by providing both kurtosis and diffusivity parameters gives unique information that is complementary to cDTI for in vivo detection of pathological changes that underlie PD-like symptomatology in TNWT-61 mouse model of PD. This result is a crucial step in search for a candidate diagnostic biomarker with translational potential and relevance for human studies.
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Hamidi, Kordiyeh; Darvish, Jamshid; Matin, Maryam M; Javanmard, Athar Sadat; Kilpatrick, C William
2017-12-01
To date, no studies have examined the tooth formation during developmental stages of brush-tailed mice (Calomyscidae) and true hamsters (Cricetidae). Herein, we compared the timing of tooth morphogenesis and FGF4 expression pattern during development of the first lower molar in Goodwin's brush-tailed mouse, Calomyscus elburzensis with two other muroid rodents; the house mouse, Mus musculus (Muridae), model organism for tooth morphogenesis, and the golden hamster, Mesocricetus auratus which shares great similarities in cusp pattern with brush-tailed mice. All three species were bred in captivity and developing embryos were isolated at different embryonic days (E). Histological evaluation of lower molars was performed and spatiotemporal pattern of FGF4 expression was determined by immunohistochemistry. Results indicated that morphogenesis of the tooth cusps starts at the beginning of the cap stage of the first lower molar (E14 in house mouse, about E11.5 in golden hamster and E22 in Goodwin's brush-tailed mouse). During the cap to bell stage (E15 in house mouse, E12 in golden hamster and at about E24 in Goodwin's brush-tailed mouse), a decrease in the expression of FGF4 was observed in the mesenchyme, except for the cusp tips. According to our observations, the developmental process of the first lower molar formation in Goodwin's brush-tailed mouse began much later as compared with the other two species. Despite the differences in the temporal pattern of molar development between these three members of the same superfamily (Muroidea), the correlation in the expression of FGF4 with specific stages of tooth morphogenesis supported its regulatory function. Anat Rec, 300:2138-2149, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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LaRosa, Domenic A; Ellery, Stacey J; Snow, Rod J; Walker, David W; Dickinson, Hayley
2016-12-01
Maternal antenatal creatine supplementation protects the brain, kidney, and diaphragm against the effects of birth asphyxia in the spiny mouse. In this study, we examined creatine's potential to prevent damage to axial skeletal muscles. Pregnant spiny mice were fed a control or creatine-supplemented diet from mid-pregnancy, and 1 d before term (39 d), fetuses were delivered by c-section with or without 7.5 min of birth asphyxia. At 24 h or 33 ± 2 d after birth, gastrocnemius muscles were obtained for ex-vivo study of twitch-tension, muscle fatigue, and structural and histochemical analysis. Birth asphyxia significantly reduced cross-sectional area of all muscle fiber types (P < 0.05), and increased fatigue caused by repeated tetanic contractions at 24 h of age (P < 0.05). There were fewer (P < 0.05) Type I and IIa fibers and more (P < 0.05) Type IIb fibers in male gastrocnemius at 33 d of age. Muscle oxidative capacity was reduced (P < 0.05) in males at 24 h and 33 d and in females at 24 h only. Maternal creatine treatment prevented all asphyxia-induced changes in the gastrocnemius, improved motor performance. This study demonstrates that creatine loading before birth protects the muscle from asphyxia-induced damage at birth.
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PET performance evaluation of MADPET4: a small animal PET insert for a 7 T MRI scanner.
Omidvari, Negar; Cabello, Jorge; Topping, Geoffrey; Schneider, Florian R; Paul, Stephan; Schwaiger, Markus; Ziegler, Sibylle I
2017-11-01
MADPET4 is the first small animal PET insert with two layers of individually read out crystals in combination with silicon photomultiplier technology. It has a novel detector arrangement, in which all crystals face the center of field of view transaxially. In this work, the PET performance of MADPET4 was evaluated and compared to other preclinical PET scanners using the NEMA NU 4 measurements, followed by imaging a mouse-size hot-rod resolution phantom and two in vivo simultaneous PET/MRI scans in a 7 T MRI scanner. The insert had a peak sensitivity of 0.49%, using an energy threshold of 350 keV. A uniform transaxial resolution was obtained up to 15 mm radial offset from the axial center, using filtered back-projection with single-slice rebinning. The measured average radial and tangential resolutions (FWHM) were 1.38 mm and 1.39 mm, respectively. The 1.2 mm rods were separable in the hot-rod phantom using an iterative image reconstruction algorithm. The scatter fraction was 7.3% and peak noise equivalent count rate was 15.5 kcps at 65.1 MBq of activity. The FDG uptake in a mouse heart and brain were visible in the two in vivo simultaneous PET/MRI scans without applying image corrections. In conclusion, the insert demonstrated a good overall performance and can be used for small animal multi-modal research applications.
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Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model.
Komla-Ebri, Davide; Dambroise, Emilie; Kramer, Ina; Benoist-Lasselin, Catherine; Kaci, Nabil; Le Gall, Cindy; Martin, Ludovic; Busca, Patricia; Barbault, Florent; Graus-Porta, Diana; Munnich, Arnold; Kneissel, Michaela; Di Rocco, Federico; Biosse-Duplan, Martin; Legeai-Mallet, Laurence
2016-05-02
Achondroplasia (ACH) is the most frequent form of dwarfism and is caused by gain-of-function mutations in the fibroblast growth factor receptor 3-encoding (FGFR3-encoding) gene. Although potential therapeutic strategies for ACH, which aim to reduce excessive FGFR3 activation, have emerged over many years, the use of tyrosine kinase inhibitor (TKI) to counteract FGFR3 hyperactivity has yet to be evaluated. Here, we have reported that the pan-FGFR TKI, NVP-BGJ398, reduces FGFR3 phosphorylation and corrects the abnormal femoral growth plate and calvaria in organ cultures from embryos of the Fgfr3Y367C/+ mouse model of ACH. Moreover, we demonstrated that a low dose of NVP-BGJ398, injected subcutaneously, was able to penetrate into the growth plate of Fgfr3Y367C/+ mice and modify its organization. Improvements to the axial and appendicular skeletons were noticeable after 10 days of treatment and were more extensive after 15 days of treatment that started from postnatal day 1. Low-dose NVP-BGJ398 treatment reduced intervertebral disc defects of lumbar vertebrae, loss of synchondroses, and foramen-magnum shape anomalies. NVP-BGJ398 inhibited FGFR3 downstream signaling pathways, including MAPK, SOX9, STAT1, and PLCγ, in the growth plates of Fgfr3Y367C/+ mice and in cultured chondrocyte models of ACH. Together, our data demonstrate that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH.
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PET performance evaluation of MADPET4: a small animal PET insert for a 7 T MRI scanner
NASA Astrophysics Data System (ADS)
Omidvari, Negar; Cabello, Jorge; Topping, Geoffrey; Schneider, Florian R.; Paul, Stephan; Schwaiger, Markus; Ziegler, Sibylle I.
2017-11-01
MADPET4 is the first small animal PET insert with two layers of individually read out crystals in combination with silicon photomultiplier technology. It has a novel detector arrangement, in which all crystals face the center of field of view transaxially. In this work, the PET performance of MADPET4 was evaluated and compared to other preclinical PET scanners using the NEMA NU 4 measurements, followed by imaging a mouse-size hot-rod resolution phantom and two in vivo simultaneous PET/MRI scans in a 7 T MRI scanner. The insert had a peak sensitivity of 0.49%, using an energy threshold of 350 keV. A uniform transaxial resolution was obtained up to 15 mm radial offset from the axial center, using filtered back-projection with single-slice rebinning. The measured average radial and tangential resolutions (FWHM) were 1.38 mm and 1.39 mm, respectively. The 1.2 mm rods were separable in the hot-rod phantom using an iterative image reconstruction algorithm. The scatter fraction was 7.3% and peak noise equivalent count rate was 15.5 kcps at 65.1 MBq of activity. The FDG uptake in a mouse heart and brain were visible in the two in vivo simultaneous PET/MRI scans without applying image corrections. In conclusion, the insert demonstrated a good overall performance and can be used for small animal multi-modal research applications.
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Maleke, Caroline; Konofagou, Elisa E
2010-01-01
In this study, the Harmonic Motion Imaging for Focused Ultrasound (HMIFU) technique is applied to monitor changes in mechanical properties of tissues during thermal therapy in a transgenic breast cancer mouse model in vivo. An HMIFU system, composed of a 4.5-MHz focused ultrasound (FUS) and a 3.3-MHz phased-array imaging transducer, was mechanically moved to image and ablate the entire tumor. The FUS transducer was driven by an amplitude-modulated (AM) signal at 15 Hz. The acoustic intensity ( I(spta)) was equal to 1050 W/cm(2) at the focus. A digital low-pass filter was used to filter out the spectrum of the FUS beam and its harmonics prior to displacement estimation. The resulting axial displacement was estimated using 1-D cross-correlation on the acquired RF signals. Results from two mice with eight lesions formed in each mouse (16 lesions total) showed that the average peak-to-peak displacement amplitude before and after lesion formation was respectively equal to 17.34 +/- 1.34 microm and 10.98 +/- 1.82 microm ( p < 0.001). Cell death was also confirmed by hematoxylin and eosin histology. HMI displacement can be used to monitor the relative tissue stiffness changes in real time during heating so that the treatment procedure can be performed in a time-efficient manner. The HMIFU system may, therefore, constitute a cost-efficient and reliable alternative for real-time monitoring of thermal ablation.
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NASA Astrophysics Data System (ADS)
Haddout, Y.; Essaghir, E.; Oubarra, A.; Lahjomri, J.
2017-12-01
Thermally developing laminar slip flow through a micropipe and a parallel plate microchannel, with axial heat conduction and uniform wall heat flux, is studied analytically by using a powerful method of self-adjoint formalism. This method results from a decomposition of the elliptic energy equation into a system of two first-order partial differential equations. The advantage of this method over other methods, resides in the fact that the decomposition procedure leads to a selfadjoint problem although the initial problem is apparently not a self-adjoint one. The solution is an extension of prior studies and considers a first order slip model boundary conditions at the fluid-wall interface. The analytical expressions for the developing temperature and local Nusselt number in the thermal entrance region are obtained in the general case. Therefore, the solution obtained could be extended easily to any hydrodynamically developed flow and arbitrary heat flux distribution. The analytical results obtained are compared for select simplified cases with available numerical calculations and they both agree. The results show that the heat transfer characteristics of flow in the thermal entrance region are strongly influenced by the axial heat conduction and rarefaction effects which are respectively characterized by Péclet and Knudsen numbers.
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Developmental Trajectory of Motor Deficits in Preschool Children with ADHD.
Sweeney, Kristie L; Ryan, Matthew; Schneider, Heather; Ferenc, Lisa; Denckla, Martha Bridge; Mahone, E Mark
2018-01-01
Motor deficits persisting into childhood (>7 years) are associated with increased executive and cognitive dysfunction, likely due to parallel neural circuitry. This study assessed the longitudinal trajectory of motor deficits in preschool children with ADHD, compared to typically developing (TD) children, in order to identify individuals at risk for anomalous neurological development. Participants included 47 children (21 ADHD, 26 TD) ages 4-7 years who participated in three visits (V1, V2, V3), each one year apart (V1=48-71 months, V2=60-83 months, V3=72-95 months). Motor variables assessed included speed (finger tapping and sequencing), total overflow, and axial movements from the Revised Physical and Neurological Examination for Subtle Signs (PANESS). Effects for group, visit, and group-by-visit interaction were examined. There were significant effects for group (favoring TD) for finger tapping speed and total axial movements, visit (performance improving with age for all 4 variables), and a significant group-by-visit interaction for finger tapping speed. Motor speed (repetitive finger tapping) and quality of axial movements are sensitive markers of anomalous motor development associated with ADHD in children as young as 4 years. Conversely, motor overflow and finger sequencing speed may be less sensitive in preschool, due to ongoing wide variations in attainment of these milestones.
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NASA Astrophysics Data System (ADS)
Haddout, Y.; Essaghir, E.; Oubarra, A.; Lahjomri, J.
2018-06-01
Thermally developing laminar slip flow through a micropipe and a parallel plate microchannel, with axial heat conduction and uniform wall heat flux, is studied analytically by using a powerful method of self-adjoint formalism. This method results from a decomposition of the elliptic energy equation into a system of two first-order partial differential equations. The advantage of this method over other methods, resides in the fact that the decomposition procedure leads to a selfadjoint problem although the initial problem is apparently not a self-adjoint one. The solution is an extension of prior studies and considers a first order slip model boundary conditions at the fluid-wall interface. The analytical expressions for the developing temperature and local Nusselt number in the thermal entrance region are obtained in the general case. Therefore, the solution obtained could be extended easily to any hydrodynamically developed flow and arbitrary heat flux distribution. The analytical results obtained are compared for select simplified cases with available numerical calculations and they both agree. The results show that the heat transfer characteristics of flow in the thermal entrance region are strongly influenced by the axial heat conduction and rarefaction effects which are respectively characterized by Péclet and Knudsen numbers.
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NASA Astrophysics Data System (ADS)
Velikovich, A. L.; Giuliani, J. L.; Clark, R. W.; Mikitchuk, D.; Kroupp, E.; Maron, Y.; Fisher, A.; Schmit, P. F.
2014-10-01
Recent progress in developing the MagLIF approach to pulsed-power driven inertial confinement fusion has stimulated the interest in observation and mitigation of the magnetic Rayleigh-Taylor instability (MRTI) of liners and Z-pinches imploded in an axial magnetic field. Theoretical analysis of these issues is particularly important because direct numerical simulation of the MRTI development is challenging due to intrinsically 3D helical structure of the fastest-growing modes. We review the analytical small-amplitude theory of the MRTI perturbation development and the weakly nonlinear theory of MRTI mode interaction, emphasizing basic physics, opportunity for 3D code verification against exact analytical solutions, and stabilization criteria. The theory is compared to the experimental results obtained at Weizmann Institute with gas-puff Z pinches and on the Z facility at Sandia with solid liners imploded in an axial magnetic field. Work supported by the US DOE/NNSA, and by the US-Israel Binational Science Foundation. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000.
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Yamamoto, Hiroaki; Shibahara, Shigeki
2016-01-01
Microphthalmia-associated transcription factor (Mitf) is a key regulator for differentiation of melanoblasts, precursors to melanocytes. The mouse homozygous for the black-eyed white (Mitfmi-bw) allele is characterized by the white-coat color and deafness with black eyes due to the lack of melanocytes. The Mitfmi-bw allele carries LINE-1, a retrotransposable element, which results in the Mitf deficiency. Here, we have established the black spotting mouse that was spontaneously arisen from the homozygous Mitfmi-bw mouse lacking melanocytes. The black spotting mouse shows multiple black patches on the white coat, with age-related graying. Importantly, each black patch also contains hair follicles lacking melanocytes, whereas the white-coat area completely lacks melanocytes. RT-PCR analyses of the pigmented patches confirmed that the LINE-1 insertion is retained in the Mitf gene of the black spotting mouse, thereby excluding the possibility of the somatic reversion of the Mitfmi-bw allele. The immunohistochemical analysis revealed that the staining intensity for beta-catenin was noticeably lower in hair follicles lacking melanocytes of the homozygous Mitfmi-bw mouse and the black spotting mouse, compared to the control mouse. In contrast, the staining intensity for beta-catenin and cyclin D1 was higher in keratinocytes of the black spotting mouse, compared to keratinocytes of the control mouse and the Mitfmi-bw mouse. Moreover, the keratinocyte layer appears thicker in the Mitfmi-bw mouse, with the overexpression of Ki-67, a marker for cell proliferation. We also show that the presumptive black spots are formed by embryonic day 15.5. Thus, the black spotting mouse provides the unique model to explore the molecular basis for the survival and death of developing melanoblasts and melanocyte stem cells in the epidermis. These results indicate that follicular melanocytes are responsible for maintaining the epidermal homeostasis; namely, the present study has provided evidence for the link between melanocyte development and the epidermal microenvironment. PMID:26930598
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Humanized Mouse Models for the Study of Human Malaria Parasite Biology, Pathogenesis, and Immunity.
Minkah, Nana K; Schafer, Carola; Kappe, Stefan H I
2018-01-01
Malaria parasite infection continues to inflict extensive morbidity and mortality in resource-poor countries. The insufficiently understood parasite biology, continuously evolving drug resistance and the lack of an effective vaccine necessitate intensive research on human malaria parasites that can inform the development of new intervention tools. Humanized mouse models have been greatly improved over the last decade and enable the direct study of human malaria parasites in vivo in the laboratory. Nevertheless, no small animal model developed so far is capable of maintaining the complete life cycle of Plasmodium parasites that infect humans. The ultimate goal is to develop humanized mouse systems in which a Plasmodium infection closely reproduces all stages of a parasite infection in humans, including pre-erythrocytic infection, blood stage infection and its associated pathology, transmission as well as the human immune response to infection. Here, we discuss current humanized mouse models and the future directions that should be taken to develop next-generation models for human malaria parasite research.
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Ducourthial, Guillaume; Leclerc, Pierre; Mansuryan, Tigran; Fabert, Marc; Brevier, Julien; Habert, Rémi; Braud, Flavie; Batrin, Renaud; Vever-Bizet, Christine; Bourg-Heckly, Geneviève; Thiberville, Luc; Druilhe, Anne; Kudlinski, Alexandre; Louradour, Frédéric
2015-01-01
We present a two-photon microendoscope capable of in vivo label-free deep-tissue high-resolution fast imaging through a very long optical fiber. First, an advanced light-pulse spectro-temporal shaping device optimally precompensates for linear and nonlinear distortions occurring during propagation within the endoscopic fiber. This enables the delivery of sub-40-fs duration infrared excitation pulses at the output of 5 meters of fiber. Second, the endoscopic fiber is a custom-made double-clad polarization-maintaining photonic crystal fiber specifically designed to optimize the imaging resolution and the intrinsic luminescence backward collection. Third, a miniaturized fiber-scanner of 2.2 mm outer diameter allows simultaneous second harmonic generation (SHG) and two-photon excited autofluorescence (TPEF) imaging at 8 frames per second. This microendoscope’s transverse and axial resolutions amount respectively to 0.8 μm and 12 μm, with a field-of-view as large as 450 μm. This microendoscope’s unprecedented capabilities are validated during label-free imaging, ex vivo on various fixed human tissue samples, and in vivo on an anesthetized mouse kidney demonstrating an imaging penetration depth greater than 300 μm below the surface of the organ. The results reported in this manuscript confirm that nonlinear microendoscopy can become a valuable clinical tool for real-time in situ assessment of pathological states. PMID:26673905
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The Adult Mouse Anatomical Dictionary: a tool for annotating and integrating data
Hayamizu, Terry F; Mangan, Mary; Corradi, John P; Kadin, James A; Ringwald, Martin
2005-01-01
We have developed an ontology to provide standardized nomenclature for anatomical terms in the postnatal mouse. The Adult Mouse Anatomical Dictionary is structured as a directed acyclic graph, and is organized hierarchically both spatially and functionally. The ontology will be used to annotate and integrate different types of data pertinent to anatomy, such as gene expression patterns and phenotype information, which will contribute to an integrated description of biological phenomena in the mouse. PMID:15774030
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Development of mechanical circulatory support devices in China.
Wang, Wei; Zhu, De-Ming; Ding, Wen-Xiang
2009-11-01
Myocardial dysfunction leading to low cardiac output syndrome is a common clinical pathophysiological state. Currently, the use of mechanical circulatory support (MCS) is an essential aspect of the treatment of patients with cardiac failure. Several groups in China are engaged in the design and development of MCS devices. These devices can be classified as pulsatile, rotary, and total artificial heart (TAH). There are two types of pulsatile pump, which are driven by air (pneumatic). One of these pumps, the Luo-Ye pump, has been used clinically for short-term support since 1998. The other is a push-plate left ventricular device, which has a variable rate mode. Various rotary devices are classified into axial and centrifugal pumps, depending on the impeller geometry. Most rotary pumps are based on the maglev principle, and some types have been used clinically. Others are still being studied in the laboratory or in animal experiments. Furthermore, certain types of total implantable pump, such as the UJS-III axial pump and the UJS-IV aortic valvo-pump, have been developed. Only one type of TAH has been developed in China. The main constituents of this artificial heart are two axial pumps, two reservoir tanks mimicking the right and left atria, flow meters, two pressure gauges, and a resistance adaptor. Although the development of mechanical assist devices in China is still in a nascent stage, a number of different types of MCS devices are currently being studied.
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Thuemmel, A E; Gwazdauskas, F C; Canseco, R S; Pearson, R E; Jochle, W
1991-06-01
Bovine morulae (d 6) were used to evaluate embryonic development in a deproteinized hemodialysate, agar embedding, and in the uterus of the immature mouse. Agar-embedded embryos were cultured in Ham's F-10 and 10% steer serum either (treatment 1) immediately after collection or (treatment 2) 24 h after storage in the uterus of the immature mouse. Unembedded embryos were cultured in Ham's F-10 containing (treatment 3) 10% steer serum, (treatment 4) 1% deproteinized hemodialysate CLB1107, or (treatment 5) 1% de-proteinized hemodialysate CLB1107 and 10% steer serum. A greater percentage of the embryos reached the hatched blastocyst stage after culture in treatments 1, 3, 4, and 5 (38.1, 34.6, 28.6, and 21.1%) than in treatment 2 (9.5%) in which embryos were stored in the immature mouse uterus for 24 h prior to in vitro culture. Final development scores for unembedded and agar-embedded embryos cultured in Ham's F-10 (5.5 +/- .3) and 10% steer serum (4.9 +/- .4) were similar and higher than those of embryos cultured in deproteinized hemodialysate CLB1107 (4.2 +/- .4), deproteinized hemodialysate CLB1107 and steer serum (4.2 +/- .4), or immature mouse uteri (3.4 +/- .4). It is concluded that deproteinized hemodialysate supplementation at 1% (vol/vol) failed to enhance embryonic development in vitro. Moreover, bovine morulae were unaffected by agar embedding and were able to develop to a limited extent following short-term storage in the uterus of the immature mouse.
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Designing Mouse Behavioral Tasks Relevant to Autistic-Like Behaviors
ERIC Educational Resources Information Center
Crawley, Jacqueline N.
2004-01-01
The importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e.,…
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Reste, Jelena; Zvagule, Tija; Kurjane, Natalja; Martinsone, Zanna; Martinsone, Inese; Seile, Anita; Vanadzins, Ivars
2015-01-01
Computer work is characterized by sedentary static workload with low-intensity energy metabolism. The aim of our study was to evaluate the dynamics of skin surface temperature in the hand during prolonged computer mouse work under different ergonomic setups. Digital infrared imaging of the right forearm and wrist was performed during three hours of continuous computer work (measured at the start and every 15 minutes thereafter) in a laboratory with controlled ambient conditions. Four people participated in the study. Three different ergonomic computer mouse setups were tested on three different days (horizontal computer mouse without mouse pad; horizontal computer mouse with mouse pad and padded wrist support; vertical computer mouse without mouse pad). The study revealed a significantly strong negative correlation between the temperature of the dorsal surface of the wrist and time spent working with a computer mouse. Hand skin temperature decreased markedly after one hour of continuous computer mouse work. Vertical computer mouse work preserved more stable and higher temperatures of the wrist (>30 °C), while continuous use of a horizontal mouse for more than two hours caused an extremely low temperature (<28 °C) in distal parts of the hand. The preliminary observational findings indicate the significant effect of the duration and ergonomics of computer mouse work on the development of hand hypothermia. PMID:26262633
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Reste, Jelena; Zvagule, Tija; Kurjane, Natalja; Martinsone, Zanna; Martinsone, Inese; Seile, Anita; Vanadzins, Ivars
2015-08-07
Computer work is characterized by sedentary static workload with low-intensity energy metabolism. The aim of our study was to evaluate the dynamics of skin surface temperature in the hand during prolonged computer mouse work under different ergonomic setups. Digital infrared imaging of the right forearm and wrist was performed during three hours of continuous computer work (measured at the start and every 15 minutes thereafter) in a laboratory with controlled ambient conditions. Four people participated in the study. Three different ergonomic computer mouse setups were tested on three different days (horizontal computer mouse without mouse pad; horizontal computer mouse with mouse pad and padded wrist support; vertical computer mouse without mouse pad). The study revealed a significantly strong negative correlation between the temperature of the dorsal surface of the wrist and time spent working with a computer mouse. Hand skin temperature decreased markedly after one hour of continuous computer mouse work. Vertical computer mouse work preserved more stable and higher temperatures of the wrist (>30 °C), while continuous use of a horizontal mouse for more than two hours caused an extremely low temperature (<28 °C) in distal parts of the hand. The preliminary observational findings indicate the significant effect of the duration and ergonomics of computer mouse work on the development of hand hypothermia.
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Caspase inhibition supports proper gene expression in ex vivo mouse limb cultures.
De Valck, D; Luyten, F P
2001-10-01
We standardized conditions for ex vivo mouse limb culture to study cartilage maturation and joint formation. We compared 12.5 d.p.c. mouse forelimbs that were cultured either mounted or freely rotating for up to 72 h. Limb outgrowth progressed ex vivo at a variable rate as compared to its development in vivo, spanning approximately 48 h. Although cartilage maturation and joint formation developed grossly normal, aberrant expression of skeletal marker genes was seen. Interestingly, no regression of the interdigital webs took place in mounted cultures, in contrast to limited webbing under freely rotating conditions. Caspase inhibition, by addition of zVAD-fmk to the culture medium of freely rotating limbs, supported proper gene expression associated with skeletal development, and prevented interdigital web regression. Taken together, a freely rotating ex vivo culture for mouse limb outgrowth that is combined with caspase inhibition provides a good model to study cartilage maturation and joint formation.
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A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer.
Betzler, Alexander M; Kochall, Susan; Blickensdörfer, Linda; Garcia, Sebastian A; Thepkaysone, May-Linn; Nanduri, Lahiri K; Muders, Michael H; Weitz, Jürgen; Reissfelder, Christoph; Schölch, Sebastian
2017-07-06
Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Genetically engineered mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in large organs such as the colon in which only a single tumor is desired. As a result, an immunocompetent, genetically engineered mouse model of colorectal cancer was developed which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor development is initiated by surgical, segmental infection of the distal colon with adeno-cre virus in compound conditionally mutant mice. The tumors can be easily detected and monitored via colonoscopy. We here describe the surgical technique of segmental adeno-cre infection of the colon, the surveillance of the tumor via high-resolution colonoscopy and present the resulting colorectal tumors.
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Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G
2013-09-01
Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic resonance imaging study to prospectively evaluate brain growth trajectories from infancy in children who develop autism spectrum disorder. The presence of excessive extra-axial fluid detected as early as 6 months and the lack of resolution by 24 months is a hitherto unreported brain anomaly in infants who later develop autism spectrum disorder. This is also the first magnetic resonance imaging evidence of brain enlargement in autism before age 2. These findings raise the potential for the use of structural magnetic resonance imaging to aid in the early detection of children at risk for autism spectrum disorder or other neurodevelopmental disorders.
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Tovmasyan, Artak; Weitner, Tin; Sheng, Huaxin; Lu, MiaoMiao; Rajic, Zrinka; Warner, David S.; Spasojevic, Ivan; Reboucas, Julio S.; Benov, Ludmil; Batinic-Haberle, Ines
2013-01-01
The different biological behavior of cationic Fe and Mn pyridylporphyrins in Escherichia coli and mouse studies prompted us to revisit and compare their chemistry. For that purpose the series of ortho and meta isomers of Fe(III) meso-tetrakis-N-alkylpyridylporphyrins, alkyl being methyl to n-octyl, were synthesized and characterized by elemental analysis, UV/vis spectroscopy, mass spectrometry, lipophilicity, protonation equilibria of axial waters, metal-centered reduction potential, E1/2 for MIIIP/MIIP redox couple (M = Fe, Mn, P=porphyrin), kcat for the catalysis of O2•− dismutation, stability towards peroxide-driven porphyrin oxidative degradation (produced in the catalysis of ascorbate oxidation by MP), ability to affect growth of SOD-deficient E. coli and toxicity to mice. Electron-deficiency of the metal site is modulated by the porphyrin ligand, which renders Fe(III) porphyrins ≥ 5 orders of magnitude more acidic than the analogous Mn(III) porphyrins, as revealed by the pKa1 of axially coordinated waters. The 5 log units difference in the acidity between the Mn and Fe sites in porphyrin translates into the predominance of tetracationic (OH)(H2O)FeP complexes relative to pentacationic (H2O)2MnP species at pH ~7.8. This is evidenced in large differences in the thermodynamic parameters - pKa of axial waters and E1/2 of MIII/MII redox couple. The presence of hydroxo ligand labilizes trans-axial water which results in higher reactivity of Fe- relative to Mn center. The differences in the catalysis of O2•− dismutation (log kcat) between Fe and Mn porphyrins is modest, 2.5-5-fold, due to predominantly outer-sphere, with partial inner-sphere character of two reaction steps. However, the rate constant for the inner-sphere H2O2-based porphyrin oxidative degradation is 18-fold larger for (OH)(H2O)FeP than for (H2O)2MnP. The in vivo consequences of the differences between the Fe- and Mn porphyrins were best demonstrated in SOD-deficient E. coli growth. Based on fairly similar log kcat(O2.− values, very similar effect on the growth of SOD-deficient E. coli was anticipated by both metalloporphyrins. Yet, while MnTE-2-PyP5+ was fully efficacious at ≥20 μM, the Fe analog, FeTE-2-PyP5+ supported SOD-deficient E. coli growth at 200-fold lower doses in the range of 0.1 to 1 μM. Moreover the pattern of SOD-deficient E. coli growth was different with Mn- and Fe porphyrins. Such results suggested different mode of action of these metalloporphyrins. Further exploration demonstrated that: (1) 0.1 μM FeTE-2-PyP5+ provided similar growth stimulation as 0.1 μM Fe salt, while 20 μM Mn salt provides no protection to E. coli; and (2) 1 μM Fe porphyrin is fully degraded by 12 hours in E. coli cytosol and growth medium; while Mn porphyrin is not. Stimulation of the aerobic growth of SOD-deficient E. coli by the Fe porphyrin is therefore due to iron acquisition. Our data suggest that in vivo, redox-driven degradation of Fe porphyrins resulting in Fe release plays a major role in their biological action. Possibly, iron reconstitutes enzymes bearing [4Fe-4S] clusters as active sites. Under same experimental conditions, (OH)(H2O)FePs do not cause mouse arterial hypotension, whereas (H2O)2MnPs do, which greatly limits the application of Mn porphyrins in vivo. PMID:23646875
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Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Toncheva, Greta; Yoshizumi, Terry T.; Frush, Donald P.
2011-01-01
Purpose: Radiation-dose awareness and optimization in CT can greatly benefit from a dose-reporting system that provides dose and risk estimates specific to each patient and each CT examination. As the first step toward patient-specific dose and risk estimation, this article aimed to develop a method for accurately assessing radiation dose from CT examinations. Methods: A Monte Carlo program was developed to model a CT system (LightSpeed VCT, GE Healthcare). The geometry of the system, the energy spectra of the x-ray source, the three-dimensional geometry of the bowtie filters, and the trajectories of source motions during axial and helical scans were explicitly modeled. To validate the accuracy of the program, a cylindrical phantom was built to enable dose measurements at seven different radial distances from its central axis. Simulated radial dose distributions in the cylindrical phantom were validated against ion chamber measurements for single axial scans at all combinations of tube potential and bowtie filter settings. The accuracy of the program was further validated using two anthropomorphic phantoms (a pediatric one-year-old phantom and an adult female phantom). Computer models of the two phantoms were created based on their CT data and were voxelized for input into the Monte Carlo program. Simulated dose at various organ locations was compared against measurements made with thermoluminescent dosimetry chips for both single axial and helical scans. Results: For the cylindrical phantom, simulations differed from measurements by −4.8% to 2.2%. For the two anthropomorphic phantoms, the discrepancies between simulations and measurements ranged between (−8.1%, 8.1%) and (−17.2%, 13.0%) for the single axial scans and the helical scans, respectively. Conclusions: The authors developed an accurate Monte Carlo program for assessing radiation dose from CT examinations. When combined with computer models of actual patients, the program can provide accurate dose estimates for specific patients. PMID:21361208
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Rat astrocytes are more supportive for mouse OPC self-renewal than mouse astrocytes in culture.
Cheng, Xuejun; Xie, Binghua; Qi, Jiajun; Zhao, Xiaofeng; Zhang, Zunyi; Qiu, Mengsheng; Yang, Junlin
2017-09-01
Mouse primary oligodendrocyte precursor cells (OPCs) are increasingly used to study the molecular mechanisms underlying the phenotype changes in oligodendrocyte differentiation and axonal myelination observed in transgenic or mutant mouse models. However, mouse OPCs are much more difficult to be isolated by the simple dissociation culture of brain tissues than their rat counterparts. To date, the mechanisms underlying the species difference in OPC preparation remain obscure. In this study, we showed that astrocytes from rats have a stronger effect than those from mouse in promoting OPC proliferation and survival in vitro. Mouse astrocytes displayed significantly weaker viability in culture and reduced potential in maintaining OPC self-renewal, as confirmed by culturing OPCs with conditioned media from rat or mouse astrocytes. These results explained the reason for why stratified cultures of OPCs and astrocytes are difficult to be achieved in mouse CNS tissues. Based on these findings, we adopted inactivated rat astrocytes as feeder cells to support the self-renewal of mouse cortical OPCs and preparation of high-purity mouse OPCs. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 907-916, 2017. © 2016 Wiley Periodicals, Inc.
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Roper, Jatin; Martin, Eric S; Hung, Kenneth E
2014-06-16
Preclinical models for colorectal cancer (CRC) are critical for translational biology and drug development studies to characterize and treat this condition. Mouse models of human cancer are particularly popular because of their relatively low cost, short life span, and ease of use. Genetically engineered mouse models (GEMMs) of CRC are engineered from germline or somatic modification of critical tumor suppressor genes and/or oncogenes that drive mutations in human disease. Detailed in this overview are the salient features of several useful colorectal cancer GEMMs and their value as tools for translational biology and preclinical drug development. Copyright © 2014 John Wiley & Sons, Inc.
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In utero imaging of mouse embryonic development with optical coherence tomography
NASA Astrophysics Data System (ADS)
Syed, Saba H.; Dickinson, Mary E.; Larin, Kirill V.; Larina, Irina V.
2011-03-01
Studying progression of congenital diseases in animal models can greatly benefit from live embryonic imaging Mouse have long served as a model of mammalian embryonic developmental processes, however, due to intra-uterine nature of mammalian development live imaging is challenging. In this report we present results on live mouse embryonic imaging in utero with Optical Coherence Tomography. Embryos from 12.5 through 17.5 days post-coitus (dpc) were studied through the uterine wall. In longitudinal studies, same embryos were imaged at developmental stages 13.5, 15.5 and 17.5 dpc. This study suggests that OCT can serve as a powerful tool for live mouse embryo imaging. Potentially this technique can contribute to our understanding developmental abnormalities associated with mutations, toxic drugs.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Labosky, P.A.; Sakaki, Hiroshi; Hogan, B.L.M.
1996-06-01
Members of the winged helix family of transcription factors are required for the normal embryonic development of the mouse. Using the interspecific backcross panel from The Jackson Laboratory, we have determined the chromosomal locations of four genes that encode winged helix containing proteins. Mf1 was assigned to mouse Chromosome 8, Mf2 to Chromosome 4, Mf3 to Chromosome 9, and Mf4 to Chromosome 13. Since Mf3 is located in a region of Chromosome 9 containing many well-characterized mouse mutations such as short ear (se), ashen (ash), and dilute (d), we have analyzed deletion mutants to determine the location of Mf3 moremore » precisely. 14 refs., 3 figs.« less
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Targeted Disruption of Mouse Yin Yang 1 Transcription Factor Results in Peri-Implantation Lethality
Donohoe, Mary E.; Zhang, Xiaolin; McGinnis, Lynda; Biggers, John; Li, En; Shi, Yang
1999-01-01
Yin Yang 1 (YY1) is a zinc finger-containing transcription factor and a target of viral oncoproteins. To determine the biological role of YY1 in mammalian development, we generated mice deficient for YY1 by gene targeting. Homozygosity for the mutated YY1 allele results in embryonic lethality in the mouse. YY1 mutants undergo implantation and induce uterine decidualization but rapidly degenerate around the time of implantation. A subset of YY1 heterozygote embryos are developmentally retarded and exhibit neurulation defects, suggesting that YY1 may have additional roles during later stages of mouse embryogenesis. Our studies demonstrate an essential function for YY1 in the development of the mouse embryo. PMID:10490658
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Defining the molecular pathologies in cloaca malformation: similarities between mouse and human
Runck, Laura A.; Method, Anna; Bischoff, Andrea; Levitt, Marc; Peña, Alberto; Collins, Margaret H.; Gupta, Anita; Shanmukhappa, Shiva; Wells, James M.; Guasch, Géraldine
2014-01-01
Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh) signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations in humans. Moreover, deranged Shh and BMP signaling is correlated with severe anorectal malformations in both mouse and humans. PMID:24524909
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Rayhan, Rakib U; Stevens, Benson W; Timbol, Christian R; Adewuyi, Oluwatoyin; Walitt, Brian; VanMeter, John W; Baraniuk, James N
2013-01-01
Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction. Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs. Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis. The right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness.
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Silva, P; Crozier, S; Veidt, M; Pearcy, M J
2005-07-01
A hydrogel intervertebral disc (IVD) model consisting of an inner nucleus core and an outer anulus ring was manufactured from 30 and 35% by weight Poly(vinyl alcohol) hydrogel (PVA-H) concentrations and subjected to axial compression in between saturated porous endplates at 200 N for 11 h, 30 min. Repeat experiments (n=4) on different samples (N=2) show good reproducibility of fluid loss and axial deformation. An axisymmetric nonlinear poroelastic finite element model with variable permeability was developed using commercial finite element software to compare axial deformation and predicted fluid loss with experimental data. The FE predictions indicate differential fluid loss similar to that of biological IVDs, with the nucleus losing more water than the anulus, and there is overall good agreement between experimental and finite element predicted fluid loss. The stress distribution pattern indicates important similarities with the biological IVD that includes stress transference from the nucleus to the anulus upon sustained loading and renders it suitable as a model that can be used in future studies to better understand the role of fluid and stress in biological IVDs.
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Almodovar, Raquel; Torre Alonso, Juan C; Batlle, Enrique; Castillo, Concepción; Collantes-Estevez, Eduardo; de Miguel, Eugenio; González, Senén; Gratacós, Jordi; Hernández, Azucena; Juanola, Xavier; Linares, Luis F; Moreno, Manuel J; Moreno, Mireia; Navarro-Compán, Victoria; Rodríguez Lozano, Carlos; Sanz, Jesus; Sellas, Agustí; Loza, Estíbaliz; Zarco, Pedro
To standardize clinical evaluation of patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) using a checklist. Qualitative study that included: 1) nominal group (18 experts); 2) literature reviews of measures used in the assessment of patients with axial SpA or PsA; and 3) focus groups, one with rheumatologists and another with patients, organized to become familiar with their opinion on medical assistance. Taking this into account, the experts selected the measures to be included in the checklist based on their relevance, feasibility, and the outcome type. The checklist includes measures for the evaluation of personal history, physical examination, activity and function, laboratory tests, imaging studies and treatments. It also defines risk factors of radiographic progression, predictors of the response to biological therapies, and comprises measures of excellence. This checklist for patients with axial SpA and PsA could help standardize daily clinical practice and improve clinical management and patient prognosis. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
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Experimental Assessment of the Hydraulics of a Miniature Axial-Flow Left Ventricular Assist Device
NASA Astrophysics Data System (ADS)
Smith, P. Alex; Cohn, William; Metcalfe, Ralph
2017-11-01
A minimally invasive partial-support left ventricular assist device (LVAD) has been proposed with a flow path from the left atrium to the arterial system to reduce left ventricular stroke work. In LVAD design, peak and average efficiency must be balanced over the operating range to reduce blood trauma. Axial flow pumps have many geometric parameters. Until recently, testing all these parameters was impractical, but modern 3D printing technology enables multi-parameter studies. Following theoretical design, experimental hydraulic evaluation in steady state conditions examines pressure, flow, pressure-flow gradient, efficiency, torque, and axial force as output parameters. Preliminary results suggest that impeller blades and stator vanes with higher inlet angles than recommended by mean line theory (MLT) produce flatter gradients and broader efficiency curves, increasing compatibility with heart physiology. These blades also produce less axial force, which reduces bearing load. However, they require slightly higher torque, which is more demanding of the motor. MLT is a low order, empirical model developed on large pumps. It does not account for the significant viscous losses in small pumps like LVADs. This emphasizes the importance of experimental testing for hydraulic design. Roderick D MacDonald Research Fund.
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The New Performance Calculation Method of Fouled Axial Flow Compressor
Xu, Hong
2014-01-01
Fouling is the most important performance degradation factor, so it is necessary to accurately predict the effect of fouling on engine performance. In the previous research, it is very difficult to accurately model the fouled axial flow compressor. This paper develops a new performance calculation method of fouled multistage axial flow compressor based on experiment result and operating data. For multistage compressor, the whole compressor is decomposed into two sections. The first section includes the first 50% stages which reflect the fouling level, and the second section includes the last 50% stages which are viewed as the clean stage because of less deposits. In this model, the performance of the first section is obtained by combining scaling law method and linear progression model with traditional stage stacking method; simultaneously ambient conditions and engine configurations are considered. On the other hand, the performance of the second section is calculated by averaged infinitesimal stage method which is based on Reynolds' law of similarity. Finally, the model is successfully applied to predict the 8-stage axial flow compressor and 16-stage LM2500-30 compressor. The change of thermodynamic parameters such as pressure ratio, efficiency with the operating time, and stage number is analyzed in detail. PMID:25197717
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One-step production of multilayered microparticles by tri-axial electro-flow focusing
NASA Astrophysics Data System (ADS)
Si, Ting; Feng, Hanxin; Li, Yang; Luo, Xisheng; Xu, Ronald
2014-03-01
Microencapsulation of drugs and imaging agents in the same carrier is of great significance for simultaneous detection and treatment of diseases. In this work, we have developed a tri-axial electro-flow focusing (TEFF) device using three needles with a novel concentric arrangement to one-step form multilayered microparticles. The TEFF process can be characterized as a multi-fluidic compound cone-jet configuration in the core of a high-speed coflowing gas stream under an axial electric field. The tri-axial liquid jet eventually breaks up into multilayered droplets. To validate the method, the effect of main process parameters on characteristics of the cone and the jet has been studied experimentally. The applied electric field can dramatically promote the stability of the compound cone and enhance the atomization of compound liquid jets. Microparticles with both three-layer, double-layer and single-layer structures have been obtained. The results show that the TEFF technique has great benefits in fabricating multilayered microparticles at smaller scales. This method will be able to one-step encapsulate multiple therapeutic and imaging agents for biomedical applications such as multi-modal imaging, drug delivery and biomedicine.
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NASA Astrophysics Data System (ADS)
Li, ZhaoYu; Chen, Tao; Yan, GuangQing
2016-10-01
A new method for determining the central axial orientation of a two-dimensional coherent magnetic flux rope (MFR) via multipoint analysis of the magnetic-field structure is developed. The method is devised under the following geometrical assumptions: (1) on its cross section, the structure is left-right symmetric; (2) the projected structure velocity is vertical to the line of symmetry. The two conditions can be naturally satisfied for cylindrical MFRs and are expected to be satisfied for MFRs that are flattened within current sheets. The model test demonstrates that, for determining the axial orientation of such structures, the new method is more efficient and reliable than traditional techniques such as minimum-variance analysis of the magnetic field, Grad-Shafranov (GS) reconstruction, and the more recent method based on the cylindrically symmetric assumption. A total of five flux transfer events observed by Cluster are studied using the proposed approach, and the application results indicate that the observed structures, regardless of their actual physical properties, fit the assumed geometrical model well. For these events, the inferred axial orientations are all in excellent agreement with those obtained using the multi-GS reconstruction technique.
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Sutherland, Daniel R; Kinsman, Luke; Angiolini, Stuart M; Rosair, Georgina M; Lee, Ai-Lan
2018-05-11
Hydroarylation of enantioenriched 1,3-disubstituted allenes has the potential to proceed with axial-to-point chirality transfer to yield enantioenriched allylated (hetero)aryl compounds. However, the gold-catalysed intermolecular reaction was previously reported to occur with no chirality transfer owing to competing allene racemisation. Herein, we describe the development of the first intermolecular hydroarylations of allenes to proceed with efficient chirality transfer and summarise some of the key criteria for achieving high regio- and stereoselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.